Prenatal Antibiotic Exposure Increases Risk for Childhood Atopic Dermatitis

Children of mothers who used antibiotics during pregnancy, especially during the second and third trimesters, had a slightly higher, dose-related risk of developing pediatric atopic dermatitis (AD), concluded authors of a retrospective cohort study published in Pediatric Allergy and Immunology.

The prevalence of pediatric AD varies geographically, but is as high as 20% in certain areas. In addition, most affected children develop symptoms of AD in infancy.

The current study was designed to evaluate whether maternal antibiotic use may be a contributing factor to AD risk in childhood. Study data were sourced from the Taiwan Maternal and Child Health Database (TMCHD). Babies (N=1,288,343) born between 2009 and 2016 were evaluated for exposure to antibiotics in utero and for diagnosis of childhood AD through 2019, defined as 3 outpatient visits or 1 hospitalization for AD.

Average maternal age was 31.88 (SD, 4.6) years and 39.5% of women received antibiotics during pregnancy during the first (17.9%), second (19.0%), and third (14.6%) trimester.

Stratified by antibiotic use in pregnancy, more boys were exposed to antibiotics (P =.0066). In addition, babies exposed to antibiotics had a higher rate of Apgar score of less than 5 at 1 minute (P =.0379) and 5 (P =.0191) minutes compared with the unexposed group. In addition, the rate of maternal comorbidities was higher among the antibiotic-exposed group (with the greatest difference noted for preeclampsia: P ≤.0469).

During a median follow-up of 61 months, 22.3% of children were diagnosed with AD, with an incidence rate of 3.69 per 1000 person-months.

Over time, the risk for AD has been decreasing; compared with delivery in 2009, risk for AD was progressively lower from 2011 (adjusted hazard ratio[aHR], 0.92) to 2016 (aHR, 0.3).

Risk for AD was associated with maternal AD (aHR, 1.24), maternal rheumatoid arthritis (aHR, 1.2), maternal asthma (aHR, 1.17), endometriosis (aHR, 1.17), maternal allergic rhinitis (aHR, 1.13), gestational diabetes (aHR, 1.12), maternal acetaminophen use (aHR, 1.11), maternal Sjögren syndrome (aHR, 1.1), maternal hyperlipidemia (aHR, 1.09), male offspring (aHR, 1.07), gestational urinary tract infection (aHR, 1.07), gestational skin infection (aHR, 1.06), gestational respiratory infection (aHR, 1.06), cesarean delivery (aHR, 1.05), maternal antibiotic use (aHR, 1.04), and preeclampsia (aHR, 1.04).

Stratified by timing of antibiotic exposure, risk for AD was associated with antibiotic use in the first (aHR, 1.03) and second (aHR, 1.02) trimesters compared with women who did not use antibiotics in that trimester. In addition, compared with women who did not have any antibiotic use in pregnancy, AD risk was associated with antibiotic use in the first (aHR, 1.04), second (aHR, 1.04), and third (aHR, 1.02) trimesters.

In a subgroup analysis of children diagnosed with AD after 1 year of age, those born to mothers who did not have asthma, allergic rhinitis, or AD were found to be at higher risk for AD (aHR, 1.11) than those born to mothers with atopic conditions (aHR, 1.06).

The authors also noted that infant use of antibiotics or acetaminophen was positively associated with subsequent development of AD.

The study authors noted a major limitation of their analysis: They did not adjust for certain covariates associated with AD risk, such as maternal smoking, dietary habits, environmental exposures (such as climate conditions and air pollution), and unmeasured factors (such as genetic susceptibility) shared by families.

The authors concluded, “[T]his cohort study revealed that maternal antibiotic use during pregnancy was associated with a slightly increased risk of childhood AD and the risk was higher in children of mothers without atopic diseases.” They emphasized that “[f]urther research should be conducted to examine whether or not this association is specifically related to pregnancy.”