Association of placental weight at birth with maternal whole blood concentration of heavy metals (cadmium, lead, mercury, selenium, and manganese): The Japan Environment and Children's Study (JECS).

BACKGROUND: Lifelong health is dependent on prenatal growth and development, influenced by the placental intrauterine environment. Charged with dual functions--exchange of oxygen and nutrients as well as a barrier against toxins--the placenta itself is susceptible to environmental exposure to heavy metals. OBJECTIVE: To examine the use of placenta weight as a biomarker for heavy metal exposure using a large Japanese cohort of pregnant women. METHODS: The placenta weight, as a biomarker of exposure to heavy metals (cadmium, lead, and mercury), was investigated using data from the Japan Environment and Children's Study (2011-2014). Selenium and manganese were included as factors directly affecting fetal growth or heavy metal toxicity. Maternal blood samples collected in the second or third trimester were used to measure heavy metal concentrations. The association between maternal blood metal concentrations and placenta weight was explored by applying Z scores and multivariable logistic regression analysis and classifying participants into quartiles (Q1, Q2, Q3, and Q4) according to metal concentrations. RESULTS: This study included a total of 73,005 singleton pregnant women who delivered via live births and met the inclusion criteria. The median heavy metal concentrations in the maternal whole blood were 0.662 ng/g cadmium, 5.85 ng/g lead, 3.61 ng/g mercury, 168 ng/g selenium, and 15.3 ng/g manganese. Regression analysis revealed a significant correlation between placenta weight Z scores and maternal blood metal concentrations: cadmium, 0.0660 (standard error = 0.0074, p < 0.001); selenium, -0.3137 (standard error = 0.0276, p < 0.001); and manganese, 0.1483 (standard error = 0.0110, p < 0.001). CONCLUSION: This study provides a robust examination of the association between heavy metal exposure and placenta weight. Cadmium and manganese showed a positive correlation with significant differences, whereas selenium showed a negative correlation. Essential elements notably affect placenta weight differently. No significant association was noted between lead or mercury and placenta weight.

Longitudinal gut mycobiota changes in Japanese infants during first three years of life.

Although fungi can have a large impact on host health through the stimulation of the immune system and toxin production, few studies have investigated the gut mycobiota during infancy, a period during which sensitivity to internal and external stimuli is high. To capture the trend in fungal colonization during infancy, we evaluated the gut mycobiota of ten Japanese infants during the first 3 years of life. Infants had two major phyla, Ascomycota (68.9%) and Basidiomycota (29.6%), and the most abundant genus was Saccharomyces (26.8%), followed by Malassezia (18.5%), Candida (12.3%), Meyerozyma (8.5%), and Penicillium (8.3%). Alpha diversity analysis revealed a significant decrease in fungal richness and evenness with age, suggesting adaptive selection of the colonizing species in the gut environment. Beta diversity analysis divided infant mycobiota into age-related clusters and showed discrete separation before and after weaning, suggesting shift in microenvironment via weaning. In the initial stage, a variety of fungal species that likely originated from an environment, such as Malassezia spp., was highly colonized and were replaced by yeasts, such as Saccharomyces, after weaning. Further studies are needed to shed light on how the passage of the series of fungal colonizations in infancy affects the development of the host immune system and the other homeostasis involved in health later in life.

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.

Individual experiences and issues in predictive genetic testing for untreatable hereditary neuromuscular diseases in Japan.

Predictive genetic testing (PT) for hereditary diseases that do not have effective treatment or prevention strategies places a psychological burden on parties and their families. There has been little research on the psychosocial aspects of PT in Japan, nor are there any guidelines. To address this gap, we conducted a questionnaire survey of parties at genetic risk for untreatable hereditary neuromuscular diseases, and the National Liaison Conference of Genetic Medicine Departments (GMDs). Of the 63 parties who responded to the survey, 10 (15.9%) had undergone PT. Of the 67 GMDs, only 18 facilities (26.9%) were conducting PT with written procedures. At least two of the six parties with such results felt that some follow-up would be helpful. One party had taken PT for preimplantation genetic testing for monogenic (PGT-M); four, who had no experience, provided free text responses indicating that PGT-M or prenatal genetic testing was chosen as a motivation. Eight were unaware of PT, and six were unaware of their blood relatives' diseases being "hereditary." The results highlighted the need to: 1) develop guidelines for PT in untreatable hereditary diseases; 2) provide access to PT information; and 3) share the "heritability" of diseases with family and relatives.

A Case Report: Two Young Children with Long QT Syndrome Type-2 Diagnosed by Presymptomatic Genetic Testing.

Long QT syndromes (LQTSs) can lead to sudden cardiac death, yet these syndromes are often asymptomatic and clinically undetected, despite the prolongation of the QT interval. Currently, when a disease-causing variant is identified in an individual, presymptomatic genetic testing is available and can form part of the recommended cascade testing to identify other family members at risk. We herein report the cases of two daughters who received presymptomatic genetic testing in infancy when the proband mother had been diagnosed with LQTS type 2 (LQT2; c.1171C > T, p.Q391X in KCNH2) after suffering from cardiac arrhythmia at 30 years of age. The daughters had a normal QTc interval, but they carried the same disease-causing variant as their mother. Children with family members who have genetically confirmed LQTS have a high risk of suffering from cardiac events later in life, so genetic testing is required. This poses a complex problem, as guidelines for medical intervention and follow-up systems among asymptomatic children with LQTS have yet to be established. Genetic testing should only be performed after adequate counseling to support children later in life. Individualized long-term genetic counseling is required for both parents and children at stages throughout life.

No association between prenatal lead exposure and neurodevelopment during early childhood in the Japan Environment and Children's Study.

Compared with the relatively well-investigated effects of childhood exposure to lead on neurocognitive deficits, those of prenatal exposure remain relatively inconclusive. We aimed to investigate the association between prenatal blood lead levels and neurodevelopmental delay during the first three years of life. From a prospective cohort of the Japan Environment and Children's Study, we analyzed a total of 80,759 children. The exposure factors were prenatal lead concentrations measured from maternal whole blood in the second/third trimesters and umbilical cord blood at birth. Neurodevelopment was assessed at 6, 12, 18, 24, 30, and 36 months old using a screening tool, the Ages and Stages Questionnaires, third edition (ASQ). The outcome measures were any suspected neurodevelopmental delay (sNDD) identified via the ASQ during the first (sNDD-1Y), second (sNDD-2Y), and third (sNDD-3Y) years of life. sNDD-1Y, 2Y, and 3Y were identified in 18.0%, 16.2%, and 17.2% of children, respectively. The geometric means of blood lead concentration in this study were much lower (0.62 µg/dL in maternal blood and 0.50 µg/dL in cord blood) than previously investigated levels. Multivariable regression models revealed that there were no associations between maternal blood lead and sNDD-1Y and 2Y and between cord blood lead and sNDD-1Y, 2Y, and 3Y. Although a higher maternal blood lead was associated with a reduced risk of sNDD-3Y (adjusted relative risk: 0.84, 95% confidence interval 0.75-0.94, per 1 increase in common logarithm of lead concentration), there were no dose-response relationships in the analysis using quintiles of lead concentrations. Using a large-scale data set, the present study demonstrated no convincing evidence for an inverse association between levels of prenatal blood lead and neurodevelopment in early childhood. Longitudinal measurements of prenatal and postnatal lead levels are needed to understand the relationship between lead exposure and neurocognitive development.

The association between early formula and reduced risk of cow's milk allergy during the first three year of life: a Japanese cohort study.

BACKGROUND: Our recent observational study showed that regular consumption of cow's milk (CM) formula during early infancy (3-6 months old) was associated with a reduced risk of CM allergy (CMA) at 12 months old. However, the long-term association is unclear. The present study was aimed to examine how long this inverse association persists after 12 months old. METHODS: This study used the dataset of an ongoing nationwide prospective cohort, the Japan Environment and Children's Study, in which participants were registered between January 2011 and March 2014. We analyzed 65,568 children followed-up until 36 months old. The exposure factors were the consumption statuses of formula milk from 0-3, 3-6, and 6-12 months old. The primary outcome was the prevalence of CMA at 6, 12, 18, 24 and 36 months old. CMA was defined as an allergic reaction and sensitization to CM protein in an individual with no or limited intake of this protein at the evaluation time, combined with physician-diagnosed food allergy. Multivariable regression models were used to estimate the association between the periods of formula consumption and the prevalence of CMA. RESULTS: The prevalence of CMA increased with a peak of 1.51% at 18 months old and then declined to 0.79% at 36 months old. Formula milk from 3-6 months old was associated with a reduced risk of CMA throughout the first 3 years of life, although the extent of the reduction was mitigated with age (adjusted relative risk: [95% confidence interval]: 0.19 [0.10-0.34] at 12 months old, 0.23 [0.16-0.33] at 18 months old, 0.41 [0.26-0.64] at 24 months old, and 0.47 [0.26-0.80] at 36 months old). The association between early formula and CMA were observed in both children with and without eczema, but more prominent and long-lasting in the former than the latter. CONCLUSIONS: Regular exposure to CM protein during infancy was associated with a reduced prevalence of CMA during early childhood. At present, however, this observational study does not necessarily encourage formula feeding, and randomized controlled trials are warranted to confirm the findings and their significance.

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.

Maternal Chronic Disease and Congenital Anomalies of the Kidney and Urinary Tract in Offspring: A Japanese Cohort Study.

RATIONALE & OBJECTIVE: Several maternal chronic diseases have been reported as risk factors for congenital anomalies of the kidney and urinary tract (CAKUT) in offspring. However, these investigations used case-control designs, and cases with isolated genitourinary CAKUT were not distinguished from cases in which CAKUT were present with extrarenal congenital anomalies (complicated CAKUT). We examined the association of maternal diseases with isolated and complicated CAKUT in offspring using data from a prospective cohort study. STUDY DESIGN: A nationwide prospective birth cohort study. SETTING & PARTICIPANTS: 100,239 children enrolled in the Japan Environment and Children's Study between January 2011 and March 2014 at 15 research centers. Physicians' diagnoses in mothers and children were collected from medical record transcripts and questionnaires. EXPOSURES: Medical histories of maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease. OUTCOMES: CAKUT diagnosed during the first 3 years of life, classified as isolated or complicated. ANALYTICAL APPROACH: Multivariable Poisson regression with generalized estimating equations accounting for clustering by clinical center. RESULTS: Among the 100,239 children, 560 (0.6%) had CAKUT, comprising 454 (81%) isolated and 106 (19%) complicated forms. The risk of isolated CAKUT was increased in children of mothers who experienced kidney disease (adjusted risk ratio [RR], 1.80 [95% CI, 1.12-2.91]) or cancer (RR, 2.11 [95% CI, 1.15-3.86]). Furthermore, the risk of complicated CAKUT was increased in children of mothers with diabetes mellitus (RR, 3.04 [95% CI, 1.64-5.61]). LIMITATIONS: Lack of standardization or prespecification of clinical definitions, diagnostic criteria, measurements, and testing. Genetic testing was not performed. CONCLUSIONS: Isolated CAKUTs and complicated CAKUTs were associated with different maternal diseases. The results may inform clinical management of pregnancy and highlight potential differences in the genesis of isolated and complicated forms of CAKUT.

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.

Current status and issues related to secondary findings in the first public insurance covered tumor genomic profiling in Japan: multi-site questionnaire survey.

In June 2019, the Japanese National Health Insurance (NHI) system introduced coverage for two types of tumor genomic profiling (TGP): FoundationOneⓇ CDx (F1) and OncoGuide™ NCC OncoPanel System (NCCOP). TGP sometimes reveals germline variants that are potentially pathogenic as secondary findings (SFs). We conducted a questionnaire-based survey to find out the operational statuses of F1 and NCCOP at institutions where TGP was performed to elucidate issues related to SFs. Responses were received from 97 of 112 institutions (86.6%). As of May 31, 2020, 88 (90.7%) and 78 (80.4%) institutions started performing F1 and NCCOP, respectively. Since F1 only examines tumor samples, germline confirmatory testing is necessary to determine whether they are actually germline pathogenic variants (GPVs). When physicians are obtaining informed consent all but 2.3% of the patients requested SF disclosure. Conversely, when presumed germline pathogenic variants (PGPVs) were detected, 46.2% were not willing to receive confirmatory tests as they wanted to prioritize cancer treatment over SFs investigation, while only 23.3% underwent confirmatory tests. Problems in cancer genomic medicine reported by clinical genetics departments included short-staffing (n = 10), insufficient interdepartmental cooperation (n = 9), inconsistent understanding of genetics among healthcare professionals (n = 8), and low utilization rate of SFs due to lack of insurance coverage for confirmatory tests and post-test health checkups (n = 8). Solutions include; determining the appropriate timing to confirm patient intent on SF disclosure, covering confirmatory tests for PGPVs by the NHI, and establishing cooperation between the oncology and clinical genetics departments.

Attitude changes toward prenatal testing among women with twin pregnancies after the introduction of noninvasive prenatal testing: A single-center study in Japan.

AIM: This study aimed to evaluate changes in prenatal testing among women with twin pregnancies before and after the introduction of noninvasive prenatal testing (NIPT). To date, no consensus on prenatal testing for twin pregnancies has been reached in Japan. METHODS: Women pregnant with twins who requested prenatal testing at Kyushu Medical Center from 2005 to 2018 were included in this study. Genetic counseling was provided to all participants. Their chosen methods of testing were collected and classified as invasive diagnosis (ID), noninvasive screening (NIS), and no test requested (NR). Parity, chorionicity, and methods of conception were assessed as attributes. The study period was divided into three terms according to testing availability in our center. RESULTS: After NIPT was introduced in our center, the use of ID methods decreased and eventually disappeared while NIS came to the forefront. NR was also the preferred choice of women with twin pregnancies before the introduction of NIPT and decreased but did not disappear after introducing NIPT. Women with twin pregnancies who underwent assisted reproduction initially showed hesitation to undergo testing but showed a strong preference for NIS after the introduction of NIPT. Differences in choice according to parity, chorionicity, and methods of conception were found before the introduction of NIPT but disappeared after introducing NIPT. CONCLUSION: Increasing information about NIPT has apparently influenced the attitudes of women with twin pregnancies to prenatal testing in Japan. In particular, those who conceive through assisted reproductive technologies exhibited a strong preference for NIPT.

Breast feeding and infant development in a cohort with sibling pair analysis: the Japan Environment and Children's Study.

OBJECTIVES: To investigate the association between breast feeding and infant development during the first year of life using sibling comparison. DESIGN: Nationwide prospective birth cohort study with sibling pair analysis. SETTING: 15 regional centres that participated in the Japan Environment and Children's Study. PARTICIPANTS: This study included 77 119 children (singleton, term birth and no malformation/severe diseases) whose mothers were registered between January 2011 and March 2014, including 3521 duos or trios of siblings. PRIMARY OUTCOME MEASURES: The primary outcome was developmental delay at 6 and 12 months of age, assessed using the Japanese translation of the Ages and Stages Questionnaires, third edition. Multivariable regression analyses adjusted for confounders were performed to estimate the risk ratios of delay associated with any or exclusive breast feeding. Pairs of siblings discordant for statuses were selected, and conditional regression analyses were conducted with a matched cohort design. RESULTS: Developmental delay was identified in 6162 (8.4%) and 10 442 (14.6%) children at 6 and 12 months of age, respectively. Any breast feeding continued until 6 months or 12 months old was associated with reduced developmental delay at 12 months of age (adjusted risk ratio (95% CI): 0.81 (0.77 to 0.85) and 0.81 (0.78 to 0.84), respectively). Furthermore, exclusive breast feeding until 3 months was associated with reduced developmental delay at 12 months of age (adjusted risk ratio, 0.86 (95% CI 0.83 to 0.90)). In sibling pair analysis, the association between any breast feeding until 12 months and reduced developmental delay at 12 months of age persisted (adjusted risk ratio, 0.64 (95% CI 0.43 to 0.93)). CONCLUSIONS: The present study demonstrated the association of continuous breast feeding with reduced developmental delay at 1 year of age using sibling pair analysis, in which unmeasured confounding factors are still present but less included. This may provide an argument to promote breastfeeding continuation.

Physical growth and neurodevelopment during the first year of life: a cohort study of the Japan Environment and Children's Study.

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

Infantile neuroblastoma and maternal occupational exposure to medical agents.

BACKGROUND: Healthcare workers are often exposed to hazardous agents and are at risk for adverse health consequences that affect not only themselves but also their infants. This study aimed to examine whether such occupational exposure increased the risk of childhood cancer in offspring. METHODS: We used the dataset of the Japan Environment and Children's Study, a nationwide birth cohort involving over 100,000 mother-child pairs. Information was obtained via successive questionnaires that were completed until the child turned 1 year of age. The parents were asked whether they occupationally handled medical agents during pregnancy. RESULTS: A total of 26 infants developed neoplasms: neuroblastoma, leukemia, and brain tumor. The incidence of neuroblastoma was significantly higher in infants whose mothers were exposed to radiation (3/2142: 140.1 per 100,000 population) than in those who were not (12/90,384: 13.3 per 100,000 population). Multivariable regression analyses revealed a close association between maternal irradiation and the development of neuroblastoma (adjusted incident rate ratio: 10.68 [95% confidence interval: 2.98‒38.27]). CONCLUSIONS: The present study demonstrated, for the first time, a potential association between maternal occupational exposure and the occurrence of neuroblastoma in offspring. Further studies involving the large pediatric cancer registries are needed to confirm these preliminary results. IMPACT: Healthcare workers are often exposed to hazardous agents and are at risk for adverse health consequences that affect not only themselves but also their infants. This study examined the association between such occupational exposure and offspring's cancers that developed until the age of 1 year. Maternal exposure to ionizing radiation was associated with infantile neuroblastoma in offspring. Further studies involving the large pediatric cancer registries are needed to confirm these preliminary results.

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.

Possible association between early formula and reduced risk of cow's milk allergy: The Japan Environment and Children's Study.

BACKGROUND: Despite evidence for the protective effects of early regular exposure to peanut and egg proteins against allergies, the optimal timing of cow's milk (CM) protein exposure is unknown. OBJECTIVE: We aimed to determine when during the first year of life CM-based formula consumption becomes associated with lower CM allergy (CMA) risk. METHODS: We used the data set of the Japan Environment and Children's Study (JECS), a nationwide birth cohort involving over 100 000 mother-child pairs. CMA was defined as an allergic reaction to a CM product in an individual not consuming CM products at the time of evaluation, combined with physician-diagnosed food allergy. For each exposure, we identified when formula milk was commenced, and its consumption status during 0-3, 3-6 and 6-12 months old. RESULTS: The prevalence of CMA was 0.23% and 1.03% at 6 and 12 months old, respectively. Multivariable regression analyses revealed that introducing regular consumption of formula within the first 3 months of age was associated with lower risk of CMA at 12 months. Regular consumption at 3-6 months was strongly associated with a reduction in 12-month CMA (adjusted relative risks [95% confidence intervals]: 0.22 [0.12-0.35]), whereas no association was observed at 0-3 months (1.07 [0.90-1.27]). CONCLUSION AND CLINICAL RELEVANCE: Regular exposure to formula milk at age 3 months or older is associated with lower CMA at 12 months old, suggesting that the effect of very early CM exposure on CMA may disappear if the exposure is brief. At present, however, the results of this observational study should not be used for formula recommendation and randomized controlled trials are required to confirm this association.

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.