Medication use before and during pregnancy in Japan: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

PURPOSE: To elucidate the status of medication use among pregnant women in Japan, by means of a multigenerational genome and birth cohort study: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). METHODS: Questionnaires were distributed to pregnant women participating in the TMM BirThree Cohort Study (from July 2013 to March 2017) around 12 weeks (early pregnancy) and 26 weeks (middle pregnancy). We analysed medication use over three periods: (1) 12 months prior to pregnancy diagnosis, (2) the period between pregnancy diagnosis and around week 12 of pregnancy, and (3) post around week 12 of pregnancy. RESULTS: In total, 19,297 women were included in the analysis. The proportion of pregnant women using medications was 49.0% prior to pregnancy diagnosis, 52.1% from diagnosis to week 12, and 58.4% post week 12 of pregnancy. The most frequently prescribed medications were loxoprofen sodium hydrate (5.5%) prior to pregnancy diagnosis, magnesium oxide (5.9%) from diagnosis to week 12, and ritodrine hydrochloride (10.5%) post week 12 of pregnancy. The number of women who used suspected teratogenic medications during early pregnancy was 96 prior to pregnancy diagnosis, 48 from diagnosis to week 12, and 54 post week 12 of pregnancy. CONCLUSION: We found that ~ 50% of the pregnant women used medications before and during pregnancy and some took potential teratogenic medications during pregnancy. In birth genomic cohort study, it is expected that investigations into the safety and effectiveness of medications used during pregnancy will advance.

Hypertensive disorders of pregnancy, neonatal outcomes and offspring developmental delay in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

INTRODUCTION: Developmental delay at an early age indicates the probability of continued problems after school age. Hypertensive disorders of pregnancy (HDP) are associated with developmental delays in offspring, with inconsistent outcomes. Neonatal outcomes vary according to HDP exposure and are relevant to development in later years. Here we aimed to clarify the relationship between HDP and developmental delay in offspring and whether neonatal outcomes mediate this association. MATERIAL AND METHODS: We used data from 5934 mother-child pairs from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, a prospective cohort study conducted in Japan between July 2013 and March 2017. The Ages and Stages Questionnaires, third edition, at 24 and 42 months of age, measured developmental delay in five areas. We performed multivariate quasi-Poisson regression and causal mediation analysis by neonatal outcomes. RESULTS: At 24 months of age, compared to offspring born from normotensive mothers, offspring born from HDP-affected mothers were more likely to experience developmental delay (risk ratio [RR] 1.29, 95% confidence interval [CI]: 1.09-1.52) in the areas of communication (RR 1.21, 95% CI: 1.00-1.45) and personal-social (RR 1.15, 95% CI: 1.03-1.28). This association was mediated by neonatal outcomes: preterm birth, neonatal asphyxia, NICU admission, and neonatal small head circumference. No association was observed between HDP and developmental delay at 42 months of age. CONCLUSIONS: Exposure to HDP during fetal life is associated with offspring developmental delay. This association is partly mediated by neonatal outcomes.

Genome-wide association study of nausea and vomiting during pregnancy in Japan: the TMM BirThree Cohort Study.

BACKGROUND: Nausea and vomiting during pregnancy (NVP) and hyperemesis gravidarum (HG), common conditions affecting most pregnant women, are highly heritable and associated with maternal and fetal morbidity. However, the pathologies underlying NVP and HG and their associated loci are scarce. METHODS: We performed genome-wide association studies (GWAS) of NVP in pregnant women (n = 23,040) who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan from July 2013 to March 2017. Participants were divided into discovery (n = 9,464) and replication (n = 10,051) stages based on the platform used for their genotyping. Loci that achieved the genome-wide significance level (p < 5.0 × 10- 8) in the discovery stage were selected for genotyping in the replication stage. A meta-analysis integrating the discovery and replication stage results (n = 19,515) was conducted. NVP-related variables were identified as categorical or continuous. RESULTS: GWAS analysis in the discovery phase revealed loci linked to NVP in two gene regions, 11q22.1 (rs77775955) and 19p13.11 (rs749451 and rs28568614). Loci in these two gene regions have also been shown to be associated with HG in a White European population, indicating the generalizability of the GWAS analyses conducted in this study. Of these, only rs749451 and rs28568614 at 19p13.11 reached the genome-wide suggestive level (p < 1.0 × 10- 5) in the replication stage; however, both loci were significant in the meta-analysis. CONCLUSIONS: NVP-related loci were identified in the Japanese population at 11q22.1 and 19p13.11, as reported in previous GWAS. This study contributes new evidence on the generalizability of previous GWAS on the association between genetic background and NVP.

Maternal social isolation and behavioral problems in preschool children: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

It is essential to clarify factors associated with mental health and behavioral problems in early childhood, because children are critical stages of life for mental health. We aimed to prospectively examine the associations between maternal social isolation and behavioral problems in preschool children. We analyzed data from 5842 mother-child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. The Lubben Social Network Scale-abbreviated version was used to assess social isolation (defined as scores < 12) one year after delivery. The Child Behavior Checklist 1½-5 was used to assess behavioral problems, and its subscales were used to assess internalizing and externalizing problems in children at 4 years of age. Multiple logistic regression analyses were conducted to examine the associations between social isolation and behavioral problems, after adjustment for age, education, income, work status, marital status, extraversion, neuroticism, depressive symptoms, child sex, and number of siblings. Multiple logistic regression analyses were also conducted for internalizing problems and externalizing problems. The prevalence of maternal social isolation was 25.4%. Maternal social isolation was associated with an increased risk of behavioral problems in children: the odds ratio (OR) was 1.37 (95% confidence interval [CI] 1.14-1.64). Maternal social isolation was also associated with increased risks of internalizing problems and externalizing problems in children: the ORs were 1.33 (95% CI, 1.12-1.59) and 1.40 (95% CI, 1.18-1.66), respectively. In conclusion, maternal social isolation one year after delivery was associated with behavioral problems in children at 4 years of age.

Factors Associated With Postpartum Smoking Relapse Among Women Who Quit in Early Pregnancy: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: While a wide range of predictors of postpartum smoking relapse have been suggested, population-based studies have rarely examined these factors exclusively among women who quit in early pregnancy. Furthermore, workplace secondhand smoke (SHS) exposure has never been examined. METHODS: We analyzed data from 10,466 pregnant women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Age, education, parity, breastfeeding, postpartum depression, SHS exposure at home, and SHS exposure at work (not working, working without SHS exposure, working with SHS exposure) were evaluated as possible predictors. Multiple logistic regression analyses were conducted to examine the associations between these factors and smoking relapse by 1 year postpartum among women who quit in early pregnancy. Analyses stratified by SHS exposure at home were also conducted. RESULTS: About one-fourth of early-pregnancy quitters had relapsed into smoking by 1 year postpartum. Lower education, multiparity, not breastfeeding, postpartum depression, and SHS exposure at home were associated with increased risks of smoking relapse. Working with SHS exposure was associated with an increased risk of smoking relapse; the multivariate-adjusted odds ratios of working without SHS exposure and working with SHS exposure compared with not working were 1.14 (95% confidence interval [CI], 0.82-1.59) and 2.18 (95% CI, 1.37-3.46), respectively. The significant association of workplace SHS exposure was observed only among women without SHS exposure at home. CONCLUSION: SHS exposure at work, as well as education, multiparity, breastfeeding, postpartum depression, and SHS exposure at home were associated with postpartum smoking relapse among early-pregnancy quitters.

Relation of Disaster Exposure With Maternal Characteristics and Obstetric Outcomes: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: The present study analyzed the relation of disaster exposure prior to pregnancy with maternal characteristics and obstetric outcomes. METHODS: The participants were 13,148 pregnant women recruited from 2013 to 2017. The women were classified into three groups by the severity of housing damage caused by the Great East Japan Earthquake of 2011: group A, house was not destroyed/did not live in the disaster area; group B, half/part of the house was destroyed; and group C, house was totally/mostly destroyed. Maternal characteristics, hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), and gestational weeks were obtained using questionnaires and medical records. Multiple logistic regression analyses were performed to investigate the relation between disaster exposure and maternal characteristics, HDP, and GDM. A structural equation model was applied to investigate the relation of disaster exposure with HDP and gestational weeks. RESULTS: The homes of about 11% of the women were totally/mostly destroyed. For groups B and C compared with those in group A, the adjusted ORs for HDP were 1.04 and 1.26 (P for trend = 0.01), and for GDM were 0.89 and 1.14 (P for trend = 0.9), respectively. Pre-pregnancy body mass index (BMI) mediated 23.2% of the relation between disaster exposure and HDP. Disaster exposure was associated with gestational weeks. CONCLUSION: Disaster exposure at least 2.5 years before pregnancy was found to be associated with maternal characteristics and the prevalence of HDP. Pre-pregnancy BMI mediated the relation between disaster exposure and the prevalence of HDP, and gestational weeks were reduced through HDP.

Association between frequency of breakfast intake before and during pregnancy and developmental delays in children: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: Although an association between maternal nutritional intake and developmental delays in children has been demonstrated, the association of the timing of meal intake and development delays remains unclear. We examined the association between breakfast intake frequency before and during pregnancy and developmental delay in children. METHODS: Of the pregnant women who participated in the Tohoku Medical Megabank Project Three-Generation Cohort Study, 7491 answered the required questions and were analyzed. The frequency of breakfast intake from pre- to early pregnancy and from early to mid-pregnancy was classified into four groups: daily, and 5-6, 3-4, and 0-2 times/week. Child developmental delays at age 2 and 3.5 years were assessed using the Ages & Stages Questionnaire, Third Edition. Logistic regression models were constructed to examine the association between breakfast intake frequency in pregnant women and developmental delays in children aged 2 and 3.5 years. RESULTS: The proportion of pregnant women who had breakfast daily was 78.1% in pre- to early pregnancy, and 82.2% in early to mid-pregnancy. The proportion of children with developmental delays was 14.7% and 13.4% at age 2 and 3.5 years, respectively. Compared with the risk in children of women who had breakfast daily from pre- to early pregnancy, children of women who had breakfast 0-2 times/week had a higher risk of developmental delays at 2 years of age: odds ratio (OR) 1.30, (95% confidence interval [CI], 1.02-1.66). The risk of developmental delays at age 2 years increased in the children of women who had breakfast 0-2 times/week in early to mid- pregnancy: OR 1.75 (95% CI, 1.32-2.32). The risk of developmental delays at age 3.5 years did not increase in the children of women who had breakfast 0-2 times/week from pre- to early and early to mid-pregnancy: OR 1.06 (95% CI, 0.81-1.39 and OR 1.15 (95% CI 0.84-1.57), respectively. CONCLUSION: For women with a low frequency of breakfast intake from pre- to mid-pregnancy there was an association with developmental delays in their children at age 2, but not at 3.5 years.

Association between frequency of breakfast intake before and during pregnancy and infant birth weight: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: Low birth weight is associated with an increased risk of developing chronic diseases in adulthood, with a particularly high incidence in Japan among developed countries. Maternal undernutrition is a risk factor for low birth weight, but the association between the timing of food intake and infant birth weight has not been investigated. This study aimed to examine the association between breakfast intake frequency among Japanese pregnant women and infant birth weight. METHODS: Of all pregnant women who participated in the Tohoku Medical Megabank Project Three Generation Cohort Study, 16,820 who answered the required questions were included in the analysis. The frequency of breakfast intake from pre- to early pregnancy and from early to mid-pregnancy was classified into four groups: every day and 5-6, 3-4, and 0-2 times/week. Multivariate linear regression models were constructed to examine the association between breakfast intake frequency among pregnant women and infant birth weight. RESULTS: The percentage of pregnant women who consumed breakfast daily was 74% in the pre- to early pregnancy period and 79% in the early to mid-pregnancy period. The average infant birth weight was 3,071 g. Compared to women who had breakfast daily from pre- to early pregnancy, those who had breakfast 0-2 times/week had lower infant birth weight (ß = -38.2, 95% confidence interval [CI]: -56.5, -20.0). Similarly, compared to women who had breakfast daily from early to mid-pregnancy, those who had breakfast 0-2 times/week had lower infant birth weight (ß = -41.5, 95% CI: -63.3, -19.6). CONCLUSIONS: Less frequent breakfast intake before and mid-pregnancy was associated with lower infant birth weight.

Associations between sugar-sweetened beverages before and during pregnancy and offspring overweight/obesity in Japanese women: the TMM BirThree Cohort Study.

OBJECTIVE: The association between high sugar-sweetened beverages (SSB) intake during pregnancy and offspring overweight/obesity has been reported only from Western countries. The objective of this study was to examine the association between SSB intake before and during pregnancy and offspring overweight/obesity among Japanese women. DESIGN: Japanese prospective birth cohort study. SETTING: We analysed mother-offspring pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017. SSB intake during pregnancy was evaluated using the FFQ and classified into three groups: none (0 g/d), medium (<195 g/d) and high (>195 g/d). Overweight or obesity at 1 year of age in offspring was defined as having a BMI Z-score greater than 2 sd, calculated based on the BMI reference data for Japanese children. Multiple logistic regression analyses were performed to examine the associations between SSB intake before and during pregnancy and offspring overweight/obesity, after adjusting for covariates. PARTICIPANTS: Japanese mother-offspring pairs (n 7114). RESULTS: The overweight/obesity rate of the offspring was 8·8 %. Pregnant women with a high intake of SSB in early to mid-pregnancy had a higher risk of overweight/obesity in their offspring compared with those who did not; the OR was 1·52 (95 % CI (1·09, 2·12)). CONCLUSIONS: High SSB intake in early to mid-pregnancy was associated with an increased risk of offspring overweight/obesity at 1 year of age.

Maternal postnatal bonding disorder and developmental delays in children: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Although there is some evidence regarding an association between maternal bonding disorder and child development, studies have mainly focused on development during the period of infancy. We aimed to examine the associations between maternal postnatal bonding disorder and developmental delays in children beyond 2 years of age. We analyzed data from 8380 mother-child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Maternal bonding disorder was defined as Mother-to-Infant Bonding Scale score of ≥5 at 1 month after delivery. The Ages & Stages Questionnaires, Third Edition, which consists of five developmental areas, was used to assess developmental delays in children at 2 and 3.5 years of age. Multiple logistic regression analyses were conducted to examine the associations between postnatal bonding disorder and developmental delays after adjustment for age, education, income, parity, feelings toward pregnancy, postnatal depressive symptoms, child's sex, preterm birth, and birth defects. Bonding disorder was associated with developmental delays in children at 2 and 3.5 years of age: the odds ratios (95% confidence intervals) were 1.55 (1.32-1.83) and 1.60 (1.34-1.90), respectively. Bonding disorder was associated with delay in communication only at 3.5 years of age. Bonding disorder was associated with delay in gross motor, fine motor, and problem solving, but not delay in the personal-social domain, at 2 and 3.5 years of age. In conclusion, maternal bonding disorder 1 month after delivery was associated with an increased risk of developmental delays in children beyond 2 years of age.

Liver steatosis and fibrosis markers' association with cardiovascular and renal damage in Japanese adults: the TMM BirThree cohort study.

INTRODUCTION AND OBJECTIVES: Patients with non-alcoholic fatty liver disease (NAFLD) are at risk for cardiovascular and chronic kidney diseases. Liver steatosis and fibrosis were assessed using the fatty liver index and fibrosis-4 index, respectively. This study aimed to examine the association between these two parameters in patients with atherosclerosis and chronic kidney disease. MATERIALS AND METHODS: The two parameters were calculated for 11,867 adults who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Intima-media thickness and estimated glomerular filtration rate were also measured. Logistic regression models were used to estimate the odds ratios (OR). RESULTS: Overall, 4257 (35.9%) and 4733 (39.9%) participants had a higher probability of liver steatosis and fibrosis, respectively. The adjusted OR of higher fatty liver index compared to lower fatty liver index for atherosclerosis and chronic kidney disease were 0.98 (95% confidence interval [CI], 0.77-1.24) and 1.79 (95% CI, 1.19-2.69), and those of higher FIB-4 compared to lower FIB-4 were 1.03 (95% CI, 0.82-1.30) and 0.79 (95% CI, 0.52-1.19) for atherosclerosis and chronic kidney disease, respectively. CONCLUSIONS: A higher FLI was associated with CKD independent of other risk factors. Further research is required to identify the causal relationship between liver fat accumulation and CKD.

Maternal social isolation in the perinatal period and early childhood development: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

PURPOSE: Studies examining the associations between maternal social relationships and early childhood development have mainly focused on social relationships after childbirth. We aimed to prospectively examine the associations between the transition of maternal social isolation from the prenatal to postnatal period and early childhood development. METHODS: We analyzed data for 6692 mother-child pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Social isolation in the prenatal and postnatal periods was assessed by the Lubben Social Network Scale-abbreviated version and categorized into four groups: none, prenatal only, postnatal only, and both. The Ages and Stages Questionnaire, Third Edition, which consists of five developmental areas, was used to assess developmental delays in children at 2 and 3.5 years of age. Multiple logistic regression analyses were conducted to examine the associations between maternal social isolation and developmental delays. RESULTS: The prevalence of social isolation in both the prenatal and postnatal periods was 13.1%. Social isolation in both the prenatal and postnatal periods was associated with developmental delays in children at 2 and 3.5 years of age: the multivariate-adjusted odds ratios (95% confidence intervals) were 1.68 (1.39-2.04) and 1.43 (1.17-1.76), respectively. Social isolation in the prenatal period only and social isolation in the postnatal period only were not associated with developmental delays in children at 2 and 3.5 years of age. CONCLUSION: Maternal social isolation in both the prenatal and postnatal periods was associated with an increased risk of developmental delays in early childhood.

Association between maternal psychological distress and children's neurodevelopment in offspring aged 4 years in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

AIM: An association between maternal psychological distress and children's development has been reported, but  reports from Japan are limited. This study aimed to examine the association of maternal psychological distress with children's neurodevelopment in Japan. METHODS: The study assessed data of 7646 mother-infant pairs in the Japanese population. We used Kessler Psychological Distress Scale, a screening tool for psychological distress, to assess maternal psychological distress in early pregnancy and 2 years postpartum and divided it into four categories: none in both the pre-natal and post-natal periods, only the pre-natal period, only the post-natal period and both the pre-natal and post-natal periods. Children's neurodevelopment was assessed using the Ages & Stages Questionnaires Third Edition (ASQ-3) at 4 years of age. ASQ-3 comprises five domains (communication, gross motor, fine motor, problem solving and personal-social), and the score of less than -2 standard deviation relative to the mean in reference was defined as having developmental delay. We conducted multivariate logistic regression analysis to examine the association between maternal psychological distress and children's neurodevelopment. RESULTS: The prevalence of developmental delay of communication, gross motor, fine motor, problem solving and personal-social were 4.0%, 4.3%, 4.9%, 3.8% and 4.6%, respectively. Maternal psychological distress in only the postpartum period and both pre-natal and postpartum periods were associated with risks of developmental delay in all domains. Maternal psychological distress in only the pre-natal period was associated with developmental delay in communication. CONCLUSIONS: Maternal psychological distress is associated with risks of children's developmental delay.

Associations of Education and Income with Secondhand Smoke Exposure Among Non-smoking Pregnant Women in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

OBJECTIVES: There is accumulating evidence that lower socioeconomic groups are more exposed to secondhand smoke (SHS) than higher ones in the general population. The objective of the study was to examine the associations of education and income with SHS exposure among non-smoking pregnant women in Japan. METHODS: We analyzed data from 11,615 non-smoking pregnant women in Japan who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017. SHS exposure was defined as indoor exposure to someone else's cigarette smoke ≥ 1 day/week during pregnancy. Multiple logistic regression analyses were conducted to examine whether pregnant women's educational attainment or equivalent household income was associated with SHS exposure, adjusting for covariates. Stratified analyses by work status were also conducted. RESULTS: The prevalence of SHS exposure during pregnancy was 32.6%; 27.6% among non-working women and 35.8% among working women. Lower educational attainment was associated with an increased risk of SHS exposure; the odds ratio of high school education or lower compared with university education or higher was 1.87 (95% confidence interval, 1.66-2.10). Lower equivalent household income was associated with an increased risk of SHS exposure; the odds ratio of the lowest compared with the highest level of income was 1.53 (95% confidence interval, 1.35-1.74). These associations did not differ between non-working women and working women. CONCLUSIONS FOR PRACTICE: Associations of education and income with SHS exposure imply that educational interventions and financial incentives are needed for pregnant women and their household smokers.

Design and Progress of Child Health Assessments at Community Support Centers in the Birth and Three-Generation Cohort Study of the Tohoku Medical Megabank Project.

The Tohoku Medical Megabank Project (TMM) has been conducting a birth and three-generation cohort study (the BirThree Cohort Study). We recruited 73,529 pregnant women and their family members for this cohort study, which included 23,143 newborns and 9,459 of their siblings. We designed and are in the process of conducting three-step health assessments for each newborn at approximately ages of 5, 10 and 16. These health assessments are administered at seven community support centers. Trained genome medical research coordinators conduct physical examinations of and collect biological specimens from each participant. The Sendai Children's Health Square has been established as the headquarters for these child health assessments and is utilized to accumulate knowledge that can facilitate the proper practice of child health assessments. We designed all the relevant health assessments facilities to allow parents and their children to participate in the health assessments concomitantly. Our centers serve as places where child participants and their parents can feel at ease as a result of the implementation of safety measures and child hospitality measures. The TMM BirThree Cohort Study is in the process of conducting strategically detailed health assessments and genome analysis, which can facilitate studies concerning the gene-environment interactions relevant to noncommunicable diseases. Through these operations, our study allows for a significant depth of data to be collected in terms of the number of biospecimens under study and the comprehensiveness of both basic and clinical data alongside relevant family information.

Fruit and vegetable consumption before and during pregnancy and developmental delays in offspring aged 2 years in Japan.

The association between fruit and vegetable consumption before and during pregnancy and offspring's physical growth has been well reported, but no study has focused on offspring's neurological development. We aimed to explore the association between maternal fruit and vegetable consumption before and during pregnancy and developmental delays in their offspring aged 2 years. Between July 2013 and March 2017, 23 406 women were recruited for the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Fruit and vegetable consumption was calculated using FFQ, and offspring's developmental delays were evaluated by the Ages & Stages Questionnaires, Third Edition (ASQ-3) for infants aged 2 years. Finally, 10 420 women and 10 543 infants were included in the analysis. Totally, 14·9 % of children had developmental delay when screened using the ASQ-3. Women in the highest quartile of vegetable consumption from pre-pregnancy to early pregnancy and from early to mid-pregnancy had lower odds of offspring's developmental delays (OR 0·74; 95 % CI 0·63, 0·89 and OR 0·70; 95 % CI 0·59, 0·84, respectively) than women in the lowest quartile. Women in the highest quartile of fruit consumption from early to mid-pregnancy had lower odds of offspring's developmental delays (OR 0·78; 95 % CI 0·66, 0·92) than women in the lowest quartile. In conclusion, high fruit and vegetable consumption before and during pregnancy was associated with a lower risk of developmental delays in offspring aged 2 years.

Risk of major congenital malformations associated with first-trimester exposure to propulsives: A health administrative database study in Japan.

PURPOSE: To evaluate the risk of major congenital malformations (MCMs) associated with first-trimester exposure to propulsives with a special focus on domperidone using a large administrative database in Japan. METHODS: A large claims database was used from January 2005 to August 2016. The dates of pregnancy onset and delivery were estimated using the developed algorithms. MCMs were defined according to the International Classification of Diseases, 10th revision codes. We compared the infants' risk of overall MCMs between women with or without first-trimester prescriptions of propulsives and estimated the odds ratios (ORs) with unadjusted and adjusted analyses. We also compared the risk of overall MCMs between women with domperidone prescriptions and those with other propulsive prescriptions during the first trimester. RESULTS: Among 38 270 women, propulsives were prescribed to 3197 women (8.4%) in the first trimester, including domperidone to 371 women (1.0%). Propulsive prescriptions in the first trimester were not significantly associated with an increased risk of overall MCMs (adjusted OR [aOR] 1.030, 95% confidence interval [CI] 0.843-1.257). Compared to the prescription of other propulsives in the first trimester, the prescription of domperidone in the first trimester was not associated with an increased risk of overall MCMs (aOR 0.724, 95% CI 0.363-1.447). CONCLUSIONS: The first-trimester prescription of propulsives, including domperidone, was not associated with an increased risk of overall MCMs.

Maternal Baseline Characteristics and Perinatal Outcomes: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study was launched in 2013 to evaluate the complex interactions of genetic and environmental factors in multifactorial diseases. The present study describes the maternal baseline profile and perinatal data of participating mothers and infants. METHODS: Expectant mothers living in Miyagi Prefecture were recruited from obstetric facilities or affiliated centers between 2013 and 2017. Three sets of self-administered questionnaires were collected, and the medical records were reviewed to obtain precise information about each antenatal visit and each delivery. Biospecimens, including blood, urine, umbilical cord blood, and breast milk, were collected for the study biobank. The baseline maternal sociodemographic characteristics, results of screening tests, and obstetric outcomes were analyzed according to the maternal age group. RESULTS: A total of 23,406 pregnancies involving 23,730 fetuses resulted in 23,143 live births. Younger maternal participants had a tendency toward a higher incidence of threatened abortion and threatened premature labor, while older age groups exhibited a significantly higher rate of low lying placenta, placenta previa, gestational diabetes, and hypertensive disorders of pregnancy. CONCLUSIONS: The present study clearly shows the distribution of maternal baseline characteristics and the range of perinatal outcomes according to maternal age group. This cohort study can provide strategic information for creating breakthroughs in the pathophysiology of perinatal, developmental, and noncommunicable diseases by collaborative data visiting or sharing.

Association of maternal psychological distress and the use of childcare facilities with children's behavioral problems: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: Childcare facilities are a factor that lowers the established association of mother's postnatal psychiatric symptoms with children's behavioral problems. However, no studies have considered the prenatal psychiatric symptoms yet. This study examined whether the use of childcare facilities moderates the association of maternal psychological distress in early pregnancy and at two years postpartum with behavioral problems in children aged four years. METHODS: The present study was based on the data from 23,130 mother-child pairs participating in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. K6 was used to classify maternal psychological distress in early pregnancy and at two years postpartum into four categories: none in both prenatal and postnatal periods (none), only the prenatal period (prenatal only); only the postnatal period (postnatal only); both prenatal and postnatal periods (both). The children's behavioral problems were assessed using the Child Behavior Checklist for Ages 1½-5 (CBCL) aged four years. The clinical range of the externalizing, internalizing, and total problem scales of the CBCL was defined as having behavioral problems. To examine whether availing childcare facilities moderates the association between maternal psychological distress and children's behavioral problems, we conducted a stratified analysis based on the use of childcare facilities or not, at two years of age. The interaction term between maternal psychological distress and use of childcare facilities was included as a covariate in the multivariate logistic regression analysis to confirm the p-value for the interaction. RESULTS: The prevalence of the clinical ranges of externalizing problems, internalizing problems, and clinical range of total problems were 13.7%, 15.4%, and 5.8%, respectively. The association of maternal psychological distress with a high risk of children's behavioral problems was significant; however, the association between prenatal only psychological distress and externalizing problems in the group that did not use childcare facilities was not significant. Interactions between the use of childcare facilities and maternal psychological distress on behavioral problems in children were not significant. CONCLUSIONS: Use of childcare facilities did not moderate the association of maternal psychological distress in early pregnancy and at two years postpartum with behavioral problems in children aged four years.

Skipping breakfast during pregnancy and hypertensive disorders of pregnancy in Japanese women: the Tohoku medical megabank project birth and three-generation cohort study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) adversely affect the prognosis of mother and child, and the prognosis depends on the subtype of HDP. Skipping breakfast may be associated with increased blood pressure due to disruption of the circadian clock, but the association with the development of HDP has not been studied. The purpose of this study was to examine the association between skipping breakfast and the development of HDP and HDP subtypes in Japanese pregnant women. METHODS: Of the pregnant women who participated in the Tohoku Medical Megabank Project Three-Generation Cohort Study, 18,839 who answered the required questions were included in the analysis. This study had a cross-sectional design. The breakfast intake frequency from pre-pregnancy to early pregnancy was classified into four groups: daily, 5-6 times per week, 3-4 times per week, and 0-2 times per week. HDP was classified into gestational hypertension (GH), chronic hypertension (CH), preeclampsia (PE), and severe preeclampsia (SuPE). Multiple logistic regression analysis and multinomial logistic analysis were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for breakfast intake frequency and development of HDP or HDP subtypes. We performed a stratified analysis based on energy intake. RESULTS: Of the participants, 74.3% consumed breakfast daily, and 11.1% developed HDP. Women who consumed breakfast 0-2 times per week had a higher risk of HDP (OR: 1.33, 95% CI: 1.14-1.56), CH (OR: 1.63, 95% CI: 1.21-2.19), and PE (OR: 1.68, 95% CI: 1.27-2.21) than those who consumed breakfast daily. No association was found between skipping breakfast and the risk of developing GH (OR: 1.26, 95% CI: 0.99-1.61) and SuPE (OR: 0.91, 95% CI: 0.55-1.49). Stratified analysis showed that the risk of developing HDP due to skipping breakfast was highest in the group with the highest daily energy intake. CONCLUSIONS: Skipping breakfast during pre-to early pregnancy is associated with the development of HDP. Further longitudinal studies are required to clarify the causal association between skipping breakfast and HDP.