Growth restriction in the prenatal period is a significant public health concern. Metals can negatively affect birth size, and pregnant women may be exposed to metal mixtures. Comprehensive studies analyzing the effects of combined metal exposure with accurate individual blood metal concentrations are limited. The current study investigated the associations between maternal metal exposure and birth size in a large, nationwide Japanese cohort using individual and mixed model approaches. Lead, cadmium, mercury, selenium, and manganese blood concentrations were measured in pregnant women in the Japan Environment and Children's Study (JECS). Measurements of infant birth size-including body weight, body length, and head and chest circumference-were collected. Linear and logistic regressions were used for birth size measurements and the odds of an infant being small in size for gestational age, respectively. Associations between combined metal mixtures and measurements at birth were evaluated using quantile g-computation and Bayesian kernel machine regression (BKMR). Of the 103,060 JECS pregnancies, 93,739 mother-infant pairs were analyzed. The linear regression models showed that lead, selenium, cadmium, and manganese-but not mercury-were associated with body weight. Cadmium was associated with length and chest circumference and mercury was associated with head circumference. Quantile g-computation revealed that manganese increased infant birth weight, length, head circumference, and chest circumference. Lead was the strongest negative factor for infant birth weight, length, head circumference, and chest circumference. The BKMR analysis revealed that the metals had an additive, rather than a synergistic effect. Metal exposure is associated with infant birth size, with lead and manganese playing a more significant role in Japan. The effects of prenatal combined metal exposure at low levels warrant public health attention.

Inadequate maternal iodine intake affects thyroid function and may impair fetal brain development. This study investigated the association between maternal iodine intake during pregnancy and neurodevelopmental delay in offspring at 1 and 3 years of age using a nationwide birth cohort: the Japan Environment and Children’s Study. We assessed dietary iodine intake during pregnancy using a food frequency questionnaire and child neurodevelopment using the Japanese translation of the Ages and Stages Questionnaire, Third Edition. The risk of delay (score below the cut-off value) for fine motor domain at 1 year of age was increased in the lowest quintile iodine intake group compared with the fourth quintile iodine intake group. The risk of delay for problem-solving at 1 year of age was increased in the lowest and second quintile iodine intake group and decreased in the highest quintile iodine intake group. The risk of delay for communication, fine motor, problem-solving, and personal–social domains at 3 years of age was increased in the lowest and second quintile iodine intake group compared with the fourth quintile iodine intake group, while the risk of delay for fine motor and problem-solving domains was decreased in the highest quintile iodine intake group. Low iodine intake levels in pregnancy may affect child neurodevelopment.

Background: Pseudohypoparathyroidism (PHP) and nonsurgical hypoparathyroidism (NS-HypoPT) are rare diseases with hypocalcemia, hyperphosphatemia, and high and low parathyroid hormone levels, respectively. In Japan, over 20 years have passed since the last survey on these diseases. We carried out a nationwide cross-sectional survey to estimate the prevalence of these diseases in 2018.Methods: We conducted a nationwide mail-based survey targeting hospitals in 2018. From a total of 13,156 departments throughout Japan, including internal medicine, pediatrics, neurology, and psychiatry, 3501 (27%) departments were selected using a stratified random sampling method. We asked each included department to report the number of patients with PHP and NS-HypoPT in 2017.Results: The overall survey response rate was 52.0% (1807 departments). The estimated number of patients with PHP and NS-HypoPT was 1484 (95% confidence interval [CI], 1143–1825) and 2304 (95% CI, 1189–3419), respectively; the prevalence per 100,000 population was 1.2 and 1.8, respectively.Conclusion: In this study, we generated estimates of the national prevalence of PHP and NS-HypoPT in Japan during 2017, which were found to be higher than those previously reported.

Summary: Background: The association between maternal antibiotic exposure during pregnancy and childhood obesity is still unclear.Objectives: The study aimed to evaluate the association between prenatal exposure to antibiotics and obesity at age 3 years using data from a large Japanese birth cohort.Methods: The Japan Environment and Children's Study is a nationwide birth cohort study. In this study, singleton vaginal full‐term births were included. Obesity was defined as body mass index ≥95th percentile according to child growth standards. Prenatal antibiotic exposure was defined as antimicrobial agent use during pregnancy and was collected from maternal interviews and medical record transcripts. Logistic regression analysis was performed to evaluate the association of prenatal antibiotic exposure with child obesity at 3 years.Results: In the crude and adjusted models with all children, maternal antibiotic exposure during pregnancy showed a marginal relationship with child obesity at 3 years. In the analyses according to exposure period and sex, exposure to antibiotics during the second/third trimester was significantly associated with obesity at the age of 3 years in female infants, but not in male infants, although the exposure during the first trimester was not in both sexes.Conclusion: Maternal antibiotic exposure during mid/late pregnancy may result in child obesity.

Purpose: Epidemiological studies have reported that environmental factors from fetal period to early childhood can influence the risk of non-communicable diseases in adulthood. This concept has been termed the developmental origins of health and disease (DOHaD). The Chiba study of Mother and Child Health (C-MACH) is a DOHaD concept-based birth cohort study which started in 2014. This study aims to investigate the effects of genetic and environmental factors, particularly fetal and postnatal living environment, on children’s health. We also aim to identify candidate biomarkers for their health status. Moreover, the second phase study of C-MACH which was initiated in 2021 aimed at expanding the sample size, especially for gut microbiota and epigenomic analysis; it also aimed at clarifying the impact of the coronavirus disease 2019 (COVID-19) pandemic on children’s health. Participants: This study consists of four hospital-based cohorts. Women who were <13 weeks pregnant and their partners were enrolled in the study. All data and biological samples will be stored in the Chiba University Centre for Preventive Medical Sciences. Findings to date: A total of 561 women and their partners provided their consent to participate in this study. Of these women, 505 completed the questionnaire during the early gestational period. The mean age of the 505 women at enrolment was 33.0 (SD, 4.5) years. The mean prepregnancy body mass index (BMI) was 21.7 (SD, 3.6) kg/m², with 74.5% of the women having a BMI of 18.5–24.9 kg/m². About 5.2% of the women smoked cigarettes during the early stages of pregnancy. Future plans: The primary study outcomes are allergies, obesity, endocrine and metabolic disorders and developmental difficulties in children. Variables related to genome, metabolome, epigenome, gut microbiota and exposome will be evaluated as health-related factors. The relationships between these outcomes and the health-related factors will be analysed.

We investigated umbilical cord serum microRNA (miRNA) profiles to identify biomarkers of a risk for obesity later in life. Participating children were divided into high‐ and low‐risk groups of obesity based on the timing of adiposity rebound and the body mass index (BMI) at 5 years and randomly selected from each group for this study. 3D‐Gene® Human miRNA Oligo Chip was performed using cord serum in five children of both groups. The most relevant miRNAs were confirmed in 33 children of the groups using the TaqMan® microRNA assay. We detected five cord serum miRNAs differentially expressed in children at high risk of obesity compared with the levels in children at low risk, namely, miR‐516‐3p and miR‐130a‐3p with increased levels and miR‐1260b, miR‐4709‐3p, and miR194‐3p with decreased levels. This study provides the first identification of altered umbilical cord serum miRNAs in childhood obesity.