Prioritization of modifiable risk factors for adverse pregnancy outcomes and neonatal mortality in rural Nepal

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ABSTRACT Nearly 3 million infants die each year in the first 28 days of life. An additional 2.6 million still births occur annually, almost universally in low resource settings. Two specific global targets have been established to address these rates: Sustainable Development Goal (SDG) 3.2 calls for a reduction in global neonatal mortality to 12/1000 live births, and the United Nations-endorsed Every Newborn Action Plan calls for every country to achieve 12 or fewer stillbirths per 1000 total births by 2030. Identifying and prioritizing potentially modifiable risk factors for late fetal and neonatal deaths is essential to meet the Sustainable Development Goals in low resource countries. In particular, identifying potential interventions for poor, rural populations is a first step to reducing health disparities common in these environments. We propose to prioritize risk factors in a secondary analysis of 45,000 pregnancies among married women of reproductive age combining data from four population-based randomized controlled trials in the southern low-lying plains of rural Nepal collected between 2010 and 2016. Data during pregnancy and through 28 days postpartum were collected across all trials using similar data collection instruments and procedures. All women of childbearing age in the study area were visited every 5 weeks to record date of last menstrual period and if a period was missed, to offer a pregnancy test. Maternal height, socioeconomic, demographic and reproductive history data were obtained on all consenting pregnancies. Women provided data on morbidity, care seeking and antenatal care visits, alcohol and tobacco use, weight, blood pressure, pulse and temperature from early in pregnancy (around 8-12 weeks) and monthly thereafter through delivery. Following the pregnancy outcome, women were interviewed about labor and delivery, and care of newborns. Live born infants were weighed as soon possible after birth. Infants in all studies were followed through 28 days of life. This study will separately characterize risk factors for mortality during four life stages: late fetal, intrapartum fetal, early neonatal (1-7 days) and late neonatal (8-28 days). The specific aims are to prioritize modifiable risk factors in pregnancy within the context of more distal and structural risk factors for 1) fresh and macerated stillbirths, 2) small-for-gestational-age/preterm, and 3) all cause and cause-specific early and late neonatal mortality. We will also examine differences in small-for-gestational-age/preterm and neonatal mortality by sex of the infant and whether sex modifies associations between adverse birth outcomes and neonatal mortality. The study will provide the requisite evidence to support design choices for intervention studies to reduce perinatal deaths, and late neonatal mortality in this and comparable settings.