Hernandezine promotes cancer cell apoptosis and disrupts the lysosomal acidic environment and cathepsin D maturation.

Hernandezine (Her), a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum, is recognized for its range of biological activities inherent to this herbal medicine. Despite its notable properties, the anti-cancer effects of Her have remained largely unexplored. In this study, we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis mechanisms. Furthermore, Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems, leading to LC3 lipidation. Our findings revealed that Her caused damage to the mitochondrial membrane, with the damaged mitochondria undergoing mitophagy, as evidenced by the elevated expression of mitophagy markers. Conversely, Her disrupted autophagic flux, demonstrated by the upregulation of p62 and accumulation of autolysosomes, as observed in the RFP-GFP-LC3 reporter assay. Initially, we determined that Her did not prevent the fusion of autophagosomes and lysosomes. However, it inhibited the maturation of cathepsin D and increased lysosomal pH, indicating an impairment of lysosomal function. The use of the early-stage autophagy inhibitor, 3-methyladenine (3-MA), did not suppress LC3II, suggesting that Her also induces noncanonical autophagy in autophagosome formation. The application of Bafilomycin A1, an inhibitor of noncanonical autophagy, diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her, thereby augmenting Her-induced cell death. These observations imply that while autophagy initially plays a protective role, the disruption of the autophagic process by Her promotes programmed cell death. This study provides the first evidence of Her's dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell death. These insights contribute to a deeper understanding of the mechanisms underlying programmed cell death, offering potential avenues for enhancing cancer prevention and therapeutic strategies.

Risk of gestational diabetes in women with PCOS based on body mass index: The Japan Environment and Children's Study.

CONTEXT: Women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM). OBJECTIVE: To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan. DESIGN: Prospective observational study using data from the Japan Environment and Children's Study (JECS). PARTICIPANTS: Singleton pregnancies in the JECS during 2011-2014 were included. Mothers with HbA1c levels of ≥6.5% in the first trimester and history of DM or steroid use during pregnancy were excluded. MAIN OUTCOME MEASURES: Participants were categorized according to their pre-pregnancy BMIs: G1 (<18.5 kg/m2), G2 (18.5-19.99 kg/m2), G3 (20.0-22.99 kg/m2), G4 (23.0-24.99 kg/m2), and G5 (≥25.0 kg/m2). The impact of PCOS on early (Ed) and late-onset (Ld) GDM for each group was estimated using a multiple logistic regression model. RESULTS: We included 92774 participants, comprising 2012 PCOS(+) cases. GDM occurrence was higher in women with PCOS (p<0.001). PCOS had no effect on GDM in G1, G2, and G3. In G4, PCOS increased the risk of Ed GDM (adjusted odds ratio [aOR]: 3.27, 95% confidence interval [CI]: 1.29-8.29). In G5, PCOS increased the risk of both Ed (aOR: 2.48, 95% CI: 1.53-4.02) and Ld GDM (aOR: 1.94, 95% CI: 1.23-3.07). CONCLUSIONS: The impact of PCOS on GDM occurrence depended on the pre-pregnancy BMIs, which may facilitate personalized preconception counseling among women with PCOS.

Prenatal risk factors of indoor environment and incidence of childhood eczema in the Japan Environment and Children's Study.

The quality of indoor environment is a risk factor for early childhood eczema and atopic dermatitis; however, its influence during pregnancy on childhood eczema in Japan has not been investigated. In this study, we aimed to determine the indoor environmental factors that are associated with eczema in children up to 3 years of age, using national birth cohort data from the Japan Environment and Children's Study (JECS). Information on indoor environments and eczema symptoms until 3 years of age was collected using self-administered questionnaires to the mothers. A total of 71,883 and 58,639 mother-child pairs at 1.5- and 3-years-old, respectively, were included in the former analyses. To account for prenatal indoor risk factors, 17,568 (1.5-years-old) and 7063 (3-years-old) children without indoor mold and/or ETS exposure were included in the final analysis. A higher mold index, gas heater use, parquet flooring use, and frequent insecticide use showed significantly increased risks for childhood eczema up to 3 years of age. These associations were consistent after stratification analysis among children whose parents did not have a history of allergies. The updated WHO guidelines on indoor air quality should be implemented based on recent findings regarding the effects of prenatal exposure to indoor dampness on health effects of children further in life, including asthma, respiratory effects, eczema, and other immunological effects.

Maternal fermented food intake and infant neurodevelopment: The Japan Environment and Children's Study.

BACKGROUND AND OBJECTIVES: Fermented foods play an important role in establishing intestinal bacterial flora, and the composition of the intestinal bacterial flora might be associated with neurodevelopment. This study investigated the association between maternal intake of fermented foods during pregnancy and early neuro-development in offspring. METHODS AND STUDY DESIGN: Data were analyzed for 73,522 pregnant women participating in the Japan Environment and Children's Study. Their intake of four common fermented foods during pregnancy was assessed using a semi-quantitative FFQ. Neurodevelopment in their infants at 1 year of age was estimated using the Ages and Stages Questionnaires. RESULTS: Multivariable logistic regression analysis showed that maternal intake of miso soup and fermented soybeans was each associated with a significantly reduced risk of delay in infant communication skills. Maternal intake of fermented soybeans and cheese was each associated with a significantly reduced risk of delay in fine motor skills in the third and fourth quartiles. For problem-solving, preventive associations were observed with maternal intake of fermented soybeans in the second and third quartiles and with maternal intake of cheese in the third and fourth quartiles. Maternal intake of yogurt was associated with a significantly reduced risk of delay in personal-social skills in the third and fourth quartiles, while that of cheese was associated with a reduced risk in the third quartile. No reductions in risk were observed for gross motor skills. CONCLUSIONS: Our results suggest that fermented food intake during pregnancy may have beneficial associations with several areas of psychomotor development in children.

Differences in health literacy related to gestational weight gain and children's birth weight according to maternal nativity status in the Japan Environment and Children's Study (JECS): a longitudinal cohort study.

OBJECTIVES: We examined literacy related to healthy gestational weight gain (GWG) in immigrant and native Japanese mothers and determined whether it is associated with children's birth weight. DESIGN: Longitudinal cohort study. SETTING: As the baseline survey in the Japan Environment and Children's Study (JECS), mothers completed self-administered questionnaires distributed by hand during pregnancy. The self-administered questionnaires used in this study were distributed by mail 6 months after delivery. Children's birth weight, actual GWG and any complications during delivery were recorded by obstetricians collaborating with JECS. PARTICIPANTS: Of 97 452 mothers who consented to participate in the JECS during pregnancy between January 2011 and March 2014, 67 953 were included in this study after exclusions for multiple births, multiple instances of consent by the same pregnant woman, miscarriages/stillbirths or withdrawal from the study within 3 years after participating. In total, 324 immigrant mothers and 963 native Japanese mothers were selected by propensity score matching for analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Data were collected on maternal literacy related to healthy GWG at the baseline survey, and data on actual GWG and children's birth weight were collected by obstetricians. The associations of knowledge about healthy GWG and mothers' actual GWG with maternal nativity status were examined using a χ2 or Student's t-test. RESULTS: More native Japanese mothers than immigrant mothers knew the appropriate GWG and reason the for needing to know this. Actual GWG was significantly higher among the immigrant mothers, but was within the recommended range. The low birthweight (LBW) incidence was significantly higher among the native mothers. CONCLUSIONS: Immigrant mothers to Japan had less knowledge about appropriate GWG, but their actual GWG was appropriate and they delivered fewer LBW infants than native Japanese mothers. These findings may indicate the presence of other protective factors for pregnancy or delivery among immigrant mothers.

Association of allergies in children younger than 3 years with levels of maternal intake of n-3 polyunsaturated fatty acids or fish during pregnancy: A nationwide birth cohort study, the Japan Environment and Children's Study.

BACKGROUND: N-3 polyunsaturated fatty acids (PUFAs) have anti-inflammatory properties and are expected to prevent the onset of allergies. However, epidemiological studies investigating the relationship between child allergies and maternal intake of n-3 PUFAs or fish have yielded inconsistent results. METHODS: Following exclusions from a dataset comprising 103,057 records from the Japan Environment and Children's Study, 72,105 participants were divided into five groups according to mothers' intake of n-3 PUFAs or fish during pregnancy to assess the risk of their children being diagnosed with allergy by 3 years old. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for child allergies were calculated using multivariable logistic regression analyses with reference to the lowest intake group. RESULTS: Levels of maternal intake of n-3 PUFAs or fish showed inverted associations (i.e., reduced risk) with the incidence of physician-diagnosed allergic rhinoconjunctivitis or parent-reported symptoms of current rhinitis with eye symptoms at different time points and the cumulative incidence from birth to 3 years of age. Inverted associations were also found for current wheeze at 1-<2 years of age and current eczema at 1-<2 and 0-<3 years of age. However, for food allergies, no significant associations were observed in the incidence in each group compared with the lowest intake group at any age. CONCLUSIONS: The findings suggest that n-3 PUFA intake during pregnancy may reduce the risk of developing allergic diseases and symptoms in children. In addition, consumption of n-3 PUFAs or fish is very unlikely to increase the risk of allergy given that the results are from a country with high fish consumption. TRIAL REGISTRATION: UMIN000030786 https://rctportal.niph.go.jp/detail/um?trial_id=UMIN000030786.

Teenage and young adult pregnancy and depression: findings from the Japan environment and children's study.

Teenage pregnancy increases the threat of depression because of its many factors. Pregnancy during young adulthood may also have several risk factors for depression compared to older pregnancies. However, data on depression in young adult pregnancies are lacking. This study investigated the association between teenage and young adult pregnancy and depression. Data from the Japan Environment and Children's study was used as a nationwide multicenter prospective cohort study. A multivariate logistic regression was performed to investigate the association between age groups (14-19, 20-24, 25-29, 30-34, ≥ 35 years) and depression, adjusted for behavioral and sociodemographic characteristics. Depression was assessed using the Kessler Psychological Distress Scale. In total, 96,808 pregnant women responded to the questionnaire. Teenage (14-19 years) and young adult (20-24 years) pregnancy were associated with an increased risk of depression compared to older pregnancy (≥ 35 years) (teenage: OR 4.28, 95% confidence interval, CI [3.24-5.64]; young adult: OR 3.00, 95% CI [2.64-3.41]). After adjusting for covariates, the magnitude of the risk of depression was attenuated. However, teenage and young adult pregnancy remained at a significantly increased risk of depression compared to older pregnancy (teenage: OR 2.38, 95% CI [1.77-3.21]; young adult: OR 2.14, 95% CI [1.87-2.46]). Our findings indicate that teenage and young adults' pregnancy are at an increased risk of depression compared to older pregnancy. These findings suggest prioritizing teenage and young pregnant women for prevention and interventions related to depression.

Maternal Dietary Vitamin D Intake during Pregnancy Is Associated with Allergic Disease Symptoms in Children at 3 Years Old: The Japan Environment and Children's Study.

INTRODUCTION: Vitamin D plays an important role in the immune system, and postnatal vitamin D insufficiency is one of the risk factors for the development of allergic disease. However, the effects of women's vitamin D intake during pregnancy on the prevalence of allergic disease in their children remain controversial. METHODS: From the Japan Environment and Children's Study, an ongoing nationwide birth cohort study, we obtained information on maternal dietary vitamin D intake determined using a food frequency questionnaire and parent-reported allergic disease symptoms based on the ISAAC questionnaire in children at 3 years of age. RESULTS: From the full dataset of 103,060 pregnancies, we analyzed complete data for 73,309 mother-child pairs. The prevalence of current wheeze, current rhinitis, current rhino-conjunctivitis, current eczema, ever asthma, ever pollinosis, and ever atopic dermatitis in the children was 17.2%, 29.7%, 3.8%, 15.2%, 9.6%, 3.7%, and 11.0%, respectively. The ORs for current rhinitis were significantly lower in the 3rd, 4th, and 5th quintiles than in the 1st quintile after adjustment for various covariates and showed a linear association. The ORs for ever pollinosis were significantly lower in the 2nd, 3rd, and 4th quintiles than in the 1st quintile, showing a U-shaped curve. There was no clear association between mothers' dietary vitamin D intake and symptoms of asthma or atopic dermatitis in their 3-year-old children. CONCLUSION: Maternal dietary vitamin D intake during pregnancy is associated with the ORs for nasal allergies in children at the age of 3 years. Further studies are warranted to evaluate the appropriate intake dose of vitamin D for pregnant women to prevent the development of nasal allergies in their children.

Impact of longer working hours on fathers' parenting behavior when their infants are 6 months old: The Japan Environment and Children's Study.

Objective: Long working hours have been suggested to affect fathers' parenting behavior, but previously reported findings have been inconsistent. This study examined the association between the working hours and parenting behavior of fathers while accounting for other factors related to their parenting behavior, using data from the Japan Environment and Children Study (JECS), a large cohort study in Japan. Methods: Data from 43,159 father-mother pairs were analyzed. The mother assessed the father's frequency of seven parenting behaviors at 6 months after delivery. Then, each behavior was classified into a high-engagement group (always and sometimes) or a low-engagement group (rarely and never). The father's weekly working hours was obtained from his responses and was classified into six levels. Results: Logistic regression analysis showed that after adjustment for covariates, fathers' weekly working hours was inversely associated with the frequency of all parenting behaviors examined in this study (p for trend <0.0001). Compared with fathers working ≥0 to ≤40 h per week, those working >65 h per week showed the following adjusted odds ratios (95% confidence intervals) for low engagement in parenting behaviors: playing at home, 2.38 (2.08-2.72); changing diapers, 2.04 (1.89-2.20); and bathing the child, 2.01 (1.84-2.18). Conclusion: This study suggests that the greater time constraints imposed by longer working hours constitute a major factor that discourages fathers from engaging in childrearing behavior. Intervention targeting long working hours could contribute to measures aimed at promoting high-engagement parenting behaviors among fathers.

Association between Cesarean section and neurodevelopmental disorders in a Japanese birth cohort: the Japan Environment and Children's Study.

BACKGROUND: The long-term effects of a Cesarean section (CS) birth on child neurodevelopment are of increasing interest. In this study, we examined the associations between mode of delivery and presence of neurodevelopmental disorders in toddlers. Moreover, given that the prevalence of several neurodevelopmental disorders such as autism spectrum disorder (ASD) is known to differ by sex, we also investigated these associations separately in male and female toddlers. METHODS: We investigated 65,701 mother-toddler pairs from the Japan Environment and Children's Study, a nationally representative children's cohort study. To investigate the associations between mode of delivery (CS or vaginal delivery) and neurodevelopmental disorders (motor delay, intellectual disability, and ASD) in 3-year-old toddlers as a whole and stratified by sex, we used logistic regression models to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). RESULTS: The morbidity of ASD at age 3 years was higher for children delivered by CS than those delivered vaginally (aOR 1.38, 95% CI 1.04-1.83). However, no such difference was evident in the case of motor delay or intellectual disability (aOR 1.33, 95% CI 0.94-1.89; aOR 1.18, 95% CI 0.94-1.49, respectively). In the analysis by sex, CS was not associated with increased risk of any of the neurodevelopmental disorders in males, but it was associated with increased risks of motor delay (aOR 1.88, 95% CI 1.02-3.47) and ASD (aOR 1.82, 95% CI 1.04-3.16) in females. CONCLUSIONS: This study provides evidence of significant associations between mode of delivery and neurodevelopmental disorders in early childhood. Females may be more sensitive to the effects of CS than males.

Relationship between prenatal checkup status and low birth weight: a nationwide birth cohort-the Japan Environment and Children's Study.

PURPOSE: We investigated the association between prenatal checkup status and low birth weight (LBW). We also sought to identify the background factors of pregnant women that influence their attendance at prenatal checkups and consider measures that might prove useful in reducing the LBW rate. METHODS: Using data from a large nationwide birth cohort study, the Japan Environment and Children's Study (JECS), the sample comprised 91,916 unique mother-infant pairs with singleton live births. The outcome variable was cases of LBW, and the exposure variable was prenatal checkup status (number of visits missed). Adjusted odds ratios (AORs) with 95% confidence intervals (CIs) were calculated by logistic regression analysis. RESULTS: AORs (95% CIs) for cases of LBW were 1.57 (1.46-1.69) for 1 missed checkup, 2.40 (1.97-2.94) for 2 missed checkups, and 2.38 (1.46-3.88) for ≥3 missed checkups. A linear trend was also observed (P < .0001). Further analysis revealed that the main risk factors for missed checkups were divorced or widowed marital status, followed by negative attitude toward pregnancy, and single marital status, whereas protective factors were being employed and better mental health in mid-late pregnancy. CONCLUSIONS: Our results suggest the importance of implementing various measures to promote regular attendance at prenatal checkups.

Longitudinal study of the relationship between number of prior miscarriages or stillbirths and changes in quality of life of pregnant women: the Japan Environment and Children's Study (JECS).

BACKGROUND: Although a history of miscarriage or stillbirth has been reported to negatively affect quality of life (QOL) during the subsequent pregnancy, the association between the number of previous miscarriages or stillbirths and QOL, as well as trends in QOL during pregnancy, has not been clarified. This study sought to determine this association during early and mid- to late pregnancy. METHODS: Data from 82,013 pregnant women who participated in the Japan Environment and Children's Study (JECS) from January 2011 to March 2014 were analyzed. In early and mid/late pregnancy, participants completed questionnaires and QOL was assessed using the Physical and Mental Component Summary (PCS and MCS, respectively) scores from the 8-item Short-Form Health Survey (SF-8). The pregnant women were divided into four groups according to number of previous miscarriages or stillbirths (0, 1, 2, and ≥ 3), and the PCS and MCS scores in early pregnancy and mid/late pregnancy were compared between group 0 and groups 1, 2, and ≥ 3. Generalized linear mixed models were used for analysis. RESULTS: PCS score in early pregnancy was lower in group 1 (ß = - 0.29, 95% confidence interval [CI] - 0.42 to - 0.15), group 2 (ß = - 0.45, 95% CI - 0.73 to - 0.18), and group ≥ 3 (ß = - 0.87, 95% CI - 1.39 to - 0.35) than in group 0. Group 1 and group ≥ 3 showed a trend for increased PCS score during pregnancy (ß = 0.22, 95% CI 0.07 to 0.37 and ß = 0.75, 95% CI 0.18 to 1.33, respectively) compared with group 0. CONCLUSIONS: PCS score in early pregnancy was lower with a more frequent history of miscarriage or stillbirth. However, in terms of changes in QOL during pregnancy, pregnant women with a history of miscarriage or stillbirth showed greater increases in PCS score during mid/late pregnancy than pregnant women with no history of miscarriage or stillbirth.

Caesarean section and childhood obesity at age 3 years derived from the Japan Environment and Children's Study.

Caesarean section (CS) birth is widely reported to be a risk factor for childhood obesity. Although susceptibility to childhood obesity is influenced by race and ethnicity, it is unclear whether this risk of childhood obesity with CS birth also applies in the Japanese population. We investigated the impact of CS birth on obesity at 3 years of age in Japanese children. We obtained data from 60,769 mother-toddler pairs in the Japan Environment and Children's Study, a large-scale birth cohort study. Obesity was determined by body mass index measured at 3 years of age. Analysis revealed that 11,241 toddlers (18.5%) had a CS birth and that 4912 toddlers (8.1%) were obese. The adjusted risk ratio for obesity at 3 years of age when born by CS compared with vaginal delivery, estimated using inverse probability of treatment weighting, was 1.16 (95% confidence interval 1.08-1.25). These results suggest that CS birth modestly increases the risk of obesity at 3 years of age in Japanese children.

Association of soap use when bathing 18-month-old infants with the prevalence of allergic diseases at age 3 years: The Japan Environment and Children's Study.

BACKGROUND: Atopic march is defined as the progression from atopic dermatitis (AD) during early life to other allergic diseases in later childhood. In a nationwide birth cohort study, the Japan Environment and Children's Study, we investigated the association of bathing habits, which are known to affect skin conditions, for infants with their later development of allergic diseases. METHODS: Pregnant women who lived in 15 designated regional centers throughout Japan were recruited. We obtained information on bathing habits for their 18-month-old infants and the prevalence of allergic diseases when they were aged 3 years. RESULTS: Data for 74,349 children were analyzed. Most 18-month-old infants were bathed or showered almost every day. When they were divided into four groups according to the frequency of soap use during bathing (every time, most of the time, sometimes, and seldom), the risk of AD later at age 3 was shown to increase in association with a decreasing frequency of soap use [most of the time: adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI) 1.05-1.34; sometimes: aOR 1.72, 95% CI 1.46-2.03; seldom: aOR 1.99, 95% CI 1.58-2.50], compared with soap use every time during bathing at 18 months of age. Similar results were obtained for food allergy but not for bronchial asthma. CONCLUSIONS: Frequent soap use when bathing 18-month-old infants was associated with a decreased risk of them developing allergic diseases at age 3. Further well-designed clinical studies are warranted to determine an effective bathing regimen for preventing the development of allergic diseases.

Dietary Intake of Vitamin D during Pregnancy and the Risk of Postpartum Depressive Symptoms: The Japan Environment and Children's Study.

Many recent clinical and epidemiological studies have demonstrated the effects of vitamin D on health, yet few studies have examined the association of dietary intake of vitamin D during pregnancy with postpartum depressive symptoms. This study examined this association in a large cohort of 74,840 pregnant women who are enrolled in the longitudinal Japan Environment and Children's Study. Dietary vitamin D intake during pregnancy (specifically after learning of the pregnancy to mid-late pregnancy) was determined using the Food Frequency Questionnaire. Postpartum depressive symptoms 1 mo after delivery were assessed using the Edinburgh Postnatal Depression Scale. Logistic regression analysis showed a reduced risk of postpartum depressive symptoms for all except the first quintile of vitamin D intake: second quintile (adjusted odds ratio [95% confidence interval]: 0.88 [0.82-0.94]), third (0.83 [0.78-0.89]), fourth (0.87 [0.81-0.93]), and fifth (0.90 [0.83-0.97]). Post-adjustment trend tests revealed a significant association between dietary vitamin D intake and postpartum depressive symptoms (p for trend=0.004). Our results revealed a higher vitamin D intake during pregnancy was associated with a lower risk of postpartum depressive symptoms 1 mo after delivery, suggesting the potential applicability of vitamin D in reducing postpartum depression.

Association of infants' feeding pattern up to 2 years postpartum with mothers' mental and physical health: the Japan Environment and Children's Study.

BACKGROUND: Exclusive breastfeeding, a longer breastfeeding duration, and interaction with the baby during lactation improve mothers' mental health. However, few studies have targeted women around 2.5 years after childbirth, when women are still considered to have been in a period of mental and physical health vulnerability. This study examined this aspect in a large cohort of mother-child pairs. METHODS: Data were obtained from 85,735 mothers in an ongoing nationwide birth cohort study in Japan. Exposures were exclusive breastfeeding (yes/no), continued breastfeeding up to 2 years (yes/no), and interaction with the baby during feeding (yes/no). Outcomes were mothers' mental and physical health 2.5 years after childbirth measured using Mental and Physical Component Summary scores (MCS and PCS scores, respectively) from the 8-item Short-Form Health Survey. Generalized additive mixed model analysis was used to derive each estimate for the three exposures and their interactions, with each "no" answer as reference. RESULTS: Exclusive breastfeeding and interaction with the baby during feeding were associated with MCS score increases of 0.28 (95%CI: 0.10-0.47) and 0.41 (95%CI: 0.29-0.54), respectively. However, no associations were found for continued breastfeeding up to 2 years and no interactions were identified. No significant differences were observed for PCS scores. LIMITATIONS: All variables were measured using a self-administered questionnaire. CONCLUSIONS: Continued exclusive breastfeeding until 6 months and interaction with the baby during feeding may help to promote mother's mental health 2.5 years after childbirth. These findings further strengthen the rationale for the World Health Organization's recommended lactation practices.

Season of birth and atopic dermatitis in early infancy: results from the Japan Environment and Children's Study.

BACKGROUND: Atopic dermatitis (AD) is reported to be more prevalent in children who were born in autumn than in spring. Here, we investigated how early the association between season of birth and eczema or AD can be observed in the postnatal period. We also examined whether specific prevalence outcomes for infant eczema and AD differed according to sex and maternal history of allergic disease in a large Japanese cohort. METHODS: Using data of 81,615 infants from the Japan Environment and Children's Study, we examined the associations of birth month or season with four different outcomes-eczema at 1 month, 6 months, and 1 year of age and physician-diagnosed AD up to 1 year of age-using multiple logistic regression analysis. We also analyzed the effect of maternal history of allergic disease on these outcomes stratified by infant sex. RESULTS: The risk of eczema at 1 month was highest in infants born in July. In contrast, infants born in autumn had higher risks of eczema at 6 months (adjusted odds ratio [aOR], 2.19; 95% confidence interval [CI], 2.10-2.30) and at 1 year (aOR, 1.08; 95% CI, 1.02-1.14) and of physician-diagnosed AD up to 1 year of age (aOR, 1.33; 95% CI, 1.20-1.47) compared with infants born in spring. Eczema and AD were more prevalent in infants with a maternal history of allergic disease, particularly boys. CONCLUSIONS: Our findings suggest that the prevalence of AD is associated with the season of observation. Eczema is prevalent in infants born in autumn, and this phenomenon was observed in infants as young as 6 months old. The risk associated with being born in autumn was particularly clear in boys with a maternal history of allergic disease. TRIAL REGISTRATION: UMIN000030786.

Cesarean section and parenting stress: Results from the Japan Environment and Children's Study.

BACKGROUND: Accumulating evidence suggests a long-term health risk of cesarean section for the mother and child, but few studies have examined the link between cesarean section and parenting stress. Here, we examined this association by exploiting a large dataset. METHODS: Participants were 65,235 mothers participating in the Japan Environment and Children's Study, an ongoing nationwide birth cohort. Outcome variables were parenting stress assessed as total score and subscale scores (representing the difficult child, parental distress, and spouse factors) on the Japanese 19-item version of the Parenting Stress Index Short Form (J-PSI-SF). Exposures were the mode of delivery, the timing of the J-PSI-SF assessment (1.5, 2.5, and 3.5 years postpartum), and the interaction between them. Multivariate regression analysis was used to calculate adjusted ß coefficients and standard error of the means (SEMs). RESULTS: The J-PSI-SF total score was higher in the cesarean section group than in the vaginal delivery group (adjusted ß = 0.24, SEM = 0.09). This increase was primarily due to higher scores for the difficult child factor (adjusted ß = 0.18, SEM = 0.05) and not to higher scores for the parental distress or spouse factor. CONCLUSIONS: Cesarean section was associated with higher parenting stress, especially in relation to the difficult child factor. Our results highlight the importance of paying particular attention to the mental health of both mother and child in the case of cesarean section.

Omega-3 fatty acid intake during pregnancy and risk of infant maltreatment: a nationwide birth cohort - the Japan Environment and Children's Study.

BACKGROUND: Intake of omega-3 polyunsaturated fatty acids (PUFAs) has favorable effects, including reducing violent and aggressive behaviors, but its association with infant maltreatment is unknown. We therefore tested the hypothesis that maternal intake of omega-3 PUFAs is associated with a lower risk of infant maltreatment. METHODS: Participants were 92 191 mothers involved in the ongoing Japan Environment and Children's Study. Omega-3 PUFA intake during pregnancy was measured using a food frequency questionnaire. Infant maltreatment was assessed using a self-reported questionnaire administered at 1 and 6 months postpartum. RESULTS: Analysis using the lowest quintile of intake as a reference revealed that the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for cases of 'hitting' decreased as quintiles increased, with values for the second to fifth quintiles of 0.93 (95% CI 0.77-1.13), 0.79 (95% CI 0.64-0.97), 0.78 (95% CI 0.64-0.96), and 0.72 (95% CI 0.59-0.89), respectively. Adjusted ORs (95% CIs) for 'shaking very hard' at 6 months were 0.87 (0.73-1.04), 0.81 (0.67-0.97), 0.73 (0.61-0.89), and 0.78 (0.65-0.94), respectively. Adjusted ORs for 'leaving alone at home' for the second to fifth quintiles were 0.92 (0.87-0.98), 0.91 (0.86-0.97), 0.94 (0.88-0.99), and 0.85 (0.80-0.90), respectively. CONCLUSIONS: Higher maternal intake of omega-3 PUFAs during pregnancy was associated with fewer cases of hitting and violent shaking and leaving the child alone at home, implying a lower risk of infant maltreatment. Our results indicate the potential applicability of omega-3 PUFAs in reducing infant maltreatment.

Effect Estimate of Time-varying Social Support and Trust on the Physical and Mental Health of Mothers at 2.5 Years Postpartum: The Japan Environment and Children's Study (JECS).

BACKGROUND: Many epidemiological studies have reported the association between various social factors and health status in mothers during and after pregnancy. However, little is known about their joint and longitudinal impact. We examined the association of lack of social support and trust during pregnancy and at 2.5 years postpartum with health status in mothers. METHODS: To adequately address time-varying exposure, marginal structural models were fitted to a pseudopopulation constructed using inverse probability weighting. The model included records of 90,071 mothers participating in the Japan Environment and Children's Study. Social support and trust were measured using a 9-item questionnaire (Q1-9). Mental and physical health were measured using Mental and Physical Component Summary scores from the 8-item Short-Form Health Survey. RESULTS: For the Mental Component Summary, the magnitude of the effect estimate was largest when participants lacked close friends/neighbors (Q4) at only 2.5 years postpartum (effect estimate, -6.23), followed by a lack in emotional support (Q2) at the same time point (effect estimate, -4.94). For the Physical Component Summary, effect estimates were negligible. The magnitude of the effect estimates of lack of social support and trust tended to be larger when there was a lack at only 2.5 years postpartum than at both time points. CONCLUSION: These findings suggest that, after childbirth, a loss in social support, particularly in an emotional aspect, carries high risk, especially for mental health. Our results highlight the importance of supporting mothers for more than a few years after pregnancy.