Cesarean Delivery, Preterm Birth, and Risk of Food Allergy: Nationwide Swedish Cohort Study of More Than 1 Million Children

Abstract

To examine the association between cesarean delivery, preterm birth, low birth weight, small for gestational age (SGA), large for gestational age (LGA), and low 5-minute Apgar score and future food allergy (FA).This was a longitudinal cohort study of more than nearly 1.1 million consecutive births (2001–2012) recorded in the Swedish Medical Birth Register for whom there were complete data regarding items of interest for the study.Data collection included sex, mode of delivery, gestational age (GA), birth weight, and 5-minute Apgar score. Hazard ratios (HRs) and confidence intervals (CIs) were calculated to estimate the association between these characteristics and FA up to 2013.FA was present in 2.5% of children (median age at diagnosis: 1.6 years; range: 0.2–12.8 years), with girls (57.1%) more likely than boys (42.9%) to have FA. FA was positively associated with cesarean delivery (HR: 1.21; 95% CI: 1.18–1.25). Very preterm birth (<32 weeks’ GA) was negatively associated with future FA (HR: 0.74; 95% CI: 0.56–0.98), but GAs of 32 to 36 and ≥42 weeks were not associated with risk of FA. The risk for future FA was increased in infants who were LGA (HR: 1.15; 95% CI: 1.10–1.19) and in those with a 5-minute Apgar score <7 (HR: 1.22; 95% CI: 1.10–1.36). In contrast, SGA was not associated with future risk of FA. Adjusting for covariates, the authors calculated that for every 1000 children delivered by cesarean, 5 extra children had FA, as compared with the reference group, and 17% of FAs in children so delivered might be attributable to the mode of delivery. In similar calculations, it was estimated that 13% of FAs in infants who were LGA and 18% of FAs in infants with low 5-minute Apgar scores were attributable to those risk factors.Analysis of a large database revealed an increased risk of future FA in children delivered by elective or emergency cesarean as compared with those delivered vaginally. Very preterm infants were at lower risk of future FA. Infants who were LGA and those with a 5-minute Apgar score <7 were also at increased risk of FA.We can only speculate reasons for the observed associations in this study. In contrast to the sterility of a cesarean delivery, vaginal delivery exposes newborns to maternal flora. With profound interest in the human microbiome, we can hypothesize that different modes of delivery affect the diversity of gut flora, placing certain groups at risk for FA, other atopic conditions, and perhaps conditions unrelated to allergy and immunology. In future prospective studies, it would be of great interest to examine the intestinal flora of children with and without FA delivered vaginally or by cesarean delivery. We can also speculate that the very preterm infants’ neonatal care (including early oral introduction of food) might induce tolerance. An important covariate not examined in all these risk groups was formula versus breastfeeding and duration of nursing. That information could not be gleaned from the database. So how do we use these data in our day-to-day practice? At the least, this study adds to the complexity in identifying risks for FA, providing “food for thought.”