Trimester-specific association between antibiotics exposure during pregnancy and childhood asthma or wheeze: the role of confounding

Ann Epidemiol. 2019 Feb;30:1-8. doi: 10.1016/j.annepidem.2018.10.003. Epub 2018 Nov 2.


Purpose: We conducted the meta-analysis to respectively evaluate the risk of prenatal antibiotics use during specific trimesters (first, second, and third trimester) on childhood asthma or wheeze and to explore whether the association was biased by potential confounding.

Methods: The quality of included articles was assessed according to Newcastle-Ottawa Quality Assessment Scale and the Strengthening the Reporting of Observational Studies in Epidemiology. A random effects model was used to calculate pooled risk ratios and corresponding 95% confidence interval (CI), and publication bias was tested by Egger statistical test.

Results: Eight studies were included finally. We found a crude positive association of prenatal antibiotics use during each pregnancy trimester and risk of childhood asthma or wheeze with RRs of 1.28 (95% CI, 1.09-1.51) for the first trimester of pregnancy, 1.25 (95% CI, 1.02-1.52) for the second trimester, and 1.25 (95% CI, 1.05-1.49) for the third trimester. However, when considering potential factors of maternal infections and presence of siblings, the relationship for each trimester was insignificant.

Conclusions: This systemic review and meta-analysis proposed a crude positive association between prenatal antibiotic use in every specific trimester and risk of childhood asthma or wheeze. However, adjustment for confounders decreased the relative risk estimates, supporting the concept that these associations are, at least in part, because of confounding by indication.

Keywords: Antibiotic; Asthma; Childhood; Confounding; Meta-analysis; Pregnancy trimester; Wheeze.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / therapeutic use
  • Asthma / etiology*
  • Child
  • Female
  • Humans
  • Odds Ratio
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Trimesters
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Respiratory Sounds / etiology*
  • Risk Factors
  • Surveys and Questionnaires


  • Anti-Bacterial Agents