Risk Assessment of Critical Obstetric Bleeding With Low-Molecular-Weight Heparin.

BACKGROUND: Use of unfractionated heparin (UFH) during the peripartum period is considered to be a higher risk of critical obstetric bleeding compared to low-molecular-weight heparin (LMWH). However, the evidence for the safety of using LMWH during the peripartum period is currently lacking. METHODS: This study retrospectively investigated a nationwide medical database to clarify the safety of using LMWH during childbirth. The Japanese Nationwide Diagnosis Procedure Combination database was retrospectively reviewed, and data from women with childbirth between 2018 and 2022 were collected. RESULTS: Among the overall 354,299 women with childbirth, 3,099 were with obstetric disseminated intravascular coagulation (DIC), 484 were with critical obstetric bleeding requiring massive red blood cell (RBC) transfusion ≥4,000 cc, and 38 were with maternal death. Among the overall women, each of the anticoagulants other than LMWH was associated with critical obstetrical bleeding with an adjusted odds ratio (aOR) greater than 1.0, while LMWH was not associated with critical obstetrical bleeding (aOR, 0.54 (95% confidence interval, 0.11-2.71)). This finding did not change in subgroup analyses among those with Cesarean section. Furthermore, UFH was associated with critical bleeding among the 3,099 women with obstetrical DIC (aOR, 3.91 (2.83-5.46)), while LMWH was not (aOR, 0.26 (0.03-1.37)). CONCLUSION: The use of UFH was significantly associated with an increased critical obstetric hemorrhage requiring massive RBC transfusion or total hysterectomy. Meanwhile, the use of LMWH was not associated with increased critical obstetric bleeding. LMWH would be safer than UFH to be used for women during childbirth.

Transcatheter arterial embolization outperforms surgery in reducing blood transfusions for postpartum vulvovaginal hematoma.

BACKGROUND: Postpartum vulvovaginal hematoma is a complication of vaginal delivery that may progress to life-threatening conditions. However, the management of hematomas, including conservative therapy, surgery, and arterial embolization, is yet to be standardized. OBJECTIVE: This study aimed to: (1) evaluate hematoma features that can be treated conservatively, and (2) determine whether surgery or transcatheter arterial embolization is superior in reducing blood transfusion. STUDY DESIGN: This cross-sectional study included postpartum women transferred to Tohoku University Hospital, Japan, between January 2016 and September 2023 for postpartum vulvovaginal hematomas. Notably, all patients except 1 underwent contrast-enhanced computed tomography. The patients were classified into the following groups: (1) the conservative group who received neither surgery nor transcatheter arterial embolization and (2) the therapeutic intervention group who received surgery or transcatheter arterial embolization. The primary analysis included all patients. Variables for the choice of therapeutic intervention, including the shock index, hemoglobin concentration at arrival, hematoma size, and presence of extravasation, were assessed using a modified Poisson regression model. The secondary analysis included patients who received therapeutic intervention (ie, surgery or transcatheter arterial embolization). Variables for estimating the total amount of blood transfusion, including shock index, hemoglobin concentration at arrival, hematoma size, type of intervention, and presence of extravasation, were analyzed using multiple linear regression. RESULTS: Fifty-seven cases were included in this study. Patients underwent conservative treatment (n=19), surgery (n=11), or transcatheter arterial embolization (n=27). In primary analysis, only the presence of extravasation was significantly associated with the choice of therapeutic intervention (adjusted risk ratio [95% confidence interval], 5.30 [1.53-18.37]). In the secondary analysis, the choice of surgery as a therapeutic option (unstandardized coefficient [95% confidence interval], 4.64 [1.15-8.13]; reference: transcatheter arterial embolization), lower hemoglobin concentration at arrival (-2.84 [-4.71 to -0.97]; 1 g/dL increment), and larger hematoma size (3.38 [1.23-5.53]; 100 cm3 increments) were significantly associated with increased blood transfusion. CONCLUSION: When a vulvovaginal hematoma does not exhibit extravasation, it can be treated conservatively regardless of size. When a therapeutic intervention is selected, transcatheter arterial embolization reduces the total amount of blood transfusion compared with surgery.

Modeling embryo-endometrial interface recapitulating human embryo implantation.

The initiation of human pregnancy is marked by the implantation of an embryo into the uterine environment; however, the underlying mechanisms remain largely elusive. To address this knowledge gap, we developed hormone-responsive endometrial organoids (EMO), termed apical-out (AO)-EMO, which emulate the in vivo architecture of endometrial tissue. The AO-EMO comprise an exposed apical epithelium surface, dense stromal cells, and a self-formed endothelial network. When cocultured with human embryonic stem cell-derived blastoids, the three-dimensional feto-maternal assembloid system recapitulates critical implantation stages, including apposition, adhesion, and invasion. Endometrial epithelial cells were subsequently disrupted by syncytial cells, which invade and fuse with endometrial stromal cells. We validated this fusion of syncytiotrophoblasts and stromal cells using human blastocysts. Our model provides a foundation for investigating embryo implantation and feto-maternal interactions, offering valuable insights for advancing reproductive medicine.

Association between Maternal Birth Weight and Prevalence of Congenital Malformations in Offspring: The Japanese Environment and Children's Study.

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that an MBW of <2500 g (low MBW) was associated with an increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075-1.792]), angioma (1.491 [1.079-2.059]), and inguinal hernia (1.746, [1.189-2.565]), while those with an MBW of ≥4000 g (high MBW) were associated with congenital anomalies of the urinary tract (2.194, [1.261-3.819]) and arrhythmia (1.775, [1.157-2.725]) compared with those with an MBW of 3000-3499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052-2.064]), congenital heart disease (1.615, [1.119-2.332]), genital organs (1.648, [1.130-2.405]), hypospadias (1.804, [1.130-2.881]), and inguinal hernia (1.484, [1.189-1.851]) in male infants and CAKUT (1.619, [1.154-2.273]) in female infants, whereas high MBW was associated with congenital heart disease (1.745, [1.058-2.877]) and CAKUT (2.470, [1.350-4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk.

Maternal birth weight as an indicator of early and late gestational diabetes mellitus: The Japan Environment and Children's Study.

AIMS: This study aimed to investigate the association of maternal birth weight (MBW) with early and late gestational diabetes mellitus (GDM). METHODS: A total of 69318 pregnant Japanese women were included in this birth cohort study. The associations between maternal birth weight and early gestational diabetes mellitus (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were investigated using a multinomial logistic regression model, with an maternal birth weight of 3000-3499 g as the reference category. RESULTS: Lower maternal birth weight was associated with higher odds of developing early and late gestational diabetes mellitus (P < 0.0001 and P < 0.0001, respectively). The adjusted odds ratios (aORs) for early gestational diabetes mellitus in participants with a MBW of <2500 g and 2500-2999 g were 1.345 (95% confidence interval [CI]: 0.912-1.984) and 1.338 (95% CI: 1.098-1.629), respectively. The aORs for late gestational diabetes mellitus in participants with a MBW of <2500 g and 2500-2999 g were, 1.657 (95% CI: 1.298-2.115) and 1.218 (95% CI: 1.058-1.402), respectively. CONCLUSIONS: Regardless of the gestational age when gestational diabetes mellitus was diagnosed, a lower maternal birth weight was associated with an increased risk of gestational diabetes mellitus. Furthermore, the association of a MBW <2500 g with late gestational diabetes mellitus tended to be stronger than that with early gestational diabetes mellitus.

Prenatal maternal glucocorticoid exposure modifies sperm miRNA profiles across multiple generations in the guinea-pig.

Maternal stress and glucocorticoid exposure during pregnancy have multigenerational effects on neuroendocrine function and behaviours in offspring. Importantly, effects are transmitted through the paternal lineage. Altered phenotypes are associated with profound differences in transcription and DNA methylation in the brain. In the present study, we hypothesized that maternal prenatal synthetic glucocorticoid (sGC) exposure in the F0 pregnancy will result in differences in miRNA levels in testes germ cells and sperm across multiple generations, and that these changes will associate with modified microRNA (miRNA) profiles and gene expression in the prefrontal cortex (PFC) of subsequent generations. Pregnant guinea-pigs (F0) were treated with multiple courses of the sGC betamethasone (Beta) (1 mg kg-1; gestational days 40, 41, 50, 51, 60 and 61) in late gestation. miRNA levels were assessed in testes germ cells and in F2 PFC using the GeneChip miRNA 4.0 Array and candidate miRNA measured in epididymal sperm by quantitative real-time PCR. Maternal Beta exposure did not alter miRNA levels in germ cells derived from the testes of adult male offspring. However, there were significant differences in the levels of four candidate miRNAs in the sperm of F1 and F2 adult males. There were no changes in miRNA levels in the PFC of juvenile F2 female offspring. The present study has identified that maternal Beta exposure leads to altered miRNA levels in sperm that are apparent for at least two generations. The fact that differences were confined to epididymal sperm suggests that the intergenerational effects of Beta may target the epididymis. KEY POINTS: Paternal glucocorticoid exposure prior to conception leads to profound epigenetic changes in the brain and somatic tissues in offspring, and microRNAs (miRNAs) in sperm may mediate these changes. We show that there were significant differences in the miRNA profile of epididymal sperm in two generations following prenatal glucocorticoid exposure that were not observed in germ cells derived from the testes. The epididymis is a probable target for intergenerational programming. The effects of prenatal glucocorticoid treatment may span multiple generations.

Association of parity with the prevalence of hypertension in Japan: The Tohoku Medical Megabank Community-based cohort study.

This study investigated the association of parity with hypertension prevalence in Japanese women while considering a clinical history of hypertensive disorders of pregnancy (HDP) and menopausal status. This cross-sectional study included 30,530 Japanese women (6700 premenopausal; 23 830 postmenopausal). The association between parity and the prevalence of hypertension was evaluated using a multiple logistic regression model with possible confounders. In premenopausal women, no statistically significant association between parity and hypertension prevalence was found. When not adjusted for current body mass index (BMI), a linear graded association was observed between parity and the prevalence of hypertension in postmenopausal women. However, the association between parity and hypertension prevalence in postmenopausal women was attenuated after adjustment for current BMI. Both current BMI and a clinical history of HDP were significantly associated with a high risk of hypertension in both premenopausal and postmenopausal women. Our results also suggest that continuous surveillance and preventive measures for hypertension should be provided for women with HDP and high parity.

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.

Prenatal hypertension as the risk of eclampsia, HELLP syndrome, and critical obstetric hemorrhage.

Critical bleeding is a common cause of maternal mortality in obstetric patients. However, the non-obstetric factors underlying critical obstetric bleeding remain uncertain. Therefore, this study aimed to clarify the impact of chronic hypertension on obstetric hemorrhage by evaluating a nationwide administrative database in Japan. Women who gave birth between 2018 and 2022 were enrolled. The primary outcome was critical hemorrhage requiring massive red blood cell (RBC) transfusion during childbirth. In total, 354, 299 eligible women were selected from the database. The maternal mortality rate was >1.0% among those who received a massive RBC transfusion (≥4000 cc), and this amount was used as the cutoff of the outcome. Critical hemorrhage was less frequent with elective Caesarean section (CS) compared with vaginal childbirth or emergent CS (odds ratio [OR], 0.38; 95% confidence interval, 0.30-0.47). Multiple logistic regression analysis adjusting for these obstetric risks revealed that a higher maternal age (adjusted OR [aOR] per 1 year, 1.07 [1.05-1.09]); oral medications with prednisolone (aOR, 2.5 [1.4-4.4]), anti-coagulants (aOR, 10 [5.4-19]), and anti-platelets (aOR, 2.9 [1.3-6.4]); and a prenatal history of hypertension (aOR, 2.5 [1.5-4.4]) and hypoproteinemia (aOR, 5.8 [1.7-20]) are the risks underlying critical obstetric hemorrhage. Prenatal history of hypertension was significantly associated with obstetric disseminated intravascular coagulation (OR, 1.9 [1.5-2.4]); Hemolysis, Elevated Liver enzymes, and Low platelet count (HELLP) syndrome (OR, 3.3 [2.7-4.2]); and eclampsia (OR, 6.1 [4.6-8.1]). In conclusion, a maternal prenatal history of hypertension is associated with the development of HELLP syndrome, eclampsia, and resultant critical hemorrhage. The incidence of HELLP syndrome and eclampsia increased more than fivefold in the presence of prenatal hypertension. However, the likelihood of subsequently developing DIC or experiencing critical bleeding did not change by the presence of prenatal hypertension.

CRISPR screening in human trophoblast stem cells reveals both shared and distinct aspects of human and mouse placental development.

The placenta serves as the interface between the mother and fetus, facilitating the exchange of gases and nutrients between their separate blood circulation systems. Trophoblasts in the placenta play a central role in this process. Our current understanding of mammalian trophoblast development relies largely on mouse models. However, given the diversification of mammalian placentas, findings from the mouse placenta cannot be readily extrapolated to other mammalian species, including humans. To fill this knowledge gap, we performed CRISPR knockout screening in human trophoblast stem cells (hTSCs). We targeted genes essential for mouse placental development and identified more than 100 genes as critical regulators in both human hTSCs and mouse placentas. Among them, we further characterized in detail two transcription factors, DLX3 and GCM1, and revealed their essential roles in hTSC differentiation. Moreover, a gene function-based comparison between human and mouse trophoblast subtypes suggests that their relationship may differ significantly from previous assumptions based on tissue localization or cellular function. Notably, our data reveal that hTSCs may not be analogous to mouse TSCs or the extraembryonic ectoderm (ExE) in which in vivo TSCs reside. Instead, hTSCs may be analogous to progenitor cells in the mouse ectoplacental cone and chorion. This finding is consistent with the absence of ExE-like structures during human placental development. Our data not only deepen our understanding of human trophoblast development but also facilitate cross-species comparison of mammalian placentas.

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.

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.

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.

A Reduction in Antenatal Steroid Dose Was Associated with Reduced Cardiac Dysfunction in a Sheep Model of Pregnancy.

Despite widespread use, dosing regimens for antenatal corticosteroid (ACS) therapy are poorly unoptimized. ACS therapy exerts a programming effect on fetal development, which may be associated with an increased risk of cardiovascular disease. Having demonstrated that low-dose steroid therapy is an efficacious means of maturing the preterm lung, we hypothesized that a low-dose steroid exposure would exert fewer adverse functional and transcriptional changes on the fetal heart. We tested this hypothesis using low-dose steroid therapy (10 mg delivered to the ewe over 36 h via constant infusion) and compared cardiac effects with those of a higher dose treatment (30 mg delivered to the ewe over 24 h by intramuscular injection; simulating currently employed clinical ACS regimens). Fetal cardiac function was assessed by ultrasound on the day of ACS treatment initiation. Transcriptomic analyses were performed on fetal myocardial tissue. Relative to saline control, fetuses in the higher-dose clinical treatment group had significantly lower ratios between early diastolic ventricular filling and ventricular filling during atrial systole, and showed the differential expression of myocardial hypertrophy-associated transcripts including ßMHC, GADD45γ, and PPARγ. The long-term implications of these changes remain unstudied. Irrespective, optimizing ACS dosing regimens to maximize respiratory benefit while minimizing adverse effects on key organ systems, such as the heart, offers a means of improving the acute and long-term outcomes associated with this important obstetric therapy.

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.

Glucocorticoid exposure modifies the miRNA profile of sperm in the guinea pig: Implications for intergenerational transmission.

Approximately 1%-3% of the adult population are treated with synthetic glucocorticoids (sGCs) for a variety of conditions. Studies have demonstrated that adversities experienced by males prior to conception may lead to abnormal neuroendocrine function and behaviors in offspring and that epigenetic factors including microRNA (miRNA) within sperm may be responsible for driving these effects. However, it remains unclear where in the epididymis sperm miRNA changes are occurring. Here, we hypothesized that sGC exposure will alter the miRNA profile of sperm in the epididymis in a region-specific manner. Adult male guinea pigs were exposed to regular drinking water (Ctrl) or water with the sGC dexamethasone (Dex; 3mg/kg) (n = 6/group) every other day for 48 days. Sperms were collected from epididymal seminal fluid in the caput and cauda regions of the epididymis and total RNA was extracted. miRNAs were assessed by miRNA 4.0 microarray; data were processed by TAC 4.0.1 and R. miRNA analysis revealed one miRNA in the caput that was significantly decreased by Dex in sperm. In the cauda, 31 miRNAs were reduced in sperm following Dex-exposure. The findings of this study demonstrate that Dex-exposure influences miRNA profile of sperm in the cauda but not the caput of the epididymis. This suggests that glucocorticoids target the epididymis to modify sperm miRNA and do not modify the miRNA content during spermiation in the testes.

Maternal lifestyle and nutrient intakes during pregnancy and exclusive breastfeeding in relation to risk factors for breast cancer: The Japan Environment and Children's Study.

Breastfeeding has many benefits for infant growth and maternal health, such as reducing breast cancer risk. However, data on maternal factors influencing breastfeeding are insufficient. To clarify the associations between maternal lifestyle and diet during pregnancy and exclusive breastfeeding (EBF), we conducted a prospective study of pregnant women within the framework of the Japan Environment and Children's Study (a nationwide birth cohort study). Of 97,413 pregnant women recruited between January 2011 and March 2014, 27,775 with a singleton first live birth whose dietary data during pregnancy and lactation data were complete were eligible. Using logistic regression, we evaluated the associations between lifestyle factors including smoking and prepregnancy body mass index and intake of nutrients (macronutrients, isoflavones, and dietary fiber), some of which are known risk factors of breast cancer, and EBF for one month postpartum (initiation of EBF). To investigate the associations of these factors with EBF for 6 months (continuation of EBF), 9582 women who had successfully completed one-month EBF were further followed up. Smoking and prepregnancy obesity were inversely associated with the initiation and continuation of EBF. Intakes of protein, fat, isoflavone, and dietary fiber were positively associated (p trend = 0.0001 for dietary fiber), and carbohydrate intake was inversely associated with the initiation of EBF. Dietary fiber intake was also associated with the continuation of EBF (p trend = 0.048). These findings indicate that maternal lifestyles during pregnancy affect lactation performance. Lifestyle adjustments during pregnancy may have favorable effects on maternal and children's health through successful breastfeeding.

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.

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.