Risk of Early-Onset Neonatal Infection with Maternal Infection or Colonization: A Global Systematic Review and Meta-Analysis

<div><p>Background</p><p>Neonatal infections cause a significant proportion of deaths in the first week of life, yet little is known about risk factors and pathways of transmission for early-onset neonatal sepsis globally. We aimed to estimate the risk of neonatal infection (excluding sexually transmitted diseases [STDs] or congenital infections) in the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.</p><p>Methods and Findings</p><p>We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, and the World Health Organization Regional Databases for studies of maternal infection, vertical transmission, and neonatal infection published from January 1, 1960 to March 30, 2013. Studies were included that reported effect measures on the risk of neonatal infection among newborns exposed to maternal infection. Random effects meta-analyses were used to pool data and calculate the odds ratio estimates of risk of infection. Eighty-three studies met the inclusion criteria. Seven studies (8.4%) were from high neonatal mortality settings. Considerable heterogeneity existed between studies given the various definitions of laboratory-confirmed and clinical signs of infection, as well as for colonization and risk factors. The odds ratio for neonatal lab-confirmed infection among newborns of mothers with lab-confirmed infection was 6.6 (95% CI 3.9–11.2). Newborns of mothers with colonization had a 9.4 (95% CI 3.1–28.5) times higher odds of lab-confirmed infection than newborns of non-colonized mothers. Newborns of mothers with risk factors for infection (defined as prelabour rupture of membranes [PROM], preterm <37 weeks PROM, and prolonged ROM) had a 2.3 (95% CI 1.0–5.4) times higher odds of infection than newborns of mothers without risk factors.</p><p>Conclusions</p><p>Neonatal infection in the first week of life is associated with maternal infection and colonization. High-quality studies, particularly from settings with high neonatal mortality, are needed to determine whether targeting treatment of maternal infections or colonization, and/or prophylactic antibiotic treatment of newborns of high risk mothers, may prevent a significant proportion of early-onset neonatal sepsis.</p><p><i>Please see later in the article for the Editors' Summary</i></p></div

Quality of data regarding care seeking for ill or suspected ill neonates: all included studies.

<p>Abbreviations: CHW, community health worker; GP, government provider; IMNCI, integrated management of childhood and neonatal illnesses, NGC, nongovernmental consultants; NGD, nongovernmental dispensers; N/A, not available; PHC, primary health care; SHC, secondary health care; TH, traditional healer.</p

Characteristics of studies that describe care seeking for ill or suspected ill neonates.

a<p>Percentage reported as a proportion of all neonates with an illness or suspected illness reported by each study.</p>b<p>Data obtained via correspondence with corresponding author.</p><p>Abbreviations: C-RCT, cluster randomized controlled trial; CHW, community health worker; ENC, essential newborn care; ENCT, essential newborn care plus thermostat; N/A, not available.</p

Quality of data regarding care seeking for ill or suspected ill neonates: summary of included studies.

<p>Abbreviations: N/A, not available.</p

Community-based studies that describe type of care sought for ill or suspected ill neonates.

a<p>Percentage reported as a proportion of all neonates with an illness or suspected illness that were included in each study. Multiple responses regarding type of care sought were permitted, as described by included studies.</p><p>Abbreviations: C, control; ENC, essential newborn care; ENCT, essential newborn care plus thermostat; I, intervention; N/A, not available.</p

Studies included in the systematic review and meta-analysis.

a<p>WHO regions: AFR: Africa; AMR: Americas; EMR: Eastern Mediterrean; EUR: Europe; SEAR: Southeast Asia; WPR: Western Pacific.</p

Maternal infection and neonatal infection.

<p>*Adjusted ORs. These studies provided estimates adjusted for confounding factors.</p

Maternal GBS colonization and neonatal infection.

<p>Maternal GBS colonization and neonatal infection.</p

Maternal colonization and neonatal colonization.

<p>Maternal colonization and neonatal colonization.</p

Flow diagram of study selection.

<p>Flow diagram of study selection.</p