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Background: Stillbirth rates are high and represent a substantial proportion of the under-5 mortality in low and middle-income countries (LMIC). In LMIC, where nearly 98% of stillbirths worldwide occur, few population-based studies have documented cause of stillbirths or the trends in rate of stillbirth over time. Methods: We undertook a prospective, population-based multi-country research study of all pregnant women in defined geographic areas across 7 sites in low-resource settings (Kenya, Zambia, Democratic Republic of Congo, India, Pakistan, and Guatemala). Staff collected demographic and health care characteristics with outcomes obtained at delivery. Cause of stillbirth was assigned by algorithm. Results: From 2010 through 2018, 573,148 women were enrolled with delivery data obtained. Of the 552,547 births that reached 500 g or 20 weeks gestation, 15,604 were stillbirths; a rate of 28.2 stillbirths per 1000 births. The stillbirth rates were 19.3 in the Guatemala site, 23.8 in the African sites, and 33.3 in the Asian sites. Specifically, stillbirth rates were highest in the Pakistan site, which also documented a substantial decrease in stillbirth rates over the study period, from 56.0 per 1000 (95% CI 51.0, 61.0) in 2010 to 44.4 per 1000 (95% CI 39.1, 49.7) in 2018. The Nagpur, India site also documented a substantial decrease in stillbirths from 32.5 (95% CI 29.0, 36.1) to 16.9 (95% CI 13.9, 19.9) per 1000 in 2018; however, other sites had only small declines in stillbirth over the same period. Women who were less educated and older as well as those with less access to antenatal care and with vaginal assisted delivery were at increased risk of stillbirth. The major fetal causes of stillbirth were birth asphyxia (44.0% of stillbirths) and infectious causes (22.2%). The maternal conditions that were observed among those with stillbirth were obstructed or prolonged labor, antepartum hemorrhage and maternal infections. Conclusions: Over the study period, stillbirth rates have remained relatively high across all sites. With the exceptions of the Pakistan and Nagpur sites, Global Network sites did not observe substantial changes in their stillbirth rates. Women who were less educated and had less access to antenatal and obstetric care remained at the highest burden of stillbirth. Study registration: Clinicaltrials.gov (ID# NCT01073475).
The Global Network’s Maternal Newborn Health Registry (MNHR) is a prospective observational study that includes all pregnant women and their outcomes in defined geographic communities (clusters). For this study, sites in the Democratic Republic of Congo (DRC) (North and South Ubangi Provinces), western Kenya, Zambia (Kafue and Chongwe), Pakistan (Thatta), India (Belagavi and Nagpur) and Guatemala (Chimaltenango) were included. Each site had between 10 and 24 study clusters, which are defined geographic areas with approximately 300–500 annual births [15]. The MNHR staff, generally community health workers or nurses, known as registry administrators (RAs), attempted to identify and screen all pregnant women residing or delivering in the study communities within 48 h of delivery. At enrollment, basic demographic information was recorded, and a follow-up visit conducted within 48 h of the delivery to obtain birth outcomes, as described in detail elsewhere [15]. The study outcome data were based on medical record review, as well as interviews with birth attendants and when applicable, the family. In addition to the prospective enrollment of pregnant women, several measures were taken to ensure accuracy of the stillbirth data, including supervisory oversight of RAs’ data, review of the ratio of stillbirth to early neonatal death to identify any potential biases, and training and review of definitions. Stillbirth was defined using a modified World Health Organization (WHO) criteria of fetal deaths occurring at ≥20 weeks gestation (or for those without gestational age available ≥500 g) [16]. Macerated stillbirths were defined as those with visible signs of maceration including skin or soft tissues changes such as skin sloughing or discoloration. In 2014, the Global Network MNHR study introduced an additional data collection tool to facilitate classification of the cause of stillbirth. Using data from the supplemental form as well as clinical information in the MNHR, a model was used to estimate one primary cause of stillbirth [17, 18]. Briefly, the hierarchal algorithm first evaluates whether the stillbirth was associated with fetal trauma (i.e., accident). Next, the presence of a major (visible) congenital anomaly is assessed for potential causality; ultrasound and other more sophisticated techniques were not routinely used. If neither is present and signs of maternal or fetal infection are observed, the stillbirth is classified as infection. If none of these are present and any maternal or fetal condition associated with intrauterine asphyxia (including preeclampsia/eclampsia, hemorrhage, obstructed or prolonged labor) is present, asphyxia is defined as the cause. Finally, preterm birth is considered the cause of death if none of the prior conditions were present and the stillbirth was less than 32 weeks gestation. If none of the conditions were present, the cause of stillbirth is classified as unknown. Risk factors for stillbirth were prospectively defined based on literature review of potential factors associated with stillbirth in low-resource settings. These included maternal clinical conditions, antenatal and delivery care as well as characteristics of the fetus that were collected as part of our routine registry. A team at each research site supervised local data collection and provided the initial review of the data collected. Then, data were entered at each study site and transmitted through a secure process to the central data coordinating center, RTI International (RTI, Durham, NC). Descriptive analyses were performed as well as log binomial models using general estimation equations to account for the correlation of outcomes within cluster to estimate relative risk of stillbirth. The incidence of stillbirth was calculated as the number of stillbirths per 1000 births (live and stillbirths > 500 g) The models which evaluated stillbirths by year were limited to those clusters which collected data within the MNHR throughout the full study period, as several sites changed the number of clusters during the study period. All data analyses were done with SAS software v.9.4 (Cary, NC). Each research site obtained local approval by the ethics review committees (INCAP, Guatemala; University of Zambia, Biomedical Research Ethics Committee, Zambia; Moi University School of Medicine, Kenya; University of Kinshasa, DRC; Aga Khan University; KLE University’s Jawharal Nehru Medical College, Belagavi, India; Lata Medical Research Foundation, Nagpur, India), the institutional review boards by partner U.S. universities and the data coordinating center (RTI). All pregnant women included in the registry provided informed consent for participation in the study.
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