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.

The association between blood pressure control in women during pregnancy and adverse perinatal outcomes: the TMM BirThree Cohort Study.

Blood pressure (BP) control in pregnancy is essential to prevent adverse outcomes. However, BP levels for hypertension treatment are inconsistent among various guidelines. This study investigated the association between BP control and adverse perinatal outcomes. A total of 18,155 mother-offspring pairs were classified into four groups according to BP after 20 gestational weeks: normal BP (<140/90 mmHg without antihypertensive drugs), high BP (≥140/90 mmHg without antihypertensive drugs), controlled BP (<140/90 mmHg with antihypertensive drugs), and uncontrolled BP (≥140/90 mmHg with antihypertensive drugs). The prevalence of small for gestational age was 1,087/17,476 offspring in normal BP, 78/604 in high BP, 5/42 in controlled BP, and 7/33 in uncontrolled BP. Compared to normal BP, adjusted odds ratios (ORs) (95% confidence intervals (CIs)) were 1.76 (1.32-2.35) for high BP, 2.08 (0.79-5.50) for controlled BP, and 2.34 (0.94-5.85) for uncontrolled BP (multiple logistic regression analysis). Similarly, the adjusted ORs (95% CIs) were 1.80 (1.35-2.41), 3.42 (1.35-8.63), and 5.10 (1.93-13.45) for high, controlled, and uncontrolled BPs for low birth weight, respectively; 1.99 (1.48-2.68), 2.70 (1.12-6.50), and 6.53 (3.09-13.82) for high, controlled, and uncontrolled BPs for preterm birth, respectively; 1.64 (1.19-2.24), 2.17 (0.88-5.38), and 2.12 (0.80-5.65) for high, controlled, and uncontrolled BPs for admission to the Neonatal Intensive Care Unit or Growing Care Unit, respectively; and 1.17 (0.70-1.95), 2.23 (0.65-7.68), and 0.91 (0.20-4.16) for high, controlled, and uncontrolled BPs for 1-min Apgar score < 7, respectively. BP ≥ 140/90 mmHg might be taken care for preventing various adverse perinatal outcomes.

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.

Screen Time at Age 1 Year and Communication and Problem-Solving Developmental Delay at 2 and 4 Years.

Importance: Whether some domains of child development are specifically associated with screen time and whether the association continues with age remain unknown. Objective: To examine the association between screen time exposure among children aged 1 year and 5 domains of developmental delay (communication, gross motor, fine motor, problem-solving, and personal and social skills) at age 2 and 4 years. Design, Participants, and Setting: This cohort study was conducted under the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Pregnant women at 50 obstetric clinics and hospitals in the Miyagi and Iwate prefectures in Japan were recruited into the study between July 2013 and March 2017. The information was collected prospectively, and 7097 mother-child pairs were included in the analysis. Data analysis was performed on March 20, 2023. Exposure: Four categories of screen time exposure were identified for children aged 1 year (<1, 1 to <2, 2 to <4, or ≥4 h/d). Main Outcomes and Measures: Developmental delays in the 5 domains for children aged 2 and 4 years were assessed using the Japanese version of the Ages & Stages Questionnaires, Third Edition. Each domain ranged from 0 to 60 points. Developmental delay was defined if the total score for each domain was less than 2 SDs from its mean score. Results: Of the 7097 children in this study, 3674 were boys (51.8%) and 3423 were girls (48.2%). With regard to screen time exposure per day, 3440 children (48.5%) had less than 1 hour, 2095 (29.5%) had 1 to less than 2 hours, 1272 (17.9%) had 2 to less than 4 hours, and 290 (4.1%) had 4 or more hours. Children's screen time was associated with a higher risk of developmental delay at age 2 years in the communication (odds ratio [OR], 1.61 [95% CI, 1.23-2.10] for 1 to <2 h/d; 2.04 [1.52-2.74] for 2 to <4 h/d; 4.78 [3.24-7.06] for ≥4 vs <1 h/d), fine motor (1.74 [1.09-2.79] for ≥4 vs <1 h/d), problem-solving (1.40 [1.02-1.92] for 2 to <4 h/d; 2.67 [1.72-4.14] for ≥4 vs <1 h/d), and personal and social skills (2.10 [1.39-3.18] for ≥4 vs <1 h/d) domains. Regarding risk of developmental delay at age 4 years, associations were identified in the communication (OR, 1.64 [95% CI, 1.20-2.25] for 2 to <4 h/d; 2.68 [1.68-4.27] for ≥4 vs <1 h/d) and problem-solving (1.91 [1.17-3.14] for ≥4 vs <1 h/d) domains. Conclusions and Relevance: In this study, greater screen time for children aged 1 year was associated with developmental delays in communication and problem-solving at ages 2 and 4 years. These findings suggest that domains of developmental delay should be considered separately in future discussions on screen time and child development.

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 being Overweight in Young Childhood and during School Age and Puberty.

To examine whether body type at birth, body weight, and obesity in early childhood are associated with overweight/obesity during school age and puberty. Data from maternal and child health handbooks, baby health checkup information, and school physical examination information of participants at birth and three-generation cohort studies were linked. Association between body type and body weight at different time intervals (at birth and at 1.5, 3.5, 6, 11, and 14 years of age) were comprehensively analyzed using a multivariate regression model adjusted for gender, maternal age at childbirth, maternal parity, and maternal body mass index, and drinking and smoking statuses at pregnancy confirmation. Children who are overweight in young childhood had a greater risk of being overweight. Particularly, overweight at one year of age during checkup was associated with overweight at 3.5 years (adjusted odds ratio (aOR), 13.42; 95% confidence interval (CI), 4.46-45.42), 6 years (aOR, 6.94; 95% CI, 1.64-33.46), and 11 years (aOR, 5.22; 95% CI, 1.25-24.79) of age. Therefore, being overweight in young childhood could increase the risk of being overweight and obese during school age and puberty. Early intervention in young childhood may be warranted to prevent obesity during school age and puberty.

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.

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 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.

Maternal postnatal bonding disorder and emotional/behavioral problems in preschool children: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: Although there is evidence that maternal perinatal mental disorders are associated with emotional/behavioral problems in children, the long-term impacts of postnatal bonding disorder remain unclear. We aimed to examine the associations between maternal postnatal bonding disorder and emotional/behavioral problems in preschool children. METHODS: We analyzed data from 7220 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 ≥5 at 1 month after delivery. The Child Behavior Checklist for Ages 1½-5 was used to assess emotional/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 of postnatal bonding disorder with emotional/behavioral, internalizing, and externalizing problems after adjustment for age, education, income, parity, prenatal psychological distress, postnatal depressive symptoms, child's sex, preterm birth, and birth defects. RESULTS: The prevalence of postnatal bonding disorder was 14.8 %. Postnatal bonding disorder was associated with an increased risk of emotional/behavioral problems in children: the odds ratio (OR) was 2.06 (95 % confidence interval [CI], 1.72-2.46). Postnatal bonding disorder was also associated with increased risks of internalizing problems and externalizing problems in children: the ORs were 1.69 (95 % CI, 1.42-2.02) and 1.90 (95 % CI, 1.59-2.26), respectively. LIMITATIONS: Bonding and problems were self-reported. CONCLUSIONS: Bonding disorder at 1 month after delivery was associated with an increased risk of emotional/behavioral problems in children at 4 years of age.

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.

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.

Dietary calcium intake was related to the onset of pre-eclampsia: The TMM BirThree Cohort Study.

This study aimed to explore the relationship between dietary electrolyte intake and the prevalence of hypertensive disorders of pregnancy (HDP) subtypes. Our analysis included 19 914 pregnant women from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. A food frequency questionnaire was used to estimate dietary calcium, potassium, sodium, and magnesium intakes. HDP was determined based on the medical records during regular antenatal care. Logistic regression analysis assessed the relationship between dietary electrolytes intake quintiles, and HDP subtypes with adjustment for basic characteristics. Dietary electrolyte intakes were applied for the prediction model. Of the cohort, 547 participants delivered with pre-eclampsia (PE), 278 with superimposed PE (SP), and 896 with gestational hypertension (GH). PE was associated with low crude calcium intake (odds ratio of the first quintile [<251 mg/day] to the fifth quintile [>623 mg/day] and 95% confidence interval, 1.31 [1.00-1.70]) and P for trend was .02. SP was not associated with any nutritional intake; however, the combined outcome of PE and SP was related to low crude calcium and potassium and energy-adjusted calcium, potassium, and magnesium intakes (P for trend, .01, .048, .02, .04, and .02, respectively). The same tendency was observed for GH. A prediction model that included crude calcium and potassium intakes performed better than a model without them. In conclusion, low dietary calcium, potassium, and magnesium were associated with higher HDP subtypes prevalence. The prediction model implied that crude calcium and potassium intakes might play a critical role in PE and SP pathogenesis.

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.

Traumatic experiences of the Great East Japan Earthquake and postpartum depressive symptoms: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

BACKGROUND: Natural disasters can have serious mental health consequences. We aimed to examine the long-term effects of the 2011 Great East Japan Earthquake (GEJE) on postpartum depressive symptoms (PDS). METHODS: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study recruited pregnant women in Miyagi Prefecture from 2013 to 2016. Data from 11,403 participants were used in this study. Women were asked about their traumatic experiences of the GEJE with questions addressing threat, witness, and loss. PDS were defined as Edinburgh Postnatal Depression Scale score ≥9 at 1 month after delivery. Multiple logistic regression analyses were conducted to examine the associations of different traumatic experiences of the GEJE and number of traumatic experiences with PDS, after adjustment for age, parity, feelings toward pregnancy, education, income, social isolation, house damage caused by the GEJE, and survey year. RESULTS: About two-fifths of women had at least one traumatic experience of the GEJE. The prevalence of PDS at 1 month after delivery was 13.3 %. Life-threatening experience and witnessing another person's actual or threatened death were associated with PDS: the odds ratios (ORs) were 1.40 (95 % confidence interval [CI], 1.24-1.59) and 1.28 (95 % CI, 1.08-1.53), respectively. Loss of close person was not associated with PDS: the OR was 1.13 (95 % CI, 0.99-1.30). Larger number of traumatic experiences of the GEJE was associated with increased risk of PDS (p for trend <0.001). LIMITATIONS: PDS was self-reported. CONCLUSIONS: Traumatic experiences of the GEJE prior to pregnancy were associated with increased risks of PDS.

Plasma metabolic disturbances during pregnancy and postpartum in women with depression.

Examining plasma metabolic profiling during pregnancy and postpartum could help clinicians understand the risk factors for postpartum depression (PPD) development. This analysis targeted paired plasma metabolites in mid-late gestational and 1 month postpartum periods in women with (n = 209) or without (n = 222) PPD. Gas chromatogram-mass spectrometry was used to analyze plasma metabolites at these two time points. Among the 170 objected plasma metabolites, principal component analysis distinguished pregnancy and postpartum metabolites but failed to discriminate women with and without PPD. Compared to women without PPD, those with PPD exhibited 37 metabolites with disparate changes during pregnancy and the 1-month postpartum period and an enriched citrate cycle. Machine learning and multivariate statistical analysis identified two or three compounds that could be potential biomarkers for PPD prediction during pregnancy. Our findings suggest metabolic disturbances in women with depression and may help to elucidate metabolic processes associated with PPD development.

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.

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.

Social isolation and insomnia among pregnant women in Japan: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

OBJECTIVES: To estimate the prevalence of insomnia and examine the association between social isolation and insomnia among pregnant women. METHODS: This cross-sectional study was part of the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017. Pregnant women were recruited at obstetric clinics and hospitals in Miyagi Prefecture, Japan. We analyzed 17,586 women who completed the questionnaires and were allowed to transcribe medical records. Insomnia was defined as the Athens Insomnia Scale score of ≥6. The Lubben Social Network Scale-abbreviated version was used to assess social isolation (defined as scores <12), and its subscales were used to assess marginal family ties and marginal friendship ties. Multiple logistic regression analyses were conducted to examine the association between social isolation and insomnia during pregnancy, adjusting for age, parity, prepregnancy body mass index, feelings toward pregnancy, education, income, work status, morning sickness, and psychological distress. Multiple logistic regression analyses were also conducted for marginal family ties and marginal friendship ties. RESULTS: The prevalence of insomnia in the second trimester was 37.3%. Women who were socially isolated were more likely to have insomnia than women who were socially integrated: the multivariate-adjusted odds ratio (OR) was 1.26 (95% confidence interval [CI], 1.16-1.36). Marginal family ties and marginal friendship ties were also associated with increased risks of insomnia: the multivariate-adjusted ORs were 1.40 (95% CI, 1.25-1.56) and 1.15 (95% CI, 1.07-1.24), respectively. CONCLUSIONS: Social isolation from family and friends was associated with increased risks of insomnia among pregnant women.