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.

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 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.

Impact of pre-pregnancy body mass index and gestational weight gain on the risk of maternal and infant pregnancy complications in Korean women.

BACKGROUND/OBJECTIVE: Healthy weight maintenance before and during pregnancy has a significant effect on pregnancy outcomes; however, there are no specific guidelines for gestational weight gain in pregnant Korean women. Therefore, we investigated the impact of pre-pregnancy body mass index (BMI) and gestational weight gain on the risk of maternal and infant pregnancy complications in pregnant Korean women. METHODS: Study participants comprised 3454 singleton pregnant women from the Korean Pregnancy Outcome Study who had baseline examination and pregnancy outcome data. Maternal pre-pregnancy BMI and gestational weight gain were categorized according to the Asia-pacific regional guidelines and the Institute of Medicine recommendations, respectively. The primary outcome was any adverse outcomes, defined as the presence of one or more of the following: hypertensive disorders of pregnancy, gestational diabetes mellitus, peripartum depressive symptom, cesarean delivery, delivery complications, preterm birth, small or large weight infant, neonatal intensive care unit admission, or a congenital anomaly. Multiple logistic regression models were applied to examine the independent and combined impact of pre-pregnancy BMI and gestational weight gain on the risk of maternal and infant outcomes. RESULTS: Obesity before pregnancy significantly increased the risk of perinatal adverse outcomes by more than 2.5 times [odds ratio (OR): 2.512, 95% confidence interval (CI): 1.817-3.473]. Compared to that in women with appropriate gestational weight gain, women with excessive weight gain had a 36.4% incremental increase in the risk of any adverse outcomes [OR: 1.364, 95% CI: 1.115-1.670]. Moreover, women who were overweight or obese before pregnancy and had excessive gestational weight gain had a three-fold increase in the risk of adverse outcomes [OR: 3.460, 95% CI: 2.210-5.417]. CONCLUSION: This study highlights the need for appropriate weight recommendations before and during pregnancy to prevent perinatal complications in Korean women of childbearing age.

Maternal disease factors associated with neonatal jaundice: a case-control study.

BACKGROUND: Neonatal jaundice is common, and despite the considerable medical costs associated with it, there are still few studies on the maternal factors associated with it. Identification of maternal factors associated with neonatal jaundice is very important in terms of prevention, screening and management of neonatal jaundice. The current study aimed to identify maternal disease factors associated with neonatal jaundice. METHODS: We compared the maternal disease diagnostic codes during pregnancy (study A) and 1 year before conception (study B) in mothers whose insurance claims data included newborns treated for neonatal jaundice before birth registration via the National Health Insurance Service-National Sample Cohort (control group). To decrease the effect of confounding variables, the neonatal jaundice and control groups were matched at a ratio of 1:10 via propensity score matching using covariates including age and income. RESULTS: The matched samples for studies A and B included 4,026 and 3,278 (jaundice group: 366 and 298) delivery cases, respectively. In both studies, the jaundice group had a higher proportion of patients who underwent cesarean section than the control group. In study A, other diseases of the digestive system had the highest odds ratio (OR) (K92; adjusted OR: 14.12, 95% confidence interval [CI]: 2.70-82.26). Meanwhile, gastritis and duodenitis had the lowest OR (K29; adjusted OR: 0.39, 95% CI: 0.22-0.69). In study B, salpingitis and oophoritis had the highest OR (N70; adjusted OR: 3.33, 95% CI: 1.59-6.94). Heartburn had the lowest OR (R12; adjusted OR: 0.29, 95% CI:0.12-0.71). CONCLUSIONS: This study identified maternal disease factors correlated with neonatal jaundice during pregnancy and 1 year before conception. Maternal risk factors for neonatal jaundice included syphilis and leiomyoma during pregnancy, and salpingo-oophoritis before pregnancy. The protective factors included infection, inflammatory diseases, and dyspepsia.

Prediction of Adverse Pregnancy Outcomes Using Crown-Rump Length at 11 to 13 + 6 Weeks of Gestation.

OBJECTIVES: To assess the risk of a fetus with a smaller or larger than expected crown-rump length (CRL) for adverse pregnancy outcomes. METHODS: The data of 960 healthy singleton pregnancies conceived via in vitro fertilization were retrospectively collected. Fetal CRL was measured between 11 and 13 + 6 weeks of gestation, and small and large fetal CRLs were defined as fetuses below the 10th and above the 90th centiles, respectively. Multiple logistic regression analysis was performed to assess the risk for adverse pregnancy outcomes. RESULTS: The mean birth weights of fetuses with small, normal, and large CRLs were 3002 g, 3205 g, and 3378 g, respectively. A small fetal CRL was associated with an increased risk of smaller-than-gestational-age neonates (adjusted odds ratio [aOR], 2.79; 95% confidence interval [CI], 1.53-5.08; P < .001) and preterm delivery before 34 gestational weeks (aOR, 6.48; 95% CI, 1.36-30.79; P = .019). A large fetal CRL was associated with an increased risk of large-for-gestational-age (LGA) neonates, and the risk persisted even after adjustment for well-known risk factors of macrosomia, such as pre-pregnancy body mass index, gestational diabetes, and excessive gestational weight gain (aOR, 3.67; 95% CI, 2.04-6.59; P < .001). However, a large fetal CRL was associated with a decreased risk of gestational diabetes (aOR, 0.10; 95% CI, 0.01-0.76; P = .026). CONCLUSIONS: Fetal CRL measured at 11 to 13 + 6 weeks gestation is worth using as a predictor of LGA as well as small for gestational age or preterm delivery.

The Korean Pregnancy Outcome Study (KPOS): Study Design and Participants.

BACKGROUND: The Korean Pregnancy Outcome Study (KPOS) was established to investigate the determinants of adverse pregnancy outcomes among Korean women. METHODS: We recruited 4,537 pregnant women between 2013 and 2017 from two tertiary centers located in Seoul, Korea, and a total of 4,195 Korean women met inclusion criteria in the baseline analysis. A range of data on socio-demographics, past medical histories, reproductive information, health-related behaviors, psychological health and clinical information were obtained using interviewer-based questionnaires and clinical assessment at 12, 24, and 36 gestational weeks (GW), delivery and 6-8 weeks postpartum. Blood samplings were performed at 12, 24 and 36 GW, and placental tissues were obtained after delivery. The main outcome of this study was pregnancy-related complications including gestational diabetes mellitus (GDM), gestational hypertension, and screening positive for peripartum depression. Depression was assessed using the Korean version of the Edinburgh Postnatal Depression Scale, and a score of ≥10 indicated a positive screen for depression. RESULTS: Among 4,195 eligible pregnant women with a median age of 33.0 years, 3,565 (85.0%) pregnancy outcomes were available in this study, including 30 miscarriages, 16 stillbirths, and 3,519 deliveries. Mean gestational age was 38.8 GW, and mean birth weight was 3,236 gram. The prevalence of pregnancy complications of GDM, hypertensive disorders, and screening positive of depression during pregnancy and postpartum was 7.0%, 1.4%, 27.8%, and 16.6%, respectively. CONCLUSIONS: We designed KPOS to identify the determinants of pregnancy-related outcomes, and it may provide effective strategies for the prevention of pregnancy complications in Korean pregnant women.

Clinical Practice Guidelines for Prenatal Aneuploidy Screening and Diagnostic Testing from Korean Society of Maternal-Fetal Medicine: (2) Invasive Diagnostic Testing for Fetal Chromosomal Abnormalities.

The Korean Society of Maternal Fetal Medicine proposed the first Korean guideline on prenatal aneuploidy screening and diagnostic testing, in April 2019. The clinical practice guideline (CPG) was developed for Korean women using an adaptation process based on good-quality practice guidelines, previously developed in other countries, on prenatal screening and invasive diagnostic testing for fetal chromosome abnormalities. We reviewed current guidelines and developed a Korean CPG on invasive diagnostic testing for fetal chromosome abnormalities according to the adaptation process. Recommendations for selected 11 key questions are: 1) Considering the increased risk of fetal loss in invasive prenatal diagnostic testing for fetal genetic disorders, it is not recommended for all pregnant women aged over 35 years. 2) Because early amniocentesis performed before 14 weeks of pregnancy increases the risk of fetal loss and malformation, chorionic villus sampling (CVS) is recommended for pregnant women who will undergo invasive prenatal diagnostic testing for fetal genetic disorders in the first trimester of pregnancy. However, CVS before 9 weeks of pregnancy also increases the risk of fetal loss and deformity. Thus, CVS is recommended after 9 weeks of pregnancy. 3) Amniocentesis is recommended to distinguish true fetal mosaicism from confined placental mosaicism. 4) Anti-immunoglobulin should be administered within 72 hours after the invasive diagnostic testing. 5) Since there is a high risk of vertical transmission, an invasive prenatal diagnostic testing is recommended according to the clinician's discretion with consideration of the condition of the pregnant woman. 6) The use of antibiotics is not recommended before or after an invasive diagnostic testing. 7) The chromosomal microarray test as an alternative to the conventional cytogenetic test is not recommended for all pregnant women who will undergo an invasive diagnostic testing. 8) Amniocentesis before 14 weeks of gestation is not recommended because it increases the risk of fetal loss and malformation. 9) CVS before 9 weeks of gestation is not recommended because it increases the risk of fetal loss and malformation. 10) Although the risk of fetal loss associated with invasive prenatal diagnostic testing (amniocentesis and CVS) may vary based on the proficiency of the operator, the risk of fetal loss due to invasive prenatal diagnostic testing is higher in twin pregnancies than in singleton pregnancies. 11) When a monochorionic twin is identified in early pregnancy and the growth and structure of both fetuses are consistent, an invasive prenatal diagnostic testing can be performed on one fetus alone. However, an invasive prenatal diagnostic testing is recommended for each fetus in cases of pregnancy conceived via in vitro fertilization, or in cases in which the growth of both fetuses differs, or in those in which at least one fetus has a structural abnormality. The guidelines were established and approved by the Korean Academy of Medical Sciences. This guideline is revised and presented every 5 years.

Clinical Practice Guidelines for Prenatal Aneuploidy Screening and Diagnostic Testing from Korean Society of Maternal-Fetal Medicine: (1) Prenatal Aneuploidy Screening.

In 2019, the Korean Society of Maternal-Fetal Medicine developed the first Korean clinical practice guidelines for prenatal aneuploidy screening and diagnostic testing. These guidelines were developed by adapting established clinical practice guidelines in other countries that were searched systematically, and the guidelines aim to assist in decision making of healthcare providers providing prenatal care and to be used as a source for education and communication with pregnant women in Korea. This article delineates clinical practice guidelines specifically for maternal serum screening for fetal aneuploidy and cell-free DNA (cfDNA) screening. A total of 19 key questions (12 for maternal serum and 7 for cfDNA screening) were defined. The main recommendations are: 1) Pregnant women should be informed of common fetal aneuploidy that can be detected, risks for chromosomal abnormality according to the maternal age, detection rate and false positive rate for common fetal aneuploidy with each screening test, limitations, as well as the benefits and risks of invasive diagnostic testing, 2) It is ideal to give counseling about prenatal aneuploidy screening and diagnostic testing at the first prenatal visit, and counseling is recommended to be given early in pregnancy, 3) All pregnant women should be informed about maternal serum screening regardless of their age, 4) cfDNA screening can be used for the screening of trisomy 21, 18, 13 and sex-chromosome aneuploidy. It is not recommended for the screening of microdeletion, 5) The optimal timing of cfDNA screening is 10 weeks of gestation and beyond, and 6) cfDNA screening is not recommended for women with multiple gestations. The guideline was reviewed and approved by the Korean Academy of Medical Sciences.

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.

Prospective clinical evaluation of Momguard non-invasive prenatal test in 1011 Korean high-risk pregnant women.

Clinical performance of the Momguard non-invasive prenatal test (NIPT) was evaluated in a cohort of Korean pregnant women. The foetal trisomies 21, 18 and 13 (T21, T18 and T13) were screened by low-coverage massive parallel sequencing in the maternal blood. Among the 1011 confirmed samples, 32 cases (3.2%) had positive NIPT results. Of these positive cases, 20 cases of T21, all cases of T18 and two cases of T13 had concordant karyotype findings. Only one case out of the remaining 979 negative NIPT samples showed a false negative result. The overall sensitivity and specificity of Momguard to detect the three chromosomal aneuploidies were 96.8% and 99.8%, respectively. Momguard is a clinically useful tool for the detection of T21, T18 and T13 in singleton pregnancy. However, as other NIPT tests, it carries the risk of false positive and false negative results. Hence, the genetic counsellors should provide these limitations to the examinees.Impact StatementWhat is already known on this subject? The NIPT approach using massive parallel sequencing (MPS) showed high sensitivity and specificity in various clinical studies. These results are based on analysis systems using their own bioinformatics algorithms.What the results of this study add? When this NIPT technology was introduced in Korea, the first biological specimens collected in Korea were transported overseas for processing in overseas laboratories and analysed by other country's analysis methods. We needed our own NIPT algorithm and developed Momguard NIPT for the first time in Korea. This study attempted to evaluate this Momguard NIPT protocol prospectively in a large number of samples obtained from three Korean hospitals.What the implications are of these findings for clinical practice and/or further research? The overall sensitivity and specificity to identify T13, T18 and T21 were 96.8% and 99.8%, respectively. These accuracy values were comparable to that of other studies. From this study, we found that Momguard is a clinically useful tool for the detection of three chromosomal aneuploidies. However, as other NIPT tests, it carries the risk of false positive and false negative results. Hence, the genetic counsellors should provide these limitations to the examinees.

Clinical Validation of Non-Invasive Prenatal Testing for Fetal Common Aneuploidies in 1,055 Korean Pregnant Women: a Single Center Experience.

BACKGROUND: Non-invasive prenatal testing (NIPT) using cell-free fetal DNA from maternal plasma for fetal aneuploidy identification is expanding worldwide. The objective of this study was to evaluate the clinical utility of NIPT for the detection of trisomies 21, 18, and 13 of high-risk fetus in a large Korean population. METHODS: This study was performed retrospectively, using stored maternal plasma from 1,055 pregnant women with singleton pregnancies who underwent invasive prenatal diagnosis because of a high-risk indication for chromosomal abnormalities. The NIPT results were confirmed by karyotype analysis. RESULTS: Among 1,055 cases, 108 cases of fetal aneuploidy, including trisomy 21 (n = 57), trisomy 18 (n = 42), and trisomy 13 (n = 9), were identified by NIPT. In this study, NIPT showed 100% sensitivity and 99.9% specificity for trisomy 21, and 92.9% sensitivity and 100% specificity for trisomy 18, and 100% sensitivity and 99.9% specificity for trisomy 13. The overall positive predictive value (PPV) was 98.1%. PPVs for trisomies 21, 18, and 13 ranged from 90.0% to 100%. CONCLUSION: This study demonstrates that our NIPT technology is reliable and accurate when applied to maternal DNA samples collected from pregnant women. Further large prospective studies are needed to adequately assess the performance of NIPT.

Effective Fetal Epigenetic Biomarkers for Noninvasive Fetal Trisomy 21 Detections.

INTRODUCTION: Recently, we identified three novel fetal-specific epigenetic DNA regions (FSERs) on chromosome 21 for detection of noninvasive fetal trisomy 21 (T21). In this study, the diagnostic accuracies of the three FSERs were assessed on a larger panel of the first-trimester pregnant women. MATERIAL AND METHODS: This study was conducted with maternal plasma collected from 167 pregnant women carrying 155 chromosomally normal and 12 T21 fetuses (10-13 gestational weeks). Accuracies of FSERs for noninvasive prenatal test of fetal T21 were estimated by the area under the receiver operator characteristic curve (AUC). RESULTS: The levels of all FSERs increased in pregnant women with T21 fetuses when compared with controls (p < 0.001 for all). The levels of the three FSERs did not differ according to maternal age, body mass index, and fetal sex at maternal blood sampling (p > 0.05 for all). In noninvasive fetal T21 detection, the AUC of FSER1, FSER2, and FSER3 were 0.859 (95% CI: 0.746-0.972), 0.919 (95% CI: 0.856-0.982), and 0.868 (95% CI: 0.746-0.990), respectively. DISCUSSION: The findings of this study suggest that all FSERs may be useful for noninvasive fetal T21 detection, regardless of maternal age, body mass index, and fetal sex.

Prospective observations study protocol to investigate cost-effectiveness of various prenatal test strategies after the introduction of noninvasive prenatal testing.

BACKGROUND: Among the non-invasive screening methods for the identification of fetal aneuploidy, NIPT (non-invasive prenatal testing) shows the highest sensitivity and specificity in high-risk pregnancies. Due to the low false positive rate of NIPT, it is assumed that the implementation of NIPT as a primary screening method may reduce the number of invasive fetal tests and result in a similar or lowered cost in the overall detection of Down syndrome. However, most previous studies are based on theoretical economic analysis. This study aims to determine the cost effectiveness of various prenatal test strategies, including NIPT, in real clinical settings in both low risk and high risk pregnancies. METHODS/DESIGN: In this prospective observational study, women (< 24 weeks) with singleton or twin pregnancies will be enrolled in 12 different healthcare institutions. The participants will be grouped based on the risks of fetal chromosomal abnormalities and will be counseled on the various screening or diagnostic methods, including NIPT, according to the aneuploidy risk. The final decision on screening or diagnostic methods will be made by patients after counseling. Questionnaires regarding factors affecting the decision on prenatal test will be answered by the participants and physicians. The economic analysis on final total costs will be compared according to the various prenatal test strategies. DISCUSSION: The results of present study are expected to have a significant impact on national policies in determining Korean prenatal screening test strategies and to help in developing novel and effective prenatal screening tests in the future.

Evaluation of extraction methods for methylated cell-free fetal DNA from maternal plasma.

PURPOSE: Recently, fetal placenta-specific epigenetic regions (FSERs) have been identified for quantification of cell-free fetal DNA (cff-DNA) for non-invasive prenatal testing (NIPT). The aim of this study was to evaluate the efficiencies of a column-based kit and magnetic bead-based kit for quantification of methylated FSERs from maternal plasma. METHODS: Maternal plasma was extracted from normal pregnant women within the gestational age of 10~13 weeks (n = 24). Total cell-free DNA (cf-DNA) was extracted using a column-based kit and magnetic bead-based kit from the plasma of the same pregnant woman, respectively. Methylated FSERs were enriched from the extracted total cf-DNA using a methyl-CpG-binding domain-based protein method. The four FSERs were simultaneously quantified by multiplex real-time polymerase chain reaction. RESULTS: Methylated FSERs were detected in all samples extracted from both kits. However, the amplification of FSERs showed significant differences in the extraction efficiency of methylated FSERs between the two extraction methods. The Ct values of methylated FSERs extracted using the column-based kit were significantly lower than those obtained using the magnetic bead-based kit (P < 0.001 for all FSERs). The quantity of methylated FSERs was significantly higher for extracted DNA using the column-based kit than that extracted using the magnetic bead-based kit (P < 0.001 for all FSERs). Time and cost for the process of extraction were similar for the column kit and magnetic bead-based kit. CONCLUSIONS: Our findings demonstrate that the column-based kit was more effective than the magnetic bead-based kit for isolation of methylated FSERs from maternal plasma as assessed by FSER detection.

Pregnancy outcomes in women reporting exposure to ofloxacin in early pregnancy.

This study aimed to analyse perinatal outcomes in ofloxacin-exposed pregnancies. This prospective study was conducted on 143 singleton pregnancies between January 2001 and April 2014, after oral ofloxacin exposure in the first trimester. A total of 33 exposed mothers were compared with 110 age-matched controls who were not exposed to teratogen. The mean maternal age was 31.4 ± 3.6 years, and the median gestational age was 4.1 weeks at the exposure. No significant differences were observed in either gestational age or in the foetal ultrasonographic long bone length between the exposed and control groups. Spontaneous abortions occurred without a significant difference (6.1% versus 10.0%, p = .733). In addition, no significant differences were found in either the stillbirths or in the major birth defects between the exposed and control groups (0% versus 2.0%, p = 1.000 and 0% versus 4.0%, p = .572, respectively). Ofloxacin has no significant effect on perinatal outcomes. Impact statement What is already known on this subject? Ofloxacin and other quinolones are avoided during pregnancy because of concerns about cartilage toxicity. But we do not find human data reporting such toxicity in a case report. What the results of this study add? Previous studies were designed for evaluation of just congenital anomaly. But in this study, we measured the fetal long bone length to replace for evaluation of fetal cartilage toxicity. In fetal stage, we can not measure the cartilage of fetus. so we measure fetal long bone length for evaluation that ofloxacin might influence to fetal cartilage growth. Even though this sample size is small. this results will be helpful to counsel pregnant women who exposed to ofloxacin during pregnancy.

Genome-wide gene expression analysis in the placenta from fetus with trisomy 21.

BACKGROUND: We performed whole human genome expression analysis in placenta tissue (normal and T21) samples in order to investigate gene expression into the pathogenesis of trisomy 21 (T21) placenta. We profiled the whole human genome expression of placental samples from normal and T21 fetuses using the GeneChip Human Genome U133 plus 2.0 array. Based on these data, we predicted the functions of differentially expressed genes using bioinformatics tools. RESULTS: A total of 110 genes had different expression patterns in the T21 placentas than they did in the normal placentas. Among them, 77 genes were up-regulated in the T21 placenta and 33 genes were down-regulated compared to their respective levels in normal placentas. Over half of the up-regulated genes (59.7%, n = 46) were located on HSA21. Up-regulated genes in the T21 placentas were significantly associated with T21 and its complications including mental retardation and neurobehavioral manifestations, whereas down-regulated genes were significantly associated with diseases, such as cystitis, metaplasia, pathologic neovascularization, airway obstruction, and diabetes mellitus. The interactive signaling network showed that 53 genes (40 up-regulated genes and 13 down-regulated genes) were an essential component of the dynamic complex of signaling (P < 1.39e-08). CONCLUSIONS: Our findings provide a broad overview of whole human genome expression in the placentas of fetuses with T21 and a possibility that these genes regulate biological pathways that have been involved in T21 and T21 complications. Therefore, these results could contribute to future research efforts concerning gene involvement in the disease's pathogenesis.

Pregnancy outcomes in women reporting ingestion of levosulpiride in early pregnancy.

This study aimed to evaluate pregnancy outcomes of women who were inadvertently exposed to levosulpiride in early pregnancy. All 162 consecutive singleton pregnant women counselled through the Korean Motherisk Program, Cheil General Hospital, between April 2001 and April 2014, on teratogenic risk after inadvertent exposure to levosulpiride in early pregnancy were enrolled in this study. The women were exposed to levosulpiride at median 4.8 gestational weeks. The rate of miscarriage was not significantly different between groups (9.2% in those exposed and 5.5% in the non-exposed; p = .084). The rate of major malformations was not significantly different between exposed (2.7%) and non-exposed pregnancies (4.4%) (p = .481). All other pregnancy outcomes between the two groups were comparable (p > .05). Our data suggest that levosulpiride causes no significant adverse effects on pregnancy outcomes and therefore may be not a major teratogen.

Early Prediction of Hypertensive Disorders of Pregnancy Using Cell-Free Fetal DNA, Cell-Free Total DNA, and Biochemical Markers.

OBJECTIVE: To evaluate the predictive value of separate and combined tests using cell-free fetal DNA (cffDNA), cell-free total DNA (cfDNA), and biochemical markers for the early detection of pregnancies with hypertensive disorders. METHODS: A nested case-control study was conducted with 135 singleton pregnancies including 17 gestational hypertension cases, 34 preeclampsia (PE) cases, and 84 controls. We performed real-time quantitative PCR to measure levels of DSCR3 and RASSF1A as cffDNA markers and HYP2 as a cfDNA marker in the first and early second trimesters. Levels of pregnancy-associated plasma protein A (PAPP-A), α-fetoprotein, ß-human chorionic gonadotropin, unconjugated estriol, and inhibin A were also determined. RESULTS: Compared with controls, the median levels and multiples of the median (MoM) values of HYP2 were significantly higher in the PE and hypertensive disorders of pregnancy (HDP) groups at 6-14 and 15-23 weeks. Frist-trimester PAPP-A MoM was significantly lower in PE and HDP than in controls. For PE and HDP, the best model included the first-trimester DSCR3, HYP2, and PAPP-A MoM values achieving detection rates of 67 and 58% at a fixed 10% false-positive rate, respectively [area under the receiver operating characteristic curve 0.832 (95% CI 0.689-0.928) for PE; 0.751 (0.607-0.863) for HDP]. DISCUSSION: The study demonstrates the potential utility of combined first-trimester cffDNA, cfDNA, and PAPP-A for the early prediction of PE.

Changes in the methylation status of DAT, SERT, and MeCP2 gene promoters in the blood cell in families exposed to alcohol during the periconceptional period.

BACKGROUND: Alcohol exposure has been shown to cause devastating effects on neurobehavioral development in numerous animal and human studies. The alteration of DNA methylation levels in gene-specific promoter regions has been investigated in some studies of human alcoholics. This study was aimed to investigate whether social alcohol consumption during periconceptional period is associated with epigenetic alteration and its generational transmission in the blood cells. METHODS: We investigated patterns of alcohol intake in a prospective cohort of 355 pairs of pregnant women and their spouses who reported alcohol intake during the periconceptional period. A subpopulation of 164 families was established for the epigenetic study based on the availability of peripheral blood and cord blood DNA. The relative methylation changes of dopamine transporter (DAT), serotonin transporter (SERT), and methyl CpG binding protein 2 (MeCP2) gene promoters were analyzed using methylation-specific endonuclease digestion followed by quantitative real-time polymerase chain reaction. RESULTS: The relative methylation level of the DAT gene promoter was decreased in the group of mothers reporting above moderate drinking (p = 0.029) and binge drinking (p = 0.037) during pregnancy. The relative methylation level of the DAT promoter was decreased in the group of fathers reporting heavy binge drinking (p = 0.003). The relative methylation levels of the SERT gene promoter were decreased in the group of newborns of light drinking mothers before pregnancy (p = 0.012) and during pregnancy (p = 0.003). The methylation level in the MeCP2 promoter region of babies whose mothers reported above moderate drinking during pregnancy was increased (p = 0.02). In addition, methylation pattern in the DAT promoter region of babies whose fathers reported heavy binge drinking was decreased (p = 0.049). CONCLUSIONS: These findings suggest that periconceptional alcohol intake may cause epigenetic changes in specific locus of parental and newborn genomes as follows: Alcohol consumption decreases the methylation level of the DAT promoter region of the parent themselves, maternal alcohol drinking during the periconceptional period decreases the methylation level of the SERT promoter region of newborns, and maternal alcohol consumption increases the methylation level of the MeCP2 promoter region of newborns.