Adverse pregnancy outcomes of cancer survivors and infectious disease in their infants: The Japan Environment and Children's Study.

Birth cohort studies examining pregnancy and infant outcomes among adolescent and young adult (AYA) cancer survivors have been limited. The present study examined whether AYA cancer affects pregnancy outcomes of survivors and infectious diseases in their infants up to 1 year of age. Pregnant women were recruited for the Japan Environment and Children's Study, a nationwide, large-scale, prospective cohort study. The present study included 103,060 pregnant women and collected questionnaire-based data during the first and second/third trimester, and at 1 month, 6 months and 1 year after delivery. Adverse pregnancy outcomes and infectious diseases in infants up to 1 year of age were compared between AYA cancer survivors and pregnant women without a history of cancer using binominal logistic regression analyses and a multiple imputation method. Of 99,816 participants (3,244 were missing), 1,102 (1.1%) had a cancer history, including 812 participants (0.8%) with a history of cervical cancer. Among cervical cancer survivors, the adjusted (a)ORs were as follows: 3.25 (95% CI, 2.31-4.57; q=0.00) for a preterm birth <34 weeks' gestation; 2.82 (95% CI, 2.31-3.44; q=0.00) for a preterm birth <37 weeks' gestation; and 1.67 (95% CI, 1.36-2.06; q=0.00) for premature rupture of the membrane. Among the other cancer survivors, the aOR for caesarean section was 1.43 (95% CI, 1.10-1.87; q=0.0). Furthermore, lower respiratory tract inflammation in 1-year-old infants born by vaginal delivery increased significantly in cases with a history of cervical cancer (aOR, 1.77; 95% CI, 1.33-2.36; q=0.00). The present study identified the risk of lower respiratory tract inflammation in 1-year-old infants born by vaginal delivery in cervical cancer survivors for the first time. In addition, the frequency of caesarean section increased in all cancer survivors. No risk of congenital anomalies or other infections were found in the total group of cancer survivors.

Epidemiological Studies of Children's Gut Microbiota: Validation of Sample Collection and Storage Methods and Microbiota Analysis of Toddlers' Feces Collected from Diapers.

The composition of human gut microbiota influences human health and disease over the long term. Since the flora in specimens can easily change at ambient temperature outside the body, epidemiological studies need feasible methods of stool specimen collection and storage to be established. We aimed to validate two methods: feces frozen-stored in tubes containing guanidine thiocyanate solution for two months after collection (Method B), and feces excreted in diapers and frozen-stored (Method C). Validation was by comparison with a gold standard Method A. Bacterial flora of five adults were sampled and stored by all three methods. Bacterial composition was examined by amplicon sequencing analysis. Bland-Altman analyses showed that Methods B and C might change relative abundances of certain bacterial flora. Thereafter, we analyzed the bacterial flora of 76 toddlers (two age groups) in stools sampled and processed by Method C. The diversity indices of toddlers' flora were less than those of adults. The relative abundance of some bacteria differed significantly between children aged 1.5 and 3 years. The specimen collection and storage methods validated in this study are worth adopting in large-scale epidemiological studies, especially for small children, provided the limited accuracy for some specific bacteria is understood.

High Maternal Total Cholesterol Is Associated With No-Catch-up Growth in Full-Term SGA Infants: The Japan Environment and Children's Study.

Objectives: Infants born small for gestational age (SGA) with no catch-up growth (No-CU) are at high risk of intellectual and developmental disabilities. However, factors leading to No-CU among SGA infants are unclear. This study aimed to examine the association between maternal total cholesterol (TC) in mid-pregnancy and No-CU at 3 years among full-term SGA infants. Study Design: The Japan Environment and Children's Study (JECS) is a nationwide prospective birth cohort study. We extracted a total of 2,222 mothers and full-term SGA infants (length and/or weight <-2 standard deviation [SD]) without congenital abnormalities from the original JECS cohort comprising a total of 104,062 fetal records. According to the distribution of maternal TC in the entire cohort, participants were classified into nine groups per each fifth percentile with the 20th-79th percentiles (204-260 mg/dl) as the reference group. No-CU was defined by a Z-score of height at 3 years <-2 SD according to the growth standard charts for Japanese children. Multivariable-adjusted logistic regression models were carried out using multiple imputations. Additionally, a multiple-adjusted restricted cubic spline model was performed in the complete dataset. Results: A total of 362 (16.3%) children were No-CU at 3 years. After adjusting for the Z-score of birth weight, age of mother, smoking status, weight gain during pregnancy, breastfeeding and meal frequency at 2 years, and parents' heights, the odds ratio (95% confidence intervals) of No-CU was 2.95 (1.28-6.80) for children whose maternal TC levels were in the highest category (≥294 mg/dl), compared to the reference group. A multiple-adjusted restricted cubic spline model showed a non-linear trend of the significant association between high maternal TC and No-CU (p for linear trend = 0.05, p for quadratic trend <0.05). Conclusion: High maternal TC at mid-pregnancy was associated with No-CU among SGA infants. Such infants should be carefully followed up to introduce appropriate growth hormonal treatment. The findings may support previous animal experimental studies which indicated that maternal high-fat diet exposure induces impairment of growth and skeletal muscle development in the offspring. Future studies are required to elucidate the detailed mechanism.

Depression symptoms during pregnancy and postpartum in patients with recurrent pregnancy loss and infertility: The Japan environment and children's study.

There are a limited number of studies in which the depression status was followed up throughout pregnancy and postpartum to 1 year after delivery though 8.6-33% of women with recurrent pregnancy loss (RPL) and 10-25% of women who undergo in vitro fertilization and embryo transfer (IVF-ET) suffer from depression. We examined whether RPL and IVF-ET affect depressive symptoms during pregnancy and postpartum. A nationwide large-scale birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted. The subjects consisted of 99,202 pregnant women recruited between January 2011 and March 2014. The Kessler Psychological Distress Scale was used for the 1st trimester, 2nd/3rd trimester and 1 year postpartum. The Edinburgh Postnatal Depression Scale was used for the first and the sixth month postpartum. The screening instruments were used to quantify depressive symptoms. Women with no live births had a significantly higher prevalence of elevated depressive symptoms throughout pregnancy and postpartum. The prevalence of elevated depressive symptoms was significantly higher in the second/third trimester among women with three or more pregnancy losses with no live births. IVF-ET was associated with reduced risk of developing depressive symptoms during all pregnancies and at 1 and 6 months after delivery in women with no live births. RPL and IVF-ET did not affect postpartum depressive symptoms, and IVF-ET rather reduced the risk of depression throughout pregnancy and postpartum. Psychological support for RPL women would be necessary.

Simultaneous quantification of pyrethroid metabolites in urine of non-toilet-trained children in Japan.

BACKGROUND: Pyrethroid (PYR) insecticides are widely used for controlling various pests. There are two types that differ in terms of usage: agricultural-purpose PYR (agriculture-PYR) and hygiene purpose PYR (hygiene-PYRs). Few studies exist on the exposure to these chemicals in small children. In this study, we conducted biomonitoring of urinary pyrethroid metabolites in 1.5-year-old children throughout the year. METHODS: Study subjects were 1075 children participating in an Aichi regional sub-cohort of the Japan Environment and Children's Study as of 18-month health check-up. The concentrations of four specific hygiene-PYR metabolites including 2,3,5,6-tetrafluoro-1,4-benzenedimethanol (HOCH2-FB-Al), and five common metabolites of hygiene- and agriculture-PYRs including 3-phenoxybenzoic acid (3PBA) and cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (DCCA), were measured in urine samples extracted from soiled diapers using a triple quadrupole gas chromatograph-mass spectrometer. RESULTS: The highest detection frequencies were for 3PBA, followed by DCCA, 1R-trans-chrysanthemum dicarboxylic acid, and HOCH2-FB-Al. Among the six metabolites, urinary concentrations were seasonally varied. However, this variation was not observed in the most studied PYR metabolite, 3PBA. Spearman's correlation analysis demonstrated a significant positive correlation between FB-Al and DCCA (r = 0.56) and HOCH2-FB-Al and 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol (r = 0.60). CONCLUSIONS: This biomonitoring survey found widespread and seasonally specific exposure to multiple hygiene- and agriculture-PYRs in 1.5-year-old Japanese children.

Repeated maternal non-responsiveness to baby's crying during postpartum and infant neuropsychological development: The Japan Environment and Children's Study.

BACKGROUND: Longitudinal adverse effects of neglect-related behaviors during postpartum, especially repeated maternal non-responsiveness to the crying baby on their neuropsychological developmental trajectory, have not been fully clarified. OBJECTIVE: This study aimed to examine the association between postpartum maternal neglect-related behaviors and infant neuropsychological outcomes using the Japan Environment and Children's Study (JECS). PARTICIPANTS AND SETTING: JECS data on 100,286 mother-child pairs were analyzed. Explanatory variables were "frequency of leaving the baby alone at home" (i.e., leaving the baby alone at home) and "frequency of ignoring the baby when he or she cries" (i.e., ignoring the crying baby) at one month postpartum. The outcomes were measured using the Japanese version of the Ages & Stages Questionnaires-Third Edition (J-ASQ-3). METHODS: After multiple imputations, logistic regression analysis was performed to evaluate the association between neglect-related behaviors and the J-ASQ-3 domains at each age. RESULTS: The "sometimes or more" group of "ignoring the crying baby" from six months to three years reported relatively consistent significant associations with developmental delay in communication (maximum adjusted odds ratio [aOR]: 1.456, 95% confidence interval [CI]: 1.261-1.682), gross motor (maximum aOR: 1.279, 95% CI: 1.159-1.411), fine motor (maximum aOR: 1.274, 95% CI: 1.113-1.457), problem-solving (maximum aOR: 1.178, 95% CI: 1.104-1.256), and personal-social domains (maximum aOR: 1.326, 95% CI: 1.255-1.402). The adverse effects of "leaving the baby alone at home" disappeared in many domains by the age of one. CONCLUSIONS: Repeated maternal non-responsiveness to baby's crying during postpartum may suppress multiple neuropsychological development during early childhood.

Impact of Ready-Meal Consumption during Pregnancy on Birth Outcomes: The Japan Environment and Children's Study.

Ready-meal consumption is increasing worldwide; however, its impact on human health remains unclear. We aimed to examine the association between processed food and beverage consumption during pregnancy and pregnancy outcomes. Pregnant women were recruited for the Japan Environment and Children's Study (JECS), a nationwide, large-scale, prospective cohort study. This study included 104,102 registered children (including fetuses or embryos) and collected questionnaire-based data during the first and second/third trimester of pregnancy. Participants' medical records were transcribed at pregnancy registration, immediately after delivery, and 1 month after delivery. Logistic regression analysis was used to estimate the association between processed food consumption and pregnancy outcomes. The incidence of stillbirth was higher in the group that consumed moderate (1-2 times per week) and high (≥3-7 times per week) amounts of ready-meals (adjusted odds ratio (aOR) = 2.054, 95% confidence interval (CI): 1.442-2.926, q = 0.002; aOR = 2.632, 95% CI: 1.507-4.597, q = 0.007, respectively) or frozen meals (aOR = 2.225, 95% CI: 1.679-2.949, q < 0.001; aOR = 2.170, 95% CI: 1.418-3.322, q = 0.005, respectively) than in the group that rarely consumed such foods. Processed food consumption during pregnancy should be carefully considered.

Can Hip-Knee Line Angle Distinguish the Size of Pelvic Incidence?-Development of Quick Noninvasive Assessment Tool for Pelvic Incidence Classification.

This study aimed to explore effective measurement angles for pelvic incidence (PI) classification and to develop a quick, noninvasive assessment tool for PI classification. We defined five variation types of hip-knee line (HKL) angles and tested the discrimination ability of the receiver operating characteristic (ROC) analysis using 125 photographs of upright standing posture from the right lateral side. ROC analysis revealed an applicable HKL angle defined by the line connecting the most raised part of the buttock and the central point of the knee and the midthigh line. The acceptable cut-off points for discriminating small or large PIs in terms of HKL angle were 18.5° for small PI (sensitivity, 0.91; specificity, 0.79) and 21.5° for large PI discrimination (sensitivity, 0.74; specificity, 0.72). In addition, we devised a quick noninvasive assessment tool for PI classification using the cut-offs of the HKL angle with a view to practical application. The results of intra- and inter-rater reliability ensured a substantial/moderate level of the tool (Cohen's kappa coefficient, 0.79; Fleiss's kappa coefficient, 0.50-0.54). These results revealed that the HKL angle can distinguish the size of the PI with a high/moderate discrimination ability. Furthermore, the tool indicated acceptable inter-/intra-rater reliability for practical applications.

Association of Maternal Total Cholesterol With SGA or LGA Birth at Term: the Japan Environment and Children's Study.

CONTEXT: Maternal cholesterol is important for fetal development. Whether maternal serum total cholesterol (maternal TC) levels in midpregnancy are associated with small (SGA) or large (LGA) for gestational age independent of prepregnancy body mass index (BMI) and weight gain during pregnancy is inconclusive. OBJECTIVE: This work aimed to prospectively investigate the association between maternal TC in midpregnancy and SGA or LGA. METHODS: The Japan Environment and Children's Study is a nationwide prospective birth cohort study in Japan. Participants in this study included 37 449 nondiabetic, nonhypertensive mothers with singleton birth at term without congenital abnormalities. Birth weight for gestational age less than the 10th percentile and greater than or equal to the 90th percentile were respectively defined as SGA and LGA by the Japanese neonatal anthropometric charts. RESULTS: The mean gestational age at blood sampling was 22.7 ±â€…4.0 weeks. After adjustment for maternal age, sex of child, parity, weight gain during pregnancy, prepregnancy BMI, smoking, alcohol drinking, blood glucose levels, household income, and study areas, 1-SD decrement of maternal TC was linearly associated with SGA (odds ratio [OR]: 1.20; 95% CI, 1.15-1.25). In contrast, 1-SD increment of maternal TC was linearly associated with LGA (OR: 1.13; 95% CI, 1.09-1.16). Associations did not differ according to prepregnancy BMI and gestational weight gain (P for interaction > .20). CONCLUSION: Maternal TC levels in midpregnancy were associated with SGA or LGA in a Japanese cohort. It may help to predict SGA and LGA. Favorable maternal lipid profiles for fetal development must be explored.

Relationship between Physical Activity and Physical and Mental Health Status in Pregnant Women: A Prospective Cohort Study of the Japan Environment and Children's Study.

To discuss appropriate physical activity (PA) levels during pregnancy, this prospective cohort study examined the relationships between PA levels before and during pregnancy and physical and mental health status. Fixed data for 104,102 pregnant women were used from the Japan Environment and Children's Study, of which data for 82,919 women were analyzed after excluding women with multiple birth and pregnancy complications. PA levels were measured using the International Physical Activity Questionnaire-Short Form. The 8-Item Short Form Health Survey was used to measure outcomes. Logistic regression with multiple imputations showed that moderate PA for over 720 min/wk and vigorous PA before pregnancy were associated with poorer mental health in the first trimester (adjusted odds ratio (AOR): 1.087-1.376. Walking in the second and third trimesters was associated with better physical and mental health (AOR: 0.855-0.932). Moderate PA over 1080 min/wk and vigorous PA in the second and third trimesters were associated with poorer mental health (AOR: 1.223-1.873). Increases over 4135.4 MET-min/wk and decreases in PA levels were associated with poorer mental and physical health (AOR: 1.070-1.333). Namely, pregnant women receiving health benefits prefer continuous walking in addition to avoiding vigorous PA and excessive changes in PA levels during pregnancy.

Relationship between delivery with anesthesia and postpartum depression: The Japan Environment and Children's Study (JECS).

BACKGROUND: Postpartum depression is one of the most commonly experienced psychological disorders for women after childbirth, usually occurring within one year. This study aimed to clarify whether women with delivery with anesthesia, including epidural analgesia, spinal-epidural analgesia, and paracervical block, had a decreased risk of postpartum depression after giving birth in Japan. METHODS: The Japan Environment and Children's Study (JECS) was a prospective cohort study that enrolled registered fetal records (n = 104,065) in 15 regions nationwide in Japan. Binomial logistic regression analyses were performed to calculate the adjusted odd ratios (aORs) for the association between mode of delivery with or without anesthesia and postpartum depression at one-, six- and twelve-months after childbirth. RESULTS: At six months after childbirth, vaginal delivery with anesthesia was associated with a higher risk of postpartum depression (aOR: 1.233, 95% confidence interval: 1.079-1.409), compared with vaginal delivery without analgesia. Nevertheless, the risk dropped off one year after delivery. Among the pregnant women who requested delivery with anesthesia, 5.1% had a positive Kessler-6 scale (K6) score for depression before the first trimester (p < 0.001), which was significantly higher than the proportions in the vaginal delivery without analgesia (3.5%). CONCLUSIONS: Our data suggested that the risk of postpartum depression at six months after childbirth tended to be increased after vaginal delivery with anesthesia, compared with vaginal delivery without analgesia. Requests for delivery with anesthesia continue to be relatively uncommon in Japan, and women who make such requests might be more likely to experience postpartum depressive symptoms because of underlying maternal environmental statuses.

Cumulative exposure assessment of neonicotinoids and an investigation into their intake-related factors in young children in Japan.

Exposure levels of neonicotinoids (NEO) in young children remain unknown, despite their widespread use and the plausible vulnerability of toddlers to environmental toxicants. Herein we aimed to clarify the exposure levels and sources of NEOs in young Japanese children. Disposable diapers were collected from 1036 children (16-23 months old) participating in an adjunct study of the Japan Environment and Children's Study between 2015 and 2016. Six NEOs and one metabolite in urine extracted from a diaper from each child were analyzed using high-performance liquid chromatography-tandem mass spectrometry. A relative potency factor approach was used to assess the cumulative exposure to NEOs equivalent to dinotefuran levels (DINRPF). The 95th percentile urinary concentration of DINRPF was 157 µg/L and 380 µg/g creatinine (Cr). Receiver operating characteristic curve analyses for the propensity scores of the possible exposure-related factors revealed that the discriminatory powers determining whether Cr-adjusted and Cr-unadjusted DINRPF concentrations exceeding the 95th percentile values were higher for the amount of each foodstuff ingested on the survey day (areas under the curve were 0.62 and 0.75, respectively) than for the exposure-related behaviors (0.60 and 0.71, respectively) or for mothers' attitudes toward food selection and preparation (0.54 and 0.57, respectively). Use of a mosquito coil, insect repellent, and mothproof net for a screen door, and playing on a lawn were associated with increased urinary NEO levels (odds ratio [OR]: 2.0-2.9), while care about the child's nutritional balance by mothers reduced urinary NEO levels (OR: 0.23-0.41). To the best of our knowledge, this is the first study that dealt with urinary concentrations and possible exposure sources of NEOs in a large number of young children. Attention to the children's behavior and diet might result in the reduction of a high exposure to NEOs in young children.

Can self-monitoring mobile health apps reduce sedentary behavior? A randomized controlled trial.

OBJECTIVE: To examine whether the self-monitoring interventions of a mobile health app reduce sedentary behavior in the short and long terms. METHOD: We designed a double-blind randomized control trial. Participants were selected from among the staff of a medical institution and registrants of an online research firm. Forty-nine participants were randomly assigned to either a control group (n = 25) or an intervention group (n = 24). The control group was given only the latest information about sedentary behavior, and the intervention was provided real-time feedback for self-monitoring in addition to the information. These interventions provided for 5 weeks (to measure the short-term effect) and 13 weeks (to measure the long-term effect) via the smartphone app. Measurements were as follows: subjective total sedentary time (SST), objective total sedentary time (OST), mean sedentary bout duration (MSB), and the number of sedentary breaks (SB). Only SST was measured by self-report based on the standardized International Physical Activity Questionnaire and others were measured with the smartphone. RESULTS: No significant results were observed in the short term. In the long term, while no significant results were also observed in objective sedentary behavior (OST, MSB, SB), the significant differences were observed in subjective sedentary behavior (SST, ßint  - ßctrl between baseline and 9/13 weeks; 1.73 and 1.50 h/d, respectively). CONCLUSIONS: Real-time feedback for self-monitoring with smartphone did not significantly affect objective sedentary behavior. However, providing only information about sedentary behavior to users with smartphones may make misperception on the amount of their subjective sedentary behavior.

Association between Prenatal Exposure to Household Pesticides and Neonatal Weight and Length Growth in the Japan Environment and Children's Study.

The effects of prenatal exposure to household pesticides on fetal and neonatal growth have not been fully clarified. The present study aims to determine the effects of prenatal exposure to pesticides on neonates' body size and growth during the first month. This study included 93,718 pairs of pregnant women and their children from the Japan Environment and Children's Study. Participants completed self-reporting questionnaires during their second or third trimesters on their demographic characteristics and frequency of pesticide use during pregnancy. Child weight, length, and sex were obtained from medical record transcripts. Birth weight and length, as well as weight and length changes over the first month, were estimated using an analysis of covariance. Frequency of exposure to almost all pesticides had no effects on birth weight and length. However, we found small but significant associations (i) between the use of fumigation insecticides and decreased birth weight, and (ii) between frequencies of exposure to pyrethroid pesticides, especially mosquito coils/mats, and suppression of neonatal length growth. Prenatal exposure to household pesticides, especially those containing pyrethroids, might adversely influence fetal and postnatal growth trajectories.

Sexual difference in 2nd-to-4th digit ratio among 1.5-year-old Japanese children: A cross-sectional study of Aichi regional adjunct cohort of the Japan Environment and Children's Study (JECS-A).

BACKGROUND: A sex difference in the second-to-fourth digit ratio (2D:4D, males < females) has been described in Japanese fetuses and children, and its possible links to autism spectrum disorders (ASDs) have been discussed. Accordingly, this sexual difference in representative neonates merits examination. AIMS: This study aimed to examine 2D:4D measurements and sexual differences in Japanese toddlers aged 1.5 years. STUDY DESIGN AND SUBJECTS: The digit lengths used to calculate 2D:4D were measured using an easy-to-use photography method. A total of 1045 JECS-A (the Aichi regional sub-cohort of the Japan Environment and Children's Study) children (males, 523; females, 522) aged 1.5 years were analyzed. RESULTS: The mean ages for the males and females were 575.3 ± 13.1 and 575.9 ± 17.1 days, respectively. Histograms of left and right 2D:4D were normally distributed regardless of sex (left male, 0.909 ± 0.048; left female, 0.913 ± 0.049, d = 0.08; right male, 0.938 ± 0.055; right female, 0.937 ± 0.049, d = 0.02). Because of high dispersion in the data, t-tests did not support a significant sex difference in 2D:4D. Post-hoc statistical power was calculated as 0.124 and the effect size for the sex difference in 2D:4D was 0.036. CONCLUSIONS: This study failed to confirm sexual differences in 2D:4D in 1.5-year-old Japanese children. This may be because digit measurement is difficult in this group, resulting in reduced effect sizes, or because rapid growth attenuates the in utero sexual dimorphism. This evidence is useful for the light it casts on the extreme male brain theory of ASDs.

Identifying characteristics of indicators of sedentary behavior using objective measurements.

OBJECTIVE: Recent attention has been focused on sedentary behavior (SB) affecting health outcomes, but the characteristics of indicators reflecting SB remain to be identified. This cross-sectional study aims to identify the characteristics of indicators of SB, focusing on the examination of correlations, reliability, and validity of sedentary variables assessed by the smartphone app. METHOD: Objectively measured data of SB of eligible 46 Japanese workers obtained from smartphones were used. We assessed the characteristics of current indicators being used with a 10-minute or 30-minute thresholds, in addition to the conventional indicators of total sedentary time, mean sedentary bout duration, and total number of sedentary bouts. They were evaluated from three perspectives: (a) association among the indicators, (b) reliability of the indicators, and (c) criterion validity. RESULTS: Total sedentary time under 10 minutes (U10) and U30 had negative associations with Total sedentary time (r = -.47 and -.21 respectively). The correlation between Mean sedentary bout duration and Total number of sedentary bouts was -.84, whereas between Mean sedentary bout duration 10, 30 and Total number of sedentary bouts were -.54 and -.21, respectively. The intraclass correlation coefficients of almost all indicators were around .80. Mean sedentary bout duration, Mean sedentary bout duration 10, Total number of sedentary bouts, Total sedentary time 30, U30 and U10 have significant differences between three BMI groups. CONCLUSION: This study comprehensively revealed the rationale of advantage in the current indicator being used with a 10-minute or 30-minute threshold, rather than the conventional total amount of SB.

Effects of long working hours and shift work during pregnancy on obstetric and perinatal outcomes: A large prospective cohort study-Japan Environment and Children's Study.

BACKGROUND: The work patterns of pregnant women may be related to adverse obstetric and perinatal outcomes. This study aimed to clarify the effects of weekly working time according to frequencies of night shifts during pregnancy on adverse outcomes in Japan. METHODS: The Japan Environment and Children's Study, a prospective cohort study, was conducted in 15 regions nationwide in Japan. The study population included pregnant women with singleton pregnancies (n = 99 744). The mothers' working hours and frequencies of night shifts during the first and the second/third trimesters were assessed using a self-administered questionnaire. Outcome data were collected from medical transcripts. RESULTS: Compared with nonworking women, women who worked during pregnancy had significantly increased adjusted odds ratios (aORs) of threatened miscarriage (maximum aOR: 1.47, 95% confidence interval [95% CI]: 1.26-1.73) and of threatened preterm labor (maximum aOR: 1.63, 95% CI: 1.41-1.87). Increased aORs were observed for hypertensive disorders of pregnancy (maximum aOR: 2.02, 95% CI: 1.39-2.93) in women working ≥36 hours per week with night shifts, for vacuum/forceps delivery (maximum aOR: 1.34, 95% CI: 1.22-1.48) at ≥36 hours with or without night shifts, and for small-for-gestational-age babies (aOR: 1.32, 95% CI: 1.10-1.59) at ≥46 hours with night shifts. In contrast, lower aORs were observed for gestational diabetes and meconium-stained amniotic fluid in women working without night shifts. CONCLUSIONS: Work during pregnancy slightly increased the risks of threatened miscarriage and threatened preterm labor. Long working hours increased the risks of hypertensive disorders of pregnancy, vacuum/forceps delivery, and small-for-gestational-age babies.

Cohort profile: Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A).

PURPOSE: Effects of fetal, perinatal and childhood environment on the health of children at birth and during later life have become a topic of concern. The Aichi regional sub-cohort of the Japan Environment and Children's Study (JECS-A) is an ongoing birth cohort of pregnant women and their children which has been used to provide unique data, as adjunct studies of JECS, on multifaceted potential factors affecting children's health. PARTICIPANTS: The JECS-A is part of the JECS which follows a total of 100 000 pairs of children and their mothers (fathers' participation is optional) across 15 regions in Japan. In JECS-A, of the 8134 pregnant women living in Ichinomiya City and Nagoya City, Japan, a total of 5721 pregnant women and their 5554 children were included. Sociodemographic and psychological data as well as biological specimens were collected from the pregnant women and their spouses (if available) in the cohort during their pregnancy. Information on children included in the JECS-A was collected from their mothers and includes demographic, behavioural, childcare, psychological and psychiatric data. Urine extracted from disposable diapers and anthropometric data were also obtained from the children. FINDINGS TO DATE: A similar distribution trend for age at delivery was confirmed between the pregnant women enrolled in the JECS-A and the national statistics of the relevant areas. However, differences in education level and household income were observed. A total of 5502 children remained in the cohort at 18 months after delivery. Compared with the national statistics, the basic demographics of the children in the cohort represented the population in the study areas. FUTURE PLANS: The enrolled children in the JECS-A will be followed until the age of 13 years. The studies that come from JECS-A will complement JECS and bring novel results with a high level of generalisability.

Endometriosis and Recurrent Pregnancy Loss as New Risk Factors for Venous Thromboembolism during Pregnancy and Post-Partum: The JECS Birth Cohort.

BACKGROUND: Since venous thromboembolism (VTE) is one of the causes of maternal mortality, several guidelines recommend prophylaxis using low molecular weight heparin for women in high-risk groups. The number of large population-based studies examining predictors for VTE has been limited, and there has been no study based on a Japanese population. OBJECTIVE: Our objective was to examine VTE risk factor during the pregnancy and post-partum period. MATERIALS AND METHODS: A nationwide birth cohort study known as the 'Japan Environment and Children's Study (JECS)' was conducted by the Ministry of the Environment. The subjects consisted of 103,070 pregnancies recruited by the JECS between January 2011 and March 2014. Pregnant women completed the questionnaires during the first and second/third trimester. Their medical records were transcribed by physicians or research coordinators at registration, just after delivery and at 1 month after delivery. RESULTS: The frequency of VTE was 7.5 per 10,000 pregnancies (77 of 103,070) during the pregnancy and post-partum period. After the adjustment of multiple covariates for each factor, endometriosis and recurrent pregnancy loss (RPL) were identified as novel independent risk factors for VTE. Adjusted odds ratios were as follows: 2.70 (95% confidence interval, 1.21-6.00) for endometriosis and 6.13 (2.48-15.16) for RPL. Threatened abortion, threatened pre-term birth, pre-term birth and caesarean section were ascertained to be risk factors for VTE. CONCLUSION: Careful attention should be given to novel predictors, such as endometriosis and a history of RPL, to prevent VTE during the pregnancy and post-partum period.

Adverse pregnancy and perinatal outcome in patients with recurrent pregnancy loss: Multiple imputation analyses with propensity score adjustment applied to a large-scale birth cohort of the Japan Environment and Children's Study.

PROBLEM: Several studies have reported the increased risk of preterm birth, premature rupture of membranes, and low birth weight in patients with recurrent pregnancy loss (RPL). There have been a limited number of large population-based studies examining adverse pregnancy and perinatal outcome after RPL. Multiple-imputed analyses (MIA) adjusting for biases due to missing data is also lacking. METHOD OF STUDY: A nationwide birth cohort study known as the "Japan Environment and Children's Study (JECS)" was conducted by the Ministry of the Environment. The subjects consisted of 104 102 registered children (including fetuses or embryos). RESULTS: No increased risk of a congenital anomaly, aneuploidy, neonatal asphyxia, or a small for date infant was observed among the children from women with a history of RPL. A novel increased risk of placental adhesion and uterine infection was found. The adjusted ORs using MIA in women with three or more PL were 1.76 (95% CI, 1.04-2.96) for a stillbirth, 1.68 (1.12-2.52) for a pregnancy loss, 2.53 (1.17-5.47) for placental adhesion, 1.87 (1.37-2.55) and 1.60 (.99-2.57) for mild and severe hypertensive disorders of pregnancy, respectively, 1.94 (1.06-3.55) for uterine infection, 1.28 (1.11-1.47) for caesarean section and .86 (.76-.98) for a male infant. CONCLUSION: MIA better quantified the risk, which could encourage women who might hesitate to attempt a subsequent pregnancy.