Interleukin-17A stimulation induces alterations in Microglial microRNA expression profiles.

BACKGROUND: Increased maternal interleukin (IL)-17A and activated microglia are pivotal factors contributing to the pathological phenotypes of maternal immune activation (MIA), developing neurodevelopmental disorders in offspring. This study aimed to determine whether IL-17A affects the microglial microRNA (miRNA) profiles. METHODS: The miRNA expression profiles of primary cultured microglia stimulated with recombinant IL-17A were examined comprehensively using miRNA sequencing and validated through qRT-PCR. The expressions of miRNAs target genes identified using bioinformatics, were investigated in microglia transfected with mimic miRNA. The target gene's expression was also examined in the fetal brains of the MIA mouse model induced by maternal lipopolysaccharide (LPS) administration. RESULTS: Primary cultured microglia expressed the IL-17A receptor and increased proinflammatory cytokines and nitric oxide synthase 2 upon treatment with IL-17A. Among the three miRNAs with |log2FC | >1, only mmu-miR-206-3p expression was significantly up-regulated by IL-17A. Transfection with the mmu-miR-206-3p mimic resulted in a significant decrease in the expression of Hdac4 and Igf1, target genes of mmu-miR-206-3p. Hdac4 expression also significantly decreased in the LPS-induced MIA model. CONCLUSIONS: IL-17A affected microglial miRNA profiles with upregulated mmu-miR-206-3p. These findings suggest that targeting the IL-17A/mmu-miR-206-3p pathway may be a new strategy for predicting MIA-related neurodevelopmental deficits and providing preventive interventions. IMPACT: Despite the growing evidence of interleukin (IL)-17A and microglia in the pathology of maternal immune activation (MIA), the downstream of IL-17A in microglia is not fully known. IL-17A altered microRNA profiles and upregulated the mmu-miR-206-3p expression in microglia. The mmu-miR-206-3p reduced autism spectrum disorder (ASD) related gene expressions, Hdac4 and Igf1. The Hdac4 expression was also reduced in the brain of MIA offspring. The hsa-miR-206 sequence is consistent with that of mmu-miR-206-3p. This study may provide clues to pathological mechanisms leading to predictions and interventions for ASD children born to mothers with IL-17A-related disorders.

New-onset postpartum hypertension in women without a history of hypertensive disorders of pregnancy: a multicenter study in Japan.

The aim of this study was to investigate the prevalence and risk factors of new-onset postpartum hypertension (PPHTN), defined as new-onset hypertension during the postpartum period, among women without a history of hypertension during pregnancy and labor. A multicenter retrospective study was conducted using clinical data of women who delivered at term between 2011 and 2018 at 12 maternity hospitals. A total of 18,295 normotensive women were eligible, after excluding those with hypertensive disorders of pregnancy or hypertension during labor. New-onset PPHTN was defined as multiple blood pressure readings of ≥ 140/90 mmHg between 1 d and 4 weeks postpartum among normotensive women throughout pregnancy. Multivariate regression analyses were performed to evaluate the risk factors for new-onset PPHTN. Among the 18,295 normotensive women, 227 (1.2%) presented with new-onset PPHTN. The prevalence was higher in women who delivered via cesarean section than in those who delivered vaginally (7.0% and 1.0%, respectively). The independent risk factors were maternal age ≥ 35 years (adjusted odds ratio 1.67, 95% confidence interval [1.10-2.53]), nulliparity (1.83 [1.24-2.71]), high normal blood pressure (systolic blood pressure [SBP] 120-129 and diastolic blood pressure [DBP] < 80) at the last prenatal check-up (1.96 [1.23-3.13]), elevated blood pressure (SBP 130-139 and/or DBP 80-89) (6.42 [4.15-9.95]), urinary protein 1+ (1.99 [1.27-3.11]), scheduled cesarean section (4.05 [1.69-9.69]), and emergency cesarean section (10.02 [5.10-19.70]). New-onset PPHTN was observed in 1.2% of the normotensive women, with women who delivered via cesarean section having the highest risk. Close postpartum blood pressure monitoring may be required for women with multiple risk factors to identify new-onset PPHTN in a timely manner and reduce adverse maternal consequences.

Altered offspring neurodevelopment in an L-NAME-induced preeclampsia rat model.

Introduction: To investigate the mechanism underlying the increased risk of subsequent neurodevelopmental disorders in children born to mothers with preeclampsia, we evaluated the neurodevelopment of offspring of a preeclampsia rat model induced by the administration of N-nitro-L-arginine methyl ester (L-NAME) and identified unique protein signatures in the offspring cerebrospinal fluid. Methods: Pregnant rats received an intraperitoneal injection of L-NAME (250 mg/kg/day) during gestational days 15-20 to establish a preeclampsia model. Behavioral experiments (negative geotaxis, open-field, rotarod treadmill, and active avoidance tests), immunohistochemistry [anti-neuronal nuclei (NeuN) staining in the hippocampal dentate gyrus and cerebral cortex on postnatal day 70], and proteome analysis of the cerebrospinal fluid on postnatal day 5 were performed on male offspring. Results: Offspring of the preeclampsia dam exhibited increased growth restriction at birth (52.5%), but showed postnatal catch-up growth on postnatal day 14. Several behavioral abnormalities including motor development and vestibular function (negative geotaxis test: p < 0.01) in the neonatal period; motor coordination and learning skills (rotarod treadmill test: p = 0.01); and memory skills (active avoidance test: p < 0.01) in the juvenile period were observed. NeuN-positive cells in preeclampsia rats were significantly reduced in both the hippocampal dentate gyrus and cerebral cortex (p < 0.01, p < 0.01, respectively). Among the 1270 proteins in the cerebrospinal fluid identified using liquid chromatography-tandem mass spectrometry, 32 were differentially expressed. Principal component analysis showed that most cerebrospinal fluid samples achieved clear separation between preeclampsia and control rats. Pathway analysis revealed that differentially expressed proteins were associated with endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins, which are involved in various nervous system disorders including autism spectrum disorders, schizophrenia, and Alzheimer's disease. Conclusion: The offspring of the L-NAME-induced preeclampsia model rats exhibited key features of neurodevelopmental abnormalities on behavioral and pathological examinations similar to humans. We found altered cerebrospinal fluid protein profiling in this preeclampsia rat, and the unique protein signatures related to endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins may be associated with subsequent adverse neurodevelopment in the offspring.

Evaluating glucose variability through OGTT in early pregnancy and its association with hypertensive disorders of pregnancy in non-diabetic pregnancies: a large-scale multi-center retrospective study.

BACKGROUND: Recent evidence suggests increased glucose variability (GV) causes endothelial dysfunction, a central pathology of hypertensive disorders of pregnancy (HDP). We aimed to investigate the association between GV in early pregnancy and subsequent HDP development among non-diabetes mellitus (DM) pregnancies. METHODS: This multicenter retrospective study used data from singleton pregnancies between 2009 and 2019. Among individuals who had 75 g-OGTT before 20 weeks of gestation, we evaluated GV by 75 g-OGTT parameters and examined its relationship with HDP development, defining an initial-increase from fasting-plasma glucose (PG) to 1-h-PG and subsequent-decrease from 1-h-PG to 2-h-PG. RESULTS: Approximately 3.0% pregnancies (802/26,995) had 75 g-OGTT before 20 weeks of gestation, and they had a higher prevalence of HDP (14.3% vs. 7.5%). The initial-increase was significantly associated with overall HDP (aOR 1.20, 95% CI 1.02-1.42), and the subsequent-decrease was associated with decreased and increased development of early-onset (EoHDP: aOR 0.56, 95% CI 0.38-0.82) and late-onset HDP (LoHDP: aOR 1.38, 95% CI 1.11-1.73), respectively. CONCLUSIONS: A pattern of marked initial-increase and minor subsequent-decrease (i.e., sustained hyperglycemia) was associated with EoHDP. Contrarily, the pattern of marked initial-increase and subsequent-decrease (i.e., increased GV) was associated with LoHDP. This provides a new perspective for future study strategies.

Intrauterine exposure to chorioamnionitis and neuroanatomical alterations at term-equivalent age in preterm infants.

PURPOSE: Infants born to mothers with chorioamnionitis (CAM) are at increased risk of developing adverse neurodevelopmental disorders in later life. However, clinical magnetic resonance imaging (MRI) studies examining brain injuries and neuroanatomical alterations attributed to CAM have yielded inconsistent results. We aimed to determine whether exposure to histological CAM in utero leads to brain injuries and alterations in the neuroanatomy of preterm infants using 3.0- Tesla MRI at term-equivalent age. METHODS: A total of 58 preterm infants born before 34 weeks of gestation at Nagoya University Hospital between 2010 and 2018 were eligible for this study (CAM group, n = 21; non-CAM group, n = 37). Brain injuries and abnormalities were assessed using the Kidokoro Global Brain Abnormality Scoring system. Gray matter, white matter, and subcortical gray matter (thalamus, caudate nucleus, putamen, pallidum, hippocampus, amygdala, and nucleus accumbens) volumes were evaluated using segmentation tools (SPM12 and Infant FreeSurfer). RESULTS: The Kidokoro scores for each category and severity in the CAM group were comparable to those observed in the non-CAM group. White matter volume was significantly smaller in the CAM group after adjusting for covariates (postmenstrual age at MRI, infant sex, and gestational age) (p = 0.007), whereas gray matter volume was not significantly different. Multiple linear regression analyses revealed significantly smaller volumes in the bilateral pallidums (right, p = 0.045; left, p = 0.038) and nucleus accumbens (right, p = 0.030; left, p = 0.004) after adjusting for covariates. CONCLUSIONS: Preterm infants born to mothers with histological CAM showed smaller volumes in white matter, pallidum, and nucleus accumbens at term-equivalent age.

Antenatal corticosteroids-to-delivery interval associates cord blood S100B levels.

AIM: Antenatal corticosteroids (ACS) are recommended for women at risk of preterm birth before 34 weeks' gestation. However, adverse effects of ACS on the fetal brain have also been reported. The time interval from ACS administration to delivery (ACS-to-delivery interval) might alter the effect of ACS on the fetal brain. This study aimed to evaluate the effect of ACS-to-delivery interval on cord blood S100 calcium-binding protein B (S100B) levels as a biomarker of brain damage. METHODS: Women who delivered between 2012 and 2020 at a tertiary medical center were divided into three groups according to ACS use and ACS-to-delivery interval, retrospectively: non-ACS, ACS ≤7 days, and ACS >7 days. Patients who did not complete the ACS regimen were excluded. The primary outcome was cord blood S100B levels. RESULTS: Cord blood S100B levels were significantly lower in the ACS ≤7 days group than in the non-ACS and ACS >7 days groups. In the multiple regression analysis, birth ≤7 days after ACS showed a significant negative association with S100B level (p < 0.001). CONCLUSIONS: Reduced S100B levels were observed in infants born ≤7 days after ACS but not in infants born >7 days after ACS. These findings suggest the importance of ACS timing to optimize its effects on the fetal brain, although further studies are required to identify these mechanisms.

Clinical significances of Bishop score and vaginal bleeding to controlled-release dinoprostone delivery system (PROPESS) efficacy for cervical ripening: A retrospective single-center study in Japan.

AIMS: To evaluate the effect of vaginal bleeding on the efficacy of controlled-release dinoprostone delivery system (PROPESS) for cervical ripening and the factors affecting the PROPESS efficacy in a Japanese clinical setting. METHODS: A total of 100 term pregnant women in whom PROPESS was used due to an unfavorable cervix (Bishop score ≤ 6) were enrolled. We retrospectively investigated which factors, including vaginal bleeding, were associated with the success of cervical ripening using logistic regression analysis. Moreover, the effect of vaginal bleeding on vaginal acidity was examined in 24 selected cases (control, 11; rupture of membrane, 4; and vaginal bleeding, 8). RESULTS: A 25 women successfully ripened the cervix (effective group), and 75 were unsuccessful (noneffective group). Bishop score at insertion (adjusted odds ratio: 1.87; 95% confidence interval: 1.23-2.86; p = 0.004), and vaginal bleeding at PROPESS insertion (adjusted odds ratio 6.63; 95% confidence interval 1.21-36.36; p = 0.029) affected cervical ripening success. The cases with vaginal bleeding showed a significantly higher vaginal pH than the control cases (median value: 6.75 and 5.0, respectively). We identified no obvious adverse outcomes, such as tachysystole, fetal heart rate abnormality, or low Apgar/pH, associated with vaginal bleeding at insertion. CONCLUSIONS: Our findings suggest that the PROPESS efficacy depends on Bishop score at insertion and that vaginal bleeding at PROPESS insertion might have a significantly positive effect on cervical ripening in term pregnant women.

Trend changes in age-related body mass index gain after coronavirus disease 2019 pandemic in Japan: a multicenter retrospective cohort study.

BACKGROUND: Accumulating studies suggest that strict lockdown with enforcement including segregation to control the coronavirus disease 2019 (COVID-19) pandemic is associated with excess weight gain, but the such lockdown was not practiced in Japan. We aimed to compare the age-related weight gain before and after the COVID-19 pandemic in Japan where achieved epidemic control based on individual voluntary action. METHODS: This multicenter retrospective cohort study used electronic data from annual health checkups for workers from January 2015 to December 2021 at four facilities belonging to the Central Clinic Group, Aichi, Japan. We defined pre-pandemic and post-pandemic periods as January 2015-December 2019 and January 2020-December 2021, respectively. Participants were grouped by sex, age, and body mass index (BMI) stratus as of 2015, and the pre-pandemic and post-pandemic age-related BMI changes in overall individuals and each specific group were compared using a paired t-test. RESULTS: The total number of eligible participants was 19,290. During the pre-pandemic period, the mean BMI increased linearly in every group. The mean age-related BMI changes in females' pre-pandemic and post-pandemic periods were + 0.11 and + 0.02 kg/m2/year, respectively. This significant decrease was also shown in males, + 0.11 in the pre-pandemic and - 0.02 kg/m2/year in the post-pandemic periods. The reduction was consistently observed in all age strata. Furthermore, a significant reduction was also observed in the normal-weight females of reproductive ages aged 15-44 years. CONCLUSIONS: This is the first report showing that age-related weight gain was reduced after the COVID-19 pandemic in Japan, which could affect the reproductive age of females.

Antenatal prediction models for outcomes of extremely and very preterm infants based on machine learning.

PURPOSE: Predicting individual risks for adverse outcomes in preterm infants is necessary for perinatal management and antenatal counseling for their parents. To evaluate whether a machine learning approach can improve the prediction of severe infant outcomes beyond the performance of conventional logistic models, and to identify maternal and fetal factors that largely contribute to these outcomes. METHODS: A population-based retrospective study was performed using clinical data of 31,157 infants born at < 32 weeks of gestation and weighing ≤ 1500 g, registered in the Neonatal Research Network of Japan between 2006 and 2015. We developed a conventional logistic model and 6 types of machine learning models based on 12 maternal and fetal factors. Discriminative ability was evaluated using the area under the receiver operating characteristic curves (AUROCs), and the importance of each factor in terms of its contribution to outcomes was evaluated using the SHAP (SHapley Additive exPlanations) value. RESULTS: The AUROCs of the most discriminative machine learning models were better than those of the conventional models for all outcomes. The AUROCs for in-hospital death and short-term adverse outcomes in the gradient boosting decision tree were significantly higher than those in the conventional model (p = 0.015 and p = 0.002, respectively). The SHAP value analyses showed that gestational age, birth weight, and antenatal corticosteroid treatment were the three most important factors associated with severe infant outcomes. CONCLUSION: Machine learning models improve the prediction of severe infant outcomes. Moreover, the machine learning approach provides insight into the potential risk factors for severe infant outcomes.

Antenatal corticosteroids and outcomes of small for gestational age infants born at 24-31 gestational weeks: a population-based propensity score matching analysis.

PURPOSE: To evaluate the effect of antenatal corticosteroid (ACS) treatment on neonatal outcomes in small for gestational age (SGA) infants born at 24-31 gestational weeks compared with non-SGA infants. METHODS: A population-based retrospective study was conducted that analyzed clinical data from the Neonatal Research Network of Japan database, which enrolls neonates born at < 32 gestational weeks and weighing 1500 g or less (n = 22,414). Propensity score matching (with the ratio of ACS to no-ACS groups of 1:1) was performed in SGA (n = 7028) and non-SGA (n = 15,386) infants, respectively. Univariate logistic and interaction analyses were performed to compare the short-term neonatal outcomes of infants with and without ACS treatment in utero. RESULTS: In the SGA and non-SGA infants, ACS treatment significantly reduced in-hospital mortality (odds ratio 0.67 95% confidence interval [0.50-0.88] and 0.62 [0.50-0.78], respectively), respiratory distress syndrome (0.77 [0.69-0.87] and 0.63 [0.58-0.68], respectively), and composite adverse outcomes (0.73 [0.58-0.91] and 0.57 [0.50-0.65], respectively). ACS treatment also significantly reduced intraventricular hemorrhage (grade III/IV), periventricular leukomalacia, and sepsis in the non-SGA infants, but not in the SGA infants. However, interaction analyses revealed no significant differences between the SGA and non-SGA infants in the efficacy of ACS treatment on short-term outcomes except for respiratory distress syndrome. CONCLUSIONS: ACS treatment was associated with beneficial effects on mortality, respiratory distress syndrome, and adverse composite outcomes in extremely and very preterm SGA infants, with similar efficacy on all neonatal outcomes except for respiratory distress syndrome observed in the non-SGA infants.

Prenatal diagnosis of distal 13q deletion syndrome in a fetus with esophageal atresia: a case report and review of the literature.

BACKGROUND: Chromosome 13q deletion syndrome shows variable clinical features related to the different potential breakpoints in chromosome 13q. The severely malformed phenotype is known to be associated with the deletion of a critical region in 13q32. However, esophageal atresia is a rare symptom and the relevant region is unknown. Thus, determining the association between accurate breakpoints and new clinical features is essential. CASE PRESENTATION: A 28-year-old Japanese primigravid woman was referred for fetal growth restriction, absence of a gastric bubble, cerebellar hypoplasia, overlapping fingers, and polyhydramnios at 31 weeks gestation. At 38 + 0 weeks, she delivered a 1774 g female infant. The infant presented with isolated esophageal atresia (Gross type A), Dandy-Walker malformation, right microphthalmia, left coloboma, overlapping fingers, pleurocentrum in the thoracic vertebrae, reduced anogenital distance, and hearing loss. Her karyotype was diagnosed as 46,XX,del(13)(q32.1-qter) by amniocentesis, but array comparative genomic hybridization after birth revealed the deletion of 13q31.3-qter. At 48 days after birth, the infant underwent surgery for esophageal atresia and was later discharged from the hospital at 7 months of age. CONCLUSION: This case report and the literature reviews supports the previous findings on the pathological roles of haploinsufficiency of the ZIC2/ZIC5 in Dandy-Walker malformation and the EFBN2 haploinsufficiency in eye malformation and hearing loss. Furthermore, the possible involvement of IRS2, COLA1, and COLA2 in eye malformation were identified. This is the first case of 13q deletion syndrome with esophageal atresia (Gross A), but it may be a symptom of VATER/VACTER association (vertebral defects, anorectal malformations, cardiac defects, tracheoesophageal fistula with or without esophageal atresia, renal malformations, and limb defects), as in the previous cases. These symptoms might also be associated with EFBN2 haploinsufficiency, although further research is required.

Optimal annual body mass index change for preventing spontaneous preterm birth in a subsequent pregnancy.

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality. Although PTB is known to recur, interpregnancy preventive strategies for PTB have not been established to date. Annual BMI change can serve as a specific target value for preventing obstetric complications during interpregnancy care/counseling. This value can also account for age-related weight gain (0.2 kg/m2/year). In a multicenter retrospective study, we investigated the optimal annual BMI change for preventing PTB recurrence using the data of individuals who had two singleton births from 2009 to 2019. The association between annual BMI change and spontaneous PTB (sPTB) was analyzed by separating cases of medically indicated PTB (mPTB) from those of sPTB. Previous history of sPTB was strongly associated with sPTB in the subsequent pregnancy (adjusted odds ratio [aOR], 12.7; 95% confidence interval [CI], 6.5-24.8). Increase in annual BMI was negatively associated with sPTB (aOR, 0.6; 95% CI 0.5-0.9). The sPTB recurrence rate was significantly lower in patients with an annual BMI change of ≥ 0.25 kg/m2/year than in those with an annual BMI change of < 0.25 kg/m2/year (7.7% vs. 35.0%, p = 0.011). Our findings suggest that age-related annual BMI gain between pregnancies may help prevent sPTB recurrence.

5p deletion with congenital diaphragmatic hernia: a case report.

BACKGROUND: 5p deletion syndrome is known as cri-du-chat syndrome, but there are no reports on congenital diaphragmatic hernia complications associated with it. CASE PRESENTATION: A 28-year-old primigravida Japanese woman was referred for 5 mm of nuchal translucency. Fetal growth restriction was found at 20 weeks, and a left-sided congenital diaphragmatic hernia was diagnosed at 24 weeks. The karyotype of the fetus was diagnosed as 46, XX, del(5)(p14) and referred to our hospital. At 36 + 6 weeks, a 1524 g female infant was delivered after premature membrane rupture, with Apgar scores of 4 and 6 at 1 and 5 minutes, respectively. The baby was intubated immediately with sedation and muscle relaxation, after birth for initial treatment for congenital diaphragmatic hernia. The peripheral blood karyotype was consistent with the prenatal result. The infant was discharged alive, without any respiratory support, after the defect of the diaphragm was repaired. CONCLUSION: The results of this study may be helpful for antenatal genetic counseling.

Molecular hydrogen has a positive impact on pregnancy maintenance through enhancement of mitochondrial function and immunomodulatory effects on T cells.

AIMS: Molecular hydrogen (H2) has attracted growing interest because of its implications in various diseases. However, the molecular mechanisms underlying the remarkable effect of a small amount of H2 remain elusive. No knowledge has been available on the role of H2 in the etiology of pregnancy disorders or its direct influence on human immune cells. Since maternal immunity, T cells in particular, plays a critical role in pregnancy maintenance. We investigated the effects of H2 on T cells and its relation to preterm birth (PTB). MAIN METHODS: Exhaled H2 concentrations in pregnant women were measured and correlated with cytokine concentrations in maternal and umbilical cord blood. H2 was added to T cells collected from healthy donors, and differentiation and proliferation were examined. Energy metabolism was also examined. H2 was administered to mice and cytokine expression was compared. KEY FINDINGS: Our prospective observational study revealed that maternal production of H2 is significantly lower in pregnant women with PTB, suggesting its potential as a biomarker for predicting PTB. We found that H2 has clear associations with several maternal cytokines, and acts as an immunomodulator by exerting mitochondrial function in human T cells. Moreover, in vivo administration of H2 to pregnant mice regulated inflammatory responses and reduced PTB caused by T cell activation, which further supports the notion that H2 may contribute to prolonged gestation through its immunomodulatory effect. SIGNIFICANCE: Measuring maternal H2-production could be a potential clinical tool in the management of PTB, and H2 may have positive impact on pregnancy maintenance.

Impact of hypertensive disorders of pregnancy on respiratory outcomes in extremely and very preterm infants: A population-based study in Japan.

OBJECTIVES: We aimed to evaluate the impact of hypertensive disorders of pregnancy (HDP) on short- and medium-term respiratory outcomes in extremely and very preterm infants using the Neonatal Research Network of Japan database. STUDY DESIGN: This was a population-based retrospective study of preterm infants weighing ≤ 1500 g born between 22 and 31 weeks of gestation between 2003 and 2017. After 1:1 stratification matching by four factors (maternal age, gestational age, parity, and year of delivery), a total of 5137 infants in each group (HDP and non-HDP groups) were selected. MAIN OUTCOME MEASURES: The association between HDP and various respiratory outcomes was evaluated using univariate and multivariate logistic regression analyses. RESULTS: In the multivariate analyses, HDP was associated with higher odds for respiratory distress syndrome (RDS) (odds ratio 1.83, 95% confidence interval [1.65-2.03]), but reduced odds of persistent pulmonary hypertension of the newborn (PPHN) (0.34 [0.26-0.46]) and inhaled nitric oxide use (0.43 [0.33-0.55]). Although HDP was associated with an increased risk of chronic lung disease (CLD) in the univariate analysis, this association was not significant after adjustment for covariates (0.94 [0.83-1.07]). No significant association was found between HDP and home oxygen therapy (HOT) and medium-term oxygen use. CONCLUSION: The impact of maternal HDP largely differed depending on respiratory disorders and respiratory support. HDP was associated with higher odds of RDS but reduced odds of PPHN. The risks for CLD, HOT, and medium-term respiratory outcomes in the HDP group were comparable to those in the non-HDP group.

The Possible Effects of Zinc Supplementation on Postpartum Depression and Anemia.

Background and Objectives: The effects of postpartum zinc supplementation are still unclear. Our purpose in this study is to investigate the association between Zn supplementation and postpartum depression, defined by an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 9, and the effect on the hematological status of postpartum women. Materials and Methods: We first investigated whether zinc supplementation affected the perioperative levels of zinc, hemoglobin, and hematocrit in 197 cases who underwent cesarean section and had postpartum anemia. Next, logistic regression analyses were performed on 148 eligible cases to determine the association between zinc supplementation and postpartum depression. Results: Postpartum zinc supplementation significantly improved the status of maternal blood zinc levels and reduced the risk of developing postpartum depression (adjusted odds ratio: 0.249; 95% confidence interval: 0.062-0.988; p = 0.048). Iron supplementation is a standard and effective strategy for treating anemia; however, the combination of oral iron plus zinc supplementation resulted in slightly significant negative effects on postpartum hemoglobin and hematocrit compared to oral iron supplementation only. Conclusions: Postpartum zinc supplementation causes a significant positive effect on postpartum depression (EPDS score ≥ 9). Zinc supplementation had a negative but transient influence on the hematological status in women with postpartum anemia treated with oral iron supplementation; however, the differences were not clinically significant. Thus, we did not regard it as an adverse effect to be considered, and postpartum zinc supplementation may be viewed as beneficial in postpartum women.

Reassessing the duration of each stage of labor and their relation to postpartum hemorrhage in the current Japanese population.

AIM: To reassess the normal duration of each stage of labor in a contemporary Japanese cohort, and to determine whether prolongation of each stage of labor increases the rate of postpartum hemorrhage (PPH) in vaginal deliveries. METHODS: Clinical data of women who delivered at term at 12 facilities between 2012 and 2018 were retrospectively collected. A total of 31 758 women were subdivided into three or four subgroups according to the duration of each stage of labor and parity. Univariate and multivariate logistic regression analyses were performed to estimate crude and adjusted odds ratios (ORs) of PPH (blood loss ≥ 1000 mL) in each subgroup, with women with the shortest durations in each subgroup used as the reference group. RESULTS: The reference range of each stage of labor was found to be shorter than that previously reported. Women with prolonged second (primiparity, adjusted OR: 1.15-1.78; multiparity, adjusted OR: 1.14-1.74) and third (primiparity, adjusted OR: 1.39-4.95; multiparity, adjusted OR: 1.46-3.80) stages of labor showed an increased risk of PPH, whereas those with prolonged first stage did not. A significantly increased risk of PPH was found both in primiparous and multiparous women with third stages of labor ≥ 5 min. CONCLUSIONS: The normal duration of each stage of labor in the Japanese population needs to be revised and well-recognized by obstetric care providers. A prolonged third stage of labor was a more important contributing factor to PPH than prolonged first or second stages.

Intrauterine exposure to hypertensive disorders of pregnancy and postnatal growth in extremely and very preterm infants.

OBJECTIVES: There is growing evidence regarding the association between rapid growth during infancy and metabolic and cardiovascular diseases later in life. We aimed to evaluate postnatal growth trajectories in extremely and very preterm infants exposed to hypertensive disorders of pregnancy (HDP) in utero. STUDY DESIGN: This multicenter retrospective study used a nationwide database of preterm infants weighing ≤1,500 g born between 22 and 31 weeks of gestation between 2003 and 2015. MAIN OUTCOME MEASURES: The Z-scores for height and weight were evaluated at three time points (at birth, corrected age of 1.5 years, and chronological age of 3 years) in 5,144 infants (HDP, n = 1,188; non-HDP, n = 3,956). Univariate and multivariate regression analyses were performed to investigate the associations between HDP exposure and accelerated postnatal growth. RESULTS: Male and female infants in the HDP group showed increased mean Z-scores for height and weight, whereas those in the non-HDP group showed decreased mean Z-scores. Multivariate analyses showed that HDP were associated with accelerated postnatal growth (Δ Z-scores) in weight in both male and female infants (ß coefficient [95% CI]; male 0.17 [0.05-0.30], female 0.27 [0.14-0.39]), but not in height (male 0.02 [-0.09 to 0.13], female 0.04 [-0.06 to 0.15]). An interaction analysis revealed no significant differences in the effects of HDP on postnatal growth between male and female infants. CONCLUSIONS: Intrauterine exposure to HDP contributes to accelerated postnatal weight growth in extremely and very preterm infants during early childhood. In addition, no sex differences were observed in postnatal growth.

Annual Body Mass Index Gain and Risk of Gestational Diabetes Mellitus in a Subsequent Pregnancy.

Introduction: Weight change during the interpregnancy is related to gestational diabetes mellitus (GDM) in the subsequent pregnancy. In interpregnancy care/counseling, the timeframe for goal setting is important, while the timing of the next conception is unpredictable and preventing age-related body weight gain is difficult. This study aimed to investigate the association between annual weight gain during the interpregnancy, which provide clearer timeframe, and GDM in subsequent pregnancies. Methods: This multicenter retrospective study was conducted by collecting data on two pregnancies of the same women in 2009-2019. The association between annual BMI gain and GDM during the subsequent pregnancy was examined. Results: This study included 1,640 pregnant women. A history of GDM [adjusted odds ratio (aOR), 26.22; 95% confidence interval (CI), 14.93-46.07] and annual BMI gain (aOR, 1.48; 95% CI, 1.22-1.81) were related to GDM during the subsequent pregnancy. In the women with a pre-pregnant BMI of <25.0 kg/m2 and without GDM during the index pregnancy, an annual BMI gain of ≥0.6 kg/m2/year during the interpregnancy were associated with GDM in subsequent pregnancies; however, in the other subgroups, it was not associated with GDM in subsequent pregnancies. Conclusions: For women with a pre-pregnant BMI of <25.0 kg/m2 and without GDM during the index pregnancy, maintaining an annual BMI gain of <0.6 kg/m2/year may prevent GDM during the subsequent pregnancy.

Machine learning prediction models for postpartum depression: A multicenter study in Japan.

AIM: Postpartum depression (PPD) and perinatal mental health care are of growing importance worldwide. Here we aimed to develop and validate machine learning models for the prediction of PPD, and to evaluate the usefulness of the recently adopted 2-week postpartum checkup in some parts of Japan for the identification of women at high risk of PPD. METHODS: A multicenter retrospective study was conducted using the clinical data of 10 013 women who delivered at ≥35 weeks of gestation at 12 maternity care hospitals in Japan. PPD was defined as an Edinburgh Postnatal Depression Scale score of ≥9 points at 4 weeks postpartum. We developed prediction models using conventional logistic regression and four machine learning algorithms based on the information that can be routinely collected in daily clinical practice. The model performance was evaluated using the area under the receiver operating characteristic curve (AUROC). RESULTS: In the machine learning models developed using clinical data before discharge, the AUROCs were similar to those in the conventional logistic regression models (AUROC, 0.569-0.630 vs. 0.626). The incorporation of additional 2-week postpartum checkup data into the model significantly improved the predictive performance for PPD compared to that without in the Ridge regression and Elastic net (AUROC, 0.702 vs. 0.630 [p < 0.01] and 0.701 vs. 0.628 [p < 0.01], respectively). CONCLUSIONS: Our machine learning models did not achieve better predictive performance for PPD than conventional logistic regression models. However, we demonstrated the usefulness of the 2-week postpartum checkup for the identification of women at high risk of PPD.