Three-Generation Cohort Study Research Articles

Prospective associations of screen time at age 2 with specific behavioral subscales at age 3: a cohort study.

We aim to discover which, if any, of the subscales of internalizing and externalizing behavioral problems at age 3 are still associated with screen time (ST) at age 2 after adjusting for behavioral problems scores at age 2. This study was conducted under the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Information was gathered prospectively, with 7207 mother-child pairs included in the analysis. Children's ST was categorized in hours a day at age 2 (<1, 1-<2, 2-<4, ≥4). We assessed children's behavioral problems using the Child Behavior Checklist for Ages 1½-5 (CBCL) at ages 2 and 3. 'Having behavioral problems' was defined by them being within a clinical range for internalizing behaviors (withdrawn, somatic complaints, anxious/depressed and emotionally reactive) and externalizing behaviors (attention problems and aggressive behaviors) at age 3. Continuous scores on each of the behavioral problem scales at age 2 were used as covariates. Greater ST for children at age 2 was associated with specific subscales for emotionally reactive and aggressive behaviors at age 3. This study found that ST is prospectively associated with some behavioral scales but not others.

Combination of taking neuropsychiatric medications and psychological distress in pregnant women, with behavioral problems in children at 2 years of age: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

To examine the association of the combination of taking neuropsychiatric medications from the onset of pregnancy to mid-pregnancy and maternal psychological distress at mid-pregnancy, with children's behavioral problems. Neuropsychiatric medication use from the onset of pregnancy to mid-pregnancy was defined by the self-reported name of the neuropsychiatric medication in the questionnaire in early and mid-pregnancy. Maternal psychological distress was defined by the Kessler Psychological Distress Scale (K6) ≥13 on the questionnaire in mid-pregnancy. We classified the participants into four categories based on the combination of taking neuropsychiatric medications and psychological distress: "None," "Medications only," "K6 ≥ 13 only," and "Both." Children's behavioral problems were assessed using the Child Behavior Checklist for Ages 1½-5 (CBCL) at 2 years of age. The clinical ranges of the internalizing and externalizing scales of the CBCL were defined as behavioral problems. We conducted a multivariable logistic regression analysis to examine the associations between the four categories of maternal exposure and children's behavioral problems. Compared with the "None" category (n = 9873), the "K6 ≥ 13 only" category (n = 308) was statistically significantly associated with internalizing and externalizing problems. In contrast, the "Medications only" (n = 93) and "Both" (n = 22) categories were not statistically significantly associated with internalizing and externalizing problems, although the point estimates of the odds ratio in the "Both" category were relatively high (1.58 for the internalizing problem and 2.50 for the externalizing problem). The category of mothers taking neuropsychiatric medications and having no psychological distress during pregnancy was not associated with children's behavioral problems in the present population.

The effect of gestational diabetes mellitus on postnatal mother-infant bonding: Findings from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study

PurposeGestational diabetes mellitus (GDM) is a common complication of pregnancy and is associated with considerable psychological burden for women. In qualitative research, women with GDM describe increased awareness about their bonding with their infant, potentially resulting from the highly medicalised nature of the condition. The primary aim is to examine quantitatively whether GDM was associated with lower mother-infant bonding in the postnatal period. MethodsData were analysed from 10,419 women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017 in Japan. GDM status was collected from hospital records and measured using the oral glucose tolerance test. Mother-infant bonding was assessed using the Japanese version of Mother-to-Infant Bonding Scale (MIBS-J) at one-month postpartum, higher scores representing lower bonding. Data were analysed in SAS using multiple regression adjusting for relevant confounders. ResultsGDM did not appear to be associated with worse mother-infant bonding scores at one-month postpartum. There was a non-significant unadjusted trend in the mean mother-infant bonding scores and the proportion with bonding disorder (n = 4 (4.12%) versus n = 969 (9.39%)) in the GDM versus non GDM group respectively, indicating higher self-reported bonding in the GDM group, and this remained not statistically significant in the adjusted analyses. ConclusionsWe observed the reverse of our hypothesis, that there was a trend for women with GDM to self-report higher bonding compared to non-GDM women. There is need to replicate this finding in cohorts specifically designed to measure GDM-specific psychological distress.

CHILD BLOOD PRESSURE AND RENAL FUNCTION DIFFERENCES BY SUBTYPES OF MATERNAL HYPERTENSIVE DISORDERS OF PREGNANCY

Objective: The objective of this study is to investigate the difference child blood pressure (BP) and renal function by subtypes of maternal hypertensive disorders of pregnancy (HDP). Design and method: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study is a prospective birth cohort study including pregnant women, children and their families. Using available data of children at 8 years old from December 2022 to March 2023, we analyzed the association between maternal HDP subtypes by extracted from medical record and systolic and diastolic BPs and estimated glomerular filtration rate (eGFR) collected at research facilities. Analysis of covariance adjusted for their sex, body mass index, small for gestational age were performed. Maternal grandparental hypertension and paternal hypertension for child BP, and maternal grandparental chronic nephritis and parental chronic nephritis were additionally adjusted. Results: A total of 684 children (357 male and 327 female) at 8 years old was included in this study. Among them, 56 children had mothers with HDP (24 gestational hypertension, 11 preeclampsia, 9 superimposed preeclampsia, 12 chronic hypertension). The mean (standard deviation) systolic/diastolic BPs and eGFR were 106.90 (10.51)/64.68 (8.77) mmHg and 110.91 (16.23) mL/min/1.73m2, respectively. Estimated systolic/diastolic BPs (standard error) of children with normotensive mothers, those with gestational hypertension mothers, those with preeclampsia mothers, those with superimposed preeclampsia mothers, and those with chronic hypertension mothers were: 106.44 (0.76)/64.58 (0.64) mmHg, 108.38 (2.11)/64.80 (1.78) mmHg, 107.59 (3.10)/64.70 (2.61) mmHg, 108.38 (3.38)/63.64 (2.85) mmHg, 112.19 (2.98)/64.58 (2.51) mmHg, respectively. Upon classification of HDP subtypes, estimated eGFR were as follows: 110.11 (1.23) mL/min/1.73m2, 111.61 (3.40) mL/min/1.73m2, 118.20 (4.99) mL/min/1.73m2, 105.13 (5.43) mL/min/1.73m2, and 119.42 (4.82) mL/min/1.73m2, respectively. The p-values were above 0.05 for the systolic and diastolic BPs and eGFR among HDP subtypes. Conclusions: The follow-up measurement is ongoing until 2026; therefore, further study with updated dataset is necessary and will be provided.

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

PurposeTo 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).MethodsQuestionnaires 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.ResultsIn 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.ConclusionWe 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.

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

BackgroundNausea 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.MethodsWe 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.ResultsGWAS 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.ConclusionsNVP-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.

Development of phenotyping algorithms for hypertensive disorders of pregnancy (HDP) and their application in more than 22,000 pregnant women

Recently, many phenotyping algorithms for high-throughput cohort identification have been developed. Prospective genome cohort studies are critical resources for precision medicine, but there are many hurdles in the precise cohort identification. Consequently, it is important to develop phenotyping algorithms for cohort data collection. Hypertensive disorders of pregnancy (HDP) is a leading cause of maternal morbidity and mortality. In this study, we developed, applied, and validated rule-based phenotyping algorithms of HDP. Two phenotyping algorithms, algorithms 1 and 2, were developed according to American and Japanese guidelines, and applied into 22,452 pregnant women in the Birth and Three-Generation Cohort Study of the Tohoku Medical Megabank project. To precise cohort identification, we analyzed both structured data (e.g., laboratory and physiological tests) and unstructured clinical notes. The identified subtypes of HDP were validated against reference standards. Algorithms 1 and 2 identified 7.93% and 8.08% of the subjects as having HDP, respectively, along with their HDP subtypes. Our algorithms were high performing with high positive predictive values (0.96 and 0.90 for algorithms 1 and 2, respectively). Overcoming the hurdle of precise cohort identification from large-scale cohort data collection, we achieved both developed and implemented phenotyping algorithms, and precisely identified HDP patients and their subtypes from large-scale cohort data collection.

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

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. 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. 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. Exposure to HDP during fetal life is associated with offspring developmental delay. This association is partly mediated by neonatal outcomes.

Risk of Major Congenital Malformations Associated with the Use of Japanese Traditional (Kampo) Medicine Containing Ephedra During the First Trimester of Pregnancy.

Japanese traditional (Kampo) medicines containing ephedra may be used to treat colds during pregnancy. There are reports that ephedrine, a component of ephedra, has a risk of teratogenicity; however, the evidence remains equivocal. This study aimed to evaluate the risk of major congenital malformations (MCMs) associated with exposure to Kampo medicines containing ephedra during the first trimester of pregnancy using the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). To 23,730 mother-infant pairs who participated in the TMM BirThree Cohort Study from July 2013 to March 2017, questionnaires in early and middle pregnancy were distributed approximately at weeks 12 and 26 of pregnancy, respectively. Infants' risk of MCMs in women who used Kampo medicines containing ephedra or acetaminophen during the first trimester was assessed, and the odds ratios (ORs) were estimated with unadjusted and adjusted analyses. Among 20,879 women, acetaminophen and Kampo medicines containing ephedra were used in 665 (3.19%) and 376 (1.80%) women, respectively, in the first trimester. Among the infants born to the mothers who used acetaminophen or Kampo medicine containing ephedra during the first trimester, 11 (1.65%) and 8 (2.13%), respectively, had overall MCMs. OR of overall MCMs was higher in women who used Kampo medicines containing ephedra than in those who used acetaminophen in the first trimester (adjusted OR, 1.45; 95% confidence interval (CIs), 0.57-3.71); however, the difference was not statistically significant. In this study, there was no statistically significant association between the use of Kampo medicines containing ephedra during the first trimester of pregnancy and the risk of MCMs. Although some point estimates of ORs exceeded 1.00, the absolute magnitude of any increased risks would be low.

How Healthy Lifestyle Habits Have Interacted with SARS-CoV-2 Infection and the Effectiveness of COVID-19 Vaccinations: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

To examine the interaction between lifestyle habits and the COVID-19 vaccinations for preventing SARS-CoV-2 infection, we analyzed 11,016 adult participants registered in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Lifestyle variables, including regular exercise, smoking and drinking habits, sleep status, body mass index, and daily breakfast consumption, were assessed from 2014 to 2019 using baseline questionnaires. Information on SARS-CoV-2 infection and the COVID-19 vaccination were also collected from March 2020 to May 2023. The study period was divided into two in the postvaccination phase: the first period (the beginning of the vaccination program) and the second period (the fourth shot onward). In the Cox proportional-hazards model analysis, the five-time vaccinations group showed a significantly lower risk of SARS-CoV-2 infection adjusted age, sex, underlying health condition, and lifestyle variables (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.76-0.86). Logistic regression analysis revealed that a higher number of vaccinations was significantly associated with a low risk of SARS-CoV-2 infection regardless of lifestyle habits (three times in the first period: odds ratio [OR] 0.19, 95% CI 0.15-0.24; five times in the second period: OR 0.07, 95% CI 0.05-0.11 vs. none). Regarding lifestyle habits, the risk reduction in those who had sleep satisfaction (OR 0.12, 95% CI 0.08-0.18) was slightly larger than in those who had sleep dissatisfaction (OR 0.23, 95% CI 0.17-0.32) in the group with the highest number of vaccinations in the first period; however, this interaction was hardly confirmed in the second period when the number of infected cases significantly increased. Our findings indicated that a higher number of COVID-19 vaccinations was associated with reduced risk of SARS-CoV-2 infection; otherwise, we may need to understand the advantages and limitations of a healthy lifestyle for preventing infection depending on the situation with vaccinations and infection spreading.

Effect of Nicotinamide Mononucleotide Concentration in Human Milk on Neurodevelopmental Outcome: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

(1) Background: Breast milk is the only source of nutrition for breastfed infants, but few studies have examined the relationship between breast milk micronutrients and infant neurodevelopmental outcome in exclusively breastfed infants. The aim of this study was to characterize the association between nicotinamide adenine dinucleotide (NAD)-related compounds in the breast milk of Japanese subjects and infant neurodevelopmental outcome. (2) Methods: A total of 150 mother-child pairs were randomly selected from the three-generation cohort of the Tohoku Medical Megabank in Japan. Infants were exclusively breastfed for up to 6 months. Breast milk was collected at 1 month postpartum, and the quantity of NAD-related substances in the breast milk was quantified. The mothers also completed developmental questionnaires at 6, 12, and 24 months. The relationship between the concentration of NAD-related substances in breast milk and developmental indicators was evaluated via ordinal logistic regression analysis. (3) Results: Nicotinamide mononucleotide (NMN) was quantified as the major NAD precursor in breast milk. The median amount of NMN in the breast milk was 9.2 μM. The NMN concentration in breast milk was the only NAD-related substance in breast milk that showed a significant positive correlation with neurodevelopmental outcome in infants at 24 months. (4) Conclusions: The results suggest that NMN in human milk may be an important nutrient for early childhood development.

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

BackgroundAlthough 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.MethodsOf 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.ResultsThe 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.ConclusionFor 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.

Establishment of the early prediction models of low-birth-weight reveals influential genetic and environmental factors: a prospective cohort study

BackgroundLow birth weight (LBW) is a leading cause of neonatal morbidity and mortality, and increases various disease risks across life stages. Prediction models of LBW have been developed before, but have limitations including small sample sizes, absence of genetic factors and no stratification of neonate into preterm and term birth groups. In this study, we challenged the development of early prediction models of LBW based on environmental and genetic factors in preterm and term birth groups, and clarified influential variables for LBW prediction.MethodsWe selected 22,711 neonates, their 21,581 mothers and 8,593 fathers from the Tohoku Medical Megabank Project Birth and Three-Generation cohort study. To establish early prediction models of LBW for preterm birth and term birth groups, we trained AI-based models using genetic and environmental factors of lifestyles. We then clarified influential environmental and genetic factors for predicting LBW in the term and preterm groups.ResultsWe identified 2,327 (10.22%) LBW neonates consisting of 1,077 preterm births and 1,248 term births. Our early prediction models archived the area under curve 0.96 and 0.95 for term LBW and preterm LBW models, respectively. We revealed that environmental factors regarding eating habits and genetic features related to fetal growth were influential for predicting LBW in the term LBW model. On the other hand, we identified that genomic features related to toll-like receptor regulations and infection reactions are influential genetic factors for prediction in the preterm LBW model.ConclusionsWe developed precise early prediction models of LBW based on lifestyle factors in the term birth group and genetic factors in the preterm birth group. Because of its accuracy and generalisability, our prediction model could contribute to risk assessment of LBW in the early stage of pregnancy and control LBW risk in the term birth group. Our prediction model could also contribute to precise prediction of LBW based on genetic factors in the preterm birth group. We then identified parental genetic and maternal environmental factors during pregnancy influencing LBW prediction, which are major targets for understanding the LBW to address serious burdens on newborns' health throughout life.

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

Whether some domains of child development are specifically associated with screen time and whether the association continues with age remain unknown. 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. 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. Four categories of screen time exposure were identified for children aged 1 year (<1, 1 to <2, 2 to <4, or ≥4 h/d). 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. 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. 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.

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. 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 3.5years of age. Multiple logistic regression analyses were conducted to examine the associations between maternal social isolation and developmental delays. 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 3.5years 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 3.5years of age. Maternal social isolation in both the prenatal and postnatal periods was associated with an increased risk of developmental delays in early childhood.

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

BackgroundLow 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.MethodsOf 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.ResultsThe 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 (β = -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 (β = -41.5, 95% CI: -63.3, -19.6).ConclusionsLess frequent breakfast intake before and mid-pregnancy was associated with lower infant birth weight.

Infertility Treatment and Hypertension in Pregnancy: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study

Infertility treatment is a possible factor in hypertensive disorders of pregnancy (HDP). Identifying the characteristics of pregnant women who have undergone infertility treatment and have a potential risk for HDP is valuable for its prevention and treatment. Using data from 12,456 pregnant Japanese women from the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study, the association between infertility treatment and HDP was analyzed. A multiple logistic regression model showed an association between infertility treatment and HDP (odds ratio, 1.34; 95% confidence interval, 1.05–1.72). In vitro fertilization/intracytoplasmic sperm injection were also associated with HDP. Moreover, these associations were observed even among women who were not overweight and did not smoke. The application of infertility treatment should be carefully considered, even among women with low modifiable risk factors.

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 4years 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 4years of age.

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.

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. 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 ≥ 1day/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. 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. Associations of education and income with SHS exposure imply that educational interventions and financial incentives are needed for pregnant women and their household smokers.

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

The present study analyzed the relation of disaster exposure prior to pregnancy with maternal characteristics and obstetric outcomes. 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. 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. 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.