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1.  Child Mortality Estimation: Appropriate Time Periods for Child Mortality Estimates from Full Birth Histories 
PLoS Medicine  2012;9(8):e1001289.
Jon Pedersen and Jing Liu examine the feasibility and potential advantages of using one-year rather than five-year time periods along with calendar year-based estimation when deriving estimates of child mortality.
Background
Child mortality estimates from complete birth histories from Demographic and Health Surveys (DHS) surveys and similar surveys are a chief source of data used to track Millennium Development Goal 4, which aims for a reduction of under-five mortality by two-thirds between 1990 and 2015. Based on the expected sample sizes when the DHS program commenced, the estimates are usually based on 5-y time periods. Recent surveys have had larger sample sizes than early surveys, and here we aimed to explore the benefits of using shorter time periods than 5 y for estimation. We also explore the benefit of changing the estimation procedure from being based on years before the survey, i.e., measured with reference to the date of the interview for each woman, to being based on calendar years.
Methods and Findings
Jackknife variance estimation was used to calculate standard errors for 207 DHS surveys in order to explore to what extent the large samples in recent surveys can be used to produce estimates based on 1-, 2-, 3-, 4-, and 5-y periods. We also recalculated the estimates for the surveys into calendar-year-based estimates. We demonstrate that estimation for 1-y periods is indeed possible for many recent surveys.
Conclusions
The reduction in bias achieved using 1-y periods and calendar-year-based estimation is worthwhile in some cases. In particular, it allows tracking of the effects of particular events such as droughts, epidemics, or conflict on child mortality in a way not possible with previous estimation procedures. Recommendations to use estimation for short time periods when possible and to use calendar-year-based estimation were adopted in the United Nations 2011 estimates of child mortality.
Editors' Summary
Background
In 2000, world leaders set, as Millennium Development Goal 4 (MDG 4), a target of reducing global under-five mortality (the number of children who die before their fifth birthday to a third of its 1990 level (12 million deaths per year) by 2015. (The MDGs are designed to alleviate extreme poverty by 2015.) To track progress towards MDG 4, the under-five mortality rate (also shown as 5q0) needs to be estimated both “precisely” and “accurately.” A “precise” estimate has a small random error (a quality indicated by a statistical measurement called the coefficient of variance), and an “accurate” estimate is one that is close to the true value because it lacks bias (systematic errors). In an ideal world, under-five mortality estimates would be based on official records of births and deaths. However, developing countries, which are where most under-five deaths occur, rarely have such records, and under-five mortality estimation relies on “complete birth histories” provided by women via surveys. These are collected by Demographic and Health Surveys (DHS, a project that helps developing countries collect data on health and population trends) and record all the births that a surveyed woman has had and the age at death of any of her children who have died.
Why Was This Study Done?
Because the DHS originally surveyed samples of 5,000–6,000 women, estimates of under-five mortality are traditionally calculated using data from five-year time periods. Over shorter periods with this sample size, the random errors in under-five mortality estimates become unacceptably large. Nowadays, the average DHS survey sample size is more than 10,000 women, so it should be possible to estimate under-five mortality over shorter time periods. Such estimates should be able to track the effects on under-five mortality of events such as droughts and conflicts better than estimates made over five years. In this study, the researchers determine appropriate time periods for child mortality estimates based on full birth histories, given different sample sizes. Specifically, they ask whether, with the bigger sample sizes that are now available, details about trends in under-five mortality rates are being missed by using the estimation procedures that were developed for smaller samples. They also ask whether calendar-year-based estimates can be calculated; mortality is usually estimated in “years before the survey,” a process that blurs the reference period for the estimate.
What Did the Researchers Do and Find?
The researchers used a statistical method called “jackknife variance estimation” to determine coefficients of variance for child mortality estimates calculated over different time periods using complete birth histories from 207 DHS surveys. Regardless of the estimation period, half of the estimates had a coefficient of variance of less than 10%, a level of random variation that is generally considered acceptable. However, within each time period, some estimates had very high coefficients of variance. These estimates were derived from surveys where there was a small sample size, low fertility (the women surveyed had relatively few babies), or low child mortality. Other analyses show that although the five-year period estimates had lower standard errors than the one-year period estimates, the latter were affected less by bias than the five-year period estimates. Finally, estimates fixed to calendar years rather than to years before the survey were more directly comparable across surveys and brought out variations in child mortality caused by specific events such as conflicts more clearly.
What Do These Findings Mean?
These findings show that although under-five mortality rate estimates based on five-year periods of data have been the norm, the sample sizes currently employed in DHS surveys make it feasible to estimate mortality for shorter periods. The findings also show that using shorter periods of data in estimations of the under-five mortality rate, and using calendar-year-based estimation, reduces bias (makes the estimations more accurate) and allows the effects of events such as droughts, epidemics, or conflict on under-five mortality rates to be tracked in a way that is impossible when using five-year periods of data. Given these findings, the researchers recommend that time periods shorter than five years should be adopted for the estimation of under-five mortality and that estimations should be pegged to calendar years rather than to years before the survey. Both recommendations have already been adopted by the United Nations Inter-agency Group for Child Mortality Estimation (IGME) and were used in their 2011 analysis of under-five mortality.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001289.
This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 IGME report on Levels and Trends in Child Mortality is available
The World Health Organization also has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages)
Further information about the Millennium Development Goals is available
Information is also available about Demographic and Health Surveys of infant and child mortality
doi:10.1371/journal.pmed.1001289
PMCID: PMC3429388  PMID: 22952435
2.  Neonatal Mortality Risk Associated with Preterm Birth in East Africa, Adjusted by Weight for Gestational Age: Individual Participant Level Meta-Analysis 
PLoS Medicine  2012;9(8):e1001292.
In an analysis of four datasets from East Africa, Tanya Marchant and colleagues investigate the neonatal mortality risk associated with preterm birth and how this changes with weight for gestational age.
Background
Low birth weight and prematurity are amongst the strongest predictors of neonatal death. However, the extent to which they act independently is poorly understood. Our objective was to estimate the neonatal mortality risk associated with preterm birth when stratified by weight for gestational age in the high mortality setting of East Africa.
Methods and Findings
Members and collaborators of the Malaria and the MARCH Centers, at the London School of Hygiene & Tropical Medicine, were contacted and protocols reviewed for East African studies that measured (1) birth weight, (2) gestational age at birth using antenatal ultrasound or neonatal assessment, and (3) neonatal mortality. Ten datasets were identified and four met the inclusion criteria. The four datasets (from Uganda, Kenya, and two from Tanzania) contained 5,727 births recorded between 1999–2010. 4,843 births had complete outcome data and were included in an individual participant level meta-analysis. 99% of 445 low birth weight (<2,500 g) babies were either preterm (<37 weeks gestation) or small for gestational age (below tenth percentile of weight for gestational age). 52% of 87 neonatal deaths occurred in preterm or small for gestational age babies. Babies born <34 weeks gestation had the highest odds of death compared to term babies (odds ratio [OR] 58.7 [95% CI 28.4–121.4]), with little difference when stratified by weight for gestational age. Babies born 34–36 weeks gestation with appropriate weight for gestational age had just three times the likelihood of neonatal death compared to babies born term, (OR 3.2 [95% CI 1.0–10.7]), but the likelihood for babies born 34–36 weeks who were also small for gestational age was 20 times higher (OR 19.8 [95% CI 8.3–47.4]). Only 1% of babies were born moderately premature and small for gestational age, but this group suffered 8% of deaths. Individual level data on newborns are scarce in East Africa; potential biases arising due to the non-systematic selection of the individual studies, or due to the methods applied for estimating gestational age, are discussed.
Conclusions
Moderately preterm babies who are also small for gestational age experience a considerably increased likelihood of neonatal death in East Africa.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
Worldwide, every year around 3.3 million babies die within their first month of life and the proportion of under-five child deaths that are now in the neonatal period (the first 28 days of life) has increased in all regions of the world and is currently estimated at 41%. Of these deaths, over 90% occur in low- and middle-income countries, and a third of all neonatal deaths occur in sub-Saharan Africa. Low birth weight (defined as <2,500 g) is one of the biggest risk factors associated with neonatal deaths but it is the causes of low birth weight, rather than the low weight itself that is thought to lead to neonatal deaths. The two main causes of low birth weight are preterm birth (delivery before 37 weeks gestation) and/or restricted growth in the womb (intra-uterine growth retardation), resulting in babies who are small for their dates (defined as being in the lowest 10% of weight expected for gestational age with reference to a US population).
Why Was This Study Done?
Despite growing international attention focused on neonatal mortality in recent years, the relative importance of low birth weight, small for gestational age, and preterm birth in causing newborn deaths remains unclear. So in this study, the researchers investigated these relationships by calculating the risk of neonatal mortality associated with preterm birth after adjusting for weight for gestational age by conducting a meta-analysis (synthesis of the data) using information from studies reporting neonatal mortality conducted in sub-Saharan Africa.
What Did the Researchers Do and Find?
The researchers identified potential African datasets and selected four out of a possible ten to include in their analysis as these studies included three essential birth outcomes: birth weight; gestational age measured using antenatal ultrasound, or neonatal assessment on the day of birth; and neonatal mortality. These four studies were conducted in Kenya, Tanzania, and Uganda, all in East Africa. The researchers analysed each study separately but also conducted a pooled statistical analysis on all four studies. To give a more detailed analysis, the researchers categorized babies into six groups taking into account whether the babies were moderately preterm (born at 34–36 weeks) or very preterm (born before 34 weeks) and whether their weight was appropriate for their gestational age.
The researchers included a total of 4,843 live births in their analysis and found that overall, 9.2% of babies were low birth weight, 4.0% were preterm, and 20.4% were small for gestational age. Amongst low birth weight babies, 26.1% were preterm, 85.0% were small for gestational age, and 98.8% were either preterm or small for gestational age. In their detailed analysis, the researchers found that the odds (chance) of death in the first 28 days of life were seven times higher for babies born low birth weight compared to those with normal birth weight, with low birth weight infants experiencing a neonatal mortality rate of 80.9/1,000 live births. The odds of death were twice as high for babies born small for gestational age compared to those born appropriate for gestational age, giving a neonatal mortality rate of 29.3/1,000 live births. Furthermore, compared to those born at term, the odds of death were over six times higher for babies born moderately preterm and almost 60 times higher for babies born very preterm with almost half of all very preterm babies dying in the first 28 days of life, giving a neonatal mortality rate 473.6/1,000 live births. However, moderately preterm babies who were small for gestational age had a much greater odds of death than moderately preterm babies who were of the appropriate weight for their gestational age.
What Do These Findings Mean?
These findings from East Africa show that babies born either small for gestational age or preterm contributed 52% of neonatal deaths. The detailed analysis suggests that babies born preterm are at the greatest risk of death, but size for gestational age also plays an important role especially in moderately preterm babies. The results from this study emphasize the pressing need to find ways to prevent preterm delivery and intra-uterine growth retardation and also illustrate the importance of measuring and reporting outcomes of individual babies.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001292.
A recent PLOS Medicine study by Oestergaard et al. has the latest global figures on neonatal mortality
UNICEF provides information on neonatal mortality
The World Health Organization (WHO) provides factsheets on the causes of neonatal mortality, including preterm birth
doi:10.1371/journal.pmed.1001292
PMCID: PMC3419185  PMID: 22904691
3.  The Reversal of Fortunes: Trends in County Mortality and Cross-County Mortality Disparities in the United States  
PLoS Medicine  2008;5(4):e66.
Background
Counties are the smallest unit for which mortality data are routinely available, allowing consistent and comparable long-term analysis of trends in health disparities. Average life expectancy has steadily increased in the United States but there is limited information on long-term mortality trends in the US counties This study aimed to investigate trends in county mortality and cross-county mortality disparities, including the contributions of specific diseases to county level mortality trends.
Methods and Findings
We used mortality statistics (from the National Center for Health Statistics [NCHS]) and population (from the US Census) to estimate sex-specific life expectancy for US counties for every year between 1961 and 1999. Data for analyses in subsequent years were not provided to us by the NCHS. We calculated different metrics of cross-county mortality disparity, and also grouped counties on the basis of whether their mortality changed favorably or unfavorably relative to the national average. We estimated the probability of death from specific diseases for counties with above- or below-average mortality performance. We simulated the effect of cross-county migration on each county's life expectancy using a time-based simulation model. Between 1961 and 1999, the standard deviation (SD) of life expectancy across US counties was at its lowest in 1983, at 1.9 and 1.4 y for men and women, respectively. Cross-county life expectancy SD increased to 2.3 and 1.7 y in 1999. Between 1961 and 1983 no counties had a statistically significant increase in mortality; the major cause of mortality decline for both sexes was reduction in cardiovascular mortality. From 1983 to 1999, life expectancy declined significantly in 11 counties for men (by 1.3 y) and in 180 counties for women (by 1.3 y); another 48 (men) and 783 (women) counties had nonsignificant life expectancy decline. Life expectancy decline in both sexes was caused by increased mortality from lung cancer, chronic obstructive pulmonary disease (COPD), diabetes, and a range of other noncommunicable diseases, which were no longer compensated for by the decline in cardiovascular mortality. Higher HIV/AIDS and homicide deaths also contributed substantially to life expectancy decline for men, but not for women. Alternative specifications of the effects of migration showed that the rise in cross-county life expectancy SD was unlikely to be caused by migration.
Conclusions
There was a steady increase in mortality inequality across the US counties between 1983 and 1999, resulting from stagnation or increase in mortality among the worst-off segment of the population. Female mortality increased in a large number of counties, primarily because of chronic diseases related to smoking, overweight and obesity, and high blood pressure.
Majid Ezzati and colleagues analyze US county-level mortality data for 1961 to 1999, and find a steady increase in mortality inequality across counties between 1983 and 1999.
Editors' Summary
Background.
It has long been recognized that the number of years that distinct groups of people in the United States would be expected to live based on their current mortality patterns (“life expectancy”) varies enormously. For example, white Americans tend to live longer than black Americans, the poor tend to have shorter life expectancies than the wealthy, and women tend to outlive men. Where one lives might also be a factor that determines his or her life expectancy, because of social conditions and health programs in different parts of the country.
Why Was the Study Done?
While life expectancies have generally been rising across the United States over time, there is little information, especially over the long term, on the differences in life expectancies across different counties. The researchers therefore set out to examine whether there were different life expectancies across different US counties over the last four decades. The researchers chose to look at counties—the smallest geographic units for which data on death rates are collected in the US—because it allowed them to make comparisons between small subgroups of people that share the same administrative structure.
What Did the Researchers Do and Find?
The researchers looked at differences in death rates between all counties in US states plus the District of Columbia over four decades, from 1961 to 1999. They obtained the data on number of deaths from the National Center for Health Statistics, and they obtained data on the number of people living in each county from the US Census. The NCHS did not provide death data after 2001. They broke the death rates down by sex and by disease to assess trends over time for women and men, and for different causes of death.
Over these four decades, the researchers found that the overall US life expectancy increased from 67 to 74 years of age for men and from 74 to 80 years for women. Between 1961 and 1983 the death rate fell in both men and women, largely due to reductions in deaths from cardiovascular disease (heart disease and stroke). During this same period, 1961–1983, the differences in death rates among/across different counties fell. However, beginning in the early 1980s the differences in death rates among/across different counties began to increase. The worst-off counties no longer experienced a fall in death rates, and in a substantial number of counties, mortality actually increased, especially for women, a shift that the researchers call “the reversal of fortunes.” This stagnation in the worst-off counties was primarily caused by a slowdown or halt in the reduction of deaths from cardiovascular disease coupled with a moderate rise in a number of other diseases, such as lung cancer, chronic lung disease, and diabetes, in both men and women, and a rise in HIV/AIDS and homicide in men. The researchers' key finding, therefore, was that the differences in life expectancy across different counties initially narrowed and then widened.
What Do these Findings Mean?
The findings suggest that beginning in the early 1980s and continuing through 1999 those who were already disadvantaged did not benefit from the gains in life expectancy experienced by the advantaged, and some became even worse off. The study emphasizes how important it is to monitor health inequalities between different groups, in order to ensure that everyone—and not just the well-off—can experience gains in life expectancy. Although the “reversal of fortune” that the researchers found applied to only a minority of the population, the authors argue that their study results are troubling because an oft-stated aim of the US health system is the improvement of the health of “all people, and especially those at greater risk of health disparities” (see, for example http://www.cdc.gov/osi/goals/SIHPGPostcard.pdf).
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050066.
A study by Nancy Krieger and colleagues, published in PLoS Medicine in February 2008, documented a similar “fall and rise” in health inequities. Krieger and colleagues reported that the difference in health between rich and poor and between different racial/ethnic groups, as measured by rates of dying young and of infant deaths, shrank in the US from 1966 to 1980 then widened from 1980 to 2002
Murray and colleagues, in a 2006 PLoS Medicine article, calculated US mortality rates according to “race-county” units and divided into the “eight Americas,” and found disparities in life expectancy across them
The US Centers for Disease Control has an Office of Minority Health and Health Disparities. The office “aims to accelerate CDC's health impact in the US population and to eliminate health disparities for vulnerable populations as defined by race/ethnicity, socioeconomic status, geography, gender, age, disability status, risk status related to sex and gender, and among other populations identified to be at-risk for health disparities”
Wikipedia has a chapter on health disparities (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
In 2001 the US Agency for Healthcare Research and Quality sponsored a workshop on “strategies to reduce health disparities”
doi:10.1371/journal.pmed.0050066
PMCID: PMC2323303  PMID: 18433290
4.  Effect of Facilitation of Local Maternal-and-Newborn Stakeholder Groups on Neonatal Mortality: Cluster-Randomized Controlled Trial 
PLoS Medicine  2013;10(5):e1001445.
Lars Åke Persson and colleagues conduct a cluster randomised control in northern Vietnam to analyze the effect of the activity of local community-based maternal-and-newborn stakeholder groups on neonatal mortality.
Please see later in the article for the Editors' Summary
Background
Facilitation of local women's groups may reportedly reduce neonatal mortality. It is not known whether facilitation of groups composed of local health care staff and politicians can improve perinatal outcomes. We hypothesised that facilitation of local stakeholder groups would reduce neonatal mortality (primary outcome) and improve maternal, delivery, and newborn care indicators (secondary outcomes) in Quang Ninh province, Vietnam.
Methods and Findings
In a cluster-randomized design 44 communes were allocated to intervention and 46 to control. Laywomen facilitated monthly meetings during 3 years in groups composed of health care staff and key persons in the communes. A problem-solving approach was employed. Births and neonatal deaths were monitored, and interviews were performed in households of neonatal deaths and of randomly selected surviving infants. A latent period before effect is expected in this type of intervention, but this timeframe was not pre-specified. Neonatal mortality rate (NMR) from July 2008 to June 2011 was 16.5/1,000 (195 deaths per 11,818 live births) in the intervention communes and 18.4/1,000 (194 per 10,559 live births) in control communes (adjusted odds ratio [OR] 0.96 [95% CI 0.73–1.25]). There was a significant downward time trend of NMR in intervention communes (p = 0.003) but not in control communes (p = 0.184). No significant difference in NMR was observed during the first two years (July 2008 to June 2010) while the third year (July 2010 to June 2011) had significantly lower NMR in intervention arm: adjusted OR 0.51 (95% CI 0.30–0.89). Women in intervention communes more frequently attended antenatal care (adjusted OR 2.27 [95% CI 1.07–4.8]).
Conclusions
A randomized facilitation intervention with local stakeholder groups composed of primary care staff and local politicians working for three years with a perinatal problem-solving approach resulted in increased attendance to antenatal care and reduced neonatal mortality after a latent period.
Trial registration
Current Controlled Trials ISRCTN44599712
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Over the past few years, there has been enormous international effort to meet the target set by Millennium Development Goal 4 to reduce the under-five child mortality rate by two-thirds and to reduce the number of maternal deaths by three-quarters, respectively, from the 1990 level by 2015. There has been some encouraging progress and according to the latest figures from the World Health Organization, in 2011, just under 7 million children aged under 5 years died, a fall of almost 3 million from a decade ago. However, currently, 41% of all deaths among children under the age of 5 years occur around birth and the first 28 days of life (perinatal and neonatal mortality). Simple interventions can substantially reduce neonatal deaths and there have been several international, national, and local efforts to implement effective care packages to help reduce the number of neonatal deaths.
Why Was This Study Done?
In order for these interventions to be most effective, it is important that the local community becomes involved. Community mobilization, especially through local women's groups, can empower women to prioritize specific interventions to help improve their own health and that of their baby. An alternative strategy might be to mobilize people who already have responsibility to promote health and welfare in society, such as primary care staff, village health workers, and elected political representatives. However, it is unclear if the activities of such stakeholder groups result in improved neonatal survival. So in this study from northern Vietnam, the researchers analyzed the effect of the activity of local maternal-and-newborn stakeholder groups on neonatal mortality.
What Did the Researchers Do and Find?
Between 2008 and 2011, the researchers conducted a cluster-randomized controlled trial in 90 communes within the Quang Ninh province of northeast of Vietnam: 44 communes were allocated to intervention and 46 to the control. The local women's union facilitated recruitment to the intervention, local stakeholder groups (Maternal and Newborn Health Groups), which comprised primary care staff, village health workers, women's union representatives, and the person with responsibility for health in the commune. The groups' role was to identify and prioritize local perinatal health problems and implement actions to help overcome these problems.
Over the three-year period, the Maternal and Newborn Health Groups in the 44 intervention communes had 1,508 meetings. Every year 15–27 unique problems were identified and addressed 94–151 times. The problem-solving processes resulted in an annual number of 19–27 unique actions that were applied 297–649 times per year. The top priority problems and actions identified by these groups dealt with antenatal care attendance, post-natal visits, nutrition and rest during pregnancy, home deliveries, and breast feeding. Neonatal mortality in the intervention group did not change over the first two years but showed a significant improvement in the third year. The three leading causes of death were prematurity/low birth-weight (36%), intrapartum-related neonatal deaths (30%), and infections (15%). Stillbirth rates were 7.4 per 1,000 births in the intervention arm and 9.0 per 1,000 births in the control arm. There was one maternal death in the intervention communes and four in the control communes and there was a significant improvement in antenatal care attendance in the intervention arm. However, there were no significant differences between the intervention and control groups of other outcomes, including tetanus immunization, delivery preparedness, institutional delivery, temperature control at delivery, early initiation of breastfeeding, or home visit of a midwife during the first week after delivery.
What Do These Findings Mean?
These findings suggest that local stakeholder groups comprised of primary care staff and local politicians using a problem-solving approach may help to reduce the neonatal mortality rate after three years of implementation (although the time period for an expected reduction in neonatal mortality was not specified before the trial started) and may also increase the rate of antenatal care attendance. However, the intervention had no effect on other important outcomes such as the rate of institutional delivery and breast feeding. This study used a novel approach of community-based activity that was implemented into the public sector system at low cost. A further reduction in neonatal deaths around delivery might be achieved by neonatal resuscitation training and home visits to the mother and her baby.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001445.
The World Health Organization provides comprehensive statistics on neonatal mortality
The Healthy Newborn Network has information on community interventions to help reduce neonatal mortality from around the world
doi:10.1371/journal.pmed.1001445
PMCID: PMC3653802  PMID: 23690755
5.  Child Mortality Estimation: Estimating Sex Differences in Childhood Mortality since the 1970s 
PLoS Medicine  2012;9(8):e1001287.
Cheryl Sawyer uses new methods to generate estimates of sex differences in child mortality which can be used to pinpoint areas where these differences in mortality merit closer examination.
Introduction
Producing estimates of infant (under age 1 y), child (age 1–4 y), and under-five (under age 5 y) mortality rates disaggregated by sex is complicated by problems with data quality and availability. Interpretation of sex differences requires nuanced analysis: girls have a biological advantage against many causes of death that may be eroded if they are disadvantaged in access to resources. Earlier studies found that girls in some regions were not experiencing the survival advantage expected at given levels of mortality. In this paper I generate new estimates of sex differences for the 1970s to the 2000s.
Methods and Findings
Simple fitting methods were applied to male-to-female ratios of infant and under-five mortality rates from vital registration, surveys, and censuses. The sex ratio estimates were used to disaggregate published series of both-sexes mortality rates that were based on a larger number of sources. In many developing countries, I found that sex ratios of mortality have changed in the same direction as historically occurred in developed countries, but typically had a lower degree of female advantage for a given level of mortality. Regional average sex ratios weighted by numbers of births were found to be highly influenced by China and India, the only countries where both infant mortality and overall under-five mortality were estimated to be higher for girls than for boys in the 2000s. For the less developed regions (comprising Africa, Asia excluding Japan, Latin America/Caribbean, and Oceania excluding Australia and New Zealand), on average, boys' under-five mortality in the 2000s was about 2% higher than girls'. A number of countries were found to still experience higher mortality for girls than boys in the 1–4-y age group, with concentrations in southern Asia, northern Africa/western Asia, and western Africa. In the more developed regions (comprising Europe, northern America, Japan, Australia, and New Zealand), I found that the sex ratio of infant mortality peaked in the 1970s or 1980s and declined thereafter.
Conclusions
The methods developed here pinpoint regions and countries where sex differences in mortality merit closer examination to ensure that both sexes are sharing equally in access to health resources. Further study of the distribution of causes of death in different settings will aid the interpretation of differences in survival for boys and girls.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
In 2000, world leaders agreed to eradicate extreme poverty by 2015. To help track progress towards this global commitment, eight Millennium Development Goals (MDGs) were set. MDG 4, which aims to reduce child mortality, calls for a reduction in under-five mortality (the number of children who die before their fifth birthday) to a third of its 1990 level of 12 million by 2015. The under-five mortality rate is also denoted in the literature as U5MR and 5q0. Progress towards MDG 4 has been substantial, but with only three years left to reach it, efforts to strengthen child survival programs are intensifying. Reliable estimates of trends in childhood mortality are pivotal to these efforts. So, since 2004, the United Nations Inter-agency Group for Child Mortality Estimation (UN IGME) has used statistical regression models to produce estimates of trends in under-five mortality and infant mortality (death before age one year) from data about childbearing and child survival collected by vital registration systems (records of all births and deaths), household surveys, and censuses.
Why Was This Study Done?
In addition to estimates of overall childhood mortality trends, information about sex-specific childhood mortality trends is desirable to monitor progress towards MDG 4, although the interpretation of trends in the relative mortality of girls and boys is not straightforward. Newborn girls survive better than newborn boys because they are less vulnerable to birth complications and infections and have fewer inherited abnormalities. Thus, the ratio of infant mortality among boys to infant mortality among girls is greater than one, provided both sexes have equal access to food and medical care. Beyond early infancy, girls and boys are similarly vulnerable to infections, so the sex ratio of deaths in the 1–4-year age group is generally lower than that of infant mortality. Notably, as living conditions improve in developing countries, infectious diseases become less important as causes of death. Thus, in the absence of sex-specific differences in the treatment of children, the sex ratio of childhood mortality is expected be greater than one and to increase as overall under-five mortality rates in developing countries decrease. In this study, the researcher evaluated national and regional changes in the sex ratios of childhood mortality since the 1970s to investigate whether girls and boys have equal access to medical care and other resources.
What Did the Researcher Do and Find?
The researcher developed new statistical fitting methods to estimate trends in the sex ratio of mortality for infants and young children for individual countries and world regions. When considering individual countries, the researcher found that for 92 countries in less developed regions, the median sex ratio of under-five mortality increased between the 1970s and the 2000s, in line with the expected changes just described. However, the average sex ratio of under-five mortality for less developed regions, weighted according to the number of births in each country, did not increase between the 1970s and 2000s, at which time the average under-five mortality rate of boys was about 2% higher than that of girls. This discrepancy resulted from India and China—the two most populous developing countries—having sex ratios for both infant and under-five mortality that remained constant or declined over the study period and were below one in the 2000s, a result that indicates excess female mortality. In China, for example, infant mortality was found to be 12% higher for boys than for girls in the 1970s, but 24% lower for boys than for girls in the 2000s. Finally, although in the less developed regions (excluding India and China) girls went from having a slight survival disadvantage at ages 1–4 years in the 1970s, on average, to having a slight advantage in the 2000s, girls remained more likely to die than boys in this age group in several Asian and African countries.
What Do These Findings Mean?
Although the quality of the available data is likely to affect the accuracy of these findings, in most developing countries the ratio of male to female under-five mortality has increased since the 1970s, in parallel with the decrease in overall childhood mortality. Notably, however, in a number of developing countries—including several each in sub-Saharan Africa, northern Africa/western Asia, and southern Asia—girls have higher mortality than boys at ages 1–4 years, and in India and China girls have higher mortality in infancy. Thus, girls are benefitting less than boys from the overall decline in childhood mortality in India, China, and some other developing countries. Further studies are needed to determine the underlying reasons for this observation. Nevertheless, the methods developed here to estimate trends in sex-specific childhood mortality pinpoint countries and regions where greater efforts should be made to ensure that both sexes have equal access to health care and other important resources during early life.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001287.
This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine
The United Nations Childrens Fund works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 UN IGME report Levels & Trends in Child Mortality is available
The World Health Organization also has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages)
Further information about the Millennium Development Goals is available
A 2011 report by the United Nations Department of Economic and Social Affairs entitled Sex Differentials in Childhood Mortality is available
doi:10.1371/journal.pmed.1001287
PMCID: PMC3429399  PMID: 22952433
6.  The Effect of Changing Patterns of Obstetric Care in Scotland (1980–2004) on Rates of Preterm Birth and Its Neonatal Consequences: Perinatal Database Study 
PLoS Medicine  2009;6(9):e1000153.
Jane Norman and colleagues analyzed linked perinatal surveillance data in Scotland and find that between 1980 and 2004 increases in spontaneous and medically induced preterm births contributed equally to the rising rate of preterm births.
Background
Rates of preterm birth are rising worldwide. Studies from the United States and Latin America suggest that much of this rise relates to increased rates of medically indicated preterm birth. In contrast, European and Australian data suggest that increases in spontaneous preterm labour also play a role. We aimed, in a population-based database of 5 million people, to determine the temporal trends and obstetric antecedents of singleton preterm birth and its associated neonatal mortality and morbidity for the period 1980–2004.
Methods and Findings
There were 1.49 million births in Scotland over the study period, of which 5.8% were preterm. We found a percentage increase in crude rates of both spontaneous preterm birth per 1,000 singleton births (10.7%, p<0.01) and medically indicated preterm births (41.2%, p<0.01), which persisted when adjusted for maternal age at delivery. The greater proportion of spontaneous preterm births meant that the absolute increase in rates of preterm birth in each category were similar. Of specific maternal complications, essential and pregnancy-induced hypertension, pre-eclampsia, and placenta praevia played a decreasing role in preterm birth over the study period, with gestational and pre-existing diabetes playing an increasing role. There was a decline in stillbirth, neonatal, and extended perinatal mortality associated with preterm birth at all gestation over the study period but an increase in the rate of prolonged hospital stay for the neonate. Neonatal mortality improved in all subgroups, regardless of obstetric antecedent of preterm birth or gestational age. In the 28 wk and greater gestational groups we found a reduction in stillbirths and extended perinatal mortality for medically induced but not spontaneous preterm births (in the absence of maternal complications) although at the expense of a longer stay in neonatal intensive care. This improvement in stillbirth and neonatal mortality supports the decision making behind the 34% increase in elective/induced preterm birth in these women. Although improvements in neonatal outcomes overall are welcome, preterm birth still accounts for over 66% of singleton stillbirths, 65% of singleton neonatal deaths, and 67% of infants whose stay in the neonatal unit is “prolonged,” suggesting this condition remains a significant contributor to perinatal mortality and morbidity.
Conclusions
In our population, increases in spontaneous and medically induced preterm births have made equal contributions to the rising rate of preterm birth. Despite improvements in related perinatal mortality, preterm birth remains a major obstetric and neonatal problem, and its frequency is increasing.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Most pregnancies last about 40 weeks but increasing numbers of babies are being born preterm, before they reach 37 weeks of gestation (gestation is the period during which a baby develops in its mother). Nowadays in the US, for example, more than half a million babies arrive earlier than expected every year (1 in 8 babies). Although improvements in the care of newborn babies (neonatal care) mean that preterm babies are more likely to survive than in the past, preterm birth remains the single biggest cause of infant death in many developed countries, and many preterm babies who survive have long-term health problems and disabilities, particularly those born before 32 weeks of gestation. Preterm births can be spontaneous or medically induced. At present, it impossible to predict which mothers will spontaneously deliver early and there is no effective way to prevent these preterm births; medically induced early labor is undertaken when either the unborn baby or mother would be at risk if the pregnancy continued to full term.
Why Was This Study Done?
Preterm birth rates need to be reduced, but before this can be done it is important to know how the causes of preterm birth, the numbers of preterm stillbirths, and the numbers of preterm babies who die at birth (neonatal deaths) or soon after (perinatal deaths) are changing with time. If, for example, the rise in preterm births is mainly due to an increase in medically induced labor and if this change in practice has reduced neonatal deaths, it would be unwise to try to reduce the preterm birth rate by discouraging medically induced preterm births. So far, data from the US and Latin America suggest that the increase in preterm births in these countries is solely due to increased rates of medically induced preterm births. However, in Europe and Australia, the rate of spontaneous preterm births also seems to be increasing. In this study, the researchers examine the trends over time and causes of preterm birth and of neonatal death and illness in Scotland over a 25-year period.
What Did the Researchers Do and Find?
By searching a Scottish database of linked maternity records and infant health and death records, the researchers identified 1.49 million singleton births that occurred between 1980 and 2004 of which nearly 90,000 were preterm births. Over the study period, the rates of spontaneous and of medically induced preterm births per 1,000 births increased by 10.7% and 41.2%, respectively, but because there were more spontaneous preterm births than medically induced preterm births, the absolute increase in the rates of each type of birth was similar. Several maternal complications including preeclampsia (a condition that causes high blood pressure) and placenta previa (covering of the opening of the cervix by the placenta) played a decreasing role in preterm births over the study period, whereas gestational and preexisting diabetes played an increasing role. Finally, there was a decline in stillbirths and in neonatal and perinatal deaths among preterm babies, although more babies remained in the hospital longer than 7 days after birth. More specifically, after 28 weeks of gestation, stillbirths and perinatal deaths decreased among medically induced preterm births but not among spontaneous preterm births.
What Do These Findings Mean?
These findings indicate that in Scotland between 1980 and 2004, increases in spontaneous and medically induced preterm births contributed equally to the rising rate of preterm births. Importantly, they also show that the increase in induced preterm births helped to reduce stillbirths and neonatal and perinatal deaths, a finding that supports the criteria that clinicians currently use to decide whether to induce an early birth. Nevertheless, preterm births still account for two-thirds of all stillbirths, neonatal deaths, and extended neonatal stays in hospital and thus cause considerable suffering and greatly increase the workload in neonatal units. The rates of such births consequently need to be reduced and, for Scotland at least, ways will have to be found to reduce the rates of both spontaneous and induced preterm births to achieve this goal while continuing to identify those sick babies who need to be delivered early to give them the best chance of survival.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000153
Tommys is a nonprofit organization that funds research and provides information on the causes and prevention of miscarriage, premature birth, and stillbirth
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish)
The Nemours Foundation, another nonprofit organization for child health, also provides information on premature babies (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on maternal and infant health (in English and Spanish)
The US National Women's Health Information Center has detailed information about pregnancy, including a section on pregnancy complications
MedlinePlus provides links to other information on premature babies and to information on pregnancy (in English and Spanish)
doi:10.1371/journal.pmed.1000153
PMCID: PMC2740823  PMID: 19771156
7.  Changes in Association between Previous Therapeutic Abortion and Preterm Birth in Scotland, 1980 to 2008: A Historical Cohort Study 
PLoS Medicine  2013;10(7):e1001481.
Gordon C. Smith and colleagues used national databases to investigate the association between previous termination of pregnancy and preterm birth in Scotland between 1980 to 2008, and whether the type of procedure was an important factor.
Please see later in the article for the Editors' Summary
Background
Numerous studies have demonstrated that therapeutic termination of pregnancy (abortion) is associated with an increased risk of subsequent preterm birth. However, the literature is inconsistent, and methods of abortion have changed dramatically over the last 30 years. We hypothesized that the association between previous abortion and the risk of preterm first birth changed in Scotland between 1 January 1980 and 31 December 2008.
Methods and Findings
We studied linked Scottish national databases of births and perinatal deaths. We analysed the risk of preterm birth in relation to the number of previous abortions in 732,719 first births (≥24 wk), adjusting for maternal characteristics. The risk (adjusted odds ratio [95% CI]) of preterm birth was modelled using logistic regression, and associations were expressed for a one-unit increase in the number of previous abortions. Previous abortion was associated with an increased risk of preterm birth (1.12 [1.09–1.16]). When analysed by year of delivery, the association was strongest in 1980–1983 (1.32 [1.21–1.43]), progressively declined between 1984 and 1999, and was no longer apparent in 2000–2003 (0.98 [0.91–1.05]) or 2004–2008 (1.02 [0.95–1.09]). A statistical test for interaction between previous abortion and year was highly statistically significant (p<0.001). Analysis of data for abortions among nulliparous women in Scotland 1992–2008 demonstrated that the proportion that were surgical without use of cervical pre-treatment decreased from 31% to 0.4%, and that the proportion of medical abortions increased from 18% to 68%.
Conclusions
Previous abortion was a risk factor for spontaneous preterm birth in Scotland in the 1980s and 1990s, but the association progressively weakened and disappeared altogether by 2000. These changes were paralleled by increasing use of medical abortion and cervical pre-treatment prior to surgical abortion. Although it is plausible that the two trends were related, we could not test this directly as the data on the method of prior abortions were not linked to individuals in the cohort. However, we speculate that modernising abortion methods may be an effective long-term strategy to reduce global rates of preterm birth.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Therapeutic termination of pregnancy is relatively common, with an estimated 40 million procedures performed worldwide every year. Until two decades ago, most terminations were performed as a surgical procedure, but now the majority of terminations are medically induced with a combination of drugs—selective progesterone receptor antagonists, such as mifepristone, and prostaglandins—that cause less damage to the woman's cervix. Although surgical terminations are still performed, nowadays prostaglandins are also used to help prevent damage to the cervix. Protecting the woman's cervix can help to reduce the risk of spontaneous preterm birth (delivery before 37 weeks gestation) in subsequent pregnancies. As many women who have abortions go on to have subsequent births, the widespread use of termination may be a significant factor in the high global rates of preterm delivery.
Why Was This Study Done?
A previous meta-analysis (a study that combines information from several studies) showed that the risk of preterm delivery was higher in women who had had a previous termination compared to women who had not. Based on this meta-analysis, UK guidelines on the care of women requesting a termination currently recommend that they be informed of the increased risk of subsequent preterm birth. However, it is biologically plausible that women undergoing medical termination or current practice for surgical termination (using prostaglandins to protect and prepare the cervix) may not have an increased risk of subsequent preterm delivery, because such approaches may cause less trauma to the cervix than traditional surgical termination. So in this study, the researchers used a large dataset from Scotland with three decades of information about previous terminations and subsequent preterm deliveries to test this possibility.
What Did the Researchers Do and Find?
The researchers linked two national databases—the Scottish Morbidity Record 02 (SMR02), which records the clinical and demographic characteristics and outcomes of all patients giving birth in Scottish maternity hospitals, and the Scottish Stillbirth and Infant Death Survey (SSBIDS), which classifies all perinatal deaths in Scotland. SMR02 data were available from 1980 onwards and also recorded each woman's self-reported total number of previous abortions, and SSBIDS data were available from 1985. Then the researchers used information from NHS National Services Scotland to examine secular trends in terminations over the past few decades, specifically, whether a recorded termination was surgical or medical, and also whether surgical abortion was preceded by cervical preparation.
Using these methods, the researchers identified that there were 757,060 live, singleton first births between 1980 and 2008 and that 56,816 women reported one previous termination, 5,790 women reported two previous terminations, and 822 women reported three previous terminations. In their analysis (adjusted for maternal characteristics) the researchers found that there was an independent association of spontaneous preterm birth, but not induced preterm birth, with previous termination. The researchers calculated that the chance (odds) of spontaneous preterm birth for one, two, and three or more previous abortions was 1.17, 1.51, and 1.64, after adjusting for maternal characteristics, including smoking. Over the time period, the researchers found that the proportion of surgical terminations without use of cervical pre-treatment decreased from 31% in 1992 to 0.4% in 2008, and over the same period the proportion of medical terminations increased from 18% to 68%. These trends are important, because in their analysis by year of delivery, the researchers found that the association between preterm delivery and previous termination was strongest in 1980–1983, progressively declined between 1984 and 1999, and was no longer present from 2000 to 2008.
What Do These Findings Mean?
These findings support the established association between previous termination and preterm delivery. But most importantly, the changes in this association over the past two decades—from strong in 1980–1983 to nonexistent in 2000–2008—a period in which the use of medical termination and pre-treatment of the cervix for surgical termination increased dramatically in Scotland, suggest that surgical termination without cervical pre-treatment is responsible for the increased risk of spontaneous preterm birth: the decrease in the proportion of this procedure over the study period may have led to the disappearance of the established association between previous termination and preterm delivery from 2000 onwards. However, these findings are limited in that the researchers could not directly test whether the two trends were related because they did not have information on the method of previous termination linked to subsequent birth outcome for individual women. However, based on the findings of this study, it is possible that using modern methods of termination of pregnancy (rather than purely surgical methods) could be a factor in reducing global rates of spontaneous preterm delivery in the future.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001481.
Wikipedia gives more information about termination of pregnancy (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
More information is available about the SMR02 dataset used in this study
The World Health Organization gives information on preterm birth
doi:10.1371/journal.pmed.1001481
PMCID: PMC3706322  PMID: 23874161
8.  Measuring Under-Five Mortality: Validation of New Low-Cost Methods 
PLoS Medicine  2010;7(4):e1000253.
n/a
Background
There has been increasing interest in measuring under-five mortality as a health indicator and as a critical measure of human development. In countries with complete vital registration systems that capture all births and deaths, under-five mortality can be directly calculated. In the absence of a complete vital registration system, however, child mortality must be estimated using surveys that ask women to report the births and deaths of their children. Two survey methods exist for capturing this information: summary birth histories and complete birth histories. A summary birth history requires a minimum of only two questions: how many live births has each mother had and how many of them have survived. Indirect methods are then applied using the information from these two questions and the age of the mother to estimate under-five mortality going back in time prior to the survey. Estimates generated from complete birth histories are viewed as the most accurate when surveys are required to estimate under-five mortality, especially for the most recent time periods. However, it is much more costly and labor intensive to collect these detailed data, especially for the purpose of generating small area estimates. As a result, there is a demand for improvement of the methods employing summary birth history data to produce more accurate as well as subnational estimates of child mortality.
Methods and Findings
We used data from 166 Demographic and Health Surveys (DHS) to develop new empirically based methods of estimating under-five mortality using children ever born and children dead data. We then validated them using both in- and out-of-sample analyses. We developed a range of methods on the basis of three dimensions of the problem: (1) approximating the average length of exposure to mortality from a mother's set of children using either maternal age or time since first birth; (2) using cohort and period measures of the fraction of children ever born that are dead; and (3) capturing country and regional variation in the age pattern of fertility and mortality. We focused on improving estimates in the most recent time periods prior to a survey where the traditional indirect methods fail. In addition, all of our methods incorporated uncertainty. Validated against under-five estimates generated from complete birth histories, our methods outperformed the standard indirect method by an average of 43.7% (95% confidence interval [CI] 41.2–45.2). In the 5 y prior to the survey, the new methods resulted in a 53.3% (95% CI 51.3–55.2) improvement. To illustrate the value of this method for local area estimation, we applied our new methods to an analysis of summary birth histories in the 1990, 2000, and 2005 Mexican censuses, generating subnational estimates of under-five mortality for each of 233 jurisdictions.
Conclusions
The new methods significantly improve the estimation of under-five mortality using summary birth history data. In areas without vital registration data, summary birth histories can provide accurate estimates of child mortality. Because only two questions are required of a female respondent to generate these data, they can easily be included in existing survey programs as well as routine censuses of the population. With the wider application of these methods to census data, countries now have the means to generate estimates for subnational areas and population subgroups, important for measuring and addressing health inequalities and developing local policy to improve child survival.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, more than 8 million children die before their fifth birthdays. Most of these deaths occur in developing countries, and most are the result of diseases or combinations of diseases that could have been prevented or treated. Measles, for example, is a major killer in low-income countries and undernutrition contributes to one-third of childhood deaths. Faced with this largely avoidable loss of young lives, in 1990, the United Nations' World Summit for Children pledged to improve the survival of children. Later, in 2000, world leaders set a target of reducing child mortality to one-third of its 1990 level by 2015 as Millennium Development Goal 4. This goal, together with seven others, is designed to alleviate extreme poverty by 2015. In 2006, for the first time since mortality records began, annual deaths among children under five fell below 10 million as a result of public-health programs such as the Measles Initiative, which has reduced global measles mortality by more than two-thirds by vaccinating 500 million children, and the Nothing but Nets campaign, which distributed insecticide-treated antimalaria nets in Africa.
Why Was This Study Done?
Although global under-five mortality is declining, it is unlikely that Millennium Development Goal 4 will be reached by 2015. Indeed, in some countries, little or no progress is being made toward this goal. To improve progress and to monitor the effects of public-health interventions, accurate, up-to-date estimates of national and subnational child mortality rates are essential. In developed countries, vital registration systems—records of all births and deaths—mean that under-five mortality rates can be directly calculated. But many developing countries lack vital registration systems, and child mortality has to be estimated using data collected in surveys. In “complete birth history” surveys, mothers are asked numerous questions about each living child and each dead child. Such surveys can be used to estimate under-five mortality accurately for recent time periods but they are expensive and time-consuming. By contrast, in “summary birth history” surveys, each mother is simply asked how many live births she had and how many of her children have survived. Under-five mortality can be indirectly calculated from this information and the age of the mother, but the current methods for making this calculation cannot provide reliable estimates of under-five mortality more recently than 3 years before the survey. In this study, therefore, the researchers develop methods for estimating more recent under-five mortality rates from summary birth histories.
What Did the Researchers Do and Find?
The researchers used data about all children born and dead children extracted from 169 Demographic and Health Surveys (DHS; a project started in 1984 to help developing countries collect data on health and population trends) covering 70 countries to develop four new methods to estimate under-five mortality. They tested these new methods and a method that combined all four approaches by comparing the estimates of under-five mortality provided by these methods and the standard indirect method to the estimates obtained from an analysis of the complete birth data in the DHS. The new methods all outperformed the standard indirect method, particularly for the most recent 5 years. The researchers also used their new methods to generate estimates of under-five mortality for each of the 233 jurisdictions in Mexico from summary birth histories collected in the 1990, 2000, and 2005 Mexico censuses. The overall trends of these subnational estimates, they report, mirrored those obtained from vital registration data.
What Do These Findings Mean?
These findings suggest that application of the new methods developed by the researchers could significantly improve the accuracy of estimates of under-five mortality based on summary birth history data. The researchers warn that although their methods can provide accurate estimates of recent under-five mortality, they might not capture rapid fluctuations in mortality such as those that occur during wars. However, they suggest, the two questions needed to generate the data required to apply these new methods could easily be included in existing survey programs and in routine censuses. Consequently, systematic application of the methods proposed in this study should provide policy makers with the information about levels, recent trends, and inequalities in child mortality that they need to accelerate efforts to reduce the global toll of childhood deaths.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000253.
This study and two related PLoS Medicine Research Articles by Obermeyer et al and by Murray et al are further discussed in a PLoS Medicine Perspective by Mathers and Boerma
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development and protection around the world; it provides information on Millennium Development Goal 4 and its Childinfo website provides detailed statistics about child survival and health (some information in several languages)
Further information about the Millennium Development Goals is available
The World Health Organization also has information about Millennium Development Goal 4 and provides estimates of child mortality rates
Information is also available about the Demographic and Health Surveys
doi:10.1371/journal.pmed.1000253
PMCID: PMC2854123  PMID: 20405055
9.  Improving the Quality of Adult Mortality Data Collected in Demographic Surveys: Validation Study of a New Siblings' Survival Questionnaire in Niakhar, Senegal 
PLoS Medicine  2014;11(5):e1001652.
Stéphane Helleringer and colleagues conducted a validation study in Niakhar, Senegal to investigate whether a new approach, sibling survival calendars, improves the quality of adult mortality data collected in demographic surveys.
Please see later in the article for the Editors' Summary
Background
In countries with limited vital registration, adult mortality is frequently estimated using siblings' survival histories (SSHs) collected during Demographic and Health Surveys (DHS). These data are affected by reporting errors. We developed a new SSH questionnaire, the siblings' survival calendar (SSC). It incorporates supplementary interviewing techniques to limit omissions of siblings and uses an event history calendar to improve reports of dates and ages. We hypothesized that the SSC would improve the quality of adult mortality data.
Methods and Findings
We conducted a retrospective validation study among the population of the Niakhar Health and Demographic Surveillance System in Senegal. We randomly assigned men and women aged 15–59 y to an interview with either the DHS questionnaire or the SSC. We compared SSHs collected in each group to prospective data on adult mortality collected in Niakhar. The SSC reduced respondents' tendency to round reports of dates and ages to the nearest multiple of five or ten (“heaping”). The SSC also had higher sensitivity in recording adult female deaths: among respondents whose sister(s) had died at an adult age in the past 15 y, 89.6% reported an adult female death during SSC interviews versus 75.6% in DHS interviews (p = 0.027). The specificity of the SSC was similar to that of the DHS questionnaire, i.e., it did not increase the number of false reports of deaths. However, the SSC did not improve the reporting of adult deaths among the brothers of respondents. Study limitations include sample selectivity, limited external validity, and multiple testing.
Conclusions
The SSC has the potential to collect more accurate SSHs than the questionnaire used in DHS. Further research is needed to assess the effects of the SSC on estimates of adult mortality rates. Additional validation studies should be conducted in different social and epidemiological settings.
Trial Registration
Controlled-Trials.com ISRCTN06849961
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Governments and international health agencies need accurate information on births and deaths in populations to help them plan health care policies and monitor the effectiveness of public health programs. The most common way of collecting information on vital statistics in an area or country is through civil registration, an administrative system used by governments to record vital events that occur in their populations. In low-to-middle-income countries that have limited resources to devote to such a system, unconventional techniques are often used to estimate mortality levels and trends. One such method is siblings' survival histories collected while conducting a health or other type of public survey. Those surveyed are asked to list all their maternal siblings by birth order and report survival status and current age (for living siblings) or age at death (for deceased siblings).
Use of siblings' survival histories leaves the accuracy of the mortality record vulnerable to reporting errors and selection bias. Selection bias is a statistical prejudice that is introduced by the choice of the individuals or groups taking part in the analysis. Reporting errors occur when an individual fails to report a sibling's death, misreports the age of a sibling, or does not recall the exact date when a sibling died.
Why Was This Study Done?
This study was conducted to estimate whether modifying a standard siblings' survival history questionnaire could improve the accuracy of data obtained. The researchers conducted a study in Niakhar, Senegal, using a modified siblings' survival history questionnaire to incorporate some innovative techniques for assisting memory recall, such as recall cues, to help prevent omissions. The researchers also introduced an event history calendar format to help with more accurate reporting of dates. This modified questionnaire is called the siblings' survival calendar.
What Did the Researchers Do and Find?
The researchers randomly assigned men and women registered by the Niakhar Health and Demographic Surveillance System, aged 15–59 years old, to an interview with the basic questionnaire or the modified siblings' survival calendar. The modifications included emphasizing the importance of accurate recall before the participant started and asking respondents to list their maternal siblings in the order that they came to the mind instead of birth order. Also, the researchers used supplementary interviewing techniques designed to stimulate the recall of potentially omitted siblings and also used an event history calendar approach for collecting data on ages at, and dates of, vital events that had affected the siblings of a respondent.
The researchers compared the results from the two survey instruments and precise data on adult mortality collected by continuous demographic surveillance in a small area of Senegal. They found that the calendar survey improved the sensitivity of survey data in recording adult female deaths. In addition, the modified questionnaire significantly reduced age and date heaping (the tendency of respondents to round off dates) observed with the basic questionnaire. The modified questionnaire took six minutes longer to complete on average than the basic questionnaire.
What Do These Findings Mean?
These findings suggest that a new approach (the siblings' survival calendar) that uses simple interview tools to improve estimates of mortality in resource-limited countries is feasible and may improve the quality of the data from siblings' survival histories, particularly in reporting female deaths. Although the study was limited by sample selectivity, limited external validity, and multiple testing, the findings suggest that this new approach has the potential to allow the collection of more accurate data from siblings' survival histories than that collected from the current questionnaire. The next step is to validate these findings in other settings.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001652.
The World Health Organization Regional Office for Africa has a page on vital statistics
Information on demographic data available in Senegal can be accessed on the website of the Agence Nationale de la Statistique et de la Démographie (in French)
The UN Statistics Division has a page on their vital registration and vital statistics coverage assessment
The World Mortality Report 2013 presents the latest mortality estimates developed by the Population Division of the United Nations, including the probability of dying between the ages of 15 and 60 years
The Institute for Health Metrics and Evaluation has developed a visualization tool that allows one to see how siblings' survival histories are adjusted to generate estimates of adult mortality
More information on Health and Demographic Surveys surveillance in Niakhar, Senegal, is available (in French) on the website of the Institut de Recherche pour le Développement
doi:10.1371/journal.pmed.1001652
PMCID: PMC4035258  PMID: 24866715
10.  Mortality in Iraq Associated with the 2003–2011 War and Occupation: Findings from a National Cluster Sample Survey by the University Collaborative Iraq Mortality Study 
PLoS Medicine  2013;10(10):e1001533.
Based on a survey of 2,000 randomly selected households throughout Iraq, Amy Hagopian and colleagues estimate that close to half a million excess deaths are attributable to the recent Iraq war and occupation.
Please see later in the article for the Editors' Summary
Background
Previous estimates of mortality in Iraq attributable to the 2003 invasion have been heterogeneous and controversial, and none were produced after 2006. The purpose of this research was to estimate direct and indirect deaths attributable to the war in Iraq between 2003 and 2011.
Methods and Findings
We conducted a survey of 2,000 randomly selected households throughout Iraq, using a two-stage cluster sampling method to ensure the sample of households was nationally representative. We asked every household head about births and deaths since 2001, and all household adults about mortality among their siblings. We used secondary data sources to correct for out-migration. From March 1, 2003, to June 30, 2011, the crude death rate in Iraq was 4.55 per 1,000 person-years (95% uncertainty interval 3.74–5.27), more than 0.5 times higher than the death rate during the 26-mo period preceding the war, resulting in approximately 405,000 (95% uncertainty interval 48,000–751,000) excess deaths attributable to the conflict. Among adults, the risk of death rose 0.7 times higher for women and 2.9 times higher for men between the pre-war period (January 1, 2001, to February 28, 2003) and the peak of the war (2005–2006). We estimate that more than 60% of excess deaths were directly attributable to violence, with the rest associated with the collapse of infrastructure and other indirect, but war-related, causes. We used secondary sources to estimate rates of death among emigrants. Those estimates suggest we missed at least 55,000 deaths that would have been reported by households had the households remained behind in Iraq, but which instead had migrated away. Only 24 households refused to participate in the study. An additional five households were not interviewed because of hostile or threatening behavior, for a 98.55% response rate. The reliance on outdated census data and the long recall period required of participants are limitations of our study.
Conclusions
Beyond expected rates, most mortality increases in Iraq can be attributed to direct violence, but about a third are attributable to indirect causes (such as from failures of health, sanitation, transportation, communication, and other systems). Approximately a half million deaths in Iraq could be attributable to the war.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
War is a major public health problem. Its health effects include violent deaths among soldiers and civilians as well as indirect increases in mortality and morbidity caused by conflict. Unlike those of other causes of death and disability, however, the consequences of war on population health are rarely studied scientifically. In conflict situations, deaths and diseases are not reliably measured and recorded, and estimating the proportion caused, directly or indirectly, by a war or conflict is challenging. Population-based mortality survey methods—asking representative survivors about deaths they know about—were developed by public health researchers to estimate death rates. By comparing death rate estimates for periods before and during a conflict, researchers can derive the number of excess deaths that are attributable to the conflict.
Why Was This Study Done?
A number of earlier studies have estimated the death toll in Iraq since the beginning of the war in March 2003. The previous studies covered different periods from 2003 to 2006 and derived different rates of overall deaths and excess deaths attributable to the war and conflict. All of them have been controversial, and their methodologies have been criticized. For this study, based on a population-based mortality survey, the researchers modified and improved their methodology in response to critiques of earlier surveys. The study covers the period from the beginning of the war in March 2003 until June 2011, including a period of high violence from 2006 to 2008. It provides population-based estimates for excess deaths in the years after 2006 and covers most of the period of the war and subsequent occupation.
What Did the Researchers Do and Find?
Interviewers trained by the researchers conducted the survey between May 2011 and July 2011 and collected data from 2,000 randomly selected households in 100 geographical clusters, distributed across Iraq's 18 governorates. The interviewers asked the head of each household about deaths among household members from 2001 to the time of the interview, including a pre-war period from January 2001 to March 2003 and the period of the war and occupation. They also asked all adults in the household about deaths among their siblings during the same period. From the first set of data, the researchers calculated the crude death rates (i.e., the number of deaths during a year per 1,000 individuals) before and during the war. They found the wartime crude death rate in Iraq to be 4.55 per 1,000, more than 50% higher than the death rate of 2.89 during the two-year period preceding the war. By multiplying those rates by the annual Iraq population, the authors estimate the total excess Iraqi deaths attributable to the war through mid-2011 to be about 405,000. The researchers also estimated that an additional 56,000 deaths were not counted due to migration. Including this number, their final estimate is that approximately half a million people died in Iraq as a result of the war and subsequent occupation from March 2003 to June 2011.
The risk of death at the peak of the conflict in 2006 almost tripled for men and rose by 70% for women. Respondents attributed 20% of household deaths to war-related violence. Violent deaths were attributed primarily to coalition forces (35%) and militia (32%). The majority (63%) of violent deaths were from gunshots. Twelve percent were attributed to car bombs. Based on the responses from adults in the surveyed households who reported on the alive-or-dead status of their siblings, the researchers estimated the total number of deaths among adults aged 15–60 years, from March 2003 to June 2011, to be approximately 376,000; 184,000 of these deaths were attributed to the conflict, and of those, the authors estimate that 132,000 were caused directly by war-related violence.
What Do These Findings Mean?
These findings provide the most up-to-date estimates of the death toll of the Iraq war and subsequent conflict. However, given the difficult circumstances, the estimates are associated with substantial uncertainties. The researchers extrapolated from a small representative sample of households to estimate Iraq's national death toll. In addition, respondents were asked to recall events that occurred up to ten years prior, which can lead to inaccuracies. The researchers also had to rely on outdated census data (the last complete population census in Iraq dates back to 1987) for their overall population figures. Thus, to accompany their estimate of 460,000 excess deaths from March 2003 to mid-2011, the authors used statistical methods to determine the likely range of the true estimate. Based on the statistical methods, the researchers are 95% confident that the true number of excess deaths lies between 48,000 and 751,000—a large range. More than two years past the end of the period covered in this study, the conflict in Iraq is far from over and continues to cost lives at alarming rates. As discussed in an accompanying Perspective by Salman Rawaf, violence and lawlessness continue to the present day. In addition, post-war Iraq has limited capacity to re-establish and maintain its battered public health and safety infrastructure.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001533
This study is further discussed in a PLOS Medicine Perspective by Salman Rawaf.
The Geneva Declaration on Armed Violence and Development website provides information on the global burden of armed violence.
The International Committee of the Red Cross provides information about war and international humanitarian law (in several languages).
Medact, a global health charity, has information on health and conflict.
Columbia University has a program on forced migration and health.
Johns Hopkins University runs the Center for Refugee and Disaster Response.
University of Washington's Health Alliance International website also has information about war and conflict.
doi:10.1371/journal.pmed.1001533
PMCID: PMC3797136  PMID: 24143140
11.  The Fall and Rise of US Inequities in Premature Mortality: 1960–2002 
PLoS Medicine  2008;5(2):e46.
Background
Debates exist as to whether, as overall population health improves, the absolute and relative magnitude of income- and race/ethnicity-related health disparities necessarily increase—or derease. We accordingly decided to test the hypothesis that health inequities widen—or shrink—in a context of declining mortality rates, by examining annual US mortality data over a 42 year period.
Methods and Findings
Using US county mortality data from 1960–2002 and county median family income data from the 1960–2000 decennial censuses, we analyzed the rates of premature mortality (deaths among persons under age 65) and infant death (deaths among persons under age 1) by quintiles of county median family income weighted by county population size. Between 1960 and 2002, as US premature mortality and infant death rates declined in all county income quintiles, socioeconomic and racial/ethnic inequities in premature mortality and infant death (both relative and absolute) shrank between 1966 and 1980, especially for US populations of color; thereafter, the relative health inequities widened and the absolute differences barely changed in magnitude. Had all persons experienced the same yearly age-specific premature mortality rates as the white population living in the highest income quintile, between 1960 and 2002, 14% of the white premature deaths and 30% of the premature deaths among populations of color would not have occurred.
Conclusions
The observed trends refute arguments that health inequities inevitably widen—or shrink—as population health improves. Instead, the magnitude of health inequalities can fall or rise; it is our job to understand why.
Nancy Krieger and colleagues found evidence of decreasing, and then increasing or stagnating, socioeconomic and racial inequities in US premature mortality and infant death from 1960 to 2002.
Editors' Summary
Background
One of the biggest aims of public health advocates and governments is to improve the health of the population. Improving health increases people's quality of life and helps the population be more economically productive. But within populations are often persistent differences (usually called “disparities” or “inequities”) in the health of different subgroups—between women and men, different income groups, and people of different races/ethnicities, for example. Researchers study these differences so that policy makers and the broader public can be informed about what to do to intervene. For example, if we know that the health of certain subgroups of the population—such as the poor—is staying the same or even worsening as the overall health of the population is improving, policy makers could design programs and devote resources to specifically target the poor.
To study health disparities, researchers use both relative and absolute measures. Relative inequities refer to ratios, while absolute inequities refer to differences. For example, if one group's average income level increases from $1,000 to $10,000 and another group's from $2,000 to $20,000, the relative inequality between the groups stays the same (i.e., the ratio of incomes between the two groups is still 2) but the absolute difference between the two groups has increased from $1,000 to $10,000.
Examining the US population, Nancy Krieger and colleagues looked at trends over time in both relative and absolute differences in mortality between people in different income groups and between whites and people of color.
Why Was This Study Done?
There has been a lot of debate about whether disparities have been widening or narrowing as overall population health improves. Some research has found that both total health and health disparities are getting better with time. Other research has shown that overall health gains mask worsening disparities—such that the rich get healthier while the poor get sicker.
Having access to more data over a longer time frame meant that Krieger and colleagues could provide a more complete picture of this sometimes contradictory story. It also meant they could test their hypothesis about whether, as population health improves, health inequities necessarily widen or shrink within the time period between the 1960s through the 1990s during which certain events and policies likely would have had an impact on the mortality trends in that country.
What Did the Researchers Do and Find?
In order to investigate health inequities, the authors chose to look at two common measures of population health: rates of premature mortality (dying before the age of 65 years) and rates of infant mortality (death before the age of 1).
To determine mortality rates, the authors used death statistics data from different counties, which are routinely collected by state and national governments. To be able to rank mortality rates for different income groups, they used data on the median family incomes of people living within those counties (meaning half the families had income above, and half had incomes below, the median value). They calculated mortality rates for the total population and for whites versus people of color. They used data from 1960 through 2002. They compared rates for 1966–1980 with two other time periods: 1960–1965 and 1981–2002. They also examined trends in the annual mortality rates and in the annual relative and absolute disparites in these rates by county income level.
Over the whole period 1960–2002, the authors found that premature mortality (death before the age of 65) and infant mortality (death before the age of 1) decreased for all income groups. But they also found that disparities between income groups and between whites and people of color were not the same over this time period. In fact, the economic disparities narrowed then widened. First, they shrank between 1966 and 1980, especially for Americans of color. After 1980, however, the relative health inequities widened and the absolute differences did not change. The authors conclude that if all people in the US population experienced the same health gains as the most advantaged did during these 42 years (i.e., as the whites in the highest income groups), 14% of the premature deaths among whites and 30% of the premature deaths among people of color would have been prevented.
What Do These Findings Mean?
The findings provide an overview of the trends in inequities in premature and infant mortality over a long period of time. Different explanations for these trends can now be tested. The authors discuss several potential reasons for these trends, including generally rising incomes across America and changes related to specific diseases, such as the advent of HIV/AIDS, changes in smoking habits, and better management of cancer and cardiovascular disease. But they find that these do not explain the fall then rise of inequities. Instead, the authors suggest that explanations lie in the social programs of the 1960s and the subsequent roll-back of some of these programmes in the 1980s. The US “War on Poverty,” civil rights legislation, and the establishment of Medicare occurred in the mid 1960s, which were intended to reduce socioeconomic and racial/ethnic inequalities and improve access to health care. In the 1980s there was a general cutting back of welfare state provisions in America, which included cuts to public health and antipoverty programs, tax relief for the wealthy, and worsening inequity in the access to and quality of health care. Together, these wider events could explain the fall then rise trends in mortality disparities.
The authors say their findings are important to inform and help monitor the progress of various policies and programmes, including those such as the Healthy People 2010 initiative in America, which aims to increase the quality and years of healthy life and decrease health disparities by the end of this decade.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed. 0050046.
Healthy People 2010 was created by the US Department of Health and Human Services along with scientists inside and outside of government and includes a comprehensive set of disease prevention and health promotion objectives for the US to achieve by 2010, with two overarching goals: to increase quality and years of healthy life and to eliminate health disparities
Johan Mackenbach and colleagues provide an overview of mortality inequalities in six Western European countries—Finland, Sweden, Norway, Denmark, England/Wales, and Italy—and conclude that eliminating mortality inequalities requires that more cardiovascular deaths among lower socioeconomic groups be prevented, as well as more attention be paid to rising death rates of lung cancer, breast cancer, respiratory disease, gastrointestinal disease, and injuries among women and men in the lower income groups.
The WHO Health for All program promotes health equity
A primer on absolute versus relative differences is provided by the American College of Physicians
doi:10.1371/journal.pmed.0050046
PMCID: PMC2253609  PMID: 18303941
12.  Child Mortality Estimation: Consistency of Under-Five Mortality Rate Estimates Using Full Birth Histories and Summary Birth Histories 
PLoS Medicine  2012;9(8):e1001296.
Romesh Silva assesses and analyzes differences in direct and indirect methods of estimating under-five mortality rates using data collected from full and summary birth histories in Demographic and Health Surveys from West Africa, East Africa, Latin America, and South/Southeast Asia.
Background
Given the lack of complete vital registration data in most developing countries, for many countries it is not possible to accurately estimate under-five mortality rates from vital registration systems. Heavy reliance is often placed on direct and indirect methods for analyzing data collected from birth histories to estimate under-five mortality rates. Yet few systematic comparisons of these methods have been undertaken. This paper investigates whether analysts should use both direct and indirect estimates from full birth histories, and under what circumstances indirect estimates derived from summary birth histories should be used.
Methods and Findings
Usings Demographic and Health Surveys data from West Africa, East Africa, Latin America, and South/Southeast Asia, I quantify the differences between direct and indirect estimates of under-five mortality rates, analyze data quality issues, note the relative effects of these issues, and test whether these issues explain the observed differences. I find that indirect estimates are generally consistent with direct estimates, after adjustment for fertility change and birth transference, but don't add substantial additional insight beyond direct estimates. However, choice of direct or indirect method was found to be important in terms of both the adjustment for data errors and the assumptions made about fertility.
Conclusions
Although adjusted indirect estimates are generally consistent with adjusted direct estimates, some notable inconsistencies were observed for countries that had experienced either a political or economic crisis or stalled health transition in their recent past. This result suggests that when a population has experienced a smooth mortality decline or only short periods of excess mortality, both adjusted methods perform equally well. However, the observed inconsistencies identified suggest that the indirect method is particularly prone to bias resulting from violations of its strong assumptions about recent mortality and fertility. Hence, indirect estimates of under-five mortality rates from summary birth histories should be used only for populations that have experienced either smooth mortality declines or only short periods of excess mortality in their recent past.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
In 1990, 12 million children died before they reached their fifth birthday. Faced with this largely avoidable loss of young lives, in 2000, world leaders set a target of reducing under-five mortality (death) to one-third of its 1990 level by 2015 as Millennium Development Goal 4 (MDG 4); this goal, together with seven others, aims to eradicate extreme poverty globally. To track progress towards MDG 4, experts need accurate estimates of the global and country-specific under-five mortality rate (U5MR, the probability of a child dying before age five). The most reliable sources of data for U5MR estimation are vital registration systems—national records of all births and deaths. Unfortunately, developing countries, which are where most childhood deaths occur, rarely have such records, so full or summary birth histories provide the data for U5MR estimation instead. In full birth histories (FBHs), which are collected through household surveys such as those conducted by Demographic and Health Surveys (DHS), women are asked for the date of birth of all their children and the age at death of any children who have died. In summary birth histories (SBHs), which are collected through household surveys and censuses, women are asked how many children they have had and how many are alive at the time of the survey.
Why Was This Study Done?
“Direct” estimates of U5MRs can be obtained from FBHs because FBHs provide detailed information about the date of death and the exposure of children to the risk of dying. By contrast, because SBHs do not contain information on children's exposure to the risk of dying, “indirect” estimates of U5MR are obtained from SBHs using model life tables (mathematical models of the variation of mortality with age). Indirect estimates are often also derived from FBHs, but few systematic comparisons of direct and indirect methods for U5MR estimation have been undertaken. In this study, Romesh Silva investigates whether direct and indirect methods provide consistent U5MR estimates from FBHs and whether there are any circumstances under which indirect methods provide more reliable U5MR estimates than direct methods.
What Did the Researcher Do and Find?
The researcher used DHS data from West Africa, East Africa, Latin America, and South/Southeast Asia to quantify the differences between direct and indirect estimates of U5MR calculated from the same data and analyzed possible reasons for these differences. Estimates obtained using a version of the “Brass” indirect estimation method were uniformly higher than those obtained using direct estimation. Indirect and direct estimates generally agreed, however, after adjustment for changes in fertility—the Brass method assumes that country-specific fertility (the number of children born to a woman during her reproductive life) remains constant—and for birth transference, an important source of data error in FBHs that arises because DHS field staff can lessen their workload by recording births as occurring before a preset cutoff date rather than after that date. Notably, though, for countries that had experienced political or economic crises, periods of excess mortality due to conflicts, or periods during which the health transition had stalled (as countries become more affluent, overall mortality rates decline and noncommunicable diseases replace infectious diseases as the major causes of death), marked differences between indirect and direct estimates of U5MR remained, even after these adjustments.
What Do These Findings Mean?
Because the countries included in this study do not have vital registration systems, these findings provide no information about the validity of either direct or indirect estimation methods for U5MR estimation. They suggest, however, that for countries where there has been a smooth decline in mortality or only short periods of excess mortality, both direct and indirect methods of U5MR estimation work equally well, after adjustment for changes in fertility and for birth transference, and that indirect estimates add little to the insights provided into childhood mortality by direct estimates. Importantly, the inconsistencies observed between the two methods that remain after adjustment suggest that indirect U5MR estimation is more susceptible to bias (systematic errors that arise because of the assumptions used to estimate U5MR) than direct estimation. Thus, indirect estimates of U5MR from SBHs should be used only for populations that have experienced either smooth mortality declines or only short periods of excess mortality in their recent past.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001296.
This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 UN IGME report Levels & Trends in Child Mortality is available
The World Health Organization has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages)
Further information about the Millennium Development Goals is available
Information is available about infant and child mortality data collected by Demographic and Health Surveys
doi:10.1371/journal.pmed.1001296
PMCID: PMC3429405  PMID: 22952436
13.  Disability Transitions and Health Expectancies among Adults 45 Years and Older in Malawi: A Cohort-Based Model 
PLoS Medicine  2013;10(5):e1001435.
Collin Payne and colleagues investigated development of disabilities and years expected to live with disabilities in participants 45 years and older participating in the Malawi Longitudinal Survey of Families and Health.
Please see later in the article for the Editors' Summary
Background
Falling fertility and increasing life expectancy contribute to a growing elderly population in sub-Saharan Africa (SSA); by 2060, persons aged 45 y and older are projected to be 25% of SSA's population, up from 10% in 2010. Aging in SSA is associated with unique challenges because of poverty and inadequate social supports. However, despite its importance for understanding the consequences of population aging, the evidence about the prevalence of disabilities and functional limitations due to poor physical health among older adults in SSA continues to be very limited.
Methods and Findings
Participants came from 2006, 2008, and 2010 waves of the Malawi Longitudinal Survey of Families and Health, a study of the rural population in Malawi. We investigate how poor physical health results in functional limitations that limit the day-to-day activities of individuals in domains relevant to this subsistence-agriculture context. These disabilities were parameterized based on questions from the SF-12 questionnaire about limitations in daily living activities. We estimated age-specific patterns of functional limitations and the transitions over time between different disability states using a discrete-time hazard model. The estimated transition rates were then used to calculate the first (to our knowledge) microdata-based health expectancies calculated for SSA. The risks of experiencing functional limitations due to poor physical health are high in this population, and the onset of disabilities happens early in life. Our analyses show that 45-y-old women can expect to spend 58% (95% CI, 55%–64%) of their remaining 28 y of life (95% CI, 25.7–33.5) with functional limitations; 45-y-old men can expect to live 41% (95% CI, 35%–46%) of their remaining 25.4 y (95% CI, 23.3–28.8) with such limitations. Disabilities related to functional limitations are shown to have a substantial negative effect on individuals' labor activities, and are negatively related to subjective well-being.
Conclusions
Individuals in this population experience a lengthy struggle with disabling conditions in adulthood, with high probabilities of remitting and relapsing between states of functional limitation. Given the strong association of disabilities with work efforts and subjective well-being, this research suggests that current national health policies and international donor-funded health programs in SSA inadequately target the physical health of mature and older adults.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The population of the world is getting older. In almost every country, the over-60 age group is growing faster than any other age group. In 2000, globally, there were about 605 million people aged 60 years or more; by 2050, 2 billion people will be in this age group. Much of this increase in the elderly population will be in low-income countries. In sub-Saharan Africa, for example, 10% of the population is currently aged 45 years or more, but by 2060, a quarter of the population will be so-called mature adults. In all countries, population aging is the result of women having fewer children (falling fertility) and people living longer (increasing life expectancy). Thus, population aging is a demographic transition, a change in birth and death rates. In low- and middle-income countries, population aging is occurring in parallel with an “epidemiological transition,” a shift from communicable (infectious) diseases to non-communicable diseases (for example, heart disease) as the primary causes of illness and death.
Why Was This Study Done?
Both the demographic and the epidemiological transition have public health implications for low-income countries. Good health is important for the independence and economic productivity of older people. Productive older people can help younger populations financially and physically, and help compensate for the limitations experienced by younger populations infected with HIV. Also, low-income countries lack social safety nets, so disabled older adults can be a burden on younger populations. Thus, the health of older individuals is important to the well-being of people of all ages. As populations age, low-income countries will need to invest in health care for mature and elderly adults and in disease prevention programs to prevent or delay the onset of non-communicable diseases, which can limit normal daily activities by causing disabilities. Before providing these services, national policy makers need to know the proportion of their population with disabilities, the functional limitations caused by poor physical health, and the health expectancies (the number of years a person can expect to be in good health) of older people in their country. In this cohort modeling study, the researchers estimate health expectancies and transition rates between different levels of disability among mature adults in Malawi, one of the world's poorest countries, using data collected by the Malawi Longitudinal Survey of Families and Health (MLSFH) on economic, social, and health conditions in a rural population. Because Malawi has shorter life expectancies and earlier onset of disability than wealthier countries, the authors considered individuals aged 45 and older as mature adults at risk for disability.
What Did the Researchers Do and Find?
The researchers categorized the participants in the 2006, 2008, and 2010 waves of the MLSFH into three levels of functional limitation (healthy, moderately limited, and severely limited) based on answers to questions in the SF-12 health survey questionnaire that ask about disabilities that limit daily activities that rural Malawians perform. The researchers estimated age–gender patterns of functional limitations and transition rates between different disability states using a discrete-time hazard model, and health expectancies by running a microsimulation to model the aging of synthetic cohorts with various starting ages but the same gender and functional limitation distributions as the study population. These analyses show that the chance of becoming physically disabled rises sharply with age, with 45-year-old women in rural Malawi expected to spend 58% of their estimated remaining 28 years with functional limitations, and 45-year-old men expected to live 41% of their remaining 25.4 years with functional limitations. Also, on average, a 45-year-old woman will spend 2.7 years with moderate functional limitation and 0.6 years with severe functional limitation before she reaches 55; for men the corresponding values are 1.6 and 0.4 years. Around 50% of moderately and 60%–80% of severely limited individuals stated that pain interfered quite a bit or extremely with their normal work during the past four weeks, suggesting that pain treatment may help reduce disability.
What Do These Findings Mean?
These findings suggest that mature adults in rural Malawi will have some degree of disability during much of their remaining lifetime. The risks of experiencing functional limitations are higher and the onset of persistent disabilities happens earlier in Malawi than in more developed contexts—the proportions of remaining life spent with severe limitations at age 45 in Malawi are comparable to those of 80-year-olds in the US. The accuracy of these findings is likely to be affected by assumptions made during modeling and by the quality of the data fed into the models. Nevertheless, these findings suggest that functional limitations, which have a negative effect on the labor activity of individuals, will become more prominent in Malawi (and probably other sub-Saharan countries) as the age composition of populations shifts over the coming years. Older populations in sub-Saharan Africa are not targeted well by health policies and programs at present. Consequently, these findings suggest that policy makers will need to ensure that additional financial resources are provided to improve health-care provision for aging individuals and to lessen the high rates of functional limitation and associated disabilities.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001435.
This study is further discussed in a PLoS Medicine Perspective by Andreas Stuck, et al.
The World Health Organization provides information on many aspects of aging (in several languages); the WHO Study on Global Ageing and Adult Health (SAGE) is compiling longitudinal information on the health and well-being of adult populations and the aging process
The United Nations Population Fund and HelpAge International publication Ageing in the Twenty-First Century is available
HelpAge International is an international nongovernmental organization that helps older people claim their rights, challenge discrimination, and overcome poverty, so that they can lead dignified, secure, and healthy lives
More information on the Malawi Longitudinal Study of Families and Health is available
doi:10.1371/journal.pmed.1001435
PMCID: PMC3646719  PMID: 23667343
14.  Birth Outcome in Women with Previously Treated Breast Cancer—A Population-Based Cohort Study from Sweden 
PLoS Medicine  2006;3(9):e336.
Background
Data on birth outcome and offspring health after the appearance of breast cancer are limited. The aim of this study was to assess the risk of adverse birth outcomes in women previously treated for invasive breast cancer compared with the general population of mothers.
Methods and Findings
Of all 2,870,932 singleton births registered in the Swedish Medical Birth Registry during 1973–2002, 331 first births following breast cancer surgery—with a mean time to pregnancy of 37 mo (range 7–163)—were identified using linkage with the Swedish Cancer Registry.
Logistic regression analysis was used. The estimates were adjusted for maternal age, parity, and year of delivery. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate infant health and mortality, delivery complications, the risk of preterm birth, and the rates of instrumental delivery and cesarean section.
The large majority of births from women previously treated for breast cancer had no adverse events. However, births by women exposed to breast cancer were associated with an increased risk of delivery complications (OR 1.5, 95% CI 1.2–1.9), cesarean section (OR 1.3, 95% CI 1.0–1.7), very preterm birth (<32 wk) (OR 3.2, 95% CI 1.7–6.0), and low birth weight (<1500 g) (OR 2.9, 95% CI 1.4–5.8). A tendency towards an increased risk of malformations among the infants was seen especially in the later time period (1988–2002) (OR 2.1, 95% CI 1.2–3.7).
Conclusions
It is reassuring that births overall were without adverse events, but our findings indicate that pregnancies in previously treated breast cancer patients should possibly be regarded as higher risk pregnancies, with consequences for their surveillance and management.
The large majority of births from women previously treated for breast cancer had no adverse events, but such pregnancies might benefit from increased surveillance and management.
Editors' Summary
Background.
More women of all ages are developing breast cancer than ever before. In the US, one woman in eight will now develop this disease during her lifetime. For most of these women, their breast cancer diagnosis will come late in life, but a fifth of breast cancers are diagnosed before the age of 50. These days, the long-term outlook for women with breast cancer is quite good; 80% of women who receive a diagnosis of breast cancer survive more than five years. These figures, together with a trend towards starting families later in life—since the late 1970s birth rates for women in their late 30s and 40s have more than doubled in the US, and in Sweden the average age for having a first baby is now 29 years—mean that many women who have had breast cancer want to have children. One estimate is that up to 7% of women who are fertile after treatment for breast cancer will later have children.
Why Was This Study Done?
Pregnancy seems to have no adverse affects on women who have had breast cancer—there is no evidence that pregnancy can trigger a relapse. However, little is known about whether the chemotherapy and radiotherapy used to treat breast cancer have any long-lasting effects that might result in a poor birth outcome such as stillbirth, low birth weight, premature delivery, or abnormalities in the baby (congenital abnormalities). In this study, the researchers assessed the risk of adverse birth outcomes in women previously treated for breast cancer in Sweden.
What Did the Researchers Do and Find?
Nearly three million singleton births that occurred between 1973 and 2002 are recorded in the Swedish Medical Birth Registry. The researchers linked this information with that in the Swedish Cancer Registry to identify 331 first births after treatment for invasive breast cancer (cancer that has spread from where it started to grow in the breast). The birth registry includes details on maternal age and health, child's birth weight, whether the delivery was preterm, and whether the child had any congenital abnormalities, so the researchers were able to compare birth outcomes in these 331 births with those in the general population. They discovered that most births after breast cancer treatment went smoothly. There was no increase in stillbirths, but there were slightly more delivery complications in the women who had had breast cancer than in the general population, and a slight increase in babies born prematurely or with low birth weight. Finally, a few more babies with congenital abnormalities were born to women after breast cancer treatment than to women in the general population.
What Do These Findings Mean?
Overall, these results should reassure women who are thinking about having children after breast cancer about the health of their future offspring. However, they do suggest that these women may need careful monitoring during late pregnancy and delivery. This result was not predicted by the researchers who performed the study. Before starting the study, they thought that there would be no difference in birth outcomes between patients previously treated for breast cancer and the general population. Furthermore, a recently published similar study in Denmark found no increased risk of preterm birth, low birth weight, or congenital abnormalities after breast cancer. Differences between the two countries in the accuracy of their registries or in the use of chemotherapy and radiotherapy treatments may account for this difference in results. Additional studies are now needed in other populations to resolve this discrepancy and to provide more information about how breast cancer treatment might affect birth outcomes. For example, the current study did not provide any information about whether specific chemotherapy regimens or different types of breast cancer might put women at a higher risk of adverse birth outcomes, or whether the time between the cancer diagnosis and treatment and the pregnancy made a difference.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030336.
MedlinePlus encyclopedia entry on breast cancer
National Cancer Institute information for patients and physicians on breast cancer, including links to pages on breast cancer and pregnancy
Cancer Research UK's information on breast cancer for patients, and statistics on breast cancer in the UK
• Wikipedia page on breast cancer (note: Wikipedia is a free online encyclopedia that anyone can edit)
Royal College of Obstetricians and Gynaecologists guidelines for physicians on pregnancy and breast cancer
doi:10.1371/journal.pmed.0030336
PMCID: PMC1564170  PMID: 16968117
15.  Child Mortality Estimation: A Global Overview of Infant and Child Mortality Age Patterns in Light of New Empirical Data 
PLoS Medicine  2012;9(8):e1001299.
Michel Guillot and colleagues did a systematic evaluation to assess what proportion of under-five mortality occurs below age one compared with at age one and above, to determine how much observed values deviate from so called “model age patterns” of under-five mortality
Background
The under-five mortality rate (the probability of dying between birth and age 5 y, also denoted in the literature as U5MR and 5q0) is a key indicator of child health, but it conceals important information about how this mortality is distributed by age. One important distinction is what amount of the under-five mortality occurs below age 1 y (1q0) versus at age 1 y and above (4q1). However, in many country settings, this distinction is often difficult to establish because of various types of data errors. As a result, it is common practice to resort to model age patterns to estimate 1q0 and 4q1 on the basis of an observed value of 5q0. The most commonly used model age patterns for this purpose are the Coale and Demeny and the United Nations systems. Since the development of these models, many additional sources of data for under-five mortality have become available, making possible a general evaluation of age patterns of infant and child mortality. In this paper, we do a systematic comparison of empirical values of 1q0 and 4q1 against model age patterns, and discuss whether observed deviations are due to data errors, or whether they reflect true epidemiological patterns not addressed in existing model life tables.
Methods and Findings
We used vital registration data from the Human Mortality Database, sample survey data from the World Fertility Survey and Demographic and Health Surveys programs, and data from Demographic Surveillance Systems. For each of these data sources, we compared empirical combinations of 1q0 and 4q1 against combinations provided by Coale and Demeny and United Nations model age patterns. We found that, on the whole, empirical values fall relatively well within the range provided by these models, but we also found important exceptions. Sub-Saharan African countries have a tendency to exhibit high values of 4q1 relative to 1q0, a pattern that appears to arise for the most part from true epidemiological causes. While this pattern is well known in the case of western Africa, we observed that it is more widespread than commonly thought. We also found that the emergence of HIV/AIDS, while perhaps contributing to high relative values of 4q1, does not appear to have substantially modified preexisting patterns. We also identified a small number of countries scattered in different parts of the world that exhibit unusually low values of 4q1 relative to 1q0, a pattern that is not likely to arise merely from data errors. Finally, we illustrate that it is relatively common for populations to experience changes in age patterns of infant and child mortality as they experience a decline in mortality.
Conclusions
Existing models do not appear to cover the entire range of epidemiological situations and trajectories. Therefore, model life tables should be used with caution for estimating 1q0 and 4q1 on the basis of 5q0. Moreover, this model-based estimation procedure assumes that the input value of 5q0 is correct, which may not always be warranted, especially in the case of survey data. A systematic evaluation of data errors in sample surveys and their impact on age patterns of 1q0 and 4q1 is urgently needed, along with the development of model age patterns of under-five mortality that would cover a wider range of epidemiological situations and trajectories.
Please see later in the article for the Editors' Summary.
Editors' Summary
Background
In 2000, world leaders agreed on eight Millennium Development Goals designed to end extreme poverty by 2015. The fourth of these goals—MDG 4—aims to reduce under-five mortality (the number of children who die before their fifth birthday) to a third of its 1990 level by 2015. A key indicator used to monitor progress towards this target is the under-five mortality rate (the probability of a child dying before his/her fifth birthday, also denoted as U5MR or 5q0). In developed countries, data collected through vital registration systems (which record all births and deaths) are used to calculate 5q0. However, developing countries, which are where most under-five deaths occur, rarely have vital registration systems, and 5q0 is estimated using data collected by programs such as the World Fertility Survey (WFS) and Demographic and Health Surveys (DHS), which conduct nationally representative surveys that ask a sample of women about their living and dead children.
Why Was This Study Done?
Although 5q0 is a key indicator of child health, it conceals important information about the age distribution of child deaths. Public health experts need to know the distribution of 5q0 with respect to 1q0 (the probability that an infant will die before age one) and 4q1 (the probability that a child reaching age one will die below age five) to help them reduce child mortality. At a given level of 5q0, high values of 1q0 indicate high levels of death from congenital (inherited) anomalies and conditions that occur around the time of birth; these deaths can be reduced by improving the care of women during pregnancy and childbirth and the care of newborn babies. By contrast, at a given level of 5q0, high values of 4q1 indicate high levels of death from infectious diseases; these deaths can be reduced by, for example, introducing immunization programs. 1q0 and 4q1 are usually estimated from observed (empirical) values of 5q0 using the Coale and Demeny or United Nations (UN) “model life tables” (mathematical models of the variation of mortality with age), which were constructed in 1966 and 1982, respectively, using the best data available. Since their construction, additional sources of data about under-five mortality have become available; in this study, the researchers systematically compare global empirical values of 1q0 and 4q1 with values obtained using model life tables.
What Did the Researchers Do and Find?
The researchers compared empirical combinations of 1q0 and 4q1 (estimated using vital registration data, WFS and DHS data, and data from Demographic Surveillance Sites in sub-Saharan Africa) with the combinations derived from 5q0 using the Coale and Demeny and UN model life tables. The empirical values mainly fell within the range provided by these tables, but there were important exceptions. For example, empirical values of 4q1 relative to 1q0 tended to be above the range provided by the model life tables for sub-Saharan African countries. This pattern was mainly because of epidemiological reasons (epidemiology is the study of disease patterns in populations), such as the occurrence of diseases such as malaria, measles, and diarrhea that generate excess mortality among children older than one year. Interestingly, the emergence of HIV does not seem to have substantially modified preexisting patterns of 1q0 versus 4q1. Importantly, the researchers also show that populations often experience changes in the age patterns of infant and child mortality as they experience an overall decline in mortality.
What Do These Findings Mean?
These findings suggest that the existing model life tables do not cover the entire global range of epidemiological situations and trajectories and must, therefore, be used with caution for estimating 1q0 and 4q1 on the basis of 5q0. The development of new model age patterns of under-five mortality that cover a wider range of epidemiological situations should improve this situation, but a systematic analysis of data errors in sample surveys and the impact of such errors on estimates of 1q0 and 4q1 is also urgently needed to ensure that public health experts have access to accurate information on child mortality. Importantly, this overview shows that a wide range of 1q0 and 4q1 combinations can occur at a given level of 5q0. Because the level of 4q1 relative to 1q0 provides important information about the disease processes occurring in a population, this finding highlights the importance of determining 1q0 and 4q1 as well as 5q0 whenever possible.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001299.
This paper is part of a collection of papers on Child Mortality Estimation Methods published in PLOS Medicine
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4, and its Childinfo website provides detailed statistics about child survival and health, including a description of the United Nations Inter-agency Group for Child Mortality Estimation; the 2011 UN IGME report Levels & Trends in Child Mortality is available
The World Health Organization also has information about Millennium Development Goal 4 and provides estimates of child mortality rates (some information in several languages)
Further information about the Millennium Development Goals is available
Information is also available about the Human Mortality Database, which holds vital registration data; the World Fertility Survey program; the Demographic and Health Surveys program; and model life tables
doi:10.1371/journal.pmed.1001299
PMCID: PMC3429403  PMID: 22952438
16.  Pregnancy and Infant Outcomes among HIV-Infected Women Taking Long-Term ART with and without Tenofovir in the DART Trial 
PLoS Medicine  2012;9(5):e1001217.
Diana Gibb and colleagues investigate the effect of in utero tenofovir exposure by analyzing the pregnancy and infant outcomes of HIV-infected women enrolled in the DART trial.
Background
Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)–recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure.
Methods and Findings
Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models.
382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0–4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (<22 wk). Of 226 live-births, seven (3%) infants died <2 wk from perinatal causes and there were seven (3%) congenital abnormalities, with no effect of in utero tenofovir exposure (p>0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12–38) months. From mothers' ART, 62/9/111 infants had no/20%–89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75–212) days. Overall, 14 infants died at median (IQR) age 9 (3–23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14 children with no effect of in utero tenofovir (p>0.1). There was no evidence that in utero tenofovir affected growth after 2 years (p = 0.38). Attained height- and weight for age were similar to general (HIV-uninfected) Ugandan populations. Study limitations included relatively small size and lack of randomisation to maternal ART regimens.
Conclusions
Overall 1-year 5% infant mortality was similar to the 2%–4% post-neonatal mortality observed in this region. No increase in congenital, renal, or growth abnormalities was observed with in utero tenofovir exposure. Although some infants died untested, absence of recorded HIV infection with combination ART in pregnancy is encouraging. Detailed safety of tenofovir for pre-exposure prophylaxis will need confirmation from longer term follow-up of larger numbers of exposed children.
Trial registration
www.controlled-trials.com ISRCTN13968779
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Currently, about 34 million people (mostly in low- and middle-income countries) are infected with HIV, the virus that causes AIDS. At the beginning of the epidemic, more men than women were infected with HIV but now about half of all people living with HIV/AIDS are women, most of who became infected through unprotected sex with an infected partner. In sub-Saharan Africa alone, 12 million women are HIV-positive. Worldwide, HIV/AIDS is the leading cause of death among women of child-bearing age. Moreover, most of the 400,000 children who become infected with HIV every year acquire the virus from their mother during pregnancy or birth, or through breastfeeding, so-called mother-to-child transmission (MTCT). Combination antiretroviral therapy (ART)—treatment with cocktails of powerful antiretroviral drugs—reduces HIV-related illness and death among women, and ART given to HIV-positive mothers during pregnancy and delivery and to their newborn babies greatly reduces MTCT.
Why Was This Study Done?
Because of ongoing international efforts to increase ART coverage, more HIV-positive women in Africa have access to ART now than ever before. However, little is known about pregnancy outcomes among HIV-infected African women taking ART throughout pregnancy for their own health or about the long-term outcomes of their offspring. In particular, few studies have examined the effect of taking tenofovir (an antiretroviral drug that is now recommended as part of first-line ART) throughout pregnancy. Tenofovir readily crosses from mother to child during pregnancy and, in animal experiments, high doses of tenofovir given during pregnancy caused bone demineralization (which weakens bones), kidney problems, and impaired growth among offspring. In this study, the researchers analyze data collected on pregnancy and infant outcomes among Ugandan and Zimbabwean HIV-positive women who took ART throughout pregnancy in the Development of AntiRetroviral Therapy in Africa (DART) trial. This trial was designed to test whether ART could be safely and effectively delivered in Africa without access to the expensive laboratory tests that are routinely used to monitor ART toxicity and efficacy in developed countries.
What Did the Researchers Do and Find?
The pregnancy outcomes of 302 women who became pregnant during the DART trial and information on birth defects among their babies were collected as part of the DART protocol; information on the survival, growth, and development of the infants born to these women was collected in a separate infant study. Most of the women who became pregnant were taking tenofovir-containing ART before and throughout their pregnancies. 58% of the pregnancies resulted in a live birth, 7% resulted in a stillbirth (birth of a dead baby at any time from 22 weeks gestation to the end of pregnancy), and 35% resulted in a termination or miscarriage (before 22 weeks gestation). Of the 226 live births, seven infants died within 2 weeks and seven had birth defects. Similar proportions of the infants exposed and not exposed to tenofovir during pregnancy died soon after birth or had birth defects. Of the 182 surviving infants who were enrolled in the infant study, 14 subsequently died at an average age of 9 months, giving a 1-year mortality of 5%. None of the surviving children who were tested (172 infants) were HIV infected. No bone fractures or major kidney problems occurred during follow-up and prebirth exposure to tenofovir in utero had no effect on growth or weight gain at 2 years (in contrast to a previous US study).
What Do These Findings Mean?
By showing that prebirth tenofovir exposure does not affect pregnancy outcomes or increase birth defects, growth abnormalities, or kidney problems, these findings support the use of tenofovir-containing ART during pregnancy among HIV-positive African women, and suggest that it could also be used to prevent women of child-bearing age acquiring HIV-infection heterosexually. Notably, the observed 5% 1-year infant mortality is similar to the 2%–4% infant mortality normally seen in the region. The absence of HIV infection among the infants born to the DART participants is also encouraging. However, this is a small study (only 111 infants were exposed to tenofovir throughout pregnancy) and women were not randomly assigned to receive tenofovir-containing ART. Consequently, more studies are needed to confirm that tenofovir exposure during pregnancy does not affect pregnancy outcomes or have any long-term effects on infants. Such studies are essential because the use of tenofovir as a treatment for women who are HIV-positive is likely to increase and tenofovir may also be used in the future to prevent HIV acquisition in HIV-uninfected women.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001217.
Information is available from the US National Institute of Allergy and infectious diseases on all aspects of HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, and summaries of recent research findings on HIV care and treatment (in several languages)
Information is available from Avert, an international AIDS nonprofit on many aspects of HIV/AIDS, including detailed information on HIV/AIDS treatment and care, women, HIV and AIDS, children, HIV and AIDS, and on HIV/AIDS and pregnancy (some information in English and Spanish); personal stories of women living with HIV are available
More information about the DART trial is available
Additional patient stories about living with HIV/AIDS are available through the nonprofit website Healthtalkonline
doi:10.1371/journal.pmed.1001217
PMCID: PMC3352861  PMID: 22615543
17.  Differences in neonatal and postneonatal mortality by race, birth weight, and gestational age. 
Public Health Reports  1987;102(2):182-192.
In recent decades, neonatal and postneonatal mortality rates have declined overall in the United States. Yet, the mortality rates for black infants continue to be approximately twice those for white infants. With the use of data from 45 of the 53 vital statistics reporting areas that participated in the 1980 National Infant Mortality Surveillance project, we extended previous State analyses to describe differences, nationally, in neonatal and postneonatal mortality risks for black and white infants according to gestational age and birth weight. After restricting our analysis to single-delivery infants with known and plausible combinations of gestational age of 26 or more weeks and birth weights of 500 grams (g) or more, the neonatal mortality risk (NMR)--that is, the number of deaths to infants less than 28 days of life per 1,000 live births--for black infants was 1.6 times higher than the NMR for whites. This difference was largely explained by two findings: First, although the NMR was lower for black than for white infants with gestational ages of less than 38 weeks and birth weights less than 3,000 g, that advantage was heavily outweighed by the higher percentage of such births among blacks, accounting for roughly two-thirds of the overall difference in NMR between blacks and whites. Second, most of the remaining difference in NMR was accounted for by higher NMRs among black infants with gestational ages of 38 or more weeks and birth weights of 3,000 g or more. A comparison of the lowest mortality risk for any combination of birth weight and gestational age showed that the black NMR was 1.89 times higher than the white NMR. The postneonatal mortality risk (PNMR)--PNMR equals the number of deaths to infants 28 days to less than 1 year of life per 1,000 neonatal survivors--for black infants was 2.09 times the PNMR for white infants. Black infants had higher PNMRs than white infants for nearly all combinations of birth weight and gestational age. Higher PNMRs among infants with gestational ages of 38 or more weeks and birth weights of 2,500 g or more accounted for 43 percent of the difference in PNMR between black infants and white infants. Eliminating the U.S. black-white infant mortality disparity will require not only reducing the higher frequency of prematurity and low birth weight among black infants, but also improving the survival during both the neonatal and postneonatal periods of term black infants with normal birth weights.
PMCID: PMC1477813  PMID: 3104975
18.  US Birth Weight/Gestational Age-Specific Neonatal Mortality: 1995–1997 Rates for Whites, Hispanics, and Blacks 
Pediatrics  2003;111(1):e61-e66.
Objective
In recent years, gains in neonatal survival have been most evident among very low birth weight, preterm, and low birth weight (LBW) infants. Most of the improvement in neonatal survival since the early 1980s seems to be the consequence of decreasing birth weight-specific mortality rates, which occurred during a period of increasing preterm and LBW rates. Although the decline in neonatal mortality has been widely publicized in the United States, research suggests that clinicians may still underestimate the chances of survival of an infant who is born too early or too small and may overestimate the eventuality of serious disability. So that clinicians may have current and needed ethnic- and race-specific estimates of the “chances” of early survival for newborn infants, we examined birth weight/gestational age-specific neonatal mortality rates for the 3 largest ethnic/racial groups in the United States: non-Hispanic whites, Hispanics, and non-Hispanic blacks. Marked racial variation in birth weight and gestational age-specific mortality has long been recognized, and growing concerns have been raised about ongoing and increasing racial disparities in pregnancy outcomes. Our purpose for this investigation was to provide an up-to-date national reference for birth weight/gestational age-specific neonatal mortality rates for use by clinicians in care decision making and discussions with parents.
Methods
The National Center for Health Statistics linked live birth-infant death cohort files for 1995–1997 were used for this study. Singleton live births to US resident mothers with a reported maternal ethnicity/race of non-Hispanic white, non-Hispanic black, or Hispanic (n = 10 610 715) were selected for analysis. Birth weight/gestational age-specific neonatal mortality rates were calculated using 250 g/2-week intervals for each ethnic/racial group.
Results
The overall neonatal mortality rates for whites, Hispanics, and blacks were 3.24, 3.45, and 8.16 neonatal deaths per 1000 live births, and the proportion of births <28 weeks was 0.35%, 0.45%, and 1.39%, respectively. Newborns who weighed <1500 g comprised <2.5% of all births in each racial/ethnic group but accounted for >50% of neonatal deaths. For whites, Hispanics, and blacks, >50% of newborns 24 to 25 weeks of gestational age survived. For most combinations of birth weights <3500 g and gestational ages of <37 weeks, the neonatal mortality rate was lowest among blacks, compared with whites or Hispanics. At these same gestational age/birth weight combinations, Hispanics have slightly lower mortality rates than whites. For combinations of birth weights >3500 g and gestational ages of 37 to 41 weeks, Hispanics had the lowest neonatal mortality rate. In these birth weight/gestational age combinations, where approximately two thirds of births occur, blacks had the highest neonatal mortality rate.
Conclusions
Compared with earlier reports, these data suggest that a substantial improvement in birth weight/gestational age-specific neonatal mortality has occurred in the United States. Regardless of ethnicity/race, the risk of a neonatal death does not exceed 50% (the suggested definition for the limit of viability), except for birth weights below 500 g and gestational ages <24 weeks. Notwithstanding, ethnic/racial variations in neonatal mortality rates continue to persist, both in overall rates and within birth weight/gestational age categories. Blacks continue to have higher proportions for preterm and LBW births, compared with either whites or Hispanics. At the same time, blacks experience lower risks of neonatal mortality for preterm and LBW infants, while having higher risks of mortality among term, postterm, normal birth weight, and macrosomic births.
doi:10.1542/peds.111.1.e61
PMCID: PMC1382183  PMID: 12509596
VLBW, very low birth weight; LBW, low birth weight; BG-NMR, birth weight/gestational age-specific neonatal mortality rate; NCHS, National Center for Health Statistics; LMP, last normal menstrual period
19.  Donor Funding for Newborn Survival: An Analysis of Donor-Reported Data, 2002–2010 
PLoS Medicine  2012;9(10):e1001332.
With recent increases in development assistance money for maternal and child health, Catherine Pitt and colleagues examine whether foreign aid specifically for newborns has changed, whether it's on par with the burden of newborn deaths worldwide, and how such funding can be tracked.
Background
Neonatal mortality accounts for 43% of global under-five deaths and is decreasing more slowly than maternal or child mortality. Donor funding has increased for maternal, newborn, and child health (MNCH), but no analysis to date has disaggregated aid for newborns. We evaluated if and how aid flows for newborn care can be tracked, examined changes in the last decade, and considered methodological implications for tracking funding for specific population groups or diseases.
Methods and Findings
We critically reviewed and categorised previous analyses of aid to specific populations, diseases, or types of activities. We then developed and refined key terms related to newborn survival in seven languages and searched titles and descriptions of donor disbursement records in the Organisation for Economic Co-operation and Development's Creditor Reporting System database, 2002–2010. We compared results with the Countdown to 2015 database of aid for MNCH (2003–2008) and the search strategy used by the Institute for Health Metrics and Evaluation. Prior to 2005, key terms related to newborns were rare in disbursement records but their frequency increased markedly thereafter. Only two mentions were found of “stillbirth” and only nine references were found to “fetus” in any spelling variant or language. The total value of non-research disbursements mentioning any newborn search terms rose from US$38.4 million in 2002 to US$717.1 million in 2010 (constant 2010 US$). The value of non-research projects exclusively benefitting newborns fluctuated somewhat but remained low, at US$5.7 million in 2010. The United States and the United Nations Children's Fund (UNICEF) provided the largest value of non-research funding mentioning and exclusively benefitting newborns, respectively.
Conclusions
Donor attention to newborn survival has increased since 2002, but it appears unlikely that donor aid is commensurate with the 3.0 million newborn deaths and 2.7 million stillbirths each year. We recommend that those tracking funding for other specific population groups, diseases, or activities consider a key term search approach in the Creditor Reporting System along with a detailed review of their data, but that they develop their search terms and interpretations carefully, taking into account the limitations described.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 1990, 12 million children—most of them living in developing countries—died before they reached their fifth birthday. Faced with this largely avoidable loss of young lives, in 2000, world leaders set a target of reducing under-five mortality (deaths) to one-third of its 1990 level by 2015 as Millennium Development Goal 4 (MDG4); this goal, together with seven others, aims to eradicate extreme poverty globally. In recent years, progress towards reducing child mortality has accelerated but remains insufficient to achieve MDG4, in part, because progress towards reducing neonatal mortality—deaths during the first 28 days of life—has been particularly slow. Neonatal deaths now account for a greater proportion of global child deaths than in 1990—43% of the 7 million children who died before their fifth birthday in 2011 died during the neonatal period. The major causes of neonatal deaths are complications of preterm and term delivery and infections. Simple interventions such as improved hygiene at birth and advice on breastfeeding can substantially reduce neonatal deaths.
Why Was This Study Done?
To achieve MDG4, more must be done to prevent deaths among newborn babies. One reason that progress in reducing neonatal mortality is slow could be insufficient donor funding (aid) for newborn health. Previous analyses by, for example, Countdown to 2015 (which tracks coverage levels for health interventions that reduce maternal, newborn, and child mortality) indicate that donor funding has increased for maternal, newborn, and child health over the past decade, but how much of this aid directly benefits newborns is unknown. Here, the researchers develop a method for tracking aid flows for newborns and examine changes in this flow over the past decade by applying their new strategy to the Organisation for Economic Co-operation and Development (OECD) Creditor Reporting System (CRS) Aid Activity database. This database collects information about official development assistance for health given (disbursed) to developing countries by member countries of the OECD Development Assistance Committee, international organizations, and some private donors.
What Did the Researchers Do and Find?
The researchers developed a comprehensive set of search terms related to newborn survival by piloting it on the Countdown to 2015 official development assistance database, which covers the years 2003–2008. They then used their list of 24 key terms to search the CRS database from 2002 (the first year for which relatively complete disbursement data are available) to 2010 (the most recent year for which data are available) and classified each retrieved project according to whether its funding activities aimed to benefit newborns exclusively or to improve the health of other population groups as well. The researchers found that key terms related to newborns were rare in disbursement records before 2005 but that their frequency increased markedly thereafter. The total value of non-research disbursements (aid provided for programmatic or advocacy activities) that mentioned any newborn search terms increased from US$38.4 million in 2002 to US$717.1 million in 2010. The value of non-research projects that exclusively benefitted newborns fluctuated; in 2010, it was $US5.7 million. Finally, the US and United Nations Children's Fund (UNICEF) provided the largest value of non-research funding mentioning newborns and exclusively benefitting newborns, respectively.
What Do These Findings Mean?
These findings indicate that the value of aid disbursements mentioning newborns or an activity likely to benefit newborns increased 20-fold between 2002 and 2010 and constituted an increasing proportion of aid for maternal, newborn, and child health. Although this increase may partly reflect increased detail in aid disbursement reporting, it is also likely to reflect an increase in donor attention to newborn survival. The accuracy of these findings is likely to be affected by limitations in the search strategy and in the CRS database, which does not capture aid flows from emerging donors such as China or from many private foundations. Moreover, because these findings take no account of domestic expenditure, they do not provide a comprehensive estimate of the value of resources available in developing countries for newborn health. Nevertheless, investment in newborn survival is unlikely to be commensurate with global newborn mortality. Thus, an expansion of programmatic funding from donors as well as increased governmental support for newborn health in developing countries is urgently needed to catalyze the scale-up of cost-effective interventions to save newborn lives and to meet MDG4.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001332.
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4 and its Childinfo website provides detailed statistics about child survival and health, including the 2012 report of UN Inter-agency Group of Child Mortality Estimation; its Committing to Child Survival: a Promise Renewed webpage includes links to its 2012 progress report, to a video about progress made in reducing child deaths worldwide, and to stories about child survival in the field
The World Health Organization has information about Millennium Development Goal 4 and about maternal, newborn, child, and adolescent health (some information in several languages)
Countdown to 2015 provides additional information on maternal, newborn, and child survival, including its 2012 report Building a Future for Women and Children
The Healthy Newborn Network (HNN) is a community of more than 70 partner organizations addressing critical knowledge gaps for newborn health providing recent data on newborn survival and analyses of country programs
Information on and access to the Organisation for Economic Co-operation Development Creditor Reporting System Aid Activities database is available
Further information about the Millennium Development Goals is available
doi:10.1371/journal.pmed.1001332
PMCID: PMC3484125  PMID: 23118619
20.  Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies 
PLoS Medicine  2013;10(4):e1001418.
Leigh Johnson and colleagues estimate the life expectancies of HIV positive South African adults who are taking antiretroviral therapy by using information from 6 programmes between 2001 and 2010.
Background
Few estimates exist of the life expectancy of HIV-positive adults receiving antiretroviral treatment (ART) in low- and middle-income countries. We aimed to estimate the life expectancy of patients starting ART in South Africa and compare it with that of HIV-negative adults.
Methods and Findings
Data were collected from six South African ART cohorts. Analysis was restricted to 37,740 HIV-positive adults starting ART for the first time. Estimates of mortality were obtained by linking patient records to the national population register. Relative survival models were used to estimate the excess mortality attributable to HIV by age, for different baseline CD4 categories and different durations. Non-HIV mortality was estimated using a South African demographic model. The average life expectancy of men starting ART varied between 27.6 y (95% CI: 25.2–30.2) at age 20 y and 10.1 y (95% CI: 9.3–10.8) at age 60 y, while estimates for women at the same ages were substantially higher, at 36.8 y (95% CI: 34.0–39.7) and 14.4 y (95% CI: 13.3–15.3), respectively. The life expectancy of a 20-y-old woman was 43.1 y (95% CI: 40.1–46.0) if her baseline CD4 count was ≥200 cells/µl, compared to 29.5 y (95% CI: 26.2–33.0) if her baseline CD4 count was <50 cells/µl. Life expectancies of patients with baseline CD4 counts ≥200 cells/µl were between 70% and 86% of those in HIV-negative adults of the same age and sex, and life expectancies were increased by 15%–20% in patients who had survived 2 y after starting ART. However, the analysis was limited by a lack of mortality data at longer durations.
Conclusions
South African HIV-positive adults can have a near-normal life expectancy, provided that they start ART before their CD4 count drops below 200 cells/µl. These findings demonstrate that the near-normal life expectancies of HIV-positive individuals receiving ART in high-income countries can apply to low- and middle-income countries as well.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
According to the latest figures, more than 34 million people worldwide currently live with HIV/AIDS. In 2011, an estimated 2.5 million people were newly infected with HIV, and in the same year 1.7 million people died from AIDS. Since the beginning of the epidemic in the 1980s, more than 60 million people have contracted HIV and nearly 30 million have died of HIV-related causes. Despite the stark statistics, the life expectancy for people infected with the AIDS virus has dramatically improved over the past decade since the introduction of an effective combination of antiretroviral drugs. In high-income countries, people who are HIV-positive can expect a near-normal life expectancy if they take these drugs (as antiretroviral treatment—ART) throughout their life.
Why Was This Study Done?
Recent studies investigating the life expectancy of people living with HIV have mostly focused on the situation in high-income settings. The situation in low- and middle-income countries is vastly different. People who are diagnosed with HIV are often late in starting treatment, treatments regimes are sometimes interrupted, and a large proportion of patients are lost to follow-up. It is important to gain a realistic estimate of life expectancy in low- and middle-income countries so patients can be given the best information. So in this study the researchers used a model to estimate the life expectancy of patients starting ART in South Africa, using data from several ART programs.
What Did the Researchers Do and Find?
The researchers used data collected from six programs in South Africa based in Western Cape, Gauteng, and KwaZulu-Natal between 2001 and 2010. The researchers calculated the observation time from the time of ART initiation to the date of death or to the end of the study. Then the researchers used a relative survival approach to model the excess mortality attributable to HIV, relative to non-HIV mortality rates in South Africa, over different periods from ART initiation.
Using these methods, the researchers found that over the time period, 37,740 adults started ART and 2,066 deaths were recorded in patient record systems. Of the 16,250 patients who were lost to follow-up, the researchers identified 2,947 further deaths in the population register. When they inputted these figures into their model, the researchers estimated that the mortality rate was 83.2 per 1,000 person-years of observation (PYO), and was higher in males (99.8 per 1,000 PYO) than in females (72.6 per 1,000 PYO). The researchers also found that the most significant factor determining the life expectancy of treated patients was their age at ART initiation: the average life expectancy of men starting ART varied between 27.6 years at age 20 and 10.1 years at age 60, while corresponding estimates in women were 36.8 and 14.4, respectively. Life expectancies were also significantly influenced by baseline CD4 counts; life expectancies in patients with baseline CD4 counts ≥200 cells/µl were between 70% and 86% of those of HIV-negative adults of the same age and sex, while patients starting ART with CD4 counts of <50 cells/µl had life expectancies that were between 48% and 61% of those of HIV-negative adults. Importantly, the researchers found that life expectancies were also 15%–20% higher in patients who survived their first 24 months after starting ART than in patients of the same age who had just started therapy.
What Do These Findings Mean?
These findings suggest that in South Africa, patients starting ART have life expectancies around 80% of normal life expectancy, provided that they start treatment before their CD4 count drops below 200 cells/µl. Although these results are encouraging, this study highlights that health services must overcome major challenges, such as dealing with late diagnosis, low uptake of CD4 testing, loss from pre-ART care, and delayed ART initiation, if near-normal life expectancies are to be achieved for the majority of HIV-positive South Africans. With the anticipated increase in the fraction of patients starting ART at higher CD4 counts in the future, long-term survival can be expected to increase even further. It is therefore critical that appropriate funding systems and innovative ways to reduce costs are put in place, to ensure the long-term sustainability of ART delivery in low- and middle-income countries.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001418.
The International Epidemiologic Databases to Evaluate AIDS has more statistical information from world regions
amfAR, the Foundation for AIDS Research, works with health care workers and AIDS organizations in developing countries to create and implement effective HIV research, treatment, prevention, and education strategies
doi:10.1371/journal.pmed.1001418
PMCID: PMC3621664  PMID: 23585736
21.  Association between Clean Delivery Kit Use, Clean Delivery Practices, and Neonatal Survival: Pooled Analysis of Data from Three Sites in South Asia 
PLoS Medicine  2012;9(2):e1001180.
A pooled analysis of data from three studies in South Asia demonstrates an association between use of clean delivery kits during home births and reduced risk of neonatal mortality.
Background
Sepsis accounts for up to 15% of an estimated 3.3 million annual neonatal deaths globally. We used data collected from the control arms of three previously conducted cluster-randomised controlled trials in rural Bangladesh, India, and Nepal to examine the association between clean delivery kit use or clean delivery practices and neonatal mortality among home births.
Methods and Findings
Hierarchical, logistic regression models were used to explore the association between neonatal mortality and clean delivery kit use or clean delivery practices in 19,754 home births, controlling for confounders common to all study sites. We tested the association between kit use and neonatal mortality using a pooled dataset from all three sites and separately for each site. We then examined the association between individual clean delivery practices addressed in the contents of the kit (boiled blade and thread, plastic sheet, gloves, hand washing, and appropriate cord care) and neonatal mortality. Finally, we examined the combined association between mortality and four specific clean delivery practices (boiled blade and thread, hand washing, and plastic sheet). Using the pooled dataset, we found that kit use was associated with a relative reduction in neonatal mortality (adjusted odds ratio 0.52, 95% CI 0.39–0.68). While use of a clean delivery kit was not always accompanied by clean delivery practices, using a plastic sheet during delivery, a boiled blade to cut the cord, a boiled thread to tie the cord, and antiseptic to clean the umbilicus were each significantly associated with relative reductions in mortality, independently of kit use. Each additional clean delivery practice used was associated with a 16% relative reduction in neonatal mortality (odds ratio 0.84, 95% CI 0.77–0.92).
Conclusions
The appropriate use of a clean delivery kit or clean delivery practices is associated with relative reductions in neonatal mortality among home births in underserved, rural populations.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, around 3.3 million babies die in the first month of life, according to data for 2009 from the World Health Organization. Although the global neonatal mortality rate declined by 28% (from 33.2 deaths per 1,000 live births to 23.9) between 1990 and 2009, the proportion of child deaths that are now in the neonatal period has increased in all regions of the world, and currently stands at 41%. This figure is concerning and neonatal mortality remains a big obstacle to the international community in meeting the target of Millennium Development Goal 4—to reduce deaths in children under 5 years by two-thirds from 1990 levels by 2015. At least 15% of all neonatal deaths are due to sepsis (systematic bacterial infection) and an estimated 30%–40% of infections are transmitted at the time of birth. Therefore preventing infections through clean delivery practices is an important strategy to reduce sepsis-related deaths in newborns and can contribute to reducing the overall burden of neonatal deaths.
Why Was This Study Done?
In South Asia, around 65% of deliveries occur at home, without skilled birth attendants, making practices around clean delivery particularly challenging. To date, evidence on the impact of clean delivery kits and clean delivery practices on neonatal mortality or sepsis-related neonatal deaths from community-based studies is scarce. In this study the researchers explored the associations between neonatal mortality, the use of clean delivery kits, and individual clean delivery practices by using data from the control arms of three cluster-randomized controlled trials conducted among rural populations in South Asia.
What Did the Researchers Do and Find?
The researchers used data from almost 20,000 (19,754) home births available from the control arms of three community-based cluster-randomized trials conducted between 2000 and 2008 in India (n = 6,841, 18 clusters), Bangladesh (n = 7,041, five clusters), and Nepal (n = 5,872, five clusters). The researchers did not include data from other previously conducted trials on clean delivery practices because of the mix of designs used in these studies and limited their analysis to live-born singleton infants delivered at home in control areas, for whom data on birth kit use were available. The researchers conducted a separate analysis for each country on kit use and clean delivery practices and also analyzed the pooled dataset for all countries while controlling for factors about the mother, the pregnancy, the delivery, and the postnatal period.
Using these methods, the researchers found that kits were used for 18.4% of home births in India, 18.4% in Bangladesh, and 5.7% in Nepal. Importantly, according to the pooled analysis, kit use was associated with a 48% relative reduction in neonatal mortality (odds ratio/chance 0.52), which was similar across all countries: 57% relative reduction in neonatal mortality in India, 32% in Bangladesh, and 49% in Nepal. Delivery practices were also important: in the pooled country analysis, the use of a boiled blade to cut the cord, antiseptic to clean the cord, a boiled thread to tie the cord, and a plastic sheet for a clean delivery surface were all associated with significant relative reductions in mortality after controlling for kit use and confounders common to all sites. The researchers found a 16% relative reduction in mortality with each additional clean delivery practice used.
What Do These Findings Mean?
These findings show that the appropriate use of a clean delivery kit and clean delivery practices could lead to substantial reductions in neonatal mortality among home births in poor rural communities with limited access to health care. The results also reinforce the importance of each clean delivery practice; hand washing and use of a sterilised blade, boiled thread, and plastic sheet were linearly associated with a reduction in neonatal deaths with each additional clean delivery practice used. Costs of such kits are low (US$0.44 in India, US$0.40 in Nepal, and US$0.27 in Bangladesh, although these costs may still be prohibitive for the poorest women), and given the impact of clean delivery kits and clean delivery practices in reducing neonatal practices, such strategies should be widely promoted by the international community.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001180.
A recent PLoS Medicine study by Oestergaard et al. has the latest figures on neonatal mortality worldwide
UNICEF has information about progress toward Millennium Development Goal 4
The United Nations Population Fund has more information about safe birth practices
The EquiNam web site describes ongoing work on socioeconomic inequalities in newborn and maternal health in Asia and Africa by some of the study authors
doi:10.1371/journal.pmed.1001180
PMCID: PMC3289606  PMID: 22389634
22.  The Promise of Prevention: The Effects of Four Preventable Risk Factors on National Life Expectancy and Life Expectancy Disparities by Race and County in the United States 
PLoS Medicine  2010;7(3):e1000248.
Majid Ezzati and colleagues examine the contribution of a set of risk factors (smoking, high blood pressure, elevated blood glucose, and adiposity) to socioeconomic disparities in life expectancy in the US population.
Background
There has been substantial research on psychosocial and health care determinants of health disparities in the United States (US) but less on the role of modifiable risk factors. We estimated the effects of smoking, high blood pressure, elevated blood glucose, and adiposity on national life expectancy and on disparities in life expectancy and disease-specific mortality among eight subgroups of the US population (the “Eight Americas”) defined on the basis of race and the location and socioeconomic characteristics of county of residence, in 2005.
Methods and Findings
We combined data from the National Health and Nutrition Examination Survey and the Behavioral Risk Factor Surveillance System to estimate unbiased risk factor levels for the Eight Americas. We used data from the National Center for Health Statistics to estimate age–sex–disease-specific number of deaths in 2005. We used systematic reviews and meta-analyses of epidemiologic studies to obtain risk factor effect sizes for disease-specific mortality. We used epidemiologic methods for multiple risk factors to estimate the effects of current exposure to these risk factors on death rates, and life table methods to estimate effects on life expectancy. Asians had the lowest mean body mass index, fasting plasma glucose, and smoking; whites had the lowest systolic blood pressure (SBP). SBP was highest in blacks, especially in the rural South—5–7 mmHg higher than whites. The other three risk factors were highest in Western Native Americans, Southern low-income rural blacks, and/or low-income whites in Appalachia and the Mississippi Valley. Nationally, these four risk factors reduced life expectancy at birth in 2005 by an estimated 4.9 y in men and 4.1 y in women. Life expectancy effects were smallest in Asians (M, 4.1 y; F, 3.6 y) and largest in Southern rural blacks (M, 6.7 y; F, 5.7 y). Standard deviation of life expectancies in the Eight Americas would decline by 0.50 y (18%) in men and 0.45 y (21%) in women if these risks had been reduced to optimal levels. Disparities in the probabilities of dying from cardiovascular diseases and diabetes at different ages would decline by 69%–80%; the corresponding reduction for probabilities of dying from cancers would be 29%–50%. Individually, smoking and high blood pressure had the largest effect on life expectancy disparities.
Conclusions
Disparities in smoking, blood pressure, blood glucose, and adiposity explain a significant proportion of disparities in mortality from cardiovascular diseases and cancers, and some of the life expectancy disparities in the US.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Life expectancy (a measure of longevity and premature death) and overall health have increased steadily in the United States over recent years. New drugs, new medical technologies, and better disease prevention have all helped Americans to lead longer, healthier lives. However, even now, some Americans live much longer and much healthier lives than others. Health disparities—differences in how often certain diseases occur and cause death in groups of people classified according to their ethnicity, geographical location, sex, or age—are extremely large and persistent in the US. On average, black men and women in the US live 6.3 and 4.5 years less, respectively, than their white counterparts; the gap between life expectancy in the US counties with the lowest and highest life expectancies is 18.4 years for men and 14.3 years for women. Disparities in deaths (mortality) from chronic diseases such as cardiovascular diseases (for example, heart attacks and stroke), cancers, and diabetes are known to be the main determinants of these life expectancy disparities.
Why Was This Study Done?
Preventable risk factors such as smoking, high blood pressure, excessive body fat (adiposity), and high blood sugar are responsible for many thousands of deaths from chronic diseases. Exposure to these risk factors varies widely by race, state of residence, and socioeconomic status. However, the effects of these observed disparities in exposure to modifiable risk factors on US life expectancy disparities have only been examined in selected groups of people and it is not known how multiple modifiable risk factors affect US health disparities. A better knowledge about how disparities in risk factor exposure contribute to health disparities is needed to ensure that prevention programs not only improve the average health status but also reduce health disparities. In this study, the researchers estimate the effects of smoking, high blood pressure, high blood sugar, and adiposity on US life expectancy and on disparities in life expectancy and disease-specific deaths among the “Eight Americas,” population groups defined by race and by the location and socioeconomic characteristics of their county of residence.
What Did the Researchers Do and Find?
The researchers extracted data on exposure to these risk factors from US national health surveys, information on deaths from different diseases in 2005 from the US National Center for Health Statistics, and estimates of how much each risk factor increases the risk of death from each disease from published studies. They then used modeling methods to estimate the effects of risk factor exposure on death rates and life expectancy. The Asian subgroup had the lowest adiposity, blood sugar, and smoking rates, they report, and the three white subgroups had the lowest blood pressure. Blood pressure was highest in the three black subgroups, whereas the other three risk factors were highest in Western Native Americans, Southern rural blacks, and whites living in Appalachia and the Mississippi Valley. The effects on life expectancy of these factors were smallest in Asians and largest in Southern rural blacks but, overall, these risk factors reduced the life expectancy for men and women born in 2005 by 4.9 and 4.1 years, respectively. Other calculations indicate that if these four risk factors were reduced to optimal levels, disparities among the subgroups in deaths from cardiovascular diseases and diabetes and from cancers would be reduced by up to 80% and 50%, respectively.
What Do These Findings Mean?
These findings suggest that disparities in smoking, blood pressure, blood sugar, and adiposity among US racial and geographical subgroups explain a substantial proportion of the disparities in deaths from cardiovascular diseases, diabetes, and cancers among these subgroups. The disparities in risk factor exposure also explain some of the disparities in life expectancy. The remaining disparities in deaths and life expectancy could be the result of preventable risk factors not included in this study—one of its limitations is that it does not consider the effect of dietary fat, alcohol use, and dietary salt, which are major contributors to different diseases. Thus, suggest the researchers, reduced exposure to preventable risk factors through the implementation of relevant policies and programs should reduce life expectancy and mortality disparities in the US and yield health benefits at a national scale.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000248.
The US Centers for Disease Control and Prevention, the US Office of Minority Health, and the US National Center on Minority Health and Health Disparities all provide information on health disparities in the US
MedlinePlus provides links to information on health disparities and on healthy living (in English and Spanish)
The US Centers for Disease Control and Prevention provides information on all aspects of healthy living
The American Heart Association and the American Cancer Society provide information on modifiable risk factors for patients and caregivers
Healthy People 2010 is a national framework designed to improve the health of people living in the US
The US National Health and Nutrition Examination Survey (NHANES) and the Behavioral Risk Factor Surveillance System (BRFSS) collect information on risk factor exposures in the US
doi:10.1371/journal.pmed.1000248
PMCID: PMC2843596  PMID: 20351772
23.  Birth weight-specific infant mortality, United States, 1960 and 1980. 
Public Health Reports  1987;102(2):151-161.
National statistics on the risk of infant mortality by birth weight were collected most recently in 1980 and 1960. (Infant mortality risk is the number of deaths of infants under 1 year of age per 1,000 live births.) In this 20-year period, the infant mortality risk (IMR) for single-delivery infants declined 53 percent, from 23.3 deaths per 1,000 live births to 11.0; 91 percent of this decline was due to lower IMRs within birth weight categories, and 9 percent was due to reduced frequency of low birth weight. The greatest reduction in neonatal mortality (under 28 days)--73 percent--occurred among infants of 1,500-1,999 grams (g) birth weight, whereas the greatest reductions in postneonatal mortality (28 days to under 1 year)--51 percent to 54 percent--occurred among infants of 3,500 g or more birth weight. Trends in IMR for black and white infants were similar, and the twofold gap between the races in IMR persisted from 1960 to 1980. For whites, reductions in the frequency of low birth weights contributed to the decline in the IMR. For blacks, the percentage of infants with birth weights of less than 1,500 g increased, and the total reduction in the IMR was attributable to lower birth weight-specific mortality risks. In some regions of the United States, failure to observe an increase in birth weight for blacks may be a reporting artifact, reflecting improved reporting of births of very small black infants in 1980. Examination of changes in perinatal mortality risks (from 20 weeks gestation to less than 28 days of life) did not suggest that infant mortality trends were substantially affected by changes in the distinction between fetal and neonatal deaths over the 20-year period. Reducing the number of low birth weight infants remains the greatest potential for future reductions in infant mortality.
PMCID: PMC1477822  PMID: 3104972
24.  The APPLe Study: A Randomized, Community-Based, Placebo-Controlled Trial of Azithromycin for the Prevention of Preterm Birth, with Meta-Analysis 
PLoS Medicine  2009;6(12):e1000191.
In a randomized trial in Malawi of azithromycin versus placebo in over 2,000 pregnant women, Jim Neilson and colleagues show no benefit of azithromycin for a number of outcomes including preterm birth and prenatal death.
Background
Premature birth is the major cause of perinatal mortality and morbidity in both high- and low-income countries. The causes of preterm labour are multiple but infection is important. We have previously described an unusually high incidence of preterm birth (20%) in an ultrasound-dated, rural, pregnant population in Southern Malawi with high burdens of infective morbidity. We have now studied the impact of routine prophylaxis with azithromycin as directly observed, single-dose therapy at two gestational windows to try to decrease the incidence of preterm birth.
Methods and Findings
We randomized 2,297 pregnant women attending three rural and one peri-urban health centres in Southern Malawi to a placebo-controlled trial of oral azithromycin (1 g) given at 16–24 and 28–32 wk gestation. Gestational age was determined by ultrasound before 24 wk. Women and their infants were followed up until 6 wk post delivery. The primary outcome was incidence of preterm delivery, defined as <37 wk. Secondary outcomes were mean gestational age at delivery, perinatal mortality, birthweight, maternal malaria, and anaemia. Analysis was by intention to treat. There were no significant differences in outcome between the azithromycin group (n = 1,096) and the placebo group (n = 1,087) in respect of preterm birth (16.8% versus 17.4%), odds ratio (OR) 0.96, 95% confidence interval (0.76–1.21); mean gestational age at delivery (38.5 versus 38.4 weeks), mean difference 0.16 (−0.08 to 0.40); mean birthweight (3.03 versus 2.99 kg), mean difference 0.04 (−0.005 to 0.08); perinatal deaths (4.3% versus 5.0%), OR 0.85 (0.53–1.38); or maternal malarial parasitaemia (11.5% versus 10.1%), OR 1.11 (0.84–1.49) and anaemia (44.1% versus 41.3%) at 28–32 weeks, OR 1.07 (0.88–1.30). Meta-analysis of the primary outcome results with seven other studies of routine antibiotic prophylaxis in pregnancy (>6,200 pregnancies) shows no effect on preterm birth (relative risk 1.02, 95% confidence interval 0.86–1.22).
Conclusions
This study provides no support for the use of antibiotics as routine prophylaxis to prevent preterm birth in high risk populations; prevention of preterm birth requires alternative strategies.
Trial registration
Current Controlled Trials ISRCTN84023116
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Most pregnancies last about 40 weeks. Labor that occurs before 37 weeks of gestation (the period during which a baby develops in its mother) is defined as a preterm birth. In industrialized countries, 5%–10% of all births are preterm. Figures for preterm births are harder to obtain for low-income countries because of uncertainties about gestational dates but, in both rich and poor countries, preterm birth is a major cause of infant death and illness around the time of birth. Babies who are born prematurely also often have long-term health problems and disabilities. There are many reasons why some babies are born prematurely. Structural problems such as a weak cervix (the neck of the womb, which dilates during labor to allow the baby to leave the mother's body) can result in a premature delivery, as can pregnancy-induced diabetes, blood-clotting disorders, bacterial infections in the vagina or the womb, and malaria. However, it is impossible to predict which mothers will spontaneously deliver early.
Why Was This Study Done?
At present there is no effective way to prevent premature births. Because infection is often associated with preterm labor and can occur early in pregnancy but remain undetected, one way to reduce the incidence of preterm births may be to give pregnant women antibiotics even when they have no obvious infection (prophylactic antibiotics). In this study, the researchers test this hypothesis by giving the antibiotic azithromycin to pregnant women living in Southern Malawi in a randomized, placebo-controlled trial. One baby in five is born before 37 weeks gestation in Southern Malawi and the women living in this part of sub-Saharan Africa have a high burden of infection. Azithromycin is a safe antibiotic that can treat many of the bacterial infections that have been implicated in preterm birth. It also has some antimalarial activity. In a randomized, placebo-controlled trial, participants are randomly assigned to receive a drug or identical-looking “dummy” tablets (placebo).
What Did the Researchers Do and Find?
The researchers enrolled more than 2,000 pregnant women into the APPLe study (Azithromycin for the Prevention of Preterm Labor) and determined the gestational age of their unborn babies using ultrasound. Half of the women were given an oral dose of azithromycin at 16–24 weeks and at 28–32 weeks gestation. The remaining women were given a placebo at similar times. The mothers and their babies were followed up until 6 weeks after delivery. There was no significant difference in the primary outcome of the study—the incidence of delivery before 37 weeks gestation—between the two groups of women. Secondary outcomes—including mean gestational age at delivery, mean birth weight, and still births and infant deaths within a week of birth—were also similar in the two groups of women. Finally, the researchers did a meta-analysis (a statistical technique that combines the results of several studies) of their study and seven published studies of routine antibiotic prophylaxis in pregnancy, which indicated that the prophylactic use of antibiotics did not alter the risk of preterm birth.
What Do These Findings Mean?
These findings provide no support for the use of antibiotics as prophylaxis to prevent preterm birth. The women included in this study had an unusually high incidence of preterm delivery and a high burden of infection so these findings may not be generalizable. The results of the meta-analysis, however, also provide no support for prophylactic antibiotics. Given that observational data have associated infection with preterm labor, why are the results of the APPLe trial and the meta-analysis negative? One possibility is that different antibiotics or dosing regimens might be more effective. Another possibility is that infection might be a secondary consequence of some other condition that causes preterm birth rather than the primary cause of early delivery. Whatever the reason for the lack of effect of prophylactic antibiotics, the researchers recommend that pregnant women should not be given antibiotics prophylactically to prevent preterm birth particularly since, in a recent study, the babies of women given antibiotics to halt ongoing preterm labor had an increased risk of developmental problems.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000191.
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish)
The Nemours Foundation, another nonprofit organization for child health, also provides information on premature babies (in English and Spanish)
Tommy's is a nonprofit organization that funds research and provides information on the causes and prevention of miscarriage, premature birth, and stillbirth
The US Centers for Disease Control and Prevention provides information on maternal and infant health (in English and Spanish)
The US National Women's Health Information Center has detailed information about pregnancy (in English and Spanish)
MedlinePlus provides links to other information on premature babies (in English and Spanish)
doi:10.1371/journal.pmed.1000191
PMCID: PMC2776277  PMID: 19956761
25.  Comparing regional infant death rates: the influence of preterm births <24 weeks of gestation 
Objective
To investigate regional variation in the registration of preterm births <24 weeks of gestation and the impact on infant death rates for English Primary Care Trusts (PCTs).
Design
Cohort study.
Setting
England.
Participants
All registered births (1 January 2005–31 December 2008) by gestational age and PCT (147 trusts) linked to infant deaths (up to 1 year of life). Late-fetal deaths at 22 and 23 weeks gestation (1 January 2005–31 December 2006).
Main outcome measures
Extremely preterm (<24 weeks) birth rate per 1000 live births and percentage of births registered as live born by PCT. Infant death rate and rank of mortality for (1) all live births and (2) live births over 24 weeks gestation by PCT.
Results
Wide between-PCT variation existed in extremely preterm birth (<24 weeks) rates (per 1000 births) (90% central range (0.31, 1.91)) and percentages of births <24 weeks of gestation registered as live born (median 52.6%, 90% central range (26.3%, 79.5%)). Consequently, the percentage of infant deaths arising from these births varied (90% central range (6.7%, 31.9%)). Excluding births <24 weeks, led to significant changes in infant mortality rankings of PCTs, with a median worsening of 12 places for PCTs with low rates of live born preterm births <24 weeks of gestation compared with a median improvement of four ranks for those with higher live birth registration rates.
Conclusions
Infant death rates in PCTs in England are influenced by variation in the registration of births where viability is uncertain. It is vital that this variation is minimised before infant mortality is used as indicator for monitoring health and performance and targeting interventions.
doi:10.1136/fetalneonatal-2011-301359
PMCID: PMC3582045  PMID: 22684158

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