Third Trimester Antibiotic Use Ups Risk for Childhood Wheeze

Laurie Barclay, MD

December 07, 2015

Antibiotic exposure during the third trimester of pregnancy is associated with excess risk of wheezing in early childhood, according to findings of an Italian birth cohort study published online December 3 in the European Respiratory Journal.

"[E]ven the large number of confounding factors considered in our study could not explain the risk of recurrent wheezing when mothers took antibiotics during their third trimester," lead author Maja Popovic, MD, from the University of Turin, Italy, said in a news release. "This is important as recurrent wheezing is a more severe condition that often predicts later unfavourable respiratory outcomes."

Using the Nascita e Infanzia: gli Effetti dell'Ambiente (NINFEA) birth cohort, the researchers evaluated the incidence of wheezing before 18 months of age in 3530 singletons with first-trimester antibiotic exposure and 3985 with third-trimester exposure.

After adjusting for confounding factors, the researchers found that antibiotic exposure in the first trimester was not associated with ever-wheezing — at least one episode of wheezing or whistling in the chest before 6 months or between 6 and 18 months (adjusted risk ratio [RR], 1.02; 95% confidence interval [CI], 0.80 - 1.30) — or recurrent wheezing — wheezing or whistling before 6 months and again between 6 and 18 months (RR, 0.99; 95% CI, 0.54 - 1.82).

Confounding factors included maternal age, education, number of other children, smoking history, paracetamol use during pregnancy, history of asthma, and any respiratory or other infections during pregnancy.

In contrast, crude RRs for third-trimester exposure were 1.34 (95% CI, 1.10 - 1.64) for ever-wheezing and 2.72 (95% CI, 1.80 - 4.11) for recurrent wheezing. After adjustment, these decreased to 1.12 (95% CI, 0.90 - 1.39) and 2.09 (95% CI, 1.32 - 3.29), respectively.

Findings were similar when restricted to antibiotic exposure exceeding 3 days or antibiotic use for nongenitourinary infections. Independent of antibiotic exposure, RRs of childhood wheezing were increased with genitourinary infections during pregnancy.

"There is some evidence to suggest that taking antibiotics [in the third trimester] alters the composition of the mother's bacteria, which when transmitted to the newborn may modify the immune system development and explain the increased susceptibility to infections and wheeze," Dr Popovic concluded in the news release.

"As we identified that this risk still exists at this late stage of pregnancy, we would suggest that more research is needed to understand this association and clarify the underlying mechanism so that practical public health interventions could be developed in order to minimise unnecessary antibiotic exposures during pregnancy."

Study limitations include reliance on self-reported data obtained using questionnaires, lack of data on specific antibiotics used, and possible recall bias.

The Compagnia di San Paolo Foundation funded this study. The authors have disclosed no relevant financial relationships.

Eur Respir J. Published online December 3, 2015. Abstract

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