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.

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.

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.

Twin pregnancies with uterine fibroids are not at increased risk for obstetric complications: single center cohort study.

BACKGROUND: Twin pregnancies with uterine fibroid(s) (UFs) may not be at increased risk for obstetric complications compared to those without UFs. However, there was no reported comparison study with obstetric outcomes and complications of twin pregnancy after myomectomy. We aimed to compare the pregnancy outcomes in twin pregnancies with or without uterine fibroid(s), and also compared in patients with previous myomectomy history in Korean women. METHODS: A cohort of twin pregnancies delivered in a single institution between January 2011 and March 2019 were retrospectively analyzed. UFs group was defined by the presence of UFs during pregnancy (≥1 fibroid, measuring ≥2 cm or multiple fibroids regardless of the size). Previous myomectomy group included patients with history of abdominal or laparoscopic or hysteroscopic myomectomy of ≥1 fibroid, measuring ≥2 cm or multiple fibroids whatever the size. Patients with monochorionic monoamniotic twins, myoma less than 2 cm in size, missed abortion or intrauterine fetal death (IUFD) of one fetus before 14 weeks, history of previous conization, and uterine anomalies were excluded. Pregnancy outcomes and obstetric complications were compared. RESULT: A total 1388 patients were included in this study, 191 (13.8%) had UFs and 89 (6.4%) had a history of myomectomy. Maternal age was younger in non-UFs group and primiparity was more common in UFs group (p < 0.001, and p = 0.019). No significant differences were found in the gestational age at delivery (p = 0.657), delivery before 37 weeks (p = 0.662), delivery before 34 weeks (p = 0.340), and sum of birth weight of twin (p = 0.307). There were also no statistical differences in rates of obstetrical complications, such as preeclampsia, gestational diabetes mellitus, placenta previa, placenta abruption, cerclage, small for gestational age, IUFD, postpartum hemorrhage and peripartum transfusion or ICU care. These obstetrical outcomes and complications showed no statistical differences between UFs group and previous myomectomy group. CONCLUSION: In patients with twin pregnancies, the presence of UFs or history of previous myomectomy did not relate to negative effects on pregnancy outcomes and obstetrical complications.

Spontaneous remission of advanced progressive poorly differentiated non-small cell lung cancer: a case report and review of literature.

BACKGROUND: Spontaneous remission (SR) of cancer is a very rare phenomenon of unknown mechanism. In particular, SR of non-small cell lung cancer (NSCLC) has been scarcely reported. We present the case of a 74-year-old woman with advanced, poorly differentiated NSCLC (highly expressing programmed death ligand-1 [PD-L1]) that progressed despite multiple lines of chemotherapy but then spontaneously remitted. CASE PRESENTATION: The patient presented with hemoptysis and was diagnosed with stage IIIA poorly differentiated NSCLC via bronchoscopic biopsy. She had an unremarkable medical history and moderate performance status. The initial treatment plan was surgery after neoadjuvant chemotherapy. Despite conventional chemotherapy, follow-up chest computed tomography (CT) showed gradual tumor progression and she decided against further treatment after fifth-line chemotherapy. However, the size of lung mass was markedly decreased on follow-up chest CT one year after ceasing chemotherapy. Also, follow-up positron emission tomography images showed decreased metabolic activity in the lung mass and a percutaneous biopsy specimen from the diminished lung mass revealed no viable tumor cells. A diagnosis of SR of NSCLC was confirmed, and the patient was without tumor progression on follow-up nine months later. Later, PD-L1 immunostaining revealed high positivity (> 99%) in initial tumor cells. CONCLUSION: Our case showing SR of poorly advanced NSCLC refractory to multiple lines of chemotherapy suggested the association between immunity and tumor regression.

Risk factors associated with an increase in the size of ground-glass lung nodules on chest computed tomography.

BACKGROUND: The detection rate of ground-glass nodules (GGNs) in the lung has increased with the increased use of low-dose computed tomography (CT) of the chest for cancer screening; however, limited data is available on the natural history, follow-up, and treatment of GGNs. The aim of this study was to identify factors associated with an increase in the size of GGNs. METHODS: A total of 338 patients (mean ages, 59.8 years; males, 35.5%) with 689 nodules who underwent chest CT at our institute between June 2004 and February 2014 were included in this study. The cut-off date of follow-up was August 2018. We analyzed the size, solidity, number, and margins of the nodules compared with their appearance on previous chest CT images. The Cox proportional hazard model was used to identify risk factors associated with nodule growth. RESULTS: The median follow-up period was 21.8 months. Of the 338 patients, 38.5% had a history of malignancy, including lung cancer (8.9%). Among the 689 nodules, the median size of the lesions was 6.0 mm (IQR, 5-8 mm), and the proportion of nodules with size ≥10 mm and multiplicity was 17.1% and 66.3%, respectively. Compared to the nodules without an increase in size, the 79 nodules with an increase in size during the follow-up period were initially larger (growth group, 7.0 mm vs. non-growth group, 6.0 mm; P = 0.027), more likely to have a size ≥10 mm (26.6% vs. 15.9%; P = 0.018), and had less frequent multiplicity (54.4% vs. 67.9%, P = 0.028). In the multivariate analysis, nodule size ≥10 mm (hazard ratio [HR], 2.044; P = 0.005), a patient history of lung cancer (HR: 2.190, P = 0.006), and solitary nodule (HR: 2.499, P < 0.001) were independent risk factors for nodule growth. CONCLUSION: Careful follow-up of GGNs is warranted in patients with a history of malignancy, a large , or a solitary nodule.

High blood neutrophil-lymphocyte ratio associated with poor outcomes in miliary tuberculosis.

BACKGROUND: It is difficult to predict the prognosis of miliary tuberculosis (TB). We hypothesized that blood neutrophil-lymphocyte ratio (NLR) is an indicator of inflammatory status to reflect independent prognostic significance in patients with miliary TB. The aim of this study is to investigate the relationship between NLR and outcome in miliary TB. METHODS: We retrospectively collected data from patients diagnosed with miliary TB in a tertiary referral hospital between January 1995 and January 2016. RESULTS: A total of 96 patients were enrolled. Seventeen patients (18%) died during hospitalization due to miliary TB, and 9 (9%) died additionally during the 1-year follow-up period. Eighteen patients (19%) were diagnosed with acute respiratory distress syndrome (ARDS). In multiple logistic regression analyses, increased NLR was associated with ARDS [adjusted odds ratio, 1.15; 95% confidence interval (CI), 1.03-1.28]. By multivariate Cox regression analysis with adjustment of known prognostic factors including age, sex, body mass index, serum aspartate aminotransferase (AST), and hemoglobin, NLR was an independent predictor of in-hospital mortality [adjusted hazard ratio (aHR), 1.08; 95% CI, 1.03-1.13] and 1-year mortality (aHR, 1.08; 95% CI, 1.05-1.12). CONCLUSIONS: Pre-treatment NLR at admission may be a useful biomarker for mortality and development of ARDS in patients with miliary TB.

Predictive factor for volume reduction of uterine fibroids after short-term use of ulipristal acetate.

OBJECTIVES: Ulipristal acetate (UPA) is a selective progesterone receptor modulator, which has been used to treat uterine fibroids. Many published reports about the outcomes indicate effective control of bleeding and reduction in the fibroid volume following both short- and long-term therapy. However, the reported volume reduction varies across different reports. Therefore, the purpose of this study was to investigate the factors that can affect the volume reduction of uterine fibroids, after short-term UPA therapy in patients with symptomatic uterine fibroids. STUDY DESIGN: Women treated with UPA for 3 months, between November 2013 and February 2017, for symptomatic uterine fibroids were evaluated retrospectively. The fibroid volume was measured using ultrasonography or magnetic resonance imaging. Response was defined as any reduction in volume after treatment and non-response was defined as no change or increase in volume. RESULTS: Totally, 152 women were treated with UPA and the median volume reduction was 13.1% (interquartile range [IQR] -16.8 to 36.7). Response to treatment was seen in 92 of 152 (60.5%) patients, while 60 women (39.5%) showed no response. Median number of fibroids in the response group was less than that in the non-response group (P = 0.030; median 2, IQR 1-4 vs. median 4, IQR 1-6). On multivariate regression analysis, fewer number of uterine fibroids was an independent factor for predicting a good response to UPA (odds ratio 0.830, CI: 0.710-0.969, P = 0.019). CONCLUSION: An independent factor that can affect the volume reduction after a 3-month UPA therapy in women with uterine fibroids was the number of fibroids. This indicates that UPA might be ineffective for volume reduction in cases with multiple leiomyomas. However, future prospective studies comparing solitary and multiple leiomyomas for response to UPA are necessary.

Global gene expression changes of amniotic fluid cell free RNA according to fetal development.

OBJECTIVE: This study aimed to evaluate the effect of in utero fetal development on the cell-free transcriptome of amniotic fluid by analyzing global gene expression in the amniotic fluid supernatant obtained at different gestational ages from euploid fetuses STUDY DESIGN: Thirteen amniotic fluid samples were obtained from five individuals at 28 gestational weeks and eight individuals at full term pregnancy. Transcriptome data previously analyzed by our group from 14 euploid mid-trimester amniotic fluid samples were used for comparative analysis. RNA was extracted from amniotic fluid supernatants, hybridized to Affymetrix GeneChip Human arrays, and the transcriptome was analyzed using the DAVID toolkit. RESULTS: We evaluated 27 samples, which were divided into three groups as follows: 14 subjects between 16 and 18 gestational weeks from our previous study (group 1), five subjects in late second trimester (group 2), and eight subjects at full term pregnancy (group 3). No genes were significantly differentially regulated between group 3 and group 2. We identified 545 probe sets that were significantly differentially expressed between group 1 and group 2 and 3 samples (FDR P-value <0.05). Based on tissue expression analysis, 396 genes that were upregulated in group 1 were enriched in the nervous system including brain and endocrine organs such as pancreas and adrenal gland. In addition, 136 genes that were upregulated in group 2 and 3 were specific to bronchioepithelial cells. Functional pathway analysis revealed that there was no significantly enriched pathway in terms of genes that were upregulated in either group 2 or group 3. Comparing the amniotic fluid cell-free transcriptome of group 1 and 2 with that of group 3, 18 genes were significantly differently modulated. CONCLUSIONS: Fetal development affects the amniotic fluid cell-free transcriptome. Fetal skin keratinization, which begins at 19 gestational weeks, might play an important role in changes in global gene expression in the amniotic fluid.

Analysis of the cell-free amniotic fluid transcriptome expressed during the euploid mid-trimester of pregnancy.

OBJECTIVE: The amniotic fluid (AF) contains cell-free RNAs (cfRNAs), which are considered to reflect the fetal status in utero. However, there are limited numbers of data to examine the AF cell-free transcriptome because amniocentesis is an invasive procedure. In this study, the AF transcriptome expressed during the euploid mid-trimester of pregnancy was characterized. STUDY DESIGN: Fourteen AF samples were collected. RNA was extracted from AF supernatant, hybridized to Affymetrix GeneChip Human arrays, and the transcriptome was analyzed by using the DAVID toolkit. RESULT: We detected 1069 genes in the 14 AF samples. The GNF atlas mapping showed that genes present in the AF were annotated with endocrine organs and blood components, including the pancreas, adrenal gland, thyroid, ovary and monocytes. The proteins encoded by the transcriptome were localized to several organs, which are directly in contact with the AF, including the placenta, lung, skin, epithelium, and kidney. During the early fetal period, there is a bi-directional diffusion between the fetus and AF. Therefore, the AF composition is similar to that of the fetal plasma. In addition, fetal urine, swallowing, pulmonary secretion, and diffusion across the placenta contribute to produce amniotic fluid by directly excreting fluid. The KEGG pathway analysis with placenta specific genes revealed that focal adhesion and extracellular matrix receptor interaction pathways were enriched. These pathways are important for the placental development. CONCLUSION: cfRNA in the amniotic fluid originates from placenta and fetal organs directly contacting the amniotic fluid as well as from diffusion of the fetal plasma across the placenta. AF transcriptome may reflect not only fetal development, but also placental development.

Maternal antimullerian hormone as a predictor of fetal aneuploidy occurring in an early pregnancy loss.

OBJECTIVE: The purpose of the study was to examine the relationship between the parameter representing ovarian reserve and the fetal aneuploidy in early spontaneous miscarriage. METHODS: A multicenter retrospective cohort study was performed in patients who were diagnosed with early pregnancy loss (≤13 gestational weeks) and examined for fetal karyotype at the CHA Gangnam Medical Center, CHA Bundang Medical Center, and CHA Gumi Medical Center between January 2011 and December 2012. Karyotyping was performed by the Genetic Laboratory of the Fertility Center of CHA Gangnam Medical Center. Medical records were reviewed for demographics, karyotype analysis and hormonal assay of ovarian reserve including antimullerian hormone (AMH) and follicle stimulating hormone. Statistical analysis was performed using SPSS software. RESULTS: A total 462 patients were included in this study. The mean age of the patients was 35.31±4.12 years and the mean AMH level was 3.88±3.50 ng/mL (n=195). Two hundred eleven conceptuses (45.7%) of patients showed the euploid and 251 (54.3%) showed the aneuploid. There are significant differences in maternal age, AMH and gestational age between fetal euploid and aneuploid groups (34.46±4.35 vs. 36.04±3.78 years, P<0.001; 4.60±3.86 vs. 3.43±3.18 ng/mL, P=0.022; 7.67±1.54 vs. 8.27±1.46 weeks, P<0.001, respectively). Multivariate analysis revealed that low AMH level and early gestational age were maternal age-independent markers for fetal aneuploid (P<0.001 and P=0.045, respectively). CONCLUSION: Low maternal AMH level might be a predicting marker for fetal aneuploid in early pregnancy loss.

Combined Screening for Early Detection of Pre-Eclampsia.

Although the precise pathophysiology of pre-eclampsia remains unknown, this condition continues to be a major cause of maternal and fetal mortality. Early prediction of pre-eclampsia would allow for timely initiation of preventive therapy. A combination of biophysical and biochemical markers are superior to other tests for early prediction of the development of pre-eclampsia. Apart from the use of parameters in first-trimester aneuploidy screening, cell-free fetal DNA quantification is emerging as a promising marker for prediction of pre-eclampsia. This article reviews the current research of the most important strategies for prediction of pre-eclampsia, including the use of maternal risk factors, mean maternal arterial pressure, ultrasound parameters, and biomarkers.

Progressive multiple cystic changes in both lungs in a patient treated with gefitinib for lung adenocarcinoma with multiple lung metastases.

Gefitinib is regarded as a relatively safe agent for the treatment of an advanced non-small cell lung cancer (NSCLC). Pulmonary toxicity such as interstitial lung disease associated with gefitinib is uncommon with an estimated all time incidence around 1% worldwide. Moreover, a case of gefitinib associated with pulmonary cystic changes has not been reported yet. In this report we present a case of progressive multiple air cystic changes in both lungs in a patient with NSCLC and intrapulmonary metastases who underwent a gefitinib therapy.

Screening models using multiple markers for early detection of late-onset preeclampsia in low-risk pregnancy.

BACKGROUND: Our primary objective was to establish a cutoff value for the soluble fms-like tyrosine kinase 1(sFlt-1)/placental growth factor (PlGF) ratio measured using the Elecsys assay to predict late-onset preeclampsia in low-risk pregnancies. Our secondary objective was to evaluate the ability of combination models using Elecsys data, second trimester uterine artery (UtA) Doppler ultrasonography measurements, and the serum fetoplacental protein levels used for Down's syndrome screening, to predict preeclampsia. METHODS: This prospective cohort study included 262 pregnant women with a low risk of preeclampsia. Plasma levels of pregnancy-associated plasma protein-A (PAPP-A) and serum levels of alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and inhibin-A were measured, and sFlt-1/PlGF ratios were calculated. All women underwent UtA Doppler ultrasonography at 20 to 24 weeks of gestation. RESULTS: Eight of the 262 women (3.0%) developed late-onset preeclampsia. Receiver operating characteristic curve analysis showed that the third trimester sFlt-1/PlGF ratio yielded the best detection rate (DR) for preeclampsia at a fixed false-positive rate (FPR) of 10%, followed by the second trimester sFlt-1/PlGF ratio, sFlt-1 level, and PlGF level. Binary logistic regression analysis was used to determine the five best combination models for early detection of late-onset preeclampsia. The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio yielded a DR of 87.5% at a fixed FPR of 5%, the combination of second and third trimester sFlt-1/PlGF ratios yielded a DR of 87.5% at a fixed FPR of 10%, the combination of body mass index and the second trimester sFlt-1 level yielded a DR of 87.5% at a fixed FPR of 10%, the combination of the PAPP-A and inhibin-A levels yielded a DR of 50% at a fixed FPR of 10%, and the combination of the PAPP-A level and the third trimester sFlt-1/PlGF ratio yielded a DR of 62.5% at a fixed FPR of 10%. CONCLUSIONS: The combination of the PAPP-A level and the second trimester sFlt-1/PlGF ratio, and the combination of the second trimester sFlt-1 level with body mass index, were better predictors of late-onset preeclampsia than any individual marker.

Maternal age-specific rates of fetal chromosomal abnormalities in Korean pregnant women of advanced maternal age.

OBJECTIVE: To evaluate the association of maternal age with occurrence of fetal chromosomal abnormalities in Korean pregnant women of advanced maternal age (AMA). METHODS: A retrospective review of the amniocentesis or chorionic villous sampling (CVS) database at Gangnam and Bundang CHA Medical Centers, between January 2001 and February 2012, was conducted. This study analyzed the incidence of fetal chromosomal abnormalities according to maternal age and the correlation between maternal age and fetal chromosomal abnormalities in Korean pregnant women ≥35 years of age. In addition, we compared the prevalence of fetal chromosomal abnormalities between women of AMA only and the others as the indication for amniocentesis or CVS. RESULTS: A total of 15,381 pregnant women were selected for this study. The incidence of aneuploidies increased exponentially with maternal age (P<0.0001). In particular, the risk of trisomy 21 (standard error [SE], 0.0378; odds ratio, 1.177; P<0.001) and trisomy 18 (SE, 0.0583; odds ratio, 1.182; P=0.0040) showed significant correlation with maternal age. Comparison between women of AMA only and the others as the indication for amniocentesis or CVS showed a significantly lower rate of fetal chromosomal abnormalities only in the AMA group, compared with the others (P<0.0001). CONCLUSION: This study demonstrates that AMA is no longer used as a threshold for determination of who is offered prenatal diagnosis, but is a common risk factor for fetal chromosomal abnormalities.