Principled Subpopulation Analysis of the Betterbirth Study and the Impact of WHO's Safe Childbirth Checklist Intervention

Background: World Health Organization (WHO) developed the Safe Childbirth Checklist as an intervention to improve care and outcomes in maternal and newborn health. In the primary BetterBirth traditional trial analysis, the intervention did not significantly improve . However, a novel subgroup-based analysis could identify subpopulations that benefited from the intervention. Methods: In this work, we employ data-driven analysis methods to identify differentiated subgroups with unexpected characteristics compared to the average population. Specifically, we aim to identify: 1) vulnerable subgroups and 2) subpopulation in the intervention arm with significantly reduced outcome. The method utilizes the existing subset scanning literature that searches over a combination of features to identify the differentiated groups. Findings: We found that low birthweight (<2.5Kg) found to represent the highest vulnerable group in both control (OR: 2·04, 95% CI: 1·91-2·18, p-value<0.001) and intervention (OR: 2·07, 95% CI: 1·93-2·21, p-value <0·001) arms. Mother-baby dyads described by normal gestational age at birth, known parity, and unknown number of abortions were found to benefit from the Checklist intervention resulting 2·6% neonatal death in the intervention arm compared to 3·66% in the control arm (OR: 0·7, 95% CI: 0·62,0·79, p-value <0·001). Interpretation: The flexibility of this data-driven approach helps to answer other subgroup-based queries in the broader global health domain. Though the statistical significance of these data-driven findings is validated, their clinical significance shall not be assumed without expert validation. Funding: The Bill & Melinda Gates Foundation provided funding for this study. Declaration of Interest: No conflicts of interest Ethical Approval: Institutions that provided review include Community Empowerment Lab, Jawaharlal Nehru Medical College, the Harvard T.H. Chan School of Public Health, Population Services International, the WHO, and the Indian Council of Medical Research.