Association of air pollution exposure during pregnancy and early childhood with children's cognitive performance and behavior at age six.

BACKGROUND: The impact of air pollution on neurodevelopment in children has attracted much attention in recent times. We aim to clarify the association between prenatal and postnatal air pollutant exposure and children's cognitive performance and behavior at age six. METHODS: This study was conducted based on a birth cohort study in Japan. Children's intelligence quotient (IQ) was assessed using the Wechsler Intelligence Scale for Children and a score <85 was deemed as low intelligence. A score ≥60 on the Child Behavior Checklist indicated behavioral problems. Exposure to outdoor fine particulate matter (PM2.5) during pregnancy and early childhood was estimated using a spatiotemporal model, while indoor concentrations of air pollutants inside subjects' homes were measured for a week when the child was of ages 1.5 and 3. The associations of exposure to air pollution during pregnancy and after childbirth with cognitive performance and behavior were analyzed using logistic regression models. RESULTS: The estimated exposure to outdoor PM2.5 during pregnancy and early childhood was not associated with decreased cognitive performance. However, exposure during the first trimester, 0-1 and 3-5 years of age was associated with children's externalizing problems (odds ratios (ORs) were 2.77 [95% confidence interval (CI): 1.05-7.29], 1.66 [95%CI: 1.05-2.62], and 1.80 [95%CI: 1.19-2.74] per interquartile range (IQR) increase, respectively). Exposure to indoor PM2.5 and coarse particles after childbirth was associated with lower full scale IQ (ORs were 1.46 [95%CI: 1.03-2.08] and 1.85 [95%CI: 1.12-3.07] per IQR increase, respectively). However, some inverse associations were also observed. CONCLUSIONS: These results suggest associations between prenatal and postnatal exposure to outdoor air pollution and behavioral problems, and between indoor air pollution after childbirth and cognitive performance at age six. However, the effects of exposure to outdoor PM2.5 during pregnancy on cognitive performance were not observed.

Analyzing the relationship between feelings about pregnancy and mother-infant bonding with the onset of maternal psychological distress after childbirth: The Japan Environment and Children's Study.

BACKGROUND: Strengthening maternal mental health from early pregnancy is essential. This study investigated the factors affecting the onset of maternal psychological distress at 12 months after childbirth in women who had not experienced it during pregnancy. METHODS: Feelings about pregnancy were assessed using a questionnaire in the first trimester, and maternal mental health was assessed using the 6-Item Kessler Psychological Distress Scale (K6) in the first and second/third trimesters and at 12 months after childbirth. Mother-infant bonding was assessed using the Japanese version of Mother-to-Infant Bonding Scale (MIBS-J) in the first, sixth, and twelfth months after childbirth. This study comprised 46,053 mothers without psychological distress (K6 ≤ 4) during pregnancy from the 97,415 mothers enrolled in the Japan Environment and Children's Study. RESULTS: The onset of psychological distress at 12 months after childbirth was associated with negative maternal feelings about pregnancy, a history of infertility treatment before the current pregnancy, and poor mother-infant bonding after childbirth. Abortion history was not associated with psychological distress. The strongest factor affecting the onset of psychological distress was mother-infant bonding (ß = 0.28), and the indirect effect of feelings about pregnancy was also observed (ß = 0.10). LIMITATIONS: We used the full version of MIBS-J consisting of 10 items at 12 months after childbirth but included only five items in the first and sixth months. CONCLUSIONS: Inadequate mother-infant bonding was associated with the onset of maternal psychological distress after childbirth. Supporting mother-infant bonding is critical throughout the perinatal period, considering maternal feelings about pregnancy.

Association of epidural analgesia during labor with neurodevelopment of children during the first three years: the Japan Environment and Children's Study.

BACKGROUND: Epidural analgesia relives pain during labor. However, the long-term effects on neurodevelopment in children remain unclear. We explored associations between exposure to epidural analgesia during labor and childhood neurodevelopment during the first 3 years of life, in the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. METHODS: Pregnant women were recruited between January 2011 and March 2014, and 100,304 live births of singleton children born at full-term by vaginal delivery, and without congenital diseases were analyzed. Data on mothers and children were collected using a self-administered questionnaires and medical record transcripts. The children's neurodevelopment was repeatedly assessed for five domains (communication, gross motor, fine motor, problem solving, and personal-social), using the Ages and Stages Questionnaires, Third Edition, at six time points from age 6 to 36 months. After adjusting for potential confounders, the associations between exposure to epidural analgesia during labor and children's neurodevelopment at each time point were assessed. RESULTS: Of the 42,172 children with valid data at all six time points, 938 (2.4%) were born to mothers who received epidural analgesia during labor. Maternal exposure to epidural analgesia was associated with neurodevelopmental delays during the first 3 years after birth. Delay risks in gross and fine motor domains were the greatest at 18 months (adjusted odds ratio (aOR) [95% confidence interval (CI)]: 1.40 [1.06, 1.84] and 1.54 [1.17, 2.03], respectively), subsequently decreasing. Delay risks in communication and problem-solving domains were significantly high at 6 and 24 months, and remained significant at 36 months (aOR [95% CI]: 1.40 [1.04, 1.90] and 1.28 [1.01, 1.61], respectively). Exposure to epidural analgesia was also associated with the incidence of problem solving and personal-social delays from 18 to 24 months old. Neurodevelopmental delay risks, except for communication, were dominant in children born to mothers aged ≥30 years at delivery. CONCLUSIONS: This study showed that maternal exposure to epidural analgesia during labor was associated with neurodevelopmental delays in children during the first 3 years after birth.

Early Developmental Signs in Children with Autism Spectrum Disorder: Results from the Japan Environment and Children's Study.

Autism spectrum disorder (ASD) is a developmental disability in early childhood. Early identification and intervention in children with ASD are essential for children and their families. This study aimed to identify the earliest signs of ASD. Using a large cohort including data from 104,062 fetal records in the Japan Environment and Children's Study, we examined the Ages and Stages Questionnaires® (ASQ-3TM) scores of children with and without ASD. The ASQ-3 comprises five domains: communication, gross motor, fine motor, problem solving, and personal-social. The ASQ-3 scores were obtained at ages 6 months, 1 year, and 3 years. There were 64,501 children with available ASQ-3 data. The number of children diagnosed with ASD was 188 (0.29%) at 3 years of age. The highest relative risk (RR) for any domain below the monitoring score at 6 months was in the communication (RR 1.90, 95% CI 1.29-2.78, p = 0.0041), followed by fine motor (RR 1.50, 95% CI 1.28-1.76, p < 0.0001) domain. A low ASQ-3 score in the communication domain at 6 months was related to an ASD diagnosis at 3 years of age. The ASQ-3 score at 6 months can contribute to the early identification of and intervention for ASD.

Effects of early-life exposure to dust mite allergen and endotoxin on the development of asthma and wheezing: The Japan Environment and Children's Study.

BACKGROUND: The effects of early-life exposure to house dust mite allergen and endotoxin on the development of asthma are unclear in the literature. We investigated the association of early-life exposure (0-36 months old) to house dust mite allergen and endotoxin with asthma incidence. METHODS: In this novel, large-scale, nationwide birth cohort study, 5017 participants were randomly selected from those who met the eligibility criteria. House dust was vacuum-sampled from the children's mattresses within homes and assayed for the presence of dust mite allergen (Der 1) and endotoxin. The participants were classified into four quartiles (Q1-Q4) according to exposure levels. We defined the incidence of asthma and wheezing using questionnaires at 12, 24, and 36 months old. Odds ratios (ORs) of the incidence of asthma and wheezing by age in Der 1 and endotoxin exposure level were estimated using logistic regression. RESULTS: The cumulative incidence rates of asthma and wheezing during 0-36 months were 10.4% and 38.1%, respectively. Significant ORs were observed in asthma onset during 12-24 months old, asthma onset during 24-36 months old, and wheezing onset during 0-12 months old in the Q4 Der 1 group. In the Q4 endotoxin group, significant positive associations between endotoxin exposure and asthma (OR 2.00, 95% confidence interval [CI]: 1.03-3.85) and wheezing (OR 1.78, 95% CI: 1.01-3.12) onset during 24-36 months old were found. CONCLUSIONS: Our results indicated that high levels of early-life exposure to Der 1 and endotoxin in mattresses may be involved in the development of asthma.

Feelings about pregnancy and mother-infant bonding as predictors of persistent psychological distress in the perinatal period: The Japan Environment and Children's Study.

Feelings about pregnancy and mother-infant bonding are associated with maternal mental health before and after childbirth. The current study examined factors associated with persistent distress at 12 months after childbirth among mothers with psychological distress in the first trimester, using data from the Japan Environment and Children's Study (JECS). Feelings about pregnancy were assessed using a questionnaire in the first trimester, and maternal mental health was assessed using the Kessler 6 (K6) in the first trimester and at 12 months after childbirth. In addition, mother-infant bonding was assessed using the Mother-to-Infant Bonding Scale Japanese version (MIBS-J) at 12 months after childbirth, and 5 items from the MIBS-J at one and six months after childbirth. Among the 97,415 mothers registered in the JECS, 24,324 mothers with psychological distress (K6 ≥ 5) in the first trimester were included in this analysis. The relationships between persistence of psychological distress at 12 months after childbirth with feelings about pregnancy and mother-infant bonding were analyzed. Both maternal negative feelings about pregnancy in the first trimester and mother-infant bonding after childbirth were significantly associated with persistent psychological distress at 12 months after childbirth (ß = 0.02, p = 0.001 and ß = 0.35, p < 0.001, respectively). The indirect effect of feelings about pregnancy on persistent distress through mother-infant bonding was also observed (ß = 0.06, p < 0.001). These findings indicate that mother-infant bonding after childbirth may be important for improving the mental health of mothers with prenatal psychological distress.

Association between the serum insulin-like growth factor-1 concentration in the first trimester of pregnancy and postpartum depression.

AIM: Patients with major depression present with an increased serum insulin-like growth factor-1 (IGF-1) concentration. However, the longitudinal relationship between serum IGF-1 levels and depression development remains unclear. This study aimed to investigate the longitudinal association between the serum IGF-1 concentration in the first trimester of pregnancy and postpartum depression development using data obtained from the Japan Environment and Children's Study (JECS). METHODS: The JECS included 97 415 pregnant women; among them, 8791 were enrolled in this study. Data regarding depression in the first trimester, postpartum depression development at 1 month after childbirth, and other covariates were collected using a self-administered questionnaire. Serum IGF-1 levels were measured in the first trimester of pregnancy. The participants were divided into four groups according to the serum IGF-1 level. RESULTS: In the first trimester, serum IGF-1 levels were not significantly associated with psychological distress in pregnant women. In the longitudinal analyses, however, postpartum depression development in mothers within the highest quartile for serum IGF-1 concentration in the first trimester was significantly less common than in those within the lowest quartile (odds ratio 0.48, 95% confidence interval 0.30-0.79). CONCLUSION: Pregnant women with a high serum IGF-1 concentration in the first trimester were less likely to develop postpartum depression than those with a low concentration. A high serum IGF-1 concentration during pregnancy may help to protect against postpartum depression development.

Association between surgical procedures under general anesthesia in infancy and developmental outcomes at 1 year: the Japan Environment and Children's Study.

BACKGROUND: The neurotoxicity of general anesthesia to the developing human brains is controversial. We assessed the associations between surgery under general anesthesia in infancy and development at age 1 year using the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. METHODS: In the JECS, 103,062 pregnancies and 104,065 fetuses were enrolled between January 2011 and March 2014. Of the 100,144 registered live births, we excluded preterm or post-term infants, multiple births, and infants with chromosomal anomalies and/or anomalies of the head or brain. Data on surgical procedures under general anesthesia in infancy were collected from self-administered questionnaires by parents at the 1-year follow-up. Developmental delay at age 1 year was assessed using the Japanese translation of the Ages and Stages Questionnaires, Third Edition (J-ASQ-3), comprising five developmental domains. RESULTS: Among the 64,141 infants included, 746 infants had surgery under general anesthesia once, 90 twice, and 71 three or more times. The percentage of developmental delay in the five domains of the J-ASQ-3 significantly increased with the number of surgical procedures. After adjusting for potential confounding factors, the risk of developmental delays in all five domains was significantly increased in infants who had surgery under general anesthesia three times or more (adjusted odds ratios: for communication domain 3.32; gross motor domain 4.69; fine motor domain 2.99; problem solving domain 2.47; personal-social domain 2.55). CONCLUSIONS: Surgery under general anesthesia in infancy was associated with an increased likelihood of developmental delay in all five domains of the J-ASQ-3, especially the gross motor domain at age 1 year. The neurodevelopment with the growth should be further evaluated among the children who had surgery under general anesthesia. TRIAL REGISTRATION: UMIN Clinical Trials Registry (number: UMIN000030786 ).

Paternal occupational exposure to chemicals and secondary sex ratio: results from the Japan Environment and Children's Study.

BACKGROUND: Declining proportions of male births have been reported in several industrialised countries. Previous reports have shown that exposure to certain chemical substances might influence the secondary sex ratio (SSR). We assessed the associations between paternal occupational exposure to chemicals and the SSR of their children using the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. METHODS: Data on paternal occupational exposure to various agents and other covariates were collected using a self-administered questionnaire to partners of pregnant female participants enrolled in the JECS. After adjusting for potential confounders, multivariable modified Poisson regression models were used to evaluate associations between paternal occupational exposures and the SSR of their children. This study was registered in the UMIN Clinical Trials Registry, number UMIN000030786. FINDINGS: The JECS study gathered data on 103 062 pregnancies, 104 065 fetuses, and 51 898 partners of pregnant women. Among 50 283 children with data on paternal occupational exposures, 25 657 were male and 24 626 were female. The proportion of boys whose fathers were regularly occupationally exposed to insecticides was 0·445 (males, n=293; females, n=366; 95% CI 0·406-0·483), which was lower than the proportion of boys whose fathers were not exposed to insecticides. After adjusting for confounding factors, regular paternal occupational exposure to insecticides (adjusted relative risk 0·86, 95% CI 0·78-0·96) and medical disinfectants (0·95, 0·90-1·00) were significantly associated with lower SSRs among their offspring compared with the offspring of fathers not exposed to these substances. INTERPRETATION: A declining proportion of boys could potentially be due to fathers working in environments in which they are exposed to chemicals. The associations between poorer semen quality and levels of reproductive and thyroid hormones require investigation. FUNDING: Ministry of the Environment of Japan.