Late Onset Sepsis Among Premature Infants and Breastfeeding

CQ #143 – May 6, 2019
by Anne Eglash MD, IBCLC, FABM
#LACTFACT
Premature infants who are breastfed have a lower risk of late-onset sepsis.
Neonatology 2019; 116:42-51

What is late-onset sepsis among premature infants, and what are the risk factors?

Late-onset sepsis (LOS) is a life-threatening infection in the blood stream that occurs after 72 hours of life. According to the authors of this week’s CQW, LOS is the most common cause of death in the neonatal intensive care unit, affecting 20-38% of premature infants in the first 120 days of life. Infants who survive LOS are at higher risk for longer hospitalization, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia, and neurodevelopmental delay. It is clear that risk factors for NEC include a lower birth weight and a lower gestational age, as well as having a central venous catheter (large IV into a major vein).

The study reviewed this week sought to evaluate risk factors for LOS by involving 755 infants from 9 different NICUs in The Netherlands and Belgium. They identified infants with LOS, and matched them with health control premature infants who were the same gestational age and birthweight. They compared many factors between the infants who developed LOS and those who didn’t, such as type of delivery, premature rupture of membranes, duration of intravenous nutrition, duration of being on a ventilator, type of feeding, antibiotics given after birth, among other factors.

Which statements do you believe are accurate about premature infants with LOS, and infant feeding? Choose 1 or more:
  1. Intravenous feeding (parenteral nutrition) was associated with increased LOS risk.
  2. Having an intravenous line (IV) and formula feeding increased the risk of LOS.
  3. Infants who receive breastmilk have a shorter duration of intravenous feeding.
  4. Intravenous feeding for more than 10 days increases the risk of LOS.
  5. The healthier gut microbiome in breastfed infants may be associated with a lower risk of LOS.

See the Answer

Correct Answers: All are correct
Neonatology 2019; 116:42-51
Sofia el Manouni el Hassani, Daniel JC Berkhout, Hendrik J Niemarkt, Sarah Mann, Willem P. de Boode, Veerly Cossey, Christian V. Hulzebos, Anton H van Kaam, Boris W Kramer, Richard A van Lingen, Johannes B van Goudoever, Daniel C Vijlbrief, Mirjam M. van Weissenbruch, Marc A. Benninga, Nanne KH de Boer, Tim GJ de Meij

Abstract

Background

Late-onset sepsis (LOS) in preterm infants is a leading cause of mortality and morbidity. Timely recognition and initiation of antibiotics are important factors for improved outcomes. Identification of risk factors could allow selection of infants at an increased risk for LOS.

Objectives

The aim was to identify risk factors for LOS.

Methods

In this multicenter case-control study, preterm infants born at </=30 weeks of gestation were included at 9 neonatal intensive care units. Detailed demographical and clinical data were collected daily up to day 28 postnatally. Clinical and demographic risk factors were identified using univariate and multivariate regression analyses in a 1:1 matched case-control cohort.

Results

In total, 755 infants were included, including 194 LOS cases (41 gram-negative cases, 152 gram-positive cases, and 1 fungus). In the case-control cohort, every additional day of parenteral feeding increased the risk for LOS (adjusted OR = 1.29; 95% CI 1.07-1.55; p = 0.006), whereas antibiotics administration decreased this risk (OR = 0.08; 95% CI 0.01-0.88; p = 0.039). These findings could largely be attributed to specific LOS-causative pathogens, since these predictive factors could be identified for gram-positive, but not for gram-negative, LOS cases. Specifically cephalosporins administration prior to clinical onset was inversely related to coagulase-negative staphylococcus LOS (CoNS-LOS) development. Formula feeding was an independent risk factor for development of CoNS-LOS (OR = 3.779; 95% CI 1.257-11.363; p = 0.018).

Conclusion

The length of parenteral feeding was associated with LOS, whereas breastmilk administration was protective against CoNS-LOS. A rapid advancement of enteral feeding, preferably with breastmilk, may proportionally reduce the number of parenteral feeding days and consequently the risk for LOS.

IABLE Comment by Anne Eglash MD, IBCLC, FABM

This study compared many different factors between the group of infants with and without late onset sepsis. They did not differ in terms of ventilation time, number of blood transfusions, type of delivery, or apgar score. The biggest risk factor for NEC was giving nutrition intravenously, and not breastfeeding. The best and likely the only true strategy to reduce the number of days of intravenous nutrition is to provide breastmilk orally, since breastfed infants achieve faster full enteral (gut) feedings than infants fed formula. That easily translates into breastfeeding reducing infant mortality, which is not a complicated ‘intervention.’ Knowing this, it seems unethical to not ensure that all premature infants have access to a 100% breastmilk diet (preferably mother’s own) immediately after birth.

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