Neonatal sepsis and mortality in low-income and middle-income countries from a facility-based birth cohort: an international multisite prospective observational study

TLDR

Neonatal sepsis is a leading cause of neonatal mortality, accounting for 99 % of deaths in low‑ and middle‑income countries. The study aimed to determine the incidence and risk factors for neonatal sepsis and all‑cause mortality among facility‑born neonates in LMICs and to identify efficient methods for early detection to guide interventions. The prospective BARNARDS cohort enrolled 30 557 neonates from 12 LMIC sites, collected data on health‑care, maternal, birth, neonatal, and environmental factors, and used clinically suspected and laboratory‑confirmed sepsis definitions with incidence calculations and modified Poisson regression and survival models to assess associations. Among 30 557 neonates, clinically suspected sepsis occurred at 166.0 per 1 000 livebirths, laboratory‑confirmed sepsis at 46.9 per 1 000 livebirths, and all‑cause mortality at 0.83 per 1 000 neonate‑days; risk factors included maternal hypertension, recent hospitalization, higher household income, large ward size, neonatal ward type, rural residence, preterm birth, perinatal asphyxia, and multiple births, with 72.5 % of confirmed sepsis cases occurring within the first three days of life.

Abstract

BackgroundNeonatal sepsis is a primary cause of neonatal mortality and is an urgent global health concern, especially within low-income and middle-income countries (LMICs), where 99% of global neonatal mortality occurs. The aims of this study were to determine the incidence and associations with neonatal sepsis and all-cause mortality in facility-born neonates in LMICs.MethodsThe Burden of Antibiotic Resistance in Neonates from Developing Societies (BARNARDS) study recruited mothers and their neonates into a prospective observational cohort study across 12 clinical sites from Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Data for sepsis-associated factors in the four domains of health care, maternal, birth and neonatal, and living environment were collected for all mothers and neonates enrolled. Primary outcomes were clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality in neonates during the first 60 days of life. Incidence proportion of livebirths for clinically suspected sepsis and laboratory-confirmed sepsis and incidence rate per 1000 neonate-days for all-cause mortality were calculated. Modified Poisson regression was used to investigate factors associated with neonatal sepsis and parametric survival models for factors associated with all-cause mortality.FindingsBetween Nov 12, 2015 and Feb 1, 2018, 29 483 mothers and 30 557 neonates were enrolled. The incidence of clinically suspected sepsis was 166·0 (95% CI 97·69–234·24) per 1000 livebirths, laboratory-confirmed sepsis was 46·9 (19·04–74·79) per 1000 livebirths, and all-cause mortality was 0·83 (0·37–2·00) per 1000 neonate-days. Maternal hypertension, previous maternal hospitalisation within 12 months, average or higher monthly household income, ward size (>11 beds), ward type (neonatal), living in a rural environment, preterm birth, perinatal asphyxia, and multiple births were associated with an increased risk of clinically suspected sepsis, laboratory-confirmed sepsis, and all-cause mortality. The majority (881 [72·5%] of 1215) of laboratory-confirmed sepsis cases occurred within the first 3 days of life.InterpretationFindings from this study highlight the substantial proportion of neonates who develop neonatal sepsis, and the high mortality rates among neonates with sepsis in LMICs. More efficient and effective identification of neonatal sepsis is needed to target interventions to reduce its incidence and subsequent mortality in LMICs.FundingBill & Melinda Gates Foundation.