Neonatal mortality among preterm infants admitted to neonatal intensive care units in India and Pakistan: A prospective study.

OBJECTIVE: To explore potential reasons for differences in preterm neonatal mortality in neonatal intensive care units (NICUs) in India and Pakistan. DESIGN: A prospective observational study, the Project to Understand and Research Stillbirth and Preterms in Southeast Asia (PURPOSe) was conducted July 2018 to February 2020. SETTING: Three hospitals in Davangere, India, and a large public hospital in Karachi, Pakistan. POPULATION: Of a total of 3,202 preterm infants enrolled, 1,512 were admitted to a study NICU. METHODS: We collected data for neonates, including length of stay, diagnoses, and diagnostic tests. MAIN OUTCOME MEASURES: Neonatal mortality, tests performed, diagnoses ascertained. RESULTS: For infants of equivalent weights and gestational ages, neonatal mortality in Pakistan was twice that in the Indian NICU. The mean newborn length of stay in Pakistan was 2 days compared with 10 days for India. Fewer diagnostics and other investigations were used to determine neonatal condition or guide treatment in the Pakistani NICU. Because of limited information from testing in Pakistan concerning clinical respiratory distress, respiratory distress syndrome appeared to be over-diagnosed, whereas other conditions including pneumonia, sepsis, necrotising entercolitis and intraventricular haemorrhage were rarely diagnosed. CONCLUSION: In the Pakistani site, the limited resources available to the NICU appeared related to a shorter length of stay and decreased diagnostic testing, likely explaining the higher mortality. With improved care, reduction in mortality among preterm neonates should be achievable.

Lessons learned in implementing the Low Birthweight Infant Feeding Exploration study: A large, multi-site observational study.

OBJECTIVE: Globally, early and optimal feeding practices and strategies for small and vulnerable infants are limited. We aim to share the challenges faced and implementation lessons learned from a complex, mixed methods research study on infant feeding. DESIGN: A formative, multi-site, observational cohort study using convergent parallel, mixed-methods design. SETTING: Twelve tertiary/secondary, public/private hospitals in India, Malawi and Tanzania. POPULATION OR SAMPLE: Moderately low birthweight infants (MLBW; 1.50-2.49 kg). METHODS: We assessed infant feeding and care practices through: (1) assessment of in-facility documentation of 603 MLBW patient charts; (2) intensive observation of 148 MLBW infants during facility admission; and (3) prospective 1-year follow-up of 1114 MLBW infants. Focus group discussions and in-depth interviews gathered perspectives on infant feeding among clinicians, families, and key stakeholders. MAIN OUTCOME MEASURES: The outcomes of the primary study were: (1) To understand the current practices and standard of care for feeding LBW infants; (2) To define and document the key outcomes (including growth, morbidity, and lack of success on mother's own milk) for LBW infants under current practices; (3) To assess the acceptability and feasibility of a system-level Infant and Young Child Feeding (IYCF) intervention and the proposed infant feeding options for LBW infants. RESULTS: Hospital-level guidelines and provision of care for MLBW infants varied across and within countries. In all, 89% of charts had missing data on time to first feed and 56% lacked discharge weights. Among 148 infants observed in-facility, 18.5% were discharged prior to meeting stated weight goals. Despite challenges during COVID, 90% of the prospective cohort was followed until 12 months of age. CONCLUSIONS: Enrolment and follow-up of this vulnerable population required additional effort from researchers and the community. Using a mixed-methods exploratory study allowed for a comprehensive understanding of MLBW health and evidence-based planning of targeted large-scale interventions. Multi-site partnerships in global health research, which require active and equal engagement, are instrumental in avoiding duplication and building a stronger, generalisable evidence base.

The causes of preterm neonatal deaths in India and Pakistan (PURPOSe): a prospective cohort study.

BACKGROUND: Preterm birth remains the major cause of neonatal death worldwide. South Asia contributes disproportionately to deaths among preterm births worldwide, yet few population-based studies have assessed the underlying causes of deaths. Novel evaluations, including histological and bacteriological assessments of placental and fetal tissues, facilitate more precise determination of the underlying causes of preterm deaths. We sought to assess underlying and contributing causes of preterm neonatal deaths in India and Pakistan. METHODS: The project to understand and research preterm pregnancy outcomes and stillbirths in South Asia (PURPOSe) was a prospective cohort study done in three hospitals in Davangere, India, and two hospitals in Karachi, Pakistan. All pregnant females older than 14 years were screened at the time of presentation for delivery, and those with an expected or known preterm birth, defined as less than 37 weeks of gestation, were enrolled. Liveborn neonates with a weight of 1000 g or more who died by 28 days after birth were included in analyses. Placentas were collected and histologically evaluated. In addition, among all neonatal deaths, with consent, minimally invasive tissue sampling was performed for histological analyses. PCR testing was performed to assess microbial pathogens in the placental, blood, and fetal tissues collected. An independent panel reviewed available data, including clinical description of the case and all clinical maternal, fetal, and placental findings, and results of PCR bacteriological investigation and minimally invasive tissue sampling histology, from all eligible preterm neonates to determine the primary and contributing maternal, placental, and neonatal causes of death. FINDINGS: Between July 1, 2018, and March 26, 2020, of the 3470 preterm neonates enrolled, 804 (23%) died by 28 days after birth, and, of those, 615 were eligible and had their cases reviewed by the panel. Primary maternal causes of neonatal death were hypertensive disease (204 [33%] of 615 cases), followed by maternal complication of pregnancy (76 [12%]) and preterm labour (76 [11%]), whereas the primary placental causes were maternal and fetal vascular malperfusion (172 [28%] of 615) and chorioamnionitis, funisitis, or both (149 [26%]). The primary neonatal cause of death was intrauterine hypoxia (212 [34%] of 615) followed by congenital infections (126 [20%]), neonatal infections (122 [20%]), and respiratory distress syndrome (126 [20%]). INTERPRETATION: In south Asia, intrauterine hypoxia and congenital infections were the major causes of neonatal death among preterm babies. Maternal hypertensive disorders and placental disorders, especially maternal and fetal vascular malperfusion and placental abruption, substantially contributed to these deaths. FUNDING: Bill & Melinda Gates Foundation.