Search

Objective Adenomyosis impacts pregnancy outcomes, although there is a lack of consensus regarding the actual effects. It is likely, however, that the severity of adenomyosis or ultrasound findings or timing of diagnosis can have different effects on adverse pregnancy outcomes (APOs). Methods In this study, we aimed to investigate the impact of the timing of adenomyosis diagnosis on pregnancy outcomes. Singleton pregnant women who delivered between 2017 and 2022 were analyzed based on the timing of adenomyosis diagnosis, using a national database. The final cohort was classified into three groups: 1) group 1, without adenomyosis; 2) group 2, those diagnosed with adenomyosis before pregnancy; and 3) group 3, those diagnosed with adenomyosis during pregnancy. Results A total of 1,226,475 cases were ultimately included in this study. Women with a diagnosis of adenomyosis had a significantly higher risk of APOs including hypertensive disorder during pregnancy (HDP), gestational diabetes mellitus (GDM), postpartum hemorrhage, placental abruption, preterm birth, and delivery of a small-for-gestational-age infant even after adjusting for covariates. In particular, concerning HDP, the risk was highest in group 3 (group 2: adjusted odds ratio [aOR], 1.15 vs. group 3: aOR, 1.36). However, the highest GDM risk was in group 2 (GDM; group 2: aOR, 1.24 vs. group 3: aOR, 1.04). Conclusion The increased risk of APO differed depending on the timing of adenomyosis diagnosis. Therefore, efforts for more careful monitoring and prevention of APOs may be necessary when such women become pregnant.

Background: Lifestyle changes, such as those related to the COVID-19 pandemic, including alterations in physical activity and dietary habits, are known to affect pregnancy outcomes. In particular, suboptimal intrauterine conditions during pregnancy are known to influence not only fetal growth but also growth during infancy. However, research on the impact of the environmental changes caused by the COVID-19 pandemic on the growth of infants and children during their early years is lacking. To address this issue, this study evaluated the effect of the COVID-19 pandemic on obesity in infants. Methods: This retrospective cohort study used the data collected from the Korea National Health Insurance (KNHI) claims database. The data of 1985,678 women who delivered infants between 2015 and 2021 were collected. Women who delivered during the pandemic and those who delivered during the pre-pandemic period were matched in a 1:1 frequency-matched pair procedure for factors such as age, hypertension, diabetes mellitus, preeclampsia, gestational diabetes mellitus, mode of delivery, gestational age at delivery, offspring sex, and birth weight. Finally, 197,580 women were enrolled. The weight and head circumference of infants (4–6 months of age) of the COVID-19 pandemic group were compared with those of the pre-pandemic group. Results: The COVID-19 pandemic group infants exhibited significantly higher weight and prevalence of obesity at 4–6 months of age compared to infants in the pre-pandemic group. After adjustment for covariates, pandemic group infants had a higher risk of obesity (odds ratio: 1.54, 95% confidence interval: 1.51–1.57) compared to the pre-pandemic group infants. Conclusion: The COVID-19 pandemic has had a notable impact on the weight of infants aged 4–6 months. This suggests that pandemic conditions may influence the growth of newborns, underscoring the importance of monitoring and assessing trends in the growth of infants born during such crises.

Abstract This study aimed to examine the impact of term LBW on short-term neonatal and long-term neurodevelopmental outcomes in children 5–7 years of age. This is a population-based cohort study that merged national data from the Korea National Health Insurance claims and National Health Screening Program for Infants and Children. The participants were women who gave birth at a gestational age of ≥ 37 weeks between 2013 and 2015 in the Republic of Korea, and were tracked during 2020 for the neurodevelopmental surveillance of their children. Among 830,806 women who gave birth during the study period, 31,700 (3.8%) of their babies weighed less than 2500 g. By Cox proportional hazard analysis, children aged 5–7 years who had LBW were associated with any developmental, motor developmental delay, cognitive developmental delay, autism spectrum, attention deficit hyperactivity disorders, and epileptic and febrile seizures.Children born with term LBW were more vulnerable to neurodevelopmental disorders at 5–7 years of age than those with normal and large birth weights. This study further substantiates counseling parents regarding the long-term outcomes of children being born underweight.

Abstract Background Primary headache disorder is a known risk factor for stroke in women and usually improves during the first trimester of pregnancy. However, despite this, some women develop headaches during pregnancy (G-HA), and the effect of this headache on subsequent stroke is unknown. In this study, we evaluated the association between G-HA and stroke after delivery in women. Methods Based on the Korean National Health Insurance Service database, we included women hospitalized for delivery between 2012 and 2013. G-HA was defined as a headache diagnosed during pregnancy. Primary outcome was any stroke that occurred during the observational periods from delivery to December 31, 2020. All diseases were identified based on data registered in the database using the International Classification of Disease-10th Revision-Clinical Modification codes. Results Of 906,187 pregnant women, G-HA was found in 56,813 (6.3%). During the observational periods, the G-HA ( +) group had a significantly higher risk of any stroke [adjusted hazard ratio (aHR) = 1.59, 95% confidence interval (CI): 1.30–1.95], ischemic stroke (aHR = 1.50, 95% CI: 1.12–2.01), hemorrhagic stroke (aHR = 1.63, 95% CI: 1.23–2.15), and intracerebral hemorrhage (aHR = 1.63, 95% CI: 1.19–2.23) than the G-HA (-) group. When analyzed considering the interaction with history of headache disorder, G-HA showed a significant association with hemorrhagic stroke, but lost its effect on ischemic stroke. Conclusions We demonstrated that G-HA was associated with subsequent stroke occurrence after delivery. However, the relationship between G-HA and ischemic stroke is mitigated by a history of pre-pregnancy headache disorder.

Background & Aims: Adverse 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 are 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. Methods: Singleton pregnant women who underwent national health screenings 1 year before pregnancy and 1 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. Results: Among 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 odds ratio [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 (adjusted OR 2.20, 95% CI 1.81–2.67, for HDP and adjusted OR 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

Abstract Presuming that the incidence of cerebral palsy (CP) in Korea is decreasing due to medical advances, we analyzed the trends and risk factors of CP in changing circumstances. We identified all women who delivered a singleton between 2007 and 2015 using the Korea National Health Insurance (KNHI). Information on pregnancy and birth was obtained by linking the KNHI claims database and data from the national health-screening program for infants and children. The 4-years incidence of CP decreased significantly from 4.77 to 2.52 per 1000 babies during the study period. The multivariate analysis revealed that the risk of developing CP was 29.5 times higher in preterm infants born before 28 weeks of gestational age, 24.5 times higher in infants born between 28 and 34 weeks, and 4.5 times higher in infants born between 34 and 36 weeks, compared to full-term appropriate for age (2.5 ~ 4 kg of body weight) infants. 5.6 times higher in those with birth weight

BackgroundDiabetes is associated with an increased risk of Parkinson’s disease dementia (PDD); however, it is unknown whether this association is dependent on continuous hyperglycemia, hypoglycemic events, or glycemic variability. We aimed to investigate the relationship between visit-to-visit fasting glucose variability and PDD development in patients with Parkinson’s disease (PD).MethodsUsing data from the Korean National Health Insurance Service, we examined 9,264 patients aged ≥40 years with de novo Parkinson’s disease (PD) who underwent ≥3 health examinations and were followed up until December 2019. Glucose variability was measured using the coefficient of variation, variability independent of the mean, and average real variability. Fine and Gray competing regression analysis was performed to determine the effect of glucose variability on incident PDD.ResultsDuring the 9.5-year follow-up period, 1,757 of 9,264 (19.0%) patients developed PDD. Patients with a higher visit-to-visit glucose variability had a higher risk of future PDD. In the multivariable adjusted model, patients with PD in the highest quartile (subdistribution hazard ratio [SHR] = 1.50, 95% CI 1.19 to 1.88), quartile 3 (SHR = 1.29, 95% CI 1.02 to 1.62), and quartile 2 (SHR = 1.30, 95% CI 1.04 to 1.63) were independently associated with a higher risk of PDD than those in the lowest quartile.ConclusionWe highlighted the effect of long-term glucose variability on the development of PDD in patients with PD. Furthermore, our findings suggest that preventive measures for constant glucose control may be necessary to prevent PDD.

Given the higher prevalence of cardiac arrhythmias in individuals with diabetes, we investigated the relationship between cardiac arrhythmias and the incidence of gestational diabetes (GDM). This retrospective cohort study utilized data from the Korean Health Insurance Service database, encompassing 1,113,729 women who gave birth between January 2007 and December 2015. After excluding those who did not undergo National Health Screening tests within 1 year prior to pregnancy, those with multifetal pregnancies, and those diagnosed with diabetes, we analyzed 365,880 singleton pregnancies without a history of diabetes. Of these, 3,253 (0.9%) had cardiac arrhythmias, including premature extra beats, supraventricular tachyarrhythmias, and/or atrial flutter/fibrillation. GDM occurred in 31,938 (8.7%) subjects during pregnancy, and was more prevalent in women with cardiac arrhythmia than in those without (14.9 vs. 8.7%, p

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

Objective The air pollution on pregnancy outcome (APPO) study is a prospective hospital-based cohort study designed to investigate the maternal and fetal effects of a particulate matter with an aerodynamic below 10 μm (PM10) and PM2.5 (below 2.5 μm) exposure. This study aims to analyze a relationship between particulate matter and adverse pregnancy outcomes and to find related biomarkers and develop management guidelines. Methods About 1,200 pregnant women are recruited for 3 years (from January 2021 to December 2023) from seven university hospitals to investigate the effects of particulate matter on pregnancy complications and adverse pregnancy outcomes. We collect biological samples by 5 mL of maternal venous blood and 15 mL of urine in each trimester of pregnancy, and 5 mL of umbilical cord blood and 2×2×2 cm of placental tissue are collected after delivery. In addition, by applying PM10 and PM2.5 concentration values and time-activity patterns from the time weighted average model, the individual predicted exposure of air pollution for the pregnant women are obtained. Results The average exposure of PM10 and PM2.5 of the participants in the entire period of pregnancy, was exceeded the World Health Organization air quality guidelines (an annual level, PM10 >15 μg/m3, PM2.5 >5 μg/m3). Moreover, it was revealed that the PM concentration was increasing toward the 3rd trimester of pregnancy. Conclusion The APPO study will be able to identify the degree of exposure to air pollution in pregnant women and use it as basic data for estimating individual exposure to particulate matter. And the results of the APPO study will facilitate in the development of health management for pregnant women against air pollution.

Abstract Background Cleansing of the vulva and perineum is recommended during preparation for vaginal delivery, and special attention is paid to cleansing before episiotomy because episiotomy is known to increase the risk of perineal wound infection and/or dehiscence. However, the optimal method of perineal cleansing has not been established, including the choice of antiseptic agent. To address this issue, we designed a randomized controlled trial to examine whether skin preparation with chlorhexidine-alcohol is superior to povidone-iodine for the prevention of perineal wound infection after vaginal delivery. Methods In this multicenter randomized controlled trial, term pregnant women who plan to deliver vaginally after episiotomy will be enrolled. The participants will be randomly assigned to use antiseptic agents for perineal cleansing (povidone-iodine or chlorhexidine-alcohol). The primary outcome is superficial or deep perineal wound infection within 30 days after vaginal delivery. The secondary outcomes are the length of hospital stay, physician office visits, or hospital readmission for infection-related complications, endometritis, skin irritations, and allergic reactions. Discussion This study will be the first randomized controlled trial aiming to determine the optimal antiseptic agent for the prevention of perineal wound infections after vaginal delivery. Trial registration ClinicalTrials.gov NCT05122169. First submitted date on 8 November 2021. First posted date on 16 November 2021

Objective The aim of this study was to evaluate the changes in twin pregnancy outcomes between 2007 and 2016 in a Korean population. Methods The data for this nationwide population-based study was obtained from the national birth registry of the Korean National Statistical Office and the Health Insurance Review & Assessment Service of Korea. Women with twin pregnancies who gave birth between 2007 and 2016 were included. Results From 2007 to 2016, the rate of twin pregnancies increased (1.37% vs. 1.91%, respectively, P

Artificial intelligence, which has been applied as an innovative technology in multiple fields of healthcare, analyzes large amounts of data to assist in disease prediction, prevention, and diagnosis, as well as in patient monitoring. In obstetrics, artificial intelligence has been actively applied and integrated into our daily medical practice. This review provides an overview of artificial intelligence systems currently used for obstetric diagnostic purposes, such as fetal cardiotocography, ultrasonography, and magnetic resonance imaging, and demonstrates how these methods have been developed and clinically applied.

Background We assessed the myocardial infarction (MI), stroke, and all-cause death risks during follow-up according to the low-density lipoprotein cholesterol (LDL-C) levels among older adults. Methods The Korean National Health Insurance Service datasets (2002 to 2020) were used for this population-based cohort study. The hazards of MI, stroke, and all-cause mortality during follow-up were analyzed according to LDL-C level in individuals aged ≥65 years without baseline cardiovascular diseases (n=1,391,616). Results During a mean 7.55 years, 52,753 MIs developed; 84,224 strokes occurred over a mean 7.47 years. After a mean 8.50 years, 233,963 died. A decrease in LDL-C was associated with lower hazards of MI and stroke. The decreased hazard of stroke in lower LDL-C was more pronounced in statin users, and individuals with diabetes or obesity. The hazard of all-cause death during follow-up showed an inverted J-shaped pattern according to the LDL-C levels. However, the paradoxically increased hazard of mortality during follow-up in lower LDL-C was attenuated in statin users and individuals with diabetes, hypertension, or obesity. In statin users, lower LDL-C was associated with a decreased hazard of mortality during follow-up. Conclusion Among the elderly, lower LDL-C was associated with decreased risks of MI and stroke. Lower LDL-C achieved by statins in the elderly was associated with a decreased risk of all-cause death during follow-up, suggesting that LDL-C paradox for the premature death risk in the elderly should not be applied to statin users. Intensive statin therapy should not be hesitated for older adults with cardiovascular risk factors including diabetes.

Abstract Birthweight is a strong determinant of a neonate’s health. The SARS-CoV-2 pandemic’s impact on birthweight has not been investigated in-depth, with inconsistent conclusions from initial studies. To assess changes in preterm birth and inappropriate birthweight between the SARS-CoV-2 pandemic and pre-pandemic periods. A nationwide birth micro-data consisted with exhaustive census of all births in 2011–2020 in South Korea was accessed to examine whether the mean birthweight and rates of under/overweight births changed significantly during the SARS-CoV-2 pandemic year (2020) compared to those of the pre-pandemic period (2011–2019). A total of 3,736,447 singleton births were analyzed. Preterm birth was defined as

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

In the original publication [...]

Abstract Background Physiologic changes during pregnancy affect the development of postpartum cerebrovascular disease (CVD) in women with Moyamoya disease. Due to the rare prevalence of Moyamoya disease and its large regional variations, large-scale based studies on the risk of CVD after delivery have not been conducted. This study aimed to evaluate whether women with Moyamoya disease have an increased risk of CVD after delivery. Methods Research data was collected from the National Health Insurance Claims Database of the Health Insurance Review and Assessment Service. Patients who delivered in Korea from 2007 to 2014 were enrolled in this study. We classified women as having CVD if they were diagnosed with any of the following conditions between delivery and December 31, 2016; cerebral infarction (I63.X in the International Classification of Diseases-10th Revision [ICD-10]) and/or intracranial hemorrhage (I61.X, I62.X in ICD-10) and/or subarachnoid hemorrhage (I60.X in ICD-10). Women with Moyamoya disease were identified as having I67.5 in ICD-10. We matched the study cohort by the ratio of 1:10 to analyze the risk CVD occurrence. The matching technique applied in this study was based on the variables of age and parity. To evaluate the adjusted hazard ratio (HR) for CVD in women with Moyamoya disease, we used multivariate Cox proportional hazard regression. Results Among a total of 3,611,216 Korean women who underwent delivered, we identified 412 women with Moyamoya disease diagnosis and 1420 age- and parity-matched women without Moyamoya disease (control). Compared to the control group, women with Moyamoya disease had a significantly higher rate of Cesarean section, overt DM, and essential hypertension (all p

Abstract Background Hypertension has been known to increase the risk of obstetric complications. Recently, the American College of Cardiology endorsed lower thresholds for hypertension as systolic blood pressure of 130-139 mmHg or diastolic blood pressure 80-89 mmHg. However, there is a paucity of information regarding the impact of pre-pregnancy blood pressure on pregnancy outcomes. We aimed to evaluate the effect of pre-pregnancy blood pressure on maternal and neonatal complications. Methods In this nationwide, population based study, pregnant women without history of hypertension and pre-pregnancy blood pressure

Abstract Background This study aimed to compare obstetric outcomes in Korean women with and without future cardiovascular disease (CVD) within 10 years after pregnancy, and assessed whether pregnancy complications are independent risk factors, and whether the combination of pregnancy complications has an additive function for risk factors for CVD. Methods This was a nationwide population-based study combining the database of the Korea National Health Insurance claims and National Health Screening Programs to assess preeclampsia, low birth weight (LBW), and preterm delivery as risk factors for CVD. Cox proportional hazards models was used to evaluate the risk of total CVD, ischemic heart disease (IHD), and stroke after the pregnancy complications, with adjustment for potential confounding variables. Results Women with CVD were likely to have a higher prevalence of pregnancy complications than women without CVD. The risk of total CVD was associated with preeclampsia (adjusted hazard ratio (HR), 1.60 [95% confidence interval (CI) 1.50–1.72]), LBW (1.20 [1.12–1.28]), and preterm delivery (1.32 [1.22–1.42]), after adjustment for confounders, including cardiovascular risk factors before pregnancy. The risk estimates of pregnancy complications for IHD were higher than those for stroke. In this study, the risk of total CVD was higher in the combined presence of preeclampsia and preterm delivery (2.23 [1.57–3.17] or all three complications (2.06 [1.76–2.40]), relative to no complications. The highest HR was noted in the risk of all pregnancy complications for IHD (2.39 [1.98–2.89]). Conclusion Preeclampsia, preterm delivery, and LBW were independently associated with CVD in young Korean women. In addition, the combination of pregnancy complications had less-than-additive effects on CVD incidence.

Particulate matter 2.5 (PM2.5) levels are associated with adverse pregnancy outcomes. In this retrospective cohort study, we examined whether the concentration of indoor PM2.5 affected pregnancy outcomes. Additionally, we evaluated biomarkers of pregnancy-related complications caused by fine dust. We collected clinical information and data based on residential addresses from the Air Korea database to assess PM2.5 exposure levels. As a multicenter prospective cohort study, we measured the indoor PM2.5 concentration and inflammatory and oxidative stress markers. The PM2.5 concentration of the low-birth-weight (LBW) delivery group was 27.21 μg/m3, which was significantly higher than that of the normal-birth-weight (NBW) group (26.23 μg/m3) (p = 0.02). When the newborns were divided by sex, the PM2.5 concentration of the LBW group was 27.89 μg/m3 in male infants, which was significantly higher than that of the NBW group (26.26 μg/m3) (p = 0.01). In the prospective study, 8-hydroxy-2-deoxyguanosine significantly increased in the high-concentration group (113.55 ng/mL, compared with 92.20 ng/mL in the low-concentration group); in the high-concentration group, the rates of preterm birth (PTB) and small size for gestational age significantly increased (p < 0.01, p = 0.01). This study showed an association between PM2.5, oxidative stress, and fetal growth, with the PTB group being more vulnerable.

IntroductionWe aimed to investigate the incidence of Parkinson’s disease (PD) by age and year for each sex as well as the modifiable risk factors for PD. Using data from the Korean National Health Insurance Service, 938,635 PD and dementia-free participants aged ≥40 years who underwent general health examinations were followed to December 2019.MethodsWe analyzed the PD incidence rates according to age, year and sex. To investigate the modifiable risk factors for PD, we used the Cox regression model. Additionally, we calculated the population-attributable fraction to measure the impact of the risk factors on PD.ResultsDuring follow-up, 9,924 of the 938,635 (1.1%) participants developed PD. The incidence of PD increased continuously from 2007 to 2018, reaching 1.34 per 1,000 person-years in 2018. The incidence of PD also increases with age, up to 80 y. Presence of hypertension (SHR = 1.09, 95% CI 1.05 to 1.14), diabetes (SHR = 1.24, 95% CI 1.17 to 1.31), dyslipidemia (SHR = 1.12, 95% CI 1.07 to 1.18), ischemic stroke (SHR = 1.26, 95% CI 1.17 to 1.36), hemorrhagic stroke (SHR = 1.26, 95% CI 1.08 to 1.47), ischemic heart disease (SHR = 1.09, 95% CI 1.02 to 1.17), depression (SHR = 1.61, 95% CI 1.53 to 1.69), osteoporosis (SHR = 1.24, 95% CI 1.18 to 1.30), and obesity (SHR = 1.06, 95% CI 1.01 to 1.10) were independently associated with a higher risk for PD.DiscussionOur results highlight the effect of modifiable risk factors for PD in the Korean population, which will help establish health care policies to prevent the development of PD.

Background The detrimental effects of excessive thyroid hormone on glucose metabolism have been widely investigated. However, the risk of diabetes in patients with long-standing hyperthyroidism, especially according to treatment modality, remains uncertain, with few longitudinal studies. Methods The risk of diabetes in patients with Graves’ disease treated with antithyroid drugs (ATDs) for longer than the conventional duration (≥2 years) was compared with that in age-and sex-matched controls. The risk was further compared according to subsequent treatment modalities after a 24-month course of ATD: continuation of ATD (ATD group) vs. radioactive iodine ablation (RIA) group. Results A total of 4,593 patients were included. Diabetes was diagnosed in 751 (16.3%) patients over a follow-up of 7.3 years. The hazard ratio (HR) for diabetes, after adjusting for various known risk factors, was 1.18 (95% confidence interval [CI], 1.10 to 1.28) in patients with hyperthyroidism. Among the treatment modality groups, the RIA group (n=102) had a higher risk of diabetes than the ATD group (n=4,491) with HR of 1.56 (95% CI, 1.01 to 2.42). Further, the risk of diabetes increased with an increase in the ATD treatment duration (P for trend=0.019). Conclusion The risk of diabetes was significantly higher in patients with long-standing Graves’ disease than in the general population, especially in patients who underwent RIA and prolonged ATD treatment. Special attention to hyperglycemia during follow-up along with effective control of hyperthyroidism may be necessary to reduce the risk of diabetes in these patients.

BackgroundMisperception of body weight is associated with various psychological and health problems, including obesity, eating disorders, and mental problems. To date, female-specific risk factors, including socioeconomic or health-related lifestyle features, or their indicative performance for the misperception in Asian women according to age groups remain unknown.ObjectivesTo investigate the prevalence and associated risk factors for the mismatch in self-perceived body weight and evaluated the classification performance of the identified risk factors across age groups in female adults.MethodsWe analyzed data of 22,121 women (age 19–97 years) from the 7-year Korea National Health and Nutrition Examination Survey dataset (2010-2016). We evaluated self-perceived body weight of the participants with their actual weight using the body mass index cut-off and grouped them by age: early adulthood (19–45), middle adulthood (46–59), and late adulthood (≥60). Logistic regression was conducted in each age group based on their weight misperception. The classification performance of the identified risk factors was evaluated with a bagging tree ensemble model with 5-fold cross-validation.Results22.2% (n=4,916) of the study participants incorrectly perceived their body weight, of which 14.1% (n=3,110) and 8.2% (n=1,806) were in the underestimated and overestimated groups. Among the age groups, the proportion of participants who misperceived their body weight was highest in late adulthood (31.8%) and the rate of overestimation was highest in early adulthood (14.1%). We found that a lower education level, absence of menopause, perception of themselves as unhealthy, and efforts for weight management were significantly associated with the overall misperception (overestimation or underestimation) of body weight across age groups. Based on the identified risk factors, the highest area under the receiver operating curve (AUROC) and accuracy of the best classification model (weight overestimation in all participants) were 0.758 and 0.761, respectively. Adding various associated lifestyle factors to the baseline model resulted in an average increase of 0.159 and 0.135 in AUROC for classifying weight underestimation and overestimation, respectively.ConclusionsAge, education level, marital status, absence of menopause, amount of exercise, efforts for weight management (gain, loss, and maintenance), and self-perceived health status were significantly associated with the mismatch of body weight.

Abstract Background Multiple gestations are associated with an increased incidence of preeclampsia. However, there exists no evidence for an association between multiple gestations and development of hypertension(HTN) later in life. This study aimed to determine whether multiple gestations are associated with HTN beyond the peripartum period. Methods In this retrospective nationwide population-based study, women who delivered a baby between January 1, 2007, and December 31, 2008, and underwent a national health screening examination within one year prior to their pregnancy were included. Subsequently, we tracked the occurrence of HTN during follow-up until December 31, 2015, using International Classification of Diseases-10th Revision codes. Results Among 362,821 women who gave birth during the study period, 4,944 (1.36%) women had multiple gestations. The cumulative incidence of HTN was higher in multiple gestations group compared with singleton group (5.95% vs. 3.78%, p

Abstract Beta-2 adrenergic receptor (B2AR) agonists, used as asthma treatments and tocolytics during pregnancy, have recently been reported to be associated with autism in their offspring. However, the particular link between autism and ritodrine, a common type of B2AR agonist used solely as tocolytics, has never been substantiated with any nationwide database. Thus, we aimed to examine the association between in utero exposure of ritodrine and the risk of autism in their offspring using a national database. This population-based cohort study was conducted by merging the Korea National Health Insurance claims database and National Health Screening Program for Infants and Children database. These databases included all women who had delivered singleton between January 2007 and December 2008 in Korea. Out of the total 770,016 mothers, 30,959 (4.02%) were exposed to ritodrine during pregnancy, and 5583 (0.73%) of their children were identified as having autism, defined until 8 years of age. According to our analysis, the overall cumulative incidence of autism up to 8 years was 1.37% in ritodrine exposure group and 0.70% in ritodrine non-exposure group (p

The endemic and pandemic caused by respiratory virus infection are a major cause of mortality and morbidity globally. Thus, broadly effective antiviral drugs are needed to treat respiratory viral diseases. Small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (U-exo) have recently gained attention as a cell-free therapeutic strategy due to their potential for safety and efficacy. Anti-viral activities of U-exo to countermeasure respiratory virus-associated diseases are currently unknown. Here, we tested the antiviral activities of U-exo following influenza A/B virus (IFV) and human seasonal coronavirus (HCoV) infections in vitro. Cells were subject to IFV or HCoV infection followed by U-exo treatment. U-exo treatment significantly reduced IFV or HCoV replication and combined treatment with recombinant human interferon-alpha protein (IFN-α) exerted synergistically enhanced antiviral effects against IFV or HCoV. Interestingly, microRNA (miR)-125b, which is one of the most abundantly expressed small RNAs in U-exo, was found to suppress IFV replication possibly via the induction of IFN-stimulated genes (ISGs). Furthermore, U-exo markedly enhanced RNA virus-triggered IFN signaling and ISGs production. Similarly, human nasal epithelial cells cultured at the air-liquid interface (ALI) studies broadly effective anti-viral and anti-inflammatory activities of U-exo against IFV and HCoV, suggesting the potential role of U-exo as a promising intervention for respiratory virus-associated diseases.

Objective Exploiting their ability to differentiate into mesenchymal lineages like cartilage, bone, fat, and muscle, and to elicit paracrine effects, mesenchymal stem cells (MSCs) are widely used in clinical settings to treat tissue injuries and autoimmune disorders. One of accessible sources of MSC is the samples used for Papanicolaou (Pap) test, which is a cervical screening method for detecting potentially pre-cancerous and cancerous alterations in the cervical cells and to diagnose genetic abnormalities in fetuses. This study aimed to identify and isolate the stem cells from Pap smear samples collected from pregnant women, and to trace the origin of these cells to maternal or fetal tissue, and characterize their stem cell properties. Methods To investigate the possibility and efficiency of establishing MSC lines from the Pap smear samples, we were able to establish 6 cell lines from Pap smear samples from 60 pregnant women at different stages of gestation. Results The 3 cell lines randomly selected among the 6 established in this study, displayed high proliferation rates, several characteristics of MSCs, and the capacity to differentiate into adipocytes, osteocytes, and chondrocytes. Our study identified that the stem cell lines obtainable from Pap smear sampling were uterine cervical stromal cells (UCSCs) and had 10% efficiency of establishment. Conclusion Despite their low efficiency of establishment, human UCSCs from Pap smear samples can become a simple, safe, low-cost, and donor-specific source of MSCs for stem cell therapy and regenerative medicine.

Abstract Background Pregnant women are at high risk of influenza-related morbidity and mortality. In addition, maternal influenza infection may lead to adverse birth outcomes. However, there is insufficient data on long-term impact of maternal influenza infection. Methods This study was conducted to assess the impact of maternal influenza infection on birth outcomes and long-term influence on infants by merging the Korea National Health Insurance (KNHI) claims database and National Health Screening Program for Infants and Children (NHSP-IC). Mother-offspring pairs were categorized by maternal influenza infection based on the ICD-10 code. Results Multivariate analysis revealed that maternal influenza infection significantly increased the risk of preterm birth (OR 1.408) and low birth weight (OR 1.198) irrespective of gestational age. The proportion of low birth weight neonates was significantly higher in influenza-infected women compared to those without influenza. However, since the fourth health screening (30–80 months after birth), the fraction of underweight was no longer different between children from influenza-infected and non-infected mothers, whereas the rates of overweight increased paradoxically in those born to mothers with influenza infection. Conclusions Maternal influenza infection might have long-term effects on the health of children and adolescents even after infancy.

Objectives The current study aimed to investigate whether pregnancy outcomes are affected by maternal rhesus (Rh) status by comparing the primigravida pregnancy outcomes of Rh-negative women with those of Rh-positive women. Methods The study data were collected from the Korea National Health Insurance Claims Database and the National Health Screening Program for Infants and Children. In total, 1,664,882 primigravida women who gave birth between January 1, 2007 and December 31, 2014, were enrolled in this study. As the risk and severity of sensitization response increases with each subsequent pregnancy, only primigravida women were enrolled. The patients were divided into 2 groups according to Rh status, and the pregnancy outcomes were compared. Results In total, 1,661,320 women in the Rh-positive group and 3,290 in the Rh-negative group were assessed. With regard to adverse pregnancy outcomes, there was no statistically significant difference between the 2 groups in terms of the prevalence of preeclampsia, postpartum hemorrhage, abruptio placenta, placenta previa, and uterine artery embolization. A univariate analysis revealed that none of the adverse pregnancy outcomes were significantly correlated to Rh status (preeclampsia: odds ratio [OR], 1.00, 95% confidence interval [CI], 0.81–1.23; postpartum hemorrhage: OR, 1.10, 95% CI, 0.98–1.24; abruptio placenta: OR, 0.80, 95% CI, 0.46–1.37; and placenta previa: OR, 1.08, 95% CI, 0.78–1.42). The adjusted ORs of postpartum hemorrhage and preterm birth did not significantly differ. Conclusion Maternal Rh status is not associated with adverse outcomes in primigravida women.

Objective This study aimed to investigate trends in the rate of cesarean sections (CSs) in South Korea from 2006 to 2015 and identify the risk factors associated with these changes. Methods Using the National Health Insurance Corporation dataset, all women who gave birth between 2006 and 2015 were included in the study. We investigated 1) the mode of delivery, 2) the complication rates during pregnancy (i.e., preeclampsia and placenta previa), and 3) pre-pregnancy factors (body mass index, hypertension [HTN], diabetes mellitus [DM], and other pre-existing medical conditions), and their trends during the study period. Results Over 10 years, the rate of CS increased from 36.3% in 2006 to 40.6% in 2015 (P

Group B streptococcus (GBS) vaccines are currently under development. Data on the natural immunity in diverse age groups will aid establishing the GBS immunization policy. In this study, thirty serum samples were collected from three age groups (neonates/infants, pregnant women, and the elderly) between August 2016 and July 2017. Serotype-specific opsonophagocytic activity (OPA) was assessed using a GBS multiplex opsonophagocytic killing assay (MOPA) against serotypes Ia, III, and V. The mean OPA titers for serotype Ia of the three age groups were not significantly different (p = .156), but tended to be lower in neonates/infants (mean ± standard deviation, 137 ± 278). For serotype III and V, the mean OPA titer of neonates/infants (338 ± 623 and 161 ± 445, respectively) was significantly lower than that of pregnant women (1377 ± 1167 and 9414 ± 6394) and the elderly (1350 ± 1741 and 3669 ± 5597) (p = .002). In conclusion, the lower levels of OPA titers against all tested serotypes in neonates/infants, despite high maternal titers, indicates that intrapartum GBS vaccinations may be required for efficient placental transfer of serotype-specific GBS antibodies with high avidity.

ABSTRACTZika virus (ZIKV) infection during pregnancy is associated with congenital brain abnormalities, a finding that highlights the urgent need to understand mother-to-fetus transmission mechanisms. Human umbilical cord mesenchymal stem cells (hUCMSCs) are susceptible to ZIKV infection but the underlying mechanisms of viral susceptibility remain largely unexplored. In this study, we have characterized and compared host mRNA and miRNA expression profiles in hUCMSCs after infection with two lineages of ZIKV, African (MR766) and Asian (PRVABC59). RNA sequencing analysis identified differentially expressed genes involved in anti-viral immunity and mitochondrial dynamics following ZIKV infection. In particular, ZIKV-infected hUCMSCs displayed mitochondrial elongation and the treatment of hUCMSCs with mitochondrial fission inhibitor led to a dose-dependent increase in ZIKV gene expression and decrease in anti-viral signalling pathways. Moreover, small RNA sequencing analysis identified several significantly up- or down-regulated microRNAs. Interestingly, miR-142-5p was significantly downregulated upon ZIKV infection, whereas cellular targets of miR-142-5p, IL6ST and ITGAV, were upregulated. Overexpression of miR-142-5p resulted in the suppression of ZIKV replication. Furthermore, blocking ITGAV expression resulted in a significant suppression of ZIKV binding to cells, suggesting a potential role of ITGAV in ZIKV entry. In conclusion, these results demonstrate both common and specific host responses to African and Asian ZIKV lineages and indicate miR-142-5p as a key regulator of ZIKV replication in the umbilical cords.

Although there is a high rate of pregnant immigrant women in Korea, little is known regarding their pregnancy outcomes. The aim of this study was to evaluate the pregnancy outcomes of immigrant women in Korea. Data for all pregnant women who gave birth between January 1, 2007 and December 31, 2016 were obtained using the Health Insurance Review and Assessment Service Database. Pregnant women were divided into two groups: Korean and immigrant women. The main outcome measures were adverse pregnancy outcomes including gestational diabetes of mellitus, preeclampsia, cesarean section, placental abrnomalities, and postpartum hemorrhage. The odds of gestational diabetes mellitus, preeclampsia, cesarean section, placental previa, placental abruptio, and postpartum hemorrhage was compared between the two groups. Among 4,439,778 pregnant women who gave birth during the study period, 168,940 (3.8%) were immigrant women. The odds of gestational diabetes mellitus (adjusted OR: 1.24; 95% CI: 1.21, 1.28), and cesarean section (adjusted OR: 1.26; 95% CI: 1.25-1.28)were higher in immigrant women than in Korean women, but the odds of preeclampsia (adjusted OR: 0.84; 95% CI: 0.81-0.86) and postpartum hemorrhage (adjusted OR 0.96, 95% CI 0.94-0.97) was lower in immigrant women than in Korean women. Immigrant women had different pregnancy outcomes. Pregnancy and postpartum management that reflects these characteristics will be necessary for immigrant women.

Background Although pregnancy‐induced hypertension (PIH) is associated with an elevated cardiovascular risk, long‐term studies or prepregnancy baseline data are scarce. Therefore, using a large nationwide cohort with prepregnancy periodic health screening data, we investigated whether clinically significant arrhythmia incidence increases after PIH. Methods and Results Data were extracted from the Korea National Health Insurance database and combined with the National Health Screening Examination database; women who gave birth between 2007 and 2015 and underwent the national health screening test within a year before pregnancy were followed up until 2016. We excluded women who had a diagnosis of arrhythmia within 1 year before pregnancy. The primary outcome was significant arrhythmia during the year after delivery. Secondary analysis included only specific diagnostic codes of arrhythmia with clinical significance. Additionally, the risk of arrhythmia was stratified by the use of magnesium sulfate. Of 2 035 684 women (PIH; n=37 297 versus normotensive pregnancy; n=1 998 387), the PIH group had a higher prepregnancy risk profile and showed a higher incidence of arrhythmia than women with normotensive pregnancies within 1 year. Women with PIH had a significantly higher risk of atrial flutter/fibrillation and atrioventricular block, but not lethal arrhythmias. Other predictors of arrhythmia development included advanced maternal age and cesarean section. Stratified analysis showed a higher risk of arrhythmia with magnesium sulfate use. Conclusions PIH was significantly associated with the development of arrhythmia within 1 year after delivery. Nevertheless, the incidence of lethal arrhythmias was not increased by PIH. Arrhythmia, especially atrial fibrillation, may largely contribute to increasing the future cardiovascular risk in women with a PIH history.

Abstract Background Obstetric hemorrhage is one of the most common causes of obstetrical morbidity and mortality, and transfusion is the most important management for hemorrhage. The aim of our study was to investigate the pre-pregnancy and pregnancy risk factors for peripartum transfusion. Methods Women who delivered a baby from 2010 to 2014 in Korea and participated in the Korean National Health Screening Program for Infants and Children were included. To analyze pre-pregnant risk factors for peripartum transfusion, an additional analysis was done for women who underwent a National Health Screening Examination within 1 year before pregnancy, including maternal waist circumference, body mass index, blood pressure, laboratory tests and history of smoking. Multivariable logistic regression analysis was used to estimate the risk factors for peripartum transfusion. Results Of the total 1,980,126 women who met the inclusion criteria, 36,868 (1.86%) were transfused at peripartum. In a multivariable regression model, the pregnancy risk factors for peripartum transfusion included maternal age above 35 years [odds ratio (OR): 1.41; 95% confidence interval (CI): 1.32–1.50], preterm birth (OR: 2.39; 95% CI: 2.15–2.65), and maternal hypertension (OR: 2.49; 95% CI: 2.24–2.77). Pre-pregnancy risk factors including fasting glucose level of more than 126 mg/dL (OR: 1.11; 95% CI: 1.02–1.20), current-smoker status (OR: 1.20; 95% CI: 1.06–1.37), and waist-circumference less than 80 cm (OR: 1.18; 95% CI: 1.06–1.30) were independently associated with peripartum blood transfusion. Conclusions Several pre-pregnancy and pregnancy risk factors were associated with peripartum blood transfusion. Some identified factors are modifiable before conception, and our study validated peripartum blood transfusion as a form of triage.

Introduction: Acute pyelonephritis (APN) is a common infection during pregnancy that increases the risk of unfavorable maternal and fetal outcomes. However, it has not been clearly elucidated which demographic and clinical characteristics are associated with the incidence of APN during pregnancy. Objective: This population-based cohort study aimed to determine the risk factors for APN during pregnancy. Methods: Using the database of the Health Insurance Review and Assessment Service of South Korea, we enrolled Korean women who delivered infants between 2010 and 2014 in Korea and had complete health examination records within 1 year of pregnancy. We performed multivariate logistic regression analysis to evaluate the risk factors for APN during pregnancy. Results: Of 370,248 women, 2,526 (0.7% of the total participants) were treated for APN while in hospitalization during pregnancy. Younger age, history of previous APN within 1 year of pregnancy, and abnormal results of health examination before pregnancy, such as high fasting glucose level (>100 mg/dL) and proteinuria, were associated with an increased risk of APN during pregnancy. Conclusion: Certain maternal demographic and clinical characteristics were associated with the incidence of APN during pregnancy, and these should be monitored closely during antenatal care.

The ovarian reserve is necessary for female fertility and endocrine health. Commonly used cancer therapies diminish the ovarian reserve, thus, resulting in primary ovarian insufficiency, which clinically presents as infertility and endocrine dysfunction. Prepubertal children who have undergone cancer therapies often experience delayed puberty or cannot initiate puberty and require endocrine support to maintain a normal life. Thus, developing an effective intervention to prevent loss of the ovarian reserve is an unmet need for these cancer patients. The selection of adjuvant therapies to protect the ovarian reserve against cancer therapies underlies the mechanism of loss of primordial follicles (PFs). Several theories have been proposed to explain the loss of PFs. The “burn out” theory postulates that chemotherapeutic agents activate dormant PFs through an activation pathway. Another theory posits that chemotherapeutic agents destroy PFs through an “apoptotic pathway” due to high sensitivity to DNA damage. However, the mechanisms causing loss of the ovarian reserve remains largely speculative. Here, we review current literature in this area and consider the mechanisms of how gonadotoxic therapies deplete PFs in the ovarian reserve.

ObjectiveThis study aimed to determine the association between preeclampsia and the postpartum development of metabolic syndrome based on the pre-pregnancy status.MethodsKorean women who delivered their first child between January 1, 2011, and December 31, 2012, were enrolled. All subjects underwent a national health screening examination conducted by the National Health Insurance Corporation 1 or 2 years prior to their first delivery and within 2 years after their first delivery.ResultsAmong the 49,065 participants, preeclampsia developed in 3,391 participants (6.9%). The prevalence of metabolic syndrome was higher postpartum in women with preeclampsia than in those without preeclampsia (4.9% vs. 2.7%, respectively, P

ObjectiveLong-term glycemic variability has recently been recognized as another risk factor for future adverse health outcomes. We aimed to evaluate the risk of gestational diabetes mellitus (GDM) according to the prepregnancy long-term fasting plasma glucose (FPG) variability.Research design and methodsA total of 164 053 women who delivered their first baby between January 1, 2012 and December 31, 2015, were selected from the Korean National Health Insurance data. All women underwent at least three national health screening examinations, and the last examination should be conducted within 2 years before their first delivery. GDM was defined as the presence of more than four times of claim of GDM (International Classification of Disease, 10th Revision (ICD-10) O24.4 and O24.9) or prescription of insulin under the ICD-code of GDM. FPG variability was assessed by variability independent of the mean (FPG-VIM), coefficient of variation, SD, and average successive variability.ResultsAmong the 164 053 women, GDM developed in 6627 (4.04%). Those in the higher quartiles of FPG-VIM showed a stepwise increased risk of GDM. In fully adjusted model, the ORs for GDM was 1.22 (95% CI 1.14 to 1.31) in women with the highest FPG-VIM quartile compared with those in the lowest quartile. The risk for GDM requiring insulin therapy was 48% increase in women in the highest quartile of FPG-VIM compared with those in the lowest quartile, while that for GDM not requiring insulin therapy was 19% increase. The association between high FPG variability and the risk of GDM was intensified in the obese and aged more than 35 years women.ConclusionsIncreased FPG variability in the prepregnancy state is associated with the risk of GDM independent of confounding factors. Therefore, prepregnancy FPG variability might be a surrogate marker of the risk of GDM.

OBJECTIVE:To evaluate not only the risk of total preterm birth (PTB) but also spontaneous preterm birth (sPTB) and indicated preterm birth (iPTB) in vanishing twin (VT). STUDY DESIGN:This is a secondary analysis of a multicenter prospective cohort study. In 12 different healthcare institutions, women with singleton pregnancies were enrolled in early pregnancy and followed up till delivery. RESULTS:A total of 4,746 women were included in the final analysis, and. the frequency of VT was 1.1% (54/4746). VT group had a higher risk for total PTB (PTB

Background: While speed, safety, and efficacy are necessary in the operation of cesarean section (CS), a number of new devices have been introduced to support the technique. This retrospective study was conducted to assess the usability and safety of knotless barbed suture, compared to conventional method, for closure of uterine myometrium during cesarean section. Methods: Patients who underwent cesarean delivery at Korea University Ansan Hospital between August 2018 and December 2019 were reviewed. Surgical outcomes including uterine closure time, operating time, estimated blood loss, and sonographic results of residual myometrial thickness at the site of incision at 6 to 8 weeks after operation were analyzed. Results: Out of total 78 women, 44 patients had knotless barbed suture and 34 patients underwent conventional suture. Compared to conventional method, the uterine closure time was significantly reduced (p = 0.012). Operative time, estimated blood loss during operation, hemoglobin difference on the third operative day, and the number of cases with transfusion, postpartum infection, and bleeding demonstrated no significant differences between the two groups. At 6 to 8 weeks after operation, transvaginal ultrasound revealed no differences in residual myometrial scar thickness. Conclusion: Knotless barbed suture resulted in significantly shorter uterine closure time and no increased rate of perioperative complications. Our work supports that knotless barbed suture can be effectively used for cesarean section.

Abstract Background A recent concept is that obesity, assessed by body mass index (BMI), is not always a sign of poor health. Thus, in order to use obesity metrics in clinical decision making, it is important to clarify the relationship between waist circumference (WC), a proxy for abdominal obesity, and mortality. Methods Data were used from 8,796,759 subjects aged between 30 and 90 years, who had participated in the Korea National Health Screening Examination between January 1, 2009 and December 31, 2009 and survived at least 1 year post screening. Data from a mean follow-up time of an additional 5.3 years (time at risk) were analyzed for the relationship between WC and mortality according to age, sex, and BMI category. Results An increased WC of more than 90 cm in men and 85 cm in women showed a definite negative influence on mortality. However, the detailed relationship between WC and mortality was J-shaped or U-shaped according to age, sex, and BMI category. In the normal BMI group, the optimal WC range with the lowest mortality was

Abstract Background Among the non-invasive screening methods for the identification of fetal aneuploidy, NIPT (non-invasive prenatal testing) shows the highest sensitivity and specificity in high-risk pregnancies. Due to the low false positive rate of NIPT, it is assumed that the implementation of NIPT as a primary screening method may reduce the number of invasive fetal tests and result in a similar or lowered cost in the overall detection of Down syndrome. However, most previous studies are based on theoretical economic analysis. This study aims to determine the cost effectiveness of various prenatal test strategies, including NIPT, in real clinical settings in both low risk and high risk pregnancies. Methods/design In this prospective observational study, women (

Abstract Background The aim of this study was to determine the effect of cerclage in women who underwent cervical conization. Methods Study data were collected from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service for 2009–2013. Women who had a conization in 2009 and a subsequent first delivery between 2009 and 2013 in Korea were enrolled. Results Among the women who had conization in 2009, 1075 women had their first delivery between 2009 and 2013. A cerclage was placed in 161 of the women who were treated by conization. The rate of preterm birth was higher in the women who were treated with cerclage following a conization compared with those without cerclage (10.56 vs 4.27, p

ObjectiveThe purpose of this study was to investigate the effects of estradiol on the expression of hypoxia-inducible factor (HIF)-1α and the differentiation of trophoblasts in human first trimester villous explant cultures.MethodsVillous explant cultures were established from first trimester human placentas (6–8 weeks of gestation, n=3). Normal villous tissues were explanted on Matrigel and incubated under 3% O2 tension for 5 days. To evaluate the effects of estradiol on the villous explant cultures, 1 ng/mL of estradiol was added to the culture medium. The morphological integrities and viabilities of the villous explants were monitored. Immunohistochemistry for α5 and α1 integrin was performed to assess differentiation of extravillous trophoblasts (EVTs). Expression of HIF-1α in villous explant cultures was evaluated by western blotting and densitometry.ResultsEVTs emerging from first trimester villous explant cultures formed outgrowths of cells from the distal ends and invaded the surrounding Matrigel. Exposure of villous explants to estradiol resulted in the decreased outgrowth of cells from the distal end and decreased expression of α5 integrin. However, estradiol treatment increased the invasion of villous explants into the surrounding Matrigel, concomitant with the increased expression of α1 integrin, indicating differentiation of EVTs into more invasive EVTs. On western blots, the expression of HIF-1α decreased significantly after treatment with estradiol under 3% O2 tension.ConclusionOur findings suggest that estradiol may downregulate expression of HIF-1α in placenta, which in turn promote trophoblast differentiation into invasive phenotype.

[This corrects the article DOI: 10.1371/journal.pone.0214600.].

This study uses machine learning and population data to analyze major determinants of preterm birth including depression and particulate matter. Retrospective cohort data came from Korea National Health Insurance Service claims data for 405,586 women who were aged 25–40 years and gave births for the first time after a singleton pregnancy during 2015–2017. The dependent variable was preterm birth during 2015–2017 and 90 independent variables were included (demographic/socioeconomic information, particulate matter, disease information, medication history, obstetric information). Random forest variable importance was used to identify major determinants of preterm birth including depression and particulate matter. Based on random forest variable importance, the top 40 determinants of preterm birth during 2015–2017 included socioeconomic status, age, proton pump inhibitor, benzodiazepine, tricyclic antidepressant, sleeping pills, progesterone, gastroesophageal reflux disease (GERD) for the years 2002–2014, particulate matter for the months January–December 2014, region, myoma uteri, diabetes for the years 2013–2014 and depression for the years 2011–2014. In conclusion, preterm birth has strong associations with depression and particulate matter. What is really needed for effective prenatal care is strong intervention for particulate matters together with active counseling and medication for common depressive symptoms (neglected by pregnant women).