Risk of Necrotizing Enterocolitis with IV Augmentin in Pregnancy
Augmentin (amoxicillin-clavulanate) should NOT be used in pregnant women at risk of preterm delivery due to an established association with neonatal necrotizing enterocolitis (NEC). 1
Key Evidence on NEC Risk
The concern about Augmentin and NEC stems from high-quality evidence in the preterm delivery setting:
A large Cochrane systematic review found a highly significant increase in NEC when beta-lactam antibiotics (specifically Augmentin) were used in preterm premature rupture of membranes (PPROM), with a relative risk of 4.60 (95% CI 1.98-10.72). 2 This represents more than a 4-fold increased risk of this serious neonatal complication.
The American College of Obstetricians and Gynecologists (ACOG) explicitly warns against using amoxicillin-clavulanic acid (Augmentin) in the setting of preterm delivery, specifically citing the increased NEC risk. 3, 4
CDC guidelines note that antibiotics administered during pregnancy may be associated with adverse neonatal outcomes, including necrotizing enterocolitis, particularly in the context of preterm labor or PPROM. 3
Clinical Context and Recommendations
When Augmentin Should Be AVOIDED:
- Any woman in preterm labor (< 37 weeks gestation) 1
- Any woman with preterm premature rupture of membranes 3, 4
- Any woman at significant risk for preterm delivery 1
When Augmentin CAN Be Used:
- Term pregnancies (≥ 37 weeks) when clinically indicated for bacterial infections 1
- Early pregnancy when preterm delivery is not anticipated 1
- The European Respiratory Society/Thoracic Society of Australia and New Zealand classifies amoxicillin-clavulanate as "Compatible" for use during pregnancy in general, but with the critical caveat about preterm delivery risk. 1
Alternative Antibiotic Recommendations
For situations requiring antibiotics in preterm settings:
- Macrolide antibiotics (erythromycin) are recommended as the safer alternative, showing significant reductions in neonatal morbidity without the NEC risk. 2
- Standard PPROM regimen: IV ampicillin and erythromycin for 48 hours, followed by oral amoxicillin (NOT Augmentin) and erythromycin for 5 days. 4
- For GBS prophylaxis in preterm delivery: IV penicillin or ampicillin (or cefazolin if penicillin-allergic). 4
Addressing Conflicting Evidence
While one 2022 French review suggested the NEC risk may not be confirmed by subsequent studies 5, and a 2008 retrospective study found no increased NEC risk 6, the most authoritative guidelines (ACOG, CDC) and the largest systematic review (Cochrane) maintain the recommendation to avoid Augmentin in preterm settings. 3, 2 The principle of "first, do no harm" dictates avoiding this medication when safer alternatives exist for preterm scenarios.
Critical Pitfalls to Avoid
- Never reflexively prescribe Augmentin for any infection in a woman with threatened preterm delivery without considering alternatives. 1, 4
- Do not confuse the safety of amoxicillin alone (which is safe) with amoxicillin-clavulanate (Augmentin), which carries the NEC risk in preterm settings. 1, 7
- Failing to assess preterm delivery risk before prescribing Augmentin to any pregnant woman. 1
Teratogenicity (Separate from NEC Risk)
Regarding structural birth defects, Augmentin does NOT increase the risk of congenital malformations when used during organogenesis. 8 The NEC concern is specifically a neonatal complication related to preterm delivery, not a teratogenic effect.