Measurement of Bisphenol A Diglycidyl Ether (BADGE), BADGE derivatives, and Bisphenol F Diglycidyl Ether (BFDGE) in Japanese infants with NICU hospitalization history.

BACKGROUND: Bisphenol A diglycidyl ether (BADGE) and Bisphenol F diglycidyl ether (BFDGE) are used in medical devices, such as intravenous sets, syringes, and catheters. Several studies have reported that these compounds are endocrine disruptors, cytotoxic, and genotoxic, raising concerns about their adverse effects on infants, in a stage of remarkable growth and development. The present study aimed to measure the serum concentrations of BADGE, derivatives of BADGE, and BFDGE in infants and examine the factors that influence them. METHODS: Ten infants admitted to the neonatal intensive care unit (NICU) were enrolled in the present study. Blood samples from each infant and questionnaires from their mothers were collected twice, at 1-2 months and 7 months of age. BADGE, BADGE·H2O, BADGE·2H2O, and BFDGE were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Serum BADGE·2H2O was identified in all infants, at both 1-2 months (2.30-157.58 ng/ml) and 7 months of age (0.86-122.85 ng/ml). One of the two infants who received invasive ventilation showed a substantially increased BADGE·2H2O concentration. There was no significant difference in BADGE·2H2O concentrations at 7 months of age between the group that ate commercial baby food at least ≥ 1 time per week and the group that did not. CONCLUSIONS: BADGE·2H2O was detected in the serum of all infants with a history of NICU hospitalization. Future studies are needed to determine the source of BADGE exposure and investigate its effects on infant development.

Sleep quality and temperament in association with autism spectrum disorder among infants in Japan.

BACKGROUND: Sleep problems and irritable temperaments are common among infants with autism spectrum disorder (ASD). The prospective association between such sleep problems and irritable temperaments and ASDs needs to be determined for elucidating the mechanism and exploring the future intervention study. Thus, in this study, we investigated whether sleep quality and temperament in 1-month-old infants are associated with the onset of ASD in 3-year-old children. We also assessed its sex-stratified associations. METHODS: We conducted a longitudinal study using data from 69,751 mothers and infants from a large-cohort study, the Japan Environment and Children's Study. We examined the prospective association between infant sleep quality and temperament at 1 month of age and ASD diagnosis by 3 years of age. RESULTS: Here we show infants with longer daytime sleep have a higher risk of later ASD than those with shorter daytime sleep (risk ratio [RR]: 1.33, 95% confidence interval [CI]: 1.01-1.75). Infants who experienced intense crying have a higher risk of ASD than those who did not (RR: 1.31, 95% CI: 1.00-1.72). There is a difference in sex in the association between a bad mood and later ASD. In particular, female infants experiencing bad moods have a higher risk of ASD than others (RR: 3.59, 95% CI: 1.91-6.75). CONCLUSIONS: The study findings provide important information for future intervention to reduce the risk of future ASD.

Sleep problems and irritable temperaments are common among infants with autism. This study looked at the sleep and temperament of nearly 70,000 1-month-old infants in Japan and whether they were subsequently diagnosed with autism spectrum disorder during the first three years of life. Children who had slept for longer during the day and were more prone to frequent, prolonged, or intense crying were more likely to have been diagnosed with Autism Spectrum Disorder by age 3. The findings of this study might be useful for those monitoring the development of autism spectrum disorder or developing support for those with autism spectrum disorders.

Association between maternal socioeconomic status and breastfeeding: Results from the Japan environment and children's study.

Although breastfeeding has various benefits for mothers and children, there are several barriers to continuing breastfeeding practices. However, little is known about the relationship between breastfeeding in Japan and maternal socioeconomic circumstances. Based on data from the Japan Environment and Children's Study (n = 75,742), we evaluated maternal socioeconomic factors associated with breastfeeding 1 year after giving birth. Socioeconomic status (education, employment status, and household income), working hours, and breastfeeding were assessed using a self-administered questionnaire. After descriptive analysis, a logistic regression analysis was conducted with adjustments for age, educational level, employment status, and household income. Mothers with higher education and full-time homemakers were more likely to breastfeed one-year-old children. Mothers working long hours (both part-time and full-time) were less likely to breastfeed their one-year-old children. To improve breastfeeding among working mothers, it may be helpful to promote awareness of breastfeeding for every mother as well as to make the workplace environment conducive for working mothers to breastfeed.

ALDH2 deficiency increases susceptibility to binge alcohol-induced gut leakiness, endotoxemia, and acute liver injury in mice through the gut-liver axis.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is the major enzyme responsible for metabolizing toxic acetaldehyde to acetate and acts as a protective or defensive protein against various disease states associated with alcohol use disorder (AUD), including alcohol-related liver disease (ARLD). We hypothesized that Aldh2-knockout (KO) mice are more susceptible to binge alcohol-mediated liver injury than wild-type (WT) mice through increased oxidative stress, gut leakiness and endotoxemia. Therefore, this study aimed to investigate the protective role of ALDH2 in binge alcohol-induced gut permeability, endotoxemia, and acute inflammatory liver injury by exposing Aldh2-KO or WT mice to a single oral dose of binge alcohol 3.5, 4.0, or 5.0 g/kg. Our findings showed for the first time that ALDH2 deficiency in Aldh2-KO mice increases their sensitivity to binge alcohol-induced oxidative and nitrative stress, enterocyte apoptosis, and nitration of gut tight junction (TJ) and adherent junction (AJ) proteins, leading to their degradation. These resulted in gut leakiness and endotoxemia in Aldh2-KO mice after exposure to a single dose of ethanol even at 3.5 g/kg, while no changes were observed in the corresponding WT mice. The elevated serum endotoxin (lipopolysaccharide, LPS) and bacterial translocation contributed to systemic inflammation, hepatocyte apoptosis, and subsequently acute liver injury through the gut-liver axis. Treatment with Daidzin, an ALDH2 inhibitor, exacerbated ethanol-induced cell permeability and reduced TJ/AJ proteins in T84 human colon cells. These changes were reversed by Alda-1, an ALDH2 activator. Furthermore, CRISPR/Cas9-mediated knockout of ALDH2 in T84 cells increased alcohol-mediated cell damage and paracellular permeability. All these findings demonstrate the critical role of ALDH2 in alcohol-induced epithelial barrier dysfunction and suggest that ALDH2 deficiency or gene mutation in humans is a risk factor for alcohol-mediated gut and liver injury, and that ALDH2 could be an important therapeutic target against alcohol-associated tissue or organ damage.

Gestational Weight Gain Growth Charts Adapted to Japanese Pregnancies Using a Bayesian Approach in a Longitudinal Study: The Japan Environment and Children's Study.

BACKGROUND: Tracking gestational weight gain (GWG) during pregnancy makes it possible to optimize pregnancy outcomes, and GWG growth curves are well suitable for this purpose. The GWG guidelines for Japanese were revised in 2021. However, currently, there are no GWG growth curves to guide women on how to gain weight to meet these guidelines. METHODS: Using data on 96,631 live births from the Japan Environment and Children's Study (JECS), we created descriptive GWG percentile curves estimating the trajectory of GWG required to meet the GWG guidelines stratified by pre-pregnancy body mass index (BMI). For both analyses, Bayesian mixed models with restricted cubic splines adjusted for maternal characteristics were used. RESULTS: GWG curves substantially differed by pre-pregnancy BMI and were higher among multiparas and those with lower maternal age and with no previous disease. We estimated that underweight, normal weight, overweight, and obese women who gain 8.4 to 11.1 kg, 6.4 to 9.1 kg, 3.8 to 6.5 kg, and <1.9 kg at 30 weeks of gestation are on the trajectory to reach the new guidelines at 40 weeks of gestation. CONCLUSION: We provide GWG percentiles curves for Japanese women, as well as GWG trajectory curves to meet the new GWG recommendations. These results may help pregnant women monitor weight during pregnancy.

Association of sleep quality with temperament among one-month-old infants in The Japan Environment and Children's Study.

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.

Association of physical activity and sleep habits during pregnancy with autistic spectrum disorder in 3-year-old infants.

Background: We hypothesized that maternal lifestyle factors, such as physical activity and sleep habits, may be associated with autism spectrum disorder (ASD) in infants. This study aimed to investigate the association between maternal physical activity and sleep before and during pregnancy with infant ASD diagnosed by the age of 3 years. Methods: We used the data from the Japan Environment and Children's Study between 2011 and 2014. The study included 103,060 pregnant women, among which, 69,969 women were analyzed. Participants were asked about their physical activity and sleep before and during pregnancy using questionnaires during pregnancy. Maternal physical activity was estimated using the international physical activity questionnaire. Based on the levels of physical activity before or during pregnancy, the participants were divided into five groups. Maternal sleep was analyzed based on sleep duration and bedtime. The outcome was diagnosis of ASD in 3-year-old infants. Results: In mothers with higher physical activity levels during pregnancy, the risk ratios (RR) for ASD in their 3-year-old infants were lower (RR = 0.61, 95% confidence interval (CI) = 0.42-0.90). In contrast, too short (<6 h) and too long (>10 h) sleep durations during pregnancy were associated with higher risk ratios for ASD than 7-8 h sleep duration (too short: RR = 1.87, 95% CI = 1.21-2.90; too long: RR = 1.56, 95% CI = 1.00-2.48). These associations were not observed before pregnancy. Conclusion: Maternal physical activity and sleep duration during pregnancy may be associated with ASD in infants.

Association of maternal hemoglobin levels during pregnancy with sleep and developmental problems in 1-year-old infants: A cohort study.

Background and Aims: Maternal hemoglobin concentration during pregnancy is reported to be associated with various perinatal outcomes and may also be associated with infant development. This study aims to investigate the association between maternal hemoglobin levels during early or mid-pregnancy and sleep and developmental problems in 1-year-old infants. Methods: We used the data of 66,935 pregnant women who were participants of the Japan Environment and Children's Study, a nationwide cohort study in Japan, between 2011 and 2014. Maternal hemoglobin level was examined at recruitment (mean gestational age, 15.3 weeks; SD, 2.85 weeks; range, 6-22 weeks). Information on infant sleep and development at the age of 1 year was acquired using a questionnaire. Infant development was evaluated using the Ages and Stages Questionnaire (ASQ). Results: The mean (SD) maternal hemoglobin level was 12.0 (1.0) g/dl. Maternal hemoglobin levels were not associated with the majority of infant sleep and developmental outcomes. In the group with maternal hemoglobin <10.0 g/dl, the risk ratio (RR) for sleep at 22:00 or later was higher than that in the reference group with 11.0 g/dl ≤ hemoglobin < 14.0 g/dl (RR 1.12, 95% confidence interval = 1.00-1.25). In the analysis with maternal hemoglobin level as a continuous variable, both high and low hemoglobin levels were associated with a higher RR of a late bedtime. In addition, a low maternal hemoglobin level was associated with a higher RR for abnormal fine motor skills in the ASQ. Conclusion: Our results suggest that a low level of maternal hemoglobin during pregnancy is associated with late bedtime and abnormal fine motor skills in 1-year-old infants. Conversely, a high level of maternal hemoglobin may also be associated with the infant's late bedtime.

Lack of catch-up in weight gain may intermediate between pregnancies with hyperemesis gravidarum and reduced fetal growth: the Japan Environment and Children's Study.

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.

Study Design and Participants' Profile in the Sub-Cohort Study in the Japan Environment and Children's Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study investigating environmental effects on children's health and development. A Sub-Cohort Study has begun, conducting extended exposure and outcome measurements by targeting a subgroup randomly selected from the JECS Main Study. We report the Sub-Cohort Study methodology and participants' baseline profiles. METHODS: Of 100,148 children in the JECS Main Study, children born after April 1, 2013 who met eligibility criteria ([1] all questionnaire and medical record data from children and their mothers collected from the first trimester to 6 months of age, [2] biospecimens [except umbilical cord blood] from children and their mothers collected at first to second/third trimester and delivery) were randomly selected for each Regional Centre at regular intervals. Face-to-face assessment of neuropsychiatric development, body measurement, paediatrician's examination, blood/urine collection for clinical testing and chemical analysis, and home visits (ambient and indoor air measurement and dust collection) are conducted. Participants are followed up at 1.5 and 3 years old for home visits, and 2, 4, 6, and 8 years old for developmental/medical examination. The details of protocols after age 10 are under discussion. RESULTS: Of 10,302 selected children, 5,017 participated. The profiles of the participating mothers, fathers and children did not substantially differ between the Main Study and Sub-Cohort Study. CONCLUSION: The JECS Sub-Cohort Study offers a platform for investigating associations between environmental exposure and outcomes.

Association of maternal sleep before and during pregnancy with sleep and developmental problems in 1-year-old infants.

This study investigated the association of maternal sleep before and during pregnancy with sleeping and developmental problems in 1-year-old infants. We used data from the Japan Environment and Children's Study, which registered 103,062 pregnancies between 2011 and 2014. Participants were asked about their sleep habits prior to and during pregnancy. Follow-up assessments were conducted to evaluate the sleep habits and developmental progress of their children at the age of 1 year. Development during infancy was evaluated using the Ages and Stages Questionnaire (ASQ). Maternal short sleep and late bedtime before and during pregnancy increased occurrence of offspring's sleeping disturbances. For example, infants whose mothers slept for less than 6 h prior to pregnancy tended to be awake for more than 1 h (risk ratio [RR] = 1.49, 95% confidence interval [CI] 1.34-1.66), sleep less than 8 h during the night (RR = 1.60, 95% CI 1.44-1.79), and fall asleep at 22:00 or later (RR = 1.33, 95% CI 1.26-1.40). Only subjective assessments of maternal sleep quality during pregnancy, such as very deep sleep and feeling very good when waking up, were inversely associated with abnormal ASQ scores in 1-year-old infants.

Influence of physical activity before and during pregnancy on infant's sleep and neurodevelopment at 1-year-old.

The aim of this study was to investigate the association between maternal physical activity (PA) before and during pregnancy and sleep and developmental problems in 1-year-old infants. We used data from a nationwide cohort study in Japan that registered 103,062 pregnancies between 2011 and 2014. Participants were asked about their PA before and during pregnancy, and the sleep and development of their children at the age of 1 year. Maternal PA was estimated using the International Physical Activity Questionnaire and was expressed in METs per week. We defined scores below the cut-off points of the Ages and Stages Questionnaire (ASQ) as abnormal for infant development. Based on the levels of PA before or during pregnancy, the participants were divided into five groups. In mothers with higher PA levels, the risk ratio for bedtime after 22:00 or abnormal ASQ scores in their 1-years-old infants were lower. These associations were observed for PA before and during pregnancy. Higher levels of maternal PA, both before and during pregnancy, may reduce sleep and developmental problems in infants.

Non-reassuring foetal status and sleep problems in 1-year-old infants in the Japan Environment and Children's Study: a cohort study.

Abnormal autonomic function may cause false-positive non-reassuring foetal status (fpNRFS) and may also cause sleeping problems after birth. However, an association between fpNRFS and sleeping problems in infants has not been reported. We previously showed an association of NRFS with temperament, including bad mood and frequent crying for long durations in 1-month-old infants. In the present study, we aimed to assess this association in 1-year-old infants. A total of 62,612 single pregnant women were included in the analysis. fpNRFS was identified from medical records. Sleep problems, such as short sleep duration or crying at night, were investigated in 1-year-old infants using a questionnaire for mothers. We used a log-binominal regression model to explore the association of fpNRFS with each sleep problem and to estimate risk ratios (RRs). The number of fpNRFS cases was 2,071, with a frequency of 3.3%. We observed an association of fpNRFS with shorter sleep duration of less than 8 h a night (RR 1.30, 95% confidence intervals [CI] 1.10-1.54), crying at night (RR 1.19, 95% CI 1.03-1.39), and bedtime after 22:00 (RR 1.09, 95% CI 1.00-1.18). fpNRFS may be associated with sleep problems in 1-year-old infants.

Association of maternal sleep before and during pregnancy with preterm birth and early infant sleep and temperament.

This study aimed to investigate the association of maternal sleep before and during pregnancy with preterm birth, infant sleep and temperament at 1 month of age. We used the data of the Japan Environment and Children's Study, a cohort study in Japan, which registered 103,099 pregnancies between 2011 and 2014. Participants were asked about their sleep before and during pregnancy, and the sleep and temperament of their newborns at 1 month of age. Preterm birth data were collected from medical records. Maternal sleep was not associated with preterm birth, but subjective sleep quality during pregnancy was associated with late preterm birth (birth at 34-36 weeks of gestation). For example, participants with extremely light subjective depth of sleep were more likely to experience preterm birth (RR = 1.19; 95% confidence interval [CI] = 1.04-1.35). Maternal sleep both before and during pregnancy seemed to be associated with infant sleep and temperament at 1 month of age. Infants, whose mothers slept for less than 6 hours before pregnancy, tended to cry intensely (RR = 1.15; 95% CI = 1.09-1.20). Maternal sleep problems before and during pregnancy were associated with preterm birth and child sleep problems and temperament.

The failure of two major formaldehyde catabolism enzymes (ADH5 and ALDH2) leads to partial synthetic lethality in C57BL/6 mice.

BACKGROUND: Exogenous formaldehyde is classified by the IARC as a Category 1 known human carcinogen. Meanwhile, a significant amount of endogenous formaldehyde is produced in the human body; as such, formaldehyde-derived DNA and protein adducts have been detected in animals and humans in the absence of major exogenous formaldehyde exposure. However, the toxicological effects of endogenous formaldehyde on individuals with normal DNA damage repair functions are not well understood. In this study, we attempted to generate C57BL/6 mice deficient in both Adh5 and Aldh2, which encode two major enzymes that metabolize endogenous formaldehyde, in order to understand the effects of endogenous formaldehyde on mice with normal DNA repair function. RESULTS: Due to deficiencies in both ADH5 and ALDH2, few mice survived past post-natal day 21. In fact, the survival of pups within the first few days after birth was significantly decreased. Remarkably, two Aldh2 -/- /Adh5 -/- mice survived for 25 days after birth, and we measured their total body weight and organ weights. The body weight of Aldh2 -/- /Adh5 -/- mice decreased significantly by almost 37% compared to the Aldh2 -/- /Adh5 +/- and Aldh2 -/- /Adh5 +/+ mice of the same litter. In addition, the absolute weight of each organ was also significantly reduced. CONCLUSION: Mice deficient in both formaldehyde-metabolizing enzymes ADH5 and ALDH2 were found to develop partial synthetic lethality and mortality shortly after birth. This phenotype may be due to the accumulation of endogenous formaldehyde. No serious phenotype has been reported in people with dysfunctional, dominant-negative ALDH2*2 alleles, but it has been reported that they may be highly susceptible to osteoporosis and neurodegenerative diseases. It is important to further investigate these diseases in individuals with ALDH2*2 alleles, including an association with decreased metabolism, and thus accumulation, of formaldehyde.

Maternal intake of one-carbon metabolism-related B vitamins and anorectal malformations in the Japan Environment and Children's Study.

The occurrence of anorectal malformations (ARM) is thought to be reduced with sufficient folate intake. However, there is no apparent evidence. We focused on enzyme cofactors for one-carbon metabolism, including folate (vitamin B9), vitamin B6 and vitamin B12, and explored the association between maternal combined intake of these B vitamins and the risk of ARM. Using baseline data from a Japanese nationwide birth cohort study between 2011 and 2014, we analysed data of 89 235 women (mean age at delivery = 31·2 years) who delivered singleton live births without chromosomal anomalies. Information on dietary intake was obtained via a FFQ focused on early pregnancy and used to estimate B vitamin intake. We also collected information on the frequency of folic acid supplement use. ARM occurrence was ascertained from medical records. We identified forty-three cases of ARM diagnosed up to the first month after birth (4·8 per 10 000 live births). In terms of individual intake of the respective B vitamins, high vitamin B6 intake was non-significantly associated with reduced odds of ARM. Compared with women in the low combined B vitamin intake group, the OR of having an infant with ARM was 0·4 (95 % CI 0·2, 1·0) in the high intake group (folate ≥400 µg/d, and upper half of vitamin B6 and/or vitamin B12). In conclusion, our cohort analysis suggested an inverse association between the combined intake of one-carbon metabolism-related B vitamins in early pregnancy and ARM occurrence.

Acetaldehyde dehydrogenase 2 deficiency increases mitochondrial reactive oxygen species emission and induces mitochondrial protease Omi/HtrA2 in skeletal muscle.

Acetaldehyde dehydrogenase 2 (ALDH2) is an enzyme involved in redox homeostasis as well as the detoxification process in alcohol metabolism. Nearly 8% of the world's population have an inactivating mutation in the ALDH2 gene. However, the expression patterns and specific functions of ALDH2 in skeletal muscles are still unclear. Herein, we report that ALDH2 is expressed in skeletal muscle and is localized to the mitochondrial fraction. Oxidative muscles had a higher amount of ALDH2 protein than glycolytic muscles. We next comprehensively investigated whether ALDH2 knockout in mice induces mitochondrial adaptations in gastrocnemius muscle (for example, content, enzymatic activity, respiratory function, supercomplex formation, and functional networking). We found that ALDH2 deficiency resulted in partial mitochondrial dysfunction in gastrocnemius muscle because it increased mitochondrial reactive oxygen species (ROS) emission (2',7'-dichlorofluorescein and MitoSOX oxidation rate during respiration) and the frequency of regional mitochondrial depolarization. Moreover, we determined whether ALDH2 deficiency and the related mitochondrial dysfunction trigger mitochondrial stress and quality control responses in gastrocnemius muscle (for example, mitophagy markers, dynamics, and the unfolded protein response). We found that ALDH2 deficiency upregulated the mitochondrial serine protease Omi/HtrA2 (a marker of the activation of a branch of the mitochondrial unfolded protein response). In summary, ALDH2 deficiency leads to greater mitochondrial ROS production, but homeostasis can be maintained via an appropriate stress response.

Does overweight before pregnancy reduce the occurrence of gastroschisis?: the Japan Environment and Children's Study.

OBJECTIVE: For several observational studies that have reported the factors related to gastroschisis, the target population in these studies was mainly residents of Europe or the US, and there is little data on the Asian population. In this study, we summarised characteristics of Japanese women who delivered infants with gastroschisis, particularly focusing on the pre-pregnancy body mass index (BMI), which was found to be inversely associated with gastroschisis in past studies, because the distribution of BMI is clearly different in Asia and the West. RESULTS: We used data from a nationwide birth cohort study which recruited pregnant women between 2011 and 2014. Among 92,796 women who delivered singleton live births, the frequency of underweight (pre-pregnancy BMI < 18.5 kg/m2) was 16.2%, reference weight (18.5-24.9 kg/m2) 73.1%, and overweight (≥ 25.0 kg/m2) 10.6%. We identified only 9 infants with gastroschisis, 2 of whose women were underweight (frequency of gastroschisis = 0.01%), 5 were in the reference group (0.01%), and 2 were overweight (0.02%). Of these 9 women, none were aged < 20 years, 2 were aged 20-29 years (frequency = 0.01%), and 7 were aged 30-39 years (0.01%). No reduction in the occurrence of gastroschisis was apparent among Japanese women who were overweight before pregnancy.

Impact of sleep duration during pregnancy on the risk of gestational diabetes in the Japan environmental and Children's study (JECS).

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 < 10 h sleep (reference group), women receiving < 5 h or ≥ 10 h sleep exhibited significantly elevated random blood glucose levels. This was associated with an elevated risk for positive GDM screening (< 5 h sleep: OR 1.17 (0.96-1.44) p = 0.126; ≥10 h sleep: OR 1.13 (1.03-1.25) p = 0.006). Calculating the risk for GDM, women sleeping < 5 h or ≥ 10 h exhibited elevated risks of 1.31-fold and 1.21 respectively. However, this trend was not found to be significant. CONCLUSIONS: Sleep is a critical factor in glucose metabolism, with both abnormally long and short sleep duration increasing random blood glucose levels in pregnant women. Moreover, the risk for positive GDM screening increases significantly with elevated sleep, ≥10 h per night. These findings are promising because they support the idea that sleep duration is a modifiable risk factor, and can be focused upon to improve health and pregnancy outcome.

Aldh2 Attenuates Stem Cell Factor/Kit-Dependent Signaling and Activation in Mast Cells.

Mitochondrial aldehyde dehydrogenase (ALDH2) metabolizes endogenous and exogenous aldehydes and protects cells against oxidative injury. Inactivating genetic polymorphisms in humans are common and associate with alcohol flush reactions. However, whether mast cell Aldh2 activity impacts normal mast cell responses is unknown. Using bone marrow-derived mast cells from Aldh2 knockout mice, we found evidence for a role of mast cell Aldh2 in Kit-mediated responses. Aldh2-deficient mast cells showed enhanced Kit tyrosine kinase phosphorylation and activity after stimulation with its ligand (stem cell factor) and augmentation of downstream signaling pathways, including Stat4, MAPKs, and Akt. The activity of the phosphatase Shp-1, which attenuates Kit activity, was reduced in Aldh2-/- mast cells, along with an increase in reactive oxygen species, known to regulate Shp-1. Reduced Shp-1 activity concomitant with sustained Kit signaling resulted in greater proliferation following Kit engagement, and increased mediator and cytokine release when Aldh2-/- mast cells were co-stimulated via Kit and FcεRI. However, FcεRI-mediated signaling and responses were unaffected. Therefore, our findings reveal a functional role for mast cell intrinsic Aldh2 in the control of Kit activation and Kit-mediated responses, which may lead to a better understanding of mast cell reactivity in conditions related to ALDH2 polymorphisms.