Outcomes, exposures, and covariates
Asthma, atopic dermatitis, wheezing, and eczema were assessed based on the doctors’ self-reported diagnoses and the information given in the participants’ questionnaires when the children were 1 year old (C1Y data). The questionnaire included whether wheezing and eczema occurred in the first year of life. This was a validated, modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire for children 6–7 years old, translated in Japanese.17-19The subjects were assigned to a cesarean or vaginal delivery group, based on the modes of delivery recorded in the Dr0m data. Moreover, participants in the cesarean delivery group were assigned to an elective or emergency group based on the reason for cesarean delivery recorded in the Dr0m data: elective cesarean delivery included repeat cesarean delivery, history of uterine surgery, placenta previa, and fetal malpresentation and emergency cesarean delivery included gestational hypertension syndrome, nonreassuring fetal status, delayed/obstructed labor, early rupture of membrane, intrauterine infection, cephalopelvic disproportion, and complication/other reason. We considered the following factors as possible confounders in the regression analyses: maternal age at pregnancy, parity, sex, gestational age (GA), small for gestational age (SGA), maternal allergy history, maternal active and passive smoking during pregnancy, maternal educational levels, annual family income, marital status, breastfeeding at six months, pet ownership, and passive smoking exposure of infants after birth. The maternal age at pregnancy (DrT1 data) was categorized as follows: < 20, 20–29, 30–39, and ≥ 40 years. Parity (DrT1 data) was categorized as 0, 1, or ≥ 2. The GA was categorized as follows: <37, 37, 38, and 39–41 weeks. Standard deviation (SD) was calculated based on Japanese neonatal anthropometric charts,20 which accounted for GA, sex, and parity. Babies with values <-1.5 SDs were defined as SGA.21 Maternal allergy history (MT1 data) was considered positive if a parent reported a history of asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, food allergies, drug allergies, contact dermatitis, or sick building syndrome. Female participants were asked to provide information about their smoking status (MT2 data), as follows: “Never”, “Previously did, but quit before recognizing current pregnancy”, “Previously did, but quit after finding out current pregnancy”, and “Yes, I still smoke”. The female participants whose responses were “Yes, I still smoke” were assigned to the smoking category, and the remaining participants were assigned to the non-smoking category.
Maternal educational periods (MT2 data) were grouped as follows: junior high school, < 10 years; high school, 10–12 years; technical/vocational college or university, 13–16 years; and graduate school, ≥ 17 years. The participants’ annual household incomes (MT2 data) were categorized as follows: < 2,000,000 Japanese yen (JPY); 2,000,000–5,999,999 JPY; 6,000,000–9,999,999 JPY; and ≥ 10,000,000 JPY. Data on marital status were obtained from MT1. Data on passive smoking exposure of infants were obtained from M1m. Data on breastfeeding and pet ownership were obtained from C6m.