The association between prenatal antibiotic exposure and adverse long-term health outcomes in children: A systematic review and meta-analysis

Background: Antibiotics are the most commonly prescribed drugs during pregnancy. The long-term health risks to children associated with prenatal antibiotic exposure are uncertain.

Objective: To identify the association between prenatal antibiotics and adverse long-term health outcomes in children.

Methods: A systematic search was done to identify original studies investigating the association between prenatal antibiotic exposure and adverse long-term health outcomes in children. Studies were excluded if: (i) antibiotics were only given during delivery or (ii) the outcome was present before antibiotic exposure.

Results: We included 158 studies, reporting 23 outcomes in 21,943,763 children, in our analysis. For the following adverse health outcomes, there was a significant association with antibiotic exposure found in two or more studies: atopic dermatitis (OR 1.27, 95% CI 1.06-1.52, p=0.01), food allergies (OR 1.25, 95% CI 1.09-1.44, p<0.01), allergic rhinoconjunctivitis (OR 1.16, 95% CI 1.15-1.17, p<0.01), wheezing (OR 1.39, 95% CI 1.14-1.69, p<0.01), asthma (OR 1.36, 95% CI 1.24-1.50, p<0.01), obesity (OR 1.36, 95% CI 1.12-1.64, p<0.01), cerebral palsy (OR 1.25, 95% CI 1.10-1.43, p<0.01), epilepsy or febrile seizure (OR 1.16, 95% CI 1.08-1.24, p<0.01), and cancer (OR 1.13, 95% CI 1.01-1.26, p=0.04).

Conclusion: Although causality cannot be implied, these findings support antibiotic stewardship efforts to ensure judicious use of antibiotics during pregnancy to avoid potential long-term health risks.