Prenatal low-dose antibiotic exposure and children allergic diseases at 4 years of age: A prospective birth cohort study

Background: Based on a medical record or questionnaire survey approach, previous epidemiological studies have investigated associations between maternal antibiotic exposure during pregnancy and childhood allergic diseases. However, biomonitoring studies on the prenatal low-dose antibiotic exposure, mainly from the environment and contaminated food, and in relation to children allergic diseases, are missing. Objectives: This research aimed to examine the associations between prenatal low-dose antibiotic exposure measured at multiple time points and children current allergic diseases at 4 years of age. Methods: The current study including 2453 mother-child pairs was based on the Ma’anshan Birth Cohort study. Selected 41 antibiotics and their two metabolites, which including human antibiotics (HAs), preferred as human antibiotics (PHAs), veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs), in urine samples from 2453 pregnant women were biomonitored through liquid chromatography-triple quadrupole tandem mass spectrometry. Information on children current allergic diseases were collected via validated questionnaires. Generalized estimating equation were used to explore the associations between the repeated measurements of maternal urinary antibiotic over three trimesters and current allergic diseases in children. Results: The detection rates of nine individual antibiotics in the three trimester during pregnancy are greater than 10%, and the 90th percentile concentration of the detected antibiotics ranges from 0.07 to 22.34 µg/g, and the 95th percentile concentration ranges from 0.17 to 59.57 µg/g. Among the participants, each one-unit concentration increment of sulfamethazine (adjusted OR=1.28, 95% CI: 1.10, 1.49, P-FDR=0.014) in the first trimester and ciprofloxacin (adjusted OR=1.17, 95% CI: 1.07, 1.28, P-FDR=0.008) in the second trimester were associated with an increased risk of current eczema in children. In the third trimester, each one-unit concentration increment of oxytetracycline (adjusted OR=1.90, 95% CI: 1.30, 2.78, P-FDR=0.014) was associated with an increased risk of current asthma in children. Gender-stratified analyses demonstrated that no gender differences were observed in the associations between prenatal antibiotic exposure and current allergic diseases in children. Conclusions: Maternal exposure to certain specific VAs or PVAs (sulfamethazine, ciprofloxacin and oxytetracycline) in different trimesters was associated with an increased risk of current asthma and current eczema in 4-year-old children. No gender differences were found in these associations. Further studies are warranted to confirm our findings and explore the potential mechanisms