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.

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.

Maternal Exposure to Fine Particulate Matter and Its Chemical Components Increasing the Occurrence of Gestational Diabetes Mellitus in Pregnant Japanese Women.

Introduction: PM2.5 exposure is a suspected risk factor for diabetes. It is hypothesized that maternal PM2.5 exposure contributes to the development of gestational diabetes mellitus (GDM). The association between PM2.5 exposure and GDM is controversial and limited evidence is available for the exposure to PM2.5 chemical components. We investigated the association between maternal exposure to total PM2.5 mass and its components, particularly over the first trimester (early placentation period), and GDM. Methods: Data were obtained from the Japan Perinatal Registry Network database, which includes all live births and stillbirths after 22 weeks of gestation at 39 cooperating hospitals in 23 Tokyo wards (2013-2015). At one fixed monitoring site, we performed daily filter sampling of fine particles and measured daily concentrations of carbon and ion components. The average concentrations of total PM2.5 and its components over the 3 months before pregnancy and the first (0-13 gestational weeks) and second (14-27 gestational weeks) trimesters were calculated and assigned to each woman. We estimated the odds ratios (ORs) of GDM in a multilevel logistic regression model. Results: Among 82,773 women (mean age at delivery = 33.7 years) who delivered singleton births, 3,953 (4.8%) had GDM. In the multiexposure period model, an association between total PM2.5 exposure and GDM was observed for exposure over the first trimester (OR per interquartile range (IQR = 3.63 µg/m3) increase = 1.09; 95% confidence interval (CI) = 1.02-1.16), but not for the 3 months before pregnancy or the second trimester. For PM2.5 components, only organic carbon exposure over the first trimester was positively associated with GDM (OR per IQR (0.51 µg/m3) increase = 1.10; 1.00-1.21). Conclusions: This is the first evidence that exposure to total PM2.5 and one of its components, organic carbon, over the first trimester increases GDM occurrence in Japan.

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 fetal eye movement density with sleeping and developmental problems in 1.5-year-old infants.

Eye movement density (EMD) is an evaluation index of rapid eye movements observed during sleep. This study aimed to investigate the association of fetal EMD with sleeping and developmental problems in infancy. We observed 60 normal singleton pregnancies (gestational age 28-37 weeks) using ultrasonography for 1 h. Fetal eye movements were counted, and EMD was calculated. Participants answered questionnaires regarding their child's sleep and development 1.5 years after their delivery. The outcomes of an infant's sleep were night awakening (yes or no), bedtime (before or after 22:00), and nighttime sleep duration (< 9 or ≥ 9 h). An infant's development was evaluated using the Child Behavior Checklist (CBCL) T-score. We found that decreased fetal EMD was associated with increased night awakening at the age of 1.5 years (odds ratio 0.84, 95% confidence interval 0.69-1.00 per unit decrease in EMD). However, fetal EMD was not associated with bedtime or nighttime sleep duration. In addition, fetal EMD was independently associated with the total problems T-score of the CBCL at the age of 1.5 years in the multivariate model (p = 0.047). In conclusion, fetal EMD may be associated with sleep and developmental problems 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.

Maternal exposure to fine particulate matter over the first trimester and umbilical cord insertion abnormalities.

BACKGROUND: Our hypothesis was that exposure to fine particulate matter (PM2.5) is related to abnormal cord insertion, which is categorized as a form of placental implantation abnormality. We investigated the association between exposure to total PM2.5 and its chemical components over the first trimester and abnormal cord insertion, which contributes to the occurrence of adverse birth outcomes. METHODS: From the Japan Perinatal Registry Network database, we used data on 83 708 women who delivered singleton births at 39 cooperating hospitals in 23 Tokyo wards (2013-2015). We collected PM2.5 on a filter and measured daily concentrations of carbon and ion components. Then, we calculated the average concentrations over the first trimester (0-13 weeks of gestation) for each woman. A multilevel logistic-regression model with the hospital as a random effect was used to estimate the odds ratios (ORs) of abnormal cord insertion. RESULTS: Among the 83 708 women (mean age at delivery = 33.7 years), the frequency of abnormal cord insertion was 4.5%, the median concentration [interquartile range (IQR)] of total PM2.5 was 16.1 (3.61) µg/m3 and the OR per IQR for total PM2.5 was 1.14 (95% confidence interval = 1.06-1.23). In the total PM2.5-adjusted models, total carbon, organic carbon, nitrate, ammonium and chloride were positively associated with abnormal insertion. Organic carbon was consistently, and nitrate tended to be, associated with specific types of abnormal insertion (marginal or velamentous cord insertion). CONCLUSIONS: Exposure to total PM2.5 and some of its components over the first trimester increased the likelihood of abnormal cord insertion.

Exposure to chemical components of fine particulate matter and ozone, and placenta-mediated pregnancy complications in Tokyo: a register-based study.

BACKGROUND: Maternal exposure to fine particulate matter (PM2.5) was associated with pregnancy complications. However, we still lack comprehensive evidence regarding which specific chemical components of PM2.5 are more harmful for maternal and foetal health. OBJECTIVE: We focused on exposure over the first trimester (0-13 weeks of gestation), which includes the early placentation period, and investigated whether PM2.5 and its components were associated with placenta-mediated pregnancy complications (combined outcome of small for gestational age, preeclampsia, placental abruption, and stillbirth). METHODS: From 2013 to 2015, we obtained information, from the Japan Perinatal Registry Network database, on 83,454 women who delivered singleton infants within 23 Tokyo wards (≈627 km2). Using daily filter sampling of PM2.5 at one monitoring location, we analysed carbon and ion components, and assigned the first trimester average of the respective pollutant concentrations to each woman. RESULTS: The ORs of placenta-mediated pregnancy complications were 1.14 (95% CI = 1.08-1.22) per 0.51 µg/m3 (interquartile range) increase of organic carbon and 1.11 (1.03-1.18) per 0.06 µg/m3 increase of sodium. Organic carbon was also associated with four individual complications. There was no association between ozone and outcome. SIGNIFICANCE: There were specific components of PM2.5 that have adverse effects on maternal and foetal health.

Trimester-Specific Association of Maternal Exposure to Fine Particulate Matter and its Components With Birth and Placental Weight in Japan.

OBJECTIVE: We investigated which trimester of exposure to PM2.5 and its components was associated with birth and placental weight, and the fetoplacental weight ratio. METHODS: The study included 63,990 women who delivered singleton term births within 23 Tokyo wards between 2013 and 2015. Each day, we collected fine particles on a filter, and analyzed their chemical constituents, including carbons and ions. Trimester-specific exposure to each pollutant was estimated based on the average daily concentrations. RESULTS: Over the third trimester, sulfate exposure tended to be inversely associated with birth weight, and decreased placental weight (difference for highest vs lowest quintile groups = -6.7 g, 95% confidence interval = -12.5 to -0.9). For fetoplacental weight ratio, there was no relationship. CONCLUSIONS: Sulfate exposure over the third trimester may reduce birth weight, particularly placental weight.

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.

A study on the association between eye movements and regular mouthing movements (RMMs) in normal fetuses between 24 to 39 weeks of gestation.

Regular Mouthing Movements (RMMs) are movements in which lips and lower jaw movements occur regularly and can be observed in the fetus using transabdominal ultrasonic tomography. In near term infants, it is known that RMMs form clusters during the quiet sleep period. The notation of RMMs is not uniform, and is described as spontaneous sucking movement or non-nutritive sucking in newborns. Non-nutritive sucking is used to evaluate neurological function after birth, but there are no fetal indicators. The purpose of this study was to clarify the changes in the RMM clusters in fetuses at 24-39 weeks of gestation, and to investigate the relationship with the non-eye movement (NEM) period, which corresponds to the quiet sleep period after birth. Subjects included 83 normal single pregnancy cases. Fetal RMMs and eye movement (EM) were observed for 60 minutes using ultrasonic tomography and recorded as moving image files. We created time series data of eye movements and mouth movements from video recordings, and calculated RMM clusters per minute within effective observation time, RMM clusters per minute in EM period, RMM clusters per minute in NEM period, mouthing movements per cluster and ratio of number of RMM clusters per minute between NEM and EM periods and analyzed using linear regression analysis. As a result, critical points were detected in at two time points, at 32-33 weeks and 36-37 weeks of gestation, in RMM clusters per minute within the effective observation time and RMM clusters per minute in NEM period, respectively. RMM clusters in human fetuses increased from 32-33 to 36-37 weeks. This change is thought to represent fetal sleep development and central nervous system development.