Early antibiotics and risk for necrotizing enterocolitis in premature infants: A narrative review

Abstract

While prompt initiation of antibiotics at birth due to concerns for early onset sepsis is common, it often leads to many preterm infants being exposed to treatment despite negative blood cultures. Such exposure to early antibiotics can impact the developing gut microbiome putting infants at increased risk of several diseases. Necrotizing enterocolitis (NEC), a devastating inflammatory bowel disease that affects preterm infants, is among the most widely studied neonatal disease that has been linked to early antibiotics. While some studies have demonstrated an increased risk of NEC, other studies have demonstrated seemingly contrary findings of decreased NEC with early antibiotics. Studies using animal models have also yielded differing findings of benefit vs. harm of early antibiotic exposure on subsequent NEC susceptibility. We thus sought to conduct this narrative review to help clarify the relationship between early antibiotics exposure and future risk of NEC in preterm infants. Our objectives are to: (1) summarize findings from human and animal studies that investigated the relationship between early antibiotics and NEC, (2) highlight important limitations of these studies, (3) explore potential mechanisms that can explain why early antibiotics may increase or decrease NEC risk, and (4) identify future directions for research.

The Detrimental Effects of Peripartum Antibiotics on Gut Proliferation and Formula Feeding Injury in Neonatal Mice Are Alleviated with Lactobacillus rhamnosus GG

“…We have also shown that postnatal supplementation with the probiotic LGG can help ameliorate the negative impact of antibiotics on intestinal proliferation and reduce gut injury. Our findings in mice support accumulating evidence from human studies regarding the increased risk of NEC with peripartum antibiotic exposure [ 18 , 22 , 26 , 72 ]. Our findings also provide supporting evidence that supplementation with probiotics may be an effective strategy to help offset the harmful effects of antibiotics.…”

Nutritional Strategies for Preterm Neonates and Preterm Neonates Undergoing Surgery: New Insights for Practice and Wrong Beliefs to Uproot

“…However, in preterm, very low-birthweight infants, each day of antibiotic treatment has been associated with an increased risk of late-onset sepsis, NEC, or death [ 97 ]. Indeed, such exposure to early antibiotics can impact the developing gut microbiome [ 98 ], gastrointestinal transit [ 99 ], stool patterns, and oral feeding tolerance [ 100 , 101 ].…”

Necrotizing enterocolitis, gut microbes, and sepsis

“…Bury and Tudehope performed a systematic review evaluating the benefits and harms of enteral antibiotic prophylaxis for NEC in low birth weight and preterm infants. They found evidence that enteral antibiotics could have a prophylactic effect on the development of NEC but also raised concerns about potential harm, particularly related to the formation of resistant bacteria 187 . Interestingly, in pigs, the beneficial effects against NEC were limited to oral and non-parenteral administration of antibiotics 188–190 .…”