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Antibiotic prophylaxis in pregnancy—benefit without harm?

Antibiotics—perhaps the single biggest advance in modern medicine. The widespread use of penicillin beginning shortly after World War II changed the way we think of infection. Peripartum infection, which was frequently a death sentence in the early part of the 20th century, is now something that we confidently prevent with a simple infusion. With this astonishing progress have also come limitations. Practitioners are now acutely aware of the risks of antibiotics: the development of resistant organisms or the potential for disastrous complications such as Clostridium difficile colitis, ironically, treated with another antibiotic. Because antibiotic use has become so commonplace in pregnancy, we rarely hesitate to use them when needed in a pregnant woman. The article by Azad et al., however, should give us pause. The authors report a secondary analysis examining the impact of maternal intrapartum antibiotic exposure on infant gut microbiota at 3 and 12 months. They found that antibiotic exposure resulted in differences in gut flora among infants, even among vaginally delivered infants, and that breast feeding modified some of these effects. Infant gut flora in the study was followed to 1 year, but long-term health outcomes remain unknown. Whether this change in flora has any immediate or long-term impact on health outcomes is also unknown. So, although it makes us wary to see changes in infant gut flora after antibiotic exposure, the findings of this study alone do not have enough of an impact to lead to a change in practice. For example, if the infants exposed to antibiotics were less likely to develop neonatal sepsis or meningitis, then a change in the microbiome of the gut flora may be a small price to pay for improved clinical outcomes. Despite the fact that practice recommendations cannot be made on the basis of this study, it would be irresponsible of us as an obstetric community to ignore the growing body of literature suggesting that antibiotic exposure in pregnancy may be associated with adverse outcomes. The ORACLE II trial’s long-term outcomes of children whose mothers were randomly allocated to receive antibiotics during preterm labour were significant for an increased risk of cerebral palsy among those exposed to antibiotics (Kenyon et al. Lancet 2008;372:1319– 27). Also of concern is a recent metaanalysis examining the impact of intrapartum group B streptococcal (GBS) prophylaxis (IAP). This Cochrane Database Review demonstrated that while IAP decreased the incidence of early onset GBS sepsis, it was not associated with a decrease in all-cause mortality (Ohlsson & Shah. Cochrane Database Syst Rev 2014;(6): CD007467). Since IAP is recommended by the Centers for Disease Control, approximately 25% of the US population, or about 1 million American women annually, are exposed to antibiotics for GBS prophylaxis alone. Recent advances in microbiome technologies using culture-independent characterisation have suggested possible associations with disruptions in gut flora and long-term health outcomes for children such as obesity and autoimmune dysfunction. The study by Azad et al. adds to the growing body of literature suggesting that we should not dismiss the potential for a long-term impact of antibiotic exposure during pregnancy. A renewed focus on antibiotic stewardship during pregnancy and research studies designed specifically to evaluate these effects should be a high funding priority.