Risk Factors of Postpartum Depression Among Korean Women: An Analysis Based on the Korean Pregnancy Outcome Study (KPOS).

BACKGROUND: Postpartum depression (PPD) can negatively affect infant well-being and child development. Although the frequency and risk factors of PPD symptoms might vary depending on the country and culture, there is limited research on these risk factors among Korean women. This study aimed to elucidate the potential risk factors of PPD throughout pregnancy to help improve PPD screening and prevention in Korean women. METHODS: The pregnant women at 12 gestational weeks (GW) were enrolled from two obstetric specialized hospitals from March 2013 to November 2017. A questionnaire survey was administered at 12 GW, 24 GW, 36 GW, and 4 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale, and PPD was defined as a score of ≥ 10. RESULTS: PPD was prevalent in 16.3% (410/2,512) of the participants. Depressive feeling at 12 GW and postpartum factors of stress, relationship with children, depressive feeling, fear, sadness, and neonatal intensive care unit admission of baby were significantly associated with a higher risk of PPD. Meanwhile, high postpartum quality of life and marital satisfaction at postpartum period were significantly associated with a lower risk of PPD. We developed a model for predicting PPD using factors as mentioned above and it had an area under the curve of 0.871. CONCLUSION: Depressive feeling at 12 GW and postpartum stress, fear, sadness, relationship with children, low quality of life, and low marital satisfaction increased the risk of PPD. A risk model that comprises significant factors can effectively predict PPD and can be helpful for its prevention and appropriate treatment.

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

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

CYP2C19 Contributes to THP-1-Cell-Derived M2 Macrophage Polarization by Producing 11,12- and 14,15-Epoxyeicosatrienoic Acid, Agonists of the PPARγ Receptor.

Although the functional roles of M1 and M2 macrophages in the immune response and drug resistance are important, the expression and role of cytochrome P450s (CYPs) in these cells remain largely unknown. Differential expression of the 12 most common CYPs (CYP1A1, 1A2, 1B1, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2, 3A4, and 3A5) were screened in THP-1-cell-derived M1 and M2 macrophages using reverse transcription PCR. CYP2C19 was highly expressed in THP-1-cell-derived M2 macrophages, but it was negligibly expressed in THP-1-cell-derived M1 macrophages at the mRNA and protein levels as analyzed by reverse transcription quantitative PCR and Western blot, respectively. CYP2C19 enzyme activity was also very high in THP-1-cell-derived M2 compared to M1 macrophages (> 99%, p < 0.01), which was verified using inhibitors of CYP2C19 activity. Endogenous levels of the CYP2C19 metabolites 11,12-epoxyeicosatrienoic acid (11,12-EET) and 14,15-EET were reduced by 40% and 50% in cells treated with the CYP2C19 inhibitor and by 50% and 60% in the culture medium, respectively. Both 11,12-EET and 14,15-EET were identified as PPARγ agonists in an in vitro assay. When THP-1-cell-derived M2 cells were treated with CYP2C19 inhibitors, 11,12- and 14,15-EETs were significantly reduced, and in parallel with the reduction of these CYP2C19 metabolites, the expression of M2 cell marker genes was also significantly decreased (p < 0.01). Therefore, it was suggested that CYP2C19 may contribute to M2 cell polarization by producing PPARγ agonists. Further studies are needed to understand the endogenous role of CYP2C19 in M2 macrophages with respect to immunologic function and cell polarization.

Intrapartum Factors Affecting Abnormal Lipid Profiles in Early Postpartum Period.

The aim of this research is to investigate the risk factors during pregnancy affect abnormal lipid profiles in women with early postpartum period. This was a single-center retrospective study including 869 women who delivered between December 2017 and May 2019. We collected total cholesterol levels, both at 24-28 GWs and 1 month before delivery. Lipid profiles such as total cholesterol, high-density lipoprotein (HDL), triglyceride (TG) and low-density lipoprotein (LDL) at 6 weeks after delivery were retrieved. Subjects were categorized into 3 groups such as normal, borderline and abnormal group according to the lipid profile levels. The risk factors associated with borderline to abnormal HDL level were body mass index (BMI) of pre-pregnancy (OR = 1.182, 95% CI: 1.116-1.252, p < 0.001), weight gain during pregnancy (OR = 1.085, 95% CI: 1.042-1.131, p < 0.001) and hypertension (HTN) (OR = 3.451, 95% CI: 1.224-9.727, p = 0.02). The risk factors associated with borderline or abnormal TG were BMI of pre-pregnancy, weight gain during pregnancy and weight reduction after delivery. HTN was associated with borderline to abnormal TG in postpartum (OR = 2.891, 95% CI: 1.168-7.156, p = 0.02), while GDM correlated purely with abnormal TG in postpartum (OR = 2.453, 95% CI: 1.068-5.630, p = 0.03). Abnormal lipid profiles in postpartum were significantly associated with BMI of pre-pregnancy, weight gain during pregnancy and weight reduction after delivery. In addition, pregnancy-related HTN was highly associated with abnormal HDL level, and GDM was associated with abnormal TG level in the early postpartum period.

Prenatal Diagnosis of Uniparental Disomy in Cases of Rare Autosomal Trisomies Detected Using Noninvasive Prenatal Test: A Case of Prader-Willi Syndrome.

Rare autosomal trisomies (RATs) other than common aneuploidies can be detected using noninvasive prenatal testing (NIPT). However, conventional karyotyping is insufficient for evaluating diploid fetuses with uniparental disomy (UPD) due to trisomy rescue. Using the diagnostic process for Prader-Willi syndrome (PWS), we aim to describe the need for additional prenatal diagnostic testing for confirming UPD in fetuses diagnosed with RATs via NIPT and its clinical implications. NIPT was performed using the massively parallel sequencing (MPS) method, and all pregnant women with RATs underwent amniocentesis. After confirming the normal karyotype, short tandem repeat (STR) analysis, methylation-specific PCR (MS-PCR), and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) were performed to detect UPD. Overall, six cases were diagnosed with RATs. There was a suspicion of trisomies of chromosomes 7, 8, and 15 in two cases each. However, these cases were confirmed to have a normal karyotype using amniocentesis. In one of six cases, PWS caused by maternal UPD 15 was diagnosed using MS-PCR and MS-MLPA. We propose that in cases where RAT is detected by NIPT, UPD should be considered following trisomy rescue. Even if amniocentesis confirms a normal karyotype, UPD testing (such as MS-PCR and MS-MLPA) should be recommended for accurate assessment, as an accurate diagnosis can lead to appropriate genetic counseling and improved overall pregnancy management.

Chromosomal Abnormality, fetal/neonatal Death and Socioeconomic Status: A Prospective Cohort Study.

OBJECTIVES: To assess the risk gradient of chromosomal abnormalities and fetal or neonatal death across a socioeconomic spectrum of pregnant women. METHODS: We used the data from the Korean Prenatal Diagnosis Study (KPDS), which included singleton pregnancies who were candidates for fetal aneuploidy screening enrolled from the Seoul Capital Area from December 2016 to April 2018. We analyzed chromosomal abnormalities which were diagnosed pre- or postnatally, and fetal or neonatal death. The highest level of education among the women and the average monthly household income were used as proxies for socioeconomic status. RESULTS: Among the 6,715 women, the majority of were 30-39 years old and university graduates, with a reported household income higher than the national median. Chromosomal abnormalities occurred in 45 women (6.7 per 1,000). Fetal or neonatal death occurred in 70 (11.3 per 1,000), excluding pregnancies affected by chromosomal abnormality diagnosis. The adjusted odds ratio for chromosomal abnormalities was higher when household income was < 4,484 USD per month. For fetal or neonatal death, the risk estimates for lower education and lower household income were generally positive but remained imprecise. CONCLUSION: We observed some evidence of an inverse association between the risk of fetal chromosomal abnormality and level of household income in a prospective cohort of pregnant women. Interventions to reduce socioeconomic disparities in perinatal health should focus on those with a low household income.

The association of maternal serum biomarkers and birth weight in twin pregnancy: a retrospective cohort study.

We retrospectively reviewed the medical records of 524 women with twin pregnancies who underwent antenatal care and gave birth in the past 12 years. Birth weight (BW) data were classified into three groups. We analysed the association between maternal serum biomarkers and BW in twin pregnancies using multiple logistic regression analysis. There were significant differences in the MoM values of pregnancy-associated plasma protein-A (PAPP-A), unconjugated oestriol (uE3) and inhibin A between low BW and healthy newborns. The inhibin A value was significantly higher in women with small-for-gestational-age (SGA) foetuses and the PAPP-A, and uE3 values were lower in the SGA group than in the other groups using the generalised linear mixed model (hierarchical modelling considering cluster effects for twins). Maternal serum biomarkers, including PAPP-A, uE3, and inhibin A, may be associated with SGA in twin pregnancy. Our results might provide useful information for SGA prediction during prenatal period in twin pregnancy. IMPACT STATEMENTWhat is already known on this subject? The SGA is more frequent in twin pregnancies than in singleton, but there is no clearly identification of the aetiology of SGA. Further, most studies have been conducted in singleton pregnancies.What do the results of this study add? The association of each maternal serum marker with SGA was assessed in the current study, and it is demonstrated that the levels of PAPP-A and uE3 in maternal serum of SGA foetuses were significantly lower than those in the other groups. In contrast, the levels of inhibin A were significantly increased in the SGA.What are the implications of these findings for clinical practice and/or further research? The maternal serum biomarker of inhibin A was a more valuable predictive factor for SGA prediction in twins. The results of this study can be used in counselling prenatal screening. Further prospective research is needed to combine with ultrasound growth parameters, which can be generalised for the prediction of SGA in twins.

Prenatal Diagnosis of Congenital Heart Diseases and Associations with Serum Biomarkers of Aneuploidy: A Multicenter Prospective Cohort Study.

PURPOSE: We assessed prenatal detection rates of congenital heart disease (CHD) and associations between maternal serum biomarkers and non-chromosomal CHD in singleton pregnancies. MATERIALS AND METHODS: This study was conducted as a secondary analysis of data obtained during a multicenter prospective cohort study that investigated the cost-effectiveness of prenatal testing for fetal aneuploidy. We analyzed the prenatal detection rate and accuracy for CHD screening via ultrasound during the second trimester, as well as associations between serum biomarkers and CHDs, in singleton newborns without chromosomal abnormalities. RESULTS: Among 6715 women, 142 (2.1%) newborns were born with CHDs, of which 67 (1.0%) newborns had major CHDs. The prenatal detection rate for all CHDs and major CHDs were 34.5% and 58.2%, respectively. After excluding isolated ventricular septal defects, the detection rate for critical CHDs was 85.9%. Women with low pregnancy-associated plasma protein A (PAPP-A) (<0.4 multiples of the median, MOM) face increased risks of non-chromosomal CHDs [adjusted odds ratio (aOR) 2.76; 95% confidence interval (CI) 1.36-5.13] and major CHDs (aOR 7.30; 95% CI 3.18-15.59), compared to those without CHDs. A higher inhibin A level (≥2.5 MOM; aOR 4.84; 95% CI 1.42-12.46) was associated with non-chromosomal major CHDs. CONCLUSION: Ultrasonography performed during the second trimester by obstetricians detected over 85% of critical CHDs. Low maternal serum PAPP-A or high inhibin-A was associated with non-chromosomal CHDs. These results may contribute to an improvement in prenatal diagnosis of CHDs.

Association Study between Mucin 4 (MUC4) Polymorphisms and Idiopathic Recurrent Pregnancy Loss in a Korean Population.

Recurrent pregnancy loss (RPL) is the loss of two or more consecutive pregnancies before 20 weeks of gestational age. Our study investigated whether mucin 4 (MUC4) polymorphisms are associated with RPL. MUC polymorphisms (rs882605 C>A, rs1104760 A>G, rs2688513 A>G, rs2258447 C>T, and rs2291652 A>G) were genotyped in 374 women with RPL and 239 controls of Korean ethnicity using polymerase chain reaction-restriction fragment length polymorphism analysis and the TaqMan probe SNP genotyping assay. Differences in genotype frequencies between cases of RPL and the controls were compared. MUC4 rs882605 C>A and rs1104760 A>G polymorphisms were associated with increased incidence of RPL in three and four or more pregnancy loss patients. The haplotype analyses showed a tendency for the allelic effect including the association of MUC4 rs882605 A and rs1104760 G alleles with increased incidence of RPL. In addition, the MUC4 rs882605 CA/MUC4 rs2258447 CC genotype combination was associated with increased RPL prevalence. The two exonic polymorphisms lead to amino acid changes of protein and may act as pathogenic variants for RPL. In conclusion, the MUC4 rs882605 C>A and MUC4 rs1104760 A>G polymorphisms were associated with the susceptibility of RPL and we considered them as potential biomarkers for RPL.

Advanced Strategy of Trophoblasts Retrieval and Isolation from the Cervix (TRIC): Comparison of Two HLA-G Antibodies for Immunomagnetic Isolation of Trophoblasts.

Trophoblasts retrieval and isolation from the cervix (TRIC) is a non-invasive method which enables analysis of fetal genetic information from the extravillous trophoblast cells (EVTs). The aim of this study was to compare the efficacy of the HLA-G antibodies­G233 and 4H84­in isolating EVT cells and provide an optimized protocol of TRIC. We analyzed EVTs from 23 pregnant women in between 5 to 20 weeks of gestation who underwent invasive prenatal testing. Two HLA-G antibodies­G233 and 4H84­were used in a subgroup of 11 and 12 samples for immunomagnetic isolation. Cells with ß-hCG expression were counted to compare the rate of isolated trophoblast cells. The rate of ß-hCG positive cells was significantly different between the G233 and the 4H84 by immunefluorescence microscopy (p < 0.001). The percentage of ß-hCG expressing cells in G233 and 4H84 groups were 62.4 ± 8.24% and 82.6 ± 7.1%, respectively (p < 0.001). The average fetal cell positive rate was 14.1 ± 3.78 in the G233 group while it was 25.8 ± 3.9 in the 4H84 group by fluorescence in situ hybridization (FISH) (p = 0.011). Immunoisolation of trophoblast cells using 4H84 HLA-G antibody was more efficient in capturing EVT cells than using G233 for successful clinical application of TRIC.

First-trimester screening model for small-for-gestational-age using maternal clinical characteristics, serum screening markers, and placental volume: prospective cohort study.

OBJECTIVE: To examine predictive value of first trimester placental volume, maternal clinical characteristics, and serum biomarkers in predicting small-for-gestational-age (SGA) singleton pregnancy. METHODS: We conducted a prospective study to determine whether SGA is associated with maternal clinical factors. Between November 2016 to May 2018, 351 women were enrolled. We included pregnant women who underwent an integrated test for aneuploidy screening. Placental volume, maternal clinical characteristics, and maternal serum pregnancy-associated plasma protein A (PAPP-A) levels in the first trimester (at 10+0-13+6 weeks) and maternal serum biomarkers after 15+0-22+6 weeks were measured. We measured the width, height, and thickness of the placenta and calculated the placental volume using an established mathematical formula; then, we analyzed the association between SGA at delivery, estimated placental volume (EPV), maternal clinical characteristics, and maternal serum biomarkers by multiple logistic regression analysis. RESULTS: In this study, 12.3% (43/351) neonates were delivered before 37 weeks of gestation, and the birth weight of 23.6% (83/351) was below the 10th percentile according to gestational age. On multivariate logistic regression, the MSAFP multiples of the median (MoM) showed the strongest association with SGA in singleton pregnancy (p < .01), and the PAPP-A MoM showed a weaker association in the multiple logistic regression than in the univariate regression (p = .0073 and .0068, respectively). Our prediction model using maternal age, maternal smoking, PAPP-A, and EPV achieved an area under the curve of 0.668 in singleton pregnancy. CONCLUSION: During the first trimester, maternal clinical characteristics, serum biomarkers, and EPV may be used for predicting the risk of SGA in singleton pregnancy.

Association of Polymorphisms in Plasminogen Activator Inhibitor-1 (PAI-1), Tissue Plasminogen Activator (tPA), and Renin (REN) with Recurrent Pregnancy Loss in Korean Women.

Recurrent pregnancy loss (RPL) is defined as two or more consecutive pregnancy losses prior to 20 weeks of gestational age. Various factors, including immune dysfunction, endocrine disorders, coagulation abnormality, and genetic disorders influence RPL. In particular, plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA), and renin (REN) have important roles in the thrombotic and thrombolytic systems, and abnormal expression of these genes have a reported negative correlation with pregnancy maintenance. Moreover, some polymorphisms of the three genes are related to expression levels and thrombotic disorder. Therefore, we investigated whether polymorphisms of PAI-1, tPA, and REN are linked to RPL. Genotyping of the six polymorphisms (PAI-1 rs11178, rs1050955, tPA rs4646972, rs2020918, REN rs1464816, and rs5707) was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and associations of the polymorphisms with RPL were evaluated by statistical analysis. The polymorphism PAI-1 rs1050955 GA+AA was associated with decreased RPL risk (AOR, 0.528; 95% CI 0.356-0.781; p = 0.001) as was the REN 10795 rs5707 GG genotype (AOR, 0.487; 95% CI 0.301-0.787; p = 0.003). In contrast, the tPA rs4646972 II genotype correlated with increased RPL risk (AOR, 1.606; 95% CI, 1.047-2.463; p = 0.030). This study provides evidence that tPA Alu rs4646972 may contribute to the risk of idiopathic RPL, but PAI-1 12068 rs1050955 and REN 10795 rs5707 are associated with a decreased risk of RPL. Therefore, these alleles may be useful as biomarkers to evaluate the risk of RPL.

Validation of a Strict Obesity Definition Proposed for Asians to Predict Adverse Pregnancy Outcomes in Korean Pregnant Women.

BACKGROUND: People are generally considered overweight and obese if their body mass index (BMI) is above 25 kg/m² and 30.0 kg/m², respectively. The World Health Organization proposed stricter criteria for Asians (≥ 23 kg/m²: overweight, ≥ 25 kg/m²: obese). We aimed to verify whether this criteria could predict adverse pregnancy outcomes in Korean women. METHODS: We included 7,547 Korean women from 12 institutions enrolled between June 2016 and October 2018. Women with no pre-pregnancy BMI data, not Korean, or lost to follow-up were excluded, leaving 6,331. The subjects were categorized into underweight, normal, overweight, class I obesity, and class II/III obesity based on a pre-pregnancy BMI of < 18.5, 18.5-22.9, 23.0-24.9, 25.0-29.9, and ≥ 30.0 kg/m², respectively. RESULTS: Overall, 13.4%, 63.0%, 11.8%, 9.1%, and 2.6% of women were underweight, normal, and overweight and had class I obesity and class II/III obesity, respectively. In the multivariable analysis adjusted for maternal age, a higher BMI significantly increased the risk of preeclampsia, gestational diabetes, preterm delivery caused by maternal-fetal indications, cesarean section, large for gestational age, and neonatal intensive care unit admission. CONCLUSION: Adverse pregnancy outcomes started to increase in those with a pre-pregnancy BMI ≥ 23.0 kg/m² after adjusting for maternal age. The modified obesity criteria could help predict adverse pregnancy outcomes in Koreans.

Effect of Endogenic and Exogenic Oxidative Stress Triggers on Adverse Pregnancy Outcomes: Preeclampsia, Fetal Growth Restriction, Gestational Diabetes Mellitus and Preterm Birth.

Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) in cells and tissues and the ability of a biological system to detoxify them. During a normal pregnancy, oxidative stress increases the normal systemic inflammatory response and is usually well-controlled by the balanced body mechanism of the detoxification of anti-oxidative products. However, pregnancy is also a condition in which this adaptation and balance can be easily disrupted. Excessive ROS is detrimental and associated with many pregnancy complications, such as preeclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM), and preterm birth (PTB), by damaging placentation. The placenta is a tissue rich in mitochondria that produces the majority of ROS, so it is important to maintain normal placental function and properly develop its vascular network to ensure a safe and healthy pregnancy. Antioxidants may ameliorate these diseases, and related research is progressing. This review aimed to determine the association between oxidative stress and adverse pregnancy outcomes, especially PE, FGR, GDM, and PTB, and explore how to overcome this oxidative stress in these unfavorable conditions.

The Role of Nuclear Factor of Activated T Cells 5 in Hyperosmotic Stress-Exposed Human Lens Epithelial Cells.

We investigated the role of nuclear factor of activated T cells 5 (NFAT5) under hyperosmotic conditions in human lens epithelial cells (HLECs). Hyperosmotic stress decreased the viability of human lens epithelial B-3 cells and significantly increased NFAT5 expression. Hyperosmotic stress-induced cell death occurred to a greater extent in NFAT5-knockout (KO) cells than in NFAT5 wild-type (NFAT5 WT) cells. Bcl-2 and Bcl-xl expression was down-regulated in NFAT5 WT cells and NFAT5 KO cells under hyperosmotic stress. Pre-treatment with a necroptosis inhibitor (necrostatin-1) significantly blocked hyperosmotic stress-induced death of NFAT5 KO cells, but not of NFAT5 WT cells. The phosphorylation levels of receptor-interacting protein kinase 1 (RIP1) and RIP3, which indicate the occurrence of necroptosis, were up-regulated in NFAT5 KO cells, suggesting that death of these cells is predominantly related to the necroptosis pathway. This finding is the first to report that necroptosis occurs when lens epithelial cells are exposed to hyperosmolar conditions, and that NFAT5 is involved in this process.

The Amniotic Fluid Cell-Free Transcriptome Provides Novel Information about Fetal Development and Placental Cellular Dynamics.

The amniotic fluid (AF) is a complex biofluid that reflects fetal well-being during development. AF con be divided into two fractions, the supernatant and amniocytes. The supernatant contains cell-free components, including placenta-derived microparticles, protein, cell-free fetal DNA, and cell-free fetal RNA from the fetus. Cell-free mRNA (cfRNA) analysis holds a special position among high-throughput analyses, such as transcriptomics, proteomics, and metabolomics, owing to its ease of profiling. The AF cell-free transcriptome differs from the amniocyte transcriptome and alters with the progression of pregnancy and is often associated with the development of various organ systems including the fetal lung, skin, brain, pancreas, adrenal gland, gastrointestinal system, etc. The AF cell-free transcriptome is affected not only by normal physiologies, such as fetal sex, gestational age, and fetal maturity, but also by pathologic mechanisms such as maternal obesity, and genetic syndromes (Down, Edward, Turner, etc.), as well as pregnancy complications (preeclampsia, intrauterine growth restriction, preterm birth, etc.). cfRNA in the amniotic fluid originates from the placenta and fetal organs directly contacting the amniotic fluid as well as from the fetal plasma across the placenta. The AF transcriptome may reflect the fetal and placental development and therefore aid in the monitoring of normal and abnormal development.

Modeling preeclampsia using human induced pluripotent stem cells.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder, affecting up to 10% of pregnancies worldwide. The primary etiology is considered to be abnormal development and function of placental cells called trophoblasts. We previously developed a two-step protocol for differentiation of human pluripotent stem cells, first into cytotrophoblast (CTB) progenitor-like cells, and then into both syncytiotrophoblast (STB)- and extravillous trophoblast (EVT)-like cells, and showed that it can model both normal and abnormal trophoblast differentiation. We have now applied this protocol to induced pluripotent stem cells (iPSC) derived from placentas of pregnancies with or without PE. While there were no differences in CTB induction or EVT formation, PE-iPSC-derived trophoblast showed a defect in syncytialization, as well as a blunted response to hypoxia. RNAseq analysis showed defects in STB formation and response to hypoxia; however, DNA methylation changes were minimal, corresponding only to changes in response to hypoxia. Overall, PE-iPSC recapitulated multiple defects associated with placental dysfunction, including a lack of response to decreased oxygen tension. This emphasizes the importance of the maternal microenvironment in normal placentation, and highlights potential pathways that can be targeted for diagnosis or therapy, while absence of marked DNA methylation changes suggests that other regulatory mechanisms mediate these alterations.

A Chatbot for Perinatal Women's and Partners' Obstetric and Mental Health Care: Development and Usability Evaluation Study.

BACKGROUND: To motivate people to adopt medical chatbots, the establishment of a specialized medical knowledge database that fits their personal interests is of great importance in developing a chatbot for perinatal care, particularly with the help of health professionals. OBJECTIVE: The objectives of this study are to develop and evaluate a user-friendly question-and-answer (Q&A) knowledge database-based chatbot (Dr. Joy) for perinatal women's and their partners' obstetric and mental health care by applying a text-mining technique and implementing contextual usability testing (UT), respectively, thus determining whether this medical chatbot built on mobile instant messenger (KakaoTalk) can provide its male and female users with good user experience. METHODS: Two men aged 38 and 40 years and 13 women aged 27 to 43 years in pregnancy preparation or different pregnancy stages were enrolled. All participants completed the 7-day-long UT, during which they were given the daily tasks of asking Dr. Joy at least 3 questions at any time and place and then giving the chatbot either positive or negative feedback with emoji, using at least one feature of the chatbot, and finally, sending a facilitator all screenshots for the history of the day's use via KakaoTalk before midnight. One day after the UT completion, all participants were asked to fill out a questionnaire on the evaluation of usability, perceived benefits and risks, intention to seek and share health information on the chatbot, and strengths and weaknesses of its use, as well as demographic characteristics. RESULTS: Despite the relatively higher score of ease of learning (EOL), the results of the Spearman correlation indicated that EOL was not significantly associated with usefulness (ρ=0.26; P=.36), ease of use (ρ=0.19; P=.51), satisfaction (ρ=0.21; P=.46), or total usability scores (ρ=0.32; P=.24). Unlike EOL, all 3 subfactors and the total usability had significant positive associations with each other (all ρ>0.80; P<.001). Furthermore, perceived risks exhibited no significant negative associations with perceived benefits (ρ=-0.29; P=.30) or intention to seek (SEE; ρ=-0.28; P=.32) or share (SHA; ρ=-0.24; P=.40) health information on the chatbot via KakaoTalk, whereas perceived benefits exhibited significant positive associations with both SEE and SHA. Perceived benefits were more strongly associated with SEE (ρ=0.94; P<.001) than with SHA (ρ=0.70; P=.004). CONCLUSIONS: This study provides the potential for the uptake of this newly developed Q&A knowledge database-based KakaoTalk chatbot for obstetric and mental health care. As Dr. Joy had quality contents with both utilitarian and hedonic value, its male and female users could be encouraged to use medical chatbots in a convenient, easy-to-use, and enjoyable manner. To boost their continued usage intention for Dr. Joy, its Q&A sets need to be periodically updated to satisfy user intent by monitoring both male and female user utterances.

The impacts of insufficient sleep and its change during pregnancy on postpartum depression: A prospective cohort study of Korean women.

OBJECTIVE: To determine the association between insufficient sleep in the prenatal period and postpartum depression (PPD), and whether changes in sleep patterns during pregnancy increase the risk of PPD. METHODS: A prospective cohort study was conducted between March 2013 and November 2017. Participants completed a sleep questionnaire pre-pregnancy and at 12, 24 and 36 gestational weeks (GW). Depressive symptoms were assessed by the Edinburgh Postnatal Depression Scale (EPDS) at 4 weeks postpartum, and the cut-off score for PPD was 10 or more. RESULTS: Of 2512 participants, 410 (16.3%) were identified as having PPD. Only insufficient sleep at 36 GW was significantly associated with PPD after adjusting for confounding factors (odds ratio 1.79, 95% confidence interval 1.40-2.27, P < 0.001). Both Group 1 (change from sufficient to insufficient) and Group 3 (sustained insufficient) demonstrated a significant risk of PPD at all starting time-points in the multivariate analysis, but no significant association was evident between Group 2 (change from insufficient to sufficient) and PPD. CONCLUSION: Insufficient sleep at 36 GW was associated with a significant risk of developing PPD. Additionally, regardless of whether women had sufficient sleep, a shift towards worsening sleep at 36 GW was highly associated with PPD.

A preeclampsia risk prediction model based on maternal characteristics and serum markers in twin pregnancy.

AIM: To develop preeclampsia (PE) risk prediction model based on maternal characteristics and serum markers at the first and second trimester in the twin pregnancy. METHODS: Between January 2005 and September 2017, we retrospectively reviewed medical records of 532 twin pregnant women who underwent maternal serum integrated test and gave birth at a Bundang CHA Medical Center. Maternal serum pregnancy-associated plasma protein A (PAPP-A) was determined at 10+0 to 13+6 weeks and the serum alpha-fetoprotein (MSAFP), human chorionic gonadotrophin (hCG), unconjugated estriol (uE3) and inhibin A were assayed at 14+0 to 22+0 weeks. We assessed the relationships of maternal characteristics and serum markers by using multiple logistic regression analysis. RESULTS: The study included 35 patients who diagnosed PE and a control group consisting of the other 497 patients in twin pregnancy. There were no significant differences in the maternal age and body mass index (BMI) between two groups. However, the gestational age and placenta weight at delivery were significantly different between groups (p < .001, p = .005, respectively. Among the maternal serum markers, inhibin A value was significantly higher in women with PE compared to those without preeclampsia (p < .001). In addition, we predicted the PE using maternal age, BMI, uE3, and inhibin A which were achieving an area under the curve of 0.73 overall in twin pregnancy. CONCLUSION: A risk prediction model of PE which combined maternal age, BMI, uE3, and inhibin A was better early predictors than any individual marker twin pregnancy.