Introduction

A comprehensive analysis of the causes of stillbirth in low- and middle-income countries concluded that lack of maternal education, high or low parity, older maternal age, and lack of access to antenatal care were significantly associated with increased risk of stillbirth [1]. Other risk factors for stillbirth include maternal nutritional status, congenital anomalies and infections during pregnancy [2,3]. Up to half of the stillbirths in low- and middle-income countries are carried to term (>36 weeks’ gestation) and weigh ≥ 2500g, suggesting that these stillbirths are potentially preventable [1].

While the epidemiology of stillbirths is not well-understood, the causes and risk factors for neonatal deaths are better known. Globally, the leading causes of neonatal mortality are preterm birth, infections and asphyxia [4]. In low- and middle-income countries, socio-demographic risk factors for neonatal deaths include maternal age, education, parity and access to antenatal and antepartum care [5-9].

Despite marked improvements in child survival, neonatal mortality constitutes 57% of the burden of child deaths in Bangladesh [10]. In Bangladesh, between 1990 and 2009, the under-5 mortality rate decreased from 148 to 52 per 1000 live births, and the infant (children < 12 months) mortality rate decreased from 102 to 41 per thousand [11]. However, this decrease in child mortality has not been accompanied by a comparable reduction in rates of neonatal (< 28 days) mortality, which was 30 per 1,000 live births in 2009 [11], a decline of 4% since 2000 [10], or of stillbirths, which declined by only 15% between 1975 and 2002 [12].

A recent study in a Dhaka slum identified birth asphyxia, sepsis and birth trauma as the main causes of neonatal mortality [13]. With 63% of the population living in rural areas, the majority of births in Bangladesh occur in rural areas where access to antenatal and obstetric care services is limited. Less than half (46%) of women living in rural Bangladesh report receiving antenatal care from medically trained personnel and only 18% report having a trained birth attendant (doctor, nurse or midwife) being present at delivery [14]. These factors likely contribute to the higher rates of stillbirths and neonatal deaths in Bangladesh.

Socio-demographic and intrapartum risk factors for adverse pregnancy outcomes have been well-studied. Whether information readily available during mid-gestation can be used to identify high-risk pregnancies in low-income settings has, to our knowledge, not been considered. We used data collected in the context of a prospective cohort study evaluating the impact of an intervention aimed at improving maternal and child nutrition and infant development in rural Bangladesh to identify the maternal and antenatal factors associated with stillbirths and neonatal deaths.

Materials and Methods

Results

We recruited 2400 pregnant women, who reported 2414 deliveries, including 17 twin births. Two women were found to be not pregnant after recruitment and one woman had not delivered five months after recruitment. We successfully contacted 2317 women at the 3-month follow-up. Reasons for loss to follow-up included being unable to locate the mother (n = 62), refusal (n = 17) and maternal death (n = 1). These households were excluded from analysis.

At the 3-month follow-up, 112 stillbirths and neonatal deaths were recorded. Verbal autopsy questionnaires were completed for all 112 deaths. The median (range) interval between death and verbal autopsy was 116 (33 - 218) days.

Of these deaths, 44 were stillbirths and 68 were neonatal deaths resulting in a stillbirth rate of 19 per 1,000 births and a neonatal mortality rate of 29 per 1,000 live births. Males comprised 60% of these deaths.

Of the stillbirths, 25 (57%) were classified as fresh. Of the neonatal deaths, 68% (n = 46) occurred during the first week of life. The leading cause of neonatal deaths was sepsis/pneumonia (48%), followed by birth asphyxia (35%) and preterm birth (19%). Causes of neonatal deaths are summarized in Table 1.

Twelve twin pairs survived the neonatal period. For one set of twins, one of the twins was stillborn, while the other survived the neonatal period. For three sets, both twins died during the neonatal period. In a fifth set, one twin died during the neonatal period.

Characteristics of stillbirths, neonatal deaths and their controls are summarized in Table 2. The proportion of mothers who received antenatal care was also similar across study groups. Compared to controls, mothers who experienced a stillbirth or neonatal death were less literate, were more likely to have a history of bleeding and eclampsia during pregnancy. Compared to controls, women who experienced a stillbirth or neonatal death were also more likely to have experienced prolonged labor and antepartum hemorrhage during delivery. The proportion of primaparous women was also similar across study groups.

Table 3 summarizes the maternal and antenatal characteristics associated with stillbirths and neonatal deaths in our study population. Socioeconomic status was not associated with increased risk for either outcome. History of bleeding during pregnancy was strongly associated with increased risk of stillbirth (adjusted odds ratio 22.4 [95% confidence interval 2.5, 197.5]) was and with increased risk of neonatal death (adjusted odds ratio 19.6 [95% confidence interval 2.1, 178.8]), whereas consuming three or more meals a day was associated with better neonatal survival (adjusted odds ratio 0.4 [95% confidence interval 0.2, 0.8]).

We also assessed the positive (PPV) and negative predictive values (NPV) of our multivariable models (see Table 4). For stillbirths, history of bleeding during pregnancy had a PPV and NPV of 83.3% and 81.8%, respectively. For neonatal deaths, history of bleeding during pregnancy and adequate maternal nutrition (≥3 meals/day) had a PPV and NPV of 80% and 81.6%, respectively.

We also investigated whether delivery and antepartum characteristics were associated with neonatal death. Antepartum hemorrhage was most strongly associated with increased risk of neonatal death (adjusted odds ratio 11.8 [95% confidence interval 2.2, 62.9]), while cesarean birth was associated with improved newborn survival (adjusted odds ratio 0.2 [95% confidence interval 0.03, 0.9]).

Discussion

Our study investigated the determinants of stillbirth and neonatal mortality in a community-based study in rural Bangladesh. Almost two-thirds (63%) of deaths in our population were fresh stillbirths or early neonatal deaths, indicating lack of access to quality obstetric care during labor and delivery. These deaths are potentially preventable if barriers to healthcare access for pregnant women are resolved. We also observed that antepartum hemorrhage was a significant risk factor for neonatal death, while consuming 3 or more meals per day during pregnancy was associated with improved neonatal survival in our population.

The main assigned causes of neonatal death in our population were birth asphyxia, sepsis and preterm birth. This order differs slightly from that reported by Lawn et al [4], who found preterm birth to be the leading cause of death among newborns, followed by infection and asphyxia. As mothers were recruited in their 7^th month of gestation, we know there were no very-early preterm births; but as follow-up was not conducted at time of birth, prevalence of later preterm birth cannot be determined. Therefore, preterm birth as cause of death may be an underestimate in our cohort.

Working in Dhaka slums, Khatun et al [13] found birth asphyxia and sepsis to be the main causes of neonatal deaths in. With 35-42% of neonatal deaths attributed to it, birth asphyxia seems to be the leading cause of neonatal mortality in Bangladesh. Therefore, programs aimed at improving newborn survival in the country will need to include interventions that treat birth asphyxia.

Previous history of stillbirth is a well-established risk factor for recurrent stillbirth and other adverse outcomes in successive pregnancies [22,23]. We did not observe this relationship in our study population. It is very difficult, if not impossible to accurately determine the underlying causes of previous stillbirths and correct them, especially in a setting similar to ours. Therefore, interventions aimed at reducing stillbirth rates in Bangladesh and other low-income settings should be similar to those aimed at improving maternal and newborn survival in general. These should include early initiation of and more rigorous antenatal care and delivering at a health facility in the presence of a skilled birth attendant.

Approximately 60% of the stillbirths and neonatal deaths in our study were male. This is not unanticipated as it is well-established that boys are predisposed towards worse survival during the neonatal period compared to girls [24,25]. Other studies conducted in similar settings and looking at determinants of neonatal survival have observed the same [26-28].

In our population, a higher proportion of mothers of newborns who survived to 3-months of age were literate compared to those women whose off-spring were stillborn or died in the neonatal period. This is not surprising. The relationship between maternal literacy/education has been well-established in similar settings [29-32]. Therefore, educating mothers and primary care-givers of newborns will constitute an important avenue for interventions aimed at child survival. Such messages can be delivered through community health works and should include information on birth preparedness, including identification of a skilled delivery attendant, as well as a health facility and means of transport in case of obstetric complications.

Less than 20% of all participants included in our study delivered at a health facility, similar to that reported from other low-income settings [33]. A major cited reason for the high proportion of home deliveries in these settings is difficulty of access to healthcare facilities [34,35]. This was certainly true in our study setting. Kishoreganj is situated in the low-lying areas of Bangladesh and a significant portion of the land remains underwater for up to 8 months out of the year. Many households live on small “islands”, which are pockets of comparatively higher ground, manually reinforced with rocks, bamboo fences and sand-filled sacks to prevent erosion. Travelling a distance of only 10 km may take many hours as those wishing to leave the “islands” need to wait to for a passing boat to take them to an access road that connects to the major highway in Kishoregangj. The travel time by boat can be as long as 60 minutes, and travel on the road can add another 60 minutes. In the dry season, the distance travelled by boat has to be completed on foot, which takes even longer. This barrier to access may be a major reason for why more than 80% of the births in our study occurred at home.

Being a twin is a risk factor for adverse pregnancy outcomes, especially in low- and middle income countries [36]. However, as there were only 17 pairs of twin births in the cohort (5 of which resulted in stillbirth or neonatal death) we could not assess the association of twinning with stillbirths or neonatal death for our population.

The higher proportion of cesarean births in children who were alive at three months of age (8% vs. 3% among those who died in the first 4 weeks of life) is indicative that there is some measure of medical oversight already in place that can identify high-risk pregnancies and convince the mother/family to deliver at a health facility. It is critical to remove the geographic barriers to access to care and ensure that health facilities in these areas are adequately equipped to deal with intrapartum complications that may arise during delivery.

About 18% of the stillbirths and neonatal deaths were due to preterm birth; a third of these may be prevented with the use of antenatal calcium supplementation to prevent pre-eclampsia and eclampsia [37]. Labor surveillance (including partograph) for the early detection of intra-partum complications can reduce early neonatal death by up to 40% [37]. Together, these two interventions might have prevented up to 22% of all stillbirths and neonatal deaths in our study.

Although there have been several studies assessing algorithms to predict risk of neonatal death based on presenting clinical signs [38,39], to our knowledge none have looked at the usefulness of maternal and antenatal characteristics in predicting risk of stillbirth and/or neonatal death. Our models, which include information readily available during mid-pregnancy, do well in accurately identifying pregnancies at higher risk of adverse outcomes. Community health workers in low-income settings, for example, can easily identify women who have had bleeding during gestation and counsel them to seek antenatal care and skilled care during delivery. This avenue may constitute an important addition to the public health arsenal improving newborn survival.

The median interval between a death and verbal autopsy in our setting was 17 weeks. This allowed for some period of mourning to have occurred, but is a source of potential recall bias in our study. For controls, data on delivery variables was obtained during the 3-month follow-up questionnaire. Given that cases in our study were newborns that died, maternal/primary care-giver recall may be differential between the cases and controls. Second, as mentioned before, one icddr,b clinician assigned cause of death after reviewing verbal autopsies. As no other independent assessment was done, validity of these assignments cannot be determined. Furthermore, only one cause was assigned to each death. Therefore, role of underlying causes, such as undernutrition was not determined.

In conclusion, the majority of stillbirths and neonatal deaths in our setting were potentially preventable with access to quality obstetric care during labor and delivery. Furthermore, maternal and antenatal characteristics can be used to identify newborns at higher risk of death. Programs designed to improve newborn survival in Bangladesh and similar settings should include a mechanism which identifies high risk pregnancies and births well before the expectant mother goes into labor. These programs should also include interventions aimed at removing barriers to healthcare access for pregnant women and their newborns.