Antibiotics and pregnancy: what are the risks for the microbiotas of the mother and the child?

Actu PRO Antibiotiques et grossesse : quels risques pour les microbiotes de la mère et de l’enfant ?

Taking antibiotics during pregnancy could cause or aggravate vaginal dysbiosis in pregnant women, which is not without consequences for their health and that of their children. This is demonstrated by three studies presented below and focusing on CIBD and premature birth. These studies corroborate recent work confirming the transmission of maternal microbiota to the fetus in utero. It should be reminded that in France, antibiotics are used in 42% of pregnancies.

 

3rd trimester at high risk

The first of these studies, conducted by a team of Swedish researchers, focuses on the already established link between microbiota and CIBD. Its aim was to determine whether exposure to antibiotics during pregnancy has an impact on the risk of the child developing Crohn's Disease (CD) or Ulcerative Colitis (UC). In a large cohort of more than 800,000 children compiled from very detailed national registers, no significant result emerged in the case of UC. Conversely, the scientists observed a virtual doubling (93%) of the risk of developing early CD (before the age of 6) in children whose mother had taken at least one antibiotic during her pregnancy, with a maximum risk in the third trimester.

An aggravating legacy

Other studies have explored this intergenerational transmission of dysbiosis in IL-10-deficient mice, a murine model of spontaneous UC. By transplanting a microbiota previously exposed to penicillin into these mice, American researchers were able to verify that the impaired flora had been reliably implanted in the females, who had passed it on to their offspring. They then examined different histological and immunological markers of colitis in their offspring up to the age of 21 weeks: all indicated a clear increase in the HAI* score (55 times higher than that observed in the control mice), suggesting a worsening of the disease.

Less systematic use of antibiotics

Finally, a British study specifically encourages a review of the systematic prophylaxis recommended against neonatal infections caused by preterm premature rupture of membranes (PPROM). This study, conducted in 250 pregnant women, demonstrated that the administration of erythromycin did not correct pre-existing dysbiosis; it rather tended to cause vaginal dysbiosis, particularly in patients whose flora was dominated by Lactobacillus, by actually reducing the number of lactobacilli. Prophylaxis proved to be particularly detrimental just before labor: not only did erythromycin not prevent early labor in 80% of cases, but it was also thought to increase the risk of chorioamnionitis, inflammation of the umbilical cord and early-onset neonatal sepsis. For all that, researchers do not dispute its benefits observed in clinical practice, which they think are linked to an anti-inflammatory effect on the placenta rather than an antibiotic action, insofar as it does not target the pathogenic bacteria responsible for membrane rupture. But they emphasize the urgency of readjusting the protocols established for the administration of antibiotics during pregnancy.

 

*HAI : Histology Activity Index

 

Sources:

Örtqvist AK et al. Fetal and early life antibiotics exposure and very early onset inflammatory bowel disease: a population-based study. Gut 2018; January

Schulfer AF et al. Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice. Nat Microbiol 2019; 3(2):234-242

Brown RG et al. Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin. BMC Med 2018; 24;16(1):9