Elizabeth M. McClure

Stillbirths: Rates, risk factors, and acceleration towards 2030

An estimated 2.6 million third trimester stillbirths occurred in 2015 (uncertainty range 2.4-3.0 million). The number of stillbirths has reduced more slowly than has maternal mortality or mortality in children younger than 5 years, which were explicitly targeted in the Millennium Development Goals. The Every Newborn Action Plan has the target of 12 or fewer stillbirths per 1000 births in every country by 2030. 94 mainly high-income countries and upper middle-income countries have already met this target, although with noticeable disparities. At least 56 countries, particularly in Africa and in areas affected by conflict, will have to more than double present progress to reach this target. Most (98%) stillbirths are in low-income and middle-income countries. Improved care at birth is essential to prevent 1.3 million (uncertainty range 1.2-1.6 million) intrapartum stillbirths, end preventable maternal and neonatal deaths, and improve child development. Estimates for stillbirth causation are impeded by various classification systems, but for 18 countries with reliable data, congenital abnormalities account for a median of only 7.4% of stillbirths. Many disorders associated with stillbirths are potentially modifiable and often coexist, such as maternal infections (population attributable fraction: malaria 8.0% and syphilis 7.7%), non-communicable diseases, nutrition and lifestyle factors (each about 10%), and maternal age older than 35 years (6.7%). Prolonged pregnancies contribute to 14.0% of stillbirths. Causal pathways for stillbirth frequently involve impaired placental function, either with fetal growth restriction or preterm labour, or both. Two-thirds of newborns have their births registered. However, less than 5% of neonatal deaths and even fewer stillbirths have death registration. Records and registrations of all births, stillbirths, neonatal, and maternal deaths in a health facility would substantially increase data availability. Improved data alone will not save lives but provide a way to target interventions to reach more than 7000 women every day worldwide who experience the reality of stillbirth.

Maternal mortality, stillbirth and measures of obstetric care in developing and developed countries

Objective: Maternal mortality and stillbirths are important adverse pregnancy outcomes, especially in developing countries. Because underlying causes of both outcomes appeared similar, the relationship between maternal mortality, stillbirth and three measures of obstetrical care were studied. Methods: Using data provided by the World Health Organization from 188 developed and developing countries, correlations and linear regression analyses between maternal mortality and stillbirth rates and cesarean section rates, skilled delivery attendance, and ≥ 4 prenatal visits) were developed. Results: Stillbirth and maternal mortality rates were strongly correlated, with about 5 stillbirths for each maternal death. However, the ratio increased from about 2 to 1 in least developed countries to 50 to 1 in the most developed countries. In developing countries, as the cesarean section rates increased from 0 to about 10%, both maternal mortality and stillbirth rates decreased sharply. Skilled delivery attendance was not associated with significant reductions in maternal mortality or stillbirth rates until coverage rates of about 40% were achieved. Four or more antenatal visits were not associated with significant reductions in maternal deaths until about 60% coverage was achieved. The same measure was associated with only modest decreases in stillbirth. Conclusion: Across countries, stillbirth was significantly associated with maternal mortality. Both stillbirth and maternal mortality were similarly related to all three measures of obstetric care. An increase in cesarean section rates from 0 to 10% was associated with sharp decreases in both maternal mortality and stillbirths.

The relationship of intrapartum and antepartum stillbirth rates to measures of obstetric care in developed and developing countries.

Background. The objective of this study was to explore the relationship between intrapartum and antepartum stillbirths and various measures of obstetric care in developing and developed countries. Methods. For 51 countries, we obtained data about intrapartum and antepartum stillbirth rates and obstetric care measures from the World Health Organisation (WHO) and other sources. Using piecewise regression techniques, the relationships between the intrapartum and antepartum stillbirth rates and the various measures of obstetric care were determined. Results. Developed countries had lower total stillbirth rates (6.0 versus 21.3/1,000 births, p = 0.0002) as well as a lower fraction of stillbirths that were intrapartum (0.16 versus 0.31, p = 0.0019). Developed country antepartum stillbirth rates were 5.2 versus 14.0/1,000 in developing countries (p = 0.0002). The highest antepartum stillbirth rates, all in southern Africa and Asia, ranged from 25 to 35/1,000 births. Intrapartum stillbirth rates averaged 0.9/1,000 births for developed countries compared to 7.3/1,000 in developing countries (p = 0.0024), but ranged as high as 20–25/1,000 births for some countries in southern Africa and Asia. The relationship between intrapartum stillbirth and the various measures of care were generally stronger than those for antepartum stillbirth. Over the entire range of values, for each 1% increase in the percentage of women with at least 4 antenatal visits, the intrapartum stillbirth rate decreased by 0.16 per 1,000 births (p<0.0001). As cesarean section rates increased from 0 to 8%, for each 1% increase, there was a decrease of 1.61 intrapartum stillbirths per 1,000 births. There was no relationship between the cesarean section rates and intrapartum stillbirth rates in developed countries. Conclusions. The intrapartum stillbirth rate is more closely related to various measures of obstetric care than the antepartum stillbirth rate. Increases in cesarean section rates up to 8% are associated with significant improvements in intrapartum stillbirth rates.

A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: The ACT cluster-randomised trial

BACKGROUND Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. METHODS In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. FINDINGS The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47,394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50,743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48,219 women in the intervention group and 867 (2%) of 51,523 in the control group (OR 1·45, 1·33-1·58, p<0·0001). INTERPRETATION Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. FUNDING Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Stillbirth in Developing Countries: A review of causes, risk factors and prevention strategies

Objective. To understand the rates, causes and risk factors for stillbirth in developing countries as well as the strategies that have been evaluated to reduce stillbirth. Methods. We searched the English literature for 2003–2008 for all articles related to stillbirth and perinatal mortality in developing countries and reviewed all related publications. Results. Despite the large number of stillbirths worldwide, the topic of stillbirths in developing countries has received very little research, programmatic or policy attention. In many developing countries, almost half of the deliveries occur at home, and under-reporting of stillbirths is a significant problem. Reliable data about rates and causes are unavailable in many areas of the world. Nevertheless, of the estimated 3.2 million stillbirths that occur yearly world-wide, the vast majority occur in developing countries. Rates in many developing countries are 10-fold greater or more than in developed countries. There is not a standard international classification system that defines cause of death, nor is there agreement about the lower limits of birthweight or gestational age that define stillbirth, making comparisons of causes of stillbirth or rates over time or between sites problematic. From available data, prolonged and obstructed labour, pre-eclampsia and various infections, all without adequate treatment, appear to account for the majority of stillbirths in developing countries. Identification and treatment of maternal syphilis has been effective in reducing stillbirth risk, as has improvements in access to emergency obstetrical services and particularly caesarean section. Conclusions. Further research is needed to understand the causes and the best preventive strategies for stillbirth specific to geographic areas. However, based on current data, better access to appropriate obstetric care, particularly during labour and delivery and better screening and treatment of syphilis should reduce developing country stillbirth rates dramatically.

Infection-related stillbirths

Summary Infection is an important cause of stillbirths worldwide: in low-income and middle-income countries, 50% of stillbirths or more are probably caused by infection. By contrast, in high-income countries only 10–25% of stillbirths are caused by infection. Syphilis, where prevalent, causes most infectious stillbirths, and is the infection most amenable to screening and treatment. Ascending bacterial infection is a common cause of stillbirths, but prevention has proven elusive. Many viral infections cause stillbirths but aside from vaccination for common childhood diseases, we do not have a clear prevention strategy. Malaria, because of its high prevalence and extensive placental damage, accounts for large numbers of stillbirths. Intermittent malarial prophylaxis and insecticide-treated bednets should decrease stillbirths. Many infections borne by animals and vectors cause stillbirths, and these types of infections occur frequently in low-income countries. Research that better defines the relation between these infections and stillbirths, and develops strategies to reduce associated adverse outcomes, should play an important part in reduction of stillbirths in low-income countries.

Stillbirths: the vision for 2020

Stillbirth is a common adverse pregnancy outcome, with nearly 3 million third-trimester stillbirths occurring worldwide each year. 98% occur in low-income and middle-income countries, and more than 1 million stillbirths occur in the intrapartum period, despite many being preventable. Nevertheless, stillbirth is practically unrecognised as a public health issue and few data are reported. In this final paper in the Stillbirths Series, we call for inclusion of stillbirth as a recognised outcome in all relevant international health reports and initiatives. We ask every country to develop and implement a plan to improve maternal and neonatal health that includes a reduction in stillbirths, and to count stillbirths in their vital statistics and other health outcome surveillance systems. We also ask for increased investment in stillbirth-related research, and especially research aimed at identifying and addressing barriers to the aversion of stillbirths within the maternal and neonatal health systems of low-income and middle-income countries. Finally, we ask all those interested in reducing stillbirths to join with advocates for the improvement of other pregnancy-related outcomes, for mothers and their offspring, so that a united front for improved pregnancy and neonatal care for all will become a reality.

Stillbirth in developing countries

Objective: To conduct a systematic review of the literature on stillbirths in developing countries.

Anemia prevalence and risk factors in pregnant women in an urban area of Pakistan.

Background Anemia affects almost two-thirds of pregnant women in developing countries and contributes to maternal morbidity and mortality and to low birthweight. Objective 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. Methods 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. Results 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. Conclusions 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.

Prevalence of Anxiety, Depression and Associated Factors Among Pregnant Women of Hyderabad, Pakistan

Background: Few studies have examined the relationship between antenatal depression, anxiety and domestic violence in pregnant women in developing countries, despite the World Health Organization’s estimates that depressive disorders will be the second leading cause of the global disease burden by 2020. There is a paucity of research on mood disorders, their predictors and sequelae among pregnant women in Pakistan. Aims: To determine the prevalence of anxiety and depression and evaluate associated factors, including domestic violence, among pregnant women in an urban community in Pakistan. Methods: All pregnant women living in identified areas of Hyderabad, Pakistan were screened by government health workers for an observational study on maternal characteristics and pregnancy outcomes. Of these, 1,368 (76%) of eligible women were administered the validated Aga Khan University Anxiety Depression Scale at 20—26 weeks of gestation. Results: Eighteen per cent of the women were anxious and/or depressed. Psychological distress was associated with husband unemployment (p = 0.032), lower household wealth (p = 0.027), having 10 or more years of formal education ( p = 0.002), a first (p = 0.002) and an unwanted pregnancy ( p < 0.001). The strongest factors associated with depression/anxiety were physical/sexual and verbal abuse; 42% of women who were physically and/or sexually abused and 23% of those with verbal abuse had depression/anxiety compared to 8% of those who were not abused. Conclusions: Anxiety and depression commonly occur during pregnancy in Pakistani women; rates are highest in women experiencing sexual/physical as well as verbal abuse, but they are also increased among women with unemployed spouses and those with lower household wealth. These results suggest that developing a screening and treatment programme for domestic violence and depression/anxiety during pregnancy may improve the mental health status of pregnant Pakistani women.