The present study utilised data from the JECS, a government-funded birth cohort study that commenced in January 2011. The JECS investigated the effects of several environmental factors, such as heavy metals and allergens, on children's health15. Pregnant women were eligible for participation in the JECS: (1) if lived in the study area at the time of the application and expected to live in Japan in the near future; (2) if they had an expected delivery date between 1 August 2011 and mid-2014; and (3) if they were able to participate without difficulty (i.e. they could complete the self-management questionnaires). The JECS protocol was reviewed and approved by the Ministry of the Environment’s Institutional Review Board on Epidemiological Studies and by the Ethics Committees of all participating institutions. The study was conducted in accordance with the Helsinki Declaration and other nationally valid regulations and guidelines. Written informed consent was obtained from all participants.
The current analysis utilised the JECS data set released in March 2018 (data set: jecs-an-20180131), from which we used the following information: (1) a self-reported questionnaire completed in the first trimester, including details about medical conditions before pregnancy, number of previous deliveries, and smoking status; (2) a self-reported questionnaire completed during the second/third trimester, which included particulars regarding socioeconomic data; (3) obstetrics outcomes and maternal medical background data, retrieved from the medical records of each participant’s institution; and (4) maternal blood sample records, collected during the first trimester. This study only involved primipara women since the risk of HDP is much higher in primipara women than in multipara women32. In the present study, we excluded cases with insufficient data, multiple pregnancies, or hypertension before pregnancy, and multipara.
Measurement of total IgE, obstetrics outcomes, and confounding factors
Blood samples were obtained from the mother during the first trimester of pregnancy. Serum total IgE titres were analysed in a contract clinical laboratory by immunological assays. Serum total IgE titres were assayed by ImmunoCAP (Thermo Fisher Scientific, Inc., Sweden)33. A high serum IgE level was defined as IgE ≥170 IU/ml based on the results of a Japanese cross-sectional study in pregnant women31. Maternal systolic and diastolic blood pressures were measured at the time of blood sample collection.
Obstetrics outcomes included HDP, gestational age at birth, and birth weight. HDP was defined as new onset hypertension (≥140/90 mmHg) after conception4. HDP was further classified into two categories: Eo-HDP (HDP onset before 34 weeks of gestation) and Lo-HDP (HDP onset after 34 weeks of gestation). SGA was defined as a birth weight less than −1.5 SDs below the population mean, corrected for gestational age and sex according to the ‘New Japanese neonatal anthropometric charts for gestational age at birth’34. PTB was defined as delivery before 37 gestational weeks. LBW was defined as birth weight <2500 g.
The following parameters were considered to be confounding factors: maternal age at delivery, BMI before pregnancy, maternal smoking status, maternal educational status, and SLE. The mothers were categorised into four age groups: <20, 20–29, 30–39, or ≥40 years. The maternal BMI before pregnancy was calculated by dividing the mother’s weight (kg) by the square of the mother’s height (m). BMI was categorised into <18.5, 18.5–25.0, or >25.0 kg/m2 1.
A self-reported questionnaire during first trimester had the following options regarding smoking history: ‘Never’, ‘Previously did. Quit prior to current pregnancy’, ‘Previously did. Quit during this pregnancy’, and ‘Currently smoking’. Women who chose ‘Currently smoking’ were considered smokers (smoking category); otherwise, they were considered non-smokers (non-smoking category).
Based on the Japanese educational system, maternal education was categorised into the following four groups: junior high school: <10, high school: 10–12, professional school or university: 13–16, and graduate school: ≥17 years of education1.
Maternal participants were requested to provide the following information regarding SLE: ‘Have you ever been diagnosed with SLE at a medical institution?’. The maternal participants who answered ’Yes’ were classified into the SLE group35. The confounding factors in this study were determined based on previously identified risk factors for HDP36–39.
First, maternal characteristics and obstetric factors were summarised according to serum IgE levels. Then, participants were categorised into one of the three following groups, the non-HDP group (defined as control), Eo-HDP group, or Lo-HDP group. The prevalence of obstetric outcomes in HDP, including PTB, LBW, and SGA, were compared across the three groups. T-test and chi-square tests were performed to compare continuous and categorical variables, respectively. To compare more than three variables, the Kruskal-Wallis (one-way analysis of variance) and chi-square tests were used. Finally, logistic regression models were used to calculate the aORs and 95% CI for HDP, Eo-HDP, and Lo-HDP. An aOR was calculated after adjusting for maternal age, BMI before pregnancy, maternal smoking during pregnancy, SLE, and maternal education. Logistic regression model analysis was performed using dummy variables for categorical variables composed of more than three categories (e.g. BMI could be categorised as <18.5, 18.5−25.0, and >25). SPSS version 26 (IBM Corp., Armonk, NY) was used for the statistical analyses. A p-value <0.05 was deemed to be statistically significant.
The datasets analysed during the current study are not publicly available due to confidentiality/research subject protections. The authors, with permission of the Eco-child Study Investigation Committee and the Japan government, can make the datasets available upon reasonable request.