Long-term cardiovascular outcome in women with preeclampsia in Korea: a large population-based cohort study and meta-analysis.

Recent studies reported the long-term cardiovascular risk of preeclampsia. However, only a few studies have investigated the association between preeclampsia and long-term cardiovascular disease in Asian populations, although there could be racial/ethnic differences in the risk of cardiovascular diseases. Therefore, we aimed to evaluate the long-term effects of preeclampsia on cardiovascular disease in an Asian population. This study included 68,658 parous women in the Health Examinees Study (HEXA) cohort of South Korea and compared the risk of long-term cardiovascular disease, including ischemic heart disease and stroke, according to the history of preeclampsia. We also performed a meta-analysis combining current study data with data from existing literature in the Asian population. Among the study population, 3413 (5.23%) women had a history of preeclampsia, and 767 (1.12%) and 404 (0.59%) women developed ischemic heart disease and stroke for 22 years. Women with a history of preeclampsia were at a higher risk for both ischemic heart disease (adjusted hazard ratio 1.66 [1.19-2.04]) and stroke (adjusted hazard ratio 1.48 [1.02-2.16]) than those without. In the meta-analysis, the pooled hazard ratio of ischemic heart disease and stroke were also increased in women with a history of preeclampsia (ischemic heart disease 1.65 [1.51-1.82]; stroke 1.78 [1.52-2.10]).

Chromosomal Microarray Analysis in Fetuses With Ultrasonographic Soft Markers: A Meta-Analysis of the Current Evidence.

BACKGROUND: Ultrasonographic soft markers are normal variants, rather than fetal abnormalities, and guidelines recommend a detailed survey of fetal anatomy to determine the necessity of antenatal karyotyping. Anecdotal reports have described cases with ultrasonographic soft markers in which chromosomal microarray analysis (CMA) revealed pathogenic copy number variants (CNVs) despite normal results on conventional karyotyping, but CMA for ultrasonographic soft markers remains a matter of debate. In this systematic review, we evaluated the clinical significance of CMA for pregnancies with isolated ultrasonographic soft markers and a normal fetal karyotype. METHODS: An electronic search was conducted by an experienced librarian through the MEDLINE, Embase, and Cochrane CENTRAL databases. We reviewed 3,338 articles (3,325 identified by database searching and 13 by a hand search) about isolated ultrasonographic soft markers, and seven ultrasonographic markers (choroid plexus cysts, echogenic bowel, echogenic intracardiac focus, hypoplastic nasal bone, short femur [SF], single umbilical artery, and urinary tract dilatation) were included for this study. RESULTS: Seven eligible articles were included in the final review. Pathogenic or likely pathogenic CNVs were found in fetuses with isolated ultrasonographic soft markers and a normal karyotype. The overall prevalence of pathogenic or likely pathogenic CNVs was 2.0% (41 of 2,048). The diagnostic yield of CMA was highest in fetuses with isolated SF (9 of 225, 3.9%). CONCLUSION: CMA could aid in risk assessment and pregnancy counseling in pregnancies where the fetus has isolated ultrasonographic soft markers along with a normal karyotype.

Placental expression quantitative trait loci in an East Asian population.

Expression quantitative trait loci (eQTL) analysis measures the contribution of genetic variation in gene expression on complex traits. Although this methodology has been used to examine gene regulation in numerous human tissues, eQTL research in solid tissues is relatively lacking. We conducted eQTL analysis on placentas collected from an East Asian population in an effort to identify gene regulatory mechanisms in this tissue. Placentas (n = 102) were collected at the time of cesarean delivery. mRNA was extracted, sequenced with NGS, and compared with matched maternal and fetal DNA arrays performed using maternal and neonatal cord blood. Linear regression modeling was performed using tensorQTL. Fine-mapping along with epigenomic annotation was used to select putative functional variants. We identified 2,703 coding genes that contained at least one eQTL with statistical significance (false discovery rate <0.05). After fine-mapping, we found 108 previously unreported eQTL variants with posterior inclusion probability >0.1. Of these, 19% were located in genomic regions with evidence from public placental epigenome suggesting that they may be functionally relevant. For example, variant rs28379289 located in the placenta-specific regulatory region changes the binding affinity of transcription factor leading to higher expression of LGALS3, which is known to affect placental function. This study expands the knowledge base of regulatory elements within the human placenta and identifies 108 previously unreported placenta eQTL signals, which are listed in our publicly available GMI eQTL database. Further studies are needed to identify and characterize genetic regulatory mechanisms that affect placental function in normal pregnancy and placenta-related diseases.

Future risk of metabolic syndrome after recurrent pregnancy loss: a cohort study using UK Biobank.

OBJECTIVE: To evaluate the risk of metabolic syndrome (MS) after recurrent pregnancy loss (RPL) using UK Biobank data. A history of pregnancy loss is associated with the development of cardiovascular diseases in the future. However, the association between RPL and subsequent MS is poorly understood. Therefore, we aimed to check the risk of MS after RPL. DESIGN: The study population was divided into 2 groups according to reproductive history: women with a history of RPL and women without a history of RPL. Recurrent pregnancy loss was defined as 2 or more spontaneous miscarriages, and MS was defined as at least 3 of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, high-blood pressure, and hyperglycemia. SETTING: UK Biobank resource. PATIENTS: The UK Biobank is a prospective cohort study that enrolled individuals aged between 40 and 69 years whose medical and reproductive histories were retrieved at enrollment. In this cohort, only women with a history of at least one pregnancy were selected. INTERVENTIONS: Recurrent pregnancy loss. MAIN OUTCOME MEASURES: The primary outcome was the prevalence of MS. The secondary outcomes were 5 diagnostic components of MS. RESULTS: We analyzed 228,674 women, including 15,702 with a history of RPL and 212,972 without a history of RPL. Women with a history of RPL have a higher prevalence of MS between the ages of 40 and 60 years (33.0% vs. 31.5%). After adjusting for covariates (age, race, number of live births, early menopause, smoking, alcohol consumption, and physical activity), the increased risk of MS after RPL remained significant (adjusted odds ratio, 1.10; 95% confidence interval, 1.06-1.15). Furthermore, in the analysis of the 5 diagnostic components of MS, a history of RPL significantly increased the risk of abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol levels, and hyperglycemia. CONCLUSION: Middle-aged women with a history of RPL have an increased risk of MS.

Transglutaminase 2 Prevents Premature Senescence and Promotes Osteoblastic Differentiation of Mesenchymal Stem Cells through NRF2 Activation.

Transglutaminase 2 (TG2) is a multifunctional enzyme that exhibits transamidase, GTPase, kinase, and protein disulfide isomerase (PDI) activities. Of these, transamidase-mediated modification of proteins regulates apoptosis, differentiation, inflammation, and fibrosis. TG2 is highly expressed in mesenchymal stem cells (MSCs) compared with differentiated cells, suggesting a role of TG2 specific for MSC characteristics. In this study, we report a new function of TG2 in the regulation of MSC redox homeostasis. During in vitro MSC expansion, TG2 is required for cell proliferation and self-renewal by preventing premature senescence but has no effect on the expression of surface antigens and oxidative stress-induced cell death. Moreover, induction of differentiation upregulates TG2 that promotes osteoblastic differentiation. Molecular analyses revealed that TG2 mediates tert-butylhydroquinone, but not sulforaphane, -induced nuclear factor erythroid 2-related factor 2 (NRF2) activation in a transamidase activity-independent manner. Differences in the mechanism of action between two NRF2 activators suggest that PDI activity of TG2 may be implicated in the stabilization of NRF2. The role of TG2 in the regulation of antioxidant response was further supported by transcriptomic analysis of MSC. These results indicate that TG2 is a critical enzyme in eliciting antioxidant response in MSC through NRF2 activation, providing a target for optimizing MSC manufacturing processes to prevent premature senescence.

Electrocardiogram-based deep learning model to screen peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy, one of the most fatal conditions during delivery, results in heart failure secondary to left ventricular systolic dysfunction. Left ventricular dysfunction can result in abnormalities in electrocardiography. However, the usefulness of electrocardiography in the identification of peripartum cardiomyopathy in pregnant women remains unclear. OBJECTIVE: This study aimed to evaluate the effectiveness of a 12-lead electrocardiography-based artificial intelligence/machine learning-based software as a medical device for screening peripartum cardiomyopathy. STUDY DESIGN: This retrospective cohort study included pregnant women who underwent transthoracic echocardiography between a month before and 5 months after delivery and underwent 12-lead electrocardiography within 30 days of echocardiography between December 2011 and May 2022 at Seoul National University Hospital. The performance of 12-lead electrocardiography-based artificial intelligence/machine learning analysis (AiTiALVSD software; version 1.00.00, which was developed to screen for left ventricular systolic dysfunction in the general population) was evaluated for the identification of peripartum cardiomyopathy. In addition, the performance of another artificial intelligence/machine learning algorithm using only 1-lead electrocardiography to detect left ventricular systolic dysfunction was evaluated in identifying peripartum cardiomyopathy. The results were obtained under a 95% confidence interval and considered significant when P<.05. RESULTS: Among the 14,557 women who delivered during the study period, 204 (1.4%) underwent transthoracic echocardiography a month before and 5 months after delivery. Among them, 12 (5.8%) were diagnosed with peripartum cardiomyopathy. The results showed that AiTiALVSD for 12-lead electrocardiography was highly effective in detecting peripartum cardiomyopathy, with an area under the receiver operating characteristic of 0.979 (95% confidence interval, 0.953-1.000), an area under the precision-recall curve of 0.715 (95% confidence interval, 0.499-0.951), a sensitivity of 0.917 (95% confidence interval, 0.760-1.000), a specificity of 0.927 (95% confidence interval, 0.890-0.964), a positive predictive value of 0.440 (95% confidence interval, 0.245-0.635), and a negative predictive value of 0.994 (95% confidence interval, 0.983-1.000). In addition, a 1-lead (lead I) artificial intelligence/machine learning algorithm showed excellent performance; the area under the receiver operating characteristic, area under the precision-recall curve, sensitivity, specificity, positive predictive value, and negative predictive value were 0.944 (95% confidence interval, 0.895-0.993), 0.520 (95% confidence interval, 0.319-0.801), 0.833 (95% confidence interval, 0.622-1.000), 0.880 (95% confidence interval, 0.834-0.926), 0.303 (95% confidence interval, 0.146-0.460), and 0.988 (95% confidence interval, 0.972-1.000), respectively. CONCLUSION: The 12-lead electrocardiography-based artificial intelligence/machine learning-based software as a medical device (AiTiALVSD) and 1-lead algorithm are noninvasive and effective ways of identifying cardiomyopathies occurring during the peripartum period, and they could potentially be used as highly sensitive screening tools for peripartum cardiomyopathy.

The Effect of Vanishing Twin on First- and Second-Trimester Maternal Serum Markers and Nuchal Translucency: A Multicenter Prospective Cohort Study.

BACKGROUND: The purpose of this study was to evaluate the effect of vanishing twin (VT) on maternal serum marker concentrations and nuchal translucency (NT). METHODS: This is a secondary analysis of a multicenter prospective cohort study in 12 institutions. Serum concentrations of pregnancy-associated plasma protein-A in the first trimester and alpha-fetoprotein (AFP), total human chorionic gonadotrophin, unconjugated estriol, and inhibin A in the second trimester were measured, and NT was measured between 10 and 14 weeks of gestation. RESULTS: Among 6,793 pregnant women, 5,381 women were measured for serum markers in the first or second trimester, including 65 cases in the VT group and 5,316 cases in the normal singleton group. The cases in the VT group had a higher median multiple of the median value of AFP and inhibin A than the normal singleton group. The values of other serum markers and NT were not different between the two groups. After the permutation test with adjustment, AFP and inhibin A remained significant differences. The frequency of abnormally increased AFP was also higher in the VT group than in the normal singleton group. CONCLUSION: VT can be considered as an adjustment factor for risk assessment in the second-trimester serum screening test.

Trend of fetal echocardiography use and comparison of medical costs for congenital heart disease treatment based on fetal echocardiography use in a Korean single center.

Background: The rate of the prenatal diagnosis of congenital heart disease is increasing along with advances in fetal echocardiography techniques. Here, we aimed to investigate the trend of the use of fetal echocardiography over time and to compare the medical costs of congenital heart disease treatment according to whether fetal echocardiography was performed. Methods: We reviewed our hospital's database, and patients who underwent the first surgery for congenital heart disease within 30 days of birth during 2005-2007, 2011-2013, and 2017-2019 were included. The severity of congenital heart disease diagnosed in each case was evaluated according to The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality Scores (STS-EACTS Mortality Scores) and Mortality Categories (STAT Mortality Categories). Results: In total, 375 patients were analyzed, and fetal echocardiography use increased significantly after the 2010s compared with in 2005-2007 (19.1% vs. 39%, p = 0.032 in Mortality Category 1-3; 15.5% vs. 69.5%, p = 0.000 in Mortality Category 4-5). Additionally, the mean STS-EACTS Mortality Score was higher in prenatally diagnosed patients than in postnatally diagnosed patients (2.287 vs. 1.787, p = 0.001). In the recent period, there was no significant difference in hospitalization durations and medical costs according to whether or not fetal echocardiography was performed. Conclusions: This single center study showed the use of fetal echocardiography is increasing. Further, prenatal diagnosis with fetal echocardiography causing no differences in medical costs in recent years. Therefore, we suggest that fetal echocardiography can be applied more widely without increasing the economic burden.

Increased risk of congenital malformations in offspring born to women with systemic lupus erythematosus in South Korea: a nationwide population-based study.

OBJECTIVES: The aim of this study was to determine the risk of congenital malformations in offspring born to women with systemic lupus erythematosus (SLE). METHODS: This nationwide population-based study included Korean women who had a singleton pregnancy. The risk of congenital malformations in women with SLE was compared with those without SLE. Multivariable analyses were performed to estimate the OR of congenital malformations. In a sensitivity analysis, the risk of malformation was compared between the offspring of women with SLE and those of propensity-matched women without SLE. RESULTS: Of a total of 3 279 204 pregnant women, 0.1% had SLE and their offspring had a higher frequency of congenital malformations (17.13% vs 11.99%, p<0.0001). After adjustment for age, parity, hypertension, diabetes, and fetal sex, the SLE group was found to be associated with an increased risk of congenital malformations in the nervous system (adjusted OR (aOR, 1.90; 95% CI, 1.20 to 3.03), eye, ear, face, and neck (aOR, 1.37; 95% CI, 1.09 to 1.71), circulatory system (aOR, 1.91; 95% CI, 1.67 to 2.20), and musculoskeletal system (aOR, 1.26; 95% CI, 1.05 to 1.52). Even after propensity matching, some of the tendencies were maintained. CONCLUSIONS: This nationwide population-based study in South Korea indicates that compared with the general population, neonates born to SLE mothers have a slightly increased risk of congenital malformations affecting the nervous system, head and neck, cardiovascular system, and musculoskeletal system. When a woman with lupus becomes pregnant, careful fetal ultrasound and newborn screening can be helpful in identifying the risk of potential malformations.

Management of the smaller twin with impending compromise in twin pregnancies complicated by selective fetal growth restriction: a questionnaire-based study of clinical practice patterns.

BACKGROUND: In twin pregnancies complicated by selective fetal growth restriction (sFGR), if the smaller twin is in the state of impending intra-uterine death (IUD), immediate delivery will reduce the risk of IUD of the smaller twin while exposing the larger twin to iatrogenic preterm birth (PTB). Therefore, the management options would either be to maintain pregnancy for the maturation of the larger twin despite the risk of IUD of the smaller twin or immediate delivery to prevent IUD of the smaller twin. However, the optimal gestational age of management transition from maintaining pregnancy to immediate delivery has not been established. The objective of this study was to evaluate the physician's perspective on the optimal timing of immediate delivery in twin pregnancies complicated by sFGR. METHODS: An online cross-sectional survey was performed with obstetricians and gynecologists (OBGYN) in South Korea. The questionnaire asked the following: (1) whether participants would maintain or immediately deliver a twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin; (2) the optimal gestational age of management transition from maintaining pregnancy to immediate delivery in a twin pregnancy with impending IUD of the smaller twin; and (3) the limit of viability and intact survival in general preterm neonates. RESULTS: A total of 156 OBGYN answered the questionnaires. In a clinical scenario of dichorionic (DC) twin pregnancy complicated by sFGR with signs of impending IUD of the smaller twin, 57.1% of the participants answered that they would immediately deliver the twin pregnancy. However, 90.4% answered that they would immediately deliver the pregnancy in the same scenario for monochorionic (MC) twin pregnancy. The participants designated 30 weeks for DC twin and 28 weeks for MC twin pregnancies as the optimal gestational age of management transition from maintaining pregnancy to immediate delivery. The participants regarded 24 weeks as the limit of viability and 30 weeks as the limit of intact survival in general preterm neonates. The optimal gestational age of management transition for DC twin pregnancy was correlated with the limit of intact survival in general preterm neonates (p < 0.001), but not with the limit of viability. However, the optimal gestational age of management transition for MC twin pregnancy was associated with both the limit of intact survival (p = 0.012) and viability with marginal significance (p = 0.062). CONCLUSIONS: Participants preferred to immediately deliver twin pregnancies complicated by sFGR with impending IUD of the smaller twin at the limit of intact survival (30 weeks) for DC twin pregnancies and at the midway between the limit of intact survival and viability (28 weeks) for MC twin pregnancies. More research is needed to establish guidelines regarding the optimal delivery timing for twin pregnancies complicated by sFGR.

Long-term adverse neurodevelopmental outcomes of discordant twins delivered at term: A nationwide population-based study.

OBJECTIVE: To evaluate long-term adverse neurodevelopmental outcomes of discordant twins delivered at term. DESIGN: Retrospective cohort study. SETTING: Nationwide (Republic of Korea). POPULATION: All twin children delivered at term between 2007 and 2010. METHODS: The study population was divided into two groups according to inter-twin birthweight discordancy: the 'concordant twin group', twin pairs with inter-twin birthweight discordancy less than 20%; and the 'discordant twin group', twin pairs with inter-twin birthweight discordancy of 20% or more. The risk of long-term adverse neurodevelopmental outcomes was compared between the concordant twin group and the discordant twin group. Long-term adverse neurodevelopmental outcomes between smaller and larger twin children within twin pairs were further analysed. The composite adverse neurodevelopmental outcome was defined as the presence of at least one of the following: motor developmental delay, cognitive developmental delay, autism spectrum disorders/attention deficit hyperactivity disorders, tics/stereotypical behaviour or epileptic/febrile seizure. MAIN OUTCOME MEASURES: Long-term adverse neurodevelopmental outcome. RESULTS: Of 22 468 twin children (11 234 pairs) included, 3412 (15.19%) twin children were discordant. The risk of composite adverse neurodevelopmental outcome was higher in the discordant twin group than in the concordant twin group (adjusted hazard ratio [HR] 1.13, 95% CI 1.03-1.24). The long-term adverse neurodevelopmental outcomes were not significantly different between smaller and larger twin children in discordant twin pairs (adjusted HR 1.01, 95% CI 0.81-1.28). CONCLUSION: In twin pairs delivered at term, an inter-twin birthweight discordancy of 20% or greater was associated with long-term adverse neurodevelopmental outcomes; and long-term adverse neurodevelopmental outcomes were not significantly different in smaller or larger twin children in discordant twin pairs.

Neonatal and developmental outcomes of very preterm twins according to the chorionicity and weight discordance.

Perinatal outcomes of twin pregnancies are determined by several factors, such as gestational age (GA), chorionicity, and discordance at birth. This retrospective study aimed to investigate the association of chorionicity and discordance with neonatal and neurodevelopmental outcomes in preterm twin infants from uncomplicated pregnancy. Data of very preterm twin infants who were both live-born between 2014 and 2019 on the chorionicity of the twin, diagnosis of the twin-to-twin syndrome (TTTS), weight discordance at birth, and neonatal and neurodevelopmental outcomes at 24 months of corrected age (CA) were collected. Of the 204 twin infants analyzed, 136 were dichorionic (DC) and 68 were monochorionic (MC), including 15 pairs with TTTS. After adjusting for GA, brain injury, including severe intraventricular hemorrhage and periventricular leukomalacia, was mostly found in the MC with TTTS group, with a higher incidence of cerebral palsy and motor delay at CA 24 months. After excluding TTTS, multivariable analysis showed no association between chorionicity and neonatal and developmental outcomes, whereas small infants among co-twins (adjusted odds ratio (aOR) 3.33, 95% confidence interval 1.03-10.74) and greater discordance (%) of weight at birth (aOR 1.04, 1.00-1.07) were associated with neurodevelopmental impairment. Monochorionicity might not determine adverse outcomes among very preterm twins from uncomplicated pregnancy.

Genome-wide polygenic risk scores for hypertensive disease during pregnancy can also predict the risk for long-term cardiovascular disease.

BACKGROUND: Hypertensive disorders during pregnancy are associated with the risk of long-term cardiovascular disease after pregnancy, but it has not yet been determined whether genetic predisposition for hypertensive disorders during pregnancy can predict the risk for long-term cardiovascular disease. OBJECTIVE: This study aimed to evaluate the risk for long-term atherosclerotic cardiovascular disease according to polygenic risk scores for hypertensive disorders during pregnancy. STUDY DESIGN: Among UK Biobank participants, we included European-descent women (n=164,575) with at least 1 live birth. Participants were divided according to genetic risk categorized by polygenic risk scores for hypertensive disorders during pregnancy (low risk, score ≤25th percentile; medium risk, score 25th∼75th percentile; high risk, score >75th percentile), and were evaluated for incident atherosclerotic cardiovascular disease, defined as the new occurrence of one of the following: coronary artery disease, myocardial infarction, ischemic stroke, or peripheral artery disease. RESULTS: Among the study population, 2427 (1.5%) had a history of hypertensive disorders during pregnancy, and 8942 (5.6%) developed incident atherosclerotic cardiovascular disease after enrollment. Women with high genetic risk for hypertensive disorders during pregnancy had a higher prevalence of hypertension at enrollment. After enrollment, women with high genetic risk for hypertensive disorders during pregnancy had an increased risk for incident atherosclerotic cardiovascular disease, including coronary artery disease, myocardial infarction, and peripheral artery disease, compared with those with low genetic risk, even after adjustment for history of hypertensive disorders during pregnancy. CONCLUSION: High genetic risk for hypertensive disorders during pregnancy was associated with increased risk for atherosclerotic cardiovascular disease. This study provides evidence on the informative value of polygenic risk scores for hypertensive disorders during pregnancy in prediction of long-term cardiovascular outcomes later in life.

Establishment of TUBB3-mCherry knock-in human pluripotent stem cell line using CRISPR/Cas9 (SNUe003-A-4).

TUBB3 is a structural neuronal protein important for multiple neuronal functions including axonal guidance and maturation. This study aimed to generate a human pluripotent stem cell (hPSC) line with a TUBB3-mCherry reporter using CRISPR/SpCas9 nuclease. The stop codon in the last exon of TUBB3 was replaced with a T2A-mCherry cassette using CRISPR/SpCas9-mediated homologous recombination. The established TUBB3-mCherry knock-in cell line exhibited typical pluripotent characteristics. The mCherry reporter faithfully replicated the endogenous level of TUBB3 upon induction of neuronal differentiation. The reporter cell line could contribute to the investigation of neuronal differentiation, neuronal toxicity, and neuronal tracing.

Long term renal outcome after hypertensive disease during pregnancy: a nationwide population-based study.

OBJECTIVE: Hypertensive disease during pregnancy increases the risk of maternal morbidity and mortality and leads to the development of multi-organ dysfunction, including kidney dysfunction. Complicated pregnancies require careful postpartum management to prevent sequelae. It is believed that kidney injury can consistently occur even after delivery; therefore, defining the chronicity and endpoint is essential for establishing diagnostic criteria. However, data on the prevalence of persistent renal complications following hypertensive disease during pregnancy are limited. In this study, we evaluated the risk of developing renal disorders in patients with a history of hypertensive disease during pregnancy. METHODS: Participants who gave birth between 2009 and 2010 were followed up for 8 years after delivery. The risk of renal disorder development after delivery was determined according to a history of hypertensive disease during pregnancy. Different factors that could affect the course of pregnancy, including age, primiparity, multiple pregnancy, preexisting hypertension, pregestational diabetes, hypertensive disease during pregnancy, gestational diabetes, postpartum hemorrhage, and cesarean section, were adjusted for using the Cox hazard model. RESULTS: Women with hypertension during pregnancy had a higher risk of developing renal disorders after delivery (0.23% vs. 1.38%; P<0.0001). This increased risk remained significant even after adjusting for covariates (adjusted hazard ratio, 3.861; 95% confidence interval [CI], 3.400-4.385] and 4.209 [95% CI, 3.643-4.864]; respectively). CONCLUSION: Hypertension during pregnancy can contribute to the development of renal disorders, even after delivery.

High intakes of iodine among women during pregnancy and the postpartum period has no adverse effect on thyroid function.

PURPOSE: Given the high consumption of seaweed soup by pregnant and lactating Korean women, concerns have been raised about excessive iodine intake. We evaluated the effects of maternal iodine intake on maternal thyroid function and birth outcomes. We also evaluated iodine intake via seaweed soup during late pregnancy and the early postpartum period. METHODS: A total of 349 pregnant women of the Ideal Breast Milk cohort were recruited in late pregnancy, of whom 302 revisited after delivery. Three-day dietary records were assessed at each visit. Blood was collected for thyroid function test. Obstetrical and birth outcomes were obtained. RESULTS: The median dietary iodine intake was 459 µg/day (interquartile range [IQR] 326.5-647.4 µg/day) during pregnancy. Dietary iodine intake by quartile was not significantly associated with maternal thyroid status, or obstetrical or neonatal outcomes. However, the dietary iodine intake in the early postpartum period was 1759 µg/day (IQR 1026.7-2491.1 µg/day) because of a marked increase in seaweed soup consumption. Of all women, 25.8% consumed seaweed soup more than once over the 3 days of dietary records when pregnant, but the figure rose to 93.4% postpartum. Of postpartum women who consumed seaweed soup daily, the median dietary iodine intakes were 1355, 2394, and 3063 µg/day (soup at one, two, and three-or-four meals). CONCLUSIONS: In these iodine-replete pregnant women, dietary iodine intake during pregnancy showed no effect on maternal thyroid function or birth outcomes. However, iodine intake in the early postpartum period was markedly increased by the frequency of seaweed soup consumption.

Metabolic dysfunction-associated fatty liver disease as a risk factor for adverse outcomes in subsequent pregnancy: a nationwide cohort study.

BACKGROUND AND PURPOSE: A recent international expert consensus opinion suggested that metabolic dysfunction-associated fatty liver disease (MAFLD) replaces nonalcoholic fatty liver disease (NAFLD), since MAFLD is a better predictor of cardiovascular disease. We estimated the prevalence of FLD in fertile females and evaluated the clinical impact of either NAFLD or MAFLD on maternal and fetal outcomes during subsequent pregnancy. METHODS: The study population included fertile females who underwent health examinations and became pregnant within 1 year of health examination. Hepatic steatosis was defined as a fatty liver index of ≥ 30. The fertile females were divided into four groups: neither-FLD, NAFLD-only, MAFLD-only, and both-FLDs. During subsequent pregnancy, the risks of adverse pregnancy outcomes, including gestational diabetes, pregnancy-associated hypertension, preterm birth, and low birthweight, were compared among the four groups. RESULTS: The study population comprised 762,401 females, including 720,606 with neither-FLD, 318 with NAFLD-only, 14,371 with MAFLD-only, and 27,106 with both-FLDs. Compared to females with neither-FLD, the risk of adverse pregnancy outcomes was higher in females with any FLD, with an adjusted OR of 1.73 (95% CI 1.25-2.41) in the NALFD-only group, 2.65 (2.53-2.77) in the MAFLD-only group, and 2.39 (2.31-2.48) in the both-FLDs group. Pregnancy outcomes (cesarean delivery, gestational diabetes, and low birthweight) were worse in females with MAFLD compared with NAFLD. CONCLUSION: Any form of FLD is a risk factor for adverse pregnancy outcomes. These data suggest that MAFLD is associated with a higher risk of adverse pregnancy outcomes for both mother and fetus than NAFLD.

Development and Validation of a Prediction Model for Need for Massive Transfusion During Surgery Using Intraoperative Hemodynamic Monitoring Data.

Importance: Massive transfusion is essential to prevent complications during uncontrolled intraoperative hemorrhage. As massive transfusion requires time for blood product preparation and additional medical personnel for a team-based approach, early prediction of massive transfusion is crucial for appropriate management. Objective: To evaluate a real-time prediction model for massive transfusion during surgery based on the incorporation of preoperative data and intraoperative hemodynamic monitoring data. Design, Setting, and Participants: This prognostic study used data sets from patients who underwent surgery with invasive blood pressure monitoring at Seoul National University Hospital (SNUH) from 2016 to 2019 and Boramae Medical Center (BMC) from 2020 to 2021. SNUH represented the development and internal validation data sets (n = 17 986 patients), and BMC represented the external validation data sets (n = 494 patients). Data were analyzed from November 2020 to December 2021. Exposures: A deep learning-based real-time prediction model for massive transfusion. Main Outcomes and Measures: Massive transfusion was defined as a transfusion of 3 or more units of red blood cells over an hour. A preoperative prediction model for massive transfusion was developed using preoperative variables. Subsequently, a real-time prediction model using preoperative and intraoperative parameters was constructed to predict massive transfusion 10 minutes in advance. A prediction model, the massive transfusion index, calculated the risk of massive transfusion in real time. Results: Among 17 986 patients at SNUH (mean [SD] age, 58.65 [14.81] years; 9036 [50.2%] female), 416 patients (2.3%) underwent massive transfusion during the operation (mean [SD] duration of operation, 170.99 [105.03] minutes). The real-time prediction model constructed with the use of preoperative and intraoperative parameters significantly outperformed the preoperative prediction model (area under the receiver characteristic curve [AUROC], 0.972; 95% CI, 0.968-0.976 vs AUROC, 0.824; 95% CI, 0.813-0.834 in the SNUH internal validation data set; P < .001). Patients with the highest massive transfusion index (ie, >90th percentile) had a 47.5-fold increased risk for a massive transfusion compared with those with a lower massive transfusion index (ie, <80th percentile). The real-time prediction model also showed excellent performance in the external validation data set (AUROC of 0.943 [95% CI, 0.919-0.961] in BMC). Conclusions and Relevance: The findings of this prognostic study suggest that the real-time prediction model for massive transfusion showed high accuracy of prediction performance, enabling early intervention for high-risk patients. It suggests strong confidence in artificial intelligence-assisted clinical decision support systems in the operating field.

Long-term cardiovascular outcomes of gestational diabetes mellitus: a prospective UK Biobank study.

BACKGROUND: Previous studies showed that gestational diabetes mellitus (GDM) can be a risk factor for subsequent atherosclerotic cardiovascular disease. However, there is a paucity of information regarding diverse cardiovascular outcomes in elderly women after GDM. In the current study, we examined whether women with a history of GDM have an increased risk for long-term overall cardiovascular outcomes. METHODS: Among the UK participants, we included 219,330 women aged 40 to 69 years who reported at least one live birth. The new incidence of diverse cardiovascular outcomes was compared according to GDM history by multivariable Cox proportional hazard models. In addition, causal mediation analysis was performed to examine the contribution of well-known risk factors to observed risk. RESULTS: After enrollment, 13,094 women (6.0%) developed new overall cardiovascular outcomes. Women with GDM history had an increased risk for overall cardiovascular outcomes [adjusted HR (aHR) 1.36 (95% CI 1.18-1.55)], including coronary artery disease [aHR 1.31 (1.08-1.59)], myocardial infarction [aHR 1.65 (1.27-2.15)], ischemic stroke [aHR 1.68 (1.18-2.39)], peripheral artery disease [aHR 1.69 (1.14-2.51)], heart failure [aHR 1.41 (1.06-1.87)], mitral regurgitation [aHR 2.25 (1.51-3.34)], and atrial fibrillation/flutter [aHR 1.47 (1.18-1.84)], after adjustment for age, race, BMI, smoking, early menopause, hysterectomy, prevalent disease, and medication. In mediation analysis, overt diabetes explained 23%, hypertension explained 11%, and dyslipidemia explained 10% of the association between GDM and overall cardiovascular outcome. CONCLUSIONS: GDM was associated with more diverse cardiovascular outcomes than previously considered, and conventional risk factors such as diabetes, hypertension, and dyslipidemia partially contributed to this relationship.

Development of early prediction model for pregnancy-associated hypertension with graph-based semi-supervised learning.

Clinical guidelines recommend several risk factors to identify women in early pregnancy at high risk of developing pregnancy-associated hypertension. However, these variables result in low predictive accuracy. Here, we developed a prediction model for pregnancy-associated hypertension using graph-based semi-supervised learning. This is a secondary analysis of a prospective study of healthy pregnant women. To develop the prediction model, we compared the prediction performances across five machine learning methods (semi-supervised learning with both labeled and unlabeled data, semi-supervised learning with labeled data only, logistic regression, support vector machine, and random forest) using three different variable sets: [a] variables from clinical guidelines, [b] selected important variables from the feature selection, and [c] all routine variables. Additionally, the proposed prediction model was compared with placental growth factor, a predictive biomarker for pregnancy-associated hypertension. The study population consisted of 1404 women, including 1347 women with complete follow-up (labeled data) and 57 women with incomplete follow-up (unlabeled data). Among the 1347 with complete follow-up, 2.4% (33/1347) developed pregnancy-associated HTN. Graph-based semi-supervised learning using top 11 variables achieved the best average prediction performance (mean area under the curve (AUC) of 0.89 in training set and 0.81 in test set), with higher sensitivity (72.7% vs 45.5% in test set) and similar specificity (80.0% vs 80.5% in test set) compared to risk factors from clinical guidelines. In addition, our proposed model with graph-based SSL had a higher performance than that of placental growth factor for total study population (AUC, 0.71 vs. 0.80, p < 0.001). In conclusion, we could accurately predict the development pregnancy-associated hypertension in early pregnancy through the use of routine clinical variables with the help of graph-based SSL.