The Role of the Aryl Hydrocarbon Receptor in Vascular Factors Related to Preeclampsia in a Smoking Mouse Model.

Smoking cigarettes is known to lower the risk of preeclampsia. The objective of this study is to evaluate the effect of smoking on the expression of soluble FMS-like tyrosine kinase-1 (sFlt-1), vascular endothelial growth factor (VEGF), and endoglin (sEng)-1 and the role of the aryl hydrocarbon receptor (AhR) in pregnant mice. We developed a smoking mouse model using a gas-filling system. One or two cigarettes per day were exposed to each of the five pregnant mice for five days a week throughout pregnancy. AhR agonist and antagonist were injected. Serum levels and expression in the placenta of sFlt-1, VEGF, and sEng-1 were analyzed and compared among the cigarette smoke and no-exposure groups after delivery. Compared to the no-smoke exposure group, the serum level of sFlt-1 was significantly decreased in the two-cigarette-exposed group (p < 0.001). When the AhR antagonist was added to the two-cigarette-exposed group, sFlt-1 levels were significantly increased compared to the two-cigarette group (p = 0.002). The levels of sFlt-1 in the AhR antagonist group did not change regardless of two-cigarette exposure (p = 0.064). With the AhR agonist, sFlt-1 decreased significantly compared to the control (p = 0.001) and AhR antagonist group (p = 0.002). The sFlt-1 level was significantly decreased after the injection of the AhR agonist compared to the control group (p = 0.001). Serum levels of VEGF were significantly decreased in the one-cigarette-exposed group compared to the control group; however, there was no difference between the control and the two-cigarette-exposed groups. The placental expression of sFlt-1, VEGF, and sEng were inconsistent. This study offers insights into the potential role of AhR on antiangiogenic sFlt-1 associated with preeclampsia. It may support the invention of a new treatment strategy for preeclampsia using AhR activation.

The Risk of Hypertension and Diabetes Mellitus According to Offspring's Birthweight in Women With Normal Body Mass Index: A Nationwide Population-Based Study.

BACKGROUND: Maladaptation to vascular, metabolic, and physiological changes during pregnancy can lead to fetal growth disorders. Moreover, adverse outcomes during pregnancy can further increase the risk of cardiovascular and metabolic diseases in mothers. Delivering a large-for-gestational-age (LGA) baby may indicate a pre-existing metabolic dysfunction, whereas delivering a small-for-gestational-age (SGA) baby may indicate a pre-existing vascular dysfunction. This study aims to assess the risk of hypertension (HTN) and diabetes mellitus (DM) in women with normal body mass index (BMI) scores who did not experience gestational DM or hypertensive disorders during pregnancy based on the offspring's birthweight. METHODS: This retrospective nationwide study included women with normal BMI scores who delivered a singleton baby after 37 weeks. Women with a history of DM or HTN before pregnancy and those with gestational DM or hypertensive disorders, were excluded from the study. We compared the risk of future maternal outcomes (HTN and DM) according to the offspring's birthweight. Multivariate analyses were performed to estimate the hazard ratio (HR) for the future risk of HTN or DM. RESULTS: A total of 64,037 women were included in the analysis. Of these, women who delivered very LGA babies (birthweight > 97th percentile) were at a higher risk of developing DM than those who delivered appropriate-for-gestational-age (AGA) babies (adjusted HR = 1.358 [1.068-1.727]), and women who delivered very SGA babies (birthweight < 3rd percentile) were at a higher risk of developing HTN than those who delivered AGA babies (adjusted HR = 1.431 [1.181-1.734]), even after adjusting for age, parity, gestational age at delivery, fetal sex, maternal BMI score, and a history of smoking. CONCLUSION: These findings provide a novel support for the use of the offspring's birthweight as a predictor of future maternal diseases such as HTN and DM.

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.

Prepregnancy Glucose Levels Within Normal Range and Its Impact on Obstetric Complications in Subsequent Pregnancy: A Population Cohort Study.

BACKGROUND: We sought to identify the influence of prepregnancy glucose levels on obstetric complications in subsequent pregnancy. METHODS: Women in Republic of Korea who had given birth between January 1st, 2007 and December 31st, 2010 were enrolled. The database of the Health Insurance Review and Assessment Service and data from a national health screening program for infants and children were used. Subjects were divided into seven groups according to their fasting glucose levels. RESULTS: 59,619 women were included for analysis, and 10.4%, 13.7%, 19.1%, 21.5%, 16.0%, 11.6%, and 7.5% women had glucose levels of < 75, 75-79, 80-84, 85-89, 90-94, 95-100 and > 100 mg/dL. Each 5 mg/dL increase in prepregnancy fasting glucose levels was associated with increased risk of gestational diabetes and macrosomia in subsequent pregnancy. Adjusted risk ratio for gestational diabetes per standard deviation prepregnancy glucose > 100 mg/dL was 2.015 (95% confidence interval, 1.649-2.462) and for macrosomia an adjusted risk ratio 1.389 (95% confidence interval, 1.147-1.682). CONCLUSION: Higher prepregnancy glucose level within normal range was related to gestational diabetes and macrosomia in following pregnancy. Our results may aid in the identification of women at future risk of obstetric complications and may guide to stratify women into normal and intensified care. TWEETABLE ABSTRACT: Higher prepregnancy glucose in normal range is associated with gestational diabetes and macrosomia.

Headaches during pregnancy and the risk of subsequent stroke.

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.

The risk for future cerebrovascular disease in pregnant women with Moyamoya disease: a nationwide population-based study in South Korea.

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 < 0.0001). Among women with Moyamoya disease, 55 (13.35%) women developed CVD within the follow-up postpartum period. The presence of Moyamoya disease was associated with an increased risk of CVD after delivery (adjusted HR 37.42; 95% confidence interval (CI) 17.50-80.02 within 2.3 years) after adjusting for pregnancy-induced hypertension, gestational diabetes mellitus, pregestational diabetes, chronic hypertension. CONCLUSION: This population based study showed that the occurrence rate of CVD after delivery was higher in women with Moyamoya disease than in those without. Therefore, careful and long-term postpartum surveillance is required for women with Moyamoya disease.

Prior pregnancy complications and maternal cardiovascular disease in young Korean women within 10 years after pregnancy.

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.

Pre-pregnancy blood pressure and pregnancy outcomes: a nationwide population-based study.

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 < 140/90 mmHg were enrolled. The primary outcome of composite morbidity was defined as any of the followings: preeclampsia, placental abruption, stillbirth, preterm birth, or low birth weight. RESULTS: A total of 375,305 pregnant women were included. After adjusting for covariates, the risk of composite morbidity was greater in those with stage I hypertension in comparison with the normotensive group (systolic blood pressure, odds ratio = 1.68, 95% CI: 1.59 - 1.78; diastolic blood pressure, odds ratio = 1.56, 95% CI: 1.42 - 1.72). There was a linear association between pre-pregnancy blood pressure and the primary outcome, with risk maximizing at newly defined stage I hypertension and with risk decreasing at lower blood pressure ranges. CONCLUSIONS: 'The lower, the better' phenomenon was still valid for both maternal and neonatal outcomes. Our results suggest that the recent changes in diagnostic thresholds for hypertension may also apply to pregnant women. Therefore, women with stage I hypertension prior to pregnancy should be carefully observed for adverse outcomes.

Women with multiple gestations have an increased risk of development of hypertension in the future.

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 < 0.01, respectively). On the Cox proportional hazards models, the risk of HTN was increased in women with multiple gestations (HR 1.35, 95% CI 1.19, 1.54) compared with those with singleton after adjustment for age, primiparity, preeclampsia, atrial fibrillation, body mass index, blood pressure, diabetes mellitus, high total cholesterol, abnormal liver function test, regular exercise, and smoking status. CONCLUSIONS: Multiple gestations are associated with an increased risk of HTN later in life. Therefore, guidelines for the management of high-risk patients after delivery should be established.

Role of sex hormones in cervical changes in a cervical excision-related preterm delivery mouse model.

Progesterone and oestrogen play important roles during parturition; however, their roles in the uterine cervix during preterm labour and delivery are unknown. We evaluated the serum progesterone and oestrogen levels and changes in their receptors (PR and ER) in the cervix in a cervical excision-associated preterm delivery mouse model. Adult female C57BL/6 mice were divided into four groups: sham, cervical excision (Ex), lipopolysaccharide (LPS) and Ex + LPS. Mating was permitted at 3 weeks post-Ex. On gestation day 16, mice were administered LPS intrauterine (100 µg/100 µL/mouse) or physiological saline (100 µL) via laparotomy. Uterine cervices and blood were sampled immediately postpartum. As a result, epithelial PR and muscular ERα were down- and upregulated, respectively, in the proximal cervix in Ex + LPS group compared to in the sham group. These results indicate that unique sex hormone effects are exerted on the uterine cervix during cervical excision-associated spontaneous preterm labour and delivery.Impact statementWhat is already known on this subject? Preterm and term parturition require the withdrawal of progesterone and the activation of oestrogen in the uterine body and systemic levels. However, we have little understanding of the role of the sex hormones in the uterine cervix.What do the results of this study add? Increased ERα-to-PR expression ratio in the proximal cervix was associated with preterm labour and delivery. ERα expression in the smooth muscle layer of the proximal cervix was higher and PR expression in the proximal cervix epithelium was lower during preterm labour and delivery.What are the implications of these findings for clinical practice and/or further research? This study revealed the differences between the roles of sex hormones and their receptors in epithelial and muscle layers of proximal and distal cervices in preterm labour and delivery.

Paradoxical long-term impact of maternal influenza infection on neonates and infants.

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.

Clinical Predictors Implicated in the Incidence of Acute Pyelonephritis during the Antepartum Period: A Population-Based Cohort Study.

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.

Serum sFlt-1, cystatin C and cathepsin B are potential severity markers in preeclampsia: a pilot study.

PURPOSE: Preeclampsia is associated with abnormal invasion of the trophoblast through decidua and subsequently altered remodeling of the maternal spiral arteries and endothelial dysfunction. This phenomenon is explained by the dysregulation of various kinds of vascular factors and proteases. The purpose of this study was to compare the circulating levels of sFlt-1, cathepsin B, and cystatin C in preeclamptic and normotensive pregnancies. STUDY DESIGN: Sixty-two pregnant women were enrolled in this prospective study. Twenty women were preeclamptic and 42 were normotensive. Serum levels of sFlt-1, cathepsin B, and cystatin C were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Circulating levels of sFlt-1, cathepsin B, and cystatin C were significantly higher in preeclamptic than in normotensive pregnant women (p < 0.001; p = 0.017; p = 0.003). Preeclamptic women with severe features demonstrated significantly higher levels of cathepsin B (p = 0.05). Serum sFlt-1 and cystatin C levels were positively correlated with elevated systolic and diastolic blood pressure. The levels of cathepsin B were positively correlated with alanine and aspartate aminotransferase. The amount of 24 h proteinuria was positively, but non-significantly correlated with sFlt-1 and cystatin C. CONCLUSIONS: In addition to sFlt-1 levels, the serum levels of cathepsin B and cystatin C significantly change when preeclampsia develops. These markers are associated with severity markers of elevated blood pressure and liver injury in preeclampsia.

Predicting peripartum blood transfusion: focusing on pre-pregnancy characteristics.

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.

Addition of Cervical Elastography May Increase Preterm Delivery Prediction Performance in Pregnant Women with Short Cervix: a Prospective Study.

BACKGROUND: We investigated whether there is a difference in elastographic parameters between pregnancies with and without spontaneous preterm delivery (sPTD) in women with a short cervix (≤ 25 mm), and examined the ability of elastographic parameters to predict sPTD in those women. METHODS: E-CervixTM (WS80A; Samsung Medison, Seoul, Korea) elastography was used to examine the cervical strain. Elastographic parameters were compared between pregnancies with and without sPTD. Diagnostic performance of elastographic parameters to predict sPTD ≤ 37 weeks, both alone and in combination with other parameters, was compared with that of cervical length (CL) using area under receiver operating characteristic curve (AUC) analysis. RESULTS: A total of 130 women were included. Median gestational age (GA) at examination was 24.4 weeks (interquartile range, 21.4-28.9), and the prevalence of sPTD was 20.0% (26/130). Both the elastographic parameters and CL did not show statistical difference between those with and without sPTD. However, when only patients with CL ≥ 1.5 cm (n = 110) were included in the analysis, there was a significant difference between two groups in elasticity contrast index (ECI) within 0.5/1.0/1.5 cm from the cervical canal (P < 0.05) which is one of elastographic parameters generated by E-Cervix. When AUC analysis was performed in women with CL ≥ 1.5 cm, the combination of parameters (CL + pre-pregnancy body mass index + GA at exam + ECI within 0.5/1.0/1.5 cm) showed a significantly higher AUC than CL alone (P < 0.05). CONCLUSION: An addition of cervical elastography may improve the ability to predict sPTD in women with a short CL between 1.5 and 2.5 cm.

Prepregnancy liver enzyme levels and risk of preeclampsia in a subsequent pregnancy: A population-based cohort study.

BACKGROUND & AIMS: Preeclampsia is a serious multisystemic disorder leading to maternal and neonatal adverse outcomes. However, little is known about the early markers of this disease. The aim of this study was to investigate the association between prepregnancy liver function and the development of preeclampsia. METHODS: We enrolled 192 571 Korean women who had their first delivery between January 1, 2008, and December 31, 2014, and had undergone a national health screening examination through the National Health Insurance Corporation during 1-2 years before delivery. RESULTS: Preeclampsia developed in 3973 (2.0%) women. The rate of development of preeclampsia was higher in women with abnormal prepregnancy liver enzyme levels than in those with normal liver enzyme levels before pregnancy. On multivariate analysis, women with abnormal alanine aminotransferase level before pregnancy had a 1.21-fold increased risk of developing preeclampsia than those with normal alanine aminotransferase level before pregnancy, after adjusting for age, family history of hypertension, hepatitis B virus carrier status, smoking, alcohol status, prepregnancy body mass index and blood pressure. Prepregnancy γ-glutamyltransferase and aspartate aminotransferase levels were not associated with the risk of preeclampsia development. CONCLUSION: Abnormal prepregnancy alanine aminotransferase level was associated with the development of preeclampsia in a subsequent pregnancy. Further studies are needed to evaluate whether early intervention for liver function before pregnancy can decrease the risk of preeclampsia.

Cerclage is associated with the increased risk of preterm birth in women who had cervical conization.

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 < 0.01, respectively). The multivariate regression analysis revealed that the women who were treated cerclage following a conization had an increased risk of preterm delivery compared with women without cerclage (odds ratio (OR), 2.6, 95% confidence interval (CI), 1.4-4.9). CONCLUSION: Our study showed that cerclage associated with an increased risk of preterm birth and preterm premature rupture of membranes in women who underwent conization. Further studies are required to clarify the mechanism by which cerclage affects the risk of preterm birth.

Preeclampsia Increases the Incidence of Postpartum Cerebrovascular Disease in Korean Population.

BACKGROUND: Multiple studies have been reported regarding preeclampsia as a possible risk factor of cerebrovascular disease (CVD). However, the correlation of preeclampsia and CVD, whether it is a cause-effect relationship or they are sharing common predisposing condition, is not well understood. Therefore, the aim of this study was to investigate the association between the preeclampsia during pregnancy and development of postpartum CVD. METHODS: A total of 1,384,550 Korean women who had a delivery between January 1, 2010 and December 31, 2012, were enrolled. Women with the risk of CVD within 1 year prior to pregnancy were excluded based on the Charlson comorbidity index. Primary endpoint was the event of CVD within a year from delivery. After exclusion, 1,075,061 women were analyzed. RESULTS: During the follow-up of 1 year postpartum, there were 25,577 preeclampsia out of 1,072,041 women without postpartum CVD (2.39%), and 121 of 3,020 women with postpartum CVD had preeclampsia before delivery (4.01%). In multivariate logistic regression analysis, women who had preeclampsia during pregnancy showed a higher risk for postpartum CVD (odds ratio, 1.64; 95% confidence interval, 1.37-1.98). CONCLUSION: The incidence of CVD after delivery was higher in women who had preeclampsia during pregnancy.

Recurrent Risk of Preterm Birth in the Third Pregnancy in Korea.

BACKGROUND: Although preterm delivery is the most common cause of infant morbidity and mortality, an obvious cause cannot be found in most cases. Preterm delivery is known to be the most important risk factor for preterm birth in a subsequent pregnancy. We aimed to evaluate the recurrence rate of premature births for subsequent pregnancies in women with a history of a preterm birth. METHODS: Study data were collected from the Korea National Health Insurance (KNHI) claims database and data from a national health-screening program for infants and children. We enrolled women who had their first delivery between January 1, 2007 and December 31, 2007 and a subsequent delivery before 2014. RESULTS: Preterm delivery had a significant higher risk of preterm birth in a subsequent singleton pregnancy. The risk of preterm birth at second pregnancy was 2.2% in women whose first delivery at ≥ 37 weeks and 18.6% in women whose first delivery at < 37 weeks (relative risks [RR], 8.64; 95% confidence interval [CI], 7.94-9.40). In the analysis of the third pregnancy, we compared women with an initial term birth followed by preterm birth and women with an initial preterm birth followed by a subsequent term birth. A history of a just preceding preterm birth at < 37 weeks was the most relevant factor for recurrence of preterm delivery in a subsequent pregnancy (26.6%, RR, 4.01; 95% CI, 2.45-6.58). CONCLUSION: We found that the prognosis of a third pregnancy was more closely related to the outcome of the second pregnancy to that of the first pregnancy.

The safety of progestogen in the prevention of preterm birth: meta-analysis of neonatal mortality.

BACKGROUND: The safety of preventive progestogen therapy for preterm birth remains to be established. This meta-analysis aimed to evaluate the effects of preventive progestogen therapy on neonatal mortality. METHODS: Randomized controlled trials (RCTs) on the preventive use of progestogen therapy, published between October 1971 and November 2015, were identified by searching MEDLINE/PubMed, EMBASE, Scopus, ClinicalTrials.gov, Cochrane Library databases, CINAHL, POPLINE, and LILACS using "progesterone" and "preterm birth" as key terms. We conducted separate analyses according to the type of progestogen administered and plurality of the pregnancy. RESULTS: Twenty-two RCTs provided data on 11,188 neonates. Preventive progestogen treatment in women with a history of preterm birth or short cervical length was not associated with increased risk of neonatal death compared to placebo in all analyzed progestogen types and pregnancy conditions. The pooled relative risks (95% confidence interval) of neonatal mortality were 0.69 (0.31-1.54) for vaginal progestogen in singleton pregnancies, 0.6 (0.33-1.09) for intramuscular progestogen in singleton pregnancies, 0.96 (0.51-1.8) for vaginal progestogen in multiple pregnancies, and 0.96 (0.49-1.9) for intramuscular progestogen in multiple pregnancies. CONCLUSIONS: The results of this meta-analysis suggest that administration of preventive progestogen treatment to women at risk for preterm birth does not appear to negatively affect neonatal mortality in single or multiple pregnancies regardless of the route of administration.