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BackgroundStreptococcus infection is a common and potentially severe bacterial infection which remains a global public health challenge, underscoring the necessity of investigating potential risk factors.AimsThe present study aims to assess the association between metal and trace element exposure and Streptococcus infection using a prospective nationwide birth cohort, the Japan Environment and Children's Study (JECS).MethodsThe JECS obtained data from over 100,000 pregnancies through 15 Regional Centres across Japan. We assessed toxic metal and trace element levels among pregnant mothers and Streptococcus infection among their children, born between 2011 and 2014, at age three to four. Analysis was performed using univariable and multivariable logistic regressions, as well as Quantile g-computation. We also conducted quartile regressions to assess the effects of higher serum selenium levels and potential interactions between selenium and mercury.ResultsAmong 74,434 infants and their mothers, univariable and multivariable regression analyses found that selenium and mercury each had an inverse association with Streptococcus infection incidence. Quantile g-computation analysis yielded results consistent with the primary regression analyses. Quartile regression suggested that serum selenium levels above the third quartile were inversely associated with later Streptococcus infection incidence, but no interaction between selenium and mercury was found.ConclusionsThese findings imply that maternal selenium exposure may have protective effects on Streptococcus infection among children. Further studies should explore the role of pediatric selenium in immune responses to infectious diseases, especially Streptococcus infection.

Abstract Objective: Pre-pregnancy weight status is related to offspring health and may influence dietary patterns during pregnancy. We aimed to evaluate the link between pre-pregnancy weight status and dietary patterns during pregnancy. Design: Dietary data were collected using a FFQ during middle or late pregnancy. Dietary patterns were identified using principal component analysis. Anthropometric data were extracted from medical charts. Multiple linear regression was used to assess associations between pre-pregnancy weight status (severely or moderately underweight, mildly underweight, normal weight, overweight and obese) and dietary patterns during pregnancy after adjusting for socio-demographic characteristics. Setting: Nationwide Japan. Participants: Pregnant Japanese women enrolled in the Japan Environment and Children’s Study, a prospective birth cohort study (n 90 765). Results: We identified three dietary patterns. Compared with women with pre-pregnancy normal weight, those with pre-pregnancy obesity were less likely to habitually consume ‘fruits and vegetables’ pattern (coefficient, –0·18; 95 % CI, –0·21, –0·14) and ‘confectionery’ pattern (coefficient, –0·18; 95 % CI, –0·21, –0·14) and more likely to consume ‘white rice and soy products’ pattern (coefficient, 0·08; 95 % CI, 0·04, 0·11), and those with severely or moderately pre-pregnancy underweight were more likely to consume ‘confectionery’ pattern (coefficient, 0·06; 95 % CI, 0·03, 0·09) during pregnancy, after adjusting for confounders. Conclusion: We found that moderately and severely pre-pregnancy underweight women and those with obesity had unhealthy dietary patterns compared to those with pre-pregnancy normal weight. Our findings suggest that prenatal dietary advice is important and should be based on the pre-pregnancy weight status.

Bruxism, the involuntary activity of masticatory muscles, is common among individuals with autism spectrum disorders (ASD). Although bruxism is bidirectionally associated with sleep issues, whether an infant's sleep duration contributes to the development of bruxism remains unknown. In this study, a dataset (n = 83,720) obtained from the Japan Environment and Children's Study, a nationwide birth cohort study, was subjected to multiple imputations using logistic regression analysis with adjustments for several maternal and child-related variables. The aim of this study was to assess whether shorter sleep duration in the neonatal period additively affected the high prevalence of parent-reported bruxism (PRB) among children with ASD. The prevalences of ASD and PRB in the participants were 1.2% and 7.2%, respectively, and the odds ratio of the increased risk of PRB prevalence in individuals with ASD (95% confidence interval) was 1.59 (1.31-1.94) after covariate adjustments. Importantly, shorter sleep duration in the neonatal period (at one month of age) was significantly associated with an increased risk of PRB prevalence in individuals with ASD. The increased occurrence of bruxism, known to be highly prevalent among children with ASD, is associated with shorter sleep duration, particularly in the neonatal stage. Based on our results, a better understanding of the development of bruxism in individuals with ASD would provide valuable information for the prevention of oral diseases.

The relationship between maternal prenatal psychological distress and epilepsy development in offspring has not yet been clarified. Herein, we used a dataset obtained from the Japan Environment and Children's Study, a nationwide birth cohort study, to evaluate the association between six-item Kessler Psychological Distress Scale (K6) scores and epilepsy among 1-3 years old. The data of 97,484 children were retrospectively analyzed. The K6 was administered to women twice: during the first half (M-T1) and second half (M-T2) of pregnancy. M-T1 ranged from 12.3-18.9 (median 15.1) weeks, and M-T2 ranged from 25.3-30.1 (median 27.4) weeks. Participants were divided into six groups based on K6 scores of two ranges (≤4 and ≥5) at M-T1 and M-T2. The numbers of children diagnosed with epilepsy at the ages of 1, 2, and 3 years were 89 (0.1%), 129 (0.2%), and 149 (0.2%), respectively. A maternal K6 score of ≥5 at both M-T1 and M-T2 was associated with epilepsy diagnosis ratios among 1-, 2-, and 3-year-old children in the univariate analysis. Moreover, multivariate analysis revealed that a maternal K6 score of ≥5 at both M-T1 and M-T2 was associated with epilepsy diagnosis ratios among 1-, 2-, and 3-year-olds. Continuous moderate-level maternal psychological distress from the first to the second half of pregnancy is associated with epilepsy among 1-, 2-, and 3-year-old children. Hence, environmental adjustments to promote relaxation such as mindfulness in pregnant women might be necessary.

BackgroundThere has been a recent decrease in the prevalence of infectious diseases in children worldwide due to the usage of vaccines. However, the association between cesarean delivery and infectious diseases remains unclear. Here, we aimed to clarify the association between cesarean delivery and the development of infectious diseases.MethodsThis study is a cross-sectional study. We used data from the Japan Environment and Children's Study, which is a prospective, nationwide, government-funded birth cohort study. The data of 104,065 records were included. Information about the mode of delivery, central nervous system infection (CNSI), otitis media (OM), upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), gastrointestinal infection (GI), and urinary tract infection (UTI) was obtained from questionnaires and medical records transcripts. Multiple logistic regression analysis was used to assess the association between cesarean delivery and CNSI, OM, URTI, LRTI, GI, and UTI risk.ResultsWe included a total of 74,477 subjects in this study, of which 18.4% underwent cesarean deliveries. After adjusting for the perinatal, socioeconomic, and postnatal confounding factors, children born by cesarean delivery did not have an increased risk of developing CNSI (95% confidence interval [CI] 0.46-1.35), OM (95% CI 0.99-1.12), URTI (95% CI 0.97-1.06), LRTI (95% CI 0.98-1.15), GI (95% CI 0.98-1.11), or UTI (95% CI 0.95-1.45).ConclusionsThis nationwide cohort study did not find an association between cesarean delivery and CNSI, OM, URTI, LRTI, GI, and UTI. However, further studies are needed to evaluate the role of cesarean delivery in the development of infectious diseases.

BackgroundIt is well known that maternal diet affects the development of offspring. Herein, the relationship between maternal intake of fermented foods during pregnancy and offspring development was investigated.MethodsThe diet of 103,060 pregnant women at >4 months of gestation who were enrolled in the Japan Environment and Children's Study was analyzed. Their intake levels of fermented soybeans (miso and natto), yogurt, and cheese were investigated. The developmental status of the offspring at 3 years of age was assessed using the Ages and Stages Questionnaires (ASQ-3). Multivariable logistic regression analysis was performed to determine the risk of maternal intake levels of the fermented foods associated with subsequent developmental delay in the offspring.ResultsIntake of cheese was associated with a reduced risk of child developmental delay in all intake level groups from the second quartile onward. Intakes of miso and yogurt were associated with a reduced risk of developmental delay in communication skills in the fourth quartile. There was no association between intake of natto and developmental delay.ConclusionMaternal consumption of fermented foods during pregnancy may reduce the risk of later developmental delay in offspring. It is therefore important to review the mother's diet for fermented foods during pregnancy. However, further studies are warranted to evaluate the factors influencing the association between diet and offspring development.

AimThis study aimed to determine whether excessive maternal weight gain during pregnancy was associated with a higher risk of prolonged labor.MethodsWe analyzed the data regarding maternal weight gain during pregnancy for the participants of Japan Environment and Children's Study (JECS), which is an ongoing nationwide prospective birth cohort study in Japan. After excluding participants with multiple pregnancies, with deliveries before 37 or beyond 42 weeks of gestation, or who had undergone cesarean section, 71,154 (nulliparous, n = 28,442) Japanese women were included. Prolonged labor was defined by a cutoff ranking at the 95th percentile and consequently defined as labor duration exceeding 12.7 h in multiparous women and exceeding 23.2 h in nulliparous women. These classifications were made according to labor curves established by the Japanese Society of Obstetrics and Gynecology Perinatal Committee developed in June 2021. Considering that no studies have conducted an investigation based on this new guideline, we analyzed the association between excessive maternal weight gain during pregnancy and prolonged labor by parity.ResultsThe overall incidence of prolonged labor was 10.2% (2,907/28,442) in nulliparous women and 6.1% (2,597/42,712) in multiparous women. Multivariable analysis indicated that excessive maternal weight gain was significantly associated with prolonged labor in nulliparous (adjusted odds ratio, 1.21; 95% confidence interval, 1.10-1.32) and multiparous women (adjusted odds ratio, 1.15; 95% confidence interval, 1.05-1.27). Kaplan-Meier survival analysis showed that as labor progressed, the percentage of women who had not yet delivered was higher among those with excessive maternal weight gain than among those with normal maternal weight gain in both the nulliparous (median labor duration 12.9 h vs 12.2 h, pConclusionExcessive maternal weight gain was significantly associated with prolonged labor in Japanese women.

BackgroundChildhood asthma is known to be affected by a range of factors, including conditions in the indoor environment. While flooring material influences indoor air conditions, the potential association between flooring materials and childhood asthma remains poorly understood in Japan.ObjectiveThe present study aims to assess the association between childhood asthma incidence and the primary flooring material with the ongoing prospective nationwide birth cohort data of the Japan Environment and Children's Study (JECS).MethodsThe JECS gathered data on mothers and children through 15 Regional Centres across Japan. The present study assessed flooring materials used in the home and asthma incidence at age four among children born between 2011 and 2014. We implemented logistic regressions, setting asthma incidence among the children as the outcome and home floor type as the exposure. Additional analyses were conducted, stratifying the home's age as a proxy for tatami age, to assess whether the potential effect of tatami flooring on asthma risk is influenced by its age.ResultsThe present study included total of 75,629 infants. For tatami flooring, the main multivariable regression and additional sub-group regression for homes over ten years old produced odds ratios of 1.09; 95% Confidence Interval (CI) [1.01-1.17] and 1.10; 95% CI [1.00-1.21] compared with flooring, respectively.ConclusionThese results imply that exposure to tatami flooring, particularly in older homes, may be associated with childhood asthma incidence. Moreover, our study highlights the importance of evaluating the relationship between regional and cultural differences between asthma and flooring materials.

Abstract Background Women with nausea and vomiting of pregnancy (NVP) have higher birth weight infants, while those with hyperemesis gravidarum, a severe manifestation of NVP, have lower birth weight infants. We aimed to investigate the associations between maternal weight loss (a consequence of hyperemesis gravidarum), NVP, and infant birth weight. Methods This study was a secondary analysis of a nationwide birth cohort in Japan. Singleton pregnancies delivered at 28–41 weeks of gestation were included in the analysis. Women were categorized based on their weight change in the 1st trimester (as a proportion to their pre-pregnancy weight: > + 3%, > 0 to + 3%, > -3 to 0%, > -5 to -3%, ≤ -5%) and severity of NVP (no nausea, only nausea, vomiting but able to eat, vomiting and unable to eat). The effects of weight change and severity of NVP on infant birth weight and small for gestational age (SGA) were assessed using regression models. We further examined how these effects could be modified by maternal weight gain up to the 2nd trimester. Results Among 91,313 women, 5,196 (5.7%) lost ≥ 5% of their pre-pregnancy weight and 9,983 (10.9%) experienced vomiting and were unable to eat in the 1st trimester. Women with weight loss ≥ 5% in the 1st trimester had infants 66 (95% CI: 53, 78) g lighter and higher odds of SGA (aOR: 1.29; 95% CI: 1.14, 1.47) than women who gained > 3% during the same period. However, when adjusting for weight gain up to the 2nd trimester, women with weight loss ≥ 5% in the 1st trimester had infants 150 (95% CI: 135, 165) g heavier and lower odds of SGA (aOR: 0.39; 95% CI: 0.33, 0.46) than those who gained > 3% during the same period. In contrast, women with more severe NVP tended to have infants with larger birth weight and lower odds of SGA compared to women without NVP. These trends were strengthened when adjusting for weight gain up to the 2nd trimester. Conclusions Our study suggests the possibility that reduced fetal growth in pregnancies with hyperemesis gravidarum may be caused by the lack of catch-up in gestational weight gain up to the 2nd trimester.

Abstract Background Although childhood undervaccination among single mother families is a concern for child healthcare, their association is still under debate. This study aimed to investigate the association between maternal marital status and the risk of childhood undervaccination and determine the mediating effect of household income. Methods We utilised prospective birth cohort from the Japan Environment and Children’s Study (JECS). Of 104,062 foetal records (children) from 97,413 mothers, 82,462 that included mothers recruited between 2011 and 2014, were analysed. Childhood undervaccination was defined as not having been vaccinated with at least one routine vaccine. A log-binomial regression analysis was used to estimate the risk ratio (RR) for the association between maternal marital status and the risk of childhood undervaccination. A causal mediation analysis was further performed to investigate the proportion of the association mediated by household income. Results Among 82,462 children, 3188 and 79,274 had unmarried and married mothers, respectively. Childhood undervaccination was observed in 1053 (33.0%) and 16,901 (21.3%) children of unmarried and married mothers, respectively. Maternal marital status was associated with a higher risk of childhood undervaccination (adjusted risk ratio [aRR], 1.34; 95% confidence interval [CI], 1.27 to 1.41). Compared with married and older mothers, both unmarried and older (aRR, 1.54; 95% CI, 1.35 to 1.77) and unmarried and younger (aRR, 1.66; 95% CI, 1.54 to 1.79) mothers were associated with a higher risk of childhood undervaccination. The causal mediation analysis showed that the proportion mediated by household income was 10.5% (95% CI, 9.9 to 11.0%). Conclusions This nationwide, prospective, large-scale birth cohort study found that a household with a single mother was associated with an increased risk of childhood undervaccination, and 10% of this association was explained by household income. These findings underscore the importance of improving the social environment among single mother families, including not only poverty but also working conditions.

Neurodevelopmental disorders (NDDs) in children are associated with a complex combination of genetic and/or environmental factors. Pre-/perinatal events are major known environmental suboptimal factors, and their individual and combined contributions vary. This study investigated the association between pre-/perinatal reduced optimality and child development observed by parents at 1 month, as well as NDDs at 3 years of age (i.e., motor delay, intellectual disability, developmental language disorder, and autism spectrum disorder), in the context of the Japan Environment and Children's Study. The study also assessed whether child development at 1 month predicted NDDs at 3 years of age. Associations between 25 pre-/perinatal factors and (a) developmental concerns at 1 month of age and (b) NDDs at 3 years were analyzed (n = 71,682). Binomial regression models were used to investigate risk ratios of the developmental outcome at each time point for total pre-/perinatal reduced optimality scale scores, as well as for individual pre-/perinatal factors of the reduced optimality scale. Finally, we assessed the ability of parental observations of offspring development at 1 month to predict NDDs at 3 years. Total reduced optimality scores were positively associated with 1-month developmental concerns and 3-year NDDs, with higher scores (i.e., a reduction in optimality) associated with an increased risk of both NDDs and earlier parental concerns. Neonatal transportation, epidural analgesia, advanced maternal age, cesarean section delivery, Apgar score ≤8, and hyperbilirubinemia were identified as individual risk factors for 3-year NDDs, overlapping with 14 risk factors for 1-month developmental concerns except Apgar score ≤8. Among six developmental items assessed at 1 month of age, concerns about gross motor function and difficulty holding/trouble calming down had the strongest associations with later-diagnosed motor delay and autism spectrum disorder, respectively. Five perinatal factors and advanced maternal age were associated with NDD at 3 years of age, as were early parental developmental concerns regarding their offspring's overall development, indicating the importance of careful follow-up of offspring born with pre-/perinatal reduced optimality. The results also implicated early parental concerns, as early as 1 month, may also be a useful indicator of later NDD status.

The hygiene hypothesis suggests that pet exposure is effective in preventing allergic disease, and some studies have reported the beneficial effects of dog exposure during fetal development or early infancy on food allergy. However, the effects of exposure to pets other than dogs on the kinds of food allergies remains unaddressed. This study aimed to explore the effect of exposure to various species of pets on the risk of food allergies. We obtained information on pet exposure and food allergy from the Japan Environment and Children's Study, a nationwide, prospective birth cohort study that included 97,413 mothers and their children. We examined the associations between exposure to various species of pets during fetal development or early infancy and the incidence risk of food allergies. We conducted logistic regression analysis for each pet species, causative food, and timing of exposure. Exposure to dogs or cats during fetal development or early infancy was estimated to reduce the incidence risk of food allergies until the age of 3 years. Dog exposure was estimated to reduce the incidence risk of egg, milk, and nut allergies, and cat exposure was estimated to reduce the incidence risk of egg, wheat, and soybean allergies. However, hamster exposure was estimated to increase the incidence risk of nut allergy. In conclusion, the association between pet exposure and food allergies might differ depending on the pet species and causative food. Continued dog and cat exposure from fetal development to infancy was estimated to reduce the incidence risk of food allergies. The findings of this study shall aid in the design of future studies.

The sex of the conceived child is a significant concern for parents. To verify whether there women have pregnancy bias toward boys or girls, we investigated whether the history of continuous same-sex pregnancy was associated with the subsequent child's sex. We prospectively analyzed data from the Japan Environment and Children's Study, a birth cohort study. We included all cases of singleton live births (n = 98 412). Women with pregnancy due to infertility treatment were excluded (n = 6255); Similarly, women with a history of miscarriage, artificial abortion, stillbirth, and multiple pregnancies, and those with missing data on the sex of the previous child were excluded. Altogether, 62 718 women were included. For the first live birth, a male-biased sex ratio of 1.055 was observed. Further, no significant difference was found in the sex ratio of the conceived child between women with one boy and those with one girl previously. However, when there were more than two children previously, the subsequently conceived child's male/female sex ratio was significantly higher among boy-only mothers than among girl-only mothers. The results indicated that several pregnant women are biased toward conceiving either boys or girls.

Abstract Background The association between a slower physical growth and poorer neurodevelopment has been established in infants born preterm or small for gestational age. However, this association is inconsistent in term-born infants, and detailed investigations in infancy, when intervention is most beneficial for improving outcomes, are lacking. We therefore examined this association separately by sex during the first year of life in term-born infants. Methods Using data collected until children reached 12 months old in an ongoing prospective cohort of the Japan Environment and Children’s Study, we analyzed 44,264 boys and 42,541 girls with singleton term-birth. The exposure variables were conditional variables that disentangle linear growth from weight gain relative to linear growth, calculated from the length and weight at birth and 4, 7 and 10 months old. Neurodevelopmental delay was identified using the Japanese-translated version of Ages & Stages Questionnaires, third edition. Results A reduced risk of neurodevelopmental delay at 6 months old was observed in children with a higher birth weight (adjusted relative risks [aRRs]: 0.91 and 0.93, 95 % confidence intervals [95 % CIs]: 0.87–0.96 and 0.88–0.98 in boys and girls, respectively) and increased linear growth between 0 and 4 months old (aRRs: 0.85 and 0.87, 95 % CIs: 0.82–0.88 and 0.83–0.91 in boys and girls, respectively). A reduced risk at 12 months was found in children with an increased linear growth between 0 and 4 months (aRRs: 0.92 and 0.90, 95 % CIs: 0.87–0.98 and 0.84–0.96 in boys and girls, respectively), boys with an increased relative weight gain between 0 and 4 months (aRR: 0.90, 95 % CI: 0.84–0.97), and girls with a higher birth weight (aRR: 0.89, 95 % CI: 0.83–0.96). Conclusions These results suggest that a slow physical growth by four months old may be a predictor of neurodevelopmental delay during infancy.

Abstract Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), are three reportedly predictive biomarkers that reflect subclinical chronic inflammatory burden. However, how these biomarkers change during pregnancy and its clinical utility among pregnant women have been rarely studied. Among 76,853 singleton pregnancies delivered at 28–41 weeks of gestation that were enrolled in the Japan Environment and Children’s Study, we observed the distribution of maternal NLR, PLR, and LMR values from week 0 to week 36 using spline curves, as well as their predictive values for preterm delivery with and without hypertensive disorders in pregnancy, placental abruption and intrauterine growth restriction (collectively termed ischemic placental disease due to their shared pathological and pathophysiological features) for measurements at 8–11 weeks, 12–17 weeks, and 18–21 weeks. NLR and PLR increased, whereas LMR decreased, with increasing gestation. High LMR and low NLR observed at 18–21 weeks, but not at earlier gestations, were associated with higher risk of preterm delivery with IPD (odds ratio 1.80 [95% CI 1.02, 3.19] per log[LMR]; odds ratio 0.49 [95% CI 0.29, 0.82] per log[NLR]). All parameters were not predictive of preterm delivery without IPD. We provide a robust reference curve for maternal blood count parameters NLR, PLR, and LMR by gestational week.

Abstract Background To examine changes in psychological distress prevalence among pregnant women in Miyagi Prefecture, which was directly affected by the Great East Japan Earthquake and tsunami, and compare it with the other, less damaged areas of Japan. Methods This study was conducted in conjunction with the Japan Environment and Children`s Study. We examined 76,152 pregnant women including 8270 in Miyagi Regional Center and 67,882 in 13 other regional centers from the all-birth fixed data of the Japan Environment and Children’s Study. We then compared the prevalence and risk of distress in women in Miyagi Regional Center and women in the 13 regional centers for 3 years after the disaster. Results Women in the Miyagi Regional Center suffered more psychological distress than those in the 13 regional centers: OR 1.38 (95% CI, 1.03–1.87) to 1.92 (95% CI, 1.42–2.60). Additionally, women in the inland area had a consistently higher prevalence of psychological distress compared to those from the 13 regional centers: OR 1.67 (95% CI, 1.18–2.38) to 2.19 (95% CI, 1.60–2.99). Conclusions The lack of pre-disaster data in the Japan Environment and Children’s Study made it impossible to compare the incidence of psychological distress before and after the March 2011 Great East Japan Earthquake. However, 3 years after the Great East Japan Earthquake, the prevalence of pregnant women with psychological distress did not improve in Miyagi Regional Center. Further, the prevalence of mental illness in inland areas was consistently higher than that in the 13 regional centers after the disaster.

Abstract Aims/Introduction We aimed to evaluate the metabolic status of pregnant women by assessing metabolic biomarkers of participants in the Japan Environment and Children’s Study, a nationwide, multicenter, pregnancy and birth cohort. Materials and Methods Pregnant women aged 14–50 years were studied in 15 centers across Japan. Clinical information was obtained using self‐administered questionnaires. Blood samples were taken during the first two trimesters to measure metabolic biomarkers. Samples were divided into seven groups according to the weeks of pregnancy. Results Among 82,972 pregnant women, 43 had only type 1 diabetes, 78 had only type 2 diabetes, 2,315 had only gestational diabetes and 354 had only dyslipidemia. Glycated hemoglobin, total cholesterol, low‐density lipoprotein cholesterol and triglyceride across all the percentiles increased as prepregnancy body mass index increased, whereas high‐density lipoprotein cholesterol levels across all the percentiles decreased as body mass index increased. Glycated hemoglobin was high in participants with type 1 diabetes or type 2 diabetes only, but not in those with gestational diabetes or hyperlipidemia only. Participants with type 2 diabetes or dyslipidemia only had high triglyceride in the first trimester, which then decreased in the second trimester. Participants with type 2 diabetes only also showed low high‐density lipoprotein cholesterol, whereas participants with dyslipidemia only showed high total cholesterol and low‐density lipoprotein cholesterol throughout. Conclusions Metabolic biomarkers were affected by blood sample timing and underlying metabolic disease. The Japan Environment and Children’s Study will clarify the influences of metabolic status during pregnancy on the health and development of the offspring in future studies.

Abstract Background Determining the appropriate preconception care to reduce the occurrence of hypertensive disorder of pregnancy (HDP) remains a challenge in modern obstetrics. This study aimed to examine the association between pre-pregnancy calcium (Ca) intake and HDP in normotensive primiparas. Methods We used data from the Japan Environment Children’s study (JECS), which is the largest birth cohort study. A total of 33,894 normotensive Japanese primiparas were recruited for JECS between January 2011 and March 2014. Participants were categorized into five groups according to pre-pregnancy Ca intake quintiles (Q1 and Q5 were the lowest and highest Ca intake groups, respectively) to compare their basic background and obstetrics outcome. Multiple logistic regressions were performed to identify the effect of pre-pregnancy Ca intake on HDP, early onset HDP, and late-onset HDP, using Ca intake thresholds of 500, 550, 650, 700, 1000, 1500, and 1500 mg. Results We found significant differences in maternal background among the Ca intake groups; in particular, there were more participants with low socioeconomic status, indicated by low education level and low household income, and smokers in the lowest Ca intake group. Multiple logistic regression did not show any significant difference with regard to HDP, early onset HDP, and late-onset HDP in each Ca intake threshold. Conclusions Despite considerable recommendations concerning Ca intake for women of reproductive age, the present study indicates that pre-pregnancy Ca intake was not associated with an increased risk of new-onset hypertension among primiparas during pregnancy. Further studies examining the effect of other pre-pregnancy dietary factors on obstetric outcomes should be considered in the formulation of earlier preventive strategies for primiparas.

Abstract Background Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development. Methods We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children’s Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age. Results Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028–1.893) or four to five different inactivated vaccines (aOR 1.544, 95% CI 1.149–2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e. wheeze (aOR 1.238, 95% CI 1.094–1.401; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007–1.299; four or five vaccines vs. a single vaccine). Conclusions Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue. Trial registration UMIN000030786 .

Abstract 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 )

Maternal intake of folic acid supplements is reportedly associated with the risk of early-onset allergies in offspring. However, only a few studies have considered the intake of both folic acid supplements and dietary folate. Here, the relationship between maternal intake of folic acid supplements and allergic symptoms such as wheeze and eczema in offspring was analyzed while considering dietary folate intake. We examined 84,361 mothers and 85,114 children in the Japan Environment and Children’s Study. The participants were divided into three groups depending on maternal folic acid supplementation (“no use,” “occasional use,” and “daily use”). Each group was then subdivided into three groups based on total folic acid and dietary folate intake. Outcomes were determined considering the wheeze and eczema status of each child at the age of 2 years. The status was based on the International Study of Asthma and Allergies in Childhood. It was found that 22.1% of the mothers took folic acid supplements daily. In contrast, 56.3% of the mothers did not take these supplements. Maternal intake of folic acid supplements was not associated with wheeze and eczema in the offspring. In contrast, only dietary folate intake was positively associated with wheeze at the age of 2 (adjusted odds ratio, 1.103; 95% confidence interval, 1.003–1.212). However, there is no scientific evidence of a biological mechanism that clarifies this result. Potential confounders such as other nutrition, outdoor/indoor air pollution, and genetic factors may have affected the results. Therefore, further studies on the association between maternal intake of folic acid and allergic symptoms at the age of 3 or above are needed to confirm the results of this study. Trial registration UMIN Clinical Trials Registry (number: UMIN000030786)

AimThe aim of this study was to examine the relationship between breastfeeding and postpartum maternal weight change.MethodThis study used data from the Japan Environment and Children's Study (JECS), an ongoing nationwide birth cohort study. Participants were categorized into two groups: full breastfeeding (FB) and non-full breastfeeding (NFB) groups. Postpartum weight changes between the FB (n = 26,340) and NFB (n = 38,129) groups were compared.ResultsAt 6 months postpartum, mean weight retention was significantly lower in the FB group than in the NFB group (0.2 vs 0.8 kg, respectively, pConclusionBreastfeeding reduced maternal weight retention, which was greater in mothers who were obese before pregnancy. For obese women, active breastfeeding may improve their health.

ObjectiveTo determine the climate conditions that affect the incidence of atopic dermatitis from infancy to 3 years old.Study designWe analyzed 100,303 children born from 2011 to 2014 for follow-up until 3 years old using cohort data from the Japan Environment and Children's Study. The study included 15 Regional Centers, including 19 prefectures across Japan. We used meteorological data of the Japan Meteorological Agency. We calculated the hazard ratio (HR) of the standard deviation and low vs. high mean values of several climate conditions in children in their first 6 months of life to determine the incidence of atopic dermatitis.ResultsThe Kaplan-Meier curve showed that children born in the months of October to December had the highest incidence of atopic dermatitis. Among climate conditions, a one standard deviation increase in the temperature (HR = 0.87), minimum temperature (HR = 0.87), and vapor pressure (HR = 0.87) showed the lowest HRs for the incidence of atopic dermatitis. These results were confirmed by an analysis by strata of the birth season. A low vapor pressure (HR = 1.26, pConclusionAmong climate conditions, a low vapor pressure is the most strongly associated with a high incidence of atopic dermatitis. Measuring vapor pressure may be useful for preventing atopic dermatitis.

BackgroundCleft lip and palate (cleft L/P) is one of the most common congenital anomalies and its etiology is assumed to be multifactorial. Recent epidemiological data involving a small number of participants suggested an association between perinatal exposure to heavy metals and cleft L/P in affected children. However, this association requires further investigation in a large cohort.MethodsThis nested case-control study used a dataset of The Japan Environment and Children's Study, which is an ongoing research project to investigate the association between environmental factors and mother-child health. Participants were enrolled between 2011 and 2014. From the records of fetuses/children, we extracted data of isolated cleft L/P cases and matched children without cleft L/P at a ratio of 1:10. The exposures of interest were in utero exposure to four metals (mercury [Hg], lead [Pb], cadmium [Cd], and manganese [Mn]), which were sampled from mothers in the second/third trimester. Conditional logistic regression was used to assess the association between heavy metal exposure and isolated cleft L/P. Three sensitivity analyses were conducted to test the robustness of the findings, including the change in case definition and statistical methods.ResultsOf 104,062 fetal records involving both live-birth and stillbirth, we identified 192 children with isolated cleft L/P and 1,920 matched controls. Overall, the blood metal levels were low (for example, median Pb level was 5.85, 6.22, and 5.75 μg/L in the total cohort, cases, and controls, respectively). Univariate and multivariate analyses showed that levels of none of the four heavy metals in the mother's blood during pregnancy were associated with the risk of cleft L/P in offspring; the adjusted odds ratios (per 1 μg/L increase) with 95% intervals were 0.96 (0.91-1.03), 1.01 (0.94-1.08), 1.00 (0.61-1.63) and 1.00 (0.97-1.03) for Hg, Pb, Cd and Mn, respectively. The results were consistent in all sensitivity analyses.ConclusionsExposure to these four metals during pregnancy was not associated with isolated cleft L/P at the low exposure level in our cohort.

We aimed to determine the risk of perinatal complications during delivery in mothers with non-normal glucose tolerance in a large Japanese birth cohort. We analysed data of 24,295 neonate-mother pairs in the Japan Environment and Children's Study cohort between 2011 and 2014. We included 67 mothers with type 1 diabetes, 102 with type 2 diabetes (determined by questionnaire), 2,045 with gestational diabetes (determined by diagnosis), and 2,949 with plasma glucose levels ≥140 mg/dL (shown by a screening test for gestational diabetes). Gestational age, birth weight, placental weight, and proportions of preterm birth, and labour and neonatal complications at delivery in mothers with diabetes were compared with those in mothers with normal glucose tolerance. Mean gestational age was shorter in mothers with any type of diabetes than in mothers without diabetes. Birth weight tended to be heavier in mothers with type 1 diabetes, and placental weight was significantly heavier in mothers with type 1 and gestational diabetes and elevated plasma glucose levels (all p

This study aimed to examine the association between infant sleep quality and temperament in one-month-old infants using a large cohort study data. We used data from the Japan Environment and Children's Study, a cohort study which follows around 100,000 women from pregnancy until their children's development. The mothers were asked about their infants' sleep and temperament using a structured questionnaire. Frequent crying (adjusted odds ratio [AOR]: 1.05, 95% confidence interval [CI]: 1.00-1.10) and intense crying (AOR: 1.19, 95% CI: 1.13-1.25) were positively associated with longer sleep periods during the day than at night. Female infants with longer daytime sleep periods than that at nighttime were more likely to cry frequently (AOR: 1.11, 95% CI: 1.04-1.20). Parous women with infants who had frequent night awakening believed their infants cried more intensely (AOR: 1.17, 95% CI: 1.03-1.31). The study demonstrated a specific association between sleep quality and temperament in one-month-old infants. Based on the results of this study, further sleep intervention studies are required to improve infant temperament.

This study aimed to investigate the impact of Chlamydia trachomatis (CT) infection on pregnancy outcome in pregnant Japanese women. We utilized the data from a nationwide birth cohort study, the Japan Environment and Children's Study (JECS), for this study. We enrolled 26,385 individuals who could refer to data on pregnancy outcomes and confounding factors, with data on CT. Binominal logistic regression models were used to determine whether pregnant women with CT positivity were at more risk of experiencing adverse pregnancy outcomes, preterm birth (PTB), preterm prelabor rupture of membrane (pPROM), low birth weight (LBW) infants, small for gestational age (SGA) births, or hypertensive disorders of pregnancy (HDP). After adjusting for maternal age, parity, marital status, smoking status, and education status, there were no significantly increased risks of PTB, pPROM, LBW infants, SGA, and HDP in the odds ratios. No significant increase in the risk of adverse pregnancy outcomes was observed in any of the subgroup analyses, which were limited to the pregnancy women in Fukushima prefecture, where CT screening could be confirmed at 28-30 weeks of gestation. We believe that the results of this study will make a significant contribution to the future of medical care for pregnant women in Japan. Our findings are important for medical practitioners to contribute to the future medical treatment of Japanese pregnant women, and also to contribute to pre-conception care for Japanese society as a whole, including pregnant women.

Abstract Background Cleft lip and/or palate is among the most prevalent congenital birth defects, and negatively affects maternal psychological status and may consequently result in higher prevalence of child maltreatment. However, the association of childbirths of infants with cleft lip and/or palate with maternal emotional involvement still remains unclear. We examined the association between childbirths of infants with cleft lip and/or palate and mother-to-infant bonding, using data from the Japan Environment and Children’s Study, a nationwide birth cohort study. Methods A cross-sectional study using the jecs-an-20,180,131 dataset was performed. A total 104,065 fetuses in 15 regional centres in Japan were enrolled after obtaining informed written consent. The Mother-to-Infant Bonding Scale, a self-report scale consisting of 10 items, was used to evaluate maternal bonding at one year after childbirth. Finally, the participants consisted of 79,140 mother-infant pairs, of which 211 mothers of infants with cleft lip and/or palate were included in our analyses. Multivariable logistic regression analysis using multiple imputation for missing data was performed to calculate the odds ratio and 95% confidence interval in the estimation of the association between bonding disorders and childbirths with cleft lip and/or palate. Results No increased risk of bonding disorders was observed among all the mothers of infants with cleft lip and/or palate (odds ratio [95% confidence interval]; 0.97 [0.63–1.48], p = 0.880), however, advanced maternal age or multiple parity may adversely affect the associations between bonding disorders and cleft lip and/or palate, respectively. After stratification with a combination of maternal age and parity, a significant association of cleft lip and/or palate with bonding disorders was found only among advanced-age multiparae (odds ratio [95% confidence interval] = 2.51 [1.17–5.37], p = 0.018), but it was weakened after additional adjustment for maternal depression. Conclusions Childbirths of infants with cleft lip and/or palate may increase the risk of bonding disorders among advanced-age multiparae, possibly through maternal depression. This finding provides valuable information for the provision of multidisciplinary cleft care.

Abstract Background Gestational diabetes mellitus (GDM) has serious effects on both mother and child. Like Type 2 Diabetes Mellitus, it is increasing in prevalence world-wide. In addition to obesity, sleep duration has been named an important risk factor. Using a large cohort study, including data from 48,787 participants of the Japan Environment and Children’s Study (JECS), we examined the association between sleep duration and both random blood glucose levels and GDM rates during pregnancy. Methods Random blood glucose levels were measured during pregnancy. GDM diagnosis was based on the results of 75 g oral glucose tolerance test. Additional anthropometric data was collected from questionnaires for statistical analysis. Results Compared to mothers averaging 7 to

Abstract Background Placenta previa and placenta accreta associate with high morbidity and mortality for both mothers and fetus. Metal exposure may have relationships with placenta previa and placenta accreta. This study analyzed the associations between maternal metal (cadmium [Cd], lead [Pb], mercury [Hg], selenium [Se], and manganese [Mn]) concentrations and placenta previa and placenta accreta. Methods We recruited 17,414 women with singleton pregnancies. Data from a self-administered questionnaire regarding the first trimester and medical records after delivery were analyzed. Maternal blood samples were collected to measure metal concentrations. The subjects were classified into four quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations. Results The odds ratio for placenta previa was significantly higher among subjects with Q4 Cd than those with Q1 Cd. The odds ratio for placenta previa was significantly higher for subjects with Q2 Pb than those with Q1 Pb. Conclusion Participants with placenta previa had higher Cd concentrations. However, this study was cross-sectional and lacked important information related to Cd concentration, such as detailed smoking habits and sources of Cd intake. In addition, the subjects in this study comprised ordinary pregnant Japanese women, and it was impossible to observe the relationship between a wide range of Cd exposure and placenta previa. Therefore, epidemiological and experimental studies are warranted to verify the relationship between Cd exposure and pregnancy abnormalities.

Abstract Background The dietary pattern of pregnant women is known to be associated with preterm birth (PTB). We investigated whether PTB was associated with intake of fermented food by using data from the Japan Environment and Children’s Study. Methods From a data set of 103,099 pregnancies, 77,667 cases at low risk for PTB were analyzed. The primary outcome measurements were based on PTB. Fermented food (miso soup, yogurt, cheese, and fermented soybeans) consumption was assessed by using a semi-quantitative food frequency questionnaire. Results Intake of miso soup, yogurt, and fermented soybeans before pregnancy significantly reduced the risk of early PTB (

The association between birth month and neurodevelopmental or psychiatric disorders has been investigated in a number of previous studies; however, the results have been inconsistent. This study investigated the association between birth month and child gross motor development at 6 and 12 months of age in a large cohort of infants (n = 72,203) participating in the Japan Environment and Children's Study (JECS). Gross motor development was assessed using the Ages and Stages Questionnaire (ASQ-3). At 6 months and 12 months, 20.7% and 14.2%, respectively, had ASQ-3 indications of gross motor problems. Birth month was strongly associated with gross motor development at both time points, particularly at 6 months. Summer-born infants had the worst outcomes at both 6 months and 12 months of age. This outcome applied to the ASQ-3 score itself and to the adjusted Relative Risk (aRR), with the highest aRRs (relative to January-born) among August-born (aRR 2.51; 95%CI 2.27-2.78 at 6 months), and June-born (aRR 1.84; 95%CI 1.63-2.09 at 12 months). Boys had better scores than girls both at 6 and 12 months of age. We speculate that seasonal factors-such as maternal vitamin D deficiency and influenza infection-affecting the fetus in early pregnancy might account for the findings.

Skin inflammation leads to altered cytokine/chemokine production and causes systemic inflammation. The systemic mechanism of atopic dermatitis (AD) is recognized to affect systemic metabolism. This study aimed to examine the relationship between early-onset persistent eczema and body weight, height, and body mass index (BMI), in addition to food allergy in a birth cohort among infants. This study design was a nationwide, multicenter, prospective birth cohort study-the Japan Environment and Children's Study (JECS). Generalized linear models were fitted for z scores of weight, height, BMI, and food allergy to evaluate the relationship between eczema and these outcomes for infants at age1, 2, and 3 years. Persistent eczema was negatively associated with height at the age of 2 years (estimated coefficient, -0.127; 95% confidence interval [CI], -0.16 to -0.095) and 3 years (-0.177; 95% CI, -0.214 to -0.139). The same tendency was also observed with weight and BMI. Early disease onset at younger than 1 year and persistent eczema had the strongest association with development of food allergy at age 3 years (OR, 11.794; 95% CI, 10.721-12.975). One phenotype of eczema with early-onset and persistent disease creates a risk of both physical growth impairment and development of food allergy. Infants who present with the early-onset and persistent type of eczema should be carefully evaluated daily for impaired physical growth and development of food allergy.

BackgroundThe influence of mothers' and fathers' educational levels in separate evaluations of asthma has not been fully investigated. This study aims to examine the associations of the mother's and fathers' educational levels with childhood wheeze and asthma adjusting for crude and pre-and post-natal modifiable risk factors.MethodsWe conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant women from 2011 to 2014. The mother's and father's educational levels were surveyed by a questionnaire during the pregnancy, and childhood wheezing and doctor-diagnosed asthma were estimated using a 3-year questionnaire. Multilevel logistic regression analysis was performed to evaluate the association between the mother's and father's educational levels and childhood wheezing and asthma, adjusted for pre-and post-natal factors.ResultsA total of 69,607 pairs of parents and their single infants were analyzed. We found 17.3% of children had wheezing and 7.7% had asthma. In crude analyses, lower educational level of parents was associated with an increased risk of childhood wheezing and asthma. After full adjustment, a lower educational level of mothers was associated with an increased risk of childhood asthma (junior high school (reference: high school); odds ratio (OR): 1.17, 95% CI, 1.01-1.36), and higher educational level, especially the mother's, was associated with an increased risk of childhood wheezing (technical junior college, technical/vocational college, or associate degree (ECD3); OR: 1.12, 95% CI, 1.06-1.18, bachelor's degree, or postgraduate degree; OR: 1.10, 95% CI, 1.03-1.18), and asthma (ECD3; OR: 1.13, 95% CI, 1.04-1.21).ConclusionsParents' lower educational level was a crude risk factor for childhood wheezing and asthma. However, an increased risk of wheezing due to mothers' higher educational level was found after adjusting for pre-and post-natal factors.

The association between maternal diet during pregnancy and allergy in offspring remains contentious. Here, we examined the association between maternal intake of vegetables and related nutrients during pregnancy and allergic diseases in offspring at one year of age. A cohort of 80,270 pregnant women enrolled in the Japan Environment and Children's Study were asked to respond to a food frequency questionnaire during pregnancy and the International Study of Asthma and Allergies in Childhood questionnaire at one year postpartum. The women were categorized into quintiles according to the energy-adjusted maternal intake of vegetables and related nutrients. Using the categorizations as exposure variables, the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were determined for the allergic outcomes, including asthma, wheeze, atopic dermatitis, eczema, and food allergy, in the offspring per quintile at one year of age. Of the 80,270 participants, 2,027 (2.5%), 15,617 (19.6%), 3,477 (4.3%), 14,929 (18.7%), 13,801 (17.2%), and 25,028 (31.3%) children experienced asthma, wheeze, atopic dermatitis, eczema, food allergy, and some form of allergic disease, respectively. The aORs of each quintile of maternal vegetable intake for all allergic outcomes were close to 1.0 compared to the lowest quintile. The lowest aOR was found in the association of maternal cruciferous vegetable intake with asthma (aOR: 0.82, 95% CI: 0.70-0.96) and highest was found in the association of maternal total vegetable intake with atopic dermatitis (aOR: 1.17, 95% CI: 1.04-1.31). The risk of allergic outcomes for the various nutrients related to vegetable consumption was close to 1.0. The maternal intake of vegetables and various related nutrients during pregnancy had little or no association with any of the allergic outcomes, including asthma, wheezing, atopic dermatitis, eczema, and food allergy, in offspring at one year.

ObjectivePlacental abruption is a significant obstetric complication that affects both maternal and neonatal mortality and morbidity. The present study examined the effect of maternal age on the incidence of placental abruption.MethodsWe used data of singleton pregnancies from the Japan Environment and Children's Study, which was a prospective birth cohort study conducted between January 2011 and March 2014 across 15 regional centers in Japan. A multiple regression model was used to identify whether maternal age (ResultsA total of 94,410 Japanese women (93,994 without placental abruption and 416 with placental abruption) were recruited. Herein, 764, 8421, 25915, 33517, and 25793 women were aged ConclusionsIn the Japanese general population, besides advanced maternal age, teenage pregnancy was associated with placental abruption. Recently, the mean maternal age has been changing in Japan. Therefore, it is important for obstetric care providers to provide proper counseling to young women based on up-to-date evidence.

Abstract Background Some studies have suggested that blastocyst transfer is associated with i) imbalance in the secondary sex ratio (SSR) (which favors male offspring), ii) increased incidence of monozygotic twins (MZT). In contrast, others have not found these changes. In this study, we evaluated the association between blastocyst transfer and SSR and MZT, considering potential parental confounders. Methods The Japan Environment and Children’s Study is a large, nationwide longitudinal birth cohort study funded by the Ministry of the Environment of Japan. We used this large dataset, including 103,099 pregnancies, to further investigate the association between blastocyst transfer, SSR and MZT, using spontaneously conceived pregnancies, non-assisted reproductive technology (non-ART) treatment (intrauterine insemination and ovulation induction with timed intercourse) and cleavage stage embryo transfer for comparison. We evaluated the association with each group, the SSR, and the frequency of MZT, calculating the adjusted odds ratio (AOR) using multivariable logistic regression analyses, adjusting for potential parental confounders such as basic health and socioeconomic status. Results For each group (spontaneous conception vs. non-ART treatment vs. cleavage stage embryo transfer vs. blastocyst transfer), the percentages of males were 51.3% vs 50.7% vs 48.9% vs 53.4% and the monozygotic twinning rates per pregnancy were 0.27% vs 0.11% vs 0.27% vs 0.99% respectively. Multivariate logistic regression analyses indicated that blastocyst transfer was significantly associated with a higher SSR and higher incidence of MZT than the other three groups (SSR: AOR 1.095, 95% CI1.001–1.198; MZT: AOR 4.229, 95% CI 2.614–6.684). Conclusions There are significant relationships between blastocyst transfer and SSR imbalance and a higher occurrence of MZT.

Abstract Background Although pregnancies conceived by assisted reproductive technology (ART) have a higher risk of maternal/perinatal complications, the overall risk of adverse outcomes necessitating advanced obstetric care has not been closely examined. The present study aimed to assess and compare the risk of maternal/perinatal complications and adverse outcomes in pregnancy and childbirth conceived by ART with those conceived naturally. Methods This study was conducted as a part of the Japan environment and children’s study (JECS), an ongoing nationwide birth cohort study in Japan. The risk of maternal/perinatal complications and adverse outcomes was assessed by mode of conception (natural conception, ovulation induction [OI] without ART, conventional in vitro fertilization and embryo transfer [IVF-ET], or intracytoplasmic sperm injection [ICSI]) using logistic regression and generalized estimating equations controlling for potential confounders. Results The final dataset included women who conceived naturally (N = 90,506), by OI without ART (N = 3939), by conventional IVF-ET (N = 1476), and by ICSI (N = 1671). Compared with women who conceived naturally, those who conceived by conventional IVF-ET were at higher risk of placenta previa (adjusted OR 2.90 [95% CI 1.94, 4.34]), morbidly adherent placenta (6.85 [3.88, 12.13]), and pregnancy-induced hypertension (1.40 [1.10, 1.78]) whereas those who conceived by ICSI had a higher risk of placental abruption (2.16 [1.20, 3.88]) as well as placenta previa (2.01 [1.29, 3.13]) and morbidly adherent placenta (7.81 [4.56, 13.38]). Women who conceived by ART had a higher risk of blood transfusion (conventional IVF-ET: 3.85 [2.52, 5.88]; ICSI: 3.76 [2.49, 5.66]) and ICU admission (conventional IVF-ET: 2.58 [1.11, 6.01]; ICSI: 3.45 [1.68, 7.06]) even after controlling for potential confounders. Neonates conceived by ART had a higher risk of preterm birth (conventional IVF-ET: 1.42 [1.13, 1.78]; ICSI: 1.31 [1.05, 1.64]). Conclusions Women who conceived by ART had a higher risk of maternal/perinatal complications necessitating advanced obstetric care. Obstetricians should be aware of the increased risk of adverse outcomes among this population.

Abstract Objective There have been increasing reports on the association between cesarean section (C-section) and the subsequent development of diseases in infants. C-section affects the diversity of microbiota in the infant’s gut. In the present study, we investigated the association between infants delivered by C-section and the development of constipation at 1 year old due to altered gut microbiota using data from the Japan Environment and Children’s Study (JECS). Results This cohort study (n = 83,019) used data from JECS, an ongoing cohort study which began in January 2011. Data on bowel movement and potential confounding factors were recorded. A log-binomial regression model was used to estimate the risk of C-section, and the results were expressed as risk ratios and their respective 95% confidence intervals. Although infants delivered by C-section were of significantly younger gestational age and lesser birth weight than vaginally delivered infants, the frequency of bowel movements was almost similar between the two, independent of the mode of delivery. The prevalence of constipation in the entire infant was 1.37%. No significant differences were observed for C-section in crude and adjusted risk ratios for constipation.

Abstract Background Few studies have examined the association of workhours and shift work (referred to here as “time-related work factors”) with dietary behaviors. We aimed to investigate this association, as well as the dietary behaviors among individuals with occupations characterized by time-related work factors. Methods A cross-sectional study was performed using data from the Japan Environment and Children’s Study. The study included 39,315 working men. Dietary behaviors (i.e., skipping breakfast, eating out, eating instant food, overeating, and eating fast) were assessed with a self-reported information from the Food Frequency Questionnaire. Logistic regression analysis was conducted to examine the associations of time-related work factors with dietary behaviors and dietary behavior tendencies among those in occupations characterized by long workhours and/or shift work. Results Long workhours were associated with high frequencies of skipping breakfast, eating out, eating instant food, overeating, and eating fast. The frequency of having shift work was associated with high frequencies of skipping breakfast, eating out, and eating instant food. Several occupations involving long workhours and/or shift work showed specific dietary behaviors; in some occupations, the level of significance changed after adjusting for time-related work factors in addition to other potential confounding factors. Conclusions Time-related work factors may help explain workers’ dietary behaviors. Long workhours and shift work may lead to poor dietary behaviors. Other factors influenced by occupation itself, such as food environment, may also influence workers’ dietary behaviors. Workhours and/or shift work, and these other work factors, should be given attention in workplace health promotion.

Abstract Background Nausea and vomiting during pregnancy (NVP) is considered to be associated with favorable fetal outcomes, such as a decreased risk for spontaneous abortion. However, the relationship between NVP and preterm births remains unknown. This study was conducted to evaluate the association between NVP and the risk of preterm births. Methods The dataset of a birth cohort study, the Japan Environment and Children’s Study (JECS), was retrospectively reviewed. Participants’ experience of NVP prior to 12 gestational weeks were evaluated by a questionnaire administered from 22 weeks of pregnancy to 1 month before delivery. NVP responses were elicited against four choices based on which the study population was divided into four subcohorts. Preterm birth was the main study outcome. Logistic regression analysis was used to quantify an association between NVP and risk of preterm birth. Results Of 96,056 women, 79,460 (82.7%) experienced some symptoms of NVP and 10,518 (10.9%) experienced severe NVP. Compared to those who did not experience NVP, women with severe NVP had lower odds for preterm birth [adjusted odds ratio (aOR) 0.84, 95% confidence interval (95% CI) 0.74–0.95]. An even lower OR was found among very preterm birth and extremely preterm birth (aOR 0.44, 95% CI 0.29–0.65). Conclusion An inverse association exists between NVP and preterm births, especially, very preterm births and extremely preterm births.

Abstract Objectives Small for gestational age infants have an increased risk of immediate complications, short-term morbidity and mortality, and long-term neurologic and metabolic disorders in adulthood. Previous research has shown that reduced sleep duration is a risk factor for SGA birth. However, only a few studies have evaluated maternal sleep as a risk factor for SGA birth. In the present study, we investigated the relationship between the amount and quality of mothers’ sleep and infants’ birth weight. Results This cohort study (n = 8631) used data from the Japan Environment and Children’s Study, an ongoing cohort study that began in January 2011. Data on sleep status (sleep duration and one indicator of sleep quality) and potential confounding factors were recorded. A log-binomial regression model was used to estimate the risk of small for gestational age birth, and the results were expressed as risk ratios and their respective 95% confidence interval. No significant results were observed for sleep duration or tiredness upon waking. Neither the amount nor the quality of mothers’ sleep was associated with the risk of small for gestational age birth.

BackgroundLimited research exists on how dietary pattern (DP) influences pregnant women's health-related quality of life (HRQOL). This study aimed to identify DPs in a cohort of 92,448 pregnant Japanese women using fixed data from the Japan Environment and Children's Study (JECS) to investigate the associations of DP with HRQOL.MethodsDuring the first trimester, DPs were assessed using the Food Frequency Questionnaire (FFQ), and HRQOL was assessed using the 8-Item Short-Form Health Survey (SF-8). DPs such as Western, Japanese and Unbalanced DP were identified through principal component analysis (PCA). Multivariable logistic model analysis was used to assess the associations between DP and HRQOL as good or poor.ResultsWe found a significant association between poor mental HRQOL in the univariate analysis for the Western DP (p = 0.014). However, this association was not significant in the multivariate analysis adjusted for basic confounders (p = 0.078). Western DP was not highly associated with poor physical HRQOL (from low-medium to high levels of intake; adjusted odds ratio [OR] 0.87-0.88, all p≤0.001, when comparing highest to lowest intake levels). A high intake of the Japanese DP was significantly associated with poor mental HRQOL and physical HRQOL (adjusted OR 1.20, pConclusionThis is the first known prospective study to establish an association between DP and HRQOL in pregnant women. We hope that our findings will help in the field of nutritional science.

Systemic lupus erythematosus, simply known as lupus, is associated with adverse obstetric outcomes. This study evaluated the incidence of preterm births (before 37 and 34 weeks), low birthweight infants (

BackgroundThe important role played by intestinal bacterial flora in human health has recently attracted public attention worldwide. Although yogurt is thought to help in preventing the onset of gastroenteritis, this property has rarely been examined in epidemiological studies.MethodThis study analyzed data obtained by the Japan Environment and Children's Study. From a dataset of 103,062 pregnancies, 82,485 were selected for this analysis. Dietary intake of fermented foods (yogurt and cheese) in 1-year-old infants was assessed with a food frequency questionnaire. Parent-reported physician-diagnosed gastroenteritis in early childhood was determined from a questionnaire conducted when the child was 1 year old.ResultThe incidence of gastroenteritis was significantly lower in infants who consumed yogurt ≥ 7 and 3-6 times/week than in infants who consumed yogurt < 1 time/week in crude models (n = 82,485) and after adjustment for covariates (adjusted odds ratio [95% confidence interval], 0.78 [0.70-0.86] versus 0.82 [0.76-0.89], respectively; n = 65,051). Frequency of weekly cheese consumption was not associated with the incidence of gastroenteritis.ConclusionConsumption of yogurt, but not cheese, at 1 year of age was associated with a reduced risk of gastroenteritis. Further studies of this association, including interventional studies, are warranted.

BackgroundPrenatal psychological stress may increase the risk of placental abruption (PA). This study aimed to clarify the effects of psychological distress during pregnancy and exposure to stressful life events in the year before or during pregnancy on the occurrence of PA in Japanese women.MethodsUsing a nationwide prospective birth cohort study, we obtained data from 103,099 women between January 2011 and March 2014. Information on exposure to 14 stressful life events and psychological distress (Kessler 6 scale) was collected using a self-administered questionnaire during pregnancy. Clinical diagnoses of PA were obtained from medical records. A total of 80,799 women with singleton births were analyzed using logistic regression models that adjusted for possible confounders.ResultsPA was diagnosed in 335 (0.4%) women. There was no significant difference in the Kessler 6 score during pregnancy between the PA group and non-PA group. Exposure to the death of a child in the year before or during pregnancy was significantly associated with PA in multigravid women (adjusted odds ratio [aOR] 3.57; 95% confidence interval [CI] 1.50-8.34). A spouse's loss of employment was significantly associated with PA in parous women (aOR 3.25; 95% CI 1.40-7.56).ConclusionsThis study identified the possible effects of exposure to the death of a child on PA occurrence that adjusted for important confounding factors.

BackgroundVitamin D has been reported to affect both innate, and acquired immunity with immune cells such as dendritic cells having the vitamin D receptors. The co-occurrence of the high prevalence of allergic diseases and vitamin D deficiency globally documented in recent decades, has prompted a hypothesis on whether there is a reasonable association between them.ObjectiveTo investigate the association between serum vitamin D deficiency and allergic symptoms.MethodsHistorical cohort. On a cohort study for the association between desert dust exposure and allergic symptoms in 3,327 pregnant women during spring and fall in 2011-2013 in Japan conducted as an adjunct study to the Japan Environment and Children's Study, we promptly acquired subjects' daily allergic symptom scores by sending a web-based questionnaire to each participant on some days. Of the 29,434 answers provided by 3,327 participating pregnant women, we extracted 13,356 answers from 1,475 pregnant women that were answered within a 3-month period after blood samplings. And we measured 25(OH)D levels on those samples to investigate the association between their vitamin D deficiency (serum 25(OH)D < 20ng/mL) and the occurrence of any allergic symptom (allergic symptom score> 0) within 3 months.ResultsSerum 25(OH)D was less than 20ng/mL in 1,233 of 1,745 samples (70.7%). The adjusted odds ratio (aOR) for occurrence of any allergic symptom in deficient cases compared with non-deficient cases was 1.33 (95% CI: 1.07-1.64, p = 0.01). Further, vitamin D deficiency significantly enhanced the risk increase at desert dust events and at pollen exposure (p-values for interaction ConclusionWe confirmed the association between serum vitamin D deficiency and allergic symptoms in Japanese pregnant women.

BACKGROUND:As a consequence of indoor occupations and reduced exposure to sunlight, concerns have been raised that vitamin D deficiency is widespread in developed countries. Vitamin D is known to be associated with increased risks of morbidity and mortality in various diseases. OBJECTIVE:To investigate the serum vitamin D status and its relation with life-style factors in pregnant Japanese women. METHODS:Among a cohort for 3,327 pregnant women who participated in an the adjunct study of the Japan Environment and Children's Study during 2011-2013, in which data were obtained on various life-style factors, including both dietary intake of vitamin D and frequency of UV exposure, this study consisted of 1,592 pregnant women, from whom 2,030 serum samples were drawn in Jan, Apr, Jul, and Oct, and the association between serum 25(OH)D level and life-style factors were analyzed using linear mixed models. RESULTS:Serum 25(OH)D levels were less than 20ng/mL in 1,486 of 2,030 samples (73.2%). There was an obvious seasonal change, with serum 25(OH)D levels of less than 20 ng/mL in 89.8% and 47.8% of samples in spring (April) and autumn (October), respectively. Both the frequency spent under sunlight and dietary intake of vitamin D were significantly associated with serum 25(OH)D level. An increase in sunlight exposure of more than 15 min for 1 to 2 days per week in non-winter, or dietary intake of 2 μg/day of vitamin D resulted in an elevation of 1 ng/mL in serum 25(OH)D levels. CONCLUSION:These findings indicate that vitamin D deficiency is very severe in Japanese pregnant women, especially those rarely exposed to sunlight. The benefits of UV rays should also be informed of when its risk is alerted, and clinicians should propose the adequate UV exposure level.

BackgroundBecause of the increased number of diagnosed cases of endometriosis or adenomyosis resulting in infertility, many women require assisted reproductive technology (ART) to become pregnant. However, incidences of obstetric complications are increased for women who conceive using ART. There has been no prospective cohort study examining the influence of endometriosis and adenomyosis on obstetric outcomes after adjusting for the confounding influence of ART therapy.ObjectiveThis study evaluated the impact of endometriosis and adenomyosis on the incidence of adverse pregnancy outcomes.Study designData were obtained from a prospective cohort study, known as the Japan Environment and Children's Study (JECS), of the incidence of obstetric complications for women with endometriosis and adenomyosis. The data of 103,099 pregnancies that resulted in live birth or stillbirth or that were terminated through abortion between February 2011 and July 2014 in Japan were included.ResultsWomen with endometriosis or adenomyosis were at increased risk for complications during pregnancy compared to those without a medical history of endometriosis (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.23 to 1.41) or adenomyosis (OR, 1.72; 95% CI, 1.37 to 2.16). Our analysis showed that the adjusted ORs for obstetric complications of pregnant women who conceived naturally or after infertility treatment that did not involve ART therapy were 1.26 (CI, 1.17 to 1.35) for pregnant women with a history of endometriosis and 1.52 (CI, 1.19 to 1.94) for those with a history of adenomyosis.ConclusionsThe presence of endometriosis and adenomyosis significantly increased the prevalence of obstetric complications after adjusting for the influence of ART outcomes.

BackgroundEvidence indicates that human circadian rhythm is affected by the intestinal microbiota, and establishment of the circadian rhythm begins during fetal development. However, the relationship between maternal fermented food intake and infant sleep duration has not been previously investigated. In this study, we examined whether dietary consumption of fermented food during pregnancy is associated with infant sleep duration at 1 year of age.MethodsThis birth cohort study used data from a nationwide government-funded study called The Japan Environment and Children's Study (JECS). After exclusions from a dataset comprising 104,065 JECS records, we evaluated 72,624 mother-child pairs where the child was 1 year old. We investigated the association between dietary intake of fermented foods during pregnancy and infant sleep duration of less than 11 h at 1 year of age.ResultsMultivariable logistic regression showed that maternal intake of fermented food, especially miso, during the pregnancy was independently associated with reduced risk of infant sleep duration of less than 11 h.ConclusionsFurther research, including interventional studies, is warranted to confirm the association between consumption of fermented foods during pregnancy and sufficient infant sleep duration.Trial registrationUMIN000030786.