Relationships among Prenatal Risk Factors, Early Life Events, and Asthma in At-Risk Children

Introduction: Asthma and wheezing in children are still not well understood but are the result of interactions between genetic, environmental, and microbiome factors prenatally and postnatally. The hygiene hypothesis suggests that birth into an environment with fewer microbial exposures may lead the developing immune system toward allergic responses and asthma. Emerging research has shown immune system development may begin in utero and the maternal placental, vaginal, and gut microbiome could influence this development. Methods: Using data from a longitudinal prospective cohort study, 300 mother-child pairs were followed from the first trimester of pregnancy through the child’s third year of life. Controlling for temporal confounders, three exposures were investigated: antibiotic use in the first year of life, prenatal antibiotic use, and maternal C-reactive protein levels. Their associations with the subsequent development of asthma by the third year of life and wheezing in the third year of life were assessed using multivariable logistic regression models. Results: Antibiotic use in the first year of life was a significant risk factor for both asthma and wheezing. After stratifying by reason for antibiotic use, the association held for respiratory use only. After adjustment, prenatal antibiotic use was a risk factor for asthma (OR: 3.1, 95% CI: 1.4–6.8) and was weakly associated with wheezing (OR: 1.8; 95% CI: 0.9–3.3). Median prenatal CRP levels were 4.9 mg/L (IQR: 3.2–7.7) in 244 mothers. Continuous prenatal CRP levels were predictive of asthma (OR: 3.2, 95% CI: 1.4, 7.6) and wheezing (OR: 2.2, 95% CI: 1.1, 4.3). Conclusions: We focused on three main risk factors; our research has helped elucidate some aspects of the development of asthma and wheezing within an at-risk urban, mostly Hispanic, cohort. We conclude the associations found between antibiotic use in young children and subsequent development of asthma and wheezing may be due to confounding by respiratory infections. However, our study suggests an association between prenatal antibiotic use and the development of asthma in at-risk children. We conclude systemic inflammation during pregnancy in at-risk mothers may reflect a prenatal environment that could increase offspring susceptibility to develop asthma and wheezing in early life.