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.