This is the first of seven articles from a preterm birth and stillbirth report. Presented here is an overview of the burden, an assessment of the quality of current estimates, review of trends, and recommendations to improve data.
Few countries have reliable national preterm birth prevalence data. Globally, an estimated 13 million babies are born before 37 completed weeks of gestation annually. Rates are generally highest in low- and middle-income countries, and increasing in some middle- and high-income countries, particularly the Americas. Preterm birth is the leading direct cause of neonatal death (27%); more than one million preterm newborns die annually. Preterm birth is also the dominant risk factor for neonatal mortality, particularly for deaths due to infections. Long-term impairment is an increasing issue.
Stillbirths are currently not included in Millennium Development Goal tracking and remain invisible in global policies. For international comparisons, stillbirths include late fetal deaths weighing more than 1000g or occurring after 28 weeks gestation. Only about 2% of all stillbirths are counted through vital registration and global estimates are based on household surveys or modelling. Two global estimation exercises reached a similar estimate of around three million annually; 99% occur in low- and middle-income countries. One million stillbirths occur during birth. Global stillbirth cause-of-death estimates are impeded by multiple, complex classification systems.
Recommendations to improve data
(1) increase the capture and quality of pregnancy outcome data through household surveys, the main data source for countries with 75% of the global burden; (2) increase compliance with standard definitions of gestational age and stillbirth in routine data collection systems; (3) strengthen existing data collection mechanisms—especially vital registration and facility data—by instituting a standard death certificate for stillbirth and neonatal death linked to revised International Classification of Diseases coding; (4) validate a simple, standardized classification system for stillbirth cause-of-death; and (5) improve systems and tools to capture acute morbidity and long-term impairment outcomes following preterm birth.
Lack of adequate data hampers visibility, effective policies, and research. Immediate opportunities exist to improve data tracking and reduce the burden of preterm birth and stillbirth.
We investigated whether maternal breast cancer affects birth outcome in a nationwide cohort study of 695 births from 1973 to 2002 of women with breast cancer with respect to preterm birth, low birth weight at term, stillbirth and congenital abnormalities as well as mean birth weight, compared with the outcomes of 33 443 births from unaffected mothers. There was no excess risk of adverse birth outcome for the 216 newborns of women with breast cancer before pregnancy. Stratification by mother's treatment did not change the results. For 37 newborns of women diagnosed during pregnancy, the prevalence ratio (PR) of preterm birth was 8.1 (95% confidence interval (CI): 3.8–17). However, 10 of the 12 preterm deliveries among these women were elective early deliveries. Among 442 births of women diagnosed in the 2 years from time of delivery, the PR of preterm birth was 1.4 (95% CI: 1.0–2.0), and the PR of low birth weight at term for boys was 2.9 (95% CI: 1.3–6.3). Overall, our results are reassuring regarding the risks of adverse birth outcome for breast cancer patients.
epidemiology; breast cancer; birth outcome; cohort study
Most maternal deaths, intrapartum-related stillbirths, and newborn deaths in low income countries are preventable but simple, effective methods for improving safety in institutional births have not been devised. Checklist-based interventions aid management of complex or neglected tasks and have been shown to reduce harm in healthcare. We hypothesized that implementation of the WHO Safe Childbirth Checklist program, a novel childbirth safety program for institutional births incorporating a 29-item checklist, would increase delivery of essential childbirth practices linked with improved maternal and perinatal health outcomes.
Methods and Findings
A pilot, pre-post-intervention study was conducted in a sub-district level birth center in Karnataka, India between July and December 2010. We prospectively observed health workers that attended to women and newborns during 499 consecutively enrolled birth events and compared these with observed practices during 795 consecutively enrolled birth events after the introduction of the WHO Safe Childbirth Checklist program. Twenty-nine essential practices that target the major causes of childbirth-related mortality, such as hand hygiene and uterotonic administration, were evaluated. The primary end point was the average rate of successful delivery of essential childbirth practices by health workers. Delivery of essential childbirth-related care practices at each birth event increased from an average of 10 of 29 practices at baseline (95%CI 9.4, 10.1) to an average of 25 of 29 practices afterwards (95%CI 24.6, 25.3; p<0.001). There was significant improvement in the delivery of 28 out of 29 individual practices. No adverse outcomes relating to the intervention occurred. Study limitations are the pre-post design, potential Hawthorne effect, and focus on processes of care versus health outcomes.
Introduction of the WHO Safe Childbirth Checklist program markedly improved delivery of essential safety practices by health workers. Future study will determine if this program can be implemented at scale and improve health outcomes.
Efforts to achieve the Millennium Development Goals (MDGs) to improve maternal and child health can be accelerated by addressing preterm birth and stillbirth. However, most global health stakeholders are unaware of the inextricable connections of these adverse pregnancy outcomes to maternal, newborn and child health (MNCH). Improved visibility of preterm births and stillbirths will help fuel investments and strengthen commitments in the discovery, development and delivery of low-cost solutions globally. This article addresses potential barriers and opportunities to increasing global awareness and understanding.
Qualitative research was conducted to analyze current knowledge, attitudes and commitments toward preterm birth and stillbirth; identify advocacy challenges; and learn more about examples of programs that successfully advocate for research and appropriate interventions. Forty-one individuals from 14 countries on six continents were interviewed. They included maternal, newborn, and child health advocates and implementers, United Nations agency representatives, policymakers, researchers, and private and government donors.
A common recognition of three advocacy challenges with regard to preterm birth and stillbirth emerged from these interviews: (1) lack of data about the magnitude and impact; (2) lack of awareness and understanding; and (3) lack of low-cost, effective and scalable interventions. Participants also identified advocacy opportunities. The first of these opportunities involves linking preterm birth and stillbirth to the MDGs, adding these outcomes to broader global health discussions and advocacy efforts, and presenting a united voice among advocates in the context of broader MNCH issues when addressing preterm birth and stillbirth. Another key opportunity is putting a human face to these tragedies—such as a parent who can speak to the personal impact on the family. Lastly, several interviewees suggested identifying and engaging champions to garner additional visibility and strengthen efforts. Ideal champions will work collaboratively with these and other maternal, newborn and child health issues. Conclusion: Advocacy efforts to add preterm births and stillbirths to broader MNCH goals, such as the MDGs, and to identify champions for these issues, will accelerate interdisciplinary efforts to reduce these adverse outcomes. The next article in this report presents an overview of related ethical considerations.
Despite the substantial global burden of preterm and stillbirth, little attention has been given to the ethical considerations related to research and interventions in the global context. Ethical dilemmas surrounding reproductive decisions and the care of preterm newborns impact the delivery of interventions, and are not well understood in low-resource settings. Issues such as how to address the moral and cultural attitudes surrounding stillbirths, have cross-cutting implications for global visibility of the disease burden. This analysis identifies ethical issues impacting definitions, discovery, development, and delivery of effective interventions to decrease the global burden of preterm birth and stillbirth.
This review is based on a comprehensive literature review; an ethical analysis of other articles within this global report; and discussions with GAPPS's Scientific Advisory Council, team of international investigators, and a community of international experts on maternal, newborn, and child health and bioethics from the 2009 International Conference on Prematurity and Stillbirth. The literature review includes articles in PubMed, Academic Search Complete (EBSCO), and Philosopher's Index with a range of 1995-2008.
Advancements in discovery science relating to preterm birth and stillbirth require careful consideration in the design and use of repositories containing maternal specimens and data. Equally important is the need to improve clinical translation from basic science research to delivery of interventions, and to ensure global needs inform discovery science agenda-setting. Ethical issues in the development of interventions include a need to balance immediate versus long-term impacts—such as caring for preterm newborns rather than preventing preterm births. The delivery of interventions must address: women's health disparities as determinants of preterm birth and stillbirth; improving measurements of impact on equity in coverage; balancing maternal and newborn outcomes in choosing interventions; and understanding the personal and cross-cultural experiences of preterm birth and stillbirth among women, families and communities.
Efforts to improve visibility, funding, research and the successful delivery of interventions for preterm birth and stillbirth face a number of ethical concerns. Thoughtful input from those in health policy, bioethics and international research ethics helped shape an interdisciplinary global action agenda to prevent preterm birth and stillbirth.
Normal and abnormal processes of pregnancy and childbirth are poorly understood. This second article in a global report explains what is known about the etiologies of preterm births and stillbirths and identifies critical gaps in knowledge. Two important concepts emerge: the continuum of pregnancy, beginning at implantation and ending with uterine involution following birth; and the multifactorial etiologies of preterm birth and stillbirth. Improved tools and data will enable discovery scientists to identify causal pathways and cost-effective interventions.
Pregnancy and parturition continuum
The biological process of pregnancy and childbirth begins with implantation and, after birth, ends with the return of the uterus to its previous state. The majority of pregnancy is characterized by rapid uterine and fetal growth without contractions. Yet most research has addressed only uterine stimulation (labor) that accounts for <0.5% of pregnancy.
The etiologies of preterm birth and stillbirth differ by gestational age, genetics, and environmental factors. Approximately 30% of all preterm births are indicated for either maternal or fetal complications, such as maternal illness or fetal growth restriction. Commonly recognized pathways leading to preterm birth occur most often during the gestational ages indicated: (1) inflammation caused by infection (22-32 weeks); (2) decidual hemorrhage caused by uteroplacental thrombosis (early or late preterm birth); (3) stress (32-36 weeks); and (4) uterine overdistention, often caused by multiple fetuses (32-36 weeks). Other contributors include cervical insufficiency, smoking, and systemic infections. Many stillbirths have similar causes and mechanisms. About two-thirds of late fetal deaths occur during the antepartum period; the other third occur during childbirth. Intrapartum asphyxia is a leading cause of stillbirths in low- and middle-income countries.
Utilizing new systems biology tools, opportunities now exist for researchers to investigate various pathways important to normal and abnormal pregnancies. Improved access to quality data and biological specimens are critical to advancing discovery science. Phenotypes, standardized definitions, and uniform criteria for assessing preterm birth and stillbirth outcomes are other immediate research needs.
Preterm birth and stillbirth have multifactorial etiologies. More resources must be directed toward accelerating our understanding of these complex processes, and identifying upstream and cost-effective solutions that will improve these pregnancy outcomes.
A detailed retrospective analysis was made of the records of 486 preterm infants, who accounted for 5-1% of all births during 1973 and 1974. Whereas preterm delivery did not contribute to perinatal mortality in terms of stillbirth, it outweighed all other causes in terms of early neonatal deaths. Preterm birth was responsible for 85% of the early neonatal deaths not due to lethal congenital deformities. Early neonatal mortality rates were closely linked both to gestational age and birth weight and to the reason for preterm birth. Early neonatal mortality was high (97 per 1000) when preterm labour was spontaneous, whether or not associated with material or fetal disease or with multiple pregnancy, but low (27 per 1000) when preterm delivery was elective. Preventing spontaneous preterm labour would considerably reduce neonatal mortality in our community.
The vast majority of global stillbirths occur in low- and middle-income countries, and in many settings, the majority of stillbirths occur antenatally, prior to the onset of labour. Poor nutritional status, lack of antenatal care and a number of behaviours increase women's risk of stillbirth in many resource-poor settings. Interventions to reduce these risks could reduce the resulting burden of stillbirths, but the evidence for the impact of such interventions has not yet been comprehensively evaluated.
This second paper of a systematic review of interventions that could plausibly impact stillbirth rates covers 12 different interventions relating to behavioural and socially mediated risk factors, including exposures to harmful practices and substances, antenatal care utilisation and quality, and maternal nutrition before and during pregnancy. The search strategy reviewed indexed medical journals on PubMed and the Cochrane Library. If any eligible randomised controlled trials were identified that were published after the most recent Cochrane review, they were added to generate new meta-analyses. Interventions covered in this paper have a focus on low- and middle-income countries, both because of the large burden of stillbirths and because of the high prevalence of risk factors including maternal malnutrition and harmful environmental exposures. The reviews and studies belonging to these interventions were graded and conclusions derived about the evidence of benefit of these interventions.
From a programmatic perspective, none of the interventions achieved clear evidence of benefit. Evidence for some socially mediated risk factors were identified, such as exposure to indoor air pollution and birth spacing, but still require the development of appropriate interventions. There is a need for additional studies on culturally appropriate behavioural interventions and clinical trials to increase smoking cessation and reduce exposure to smokeless tobacco. Balanced protein-energy supplementation was associated with reduced stillbirth rates, but larger well-designed trials are required to confirm findings. Peri-conceptional folic acid supplementation significantly reduces neural tube defects, yet no significant associated reductions in stillbirth rates have been documented. Evidence for other nutritional interventions including multiple micronutrient and Vitamin A supplementation is weak, suggesting the need for further research to assess potential of nutritional interventions to reduce stillbirths.
Antenatal care is widely used in low- and middle-income countries, and provides a natural facility-based contact through which to provide or educate about many of the interventions we reviewed. The impact of broader socially mediated behaviors, such as fertility decision-making, access to antenatal care, and maternal diet and exposures like tobacco and indoor air pollution during pregnancy, are poorly understood, and further research and appropriate interventions are needed to test the association of these behaviours with stillbirth outcomes. For most nutritional interventions, larger randomised controlled trials are needed which report stillbirths disaggregated from composite perinatal mortality. Many antepartum stillbirths are potentially preventable in low- and middle-income countries, particularly through dietary and environmental improvement, and through improving the quality of antenatal care – particularly including diagnosis and management of high-risk pregnancies – that pregnant women receive.
In a Danish nationwide cohort study of 292 births from 1973 to 2002 in women with Hodgkin's disease (HD), we compared birth outcome with 14 042 births from a cohort of mothers without cancer. We found no substantially increased risk of preterm birth, low birth weight at term, or stillbirth and no difference in proportion of male newborns for 192 children of women with HD before pregnancy. The prevalence odds ratio (POR) for congenital abnormalities was 1.7 (95% confidence interval (CI): 0.9–3.1). Among 15 newborns of mothers diagnosed during pregnancy, the POR of preterm birth was 26.6 (95% CI: 8.5–83.0), but five out of the eight preterm deliveries among these women were elective. We found no substantially increased risk of adverse birth outcome among 85 newborns of women diagnosed within 2 years postpartum, though effect estimates were imprecise. The overall findings are reassuring, they cannot exclude the possibility of an increased risk of congenital abnormalities for newborns of women diagnosed with HD before pregnancy.
Hodgkin's disease; epidemiology; pregnancy; birth outcome; cohort study
Approximately one million stillbirths occur annually during labour; most of these stillbirths occur in low and middle-income countries and are associated with absent, inadequate, or delayed obstetric care. The low proportion of intrapartum stillbirths in high-income countries suggests that intrapartum stillbirths are largely preventable with quality intrapartum care, including prompt recognition and management of intrapartum complications. The evidence for impact of intrapartum interventions on stillbirth and perinatal mortality outcomes has not yet been systematically examined.
We undertook a systematic review of the published literature, searching PubMed and the Cochrane Library, of trials and reviews (N = 230) that reported stillbirth or perinatal mortality outcomes for eight interventions delivered during labour. Where eligible randomised controlled trials had been published after the most recent Cochrane review on any given intervention, we incorporated these new trial findings into a new meta-analysis with the Cochrane included studies.
We found a paucity of studies reporting statistically significant evidence of impact on perinatal mortality, especially on stillbirths. Available evidence suggests that operative delivery, especially Caesarean section, contributes to decreased stillbirth rates. Induction of labour rather than expectant management in post-term pregnancies showed strong evidence of impact, though there was not enough evidence to suggest superior safety for the fetus of any given drug or drugs for induction of labour. Planned Caesarean section for term breech presentation has been shown in a large randomised trial to reduce stillbirths, but the feasibility and consequences of implementing this intervention routinely in low-/middle-income countries add caveats to recommending its use. Magnesium sulphate for pre-eclampsia and eclampsia is effective in preventing eclamptic seizures, but studies have not demonstrated impact on perinatal mortality. There was limited evidence of impact for maternal hyperoxygenation, and concerns remain about maternal safety. Transcervical amnioinfusion for meconium staining appears promising for low/middle income-country application according to the findings of many small studies, but a large randomised trial of the intervention had no significant impact on perinatal mortality, suggesting that further studies are needed.
Although the global appeal to prioritise access to emergency obstetric care, especially vacuum extraction and Caesarean section, rests largely on observational and population-based data, these interventions are clearly life-saving in many cases of fetal compromise. Safe, comprehensive essential and emergency obstetric care is particularly needed, and can make the greatest impact on stillbirth rates, in low-resource settings. Other advanced interventions such as amnioinfusion and hyperoxygenation may reduce perinatal mortality, but concerns about safety and effectiveness require further study before they can be routinely included in programs.
Preterm birth is the major cause of perinatal morbidity and mortality in the developed world, and spontaneous preterm labor is the commonest cause of preterm birth. Interventions to treat women in spontaneous preterm labor have not reduced the incidence of preterm births but this may be due to increased risk factors, inclusion of births at the limits of viability, and an increase in the use of elective preterm birth. The role of antibiotics remains unproven. In the largest of the randomized controlled trials, evaluating the use of antibiotics for the prevention of preterm births in women in spontaneous preterm labor, antibiotics against anaerobes and bacterial vaginosis-related organisms were not included, and no objective evidence of abnormal genital tract flora was obtained. Atosiban and nifedipine are the main tocolytic agents used to treat women in spontaneous preterm labor, but atosiban is the tocolytic agent with the fewest maternal – fetal side effects. A well conducted randomized controlled trial comparing atosiban with nifedipine for their effectiveness and safety is needed.
preterm labor; preterm births; management; tocolytics; atosiban
Data on birth outcome in women diagnosed with cancer before, during, or shortly after pregnancy are very sparse. The purpose of this review was to summarize the existing epidemiologic evidence of the adverse effect of breast cancer, cutaneous malignant melanoma, and Hodgkin’s disease on birth outcome.
The MEDLINE database was used to review the literature systematically. Studies that examined the following outcomes were included: preterm birth, low birth weight, low birth weight at term, stillbirths, congenital abnormalities, male proportion of newborns, and mean birth weight. Studies were grouped according to whether the woman had been diagnosed with the specific cancer before, during, or shortly after pregnancy.
Few data exist on birth outcome in women with breast cancer, melanoma, or Hodgkin’s disease. The overall results from the limited number of studies, which included a comparison group for birth outcome, were reassuring. However, for women diagnosed with breast cancer before pregnancy, the only 2 studies that included comparison groups for birth outcome had conflicting results regarding the risk of preterm birth and congenital abnormalities. Furthermore, a recent cohort study of birth outcome in women who were diagnosed with Hodgkin’s disease before pregnancy indicated a slightly increased risk of congenital abnormalities among the newborns.
Overall, the existing studies offer reassuring results concerning the risks of adverse birth outcome for women diagnosed with breast cancer, melanoma, or Hodgkin’s disease before, during or shortly after pregnancy. A limitation of most studies was the imprecise risk estimates caused by the small number of adverse birth outcomes and the lack of results stratified by treatment. Therefore, international collaboration is necessary in the future, to obtain more precise risk estimates for adverse birth outcomes, and to allow stratified analyses according to, for example, treatment.
epidemiology; breast cancer; melanoma; Hodgkin’s disease; birth outcome
Infection is a well acknowledged cause of stillbirths and may account for about half of all perinatal deaths today, especially in developing countries. This review presents the impact of interventions targeting various important infections during pregnancy on stillbirth or perinatal mortality.
We undertook a systematic review including all relevant literature on interventions dealing with infections during pregnancy for assessment of effects on stillbirths or perinatal mortality. The quality of the evidence was assessed using the adapted Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach by Child Health Epidemiology Reference Group (CHERG). For the outcome of interest, namely stillbirth, we applied the rules developed by CHERG to recommend a final estimate for reduction in stillbirth for input to the Lives Saved Tool (LiST) model.
A total of 25 studies were included in the review. A random-effects meta-analysis of observational studies of detection and treatment of syphilis during pregnancy showed a significant 80% reduction in stillbirths [Relative risk (RR) = 0.20; 95% confidence interval (CI): 0.12 - 0.34) that is recommended for inclusion in the LiST model. Our meta-analysis showed the malaria prevention interventions i.e. intermittent preventive treatment (IPTp) and insecticide-treated mosquito nets (ITNs) can reduce stillbirths by 22%, however results were not statistically significant (RR = 0.78; 95% CI: 0.59 – 1.03). For human immunodeficiency virus infection, a pooled analysis of 6 radomized controlled trials (RCTs) failed to show a statistically significant reduction in stillbirth with the use of antiretroviral in pregnancy compared to placebo (RR = 0.93; 95% CI: 0.45 – 1.92). Similarly, pooled analysis combining four studies for the treatment of bacterial vaginosis (3 for oral and 1 for vaginal antibiotic) failed to yield a significant impact on perinatal mortality (OR = 0.88; 95% CI: 0.50 – 1.55).
The clearest evidence of impact in stillbirth reduction was found for adequate prevention and treatment of syphilis infection and possibly malaria. At present, large gaps exist in the growing list of stillbirth risk factors, especially those that are infection related. Potential causes of stillbirths including HIV and TORCH infections need to be investigated further to help establish the role of prevention/treatment and its subsequent impact on stillbirth reduction.
Anaemia during pregnancy is major health problem. There is conflicting literature regarding the association between anaemia and its severity and maternal and perinatal outcomes.
This is a retrospective case-control study conducted at Kassala hospital, eastern Sudan. Medical files of pregnant women with severe anaemia (haemoglobin (Hb) < 7 g/dl, n = 303) who delivered from January 2008 to December 2010 were reviewed. Socio-demographic and obstetric data were analysed and compared with a similar number of women with mild/moderate anaemia (Hb = 7-10.9 g/dl, n = 303) and with no anaemia (Hb > 11 g/dl, n = 303). Logistic regression analysis was performed separately for each of the outcome measures: preeclampsia, eclampsia, preterm birth, low birth weight (LBW) and stillbirth.
There were 9578 deliveries at Kassala hospital, 4012 (41.8%) women had anaemia and 303 (3.2%) had severe anaemia. The corrected risk for preeclampsia increased only in severe anaemia (OR = 3.6, 95% CI: 1.4-9.1, P = 0.007). Compared with women with no anaemia, the risk of LBW was 2.5 times higher in women with mild/moderate anaemia (95% CI: 1.1-5.7), and 8.0 times higher in women with severe anaemia (95% CI: 3.8-16.0). The risk of preterm delivery increased significantly with the severity of anaemia (OR = 3.2 for women with mild/moderate anaemia and OR = 6.6 for women with severe anaemia, compared with women with no anaemia). The corrected risk for stillbirth increased only in severe anaemia (OR = 4.3, 95% CI: 1.9-9.1, P < 0.001).
The greater the severity of the anaemia during pregnancy, the greater the risk of preeclampsia, preterm delivery, LBW and stillbirth. Preventive measures should be undertaken to decrease the prevalence of anaemia in pregnancy.
To compare perinatal and maternal outcomes in Tuzla Canton during the 1992-1995 war in Bosnia and Herzegovina with those before (1988-1991) and after (2000-2003) the war.
We retrospectively collected data on a total of 59 707 liveborn infants and their mothers from the databases of Tuzla University Department for Gynecology and Obstetrics and Tuzla Institute for Public Health. Data on the number of live births, stillbirths, early neonatal deaths, causes of death, gestational age, and birth weights were collected. We also collected data on the number of medically unattended deliveries, examinations during pregnancy, preterm deliveries, and causes of maternal deaths. Perinatal and maternal outcomes were determined for each study period.
There were 23 194 live births in the prewar, 18 302 in the war, and 18 211 in the postwar period. Prewar perinatal mortality of 23.3 per 1000 live births increased to 25.8 per 1000 live births during the war (P<0.001), due to a significant increase in early neonatal mortality (10.3‰ before vs 15.1‰ after the war, P<0.001). After the war, both perinatal mortality (14.4‰) and early neonatal mortality (6.6‰) decreased (P<0.001 for both). The most frequent cause of early neonatal death during the war was prematurity (55.7%), with newborns most often dying within the first 24 hours after birth. During the war, there were more newborns with low birth weight (<2500 g), while term newborns had lower average body weight. Women underwent 2.4 examinations during pregnancy (5.4 before and 6.3 after the war, P<0.001 for both) and 75.9% had delivery attended by a health care professional (99.1% before and 99.8% after the war; P<0.001 for both). Maternal mortality rate of 65 per 100 000 deliveries during the war was significantly higher than that before (39 per 100 000 deliveries) and after (12 per 100 000 deliveries) the war (P<0.001 for both).
Perinatal and maternal mortality in Tuzla Canton were significantly higher during the war, mainly due to lower adequacy and accessibility of perinatal and maternal health care.
Of the global burden of 2.6 million stillbirths, around 1.2 million occur during labour i.e. are intrapartum deaths. In low-/middle-income countries, a significant proportion of women give birth at home, usually in the absence of a skilled birth attendant. This review discusses the impact of skilled birth attendance (SBA) and the provision of Emergency Obstetric Care (EOC) on stillbirths and perinatal mortality.
A systematic literature search was performed on PubMed/MEDLINE, Cochrane Database and the WHO regional libraries. Data of all eligible studies were extracted into a standardized Excel sheet containing variables such as participants’ characteristics, sample size, location, setting, blinding, allocation concealment, intervention and control details and limitations. We undertook a meta-analysis of the impact of SBA on stillbirths. Given the paucity of data from randomized trials or robust quasi-experimental designs, we undertook an expert Delphi consultation to determine impact estimates of provision of Basic and Comprehensive EOC on reducing stillbirths if there would be universal coverage (99%).
The literature search yielded 871 hits. A total of 21 studies were selected for data abstraction. Our meta-analysis on community-based skilled birth attendance based on two before-after studies showed a 23% significant reduction in stillbirths (RR = 0.77; 95% CI: 0.69 – 0.85). The overall quality grade of available evidence for this intervention on stillbirths was ‘moderate’. The Delphi process supported the estimated reduction in stillbirths by skilled attendance and experts further suggested that the provision of Basic EOC had the potential to avert intrapartum stillbirths by 45% and with provision of Comprehensive EOC this could be reduced by 75%. These estimates are conservative, consistent with historical trends in maternal and perinatal mortality from both developed and developing countries, and are recommended for inclusion in the Lives Saved Tool (LiST) model.
Both Skilled Birth Attendance and Emergency/or Essential Obstetric Care have the potential to reduce the number of stillbirths seen globally. Further evidence is needed to be able to calculate an effect size.
Exposure to household air pollution (HAP) from cooking with solid fuels affects 2.8 billion people in developing countries, including children and pregnant women. The aim of this review is to propose intervention estimates for child survival outcomes linked to HAP.
Systematic reviews with meta-analysis were conducted for ages 0-59 months, for child pneumonia, adverse pregnancy outcomes, stunting and all-cause mortality. Evidence for each outcome was assessed against Bradford-Hill viewpoints, and GRADE used for certainty about intervention effect size for which all odds ratios (OR) are presented as protective effects.
Reviews found evidence linking HAP exposure with child ALRI, low birth weight (LBW), stillbirth, preterm birth, stunting and all-cause mortality. Most studies were observational and rated low/very low in GRADE despite strong causal evidence for some outcomes; only one randomised trial was eligible.Intervention effect (OR) estimates of 0.64 (95% CI: 0.55, 0.75) for ALRI, 0.71 (0.65, 0.79) for LBW and 0.66 (0.54, 0.81) for stillbirth are proposed, specific outcomes for which causal evidence was sufficient. Exposure-response evidence suggests this is a conservative estimate for ALRI risk reduction expected with sustained, low exposure. Statistically significant protective ORs were also found for stunting [OR=0.79 (0.70, 0.89)], and in one study of pre-term birth [OR=0.70 (0.54, 0.90)], indicating these outcomes would also likely be reduced. Five studies of all-cause mortality had an OR of 0.79 (0.70, 0.89), but heterogenity precludes a reliable estimate for mortality impact. Although interventions including clean fuels and improved solid fuel stoves are available and can deliver low exposure levels, significant challenges remain in achieving sustained use at scale among low-income households.
Reducing exposure to HAP could substantially reduce the risk of several child survival outcomes, including fatal pneumonia, and the proposed effects could be achieved by interventions delivering low exposures. Larger impacts are anticipated if WHO air quality guidelines are met. To achieve these benefits, clean fuels should be adopted where possible, and for other households the most effective solid fuel stoves promoted. To strengthen evidence, new studies with thorough exposure assessment are required, along with evaluation of the longer-term acceptance and impacts of interventions.
Increasing evidence suggests that maternal gingivitis and periodontitis may be a risk factor for preterm birth and other adverse pregnancy outcomes.
To assess the relationship between periodotitis and preterm birth. Methods: A retrospective study which included 230 pregnant women, and the delivery follow up to determine the correlation between periodontitis and preterm birth.
The study indicates that periodontal infection can lead to placental-fetal exposure and, when coupled with a fetal inflammatory response, can lead to preterm delivery. Periodontitis is correlated with preterm birth, so early diagnosis and a careful treatment are very important issues.
In 2009 at the Neurology Clinic CCUS have treated 34 patients who passed the committee for recommendation to interferon therapy (25 women and 9 men). The diagnosis of multiple sclerosis is safe based on the criteria of international panel in 2000. EDSS Average score for men was 1.8, 1.9 for women, the total EDSS score was 1.8. The gender ratio is 3:1 in women than in men. Sixteen patients received interferon by the Commission for multiple sclerosis, the Federal Ministry of Health and their therapy was initiated at the clinic.
Periodontitis is one of the main causes of preterm-premature rupture of membranes and a proper treatment is the best solution for this pathology.
Periodontitis; preterm birth; preterm-premature rupture of amniotic membranes; neonatal morbidity; risk faktor.
Tumor necrosis factor-α inhibitors (anti-TNFs) are effective in the treatment of inflammatory bowel disease (IBD) recalcitrant to conventional medical therapy. As the peak incidence of IBD overlaps with the prime reproductive years, it is crucial to establish pharmacologic regimens for women of childbearing age that achieve effective disease control without posing significant fetal harm. A systematic literature review was performed to identify all human studies with birth outcomes data after maternal exposure to infliximab, adalimumab, or certolizumab pegol within 3 mo of conception or during any trimester of pregnancy. Live births, spontaneous abortions or stillbirths, preterm or premature births, low birth weight or small for gestational age infants, and congenital abnormalities were recorded. Fifty selected references identified 472 pregnancy exposures. The subsequent review includes general information regarding anti-TNF therapy in pregnancy followed by a summary of our findings. The benefits of biologic modalities in optimizing disease control during pregnancy must be weighed against the potential toxicity of drug exposure on the developing fetus. Although promising overall, there is insufficient evidence to prove absolute safety for use of anti-TNFs during pregnancy given the limitations of available data and lack of controlled trials.
Tumor necrosis factor-α inhibitors; Pregnancy; Congenital abnormalities; Safety; Infliximab; Adalimumab; Certolizumab
Maternal socioeconomic status (SES) is an important determinant of inequity in maternal and fetal health. We sought to determine the extent to which associations between adverse birth outcomes and SES can be identified using individual-level measures (maternal level of education) and community-level measures (neighbourhood income).
In Quebec, the birth registration form includes a field for the mother's years of education. Using data from birth registration certificates, we identified all births from 1991 to 2000. Using maternal postal codes that can be linked to census enumeration areas, we determined neighbourhood income levels that reflect SES.
Lower levels of both maternal education and neighbourhood income were associated with elevated crude risks of preterm birth, small-for-gestational-age (SGA) birth, stillbirth and neonatal and postneonatal death. The effects of maternal education were stronger than, and independent of, those of neighbourhood income. Compared with women in the highest neighbourhood income quintile, women in the lowest quintile were significantly more likely to have a preterm birth (adjusted odds ratio [OR] 1.14, 95% confidence interval [CI] 1.10–1.17), SGA birth (OR 1.18, 95% CI 1.15–1.21) or stillbirth (OR 1.30, 95% CI 1.13–1.48); compared with mothers who had completed community college or at least some university, mothers who had not completed high school were significantly more likely to have a preterm birth (adjusted OR 1.48, 95% CI 1.44–1.52), SGA birth (OR 1.86, 95% CI 1.82–1.91) or stillbirth (OR 1.54, 95% CI 1.36–1.74).
Individual and, to a lesser extent, neighbourhood-level SES measures are independent indicators for subpopulations at risk of adverse birth outcomes. Women with lower education levels and those living in poorer neighbourhoods are more vulnerable to adverse birth outcomes and may benefit from heightened clinical vigilance and counselling.
Each year, 287,000 women die from complications related to pregnancy or childbirth, and 3.8 million newborns die before reaching 28 days of life. The near totality (99%) of maternal and neonatal deaths occurs in low- and middle-income countries (LMICs). Utilization of essential obstetric care services including postnatal care (PNC) largely contributes to the reduction of maternal and neonatal mortality and morbidity. There is a strong need to evaluate the evidence on the unmet needs in utilization of PNC services to inform health policy planning. Our objective is to assess systematically the socioeconomic, geographic and demographic inequalities in the use of PNC interventions in low- and middle-income countries.
The current protocol adopts a strategy informed by the guidelines of The Cochrane Handbook for Systematic Reviews. Our systematic review will identify studies in English, French, Spanish, Portuguese and Chinese – provided inclusion of an English abstract - from 1960 onwards, by searching MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and the gray literature. Study selection criteria include research setting, study design, reported outcomes and determinants of interest. Our primary outcome is the utilization of PNC services, and determinants of concern are: 1) socioeconomic status (for example, income, education); 2) geographic determinants (for example, distance to a health center, rural versus urban residence); and 3) demographic determinants (for example, ethnicity, immigration status). Screening, data abstraction, and scientific quality assessment will be conducted independently by two reviewers using standardized forms. Where feasible, study results will be combined through meta-analyses to obtain a pooled measure of association between utilization of PNC services and key determinants. Results will be stratified by countries’ income levels (World Bank classification).
Our review will inform policy-making with the aim of decreasing inequalities in utilization of PNC services. This research will provide evidence on unmet needs for PNC services in LMICs, knowledge gaps and recommendations to health policy planners. Our research will help promote universal coverage of quality PNC services as an integral part of the continuum of maternal and child health care. This protocol was registered with the Prospero database (registration number: CRD42013004661).
Postnatal care; Health services utilization; Maternal health; Low- and middle-income countries; Inequalities; Systematic review; Protocol
Many stillbirths show evidence of fetal growth restriction, and most occur at preterm gestational age. The objective of this study is to compare birth weights at preterm gestational ages between live births and stillbirths, and between those occurring before or during labour.
Based on singleton births from the United States (U.S.) 2003–2005 (n=902,491) and Sweden 1992–2001 (n=946,343), we compared birth weights between singleton live births and stillbirths at 24–36 completed weeks of gestation from the U.S. and at 28–42 completed weeks from Sweden.
In both the U.S. and Sweden, stillbirth weight-for-gestational-age z-scores were at least one standard deviation lower than live birth z-scores at all preterm gestational ages (GA). In Sweden, no birth weight difference was observed between antepartum and intrapartum stillbirths at preterm GAs, whereas birth weights among intrapartum stillbirths were similar to those among live births at 37–42 weeks.
Birth weights observed at preterm gestation are abnormal, but preterm stillbirths appear to be more growth-restricted than preterm live birth. Similar birth weights among ante- and intrapartum preterm stillbirths suggest serious fetal compromise before the onset of labor.
Stillbirth; Preterm birth; Fetal growth; Intrauterine growth restriction
Twin pregnancies in low- and middle-income countries (LMICs) pose a high risk to mothers and newborns due to inherent biological risks and scarcity of health resources. We conducted a secondary analysis of the WHO Global Survey dataset to analyze maternal and perinatal outcomes in twin pregnancies and factors associated with perinatal morbidity and mortality in twins.
We examined maternal and neonatal characteristics in twin deliveries in 23 LMICs and conducted multi-level logistic regression to determine the association between twins and adverse maternal and perinatal outcomes.
279,425 mothers gave birth to 276,187 (98.8%) singletons and 6,476 (1.2%) twins. Odds of severe adverse maternal outcomes (death, blood transfusion, ICU admission or hysterectomy) (AOR 1.85, 95% CI 1.60–2.14) and perinatal mortality (AOR 2.46, 95% CI 1.40–4.35) in twin pregnancies were higher, however early neonatal death (AOR 2.50, 95% CI 0.95–6.62) and stillbirth (AOR 1.22, 95% CI 0.58–2.57) did not reach significance. Amongst twins alone, maternal age <18, poor education and antenatal care, nulliparity, vaginal bleeding, non-cephalic presentations, birth weight discordance >15%, born second, preterm birth and low birthweight were associated with perinatal mortality. Marriage and caesarean section were protective.
Twin pregnancy is a significant risk factor for maternal and perinatal morbidity and mortality in low-resource settings; maternal risk and access to safe caesarean section may determine safest mode of delivery in LMICs. Improving obstetric care in twin pregnancies, particularly timely access to safe caesarean section, is required to reduce risk to mother and baby.
There is a lack of data on the safety of midwife-led maternity care in remote or indigenous communities. In a de facto natural “experiment”, birth outcomes were assessed by primary birthing attendant in two sets of remote Inuit communities.
A geocoding-based retrospective birth cohort study in 14 Inuit communities of Nunavik, Canada, 1989–2000: primary birth attendants were Inuit midwives in the Hudson Bay (1529 Inuit births) vs western physicians in Ungava Bay communities (1197 Inuit births). The primary outcome was perinatal death. Secondary outcomes included stillbirth, neonatal death, post-neonatal death, preterm, small-for-gestational-age and low birthweight birth. Multilevel logistic regression was used to obtain the adjusted odds ratios (aOR) controlling for maternal age, marital status, parity, education, infant sex and plurality, community size and community-level random effects.
The aORs (95% confidence interval) for perinatal death comparing the Hudson Bay vs Ungava Bay communities were 1.29 (0.63 to 2.64) for all Inuit births and 1.13 (0.48 to 2.47) for Inuit births at ≥28 weeks of gestation. There were no statistically significant differences in the crude or adjusted risks of any of the outcomes examined.
Risks of perinatal death were somewhat but not significantly higher in the Hudson Bay communities with midwife-led maternity care compared with the Ungava Bay communities with physician-led maternity care. These findings are inconclusive, although the results excluding extremely preterm births are more reassuring concerning the safety of midwife-led maternity care in remote indigenous communities.
PMID: 19286689 CAMSID: cams388
To identify possible prepregnancy risk factors for antepartum stillbirth and determine if these factors identify women at higher risk for term stillbirth.
This retrospective cohort study of prepregnancy risk factors compared 712 singleton antepartum stillbirths to 174,097 singleton live births at or after 23 weeks of gestation. The risk of term antepartum stillbirth was then assessed in a subset of 155,629 singleton pregnancies.
In adjusted multivariable analyses, black race, Hispanic ethnicity, maternal age 35 years or older, nulliparity, prepregnancy body mass index (BMI) 30 kg/m2 or higher, preexisting diabetes, chronic hypertension, smoking, and alcohol use were independently associated with stillbirth. Prior cesarean delivery and history of preterm birth were associated with increased stillbirth risk in multiparas. The risk of a term stillbirth for women who were white, 25–29 years old, normal weight, multiparous, no chronic hypertension, and no preexisting diabetes was 0.8 per 1,000. Term stillbirth risk increased with these conditions: preexisting diabetes (3.1 per 1,000), chronic hypertension (1.7 per 1,000), black race (1.8 per 1,000), maternal age 35 years or older (1.3 per 1,000), BMI 30 kg/m2 or higher, (1/1000) and nulliparity (0.9 per 1,000).
There are multiple independent risk factors for antepartum stillbirth. However, the value of individual risk factors of race, parity, advanced maternal age (35– 39 years old) and BMI to predict term stillbirth is poor. Our results do not support routine antenatal surveillance for any of these risk factors when present in isolation.