Elsevier

Seminars in Perinatology

Volume 27, Issue 4, August 2003, Pages 293-301
Seminars in Perinatology

Infections in VLBW infants: studies from the NICHD neonatal research network

https://doi.org/10.1016/S0146-0005(03)00046-6Get rights and content

Abstract

Infection is a serious complication among very low birth weight (VLBW) preterm infants hospitalized in neonatal intensive care units. This article reviews studies from the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network including infection data from observational studies and randomized controlled trials. Blood culture-proven early-onset sepsis (≤ 72 hours) was found in less than 2% of VLBW infants, but was associated with substantial morbidity and mortality. A change in pathogens causing early-onset sepsis among Network patients has been observed over the past decade, with a significant reduction in early-onset group B streptococcal infections, but also a significant increase in early-onset Escherichia coli infections. This change is particularly worrisome, because of the high death rate associated with gram-negative infections, including E coli. Late-onset (> 72 hours) sepsis developed in almost a quarter of infants. The vast majority of infections were caused by gram-positive agents, especially coagulase-negative staphylococci. The risk of late-onset sepsis was inversely related to birth weight and gestational age. Infants with late-onset sepsis were at increased risk for a number of neonatal morbidities, for prolonged hospitalization, and for death. The percentage of deaths attributed to infection increased with increasing postnatal age. The increasing survival of extremely immature infants has resulted in a cohort of infants at prolonged risk for acquired infection. Successful strategies to reduce infections among VLBW infants would improve survival, reduce neonatal morbidity, and reduce the high medical and social costs of VLBW infant care.

Section snippets

Randomized clinical trials

The Network conducted or participated in 11 randomized controlled trials (RCTs) that span a wide array of neonatal problems (Table 1). 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 Infection was the primary study outcome for 2 of these trials: “A controlled trial of intravenous immune globulin (IVIG) to reduce nosocomial infections in VLBW infants”3 and “Parenteral glutamine supplementation in extremely low birth weight (ELBW) infants: A multicenter randomized clinical trial.”12 In the IVIG trial, 2,416

Registry data: published observational studies

The Network has maintained a registry of all VLBW infants born and/or cared for at participating centers since 1987. The registry was developed to describe the populations at each participating center, to survey neonatal practices, to assess neonatal morbidity and mortality rates, and to provide information for planning randomized clinical trials.14, 15, 16, 17, 18 Information related to infection has always been included in the registry, although definitions and the exact variables collected

Studies of antenatal corticosteroids

A National Institutes of Health (NIH) Consensus Conference on the effect of corticosteroids for fetal maturation on perinatal outcomes was convened to evaluate scientific data on the use and impact of antenatal steroids.19 An aritcle summarizing Network data on antenatal steroids was presented.20 Antenatal steroid use and clinical outcomes were evaluated for 9,949 infants enrolled in the Network’s VLBW registry between 1988 and 1992. Antenatal steroid use was classified as complete (mother

Infection studies

The Network has published several studies that specifically address infection in VLBW infants. Fanaroff et al22 reviewed data from the Network’s IVIG trial to determine the incidence, clinical presentation, laboratory features, risk factors, morbidity, and mortality associated with late-onset septicemia in VLBW patients enrolled in the trial. Sixteen percent (395 of 2,416) of infants enrolled in the trial developed late-onset sepsis over the study period. The predominant presenting clincial

Conclusion

Early and late-onset infections remain important causes of morbidity and mortality among VLBW preterm infants. Although various maternal and infant risk factors have been noted, extreme prematurity is the greatest risk for infection. The increasing survival of extremely immature very low birth weight infants has resulted in a cohort of infants at prolonged risk for acquired infection. Because acquired infection is a common occurrence among VLBW infants that results in considerable morbidity and

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