More research needed to determine if prenatal antibiotic exposure triggers atopic march

Prenatal antibiotic exposure appeared linked to increased susceptibility to childhood asthma and diseases implicated in the atopic march, including wheeze, eczema/dermatitis and allergic rhinitis, according to a review published in Allergy.

However, there was large heterogeneity between the studies in the review with low-quality certainty of evidence, indicating a need for more research, Alissa Cait, PhD, postdoctoral researcher at Malaghan Institute of Medical Research in Wellington, New Zealand, and colleagues wrote.

According to the researchers, the atopic march begins in infancy with atopic dermatitis, food allergy or wheeze and then progresses to asthma and/or allergic rhinitis. Their review included 11 prospective and 16 retrospective studies published between 2002 and 2020.

One study found a significant association between prenatal antibiotic exposure and atopic sensitization at age 4 years (RR = 1.57; 95% CI, 1.11-2.22), although another found no association at age 1 year (RR = 1.13; 95% CI, 0.93-1.37).

Also, one study found a significant association between antibiotic use during pregnancy and development of food allergy (RR = 1.81; 95% CI, 1.11-2.95).

Five studies found prenatal exposure to antibiotics to be a risk factor for the development of dermatitis/eczema (RR = 1.28; 95% CI, 1.06-1.53), although the researchers cautioned that these studies were quite heterogenous, with four of them likely underpowered.

Three studies found an increased risk for childhood allergic rhinitis in association with childhood asthma with prenatal antibiotic exposure (RR = 1.13; 95% CI, 1.02-1.25). A sunset plot, however, indicated that these studies likely were underpowered.

Eight of the nine studies on childhood wheeze found a positive trend between prenatal antibiotic exposure and its development, with a statistically significant relationship in four of these studies (RR = 1.51; 95% CI, 1.17-1.94). But again, the researchers found that heterogeneity in the data was substantial, with six studies likely underpowered.

Additionally, there was a strong association between prenatal antibiotic exposure and the risk for developing childhood asthma in 20 studies (RR = 1.28; 95% CI, 1.22-1.34) with a statistically significant relationship in 18 of these studies. Heterogeneity in these studies was considerable, but the researchers found no indication of significant publication bias, with a sunset plot indicating that most studies had high power.

Three studies found that antibiotics administered during the third trimester had a significant association with childhood wheeze (RR = 1.76; 95% CI, 1.11-2.79) but not during the first (RR = 1.13; 95% CI, 0.95-1.34) or second (RR = 1.13; 95% CI, 0.99-1.29) trimesters.

Eight studies found increased risk for developing childhood asthma with antibiotics taken during the first (RR = 1.17; 95% CI, 1.02-1.35), second (RR = 1.22; 95% CI, 1.1-1.35) and third (RR = 1.21; 95% CI, 1.1-1.34) trimesters.

The researchers also stratified risk for childhood asthma based on classes of antibiotics, with increased risk observed for penicillin (RR = 1.27; 95% CI, 1.19-1.36), macrolides (RR = 1.36; 95% CI, CI = 1.16-1.59), sulphonamides/trimethoprim (RR = 1.27; 95% CI, 1.11-1.46), nitrofurantoin (RR = 1.17; 95% CI, 1.01-1.334) and chloramphenicol (RR = 1.77; 95% CI, 1.18-2.65) but not with cephalosporins (RR = 1.26; 95% CI, 0.92-1.74). These results should be interpreted with caution, the researchers wrote, due to the scarcity of studies.

Despite evidence indicating risks for childhood asthma with antibiotic use during pregnancy, the researchers found that the effect evaluates were of low quality. Also, the effect evaluates of childhood dermatitis and allergic rhinitis were very low quality, and the effects of wheeze were low quality as well. The researchers attributed this lack of quality to the high heterogeneity and publication bias of the studies.

Considering these limitations, the researchers called for more research to provide firm conclusions about the risks that prenatal antibiotic exposure presents for childhood asthma and the atopic march.