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Prophylactic antenatal N-Acetyl Cysteine administration combined with postnatal administration can decrease mortality

Osnat Zmora1, Ola Gutzeit2, Linoy Segal2

  • 1Department of Pediatric Surgery, Shamir Medical Center, Zerifin, Israel.

Plos One
|June 2, 2020
PubMed
Summary

Antenatal N-Acetyl Cysteine (NAC) significantly reduced mortality and intestinal injury markers in a rat model of necrotizing enterocolitis (NEC). This suggests antenatal NAC could be a novel prophylactic treatment for high-risk pregnancies.

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Area of Science:

  • Neonatal research
  • Gastroenterology
  • Pharmacology

Background:

  • Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease affecting neonates, particularly premature infants.
  • Currently, no effective prophylactic treatments exist for NEC, apart from breast milk and gradual enteral feeding.
  • Antenatal prophylaxis for NEC is also unavailable.

Purpose of the Study:

  • To investigate the potential protective effects of antenatal N-Acetyl Cysteine (NAC) against NEC-induced intestinal damage and mortality.
  • To evaluate NAC's efficacy in a validated rat model of NEC.

Main Methods:

  • Newborn Sprague-Dawley rats were assigned to five groups: control, NEC, NEC with postnatal NAC, NEC with antenatal NAC, and NEC with both antenatal and postnatal NAC.
  • NEC was induced via hypoxia and formula feeding.
  • Intestinal tissue was analyzed for inflammatory markers (TNF-α, IL-6, IL-1β), NFkB p65, iNOS, and cleaved caspase 3 expression at the protein and mRNA levels.

Main Results:

  • Pup mortality was significantly lower in the group receiving both antenatal and postnatal NAC compared to the NEC group (11% vs. 34%).
  • NEC significantly increased intestinal injury markers compared to controls.
  • All NAC treatment groups showed significant reductions in these markers compared to the NEC group, with the most substantial decrease observed with combined antenatal and postnatal NAC administration.

Conclusions:

  • Antenatal administration of N-Acetyl Cysteine (NAC) effectively reduced NEC-related mortality and intestinal injury markers in a rat model.
  • Antenatal NAC shows promise as a novel prophylactic strategy for preventing NEC in pregnancies at risk for preterm birth.