Background
Stillbirth has long been a large, yet mostly hidden burden of disease in the developing world [
1‐
3]. Recent studies have drawn attention to the high global burden of an estimated 3.2 million annual stillbirths [
2,
4]. Most stillbirths could be prevented by improving access to quality prenatal and obstetric care that is standard in wealthy countries [
2]. Global estimates suggest that about one-third of stillbirths occur during the intrapartum period [
5]. However, a five-country prospective study of stillbirth found only 17% of stillbirths were macerated, suggesting a higher proportion were intrapartum [
6]. Estimating the timing of stillbirth is often challenging in low resource settings,[
2,
7] and timing could not be determined in 46% of the stillbirths in an Egyptian study [
7]. Nevertheless, some estimates suggest that up to 50% of stillbirths may be attributed to intrapartum conditions in settings with poor access to obstetric care [
3]. The primary causes of stillbirth are thought to be prolonged and obstructed labor, hypertensive disorders of pregnancy and maternal infections [
2,
3].
Lack of data in countries with the highest stillbirth rates, due to poor vital registration systems and a low proportion of births or deaths in health facilities, is a critical barrier to addressing the problem of stillbirths [
1,
2,
8,
9]. Measurement of stillbirths in community settings is particularly challenging, and verbal autopsy studies have often been used to assign causes of under-five child and neonatal deaths in settings where most deaths occur outside of facilities or a physician's care [
9‐
15]. This methodology has also been used recently to ascertain causes of stillbirth [
7,
16‐
18]. The main objectives of this paper were to estimate rates, types, and causes of stillbirths, using pregnancy history and verbal autopsy data from a large-scale survey conducted in rural Sylhet district of Bangladesh.
Results
A total of 48,192 births and 1,748 stillbirths were recorded during 2003 - 2005, resulting in a stillbirth rate of 36.3 per 1000 total births (95% CI: 34.6-38.0 per 1000 total births) (Table
2). Verbal autopsy interviews were completed for 1584 stillbirths (90.6%). The most common reason for incomplete interview was absence of any respondent (45%, 74/164). Background characteristics and recall period between pregnancy termination and verbal autopsy interview did not vary by interview status (Table
3). Among those who completed the interview, about 80% delivered at home, 20% were assisted by neither health personnel nor a traditional birth attendant, and the majority delivered vaginally without any assistance or only with manual assistance (Table
3). The main respondent was the mother in 98.1% (1554/1584) of the completed interviews. Among the 1554 stillbirths, 164 (10.6%) were reported by 80 women who had 2 or more stillbirths during the period through multiple births and/or repeated pregnancies. The mean recall period was 25 months (standard deviation: 11, range [
3,
44], n = 1554).
Table 2
Number of births and stillbirths by year
2003 | 16,985 | 609 | 35.9 | 544 | 537 | 323 | (60.1) | 214 | (39.9) |
2004 | 15,392 | 563 | 36.6 | 510 | 492 | 302 | (61.4) | 190 | (38.6) |
2005 | 15,815 | 576 | 36.4 | 530 | 525 | 340 | (64.8) | 185 | (35.2) |
Total
|
48,192
|
1,748
| 36.3 |
1,584
|
1,554
|
965
| (62.1) |
589
| (37.9) |
Table 3
Background characteristics of stillbirths by verbal autopsy interview status
Sex | | | | |
Male | 108 | (65.9) | 892 | (56.3) | |
Female | 55 | (33.5) | 678 | (42.8) | |
Missing | 1 | (0.6) | 14 | (0.9) | 0.063 |
Maternal age | | | | |
14-19 | 2 | (1.2) | 34 | (2.1) | |
20-24 | 33 | (20.1) | 345 | (21.8) | |
25-29 | 44 | (26.8) | 434 | (27.4) | |
30-34 | 38 | (23.2) | 343 | (21.7) | |
35-39 | 31 | (18.9) | 286 | (18.1) | |
40-44 | 11 | (6.7) | 109 | (6.9) | |
45+ | 5 | (3.0) | 33 | (2.1) | 0.946 |
Maternal education | | | | |
None | 86 | (52.4) | 755 | (47.7) | |
Primary incomplete | 19 | (11.6) | 170 | (10.7) | |
Primary complete | 28 | (17.1) | 308 | (19.4) | |
Secondary+ | 31 | (18.9) | 351 | (22.2) | 0.581 |
Interval between VA interview and end of pregnancy (months) | | |
0-11 | 24 | (14.6) | 289 | (18.2) | |
12-23 | 47 | (28.7) | 445 | (28.1) | |
24-35 | 52 | (31.7) | 530 | (33.5) | |
36-44 | 41 | (25.0) | 320 | (20.2) | 0.408 |
Plurality | | | | |
Singleton | | | 1,469 | (92.7) | |
Multiple births | | | 115 | (7.3) | |
Delivery place | | | | |
Home | | | 1,253 | (79.1) | |
Facility | | | 312 | (19.7) | |
On the way to a facility | | | 9 | (0.6) | |
Other | | | 10 | (0.6) | |
Delivery attendant | | | | |
None | | | 175 | (11.0) | |
Family/Relatives | | | 167 | (10.5) | |
Doctor | | | 187 | (11.8) | |
Nurse/midwife | | | 135 | (8.5) | |
Other health personnel* | | | 24 | (1.5) | |
Traditional birth attendant † | | | 878 | (55.4) | |
Quack | | | 8 | (0.5) | |
Other | | | 10 | (0.6) | |
Delivery mode | | | | |
Vaginal delivery without assistance | | | 1,019 | (64.3) | |
Vaginal delivery with manual assistance | | | 439 | (27.7) | |
Vaginal delivery with vacuum/forceps | | | 20 | (1.3) | |
cesarean section after failure of instrument | | | 56 | (3.5) | |
cesarean section | | | 50 | (3.2) | |
Overall, 62% of stillbirths were classified as antepartum and 38% were intrapartum. However, in 131 of 965 antepartum stillbirths (13.6%), mothers reported paradoxically that the body was macerated yet that fetal movement had ceased prior to delivery, indicating potential reporting errors. In another 493 antepartum stillbirths, mothers reported cessation of fetal movement before onset of labor but no presence of maceration. The vast majority of the stillbirths occurred in term pregnancies, but, compared to intrapartum stillbirths, a larger proportion of antepartum stillbirths were in preterm pregnancies (Table
4). The distributions were comparable across the three years of the study (Table
2).
Table 4
Distribution of gestational age by timing of stillbirths: antepartum and intrapartum (n = 1554)*
7 | 123 | (12.7) | 59 | (10.0) |
8 | 110 | (11.4) | 33 | (5.6) |
9 | 730 | (75.6) | 496 | (84.2) |
10 | 2 | (0.2) | 1 | (0.2) |
Among antepartum stillbirths, based on the hierarchy of causes, about 29% had symptoms suggestive of maternal conditions, including infections (19%), hypertensive disorders (9%), or severe anemia (2%) (Table
5). Another 10% had maternal hemorrhage during pregnancy, and about 3% had congenital anomalies. A cause could not be assigned for 58% of the antepartum stillbirths using this methodology.
Table 5
Distributions of causes of stillbirths: antepartum and intrapartum (n = 1554)
Antepartum
|
Total
|
965
| |
965
| (100.0) |
| Congenital abnormality | 25 | (2.6) | 25 | (2.6) |
| Maternal hemorrhage | 101 | (10.5) | 100 | (10.4) |
| Maternal hypertensive disorder | 90 | (9.3) | 82 | (8.5) |
| Maternal infections | 225 | (23.3) | 179 | (18.6) |
| Maternal severe anemia | 28 | (2.9) | 16 | (1.7) |
| Unexplained* | - | - | 563 | (58.3) |
Intrapartum
|
Total
|
589
| |
589
| (100.0) |
| Congenital abnormality | 5 | (0.8) | 5 | (0.9) |
| Intrapartum hypoxia | 322 | (54.7) | 319 | (54.2) |
| Preterm labour | 67 | (11.4) | 43 | (7.3) |
| Maternal hypertensive disorder | 53 | (9.0) | 27 | (4.6) |
| Maternal infections | 104 | (17.7) | 32 | (5.4) |
| Unexplained* | - | - | 163 | (27.7) |
The primary cause of about half of intrapartum stillbirths was intrapartum hypoxia, according to the hierarchy (Table
5), among which the most common cause was malpresentation (48%) (results not shown). Small proportions of intrapartum stillbirths were due to preterm labour (7.3%), maternal infections (5.4%), and maternal hypertensive disorders (4.6%). A cause could not be assigned in 28% of intrapartum stillbirths. Overall, 19% and 14% of the total stillbirths were due to obstetric complications and maternal infections, respectively. We further analyzed causes among singleton births only (n = 1444) (Table
6), and results were comparable with those based on all births.
Table 6
Distributions of causes of stillbirths among singleton births only: antepartum and intrapartum (n = 1444)
Antepartum
|
Total
|
912
| |
912
| (100.0) |
| Congenital abnormality | 24 | (2.6) | 24 | (2.6) |
| Maternal hemorrhage | 93 | (10.2) | 92 | (10.1) |
| Maternal hypertensive disorder | 84 | (9.2) | 77 | (8.4) |
| Maternal infections | 214 | (23.5) | 171 | (18.8) |
| Maternal severe anemia | 28 | (3.1) | 16 | (1.8) |
| Unexplained* | - | - | 532 | (58.3) |
Intrapartum
|
Total
|
532
| |
532
| (100.0) |
| Congenital abnormality | 5 | (0.9) | 5 | (0.9) |
| Intrapartum hypoxia | 278 | (52.3) | 275 | (51.7) |
| Preterm labour | 36 | (6.8) | 22 | (4.1) |
| Maternal hypertensive disorder | 50 | (9.4) | 29 | (5.5) |
| Maternal infections | 96 | (18.1) | 30 | (5.6) |
| Unexplained* | - | - | 171 | (32.1) |
Sixty-two antepartum stillbirths and 117 intrapartum stillbirths met cases definitions of multiple causes, based on the non-hierarchical approach. Table
7 presents distribution of causes of stillbirths allowing for multiple causes based on the non-hierarchical approach, suggesting the primary-cause results were sensitive to changes in the hierarchy applied. For example, 23 antepartum stillbirths met the case definitions for maternal hemorrhage as well as maternal infections, and either cause was determined as the primary cause, depending on the order of the hierarchy.
Table 7
Overlapping multiple causes of stillbirths based on the non-hierarchical approach: antepartum and intrapartum (n = 1554)
Congenital abnormality (n = 25) | | | 1 | (4.0) | 2 | (8.0) | 5 | (20.0) | 1 | (4.0) | 17 | (68.0) |
Maternal hemorrhage (n = 101) | 1 | (1.0) | | | 6 | (5.9) | 23 | (22.8) | 2 | (2.0) | 73 | (72.3) |
Maternal hypertensive disorder (n = 90) | 2 | (2.2) | 6 | (6.7) | | | 21 | (23.3) | 6 | (6.7) | 59 | (65.6) |
Maternal infections (n = 225) | 5 | (2.2) | 23 | (10.2) | 21 | (9.3) | | | 6 | (2.7) | 175 | (77.8) |
Maternal severe anemia (n = 28) | 1 | (3.6) | 2 | (7.1) | 6 | (21.4) | 6 | (21.4) | | | 16 | (57.1) |
Intrapartum (n = 589)
| Overlap with | | |
Cause | Congenital abnormality (n = 5) | Intrapartum hypoxia (n = 322) | Preterm labour (n = 67) | Maternal hypertensive disorder (n = 53) | Maternal infections (n = 104) | No overlap with other causes |
| n | (%) | n | (%) | n | (%) | n | (%) | n | (%) | n | (%) |
Congenital abnormality (n = 5) | | | 3 | (0.9) | 1 | (1.5) | 0 | (0.0) | 2 | (1.9) | 0 | (0.0) |
Intrapartum hypoxia (n = 322) | 3 | (60.0) | | | 23 | (34.3) | 23 | (43.4) | 61 | (58.7) | 220 | (68.3) |
Preterm labour (n = 67) | 1 | (20.0) | 23 | (7.1) | | | 3 | (5.7) | 7 | (6.7) | 36 | (53.7) |
Maternal hypertensive disorder (n = 53) | 0 | (0.0) | 23 | (7.1) | 3 | (4.5) | | | 10 | (9.6) | 21 | (39.6) |
Maternal infections (n = 104) | 2 | (40.0) | 61 | (18.9) | 7 | (10.4) | 10 | (18.9) | | | 32 | (30.8) |
Discussion
We used pregnancy history and verbal autopsy data to examine levels, timing, and causes of stillbirth in a rural population in Bangladesh, contributing to limited literature on stillbirth in developing countries. The estimated stillbirth rate was about 36 per 1000 total births. About 60% and 40% of these stillbirths were classified as antepartum and intrapartum, respectively. Maternal infections and hypertensive disorders, for which various interventions are available, contributed to about 21% of total stillbirths. About 50% of intrapartum stillbirths or 19% of all stillbirths were attributed to obstetric complications.
The estimated proportion of intrapartum stillbirths was roughly comparable with that reported in population-level studies conducted in Pakistan[
18] and Ghana,[
17] although the reported proportion ranged widely in other population-based studies, from 25% globally[
5] to 86% in Nepal [
29]. High proportions of intrapartum stillbirths were reported in studies where antepartum stillbirths were defined as "macerated",[
6,
29] whereas our study assigned antepartum stillbirth to those that were macerated or for which the mother reported that fetal movement stopped before the onset of labor. Our results are in agreement with previous studies in developing countries that have attributed high rates of stillbirth to the presence of a high burden of maternal conditions during pregnancy and obstetric complications during labor and delivery [
17,
18,
30‐
32]. The cesarean section rate in our study population was relatively low (4.7%), suggesting there was an unmet need for emergency obstetric care which contributed to risk for intrapartum stillbirth. Direct comparison of our results on individual causes to previous studies is limited, however, due to differences in methodology. In addition to differences in questionnaires and definitions of causes across studies,[
2,
6,
28,
33] previous studies employed varying methods to assign causes such as physician review of the verbal autopsy data with[
17] or without[
18,
30‐
32] structured hierarchical algorithms.
Despite limitations, verbal autopsy methodology is the only feasible method currently available for use in defining causes of stillbirths in settings where most births and deaths take place at home and a functional vital registration system does not exist [
2,
9,
33,
34]. In our study, well-trained field workers from the community administered the questionnaire, which was locally adapted to include culturally appropriate terms describing signs and symptoms. Further, high response rates in a population defined through a census and found to have high mortality provided complete verbal autopsy data on about 1600 stillbirths over the three-year study period.
Our findings, however, have a number of limitations. First, the most critical limitation is possible underestimation of stillbirths using pregnancy histories, as reported in a previous study [
35]. In the home-care arm of our study, based on the prospective pregnancy and birth surveillance data collected by community health workers,[
36,
37] the stillbirth rate during 2004-2005 was estimated to be 50.4 per 1000 total births (562/11174), about 35% higher than our corresponding estimate based on retrospective pregnancy histories. While our neonatal mortality rate estimates were comparable between the prospective surveillance and retrospective pregnancy history data (data not shown), socio-cultural taboo might have discouraged reporting stillbirths in the retrospective survey of pregnancy histories [
2]. Improvements in questionnaires and/or field administration of the questionnaire are needed to improve the ascertainment of stillbirth in pregnancy histories [
7,
18,
21,
29]. It is possible that women were more likely to omit antepartum stillbirths, especially those which occurred earlier during pregnancy, than intrapartum stillbirths,[
17,
35] potentially underestimating the burden of antepartum stillbirths. However, this needs further confirmation.
Second, we estimated timing of stillbirths based on maternal-report to two questions in the verbal autopsy questionnaire - 'macerated body' and 'cessation of fetal movement before labor'. However, accuracy of classification based on such reporting has not been validated,[
9] and our results suggested potential issues in classification. Classification of stillbirths into antepartum and intrapartum would require examination of fetal remains for presence of signs indicating whether the fetus died more or less than 12 hours before delivery (antepartum and intrapartum stillbirths, respectively),[
5] although there is potential misclassification using this definition [
2,
5,
9]. However, socio-cultural factors may encourage rapid and secretive disposal of fetal remains in many cultures [
2]. Mothers might not have seen the remains and/or family members who buried the remains might not have conveyed details of the remains to mothers, raising potential issues in validity of maternal report in questions regarding appearance of the remains. We speculate that macerated body might have been under-reported in our population.
Third, our case definitions used in both non-hierarchical and hierarchical expert algorithms, have not been validated. Use of the World Health Organization standardized verbal autopsy questionnaire along with the algorithms is likely to have low sensitivity for certain case definitions. For example, we only measured the lethal congenital abnormalities of the head and neural tube defects, and stillbirths due to other common congenital abnormalities, including chromosomal abnormalities and major cardiac defects were not included. Measurement of maternal infections is based on only two symptoms, whereas asymptomatic infections, including urinary and reproductive tract infections, are important causes of stillbirths. Hypertensive disorders and anemia may be underreported in this setting, since the definition consisted of convulsion or hypertension during pregnancy diagnosed by a health worker, while antenatal screening is not universal and is often of poor quality in the study area. A substantial proportion of stillbirths (49% of total) was unexplained in our study, but this level is comparable to previous studies using verbal autopsy data [
17,
18]. Even in settings with adequate obstetric care, stillbirth often remains an event without clear cause [
38].
In addition, the high degree of overlap between causes in our data suggests that the results are sensitive to changes in the hierarchy applied. There is relatively little experience in the use of verbal autopsy and hierarchical algorithms to assign the primary cause for stillbirth,[
33] whereas there is ample experience of using verbal autopsy to ascertain causes of neonatal deaths [
10‐
14,
39] and growing agreement exists regarding use of hierarchical algorithms to assign the primary causes of neonatal deaths [
15,
40]. Only one study, using data from the Obaapa trial conducted in rural central Ghana, validated hierarchical algorithms to assign primary cause of stillbirths based on verbal autopsy data. The study reported high sensitivity and specificity of their algorithm in identifying intrapartum stillbirths due to obstetric complications but lower validity for other causes compared to physician review [
16]. Also, sensitivity and specificity were generally lower for identifying causes of stillbirths compared to causes of neonatal deaths [
16].
Finally, the mean recall period of 25 months in our study is longer than that generally reported [
28]. However, the relationship between reporting errors and recall periods has been studied mainly using verbal autopsy data for adult deaths, where the respondent's recall may not be as accurate as maternal recall of symptoms and signs preceding stillbirths or child deaths [
28].
Despite these limitations in measurements, our findings on stillbirth burden and etiology have important programmatic implications for preventing stillbirths in rural Bangladesh and in similar settings. About half of the intrapartum stillbirths, or about 19% of total stillbirths, resulted from obstetric complications. Maternal conditions, including hypertensive disorders, infections, and anemia, contributed to 29% of antepartum stillbirths and 11% of intrapartum stillbirths. In particular, maternal infections contributed to 14% of total stillbirths in our population, suggesting the need to address this complication at the community level. A recent population-based study on neonatal bacteremia also suggested the potential significance of preventing vertical transmission of maternal infections to reduce neonatal infections in communities [
27].
Preventive and curative interventions to address maternal complications are available, but have not been scaled up effectively in many low-resource settings [
41,
42]. Maternal infections during pregnancy include a variety of conditions such as urinary and reproductive tract infections, sexually transmitted infections, malaria, and infection following or causing premature rupture of membranes. Prophylactic antibiotic treatment may reduce the risk of maternal infections and premature rupture of the membranes,[
43,
44] although evidence on the reduction in perinatal mortality is inconclusive [
42]. Routine screening and treatment of syphilis is an effective intervention to reduce perinatal mortality, although the disease burden is thought to be low in our study population [
41,
42]. Prophylactic treatment and insecticide-treated bednets are also effective interventions to reduce perinatal mortality in malaria endemic areas [
41,
42,
45‐
47]. Hypertensive disorders during pregnancy include a wide range of conditions,[
48,
49] but pregnancy-induced hypertension and preeclampsia may be effectively prevented with calcium supplementation during pregnancy [
41,
42,
50]. Finally, nutritional interventions during pregnancy to address both macro- and micronutrient deficiencies have the potential to address important contributing factors for stillbirths,[
41] although further evidence of their effectiveness in reducing stillbirths is needed [
41,
51].
In order to reduce intrapartum stillbirths, strategies to improve access to skilled childbirth care and management of obstetric complications during labor and delivery are essential [
41,
52,
53]. Such interventions include improving birth preparedness[
54,
55] and increasing access to skilled birth attendance at home[
56‐
59] and high quality emergency obstetric care, in particular including Caesarean section and access to essential drugs [
53,
60,
61]. To improve access to these interventions, strategies such as community mobilization, financial incentive schemes, and community referral/transport systems have been suggested to be promising [
62]. Magnesium sulfate can effectively prevent eclamptic seizures during labor, although its impact on perinatal mortality has not been demonstrated [
52]. Finally, maintaining quality of care during labor is essential as improper use of uterotonics is associated with increased risk of stillbirth [
63].
Acknowledgements
This research was funded by the United States Agency for International Development (USAID), through cooperative agreements with the Johns Hopkins Bloomberg School of Public Health and the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) and by the Saving Newborn Lives program of Save the Children-US through a grant from the Bill & Melinda Gates Foundation. Projahnmo was comprised of the ICDDR,B; the Bangladesh government's Ministry of Health and Family Welfare; Bangladeshi nongovernmental organizations, including Shimantik, Save the Children-US, Dhaka Shishu Hospital and the Institute of Child and Mother Health; and the Johns Hopkins Bloomberg School of Public Health. We thank the many individuals in Sylhet district who gave their time generously and the field and data management staff of Projahnmo who worked tirelessly. We thank the members of the Projahnmo Technical Review Committee, the Bangladesh Ministry of Health and Family Welfare colleagues at the sub-district, district and central levels, and the members of the Shimantik Executive Committee for their valuable help and advice. The critical innovative inputs of Projahnmo study group members are acknowledged. The Projahnmo Study Group includes (in alphabetical order): Jahiruddin Ahmed, Saifuddin Ahmed, Ashraful Alam, Nabeel Ashraf Ali, Ahmed Al-Kabir, Arif Billah Al-Mahmud, Ahmed Al-Sabir, Tariq Anwar, Abdullah H. Baqui, Nazma Begum, Robert E. Black, Atique Iqbal Chowdhury, Mohiuddin Chowdhury, Sameena Chowdhury, Gary L. Darmstadt, Milan Krishna Das, Shams El-Arifeen, Zafar Ahmad Hakim, A.K.M. Fazlul Haque, Quamrul Hasan, Daniel Hossain, Shahla Khatun, Paul Law, Amnesty LeFevre, Ishtiaq Mannan, Qazi Sadequr Rahman, Syed Moshfiqur Rahman, Samir K. Saha, Mathuram Santosham, Habibur Rahman Seraji, Rasheduzzaman Shah, Ashrafuddin Siddik, Uzma Syed, Hugh Waters, Emma K. Williams, Peter J. Winch, and K. Zaman.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
AHB, SEA, GLD, and REB participated in the research and intervention design and implementation, data collection, data analysis and manuscript writing. YC participated in data analysis and manuscript writing. EKW participated in manuscript writing. IM participated in the research and intervention design and implementation and data collection. All authors contributed to preparation of the manuscript.