Study design and population
This study was based on a prospective, observational, birth cohort designed to study various exposures that could influence health and development in early life. A complete description of the cohort has been reported elsewhere [19]. Ethics approval for this study was granted by the Independent Ethics Committee Institute of Clinical Pharmacology, Central South University, Changsha, China (Project number: CTXY- 130041-3-2). Briefly, women who delivered live-born babies in three Streets of Kaifu District, Changsha City, had no history of mental illnesses or brain diseases, agreed to participate and provided their written informed consents, were recruited between Jan 1, 2015, and Dec 31, 2015. Eventually, 976 eligible mother-child pairs constituted the final birth cohort.
Data collection
After delivery, baseline data regarding demographic characteristics and potential influencing factors for allergic outcomes were collected. Follow-up investigations collecting data on early-life exposures, infant feeding, and allergic outcomes were collected at 1, 3, 6, 8, and 12 months of age respectively with questionnaires. The infantile principal caregiver (usually mothers) completed questionnaires with a well-trained investigator during home visits at birth and at 12 months of age. Telephone interviews were performed at other time points.
Definitions
The status of food allergy and eczema in the infant was assessed by a well-trained investigator and the definitions of these were standardized at each follow-up home visit and interview.
Food allergy: Due to ethical considerations, safety concerns and resource limitations, oral food challenges (OFC) were not performed. Infantile food allergy was determined by an affirmative answer to the following question: “Has your child ever had a doctor-diagnosed food allergy or experienced an allergic reaction immediately to a specific kind of food upon consumption as follows: swollen lips or face, urticaria, wheezing, vomiting, diarrhea, constipation)?” If the caregiver answered yes, the type of food involved was also ascertained.
Eczema: Infantile eczema was determined by an affirmative answer to the following question: “Has your child ever had a doctor-diagnosed eczema or had an itchy rash (excluding contact dermatitis) treated with topical steroid?”
An infant was deemed to have that specific allergic outcome when the question was answered affirmatively at any stage of the follow-up within 12 months.
Exposures
The prenatal and early-life variables used in this study include: maternal age (continuous), pre-pregnancy BMI (continuous), maternal education (> 12 years; yes, no), multiple pregnancy (twin/triplet pregnancy; yes, no), caesarean section (yes, no), maternal active or passive smoking during pregnancy (yes, no), exposure to antibiotics during pregnancy (yes, no), post-partum depression at 1 month after childbirth (yes, no), family income per capita (> 5000 yuan/month; yes, no), parental history of allergy (yes, no), maternal milk or milk products consumption during pregnancy (≤ 2 times a week, 3–4 times a week, ≥ 5 times a week), eggs consumption (≤ 2 times a week, 3–4 times a week, ≥ 5 times a week), beans or bean products consumption (< 1 time a week, 1–2 times a week, 3–4 times a week, ≥ 5 times a week), nuts consumption (< 1 time a week, 1–2 times a week, 3–4 times a week, ≥ 5 times a week), aquatic products consumption (< 1 time a week, 1–2 times a week, ≥ 3 times a week), infant’s sex (male, female), birth weight (< 2500 g; yes, no), preterm birth (< 37 weeks of gestation; yes, no), season of birth (autumn-winter; yes, no), number of older siblings (0, ≥1), domestic pets kept at birth (yes, no), exclusive breast-feeding (≥ 6 months; yes, no), solid food introduced (< 6 months; yes, no), and exposure to antibiotics through medication during the first year of life (yes, no).
Post-partum depression at 1 month after childbirth was evaluated using the Edinburgh Postnatal Depression Scale (EPDS), with a score of > 10 indicating women with probable post-partum depression [20]. Parental history of allergy was defined as either the mother or the father has a history of food allergy, eczema, asthma or allergic rhinitis. Maternal diet during pregnancy was collected using a food frequency questionnaire after delivery. Mothers filled out their average intake frequency during pregnancy for each food item, with frequencies defined as never, < 1 time a week, 1–2 times a week, 3–4 times a week and ≥ 5 times a week. Some categories were combined due to small sample size. Aquatic products were defined as fish, shrimp, crab, and shellfish. When evaluating the relationship between antibiotic exposure through medication and allergic outcomes during the first year of life, the chronology of antibiotic exposure and food allergy/eczema was taken into consideration, respectively. Infants were considered exposed if the exposure was reported in a former or the same follow-up questionnaire as the outcome, while those who were exposed after the onset of the outcome were considered as unexposed.
Statistical analysis
Data are presented as means ± SDs for continuous variables and frequencies with percentages for categorical variables. For univariate analysis, Independent t tests were used for continuous variables, while χ2 or Fisher exact tests were used for categorical variables. We fitted a multivariate logistic regression model for food allergy and eczema, respectively; infant’s sex and parental history of allergy as well as other exposure variables that were associated with any one of the two outcomes with a P value less than 0.2 in the univariate analysis were included in both models. All statistical analyses were conducted using SPSS version 18.