Grace Chan and coauthors conducted a systematic review and meta-analysis of studies evaluating the risk of neonatal infection or colonization during the first seven days of life among newborns of mothers with bacterial infection or colonization during the intrapartum period.
Please see later in the article for the Editors' Summary
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.
Methods and Findings
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.
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.
Please see later in the article for the Editors' Summary
Millennium Development Goal 4 (MDG4)—one of eight goals agreed by world leaders in 2000 to eradicate extreme poverty globally—aims to reduce under-five mortality (deaths) to one-third of its 1990 level (12 million deaths). Progress towards reducing child mortality has accelerated recently, but MDG4 is unlikely to be met, partly because of slow progress towards reducing neonatal mortality—deaths during the first 28 days of life. Neonatal deaths now account for a greater proportion of global child deaths than in 1990. Nearly half of the children who die before their fifth birthday die during the neonatal period, with babies born in low-middle-income countries in sub-Saharan Africa and southern Asia being at the highest risk of neonatal death. Bacterial infections such as infections of the bloodstream (bacteremia/sepsis), lungs (pneumonia), and the brain's protective covering (meningitis) are responsible for a quarter of neonatal deaths. Newborns can acquire infections during birth by picking up bacteria (in particular Group B streptococcus or GBS) that are present in their mother's reproductive tract and that may or may not cause disease in the mother. Bacteria colonizing the maternal perineum (the area between the anus and the vagina) can move up the vaginal canal into the amniotic sac (the fluid-filled bag in which the baby develops). Maternal bacteremia is another source of bacterial transmission from mother to fetus. Other risk factors for neonatal infection include pre-labor rupture of the membranes (PROM) of the amniotic sac, preterm PROM, and prolonged rupture of membranes.
Why Was This Study Done?
In high-income settings, prophylactic (preventative) antibiotic treatment during labor (based on microbiological screening or risk factors such as PROM) and early diagnosis and treatment of sepsis in newborn babies has greatly reduced deaths from early-onset neonatal bacterial infection. Yet, relatively little is known about the risk factors and transmission pathways for this condition globally. In this global systematic review and meta-analysis, the researchers estimate the risk of neonatal bacterial infections (excluding sexually transmitted diseases) among newborns of mothers with bacterial infection or colonization around the time of birth. A systematic review uses predefined criteria to identify all the research on a given topic; meta-analysis is a statistical method for combining the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 83 studies (only seven of which were undertaken in settings with high neonatal mortality) that included data on laboratory-confirmed maternal infection, maternal infection indicated by clinical signs and symptoms, maternal colonization (positive bacterial cultures from the reproductive tract without any signs or symptoms of infection), or risk factors for infection such as PROM and data on neonatal infection (laboratory-confirmed or clinically indicated) or colonization. Because different studies used different definitions for infection and colonization, the researchers pooled the data from subsets of the studies using random effects meta-analysis, which allows for heterogeneity (inconsistencies) between studies. Newborns of mothers with laboratory-confirmed infection had a 6.6-fold higher risk of laboratory-confirmed infection than newborns born to mothers without laboratory-confirmed infection. Newborns of mothers with bacterial colonization had a 9.4-fold higher risk of laboratory-confirmed infection than newborns of non-colonized mothers. Finally, compared to newborns of mothers without risk factors for infection, newborns of mothers with PROM or other risk factors had a 2.3-fold higher risk of infection.
What Do These Findings Mean?
These findings indicate that an increased risk of early-onset neonatal infection is associated with maternal infection and maternal colonization and provide some quantification of the excess risk. Because all the studies were facility-based and mostly from urban settings in high-income countries, these findings provide no information about the risk of neonatal infection among home births, rural births or births at community facilities in low-income countries, which limits their generalizability. Other aspects of the studies included in this systematic review and meta-analysis are also likely to limit the accuracy of the findings. Nevertheless, these findings suggest that better diagnosis and treatment of maternal infections and colonization in low- to middle-income countries where neonatal mortality is high might substantially reduce the incidence of neonatal infections and that the development of a simple algorithm that combines clinical signs and risk factors to diagnose maternal infections might be useful in regions where laboratory facilities are unavailable. Moreover, they highlight the need for more studies of maternal and neonatal infection and colonization in resource-poor settings with high neonatal mortality.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001502.
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development, and protection around the world; it provides information on Millennium Development Goal 4 and its Childinfo website provides detailed statistics about neonatal survival and health; its Committing to Child Survival: a Promise Renewed webpage includes links to its 2012 progress report and to a video about how new health centers are helping India battle high neonatal death rates
The World Health Organization has information about Millennium Development Goal 4 and about newborn health (some information in several languages)
Countdown to 2015 provides additional information on maternal, newborn, and child survival, including its 2012 report Building a Future for Women and Children
Kidshealth, a resource provided by the not-for-profit Nemours Foundation, has information on neonatal infections for parents (in English and Spanish)
The MedlinePlus Encyclopedia has a page on neonatal sepsis (in English and Spanish)
A personal story about fatal neonatal bacterial meningitis is available on the website of Meningitis UK, a not-for profit organization; the site also includes a survivor story