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Background: The Tohoku Medical Megabank Project has initiated the Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study) including genomic and omics investigations and conducted a self-administered food frequency questionnaire with the response option “constitutionally unable to eat or drink it” for individual food items (TMM-FFQ) for pregnant women. This study evaluated the validity of the TMM-FFQ among pregnant women.Methods: Participants comprised 122 pregnant women aged ≥20 years residing in Miyagi Prefecture who completed weighed food records (WFRs) for 3 days as reference intake and the TMM-FFQ during mid-pregnancy. Correlations between nutrient or food group intakes based on the WFR and the TMM-FFQ were calculated using Spearman’s rank correlation coefficients (CCs), adjusting for energy intake and correcting for random within-individual variation of WFR. Cross-classification was also conducted according to quintiles using the WFR and TMM-FFQ data.Results: The percentages of participants who chose the “constitutionally unable to eat or drink it” option were >3% for seven food and drink items. CCs were >0.30 for 31 nutrients; the median across energy and 44 nutrients was 0.41. CCs were >0.30 for 14 food groups; the median across 20 food groups was 0.35. The median percentages of cross-classification into exact plus adjacent quintiles and extreme quintiles were 63.1% and 3.3% for energy and nutrients and 61.9% and 4.1% for food groups, respectively.Conclusion: The validity of the TMM-FFQ compared with the WFR was reasonable for certain nutrients and food groups among pregnant women in the TMM BirThree Cohort Study.

Purpose To separately perform visual and texture analyses of the axial, coronal, and sagittal planes of T2-weighted images and identify the optimal method for differentiating between the normal placenta and placenta accreta spectrum (PAS). Methods Eighty consecutive patients (normal group, n  = 50; PAS group, n  = 30) underwent preoperative MRI. A scoring system (0–2) was used to evaluate the degree of abnormality observed in visual analysis (bulging, abnormal vascularity, T2 dark band, placental heterogeneity). The axial, coronal, and sagittal planes were manually segmented separately to obtain texture features, and seven combinations were obtained: axial; coronal; sagittal; axial and coronal; axial and sagittal; coronal and sagittal; and axial, coronal, and sagittal. Feature selection using the least absolute shrinkage and selection operator method and model construction using a support vector machine algorithm with k-fold cross-validation were performed. AUC was used to evaluate diagnostic performance. Results The AUC of visual analysis was 0.75. The model ‘coronal and sagittal’ had the highest AUC (0.98) amongst the seven combinations. The fivefold cross-validation for the model ‘coronal and sagittal’ showed AUCs of 0.85 and 0.97 in training and validation sets, respectively. The AUC of the model ‘coronal and sagittal’ for all subjects was significantly higher than that of visual analysis (0.98 vs. 0.75; p  < 0.0001). Conclusion The model ‘coronal and sagittal’ can accurately differentiate between the normal placenta and PAS, with a significantly better diagnostic performance than visual analysis. Texture analysis is an optimal method for differentiating between the normal placenta and PAS.

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.

Previous literature has highlighted the importance of maternal behavior during the prenatal period for the upbringing of healthy adults. During pregnancy, fetal health assessments are mainly carried out non-invasively by monitoring fetal growth and heart rate (HR) or RR interval (RRI). Despite this, research entailing prediction of fHRs from mHRs is scarce mainly due to the difficulty in non-invasive measurements of fetal electrocardiogram (fECG). Also, so far, it is unknown how mHRs are associated with fHR over the short term. In this study, we used two machine learning models, support vector regression (SVR) and random forest (RF), for predicting average fetal RRI (fRRI). The predicted fRRI values were compared with actual fRRI values calculated from non-invasive fECG. fRRI was predicted from 13 maternal features that consisted of age, weight, and non-invasive ECG-derived parameters that included HR variability (HRV) and R wave amplitude variability. 156 records were used for training the models and the results showed that the SVR model outperformed the RF model with a root mean square error (RMSE) of 29 ms and an average error percentage (< 5%). Correlation analysis between predicted and actual fRRI values showed that the Spearman coefficient for the SVR and RF models were 0.31 ( P  < 0.001) and 0.19 ( P  < 0.05), respectively. The SVR model was further used to predict fRRI of 14 subjects who were not included in the training. The latter prediction results showed that individual error percentages were (≤ 5%) except in 3 subjects. The results of this study show that maternal factors can be potentially used for the assessment of fetal well-being based on fetal HR or RRI.

Intravenous medications are frequently administered through shared catheter lines in neonatal intensive care units (NICUs) due to the limited venous access in preterm infants, raising concerns about drug incompatibilities that may cause serious complications. Hydrocortisone sodium (HDC), ampicillin (ABPC), and cefotaxime (CTX) are commonly used in NICUs and are often co-administered with unfractionated heparin (UFH), which is routinely infused to prevent catheter occlusion. This study evaluated the physicochemical compatibility of HDC, ABPC, and CTX when mixed with UFH. Each drug was combined with UFH at equal volumes, and the mixtures were assessed immediately and after 3 h of storage by visual inspection, pH measurement, UV absorbance, and HPLC-UV analysis. No precipitation, turbidity, or color changes were observed in any mixture, and UV absorbance showed no relevant deviations compared with controls. Slight pH variations were detected but remained within acceptable limits. In semi-quantitative HPLC analysis, relative peak area changes were all below 10%, indicating no major degradation of the drugs. These findings suggest that HDC, ABPC, and CTX maintain acceptable physicochemical compatibility when co-administered with UFH, supporting their safe concomitant use in NICU practice.

Personality has been shown to predict postpartum depressive symptoms (PDS) assessed by the Edinburgh Postnatal Depression Scale (EPDS). However, existing studies have not considered the underlying symptom dimensions in the EPDS. We analyzed data from 15,012 women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Personality was assessed in middle pregnancy using the short-form Eysenck Personality Questionnaire-Revised. PDS were defined as EPDS score ≥ 9 at 1 month after delivery. The EPDS items were further divided into three dimensions: depressed mood, anxiety, and anhedonia. Multiple analyses were conducted to examine the associations of each personality scale with PDS and three dimensions in the EPDS, adjusting for age, parity, mode of delivery, education, income, and social isolation. The prevalence of PDS assessed by the EPDS at 1 month after delivery was 13.1%. Higher neuroticism scores were associated with PDS (odds ratio [OR], 2.63; 95% confidence interval [CI], 2.48 to 2.79) and all three dimensions (all p  < 0.001). Lower extraversion scores were associated with PDS (OR, 0.74; 95% CI, 0.70 to 0.78) and all three dimensions (all p  < 0.001). Lower psychoticism scores were associated with PDS (OR, 0.89; 95% CI, 0.85 to 0.94) and anxiety ( p  < 0.001), but not with depressed mood ( p  = 0.20) or anhedonia ( p  = 0.92). In conclusion, higher neuroticism and lower extraversion were associated with PDS and the three underlying dimensions in the EPDS, while lower psychoticism was associated with anxiety, but not with depressed mood or anhedonia.

This study investigated the association between maternal home blood pressure (HBP) trajectory during pregnancy and infant birth weight. A total of 755 pregnant women were included in this prospective cohort study. A group-based trajectory model identified six trajectory groups for home systolic blood pressure (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). Next, the association of HBP trajectory groups with infant birth weight was evaluated using a general linear model considering potential confounding factors. For home SBP and MAP, the trajectory groups with a low-steep J-curve, moderate J-curve, little high J-curve, and high J-curve were significantly associated with lower infant birth weight than the low-J-curve group. Among the trajectory groups for home DBP, the moderate–steep J-curve, little high J-curve, and high J-curve were significantly associated with lower infant birth weight than the group with low-J-curve. The effect sizes of the trajectory groups varied in infant birth weight from −0.21 standard deviations (SDs) (95% confidence interval (CI): −0.42 to −0.01 SD) to −1.13 SD (95% CI: −1.54 to −0.72 SD). In the analyses of infant birth weight in grams, effect sizes that were significantly associated with infant birth weight varied from −84 g (95% CI: −167 to −1 g) to −567 g (95% CI: −732 to −402 g). Trajectory groups with a moderate–reverse J-curve for home SBP, DBP, and MAP were not significantly associated with infant birth weight. Maternal HBP trajectory during pregnancy was an indicator of infant birth weight. Further studies evaluating the associations between HBP during pregnancy and other perinatal outcomes are needed.

Amniotic epithelial cells (AECs) have immunomodulatory and anti-inflammatory properties that may improve outcomes in cell transplantation. However, their effect on islet engraftment after intraportal co-transplantation remains unclear. We evaluated the impact of co-transplanting syngeneic 600 islet equivalents (IEQs) with human AECs (hAECs) via the portal vein in a rat streptozotocin-induced diabetes model. The co-transplantation (Co-Tx) group showed normalization of blood glucose levels within 7 days after transplantation, sustained normoglycemia thereafter, and achieved a higher diabetes reversal rate than controls (100% vs. 71.4%, p < 0.01). Serum CXCL1 levels were significantly lower in the Co-Tx group indicating suppression of early inflammatory responses. Thrombin-antithrombin complex (TAT) levels also tended to be lower, raising the possibility of attenuation of the instant blood-mediated inflammatory reaction (IBMIR). In contrast, no significant differences were observed in VEGF levels or intrahepatic microvascular density. Co-transplantation with hAECs enhances islet engraftment likely through suppression of early inflammation, highlighting their potential as an adjunctive cellular therapy in islet transplantation.

Aims This study investigated the association between maternal age and early and late gestational diabetes mellitus (GDM). Methods In total, 72,270 pregnant women were included in this prospective birth cohort study. Associations between maternal age and early GDM (diagnosed at <24 gestational weeks) and late GDM (diagnosed at ≥24 gestational weeks) were evaluated using a multinomial logistic regression model with possible confounding factors. The reference category was maternal age of 30–34.9 years. Results Higher maternal age was associated with higher odds of early and late GDM (P‐value for trend <0.0001 and <0.0001, respectively). The adjusted odds ratios (aORs) for early GDM with maternal age of 35–39.9 years and ≥40 were 1.399 (95% confidence interval [CI]: 1.134–1.725) and 2.494 (95% CI: 1.828–3.402), respectively. The aORs for late GDM with maternal age of 35–39 years and ≥40 were 1.603 (95% CI: 1.384–1.857) and 2.276 (95% CI: 1.798–2.881), respectively. Conclusions Higher maternal age was associated with an increased risk of GDM regardless of when GDM was diagnosed. The association between maternal age and early GDM was similar to that between maternal age and late GDM. Higher maternal age was associated with an increased risk of GDM regardless of when GDM was diagnosed. The association between maternal age and early GDM was similar to that between maternal age and late GDM.

Background Antenatal steroid therapy for fetal lung maturation is routinely administered to women at risk of preterm delivery. There is strong evidence to demonstrate benefit from antenatal steroids in terms of survival and respiratory disease, notably in infants delivered at or below 32 weeks’ gestation. However, dosing remains unoptimized and lung benefits are highly variable. Current treatment regimens generate high-concentration, pulsatile fetal steroid exposures now associated with increased risk of childhood neurodevelopmental diseases. We hypothesized that damage-associated changes in the fetal hippocampal transcriptome would be independent of preterm lung function. Methods Date-mated ewes carrying a single fetus at 122 ± 2dGA (term = 150dGA) were randomized into 4 groups: (i) Saline Control Group, 4×2ml maternal saline intramuscular(IM) injections at 12hr intervals ( n  = 11); or (ii) Dex High Group, 2×12mg maternal IM dexamethasone phosphate injections at 12hr intervals followed by 2×2ml IM saline injections at 12hr intervals ( n  = 12; representing a clinical regimen used in Singapore); or (iii) Dex Low Group, 4×1.5mg maternal IM dexamethasone phosphate injections 12hr intervals ( n  = 12); or (iv) Beta-Acetate Group, 1×0.125mg/kg maternal IM betamethasone acetate injection followed by 3×2ml IM sterile normal saline injections 12hr intervals ( n  = 8). Lambs were surgically delivered 48hr after first maternal injection at 122–125dGA, ventilated for 30min to establish lung function, and euthanised for necropsy and tissue collection. Results Preterm lambs from the Dex Low and Beta-Acetate Groups had statistically and biologically significant lung function improvements (measured by gas exchange, lung compliance). Compared to the Saline Control Group, hippocampal transcriptomic data identified 879 differentially significant expressed genes (at least 1.5-fold change and FDR < 5%) in the steroid-treated groups. Pulsatile dexamethasone-only exposed groups (Dex High and Dex Low) had three common positively enriched differentially expressed pathways related in part to neurodegeneration (“Prion Disease”, “Alzheimer’s Disease”, “Arachidonic Acid metabolism”). Adverse changes were independent of respiratory function during ventilation. Conclusions Our data suggests that exposure to antenatal steroid therapy is an independent cause of damage- associated transcriptomic changes in the brain of preterm, fetal sheep. These data highlight an urgent need for careful reconsideration and balancing of how antenatal steroids are used, both for patient selection and dosing regimens.