The Causes of Stillbirths in South Asia: Results from a Prospective Study in India and Pakistan (PURPOSe)

Background: South Asia contributes more than one-third of all global stillbirths, yet the cause of stillbirth remains largely unstudied in this region. New investigations, including novel assessment of placental and fetal tissues, facilitate more precise determination of the underlying causes of stillbirth. We sought to assess underlying and contributing causes of stillbirth from settings in India and Pakistan. Methods: The Project to Understand and Reduce Stillbirth and Preterm birth in Southeast Asia (PURPOSe) was established in hospitals in central India and south Pakistan to collect standardized, prospective data from women delivering in those health facilities to better understand causes of stillbirth and causes of death in preterm newborns. Here, we analyzed data from stillbirths. An expert panel reviewed available data for all stillbirths eligible for the study to determine the primary and contributing maternal, placental, and fetal causes of death. Findings: Between September 2018 and February 2020, 981 eligible stillbirths were enrolled and, of those, 611 had their cases reviewed by the expert panel. The primary maternal causes of stillbirth were hypertensive disease (36·1%), followed by severe anemia (10·8%) while the primary placental causes were maternal and fetal vascular malperfusion (47·9%). The primary fetal cause of stillbirth was intrauterine hypoxia (71·5%). When we assessed the overlap of main causes, 18·9% of all stillbirths had intrauterine hypoxia, placental malperfusion, and eclampsia/pre-eclampsia indicated as primary causes of death. Infection, including of the placenta, its membranes and in the fetus, as well as congenital anomalies also were causative for stillbirth. Interpretation: In South Asia, fetal asphyxia is the major cause of stillbirth. Several placental lesions, especially those associated with maternal and fetal vascular malperfusion and placental abruption play an important role in the pathway through asphyxia to fetal death. Maternal hypertension and especially preeclampsia is often the primary maternal condition associated with this pathway. Funding: Bill & Melinda Gates Foundation Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: The study was reviewed and approved by the ethics review committees at the Aga Khan University (Karachi, Pakistan), KLE Academy of Higher Education and Research (Belagavi, India), J.J.M. Medical College (Davangere, India), and RTI International (Durham, NC US). All women provided informed written consent prior to participation in the study.