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Fetal growth restriction (FGR) is one of the leading causes of perinatal morbidity and mortality. Many studies have reported an association between FGR and fetal Doppler indices focusing on umbilical artery (UA), middle cerebral artery (MCA), and ductus venosus (DV). The uteroplacental-fetal circulation which affects the fetal growth consists of not only UA, MCA, and DV, but also umbilical vein (UV), placenta and uterus itself. Nevertheless, there is a paucity of large-scale cohort studies that have assessed the association between UV, uterine wall, and placental thickness with perinatal outcomes in FGR, in conjunction with all components of the uteroplacental-fetal circulation. Therefore, this multicenter study will evaluate the association among UV absolute flow, placental thickness, and uterine wall thickness and adverse perinatal outcome in FGR fetuses. This multicenter retrospective cohort study will include singleton pregnant women who undergo at least one routine fetal ultrasound scan during routine antepartum care. Pregnant women with fetuses having structural or chromosomal abnormalities will be excluded. The U-AID indices (UtA, UA, MCA, and UV flow, placental and uterine wall thickness, and estimated fetal body weight) will be measured during each trimester of pregnancy. The study population will be divided into two groups: (1) FGR group (pregnant women with FGR fetuses) and (2) control group (those with normal growth fetus). We will assess the association between U-AID indices and adverse perinatal outcomes in the FGR group and the difference in U-AID indices between the two groups. [ABSTRACT FROM AUTHOR]

This study aimed to develop an early pregnancy risk scoring model for pregnancy-associated hypertension (PAH) based on maternal pre-pregnancy characteristics, such as mean arterial pressure (MAP), pregnancy-associated plasma protein-A (PAPP-A) or neither. The perinatal databases of seven hospitals from January 2009 to December 2020 were randomly divided into a training set and a test set at a ratio of 70:30. The data of a total pregnant restricted population (women not taking aspirin during pregnancy) were analyzed separately. Three models (model 1, pre-pregnancy factors only; model 2, adding MAP; model 3, adding MAP and PAPP-A) and the American College of Obstetricians and Gynecologists (ACOG) risk factors model were compared. A total of 2840 (8.11%) and 1550 (3.3%) women subsequently developed PAH and preterm PAH, respectively. Performances of models 2 and 3 with areas under the curve (AUC) over 0.82 in both total population and restricted population were superior to those of model 1 (with AUCs of 0.75 and 0.748, respectively) and the ACOG risk model (with AUCs of 0.66 and 0.66) for predicting PAH and preterm PAH. The final scoring system with model 2 for predicting PAH and preterm PAH showed moderate to good performance (AUCs of 0.78 and 0.79, respectively) in the test set. "A risk scoring model for PAH and preterm PAH with pre-pregnancy factors and MAP showed moderate to high performances. Further prospective studies for validating this scoring model with biomarkers and uterine artery Doppler or without them might be required". [ABSTRACT FROM AUTHOR]

This study investigated the effects of amnioreduction before physical examination-indicated cerclage on pregnancy outcomes using a propensity score matching analysis. This multicenter retrospective cohort study included women who underwent cerclage operations due to painless cervical dilation in the second trimester (14–28 weeks). The primary outcome was the time from operation until delivery. Secondary outcomes included preterm birth rate and neonatal outcomes. Primary and secondary outcomes were compared between those with amnioreduction and those without amnioreduction. Of 103 women, 31 received preoperative amnioreduction (amnioreduction group) and 72 women did not (no-amnioreduction group). Since there were differences in baseline characteristics and preoperative ultrasound findings between the two groups, we matched 25 women with amnioreduction and 25 women without amnioreduction using a propensity score. In the matched cohort, the amnioreduction group showed a shorter time from operation to delivery than the group without amnioreduction and the hazard ratio of amnioreduction was 2.5 (95% confidence interval; 1.4–4.7). In addition, the preterm birth rate before 28 weeks of gestation and the neonatal composite outcome were higher in the amnioreduction group than that in the group without amnioreduction. Amnioreduction before physical examination-indicated cerclage was associated with poor pregnancy and neonatal outcomes. Therefore, careful consideration is required when performing amnioreduction before cerclage operation. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Pregnant women were excluded from vaccination against Coronavirus 2019 (COVID-19) until September 2021 in South Korea. Although vaccination for pregnant women started in October 2021, vaccine acceptance in pregnant women is yet unknown. This cross-sectional study aimed to investigate COVID-19 vaccine acceptance during pregnancy and influencing factors. An anonymous survey was distributed in obstetrics departments to all pregnant or postpartum women, during the prenatal or postpartum visit. The proportion of self-reported COVID-19 vaccination during pregnancy among 436 women was 26.6%. Pregnancy-related independent factors influencing maternal COVID-19 vaccination were "received vaccine information about from obstetrics and gynecology (OBGYN) doctors" (OR 3.41, 95% CI 2.05–5.65), "cohabitant COVID-19 vaccination" (OR 2.43, 95% CI 1.06–5.59), and "second trimester" (OR 7.35, 95% CI 1.54–35.15). In women who did not want to get vaccinated, the most common reason for COVID-19 vaccination hesitancy was concern that COVID-19 vaccine might affect the fetus (91.7%, 243/266), followed by distrust in COVID-19 vaccine effectiveness (42.6%, 113/266). This study showed that providing information about maternal COVID-19 vaccination, especially by OBGYN doctors, is crucial for increasing vaccination coverage in pregnant women. Providing updated evidence of COVID-19 vaccine efficacy and safety in pregnant women may be also helpful for increasing vaccine acceptance. [ABSTRACT FROM AUTHOR]

This study was a multicenter retrospective cohort study of term nulliparous women who underwent labor, and was conducted to develop an automated machine learning model for prediction of emergent cesarean section (CS) before onset of labor. Nine machine learning methods of logistic regression, random forest, Support Vector Machine (SVM), gradient boosting, extreme gradient boosting (XGBoost), light gradient boosting machine (LGBM), k-nearest neighbors (KNN), Voting, and Stacking were applied and compared for prediction of emergent CS during active labor. External validation was performed using a nationwide multicenter dataset for Korean fetal growth. A total of 6549 term nulliparous women was included in the analysis, and the emergent CS rate was 16.1%. The C-statistics values for KNN, Voting, XGBoost, Stacking, gradient boosting, random forest, LGBM, logistic regression, and SVM were 0.6, 0.69, 0.64, 0.59, 0.66, 0.68, 0.68, 0.7, and 0.69, respectively. The logistic regression model showed the best predictive performance with an accuracy of 0.78. The machine learning model identified nine significant variables of maternal age, height, weight at pre-pregnancy, pregnancy-associated hypertension, gestational age, and fetal sonographic findings. The C-statistic value for the logistic regression machine learning model in the external validation set (1391 term nulliparous women) was 0.69, with an overall accuracy of 0.68, a specificity of 0.83, and a sensitivity of 0.41. Machine learning algorithms with clinical and sonographic parameters at near term could be useful tools to predict individual risk of emergent CS during active labor in nulliparous women. [ABSTRACT FROM AUTHOR]

Background & Aims: Elevated liver enzymes are associated with later development of type 2 diabetes mellitus. The objective of this study was to assess the association between prepregnancy liver enzyme levels and subsequent risk of gestational diabetes mellitus. Methods: Data from a total of 236,109 women who participated in the National Health Screening Examination between 2011 and 2015 was analysed. Multivariate logistic regression analyses were performed to estimate the risk of developing gestational diabetes mellitus in relation to pregravid liver enzyme levels. Subgroup analyses were performed according to pregravid obesity and metabolic syndrome (MetS). Results: Approximately 5.7% and 1.1% of women developed gestational diabetes mellitus with and without insulin treatment requirement respectively. Pregravid gamma‐glutamyl transferase and alanine aminotransferase levels with greater than or equal to the 4th quartile were associated with significantly increased risks of gestational diabetes mellitus requiring insulin treatment in women with obesity and with MetS, (odds ratios [ORs] with 6.228 and 9.505, respectively, P <.001 for both). In women without obesity and without MetS, the risks of gestational diabetes mellitus requiring insulin treatment were also significant (ORs with 2.837 and 3.029, respectively, P <.001 for both). The elevated pregravid liver enzymes were associated with gestational diabetes mellitus without insulin treatment requirement, but minimally. Conclusions/interpretation: The elevated pregravid liver enzyme levels were significantly associated with the subsequent risk of gestational diabetes mellitus, especially gestational diabetes mellitus requiring insulin treatment, not only in women with obesity or MetS, but also in women without obesity or MetS. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to investigate the independent influence of maternal age on the risk of emergency cesarean section (CS) due to nonreassuring fetal heart rate or arrest disorder. Methods: This was a cross-sectional study on women with nulliparous pregnancies, who are attempting vaginal delivery at term and have a cephalic presentation without the indication of elective CS at the onset of labor. The primary outcome was the rate of emergency CS. Independent risk factors were elucidated using multivariate logistic regression analysis. Results: Of 3513 women, 541 (15.4%) delivered by emergency CS during a trial of vaginal delivery, with theses being due to nonreassuring fetal heart rate (N = 150) or arrest disorder (N = 391). In univariate analysis, both individual CS rate due to nonreassuring fetal heart rate or arrest disorder and total emergent CS rate increased with maternal age. The risk of emergency CS was also significantly higher when labor induction was performed (odds ratio (OR) 2.489, 95% confidence interval (CI) 2.043–3.033), while fetal weight was heavier (neonatal weight ≥3.5 kg; OR 2.396, 95% CI 1.956–2.934), and maternal BMI was higher (before pregnancy ≥25 kg/m2; OR 2.751, 95% CI 1.980–3.823, at delivery ≥28 kg/m2; OR 2.375 95% CI 1.915–2.946). Multivariate stepwise regression analysis showed a statistically significant increase in the risk of total emergency CS in mothers over 35 years of age, compared to that in women less than 30 years old (35–39 years group; adjusted OR 1.805 95% CI 1.347–2.418, ≥40 years group; adjusted OR 4.659 95% CI 2.709–8.013). CS due to nonreassuring fetal heart rate increased in mothers over 40 years of age (adjusted OR 5.354, 95% CI 2.386–12.017) and CS due to arrest disorder was also increased in mothers over 30 years of age (30–34 years group; adjusted OR 1.343, 95% CI 1.010–1.785, 35–39 years group; adjusted OR 1.906, 95% CI 1.357–2.679, ≥40 years group; adjusted OR 4.663, 95% CI 2.480–8.768). Similar to the result of univariate analysis, labor induction increased the risk of emergency CS (adjusted OR 2.241, 95% CI 1.828–2.747). Conclusions: Advanced maternal age is an independent risk factor of emergency CS due to nonreassuring fetal heart rate or arrest disorder during the trial of vaginal delivery. The risk of emergency CS was also increased when labor induction was performed. Therefore, the risk of emergency CS needs to be considered, especially when the labor induction is planned, in women aged 40 or more. [ABSTRACT FROM AUTHOR]

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<34 weeks, 2.1% vs. 14.8%, p<0.001; PTB<32 weeks, 1.6% vs. 13.0%, p<0.001; PTB<28 weeks, 0.9% vs. 13.0%, p<0.001) than singleton group. The VT group had increased risk for both sPTB and iPTB (<34 weeks, <32 weeks, and <28 weeks), and this increased risk for sPTB and iPTB in VT group remained significant even after controlling for confounders such as maternal age, parity, pre-pregnancy BMI, and mode of conception. Conclusion: Vanishing twin can be an independent risk factor for both sPTB and iPTB when compared with singleton pregnancy. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the current perinatal outcomes among infants born late-preterm and early-term compared to those born full-term and evaluate the optimal gestational age for delivery.Methods: We performed a retrospective cohort study for births occurred at Seoul St. Mary's Hospital over the past 7 years. Statistical comparison was performed using χ2 test and multivariable logistic regression models.Results: A total of 7580 women met the study criteria. Compared to 39 weeks, delivery at late-preterm and early-term had higher risk of composite morbidity, including respiratory morbidities, intracranial hemorrhage (ICH), and admission to neonatal intensive care unit (NICU) (34 weeks adjusted odds ratio [aOR]: 132.54; 95% confidence interval (CI): 74.00-240.10; 37 weeks aOR: 2.14; 95%CI: 1.65-2.77). The risks of sepsis and necrotizing enterocolitis in deliveries before 36 weeks and the risk of feeding difficulty in deliveries before 37 weeks were significantly higher than those of 39 weeks. Neonatal morbidity at deliveries was not significantly different between 38 and 39 weeks.Conclusions: Neonatal morbidities at late-preterm births are significant and surveillance for them seems increasing. Obstetricians should recognize the risk of respiratory morbidity, ICH, and NICU admission for deliveries before 38 weeks' gestation. [ABSTRACT FROM AUTHOR]

Purpose: To examine the competing risks of stillbirth versus infant death and to evaluate the optimal time of delivery in the population of small for gestational age (SGA) and non-SGA late preterm and term fetuses. Methods: This was a retrospective national cohort study of all singleton births between 34 0/7 and 42 6/7 weeks of gestation using the Korean vital statistics (n = 2,106,159). We compared the risk of infant mortality with a composite of fetal–infant mortality risk that would occur after expectant management for one additional week and evaluated the optimal time of delivery, in SGA and non-SGA pregnancies. Results: In the total population, the risk of expectant management became significantly higher than the risk of delivery, at 39 weeks and beyond, similar with non-SGA group. In the SGA group, the risk of stillbirth was significantly greater at all GAs than for non-SGA pregnancies, and the risk of infant death was significantly increased until 38 weeks (25.8 per 10,000 live births, 95% CI 20.11–32.47), and the risk of stillbirth was significantly increased at 41 weeks (11.65 per 10,000 ongoing pregnancies, 95% CI 6.95–18.09), compared to 39 weeks (12 per 10,000 live births, 95% CI 8.98–15.64 and 5.12 per 10,000 ongoing pregnancies, 95% CI 3.84–6.66, respectively). Conclusion: In Korean women, delivery between 39 and 41 weeks minimizes fetal/infant mortality, in non-SGA pregnancies. In uncomplicated SGA pregnancies, delivery between 39 and 40 weeks can be considered to decrease risk of infant death and stillbirths. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to analyze recent trends of multiple birth rates (MBR) and fetal/neonatal/infant mortalities according to the number of gestations in Korea. Methods: Data from 2009 to 2015 of live births, infant deaths and stillbirths were obtained from the Korean Vital Statistics. Neonatal mortality rate (NMR), infant mortality rate (IMR), and fetal mortality rate (FMR) in singleton, twin and triplet pregnancies were analyzed according to gestational period (GP; ≤ 23, 24–27, 28–31, and 32–36 weeks). Results: From 2009 to 2015, twin and triplet birth rates increased 34.5% and 154.3%, respectively. In twin births, NMR and FMR have been decreased significantly (from 10.92 to 8.62, p = 0.034 and from 41.00 to 30.55, p< 0.001, respectively), but IMR did not show significant decrease. There was no significant change of NMR, IMR, and FMR, in triplet births. Overall, in singleton, twin, and triplet births, NMR was 1.26 ± 0.09, 10.6 ± 1.12, and 34.32 ± 11.72, respectively, and IMR was 2.38 ± 0.26, 14.52 ± 1.38, and 41.13 ± 12.2, respectively. FMRs were 12 ± 1.73, 35.99 ± 3.55, and 88.85 ± 16.55, respectively, in singleton, twin, and triplet pregnancies. In spite of decreasing trends in overall mortalities, the odds ratios of NMRs and IMRs in 2015 were approximately 9-fold and 6-fold higher, respectively, in twin births, and approximately 37-fold and 20-fold higher, respectively, in triplet births, than those in singleton births. There were no significant differences in odds ratios of NMRs and IMRs at GP 32–36 among single, twin, and triplet births, although the odds ratios of FMR at GP 32–36 in triplet gestation was significantly higher than those in singleton and twin gestation. Conclusion: Neonatal/infant mortality in multiple births is still significantly high, which is mainly related with preterm birth. Close fetal monitoring is needed to prevent fetal death in triplet pregnancies, after 32 gestational weeks. [ABSTRACT FROM AUTHOR]

The etiology of imperforate anus, a major phenotype of anorectal malformation (ARM), is still unknown and not a single gene has been reported to be associated with it. We studied a Korean family with six affected members with imperforate anus across three generations by whole exome sequencing and identified a missense mutation in the EBF2 gene (c.215C > T; p.Ala72Val). This mutation is completely segregated with the disease phenotype in the family and is evolutionarily highly conserved among diverse vertebrates. Also, this mutation was predicted to be functionally damaging. These results support that missense mutation in the EBF2 c.215C > T (p.Ala72Val) is very likely to contribute to the pathogenesis of ARM in this family. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between placenta and perinatal outcomes, in preterm infants born to mothers with preterm premature rupture of fetal membrane (PPROM).Methods: We report detailed histology of placentas and perinatal outcomes of infants from 79 PPROM pregnancies. Placental histologic pattern and adverse perinatal outcomes were assessed by logistic regression, adjusting for gestational age at birth, birth weight and interval from rupture of membrane to delivery.Results: Mean gestational age at membrane rupture was 29.5 ± 3.4 weeks. The incidence of histologic chorioamnionitis (HCA), fetal inflammatory response (FIR) and vascular thrombotic abnormalities in placental histologic examination were 63.3, 25.3 and 78.5%, respectively. Neonates with FIR showed significantly higher incidence of periventricular leukomalacia (PVL) (85% versus 59.3%, p = 0.0364) at brain ultrasonography, than neonates without FIR, in univariate analysis, but not in logistic regression analysis. In logistic regression analysis, the odds ratio of low Apgar score at 1 min in the neonates with clinical chorioamnionitis was 5.009 (95% CI, 1.242-20.195). The odds ratio of neonatal seizure in the neonates with FIR and vascular thrombotic problem was 7.486 (95% CI, 1.617-34.653).Conclusions: Our findings support the association between FIR with vascular thrombotic problem in placenta and neonatal seizure, in pregnancies with PPROM. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of the occiput posterior (OP) position on dystocia and perinatal outcomes. Methods: This was a prospective cohort study of 162 primiparous women. We performed intrapartum sonography, and fetal occiput positions were recorded. The relationships between the position of the occiput and the course of labor and perinatal outcomes were investigated. Statistical analysis was performed using SAS 9.2. Results: Fifty-six of 162 fetuses were found to be in the OP position during the first stage of labor. Eight (80.0%) of 10 fetuses in the OP position during the second stage were among the 56 that were in OP position during the first stage. The rate of cesarean sections performed in the OP position group during the first stage was significantly higher than the rate in the non-OP position group (37.5% versus 8.5%,p < 0.0001). The duration of the second stage of labor was longer and neonatal complications occurred more frequently in the OP position group during the second stage than in the non-OP position group (77.9  ±  33.4 min versus 52.2  ± 26.6 min,p = 0.0104; 50.0% versus 17.2%,p = 0.0118). Conclusions: The OP position may be a useful predicator for labor dystocia that can lead to poor neonatal outcomes. [ABSTRACT FROM PUBLISHER]

We used a hydrogel-mediated dual drug delivery approach, based on an injectable glycol chitosan (GC) hydrogel, doxorubicin hydrochloride (DOX⋅HCl), and a complex of beta-cyclodextrin (β-CD) and paclitaxel (PTX) (GDCP) for breast cancer therapy in vitro and in vivo. The hydrogel was swollen over 3 days and remained so thereafter. After an initial burst period of 7 hours, the two drugs were released in a sustained manner for 7 days. The in vitro cell viability test showed that GDCP had a better anticancer effect than well plate and DOX⋅HCl/PTX (DP). In addition, the in vivo tests, which evaluated the anticancer effect, systemic toxicity, and histology, proved the feasibility of GDCP as a clinical therapy for breast cancer. [ABSTRACT FROM AUTHOR]

Objectives: Since late preterm neonates are physiologically less mature than term neonates, the use of antenatal corticosteroids in the late preterm period has been recommended. The use of tocolytics can also be considered to gain valuable time for using antenatal corticosteroids in the late preterm period. In this study, we examined the efficacy of tocolytics on prolonging pregnancy in the late preterm period, by comparing women who received tocolytics with those who received none.Study Design: This retrospective cohort study included women who were admitted due to preterm labor after 34 weeks of gestation and delivered in the late preterm period. Primary outcome was time from admission to delivery (days). Secondary outcomes were the proportion of preterm births within 2 days, and within 7 days, completed cycles of antenatal corticosteroids, and the neonatal outcomes. Primary and secondary outcomes were compared according to the use of tocolytics. Propensity score matching was performed to create comparable groups. The maternal age, pre-pregnancy body mass index, nulliparity, history of preterm birth, hypertensive disease during pregnancy, gestational diabetes mellitus, history of preterm labor, gestational age at admission, cervical length, and the number of contractions were the baseline characteristics included in the propensity score.Results: Of 275 women, 44 women received tocolytics (tocolytics group) and 231 women did not (no tocolytics group). We matched 44 women who received tocolytics and 44 women who didn't. The tocolytics group was shown to exhibit a longer time from admission to delivery than the no tocolytics group, with a hazard ratio for tocolytics of 0.4 (95 % confidence interval, 0.2-0.6). In addition, the proportion of preterm births occurring within 2 days and 7 days were lower in those receiving tocolytics compared to those that didn't.Conclusion: In this propensity score matched-study, the use of tocolytics had a significant effect on pregnancy prolongation, which allows more time for use of corticosteroids in women with preterm labor after 34 weeks of gestation. [ABSTRACT FROM AUTHOR]