Antibiotic exposure during pregnancy tied to VEO-IBD risk in offspring
Exposure to antibiotics during pregnancy, but not in infantile age, appears to carry an increased risk of developing very early onset (VEO) inflammatory bowel disease (IBD) in children, as reported in a study from Sweden.
The population-based study included 827,239 children (51.4 percent male) born between 2006 and 2013, among whom 140,665 (17 percent) had been exposed to systemic antibiotic in utero and 539,809 had been exposed in infantile age (65.3 percent). There were 51 who developed IBD (Crohn’s disease [CD] and/or ulcerative colitis [UC]), 20 with CD only and 24 with UC only. First IBD diagnosis was established at a median of 2.0 years.
Cox proportional hazard regression analysis showed that compared with general population controls, children exposed to antibiotics during pregnancy had a twofold increased risk of IBD (adjusted HR [aHR], 1.93; 95 percent CI, 1.06–3.50). This was also true for both CD (aHR, 2.48; 1.01–6.08) and UC (aHR, 1.25; 0.47–3.26).
On the other hand, exposure to systemic antibiotics during the first year of life was not significantly associated with the risk of first IBD diagnosis from 2 years of age, with the aHRs in exposed children vs controls being 1.11 (0.57–2.15) for IBD, 0.72 (0.27–1.92) for CD and 1.23 (0.45–3.39) for UC. Moreover, no dose-response association was observed between increasing number of prescriptions for systemic antibiotics in infantile age and IBD.
In sensitivity analysis excluding children diagnosed with gastroenteritis 12 months prior to the first diagnosis of IBD, the risk estimates with antibiotic exposure during pregnancy were no longer significant for IBD (aHR, 1.68; 0.88–3.21) and CD (aHR, 2.51; 0.96–6.56), and the associations with exposure in infantile age remained nonsignificant.
With regard to the influence of antibiotics on the risk of acquiring IBD, the investigators pointed out that the two may be causally related, with antibiotics potentially exerting an effect on the microbiome, causing a reduced diversity and an increased dysbiosis. [Cell Host Microbe 2014;15:382-392]
Meanwhile, a dysbiosis in the gut microbiota—characterized by reduction of beneficial bacteria, such as Faecalibacterium prausnitzii and Ruminococcaceae, and an increase of pathogens or pathobionts—has consistently been observed in patients with IBD, especially ileal CD. [Nat Microbiol 2017;2:17004]
Despite the presence of several limitations, the study indicates that antibiotic exposure in late pregnancy can lead to changes in the microbiome of the child, the investigators said. However, more work is needed to confirm the data.
The investigators also stressed that antibiotics should still be used during pregnancy when needed, given the very low absolute risk of VEO-IBD.