Effect of a Patient Blood Management Program on the Appropriateness of Red Blood Cell Transfusion and Clinical Outcomes in Elderly Patients Undergoing Hip Fracture Surgery

Background@#Elderly patients with hip fractures frequently receive perioperative transfusions, which are associated with increased morbidity and mortality. This study aimed to evaluate the impact of a patient blood management (PBM) program on the appropriateness of red blood cell (RBC) transfusion and clinical outcomes in geriatric patients undergoing hip fracture surgery. @*Methods@#In 2018, the revised PBM program was implemented at the Korea University Anam Hospital, Seoul, Republic of Korea. Elderly patients aged ≥ 65 years who underwent hip fracture surgery from 2017 to 2020 were evaluated. Clinical characteristics and outcomes were analyzed according to the timing of PBM implementation (pre-PBM, early-PBM, and late-PBM). Multiveriate regression analysis was used to evaluate the risk factors of the adverse outcomes, such as in-hospital mortality or 30-day readmission. @*Results@#A total of 884 elderly patients were included in this study. The proportion of patients who received perioperative RBC transfusions decreased significantly (43.5%, 40.1%, and 33.2% for pre-PBM, early-PBM, and late-PBM, respectively; P = 0.013). However, the appropriateness of RBC transfusion significantly increased (54.0%, 60.1%, and 94.7%, respectively; P < 0.001). The duration of in-hospital stay and 30-day readmission rates significantly decreased. Multivariable regression analysis revealed that RBC transfusion (odds ratio, 1.815; 95% confidence interval, 1.137–2.899; P = 0.013) was significantly associated with adverse outcomes. @*Conclusion@#Implementing the PBM program increased the appropriateness of RBC transfusion without compromising transfusion quality and clinical outcomes. Therefore, adopting the PBM program may improve the clinical management of elderly patients following hip fracture surgery.

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 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 abstractHigher prepregnancy glucose in normal range is associated with gestational diabetes and macrosomia.

Artificial intelligence in obstetrics

This study reviews recent advances on the application of artificial intelligence for the early diagnosis of various maternal-fetal conditions such as preterm birth and abnormal fetal growth. It is found in this study that various machine learning methods have been successfully employed for different kinds of data capture with regard to early diagnosis of maternal-fetal conditions. With the more popular use of artificial intelligence, ethical issues should also be considered accordingly.

The Present and Future Status of Maternal and Child Health From the Perspective of Unification Medicine

As North Korea’s healthcare sector loses functionality under the collapsing socialist system, the gap in medical care between North and South Korea is widening. As a result, we expect that the social safety network will disintegrate in the medical field after unification, and in view of this, our study analyzes the infants and mothers who are likely to be most affected at this time to establish a direction for the promotion of unification in the future. Maternal health in North and South Korea was analyzed by the prevalence of anemia, maternal mortality ratio, prenatal and postpartum visits, and child health was analyzed by chronic malnutrition, vaccination penetration rate, and infant mortality rate to evaluate North Korea's poor nutritional conditions and medical system. The introduction of the legal system related to maternal and child health in North and South Korea includes prenatal and postpartum management and labor. Under this legal system, North Korea includes accessibility to hospitals and children's nutrition management issues, and South Korea includes subfertility treatment and postpartum care centers. As a countermeasure to the low birth rate problem emerging in both countries, the governments are providing work leave and economic support. In order to make effective use of the maternal health indicators from a unified scientific perspective, they should be calculated and codeveloped by both North and South Korea, and a multifaceted approach is needed through the setting of additional indicators such as the perinatal mortality rate.

A Survey on Public Perceptions of Low Fertility: A Social Research Panel Study

Background@#It was reported that South Korea showed the greatest decline in the fertility rate among the entire OECD countries over the last 30 years with the total fertility rate (TFR) of 0.84 persons in 2020. Despite the efforts of the Korean government, the TFR has decreased constantly. This study intended to analyze the perception of Koreans toward pregnancy and childbirth regarding the low fertility rate in South Korea for understanding the causes of constantly decreased low fertility. @*Methods@#This study carried out an online survey based on 1,002 men and women aged 19 to 59 years old for six days from October 21 to October 26 in 2021 in cooperation with Gallup Korea. This study analyzed the perception of people toward low fertility, the severity of low fertility, and level of interest in low fertility to inspect awareness of the severity of low fertility in South Korea through a survey. @*Results@#It was found that 62%, 52%, and 72% of entire participants, women, and men agreed on a question “It is better to get married”. As for women’s age, a positive response for this question was derived from 34.2% (20s), 43.1% (30s), 53.4% (40s), and 71.4% (50s), respectively (P < 0.001). In a question “the necessity of children”, a positive response for this question was derived from 34.7% (20s), 58.3% (30s), 75.9% (40s), and 83.5% (50s) of female respondents, respectively (P < 0.001). Positive responses were shown 39.2%, 60.0%, 79.7%, and 81.5% of female participants in their 20s, 30s, 40s, and 50s agreed on the question “My children make me happy in my life”, respectively (P < 0.001). @*Conclusion@#This study found that a decrease in the TFR was affected mainly by the negative perception of women in their 20s and 30s toward marriage, childbirth, and the necessity of children. Therefore, further research should be conducted to develop policies that focus on these significant variables to overcome the worsening low fertility problem.

Analysis of Research Status on Disease of Women and Children in North Korea: Literature Analysis Through Academic Journals

Purpose@#Since the division of the Korean Peninsula into South and North Korea in 1948, the gaps in the medical system and the socioeconomic status between these 2 countries has expanded. The purpose of this study was to analyze the distribution of different areas of research, as well as the types of research that was conducted in the North Korean medical journal, ‘Pediatrics, Obstetrics and Gynecology.’ This study aimed to specifically investigate the medical research status of healthcare in women and children. @*Methods@#This study analyzed a total of 949 papers that were published in the North Korean medical journal, ‘Pediatrics, Obstetrics and Gynecology.’ Papers from January 2015 to December 2019 were included. For the analysis, the 8th Korean Standard Classification of Diseases, disease name, subspecialty classification, and research classifications were extracted from the papers.Result: Of the 949 papers included in the analysis, 495, 366, and 88 studies were conducted in the major fields of obstetrics and gynecology, pediatrics, and on breast surgery, respectively. Within the field of obstetrics and gynecology, the most studied subspecialties were maternal and fetal medicine, general gynecology, and gynecologic oncology. To a lesser extent, the following subspecialties were reported: gynecologic endocrinology (6.7%), infertility (6.3%), and urogynecology (approximately 1%). @*Conclusion@#Although North Korean papers differ from those published worldwide (due to government intervention), they are still a useful source of information as they are easier to access than alternative data sources. The results from this study have implications for understanding the distribution of research on different areas of healthcare, as well as the burden of healthcare in North Korea.

Coronavirus Disease 2019 Vaccination during Pregnancy

Several vaccines have been developed to combat the coronavirus disease 2019 (COVID-19), including messenger Ribonucleic acid (mRNA, Pfizer-BioNtech, and Moderna) and viral vector (AstraZeneca and Janssen) types. Unfortunately, reports of COVID-19 exposure during pregnancy are scarce, as pregnancy and breastfeeding were among the exclusion criteria in the efficacy and safety studies of major COVID-19 vaccines. The U.S. Centers for Disease Control and Prevention recently included pregnancy as a risk factor for severe COVID-19 infection, although the absolute risk is low. Previous experience in pregnant women with mRNA vaccines is lacking despite such vaccines not using live viruses, being unable to cause disease, not interacting with an individual's DNA, and being unable to cause genetic mutations. In addition, previous studies in animals have not revealed any safety issues with such vaccine types for female reproduction or fetal development. Vaccine-induced antibody titers were equivalent in pregnant and lactating women versus non-pregnant women. Given the data on increased mortality and morbidity associated with COVID-19 during pregnancy, it may be unethical to withhold vaccinations based on a theoretical risk and a lack of clinical research in this population. Additionally, a careful review of the vaccination recommendations for pregnant women by the academic community and government through additional efficacy and safety studies tailored to the situation in Korea is needed.

Association of Gastroesophageal Reflux Disease with Preterm Birth: Machine Learning Analysis

Background@#This study used machine learning and population data for testing the associations of preterm birth with gastroesophageal reflux disease (GERD) and periodontitis. @*Methods@#Retrospective cohort data came from Korea National Health Insurance Service claims data for all women who aged 25–40 years and gave births for the first time as singleton pregnancy during 2015–2017 (405,586 women). The dependent variable was preterm birth during 2015–2017 and the independent variables were GERD (coded as no vs. yes) for each of the years 2002–2014, periodontitis (coded as no vs. yes) for each of the years 2002–2014, age (year) in 2014, socioeconomic status in 2014 measured by an insurance fee, and region (city) (coded as no vs. yes) in 2014. Random forest variable importance was adopted for finding main predictors of preterm birth and testing its associations with GERD and periodontitis. @*Results@#Based on random forest variable importance, main predictors of preterm birth during 2015–2017 were socioeconomic status in 2014, age in 2014, GERD for the years 2012, 2014, 2010, 2013, 2007 and 2009, region (city) in 2014 and GERD for the year 2006. The importance rankings of periodontitis were relatively low. @*Conclusion@#Preterm birth has a stronger association with GERD than with periodontitis. For the prevention of preterm birth, preventive measures for GERD would be essential together with the improvement of socioeconomic status for pregnant women. Especially, it would be vital to promote active counseling for general GERD symptoms (neglected by pregnant women).

Introduction of Community-Based Preconception Care for Men and Women of Childbearing Age in Seoul

Community-based preconception care for men and women of childbearing age has been introduced in Seoul. The program aims to focus on problem areas such as low birth rate, fertility issues potentially due to late marriages, preterm or premature births, and low-birthweight in newborn babies. The district administration officials of Seoul, as well as, academics from the Korean Society of Maternal and Child Health, developed a protocol by using a questionnaire and laboratory test for screening risk factors in pregnancy. The protocol was tested on a trial basis in four local districts in Seoul from July 2017 to 2018, extended to 12 local districts in 2019, and all 25 districts in Seoul in 2020. The protocol includes AntiMullerian Hormone tests to assess women’s ovarian reserve and male health checkups that include semen analysis and physical examinations of genitalia. These tests are conducted for early detection and treatment of infertility, especially in cases of late marriages. In order to prevent women being abandoned during pregnancy (leading them to single-parenting), the protocol also emphasizes building a gender-sen sitive environment by encouraging more male participation. A monitoring group comprised of Seoul city district officials and academics from the Korean Society of Maternal and Child Health, regularly visited the local districts to observe improvements and keep the program officials up to date. In addition, the group also conducted a mobile phone survey for feedback on the program. The interest and support of the resi dents in Seoul city, and positive results and development in pregnancy care and childbirth, are needed to stabilize and extend this protocol.

Secular trends in cesarean sections and risk factors in South Korea (2006–2015)

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<0.01). The rate of CS increased in primiparous women, women with multiple pregnancy, and women with preeclampsia. Maternal age and the incidence of placenta previa also increased. In contrast, the rate of vacuum deliveries and vaginal birth after CS decreased during the study period. The rate of women with pre-pregnancy obesity and DM increased, but the rate of women with pre-pregnancy HTN decreased. @*Conclusion@#The rate of CS in South Korea increased from 2006 to 2015. This trend may reflect changes in the rate of different risk factors. Identifying the causes of the increasing CS trend observed in this study will allow clinicians to monitor these factors and possibly reduce the rate of CS.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth

BACKGROUND@#This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB).@*METHODS@#This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy.@*RESULTS@#For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy.@*CONCLUSION@#Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

Determinants of Spontaneous Preterm Labor and Birth Including Gastroesophageal Reflux Disease and Periodontitis

Background@#Periodontitis is reported to be associated with preterm birth (spontaneous preterm labor and birth). Gastroesophageal reflux disease (GERD) is common during pregnancy and is expected to be related to periodontitis. However, little research has been done on the association among preterm birth, GERD and periodontitis. This study uses popular machine learning methods for analyzing preterm birth, GERD and periodontitis. @*Methods@#Data came from Anam Hospital in Seoul, Korea, with 731 obstetric patients during January 5, 1995 - August 28, 2018. Six machine learning methods were applied and compared for the prediction of preterm birth. Variable importance, the effect of a variable on model performance, was used for identifying major determinants of preterm birth. @*Results@#In terms of accuracy, the random forest (0.8681) was similar with logistic regression (0.8736). Based on variable importance from the random forest, major determinants of preterm birth are delivery and pregestational body mass indexes (BMI) (0.1426 and 0.1215), age (0.1211), parity (0.0868), predelivery systolic and diastolic blood pressure (0.0809 and 0.0763), twin (0.0476), education (0.0332) as well as infant sex (0.0331), prior preterm birth (0.0290), progesterone medication history (0.0279), upper gastrointestinal tract symptom (0.0274), GERD (0.0242), Helicobacter pylori (0.0151), region (0.0139), calcium-channel-blocker medication history (0.0135) and gestational diabetes mellitus (0.0130). Periodontitis ranked 22nd (0.0084). @*Conclusion@#GERD is more important than periodontitis for predicting and preventing preterm birth. For preventing preterm birth, preventive measures for hypertension, GERD and diabetes mellitus would be needed alongside the promotion of effective BMI management and appropriate progesterone and calcium-channel-blocker medications.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth

BACKGROUND: This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB).METHODS: This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy.RESULTS: For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy.CONCLUSION: Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

Effect of Cervical Cerclage on the Risk of Recurrent Preterm Birth after a Twin Spontaneous Preterm Birth

BACKGROUND@#This study aimed to evaluate the effect of cervical cerclage on the recurrence risk for preterm birth in singleton pregnant women after a twin spontaneous preterm birth (sPTB).@*METHODS@#This multicenter retrospective cohort study included women who had a singleton pregnancy from January 2009 to December 2018 at 10 referral hospitals and a twin sPTB before the current pregnancy. We compared the cervical lengths during pregnancy and pregnancy outcomes, according to the placement of prophylactic or emergency cerclage. We evaluated the independent risk factors for sPTB (< 37 weeks of gestation) in a subsequent singleton pregnancy.@*RESULTS@#For the index singleton pregnancy, preterm birth occurred in seven (11.1%) of 63 women. There was no significant difference in the cervical lengths during pregnancy in women with and without cerclage. In a multivariate logistic regression analysis, the placement of emergency cerclage was an independent risk factor for subsequent singleton preterm birth (odds ratio [OR], 93.188; 95% confidence interval [CI], 1.633–5,316.628; P = 0.027); however, the placement of prophylactic cerclage (OR, 19.264; 95% CI, 0.915–405.786; P = 0.057) was not a factor. None of the women who received prophylactic cerclage delivered before 35 weeks' gestation in the index singleton pregnancy.@*CONCLUSION@#Cerclage did not lower the risk of preterm birth in a subsequent singleton pregnancy after a twin sPTB. However, emergency cerclage was an independent risk factor for preterm birth and there was no preterm birth before 35 weeks' gestation in the prophylactic cerclage group. Therefore, close monitoring of the cervical length and prophylactic cerclage might be considered in women who have experienced a twin sPTB at extreme gestation.

Determinants of Spontaneous Preterm Labor and Birth Including Gastroesophageal Reflux Disease and Periodontitis

Background@#Periodontitis is reported to be associated with preterm birth (spontaneous preterm labor and birth). Gastroesophageal reflux disease (GERD) is common during pregnancy and is expected to be related to periodontitis. However, little research has been done on the association among preterm birth, GERD and periodontitis. This study uses popular machine learning methods for analyzing preterm birth, GERD and periodontitis. @*Methods@#Data came from Anam Hospital in Seoul, Korea, with 731 obstetric patients during January 5, 1995 - August 28, 2018. Six machine learning methods were applied and compared for the prediction of preterm birth. Variable importance, the effect of a variable on model performance, was used for identifying major determinants of preterm birth. @*Results@#In terms of accuracy, the random forest (0.8681) was similar with logistic regression (0.8736). Based on variable importance from the random forest, major determinants of preterm birth are delivery and pregestational body mass indexes (BMI) (0.1426 and 0.1215), age (0.1211), parity (0.0868), predelivery systolic and diastolic blood pressure (0.0809 and 0.0763), twin (0.0476), education (0.0332) as well as infant sex (0.0331), prior preterm birth (0.0290), progesterone medication history (0.0279), upper gastrointestinal tract symptom (0.0274), GERD (0.0242), Helicobacter pylori (0.0151), region (0.0139), calcium-channel-blocker medication history (0.0135) and gestational diabetes mellitus (0.0130). Periodontitis ranked 22nd (0.0084). @*Conclusion@#GERD is more important than periodontitis for predicting and preventing preterm birth. For preventing preterm birth, preventive measures for hypertension, GERD and diabetes mellitus would be needed alongside the promotion of effective BMI management and appropriate progesterone and calcium-channel-blocker medications.

Secular trends in cesarean sections and risk factors in South Korea (2006–2015)

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<0.01). The rate of CS increased in primiparous women, women with multiple pregnancy, and women with preeclampsia. Maternal age and the incidence of placenta previa also increased. In contrast, the rate of vacuum deliveries and vaginal birth after CS decreased during the study period. The rate of women with pre-pregnancy obesity and DM increased, but the rate of women with pre-pregnancy HTN decreased. @*Conclusion@#The rate of CS in South Korea increased from 2006 to 2015. This trend may reflect changes in the rate of different risk factors. Identifying the causes of the increasing CS trend observed in this study will allow clinicians to monitor these factors and possibly reduce the rate of CS.

Artificial Neural Network Analysis of Spontaneous Preterm Labor and Birth and Its Major Determinants

BACKGROUND: Little research based on the artificial neural network (ANN) is done on preterm birth (spontaneous preterm labor and birth) and its major determinants. This study uses an ANN for analyzing preterm birth and its major determinants.

Grading System for the Management of Pregnant Women

Several studies have reported adequate patient transfer to higher level hospitals according to the risk for improving perinatal outcomes. According to these reports, countries across the world divide the levels of maternal care on the basis of the assessment of hospital facilities and medical services as well as the assessment of high-risk pregnancies while evaluating the cases of and risks associated with maternal care that can be addressed by these hospitals at each level. Because the level of and policies on maternal care vary across countries, we aimed to evaluate risk assessments and introduction of treatment facility classifications in different countries. In Korea, birth rate is declining and the number of elderly pregnant women is increasing, whereas the number of hospitals that can deliver a baby and care for mothers at high risk is decreasing. We, therefore, need to establish an infrastructure for medically vulnerable areas, a localization center, and a medical personnel supplement. Moreover, establishing detailed guidelines and criteria for different levels of maternal care is necessary. The new guidelines will also need to supplement the policies on the requirement of well-trained obstetricians and of low medical insurance fee.

Effects of estradiol on HIF-1α expression and trophoblast differentiation in first trimester villous explant cultures

OBJECTIVE: The 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. METHODS: Villous 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. RESULTS: EVTs 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. CONCLUSION: Our findings suggest that estradiol may downregulate expression of HIF-1α in placenta, which in turn promote trophoblast differentiation into invasive phenotype.

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.