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1.  Association Between Stillbirth and Illicit Drug Use and Smoking During Pregnancy 
Obstetrics and gynecology  2014;123(1):113-125.
To compare illicit drug and smoking use in pregnancies with and without stillbirth.
The Stillbirth Collaborative Research Network conducted a case-control study from March 2006 to September 2008, covering more than 90% of deliveries to residents of five a priori defined geographically diverse regions. The study attempted to include all stillbirths and representative liveborn controls. Umbilical cord samples from cases and controls were collected and frozen for subsequent batch analysis. Maternal serum was collected at delivery and batch analyzed for cotinine.
For 663 stillbirth deliveries, 418 (63%) had cord homogenate and 579 (87%) had maternal cotinine assays performed. For 1,932 live birth deliveries, 1,050 (54%) had cord homogenate toxicology and 1,545 (80%) had maternal cotinine assays performed. A positive cord homogenate test for any illicit drug was associated with stillbirth (OR 1.94; 95% CI 1.16, 3.27). The most common individual drug was cannabis (OR 2.34; 95% CI 1.13, 4.81), although the effect was partially confounded by smoking. Both maternal self-reported smoking history and maternal serum cotinine levels were associated in a dose-response relationship with stillbirth. Positive serum cotinine < 3 ng/ml and no reported history of smoking (proxy for passive smoke exposure) also was associated with stillbirth (OR 2.06; 95% CI 1.24, 3.41).
Cannabis, smoking, illicit drug use, and apparent exposure to second-hand smoke, separately or in combination, during pregnancy were associated with an increased risk of stillbirth. As cannabis use may be increasing with increased legalization, the relevance of these findings may increase as well.
PMCID: PMC3931517  PMID: 24463671
2.  A multi-country study of the “intrapartum stillbirth and early neonatal death indicator” in hospitals in low-resource settings 
To determine the feasibility of introducing a simple indicator of quality of obstetric and neonatal care and to determine the proportion of potentially avoidable perinatal deaths in hospitals in low-income countries.
Between September 1, 2011, and February 29, 2012, data were collected from women who had a term pregnancy and were admitted to the labor ward of 1 of 6 hospitals in 4 low-income countries. Fetal heart tones on admission were monitored, and demographic and birth data were recorded.
Data were obtained for 3555 women and 3593 neonates (including twins). The doptone was used on 97% of women admitted. The overall perinatal mortality rate was 34 deaths per 1000 deliveries. Of the perinatal deaths, 40%–45% occurred in the hospital and were potentially preventable by better hospital care.
The results demonstrated that it is possible to accurately determine fetal viability on admission via a doptone. Implementation of doptone use, coupled with a concise data record, might form the basis of a low-cost and sustainable program to monitor and evaluate efforts to improve quality of care and ultimately might to help to reduce the in-hospital component of perinatal mortality in low-income countries.
PMCID: PMC3893914  PMID: 23796259
Doptone; Fetal heart tones; Hospital-based perinatal mortality; Neonatal mortality; Perinatal mortality; Stillbirth
3.  A review of studies with chlorhexidine applied directly to the umbilical cord 
American journal of perinatology  2013;30(8):10.1055/s-0032-1329695.
Infection-related neonatal mortality due to omphalitis in developing country home births is an important public health problem. Three cluster randomized trials of 4% chlorhexidine applied to the umbilical cord stump from 1 to multiple times in the days following a home birth have evaluated this intervention compared to other types of cord care on the development of omphalitis and neonatal mortality. Each of the 3 studies showed significant reductions in either omphalitis, neonatal mortality, or both with the 4% chlorhexidine. However, the optimal dosing schedule remains uncertain. While further studies are needed to clarify this issue, from the 3 studies it is now clear that with a minimum of one application of 4% chlorhexidine to the umbilical cord stump following delivery, the incidence of omphalitis and neonatal mortality can be reduced, especially in preterm newborns. This intervention, which is safe, inexpensive and requires minimal training and skill, should strongly be considered for adoption wherever home births occur.
PMCID: PMC3875170  PMID: 23254380
4.  Fetal Growth and Risk of Stillbirth: A Population-Based Case–Control Study 
PLoS Medicine  2014;11(4):e1001633.
Radek Bukowski and colleagues conducted a case control study in 59 US hospitals to determine the relationship between fetal growth and stillbirth, and find that both restrictive and excessive growth could play a role.
Please see later in the article for the Editors' Summary
Stillbirth is strongly related to impaired fetal growth. However, the relationship between fetal growth and stillbirth is difficult to determine because of uncertainty in the timing of death and confounding characteristics affecting normal fetal growth.
Methods and Findings
We conducted a population-based case–control study of all stillbirths and a representative sample of live births in 59 hospitals in five geographic areas in the US. Fetal growth abnormalities were categorized as small for gestational age (SGA) (<10th percentile) or large for gestational age (LGA) (>90th percentile) at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms. Gestational age at death was determined using an algorithm that considered the time-of-death interval, postmortem examination, and reliability of the gestational age estimate. Data were weighted to account for the sampling design and differential participation rates in various subgroups. Among 527 singleton stillbirths and 1,821 singleton live births studied, stillbirth was associated with SGA based on population, ultrasound, and individualized norms (odds ratio [OR] [95% CI]: 3.0 [2.2 to 4.0]; 4.7 [3.7 to 5.9]; 4.6 [3.6 to 5.9], respectively). LGA was also associated with increased risk of stillbirth using ultrasound and individualized norms (OR [95% CI]: 3.5 [2.4 to 5.0]; 2.3 [1.7 to 3.1], respectively), but not population norms (OR [95% CI]: 0.6 [0.4 to 1.0]). The associations were stronger with more severe SGA and LGA (<5th and >95th percentile). Analyses adjusted for stillbirth risk factors, subset analyses excluding potential confounders, and analyses in preterm and term pregnancies showed similar patterns of association. In this study 70% of cases and 63% of controls agreed to participate. Analysis weights accounted for differences between consenting and non-consenting women. Some of the characteristics used for individualized fetal growth estimates were missing and were replaced with reference values. However, a sensitivity analysis using individualized norms based on the subset of stillbirths and live births with non-missing variables showed similar findings.
Stillbirth is associated with both growth restriction and excessive fetal growth. These findings suggest that, contrary to current practices and recommendations, stillbirth prevention strategies should focus on both severe SGA and severe LGA pregnancies.
Please see later in the article for the Editors' Summary
Editors' Summary
Pregnancy is usually a happy time, when the parents-to-be anticipate the arrival of a new baby. But, sadly, about 20% of pregnancies end in miscarriage—the early loss of a fetus (developing baby) that is unable to survive independently. Other pregnancies end in stillbirth—fetal death after 20 weeks of pregnancy (in the US; after 24 weeks in the UK). Stillbirths, like miscarriages, are common. In the US, for example, one in every 160 pregnancies ends in stillbirth. How women discover that their unborn baby has died varies. Some women simply know something is wrong and go to hospital to have their fears confirmed. Others find out when a routine check-up detects no fetal heartbeat. Most women give birth naturally after their baby has died, but if the mother's health is at risk, labor may be induced. Common causes of stillbirth include birth defects and infections. Risk factors for stillbirth include being overweight and smoking during pregnancy.
Why Was This Study Done?
Stillbirths are often associated with having a “small for gestational age” (SGA) fetus. Gestation is the period during which a baby develops in its mother's womb. Gestational age is estimated from the date of the woman's last menstrual period and/or from ultrasound scans. An SGA fetus is lighter than expected for its age based on observed distributions (norms) of fetal weights for gestational age. Although stillbirth is clearly associated with impaired fetal growth, the exact relationship between fetal growth and stillbirth remains unclear for two reasons. First, studies investigating this relationship have used gestational age at delivery rather than gestational age at death as an estimate of fetal age, which overestimates the gestational age of stillbirths and leads to errors in estimates of the proportions of SGA and “large for gestational age” (LGA) stillbirths. Second, many characteristics that affect normal fetal growth are also associated with the risk of stillbirth, and this has not been allowed for in previous studies. In this population-based case–control study, the researchers investigate the fetal growth abnormalities associated with stillbirth using a new approach to estimate gestational age and accounting for the effect of characteristics that affect both fetal growth and stillbirth. A population-based case–control study compares the characteristics of patients with a condition in a population with those of unaffected people in the same population.
What Did the Researchers Do and Find?
The researchers investigated all the stillbirths and a sample of live births that occurred over 2.5 years at 59 hospitals in five US regions. They used a formula developed by the Stillbirth Collaborative Research Network to calculate the gestational age at death of the stillbirths. They categorized fetuses as SGA if they had a weight for gestational age within the bottom 10% (below the 10th percentile) of the population and as LGA if they had a weight for gestational age above the 90th percentile at death (stillbirth) or delivery (live birth) using population, ultrasound, and individualized norms of fetal weight for gestational age. Population norms incorporate weights for gestational age from normal pregnancies and from pregnancies complicated by growth abnormalities, whereas the other two norms include weights for gestational age from normal pregnancies only. Having an SGA fetus was associated with a 3- to 4-fold increased risk of stillbirth compared to having a fetus with “appropriate” weight for gestational age based on all three norms. LGA was associated with an increased risk of stillbirth based on the ultrasound and individualized norms but not the population norms. Being more severely SGA or LGA (below the 5th percentile or above the 95th percentile) was associated with an increased risk of stillbirth.
What Do These Findings Mean?
These findings indicate that, when the time of death is accounted for and norms for weight for gestational age only from uncomplicated pregnancies are used, stillbirth is associated with both restricted and excessive fetal growth. Overall, abnormal fetal growth was identified in 25% of stillbirths using population norms and in about 50% of stillbirths using ultrasound or individualized norms. Although the accuracy of these findings is likely to be affected by aspects of the study design, these findings suggest that, contrary to current practices, strategies designed to prevent stillbirth should focus on identifying both severely SGA and severely LGA fetuses and should use norms for the calculation of weight for gestational age based on normal pregnancies only. Such an approach has the potential to identify almost half of the pregnancies likely to result in stillbirth.
Additional Information
Please access these websites via the online version of this summary at
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on stillbirth
Tommy's, a UK nonprofit organization that funds research into stillbirth, premature birth, and miscarriage and provides information for parents-to-be, also provides information on stillbirth (including personal stories)
The UK National Health Service Choices website provides information about stillbirth (including a video about dealing with grief after a stillbirth)
MedlinePlus provides links to other resources about stillbirth (in English and Spanish)
Information about the Stillbirth Collaborative Research Network is available
PMCID: PMC3995658  PMID: 24755550
5.  A Population-based Case-Control Study of Stillbirth: The Relationship of Significant Life Events to the Racial Disparity for African Americans 
American Journal of Epidemiology  2013;177(8):755-767.
Stillbirths (fetal deaths occurring at ≥20 weeks' gestation) are approximately equal in number to infant deaths in the United States and are twice as likely among non-Hispanic black births as among non-Hispanic white births. The causes of racial disparity in stillbirth remain poorly understood. A population-based case-control study conducted by the Stillbirth Collaborative Research Network in 5 US catchment areas from March 2006 to September 2008 identified characteristics associated with racial/ethnic disparity and interpersonal and environmental stressors, including a list of 13 significant life events (SLEs). The adjusted odds ratio for stillbirth among women reporting all 4 SLE factors (financial, emotional, traumatic, and partner-related) was 2.22 (95% confidence interval: 1.43, 3.46). This association was robust after additional control for the correlated variables of family income, marital status, and health insurance type. There was no interaction between race/ethnicity and other variables. Effective ameliorative interventions could have a substantial public health impact, since there is at least a 50% increased risk of stillbirth for the approximately 21% of all women and 32% of non-Hispanic black women who experience 3 or more SLE factors during the year prior to delivery.
PMCID: PMC3625065  PMID: 23531847
African Americans; case-control studies; continental population groups; life change events; psychosocial stress; socioeconomic factors; stillbirth; stress
7.  Stillbirth and early neonatal mortality in rural Central Africa 
To develop a prospective perinatal registry that characterizes all deliveries, differentiates between stillbirths and early neonatal deaths (ENDs), and determines the ratio of fresh to macerated stillbirths in the northwest Democratic Republic of Congo.
Birth outcomes were obtained from 4 rural health districts.
A total of 8230 women consented, END rate was 32 deaths per 1000 live births, and stillbirth rate was 33 deaths per 1000 deliveries. The majority (75%) of ENDs and stillbirths occurred in neonates weighing 1500 g or more. Odds of stillbirth and END increased in mothers who were single or who did not receive prenatal care, and among premature, low birth weight, or male infants. The ratio of fresh to macerated stillbirths was 4:1.
Neonates weighing 1500 g or more at birth represent a group with a high likelihood of survival in remote areas, making them potentially amenable to targeted intervention packages. The ratio of fresh to macerated stillbirths was approximately 10-fold higher than expected, suggesting a more prominent role for improved intrapartum obstetric interventions.
PMCID: PMC3972762  PMID: 19201402
Africa; Early neonatal death; Fresh and macerated stillbirth; Low-income country
8.  The MANDATE model for evaluating interventions to reduce postpartum hemorrhage 
To create a comprehensive model of the comparative impact of various interventions on maternal, fetal, and neonatal (MFN) mortality.
The major conditions and sub-conditions contributing to MFN mortality in low-resource areas were identified, and the prevalence and case fatality rates documented. Available interventions were mapped to these conditions, and intervention coverage and efficacy were identified. Finally, a computer model developed by the Maternal and Neonatal Directed Assessment of Technology (MANDATE) initiative estimated the potential of current and new interventions to reduce mortality.
For PPH, the sub-causes, prevalence, and MFN case fatality rates were calculated. Available interventions were mapped to these sub-causes. Most available interventions did not prevent or treat the overall condition of PPH, but rather sub-conditions associated with hemorrhage and thus prevented only a fraction of the associated deaths.
The majority of current interventions address sub-conditions that cause death, rather than the overall condition; thus, the potential number of lives saved is likely to be overestimated. Additionally, the location at which mother and infant receive care affects intervention effectiveness and, therefore, the potential to save lives. A comprehensive view of MFN conditions is needed to understand the impact of any potential intervention.
PMCID: PMC3628756  PMID: 23313144
Low-income countries; Maternal mortality; Model; Postpartum hemorrhage; Stillbirth
9.  Infection and stillbirth 
Infection may cause stillbirth by several mechanisms, including direct infection, placental damage, and severe maternal illness. Various organisms have been associated with stillbirth, including many bacteria, viruses, and protozoa. In developed countries, between 10% and 25% of stillbirths may be caused by an infection, whereas in developing countries, which have much higher stillbirth rates, the contribution of infection is much greater. In developed countries, ascending bacterial infection, both before and after membrane rupture, with organisms such as Escherichia coli, group B streptococci, and Ureaplasma urealyticum is usually the most common infectious cause of stillbirth. However, in areas where syphilis is prevalent, up to half of all stillbirths may be caused by this infection alone. Malaria may be an important cause of stillbirth in women infected for the first time in pregnancy. The two most important viral causes of stillbirth are parvovirus and Coxsackie virus, although a number of other viral infections appear to be causal. Toxoplasma gondii, leptospirosis, Listeria monocytogenes, and the organisms that cause leptospirosis, Q fever, and Lyme disease have all been implicated as etiologic for stillbirth. In certain developing countries, the stillbirth rate is high and the infection-related component so great that achieving a substantial reduction in stillbirth should be possible by reducing maternal infections. However, because infection-related stillbirth is uncommon in developed countries, and because those that do occur are caused by a wide variety of organisms, reducing this etiologic component of stillbirth much further will be difficult.
PMCID: PMC3962114  PMID: 19285457
Chorioamnionitis; Infection; Stillbirth
10.  Preconception maternal nutrition: a multi-site randomized controlled trial 
Research directed to optimizing maternal nutrition commencing prior to conception remains very limited, despite suggestive evidence of its importance in addition to ensuring an optimal nutrition environment in the periconceptional period and throughout the first trimester of pregnancy.
Methods/Study design
This is an individually randomized controlled trial of the impact on birth length (primary outcome) of the time at which a maternal nutrition intervention is commenced: Arm 1: ≥ 3 mo preconception vs. Arm 2: 12-14 wk gestation vs. Arm 3: none.
192 (derived from 480) randomized mothers and living offspring in each arm in each of four research sites (Guatemala, India, Pakistan, Democratic Republic of the Congo). The intervention is a daily 20 g lipid-based (118 kcal) multi-micronutient (MMN) supplement. Women randomized to receive this intervention with body mass index (BMI) <20 or whose gestational weight gain is low will receive an additional 300 kcal/d as a balanced energy-protein supplement. Researchers will visit homes biweekly to deliver intervention and monitor compliance, pregnancy status and morbidity; ensure prenatal and delivery care; and promote breast feeding. The primary outcome is birth length. Secondary outcomes include: fetal length at 12 and 34 wk; incidence of low birth weight (LBW); neonatal/infant anthropometry 0-6 mo of age; infectious disease morbidity; maternal, fetal, newborn, and infant epigenetics; maternal and infant nutritional status; maternal and infant microbiome; gut inflammatory biomarkers and bioactive and nutritive compounds in breast milk. The primary analysis will compare birth Length-for-Age Z-score (LAZ) among trial arms (independently for each site, estimated effect size: 0.35). Additional statistical analyses will examine the secondary outcomes and a pooled analysis of data from all sites.
Positive results of this trial will support a paradigm shift in attention to nutrition of all females of child-bearing age.
Trial registration NCT01883193.
PMCID: PMC4000057  PMID: 24650219
Preconception; Maternal; Nutrition; Birth length; Epigenetics; Microbiome
11.  Disparities in interventions for child and maternal mortality 
Lancet  2012;379(9822):1178-1180.
PMCID: PMC3957338  PMID: 22464372
Accurate assignment of gestational age at time of fetal death is important for research and clinical practice. An algorithm to estimate gestational age (GA) at fetal death was developed and evaluated.
The algorithm developed by the Stillbirth Collaborative Research Network (SCRN) incorporated clinical and postmortem data. The SCRN conducted a population-based case-control study of women with stillbirths and live births from 2006 to 2008 in five geographic catchment areas. Rules were developed to estimate a due date, identify an interval during which death likely occurred, and estimate GA at the time of fetal death. Reliability of using fetal foot length to estimate GA at death was assessed.
The due date estimated for 620 singleton stillbirths studied was considered clinically reliable for 87%. Only 25.2% of stillbirths were documented alive within two days before diagnosis and 47.6% within one week of diagnosis. The algorithm-derived estimate of GA at time of fetal death was 1 or more weeks earlier than the GA at delivery for 43.5% of stillbirths. GA estimated from fetal foot length agreed with GA by algorithm within two weeks for 75% within a subset of well-dated stillbirths.
Precise assignment of GA at death, defined as reliable dating criteria and a short interval (≤1 week) during which fetal death was known to have occurred, was possible in 46.6% of cases. Fetal foot length is a relatively accurate measure of GA at death and should be collected in all stillbirth cases.
PMCID: PMC3564237  PMID: 23374059
13.  The Association of Parasitic Infections in Pregnancy and Maternal and Fetal Anemia: A Cohort Study in Coastal Kenya 
Relative contribution of these infections on anemia in pregnancy is not certain. While measures to protect pregnant women against malaria have been scaling up, interventions against helminthes have received much less attention. In this study, we determine the relative impact of helminthes and malaria on maternal anemia.
A prospective observational study was conducted in coastal Kenya among a cohort of pregnant women who were recruited at their first antenatal care (ANC) visit and tested for malaria, hookworm, and other parasitic infections and anemia at enrollment. All women enrolled in the study received presumptive treatment with sulfadoxine-pyrimethamine, iron and multi-vitamins and women diagnosed with helminthic infections were treated with albendazole. Women delivering a live, term birth, were also tested for maternal anemia, fetal anemia and presence of infection at delivery.
Principal Findings
Of the 706 women studied, at the first ANC visit, 27% had moderate/severe anemia and 71% of women were anemic overall. The infections with highest prevalence were hookworm (24%), urogenital schistosomiasis (17%), trichuria (10%), and malaria (9%). In adjusted and unadjusted analyses, moderate/severe anemia at first ANC visit was associated with the higher intensities of hookworm and P. falciparum microscopy-malaria infections. At delivery, 34% of women had moderate/severe anemia and 18% of infants' cord hemoglobin was consistent with fetal anemia. While none of the maternal infections were significantly associated with fetal anemia, moderate/severe maternal anemia was associated with fetal anemia.
More than one quarter of women receiving standard ANC with IPTp for malaria had moderate/severe anemia in pregnancy and high rates of parasitic infection. Thus, addressing the role of co-infections, such as hookworm, as well as under-nutrition, and their contribution to anemia is needed.
Author Summary
International guidelines recommend routine prevention and treatments which are safe and effective during pregnancy to reduce hookworm, malaria and other infections among pregnant women living in geographic areas where these infections are prevalent. Despite their effectiveness, programs to address common infections such as hookworm, schistosomiasis and malaria during pregnancy have not been widely adopted. Hookworm, malaria and other infections have been associated with anemia in children, but the studies on the impact of these infections on anemia in pregnancy have not been as clear. This study was undertaken to evaluate the prevalence of parasitic infections among women attending antenatal care which provided the nationally recommended malaria preventive treatment program in coastal Kenya. At the first ANC visit, more than 70% of women were anemic, nearly one-fourth had hookworm and about 10% had malaria. Women with high levels of hookworm or malaria infections were at risk of anemia.
PMCID: PMC3937317  PMID: 24587473
14.  Exposure of Pregnant Women to Indoor Air Pollution: A Study from nine low and middle income countries 
We studied exposure to solid fuel smoke and second-hand tobacco smoke among pregnant women in south Asia, Africa and Latin America.
Prospective cross-sectional survey.
Antenatal clinics in Argentina, Brazil, Ecuador, Guatemala, Uruguay, Democratic Republic of Congo, Zambia, India and Pakistan.
A total of 7961 pregnant women in ten sites in nine countries were interviewed between October 2004 and September 2005.
A standardized questionnaire on exposure to indoor air pollution (IAP) and to secondhand smoke was administered to pregnant women during antenatal care.
Main Outcome Measures
Exposure to IAP and second-hand tobacco smoke.
South Asian pregnant women commonly reported use of wood (49.1%–89.7%), crop residue and animal dung for cooking and heating fuel. African pregnant women reported higher use of charcoal (85.4%–93.5%). Latin American pregnant women had greater use of petroleum gas. Among south Asian women, solid fuel use and cooking on an open flame inside the home were common. There was a significant association between solid fuel use and allowing smoking within the home at the Asian sites and in Zambia (p<0.05).
Pregnant women from low/middle income countries were commonly exposed to IAP secondary to use of solid fuels. Among these populations, exposure to second-hand tobacco smoke was also common. This combination of exposures likely increases the risk of poor pregnancy outcomes among the most vulnerable women. Our study highlights the importance of further research on the combined impact of IAP and second-hand tobacco smoke exposures on adverse maternal and perinatal outcomes.
PMCID: PMC3928066  PMID: 19961275
Pregnancy; indoor air pollution; second-hand tobacco smoke exposure; smoking
15.  First look: a cluster-randomized trial of ultrasound to improve pregnancy outcomes in low income country settings 
In high-resource settings, obstetric ultrasound is a standard component of prenatal care used to identify pregnancy complications and to establish an accurate gestational age in order to improve obstetric care. Whether or not ultrasound use will improve care and ultimately pregnancy outcomes in low-resource settings is unknown.
This multi-country cluster randomized trial will assess the impact of antenatal ultrasound screening performed by health care staff on a composite outcome consisting of maternal mortality and maternal near-miss, stillbirth and neonatal mortality in low-resource community settings. The trial will utilize an existing research infrastructure, the Global Network for Women’s and Children’s Health Research with sites in Pakistan, Kenya, Zambia, Democratic Republic of Congo and Guatemala. A maternal and newborn health registry in defined geographic areas which documents all pregnancies and their outcomes to 6 weeks post-delivery will provide population-based rates of maternal mortality and morbidity, stillbirth, neonatal mortality and morbidity, and health care utilization for study clusters. A total of 58 study clusters each with a health center and about 500 births per year will be randomized (29 intervention and 29 control). The intervention includes training of health workers (e.g., nurses, midwives, clinical officers) to perform ultrasound examinations during antenatal care, generally at 18–22 and at 32–36 weeks for each subject. Women who are identified as having a complication of pregnancy will be referred to a hospital for appropriate care. Finally, the intervention includes community sensitization activities to inform women and their families of the availability of ultrasound at the antenatal care clinic and training in emergency obstetric and neonatal care at referral facilities.
In summary, our trial will evaluate whether introduction of ultrasound during antenatal care improves pregnancy outcomes in rural, low-resource settings. The intervention includes training for ultrasound-naïve providers in basic obstetric ultrasonography and then enabling these trainees to use ultrasound to screen for pregnancy complications in primary antenatal care clinics and to refer appropriately.
Trial registration (NCT # 01990625)
PMCID: PMC3996090  PMID: 24533878
Maternal mortality; Maternal near miss; Perinatal mortality; Obstetric ultrasound; Low-income countries
16.  Intrapartum Perinatal Mortality 
Indian pediatrics  2012;49(3):187-188.
PMCID: PMC3918931  PMID: 22484737
17.  Prenatal Tobacco Prevention and Cessation Interventions for Women in Low- and Middle-Income Countries 
Although the prevalence of tobacco use is decreasing in many high-income countries, it is increasing in many low-and middle-income countries. The health and economic burden of increasing tobacco use and dependence is predictable and will have devastating effects in countries with limited resources, particularly for vulnerable populations such as pregnant women. We sought to review effective tobacco prevention and intervention strategies for decreasing tobacco use and secondhand smoke exposure before and during pregnancy in high-, middle-, and low-income countries. We reviewed several types of interventions, including population-level efforts (increasing tobacco prices, implementing tobacco control policies), community interventions, clinical interventions, and pharmacological treatments.
A second purpose of this report is to present findings of an international expert working group that was convened to review the evidence and to establish research priorities in the following areas: 1) preventing the uptake and reducing tobacco use among girls and women of reproductive age and 2) reducing tobacco use and secondhand smoke exposure among pregnant women. The working group considered the evidence on existing interventions in terms of burden of disease, intervention impact, intervention costs, feasibility of integration into existing services, uniqueness of the contribution, and overall feasibility. Finally, we present the working group’s recommendations for intervention research priorities.
PMCID: PMC3918940  PMID: 20235895
Global; tobacco; perinatal and reproductive health
18.  Prevalence of Suicidal Thoughts and Attempts Among Pregnant Pakistani Women 
To determine the prevalence of suicidal thoughts and attempts and to identify demographic variables and mental health correlates such as anxiety/depression and domestic violence among pregnant women in an urban community in Pakistan.
Cross sectional data from a prospective cohort study are presented.
Women enrolled in an antenatal care clinic and followed to delivery in an urban area of Pakistan
Cohort of pregnant women in Pakistan.
1,369 pregnant women were enrolled and interviewed regarding various maternal characteristics and pregnancy outcomes, and were asked specific questions about suicidal thoughts and attempts and administered the Aga Khan University Anxiety Depression Scale at 20–26 weeks of gestation.
Main outcome measures
Suicidal thoughts and attempts, verbal, sexual or physical abuse.
Overall, 148 of the 1369 (11%) women studied had considered suicide. Of these, 148 women, 67 (45%) had attempted suicide. Eighteen percent of the women were classified as having depression/anxiety, almost half (48%) reported experiencing verbal abuse and 20% reported physical/sexual abuse. Women who had anxiety/depression or had experienced verbal or physical/sexual abuse were significantly more likely to have had suicidal thoughts and attempts.
Women at greatest risk for having suicidal thoughts or a suicide attempt were those who were depressed/anxious and had experienced some form of domestic abuse. With the high prevalence of these conditions, attention should be given to the establishment of effective mental health treatment programs for pregnant women.
PMCID: PMC3918941  PMID: 21050149
Suicidal thoughts; suicide attempts; pregnancy; abuse; anxiety/depression
19.  High Mortality Rates for Very Low Birth Weight Infants in Developing Countries Despite Training 
Pediatrics  2010;126(5):e1072-e1080.
The goal was to determine the effect of training in newborn care and resuscitation on 7-day (early) neonatal mortality rates for very low birth weight (VLBW) infants. The study was designed to test the hypothesis that these training programs would reduce neonatal mortality rates for VLBW infants.
Local instructors trained birth attendants from 96 rural communities in 6 developing countries in protocol and data collection, the World Health Organization Essential Newborn Care (ENC) course, and a modified version of the American Academy of Pediatrics Neonatal Resuscitation Program (NRP), by using a train-the-trainer model. To test the impact of ENC training, data on infants of 500 to 1499 g were collected by using a before/after, active baseline, controlled study design. A cluster-randomized, controlled trial design was used to test the impact of the NRP.
A total of 1096 VLBW (500–1499 g) infants were enrolled, and 98.5% of live-born infants were monitored to 7 days. All-cause, 7-day neonatal mortality, stillbirth, and perinatal mortality rates were not affected by ENC or NRP training.
Neither ENC nor NRP training of birth attendants decreased 7-day neonatal, stillbirth, or perinatal mortality rates for VLBW infants born at home or at first-level facilities. Encouragement of delivery in a facility where a higher level of care is available may be preferable when delivery of a VLBW infant is expected.
PMCID: PMC3918943  PMID: 20937655
neonatal mortality; perinatal mortality; stillbirth; developing countries; health care systems; very low birth weight; prematurity
20.  Anemia prevalence and risk factors in pregnant women in an urban area of Pakistan 
Food and nutrition bulletin  2008;29(2):132-139.
Anemia affects almost two-thirds of pregnant women in developing countries and contributes to maternal morbidity and mortality and to low birthweight.
To determine the prevalence of anemia and the dietary and socioeconomic factors associated with anemia in pregnant women living in an urban community setting in Hyderabad, Pakistan.
This was a prospective, observational study of 1,369 pregnant women enrolled at 20 to 26 weeks of gestation and followed to 6 weeks postpartum. A blood sample was obtained at enrollment to determine hemoglobin levels. Information on nutritional knowledge, attitudes, and practice and dietary history regarding usual food intake before and during pregnancy were obtained by trained interviewers within 1 week of enrollment.
The prevalence of anemia (defined by the World Health Organization as hemoglobin < 11.0 g/dL) in these subjects was 90.5%; of these, 75.0% had mild anemia (hemoglobin from 9.0 to 10.9 g/dL) and 14.8% had moderate anemia (hemoglobin from 7.0 to 8.9 g/dL). Only 0.7% were severely anemic (hemoglobin < 7.0 g/dL). Nonanemic women were significantly taller, weighed more, and had a higher body mass index. Multivariate analysis after adjustment for education, pregnancy history, iron supplementation, and height showed that drinking more than three cups of tea per day before pregnancy (adjusted prevalence odds ratio [aPOR], 3.2; 95% confidence interval [CI], 1.3 to 8.0), consumption of clay or dirt during pregnancy (aPOR, 3.7; 95% CI, 1.1 to 12.3), and never consuming eggs or consuming eggs less than twice a week during pregnancy (aPOR, 1.7; 95% CI, 1.1 to 2.5) were significantly associated with anemia. Consumption of red meat less than twice a week prior to pregnancy was marginally associated with anemia (aPOR, 1.2; 95% CI, 0.8 to 1.8) but was significantly associated with lower mean hemoglobin concentrations (9.9 vs. 10.0 g/dL, p = .05) during the study period. A subanalysis excluding women with mild anemia found similar associations to those of the main model, albeit even stronger.
A high percentage of women at 20 to 26 weeks of pregnancy had mild to moderate anemia. Pica, tea consumption, and low intake of eggs and red meat were associated with anemia. Women of childbearing age should be provided nutritional education regarding food sources of iron, especially prior to becoming pregnant, and taught how food choices can either enhance or interfere with iron absorption.
PMCID: PMC3917507  PMID: 18693477
Anemia; developing countries; pregnancy
21.  A conference report on prenatal corticosteroid use in low- and middle-income countries 
To evaluate the evidence for prenatal corticosteroid use in low- and middle-income countries and to make recommendations regarding implementation and further research.
Studies and meta-analyses on prenatal corticosteroids relevant to low- and middle-income countries were identified and reviewed at the Maternal and Child Health Integrated Project (MCHIP) Antenatal Corticosteroid Conference held in Washington on October 19, 2010.
There is strong evidence regarding the effectiveness of prenatal corticosteroid use in hospitals in high- and middle-income countries, usually in settings with high-level newborn care. For births occurring in hospitals in low-income countries without high-level neonatal care or for births outside hospitals, no studies have been conducted to evaluate prenatal corticosteroid use. The efficacy and safety of prenatal corticosteroid use in these settings must be evaluated.
The conference working group recommended expanding the use of prenatal corticosteroids in hospitals with high-level newborn care in low-income countries. For other low-income country settings, further research regarding efficacy and safety should precede the widespread introduction of prenatal corticosteroids.
PMCID: PMC3910250  PMID: 21930269
Low-resource countries; Prenatal corticosteroids; Preterm birth
22.  Stillbirth in Developing Countries: A review of causes, risk factors and prevention strategies 
In reviewing the research on stillbirth in developing countries, it becomes clear that because almost half of the deliveries in these settings occur at home, under-reporting of stillbirths is a significant problem, and reliable data about rates and causes are unavailable in some areas of the world. Nevertheless, of the estimated 3 million stillbirths which occur yearly, the vast majority in developing countries, with rates in many developing countries ten-fold higher than elsewhere. Classification systems have been adapted for developing countries; however, there is not a standard international system, nor is there agreement about stillbirth definitions making comparisons of cause of stillbirth over time or between sites problematic. From available data, prolonged and obstructed labor, and various infections all without adequate treatment, appear to account for the majority of stillbirths in developing countries. Strategies that have effectively reduced stillbirth in developed countries have had mixed results in developing countries or have not yet been tested; however, identification and treatment of infections such as syphilis has been shown effective in reducing stillbirth risk, while strategies to improve obstetric care have not been widely evaluated. Despite the large number of stillbirths worldwide, the topic of stillbirths in developing countries has received very little research, programmatic or policy attention. Better access to appropriate obstetric care, especially during labor, should reduce developing country stillbirth rates dramatically.
PMCID: PMC3893926  PMID: 19089779
stillbirth; developing countries; perinatal mortality
23.  Maternal Mortality: Editorial for AJOBGYN 
PMCID: PMC3893928  PMID: 22083050
24.  Infectious Causes of Stillbirth: A Clinical Perspective 
Untreated infection may cause stillbirth by several mechanisms, including direct fetal infection, placental damage, and severe maternal illness. Many bacteria, viruses, and protozoa have been associated with stillbirth. In developed countries, up to 24% of stillbirths have been attributed to infection, although with increased availability of sophisticated diagnostics and rigorous screening, it appears likely that higher numbers may actually be associated with infection. In developed countries, ascending bacterial infection is usually the most common infectious cause of stillbirth, with a number of viral infections also an important factor. Screening, prevention and treatment of maternal infections are important to reduce stillbirth risk.
PMCID: PMC3893929  PMID: 20661048
Stillbirth; infection; chorioamnionitis
Lancet  2010;375(9724):1482-1490.
Infection is an important cause of stillbirth world-wide; in low and middle income countries (LMICs), 50% or more are likely caused by infection. In contrast, in high income countries, only10-25% of stillbirths are caused by infection. Syphilis, where prevalent, causes the majority of infectious stillbirths and is the infection most amenable to screening and treatment. Ascending bacterial infection is a common cause of stillbirth, but prevention has proven elusive. Many viral infections are causal for stillbirth but aside from vaccination for common childhood diseases, it is unclear how most viral-caused stillbirths may be prevented. Malaria, because of its high prevalence and extensive placental damage accounts for large numbers of stillbirths. Intermittent malarial prophylaxis and insecticide impregnated bed nets should decrease stillbirths. Many animal and vector-borne infections cause stillbirth. Because this relationship is especially important in LMICs, research that more clearly defines this relationship is crucial to reduce the unacceptably high stillbirth rates in those areas.
PMCID: PMC3893931  PMID: 20223514
Stillbirth; infection; congenital syphilis; vector-borne infections

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