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.

Progress report of the Tohoku Medical Megabank Community-Based Cohort Study: Study profile of the repeated center-based survey during second period in Miyagi Prefecture.

BACKGROUND: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period (2nd period survey) of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey. METHODS: The 2nd period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the 2nd period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The 2nd period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). RESULTS: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the 2nd period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the 2nd period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. CONCLUSIONS: The 2nd period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

Relationships of Fat Mass Index and Fat-Free Mass Index with Low-Density Lipoprotein Cholesterol Levels in the Tohoku Medical Megabank Community-Based Cohort Study.

AIMS: Although fat mass (FM) and fat-free mass (FFM) have an impact on lipid metabolism, the relationship between different body composition phenotypes and lipid profiles is still unclear. By dividing the FM and FFM by the square of the height, respectively, the f at mass index (FMI) and fat-free mass index (FFMI) can be used to determine the variations in body composition. This study aimed to investigate the relationship of combined FMI and FFMI with low-density lipoprotein cholesterol (LDL-C) levels. METHODS: This cross-sectional study comprised 5,116 men and 13,630 women without cardiovascular disease and without treatment for hypertension, and diabetes. Following sex-specific quartile classification, FMI and FFMI were combined into 16 groups. Elevated LDL-C levels were defined as LDL-C ≥ 140 mg/dL and/or dyslipidemia treatment. Multivariable logistic regression models were used to examine the relationships between combined FMI and FFMI and elevated LDL-C levels. RESULTS: Overall, elevated LDL-C levels were found in 1,538 (30.1%) men and 5,434 (39.9%) women. In all FFMI subgroups, a higher FMI was associated with elevated LDL-C levels. Conversely, FFMI was inversely associated with elevated LDL-C levels in most FMI subgroups. Furthermore, the groups with the highest FMI and lowest FFMI had higher odds ratios for elevated LDL-C levels than those with the lowest FMI and highest FFMI. CONCLUSIONS: Regardless of FFMI, FMI was positively associated with elevated LDL-C levels. Conversely, in the majority of FMI subgroups, FFMI was inversely associated with elevated LDL-C levels.

Relationship between traditional risk factors for hypertension and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study.

Risk factors for hypertension have been emphasized in the Japanese Society of Hypertension Guidelines for the Management of Hypertension. However, large-scale studies on the association of smoking, potassium excretion, and gamma-glutamyl transferase level with BP in the Japanese population are limited. We conducted a cross-sectional study to examine the association between hypertension risk factors and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study (23,446 men and 38,921 women aged ≥20 years). A model adjusted for age, body mass index, smoking status, drinking status, estimated daily salt intake, potassium excretion, (or urinary sodium-to-potassium ratio), gamma-glutamyl transferase, physical activity, education level, status of damage to homes during the Great East Japan Earthquake, and residential areas was used. The average age and systolic blood pressure were 62.5 (10.3) years for men and 59.6 (11.3) years for women, 128.9 (16.7) mmHg for men and 124.7 (17.5) mmHg for women, respectively. Body mass index estimated daily salt intake, urinary sodium-to-potassium ratio and gamma-glutamyl transferase levels were positively associated with systolic blood pressure. Compared with never-drinkers, current drinkers who consumed 23-45 g/day and ≥46.0 g/day had significantly increased systolic blood pressure. Conversely, current smokers (1-10 cigarettes/day and 11-20 cigarettes/day) were inversely associated with systolic blood pressure compared to never-smokers. Overall, systolic blood pressure was associated with gamma-glutamyl transferase and hypertension risk factors, including body mass index, alcohol consumption, estimated daily salt intake, urinary sodium-to-potassium ratio, and potassium excretion. Our findings support the notion that lifestyle modifications should be attempted to prevent hypertension.

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.

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.

Maternal birth weight as an indicator of early-onset and late-onset hypertensive disorders of pregnancy: The Japan Environment and Children's study.

OBJECTIVES: This study aimed to investigate the association between maternal birth weight (MBW) and hypertensive disorders of pregnancy (HDP) according to the gestational age when HDP develops. STUDY DESIGN: A total of 77,345 subjects were included in this prospective birth cohort study. The association between MBW and HDP was investigated by a multinomial logistic regression model. MAIN OUTCOME MEASURES: Early-onset HDP (EO-HDP), preterm late-onset HDP (preterm LO-HDP), and term late-onset HDP (term LO-HDP). RESULTS: Lower MBW was associated with higher odds of preterm and term LO-HDP (p-values for trend < 0.0001 and = 0.0005, respectively). A linear association between MBW and EO-HDP was observed (p-values for trend = 0.0496). The shape of the association between MBW and preterm LO-HDP was a combination of the associations between MBW with EO-HDP or LO-HDP. The effect size of the association between MBW < 2,500 g and EO-HDP was lower than that of MBW < 2,500 g with preterm or term LO-HDP. The adjusted odds ratios for EO-HDP, preterm LO-HDP, and term LO-HDP in subjects with MBW < 2,500 g were 1.052 (95 % confidence interval [CI]: 0.665-1.664), 1.745 (95 % CI: 1.220-2.496), and 1.496 (95 % CI: 1.154-1.939), respectively. CONCLUSIONS: MBW was associated with HDP, regardless of gestational age when HDP developed. Furthermore, the association of MBW < 2,500 g with preterm or term LO-HDP was stronger than that with EO-HDP.

Timing of Primary Tooth Eruption in Infants Observed by Their Parents.

BACKGROUND: The timing of primary teeth eruption is a visible indicator of infant physical growth other than body weight or height. It also reflects neurological integrity and development as well as nutrition, socioeconomic state, or underlying diseases. Therefore, the timing of primary teeth eruption is one of the major concerns for parents in health checkups for infants and children. However, the detailed developmental timing of teeth eruption differs depending on the survey methodology, country, or generation. We hypothesized that the timing of primary teeth eruption differs between the medical checkup by dentists and the daily records by parents. METHODS: We conducted a questionnaire survey on the date of eruption of primary teeth as an adjunct study among Miyagi Regional Center participants in the Japan Environment and Children's Study (JECS), a large-scale birth cohort study. A total of 1695 responses (3793 participants) were analyzed. RESULTS: The median ages of eruption were 7.1 months (male) and 7.6 months (female) for mandibular primary central incisors, 8.7 months (male) and 9.2 months (female) for maxillary primary central incisors, 10.0 months (male) and 10.3 months (female) for maxillary primary lateral incisors, and 10.4 months (male) and 10.8 months (female) for mandibular primary lateral incisors, which were earlier than the reported timings based on dental check-ups. Comparing the eruption time of preterm and term infants, the eruption time was earlier in preterm infants in the corrected ages. CONCLUSIONS: The eruption timing observed and described by the parents is earlier than that examined by dentists at regular check-ups. In addition to examining the primary teeth eruption of full-term birth children, we also examined that of preterm birth children because of the increasing number of premature births. To the best of our knowledge, this is the first report from a large cohort study to clarify the eruption time of primary teeth monitored by parents.

Influence of Diabetes Family History on the Associations of Combined Genetic and Lifestyle Risks with Diabetes in the Tohoku Medical Megabank Community-Based Cohort Study.

AIM: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations. METHODS: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment. RESULTS: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92-7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73-6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65-3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes. CONCLUSIONS: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.

The risk of withdrawal from hypertension treatment in coastal areas after the Great East Japan Earthquake: the TMM CommCohort Study.

This study aimed to examine whether risk of withdrawal from HTTx was higher in coastal areas that were severely damaged by tsunami than in inland areas. We conducted a cross-sectional study of 9218 participants aged ≥20 years in Miyagi, Japan. The odds ratios (ORs) and confidence interval (CI) for withdrawal from HTTx in coastal and inland groups were compared using multivariate logistic regression analysis, adjusting for potential confounders. In total, 194 of 5860 and 146 of 3358 participants in the inland and coastal groups, respectively, withdrew from HTTx treatment. OR (95%CI) of withdrawal from HTTx in the coastal group was 1.46 (1.14-1.86) compared to the inland group. According to housing damage, ORs (95% CI) in the no damage, partially destroyed, and more than half destroyed coastal groups compared with the no damage inland group were 1.62 (1.04-2.50), 1.69 (1.17-2.45), and 1.08 (0.71-1.65), respectively. In conclusion, the risk of HTTx withdrawal for participants whose homes in coastal areas were relatively less damaged was significantly higher compared with those in inland areas, while the risk of HTTx withdrawal for participants whose homes were more than half destroyed was not. Post-disaster administrative support for disaster victims is considered vital for continuation of their treatment.

Factors associated with postpartum smoking relapse at early postpartum period of Japanese women in the Japan Environmental and Children's Study.

BACKGROUND: Postpartum smoking relapse is a serious public health concern. Previous studies have identified several risk factors for postpartum smoking relapse; however, very little is known about the predictors of early postpartum smoking relapse. This study aimed to determine postpartum smoking relapse status and its associated risk factors at 1 month postpartum among Japanese women. METHODS: Data were obtained from 93,851 mothers with live births in an ongoing birth cohort study, the Japan Environment and Children's Study. Data on smoking status and confounding variables were collected using self-administered questionnaires and medical record transcripts. Self-administered questionnaires were administered during the first trimester, second/third trimester, and 1 month after delivery. A multiple logistic regression analysis was performed. RESULTS: Among the 14,326 mothers who smoked during pregnancy, 10,917 (76.2%) quit smoking during pregnancy. Subsequently, 617 (5.7%) of the mothers who had quit relapsed smoking at 1 month postpartum. Maternal age (≤24, ≥35), maternal education (≤12 years), parity (≥Second), feeding method (Formula milk), partner smoking status during pregnancy (Smoker), number of cigarettes per day before the cessation of smoking (≥11), maternal alcohol consumption at 1-month postpartum (Drinker), postpartum depression (EPDS score ≥9), and spending time at the parents' home after delivery (≥14 days) were associated with smoking relapse. CONCLUSIONS: A certain number of mothers relapsed even 1 month postpartum. Besides mother's alcohol and smoking habit before pregnancy, breastfeeding and partner smoking are important factors in early postpartum smoking relapse in Japan.

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

BACKGROUND: Low 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. METHODS: We 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. RESULTS: We 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. CONCLUSIONS: We 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.

Association of Central Blood Pressure and Carotid Intima Media Thickness with New-Onset Hypertension in People with High Normal Blood Pressure.

AIM: People with high normal blood pressure (BP) have a higher risk of cardiovascular events than those with normal BP; therefore, progression to hypertension (HT) should be prevented. We aimed to assess the HT risk using central BP and carotid intima media thickness (CIMT) in people with high normal BP. METHODS: This prospective cohort study used the Tohoku Medical Megabank Community-Based Project Cohort Study (conducted from 2013 in Miyagi Prefecture in Japan). The participants had a high normal BP, defined as a systolic BP of 120-139 mmHg and diastolic BP ＜90 mmHg using brachial BP measurement during the baseline survey. The outcome was new-onset HT during the secondary survey, conducted four years after the baseline survey. RESULTS: Overall, 4,021 participants with high normal BP during the baseline survey, with an average age of 58.7 years, were included; 1,030 (26%) were diagnosed with new-onset HT during the secondary survey, 3.5±0.7 years after the baseline survey. The multivariable odds ratio (95% confidence interval) for HT in the highest versus lowest quartile of central BP was 1.7 (1.2-2.4, p=0.0030), and that of CIMT was 1.8 (1.4-2.4, p＜0.001). Subgroup analysis according to age (＜60 and ≥ 60 years) and sex revealed that the central BP was influential in groups with younger age and female individuals; CIMT was influential in all groups. CONCLUSIONS: Higher central BP and thicker CIMT at the baseline were correlated with new-onset HT in individuals with high normal BP, independent of brachial systolic BP and other cardiovascular risk factors.

Comprehensive evaluation of machine learning algorithms for predicting sleep-wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability.

Introduction: Perinatal women tend to have difficulties with sleep along with autonomic characteristics. This study aimed to identify a machine learning algorithm capable of achieving high accuracy in predicting sleep-wake conditions and differentiating between the wake conditions before and after sleep during pregnancy based on heart rate variability (HRV). Methods: Nine HRV indicators (features) and sleep-wake conditions of 154 pregnant women were measured for 1 week, from the 23rd to the 32nd weeks of pregnancy. Ten machine learning and three deep learning methods were applied to predict three types of sleep-wake conditions (wake, shallow sleep, and deep sleep). In addition, the prediction of four conditions, in which the wake conditions before and after sleep were differentiated-shallow sleep, deep sleep, and the two types of wake conditions-was also tested. Results and Discussion: In the test for predicting three types of sleep-wake conditions, most of the algorithms, except for Naïve Bayes, showed higher areas under the curve (AUCs; 0.82-0.88) and accuracy (0.78-0.81). The test using four types of sleep-wake conditions with differentiation between the wake conditions before and after sleep also resulted in successful prediction by the gated recurrent unit with the highest AUC (0.86) and accuracy (0.79). Among the nine features, seven made major contributions to predicting sleep-wake conditions. Among the seven features, "the number of interval differences of successive RR intervals greater than 50 ms (NN50)" and "the proportion dividing NN50 by the total number of RR intervals (pNN50)" were useful to predict sleep-wake conditions unique to pregnancy. These findings suggest alterations in the vagal tone system specific to pregnancy.

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 of severe maternal morbidity with bonding impairment and self-harm ideation: A multicenter prospective cohort study.

BACKGROUND: Evidence on the association between severe maternal morbidity (SMM) and mother-infant bonding and self-harm ideation is limited. We aimed to examine these associations and the mediating effect of Neonatal Intensive Care Unit (NICU) admission at one-month postpartum. METHODS: This multicenter, prospective cohort study was conducted in Japan (n = 5398). SMM included preeclampsia, eclampsia, severe postpartum hemorrhage, placental abruption, and a ruptured uterus. Lack of affection (LA) and Anger and Rejection (AR) were assessed using the Mother-Infant Bonding Scale (MIBS), and self-harm ideation was assessed using the 10th item of the Edinburgh Postnatal Depression Scale (EPDS). Linear and logistic regression models were used to examine the association between SMM and MIBS score and self-harm ideation. A structural equation model (SEM) was employed to examine the mediating effect of NICU admission on the association between SMM and mother-infant bonding and postpartum depressive symptoms. RESULTS: Women with SMM had a 0.21 (95 % confidence interval [CI]: 0.03-0.40) point higher MIBS score and a decreasing trend in the risk of self-harm ideation (odds ratio 0.28, 95 % CI: 0.07-1.14) compared to those without SMM. SEM analysis revealed that SMM was associated with MIBS partially through NICU admission. LIMITATIONS: EPDS scores during pregnancy could be an unmeasured confounder. CONCLUSIONS: Women with SMM had higher MIBS scores, particularly on the LA subscale, which was partially mediated by NICU admission. Psychotherapy to support parent-infant relationships is necessary for women with SMM.

Factors associated with new onset of father-to-infant bonding failure from 1 to 6 months postpartum: an adjunct study of the Japan environment and children's study.

PURPOSE: This study aimed to determine the factors associated with new onset father-to-infant (paternal) bonding failure from 1 to 6 months postpartum. METHODS: This was a prospective birth-cohort study. Paternal bonding failure was evaluated using the Japanese version of the Mother-to-Infant Bonding Scale (MIBS-J) at 1 and 6 months postpartum. For cut-off scores, overall bonding failure, MIBS-J total scores ≥ 5; subscale for lack of affection, MIBS-J_LA scores ≥ 3; and subscale for anger/rejection, MIBS-J_AR scores ≥ 3 were used in this study. Multivariate regression analysis was performed to analyze relative variables. RESULTS: We analyzed 872 fathers. The frequency of new-onset overall bonding failure, lack of affection, and anger/rejection was 5.6%, 4.9%, and 6.3%, respectively. For new-onset overall bonding failure, significant associated factors were paternal childcare leave (adjusted odds ratio [AOR] 3.192; 95% confidence interval [CI] 1.203-8.469), paternal new-onset depression symptoms (AOR 3.181; 95% Cl 1.311-7.716), and maternal new-onset overall bonding failure (AOR 4.595; 95% Cl 1.119-18.866). For new-onset lack of affection, significant associated factors were preterm birth (AOR 4.189; 95% Cl 1.473-11.913) and paternal new-onset depression symptoms (AOR 3.290; 95% Cl 1.294-8.362). For new-onset anger and rejection, significant associated factors were paternal childcare leave (AOR 3.142; 95% Cl 1.138-8.676), paternal new-onset depression symptoms (AOR 2.829; 95% Cl 1.133-7.068), and maternal new-onset anger/rejection (AOR 7.064; 95% Cl 2.300-21.700). CONCLUSIONS: The factors associated with new-onset paternal bonding failure from 1 to 6 months postpartum were paternal childcare leave, preterm birth, paternal postpartum depression symptoms, and maternal bonding failure.

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 low levels of anti-inflammatory cytokines during pregnancy and postpartum depression.

AIM: Previous studies based on a relatively limited number of subjects have indicated potential associations between plasma cytokine concentrations in perinatal women and postpartum depression (PPD). This report aimed to examine alterations in cytokine levels during pregnancy and after delivery by measuring nine cytokines in prenatal and postnatal plasma samples in a large cohort. METHODS: A nested, case-control study was conducted using plasma samples from 247 women with PPD (Edinburgh Postnatal Depression Scale: EPDS ≥9) and 243 age-matched control (EPDS ≤2) women from among perinatal women who participated in the Tohoku Medical Megabank three-generation cohort. Concentrations of nine plasma cytokines (IFN-γ, IL-1ß, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, and TNF-α) in plasma collected at the time of enrollment during pregnancy and 1 month after delivery were determined using an immunoassay kit. RESULTS: Cross-sectional comparisons of cytokine levels during pregnancy and after delivery indicated that the PPD group maintained significantly lower plasma IL-4 levels during pregnancy and after delivery than the control group, and that plasma IL-4 levels decreased significantly during pregnancy regardless of PPD status. Plasma IL-10 levels were significantly higher during pregnancy than after delivery only among healthy controls, and plasma IL-10 levels were significantly higher in the control group than in the PPD group. Moreover, IFN-γ, IL-6, IL-12p40, and TNF-α levels were significantly lower during pregnancy compared with after delivery regardless of PPD status. CONCLUSIONS: These results suggest a potential protective effect of the anti-inflammatory cytokines IL-4 and IL-10 during pregnancy against the development of PPD.

Association between poor parent-daughter relationships and the risk of hyperglycemia in pregnancy: a hospital-based prospective cohort study in Japan.

BACKGROUND: Adverse child experiences (ACEs), childhood maltreatment and household dysfunction, are risk factors of hyperglycemia in pregnancy (HIP), including diabetes before pregnancy, gestational diabetes (GDM), and overt diabetes in pregnancy, through increased risk of unhealthy behaviors, obesity, and stress response system dysfunction. While ACEs are often difficult to be assessed in hospital settings, parent-daughter relationship, that is, pregnant women's relationship with their parents can be considered as a measurable maker for ACEs that may be associated with HIP. The purpose of this study is to examine the association between poor parent-daughter relationship and HIP. METHODS: Hospital-based prospective cohort study was conducted in Japan (N = 6,264). Women visiting participating 58 facilities for delivery between April 2019 and March 2020 were included. Parent-daughter relationship was assessed by a questionnaire asking whether participants were satisfied with their relationship with their parents. HIP was diagnosed based on the criteria used in Japan. A multiple logistic regression model was applied to adjust for covariates. RESULTS: Pregnant women who were not very satisfied and not satisfied at all with the relationship with their parents, and HIP were 343 (5.5%), 74 (1.2%), and 274 (4.4%), respectively. Pregnant women who were not very satisfied with their parent-daughter relationship showed a significant positive association with HIP in the crude model (odds ratio (OR): 1.71, 95% confidence interval (CI): 1.11-2.63). When stratified by psychiatric disease history, we found a significant positive association among those without psychiatric disease history (OR: 1.77, 95% CI: 1.11-2.84), but not among those with psychiatric disease history (OR: 0.61, 95% CI: 0.16-2.28). CONCLUSIONS: Poor parent-daughter relationship was associated with the risk of HIP among pregnant women without psychiatric disease history, suggesting that this simple question could be used to estimate the risk of HIP when it was challenging to inquire directly about ACEs. Further research is needed to elucidate the mechanism of the association.