Background Biological maturity at birth does not always align with gestational age, and this discordance can be quantified as gestational age acceleration (GAA) using DNA methylation-based epigenetic clocks. Monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA) twin pregnancies differ in placental sharing and hemodynamic environment, but whether these differences influence GAA remains unknown. We analyzed cord blood DNA methylation data from 49 monozygotic twin pairs (26 DCDA, 23 MCDA), estimating GAA using two DNA methylation-based gestational age clocks, to compare GAA between chorionicity groups among full-term neonates. Results Both clocks showed good within-pair GAA concordance, and GAA was consistently higher in MCDA than in DCDA pairs. Among full-term neonates, MCDA twins had significantly higher GAA according to one clock than DCDA twins (0.34 ± 0.96 vs. −0.27 ± 0.80 weeks; p = 0.010), while the other clock showed a similar directional trend without reaching statistical significance (p = 0.11). Regression analysis confirmed that MCDA chorionicity among full-term twins was associated with higher GAA relative to full-term DCDA twins (β = 0.64 weeks; 95% CI 0.02–1.26; p = 0.044), and this association remained robust in most sensitivity analyses adjusting for clinical and obstetric covariates. Preterm birth was not significantly associated with GAA by either clock. Conclusions Among full-term twins, chorionicity was independently associated with GAA, with MCDA twins exhibiting higher epigenetic maturity than DCDA twins, despite having the same gestational age at birth. These findings suggest that the hemodynamic environment associated with placental sharing — rather than gestational age at birth alone — may contribute to epigenetic maturation in twin pregnancies, raising the possibility that chorionicity should be further investigated as a biological variable relevant to neonatal risk stratification.

Prior studies have reported higher rates of pregnancy complications among racially and ethnically minoritized populations, highlighting structural inequities and social determinants of health. Migrant women may represent a socially vulnerable group with potential disparities in access to and utilization of maternity care. Although Korea operates a universal health coverage system that provides comprehensive maternity services to all pregnant women, including migrants, non-financial barriers may still influence care utilization and outcomes. This study evaluated prenatal care utilization and obstetric complications among migrant women in Korea. We conducted a nationwide, population-based cross-sectional study using National Health Insurance claims data in Korea. Migrant women were defined as foreign-national women registered in Korea’s resident registration system. Prenatal care utilization was assessed based on the number of prenatal visits, and obstetric complications were defined as the occurrence of any major pregnancy- or delivery-related complication. Prenatal care utilization and obstetric complications were compared between migrant women and Korean-born women, and adjusted odds ratios with 95

Objective:To evaluate changes in cesarean section (CS) rates in South Korea before and during the coronavirus disease 2019 (COVID-19) pandemic. Methods:This retrospective cohort study analyzed all deliveries recorded in the Korean National Health Insurance Service database (2015-2021). We compared CS rates between pre-pandemic (2015-2019) and pandemic (2020-2021) periods. Interrupted time-series analysis (ITSA) assessed temporal changes, stratified by parity. Sensitivity analyses evaluated a low-risk group, excluding major complications, and a term singleton nulliparous subgroup to assess changes in medical indications. Results:Of 2,255,524 deliveries, the overall CS rate increased from 45.7% to 56.8% (P<0.001). ITSA demonstrated a consistent pre-pandemic upward trend (relative risk [RR], 1.0023; 95% confidence interval [CI], 1.0022-1.0024) and a modest immediate increase at the onset of the pandemic (RR, 1.0097; 95% CI, 1.0011-1.0184), with no sustained slope changes. The low-risk CS rate rose from 29.5% to 42.0% (P<0.001), showing a similar immediate-onset increase (RR, 1.0087; 95% CI, 1.0005-1.017). The term singleton nulliparous rate increased from 43.1% to 56.4% (P<0.001), driven entirely by the pre-pandemic trend (RR, 1.0029; 95% CI, 1.0028-1.0030), with no statistically significant immediate pandemic effect (RR, 1.0089; 95% CI, 0.9994-1.0184). Conclusion:The COVID-19 pandemic was associated with a brief, immediate rise in overall CS rates but did not alter the long-term upward trends. This suggests persistent structural factors - such as a medico-legal environment, obstetrician shortages, and evolving practice norms - primarily drive South Korea's rising CS rates, rather than immediate clinical disruptions.

Background To describe current practice patterns and compare the effectiveness and safety of uterotonic agents for postpartum hemorrhage prevention after vaginal delivery. Methods This retrospective study used data prospectively collected from a multicenter cohort derived from a registered clinical trial (NCT05122169) conducted at nine obstetric centers in South Korea between December 2021 and July 2025. Patterns of uterotonic agent use were described, followed by comparative analyses among women who underwent vaginal delivery. Postpartum hemorrhage–related outcomes, including hemoglobin decrease by ≥ 2 g/dL, blood transfusion, and invasive hemostatic interventions, were compared using unadjusted analyses and multivariable logistic regression. Results Carbetocin was the most frequently used uterotonic agent (47.8%) in 2,585 women. Its use as a monotherapy was associated with lower rates of hemoglobin decrease by ≥ 2 g/dL compared with oxytocin-only use. In multivariable analyses, carbetocin-only use tended to be associated with lower odds of hemoglobin decrease by ≥ 2 g/dL compared with oxytocin-only use, although without statistical significance. The use of carbetocin in combination with additional uterotonic agents was associated with higher odds of hemoglobin decrease by ≥ 2 g/dL compared with carbetocin-only use. Conclusions This study provides a comprehensive analysis of uterotonic agent use in Korean obstetric practice, offering an evidence-based insight into the clinical importance of carbetocin use in vaginal delivery.

BackgroundMaternal chronic kidney disease (CKD) is associated with an increased risk of adverse pregnancy outcomes. However, the overall risk of congenital malformations (CMs) in offspring of mothers with kidney disease, including CKD and end-stage kidney disease (ESKD), remains unclear.MethodsIn this nationwide cohort study, we analyzed National Health Insurance Service (NHIS) data from 2,680,092 women who gave birth between 2008 and 2017. Major CMs were identified using the International Classification of Diseases-10 (ICD-10) codes during the first 12 months after birth. A multivariable generalized estimating equation model was used to compare the risk of CMs between women with CKD or ESKD, including those on dialysis and post-kidney transplantation (KT), and healthy controls.ResultsMajor CMs prevalence is 4.79% in offspring of healthy mothers, 5.29% in CKD mothers, and 9.65% in ESKD mothers, with congenital heart defects being the most common anomaly across all groups. After adjustment, mothers with kidney diseases show a higher risk of major CMs than healthy controls (adjusted odds ratio [aOR], 1.07; 95% confidence interval [CI], 1.03-1.11 in CKD; aOR, 1.71; 95% CI, 1.16-2.52 in ESKD, respectively). Among ESKD patients, KT recipients show an increased risk (aOR, 1.65; 95% CI, 1.06-2.59), but dialysis patients do not reach statistical significance (aOR, 2.02; 95% CI, 0.92-4.41).ConclusionsOur findings suggest that neonates born to mothers with kidney diseases have an increased risk of CMs compared to those born to healthy mothers.

Abstract Background Prenatal growth restriction has been associated with adverse neonatal and long- term health outcomes, yet the epigenetic mechanisms by which an adverse intrauterine environment shapes fetal immune development remain incompletely understood. Monozygotic dichorionic-diamniotic twins with selective fetal growth restriction (sFGR) provide a unique human model for investigating environmentally driven developmental programming independent of genetic variation and inter-twin placental vascular anastomoses. Methods Umbilical cord blood buffy coat samples were collected from three sFGR and two gestational age-matched concordant control twin pairs. Bulk RNA sequencing and genome-wide DNA methylation analysis were performed, followed by differential expression, pathway enrichment, hematopoietic and immune module analyses, differential methylation, and integrative transcriptomic-epigenomic analyses. Results Compared with concordant control twin pairs, discordant twins exhibited broad attenuation of immune and inflammatory transcriptional programs alongside enrichment of erythroid- and hypoxia-related pathways, consistent with adaptive hematopoietic responses to intrauterine stress. Within discordant twin pairs, the growth-restricted co-twins displayed marked transcriptional asymmetry characterized by selective enrichment of cytotoxic lymphoid signatures despite global suppression of myeloid and antigen-presenting cell-associated programs. Integrated transcriptomic and epigenomic analyses further revealed coordinated epigenetic remodeling, with hypomethylated regions in growth-restricted twins enriched for immune regulatory pathways, including T cell differentiation and leukocyte activation. At selected loci, concordant hypomethylation and increased gene expression suggested a potential epigenetic basis for the observed immune remodeling. Conclusions These findings suggest that intrauterine growth restriction is associated with coordinated hematopoietic and immune reprogramming at birth, consistent with both compositional and cell-intrinsic alterations. In genetically identical twins, relative growth divergence was associated with polarized transcriptional states, highlighting how intrauterine environmental differences may shape early immune development independent of genetic background.

OBJECTIVE:To assess the association between COVID-19 vaccination and the risk of the abnormal uterine bleeding (AUB) specifically focusing on vaginal or uterine bleeding that requires hospital care in women. METHODS:We used a nationwide database in the Republic of Korea that combined COVID-19 registry data, which contains information on COVID-19 vaccination, with the claims database of the National Health Insurance Service. We included women aged 16-64 who received their first vaccine dose and were newly diagnosed with AUB in inpatient or outpatient settings within 180 days after receiving the first dose. A population-based self-controlled case series analysis was used to estimate the incidence rate ratio (IRR) during the risk periods, including 1-14, 1-21, and 1-28 days after each vaccine dose, compared to the baseline period. The baseline period was defined as the period of 1-180 days following the first vaccine dose, excluding the periods that corresponds to the risk periods. To address the SCCS assumption violation from recurrent nature, only the first event during the observation period was considered. RESULTS:Among 83,422 eligible patients, the risk of AUB requiring hospital care within 14 days following COVID-19 vaccination was slightly elevated compared to the baseline period (IRR 1.04, 95 % CI 1.02-1.06). The risk was notably higher after the first dose, regardless of the risk interval (14-day risk period: IRR 1.12, 95 % CI 1.09-1.15; 21-day risk period: IRR 1.08, 95 % CI 1.06-1.10; 28-day risk period: IRR 1.07, 95 % CI 1.05-1.09). No significant increase was observed after the second and third doses. CONCLUSION:This study found a modest increase in healthcare utilization for AUB after the first dose of COVID-19 vaccination. However, this trend diminished with subsequent doses, showing no significantly increased risk. These findings should be interpreted while considering factors that influence healthcare-seeking behavior for unexpected vaginal or uterine bleeding.

The genetic risk for hypertensive disorders of pregnancy is linked with the development of atherosclerotic cardiovascular disease. However, the effects of lifestyle and metabolic syndrome on atherosclerotic cardiovascular disease have not been evaluated. Here, we assess the long-term association between these factors and atherosclerotic cardiovascular disease in women with genetic risk for hypertensive disorders of pregnancy. We evaluate the genetic risk for hypertensive disorders of pregnancy using a genome-wide polygenic risk score derived from a large-scale GWAS. The incidence of atherosclerotic cardiovascular disease is evaluated according to genetic risk, lifestyle, and metabolic syndrome. Individuals with a very high genetic risk for hypertensive disorders of pregnancy have a 53.0% higher chance of developing atherosclerotic cardiovascular disease than those with a low genetic risk. However, the risk of developing atherosclerotic cardiovascular disease is reduced by up to 64.6% through the maintenance of an ideal metabolic syndrome status and a healthy lifestyle in the high genetic risk group (top 20%), and by up to 65.4% in the low genetic risk group (bottom 20%). These findings emphasize that maintaining a healthy lifestyle in women is equally effective at reducing the risk of atherosclerotic cardiovascular disease independent of genetic risk for hypertensive disorders of pregnancy.

Importance:Recent guidelines have recommended corticosteroid injection in women with singleton pregnancies at risk of late preterm delivery. However, the effectiveness of antenatal corticosteroid administration in women with twin pregnancies at risk of late preterm delivery has not been evaluated, and studies on this population are lacking. Objective:To evaluate whether antenatal betamethasone administration reduces the risk of neonatal respiratory morbidity in late preterm twin neonates. Design, Setting, and Participants:In this multicenter randomized trial, twin-pregnant women at 34 weeks 0 days to 36 weeks 5 days of gestation at risk of late preterm delivery were enrolled across 8 university-based clinical centers in Korea. Data were collected between May 2018 and July 2024. Intention-to-treat analysis was performed. Intervention:The participants received 2 injections of betamethasone or placebo after randomization (1:1). Main Outcomes and Measures:The primary outcome was perinatal death within 72 hours after birth or severe neonatal respiratory morbidity. The exploratory outcomes were mild neonatal respiratory morbidities, other neonatal respiratory morbidities, other neonatal complications, or maternal complications. Results:A total of 812 participants were randomized and analyzed, with 410 in the intervention group (median [IQR] age, 35 [33-37] years) and 402 in the placebo group (median [IQR] age, 35 [32-38] years). Among 1620 neonates (818 in the intervention group and 802 in the placebo group), there were no perinatal deaths in either group, and severe neonatal respiratory morbidity occurred in 99 neonates (6.1%), with lower risk in the betamethasone group than in the placebo group (39 [4.8%] vs 60 [7.5%]; relative risk [RR], 0.64 [95% CI, 0.42-0.98]). For the exploratory outcomes, continuous positive airway pressure use for 2 hours or more (RR, 0.58 [95% CI, 0.35-0.95]) and transient tachypnea of the newborn (RR, 0.47 [95% CI, 0.25-0.89]) were lower in the betamethasone group. The risk of primary outcome and mild respiratory morbidities was reduced only in neonates delivered between 12 hours or more and less than 7 days after the first betamethasone administration. The risk of neonatal hypoglycemia was increased in the betamethasone group (128 [15.6%] vs 94 [11.7%]; RR, 1.33 [95% CI, 1.01-1.75]), but the risk of neonatal sepsis or maternal chorioamnionitis did not differ between the 2 groups. Conclusions and Relevance:In this randomized clinical trial, antenatal betamethasone administration in women with twin pregnancies at risk of late preterm delivery significantly reduced the risk of neonatal respiratory morbidity. The outcomes from this study could serve as a valuable reference in clinical management of twin pregnancies at risk of late preterm delivery. Trial Registration:ClinicalTrials.gov Identifier: NCT03547791.

OBJECTIVES Adverse pregnancy outcomes (APOs) and low socioeconomic status (SES) are both associated with an increased long-term risk of atherosclerotic cardiovascular disease (ASCVD). In this analysis, we evaluated whether the association between a history of APO and ASCVD risk varies across different SES groups. METHODS We conducted this analysis using data from the UK Biobank, a large prospective cohort including participants aged 40 years to 69 years recruited between 2006 and 2010, with ongoing follow-up. APOs included hypertensive disorders of pregnancy, gestational diabetes mellitus, low birth weight (<2.5 kg), and stillbirth. At enrollment, SES was assessed using the following indicators: household income, education, employment, and Townsend Deprivation Index. The adjusted hazard ratio (aHR) for new-onset ASCVD was analyzed according to history of APO and SES categories. RESULTS Among 146,064 women, those with a history of APO had a higher risk of new-onset ASCVD and overall lower SES—including lower income, less education, higher unemployment, and greater deprivation—compared with those without APO (p<0.001). The increased ASCVD risk associated with APO history was significant only in the low SES group (aHR, 1.26; 95% confidence interval [CI], 1.16 to 1.36), but not in the high SES group (aHR, 1.07; 95% CI, 0.74 to 1.55, p=0.716). CONCLUSIONS We found that women with low SES were more vulnerable to the adverse effects of APO history, resulting in a greater increase in ASCVD risk. This study highlights the need for SES-tailored preventive policies to reduce long-term cardiovascular disease in women with a history of APO.

This study aims to identify early metabolomic biomarkers of gestational diabetes mellitus (GDM) and evaluate their association with hepatic steatosis. We compared maternal serum metabolomic profiles between women who developed GDM (n = 118) and matched controls (n = 118) during the first (10–14 gestational weeks) and second (24–28 gestational weeks) trimesters using ultra-performance liquid chromatography coupled with mass spectrometry. Mediation analysis was performed to evaluate the mediating role of metabolic dysfunction-associated steatotic liver disease (MASLD) in the relationship between metabolites and subsequent development of GDM. A refined prediction model was developed to predict GDM using established clinical factors and selected metabolites. Significant alterations in circulating metabolites, including amino acids, bile acids, and phospholipids, were observed in the GDM group compared to controls during early pregnancy. Mediation analysis revealed that several metabolites, including glycocholic acid (proportion mediated (PM) = 31.9 Gestational diabetes mellitus (GDM) is a common pregnancy complication with significant health risks. Early identification of women at high risk for GDM is crucial for timely intervention and improved outcomes. What alterations in circulating metabolites during early pregnancy are associated with subsequent GDM development? Does metabolic dysfunction-associated steatotic liver disease (MASLD) mediate the association between specific metabolites and GDM risk? Significant alterations in bile acids, amino acids, phosphatidylethanolamines, and phosphatidylinositols were observed in early pregnancy sera of women who later developed GDM. MASLD significantly mediated the effects of several metabolites on GDM risk, with mediation proportions ranging from 9.7 to 31.9

Recent guidelines have recommended corticosteroid injection in women with singleton pregnancies at risk of late preterm delivery. However, the effectiveness of antenatal corticosteroid administration in women with twin pregnancies at risk of late preterm delivery has not been evaluated, and studies on this population are lacking. To evaluate whether antenatal betamethasone administration reduces the risk of neonatal respiratory morbidity in late preterm twin neonates. In this multicenter randomized trial, twin-pregnant women at 34 weeks 0 days to 36 weeks 5 days of gestation at risk of late preterm delivery were enrolled across 8 university-based clinical centers in Korea. Data were collected between May 2018 and July 2024. Intention-to-treat analysis was performed. The participants received 2 injections of betamethasone or placebo after randomization (1:1). The primary outcome was perinatal death within 72 hours after birth or severe neonatal respiratory morbidity. The exploratory outcomes were mild neonatal respiratory morbidities, other neonatal respiratory morbidities, other neonatal complications, or maternal complications. A total of 812 participants were randomized and analyzed, with 410 in the intervention group (median [IQR] age, 35 [33-37] years) and 402 in the placebo group (median [IQR] age, 35 [32-38] years). Among 1620 neonates (818 in the intervention group and 802 in the placebo group), there were no perinatal deaths in either group, and severe neonatal respiratory morbidity occurred in 99 neonates (6.1%), with lower risk in the betamethasone group than in the placebo group (39 [4.8%] vs 60 [7.5%]; relative risk [RR], 0.64 [95% CI, 0.42-0.98]). For the exploratory outcomes, continuous positive airway pressure use for 2 hours or more (RR, 0.58 [95% CI, 0.35-0.95]) and transient tachypnea of the newborn (RR, 0.47 [95% CI, 0.25-0.89]) were lower in the betamethasone group. The risk of primary outcome and mild respiratory morbidities was reduced only in neonates delivered between 12 hours or more and less than 7 days after the first betamethasone administration. The risk of neonatal hypoglycemia was increased in the betamethasone group (128 [15.6%] vs 94 [11.7%]; RR, 1.33 [95% CI, 1.01-1.75]), but the risk of neonatal sepsis or maternal chorioamnionitis did not differ between the 2 groups. In this randomized clinical trial, antenatal betamethasone administration in women with twin pregnancies at risk of late preterm delivery significantly reduced the risk of neonatal respiratory morbidity. The outcomes from this study could serve as a valuable reference in clinical management of twin pregnancies at risk of late preterm delivery. ClinicalTrials.gov Identifier: NCT03547791

Background: Pregnancy and delivery are known to increase the risk of cerebrovascular events (CVEs) in patients with moyamoya disease (MMD). This study determined the frequency, risk factors, and outcome of CVEs during pregnancy in MMD. Methods: We conducted a multicenter study involving 171 MMD patients with 196 deliveries across four Korean tertiary institutions between 1990 and 2023. Data on MMD-related clinical, imaging, and operative findings were collected. We analyzed CVEs and pregnancy outcomes, including delivery mode and anesthesia. Univariate and multivariate analyses were performed to identify risk factors for peripartum CVEs. Results: Peripartum CVEs occurred in 5.6% of pregnancies, with intracerebral hemorrhage being the most common, followed by cerebral infarction. CVEs were more common in women diagnosed with MMD during pregnancy (85.7% vs. 2.6% in women diagnosed before pregnancy) and in women who had not completed revascularization before pregnancy or were hemodynamically unstable: 55.6% versus 1.1%. Delivery mode and anesthesia showed no significant association with the occurrence of CVEs. Multivariate analysis revealed that the “non-revascularized or hemodynamically unstable” group remained a significant risk factor for peripartum CVEs (adjusted odds ratio (OR) = 353.23, P < 0.001). CVEs resulted in maternal functional impairment in 4 of 11 affected cases (36.4%) and fetal loss in 2 of 11 cases (18.2%). Conclusion: This study highlights the protective effect of revascularization on peripartum CVEs and proposes a structured clinical protocol, recommending prepregnancy hemodynamic assessment and neurosurgical consultation. Women diagnosed with MMD during pregnancy and those in the “non-revascularized or hemodynamically unstable” group should be considered a high-risk group for peripartum CVEs.

OBJECTIVE:To investigate whether genetic predisposition to pre-eclampsia (PE), measured by a polygenic risk score (PRS), is associated with incident hypertension and cardiovascular disease (CVD) after delivery in Asian women. DESIGN:Prospective population-based cohort study. SETTING:Data were utilised from the Korean Genome and Epidemiology Study and additional multicentre cohorts. POPULATION:35 872 parous Korean women aged 40-80 years at last surveillance, with genotype data, no history of hypertension or CVD before delivery, and complete clinical information. For external validation, 559 parous Korean women were included. METHODS:The PE-PRS was calculated for Asian women, and the study population was divided into the high PE-PRS and low PE-PRS groups. The long-term risks of incident hypertension and CVD (ischaemic heart disease or stroke) after delivery were compared between the groups. MAIN OUTCOME MEASURES:Incident hypertension and CVD after delivery. RESULTS:Women in the high PE-PRS group had an increased risk of developing hypertension (adjusted hazard ratio [aHR] 1.25, 95% CI 1.17-1.34) and ischaemic heart disease (aHR 1.28, 95% CI 1.07-1.54) compared to the low PE-PRS group. The risk of hypertension was highest among women with both a history of PE and a high PE-PRS. CONCLUSIONS:Genetic predisposition to PE, as measured by the PE-PRS, is associated with an elevated risk of incident hypertension and ischaemic heart disease in Asian women. These findings suggest the potential utility of the PE-PRS as a complementary tool in assessing individualised hypertension risk in parous women.

Timely detection of abnormal cardiotocography (CTG) during labor plays a crucial role in enhancing fetal prognosis. Recent research has explored the use of deep learning for CTG interpretation, most studies rely on small, localized datasets or focus on outcomes less relevant to clinical practice. To address these limitations, we developed a clinically applicable model using a large-scale, nationwide CTG dataset with reliable annotations provided by a board-certified obstetrician. Our study utilized 22,522 deliveries from 14 hospitals, each including cardiotocography (CTG) recordings of up to 75 min in length. The CTG signals were segmented into 5-minute intervals, resulting in a total of 519,800 person-minutes of analyzed data. We trained and validated a deep learning model based on CTG segments for classifying normal and abnormal CTGs. In the independent test dataset, the model achieved an AUC (area under the receiver operating characteristic curve) of 0.880 and PRC (area under the precision-recall curve) of 0.625 in internal tests. External tests across three datasets achieved AUCs of 0.862, 0.895, and 0.862 and PRCs of 0.553, 0.615, and 0.601. Our study results show the potential of the deep learning for automated CTG interpretation. We will evaluate this model in future prospective studies to assess the model's clinical applicability.

BACKGROUND:In women with singleton pregnancy who are at risk of late preterm delivery, administration of antenatal corticosteroids is recommended to reduce neonatal respiratory complications. However, the adoption of this practice is not widely accepted in twin pregnancies because of a lack of evidence regarding both the effectiveness and long-term safety of corticosteroids. This study was conducted to evaluate the long-term neurodevelopmental outcomes of twins according to the administration of antenatal corticosteroid in late preterm. METHODS:This nationwide population based retrospective cohort study included twins who were delivered late preterm (34+0-36+6 weeks) between 2007 and 2010. The study population were divided into 2 groups according to the administration of preterm antenatal corticosteroids. Group 1 included twins from mothers who were administered antenatal corticosteroids in late preterm (with late preterm corticosteroids), and group 2 included twins whose mothers were not administered antenatal corticosteroid (without corticosteroids). The risk of long-term adverse neurodevelopmental outcomes was compared between the 2 groups. The composite adverse neurodevelopmental outcome was defined as the occurrence of at least one of the following: autism, cerebral palsy, speech articulation disorder, developmental disorders of scholastic skills, or developmental disorders of motor function. RESULTS:During the study period, 9,450 children met the inclusion criteria: 1,476 children in group 1 (with late preterm corticosteroids) and 7,974 children in group 2 (without corticosteroids). There was no statistically significant difference in the long-term adverse neurodevelopmental outcomes between the 2 groups. This result was consistent even after adjusting for covariates (adjusted hazard ratio 0.973 [95% confidence interval, 0.811-1.166]). CONCLUSION:The risk of long-term adverse neurodevelopmental outcomes did not increase after antenatal corticosteroid administration in twin children who were born in late preterm.

Background and AimsAdverse pregnancy outcomes (APOs) can worsen cardiometabolic risk factors in women, raising their likelihood of developing cardiometabolic diseases at a young age after their initial pregnancy. Nevertheless, there is limited data on the risk of newly developing metabolic dysfunction-associated steatotic liver disease (MASLD) in women who have had APOs. This study aimed to evaluate the risk of new-onset MASLD after experiencing APOs.MethodsSingleton pregnant women who underwent national health screenings one year before pregnancy and one year after delivery were included in this study. APOs were defined as the presence of at least one of the followings: hypertensive disorders of pregnancy (HDP), gestational diabetes mellitus (GDM), preterm birth, low birth weight, and placental abruption. The primary outcome was new-onset MASLD based on the presence of APOs.ResultsAmong 80,037 study participants, 9,320 (11.6%) experienced APOs during pregnancy. Women who experienced APOs had an increased risk of developing new-onset MASLD after delivery even after adjustments for various covariates (adjusted OR, 1.58; 95% CI, 1.45–1.72). In particular, women who experienced either HDP or GDM showed a significantly increased risk of developing new-onset MASLD (aOR, 2.20; 95% CI, 1.81–2.67 for HDP and aOR, 1.83; 95% CI, 1.65–2.03 for GDM). Moreover, there was a tendency toward an increased risk of new-onset MASLD according to the number of APOs. (P<0.001 for trend of odds).ConclusionsAPOs were associated with the risk of new-onset MASLD after delivery. Specifically, only HDP or GDM were identified as risk factors for new-onset MASLD.Impact and implicationsThis nationwide cohort study confirms that postpartum women with a history of adverse pregnancy outcomes (APOs) are at an increased risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). These findings may bring us one step closer to understanding the exact mechanisms underlying such an important association between prior APOs and cardiovascular disease (CVD) risk among postpartum women. This bidirectional association between APOs and MASLD highlights the importance of considering pregnancy history in assessing CVD risk in women. It suggests a need for closer monitoring and lifestyle interventions for women with a history of APOs to reduce the risk of MASLD and subsequent CVD complications.

Adverse pregnancy outcomes (APO) have been reported to increase the risk of long-term cardiovascular or metabolic disease later in life. In the current study, we tried to evaluate the risk of dementia in middle-aged women according to the history of APO. The UK Biobank is a prospective cohort study from 2006 to 2010, encompassing > 500,000 individuals at 40-60 years from the United Kingdom. Among them, we included 220,395 women and compared the new onset of dementia according to the history of APO using the Cox proportional hazard model. In middle-aged women, dementia has newly occurred in a total of 3,047 women (1.38%) during follow up. Among APOs, only history of stillbirth increased the risk of dementia whereas other APOs such as hypertensive disease in pregnancy, gestational diabetes mellitus, and recurrent spontaneous abortion was not associated with the risk of dementia. Even after adjusting the confounding variables, women who had a history of stillbirth increased risk of a new onset of dementia. (HR 1.1855, p=0.048). History of stillbirth was associated with an increased risk of dementia and should be also considered as a risk factor for dementia.

Premature rupture of membranes (PROM) is defined as rupture of fetal membranes before the onset of labor. Prolactin (PRL) is secreted by decidual membranes and accumulated significantly in the amniotic fluid during pregnancy. PRL could ameliorate inflammation and collagen degradation in fetal membranes. However, the role of PRL in amniotic membrane is not well characterized. We isolated human amniotic epithelial stem cells (hAESCs) from human fetal membranes to study the effect of PRL on proliferation, migration, and antioxidative stress. Amniotic pore culture technique (APCT) model was constructed to evaluate the tissue regeneration effect in vitro. The potential targets and pathways of PRL acting in amnion via integrated bioinformatic methods. PRL had a dose-dependent effect on hAESCs in vitro. PRL (500 ng/mL) significantly improved the viability of hAESCs and inhibited cell apoptosis, related to the upregulation of CCN2 expression and downregulation of Bax, Caspase 3, and Caspase 8. PRL accelerated migration process in hAESCs via downregulation of MMP2, MMP3, and MMP9. PRL attenuated the cellular damage and mitochondrial dysfunction induced by hydrogen peroxide in hAESCs. PRL accelerated the healing process in the APCT model significantly. The top 10 specific targets (IGF1R, SIRT1, MAP2K1, CASP8, MAPK14, MCL1, NFKB1, HIF1A, MTOR, and HSP90AA1) and signaling pathways (such as HIF signaling pathway) were selected using an integrated bioinformatics approach. PRL improves the viability and antioxidative stress function of hAESCs and the regeneration of ruptured amniotic membranes in vitro. Thus, PRL has great therapeutic potential for prevention and treatment of ruptured membranes.

IntroductionAlthough the safety and effectiveness of COVID-19 vaccination during pregnancy have been proven, there is still little data explaining neonatal outcomes of maternal pre-pregnancy vaccination.MethodsHere, we investigated the impact of vaccination and SARS-CoV-2 infection on maternal-neonate immune response in a cohort study involving 141 pregnant individuals, and defined the importance of maternal COVID-19 vaccination timing for its effectiveness.Results and discussionOur data indicate that vertically transferred maternal hybrid immunity provides significantly better antiviral protection for a neonate than either maternal post-infection or post-vaccination immunity alone. Higher neutralization potency among mothers immunized before pregnancy and their newborns highlights the promising role of pre-pregnancy vaccination in neonatal protection. A comparison of neutralizing antibody titers calculated for each dyad suggests that infection and pre-/during-pregnancy vaccination all support transplacental transfer, providing the offspring with strong passive immunity against SARS-CoV-2. Analysis of neutralizing antibody levels in maternal sera collected during pregnancy and later during delivery shows that immunization may exert a positive effect on maternal protection.