The Effect of Vanishing Twin on Firstand 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 secondtrimester serum screening test.

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/m 2 and 30.0 kg/m 2 , 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 followup 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.

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.

Randomized, Double-Blind, Placebo-Controlled Trial on the Efficacy of Hyaluronidase in Preventing Perineal Trauma in Nulliparous Women

Addition of Cervical Elastography May Increase Preterm Delivery Prediction Performance in Pregnant Women with Short Cervix: a Prospective Study

BACKGROUND: We investigated whether there is a difference in elastographic parameters between pregnancies with and without spontaneous preterm delivery (sPTD) in women with a short cervix (≤ 25 mm), and examined the ability of elastographic parameters to predict sPTD in those women. METHODS: E-CervixTM (WS80A; Samsung Medison, Seoul, Korea) elastography was used to examine the cervical strain. Elastographic parameters were compared between pregnancies with and without sPTD. Diagnostic performance of elastographic parameters to predict sPTD ≤ 37 weeks, both alone and in combination with other parameters, was compared with that of cervical length (CL) using area under receiver operating characteristic curve (AUC) analysis. RESULTS: A total of 130 women were included. Median gestational age (GA) at examination was 24.4 weeks (interquartile range, 21.4–28.9), and the prevalence of sPTD was 20.0% (26/130). Both the elastographic parameters and CL did not show statistical difference between those with and without sPTD. However, when only patients with CL ≥ 1.5 cm (n = 110) were included in the analysis, there was a significant difference between two groups in elasticity contrast index (ECI) within 0.5/1.0/1.5 cm from the cervical canal (P < 0.05) which is one of elastographic parameters generated by E-Cervix. When AUC analysis was performed in women with CL ≥ 1.5 cm, the combination of parameters (CL + pre-pregnancy body mass index + GA at exam + ECI within 0.5/1.0/1.5 cm) showed a significantly higher AUC than CL alone (P < 0.05). CONCLUSION: An addition of cervical elastography may improve the ability to predict sPTD in women with a short CL between 1.5 and 2.5 cm.

How much have the perinatal outcomes of triplet pregnancies improved over the last two decades?

OBJECTIVE: This study was conducted to demonstrate the temporal trends in perinatal outcomes of triplet pregnancies over the last two decades. METHODS: The medical records of patients with triplet pregnancies at two Korean tertiary-care hospitals from 1992 to 2012 were retrospectively reviewed in regard to maternal and neonatal outcomes. The study was divided into two periods for analysis: period I (1992–2001) and period II (2003–2012). RESULTS: Over a 21-year period, 65 women with triplet pregnancies and 185 neonates were analyzed. Period II, when compared with period I, was associated with improved maternal outcomes, characterized by a decreased incidence of preeclampsia (31.8% vs. 2.3%, P=0.002) and anemia (68.2% vs. 30.2%, P=0.003) during pregnancy. Regarding neonatal aspects, the composite morbidity of period II was significantly decreased compared with that of period I, as assessed with a generalized estimating equation for logistic regression (26.2% vs. 8.1%, P=0.03). Multivariable analysis revealed that the gestational age at delivery and the period were significantly associated with the composite neonatal morbidity (P<0.001 and 0.007, respectively). CONCLUSION: Improved neonatal morbidity was associated with a higher gestational age at delivery and with the more recent decade.

Wharton Jelly Hair in a Case of Umbilical Cord Stricture and Fetal Death

No abstract available.

Ex utero intrapartum treatment procedure in two fetuses with airway obstruction

The ex utero intrapartum treatment (EXIT) procedure was introduced to reduce fetal hypoxic damage while establishing an airway in fetuses with upper and lower airway obstruction. Delivery of the fetal head and shoulders while maintaining the uteroplacental circulation offers time to secure the fetal airway. Here, we report two cases of EXIT procedure for fetal airway obstruction, which were successfully managed with extensive preoperative planning by a professional multidisciplinary team.

Korean physicians' attitudes toward the prenatal screening for fetal aneuploidy and implementation of non-invasive prenatal testing with cell-free fetal DNA

PURPOSE: Physicians' attitudes may have a strong influence on women's decision regarding prenatal screening options. The aim of this study is to assess the physicians' attitudes toward prenatal screening for fetal aneuploidy including non-invasive prenatal testing (NIPT) in South Korea. MATERIALS AND METHODS: Questionnaires were distributed and collected at several obstetrics-gynecological conferences and meetings. The questionnaire included 31 multiple choice and 5 fill-in-the-blank questions. Seven questions requested physicians' demographic information, 17 questions requested information about the NIPT with cell-free fetal DNA, and 12 questions requested information about general prenatal screening practices. RESULTS: Of the 203 obstetricians that completed the survey. In contrast with professional guidelines recommending the universal offering of aneuploidy screening, only 53.7% answered that prenatal aneuploidy testing (screening and/or invasive diagnostic testing) should be offered to all pregnant women. Physicians tended to have positive attitudes toward the clinical application of NIPT as both primary and secondary screening methods for patients at high-risk for fetal trisomy. However, for patients at average-risk for fetal trisomy, physicians tended to have positive attitudes only as a secondary screening method. Physicians with more knowledge about NIPT were found to tend to inform their patients that the detection rate of NIPT is higher. CONCLUSION: This is the first study to investigate expert opinion on prenatal screening in South Korea. Education of physicians is essential to ensure responsible patient counseling, informed consent, and appropriate management after NIPT.

Impaction of an intrathoracic kidney acted as a shield against herniation of the abdominal viscera in a case of right congenital diaphragmatic hernia

We describe a case of an intrathoracic kidney combined with right congenital diaphragmatic hernia (CDH) that was diagnosed at 32 weeks of gestation. Although it has been well established that a right CDH shows a poorer outcome than a left CDH, our present case showed a good outcome because there was no herniation of other abdominal viscera, except for the right kidney. Our findings in this case indicate that impaction of the intrathoracic kidney may act as a 'shield' against further herniation of other abdominal viscera into the thoracic cavity.

An extremely rare case of prenatally diagnosed absent both aortic and pulmonary valves

We describe a case of absent aortic and pulmonary valves, diagnosed at 16.4 weeks of gestation. Fetal echocardiography showed cardiomegaly with dilated both ventricles. No valve leaflets were observed in the aorta and pulmonary artery, and a typical to-and-fro flow pattern was noted in both great arteries on color Doppler imaging. Fetal hydrops was also detected. Follow-up ultrasonographic evaluation at 19 weeks demonstrated intrauterine fetal death. Postmortem autopsy revealed the absence of both aortic and pulmonary valve leaflets. To the best of our knowledge, this is the earliest diagnosed case of absent both aortic and pulmonary valves and only the second case to be diagnosed prenatally.

An extremely rare case of prenatally diagnosed absent both aortic and pulmonary valves

We describe a case of absent aortic and pulmonary valves, diagnosed at 16.4 weeks of gestation. Fetal echocardiography showed cardiomegaly with dilated both ventricles. No valve leaflets were observed in the aorta and pulmonary artery, and a typical to-and-fro flow pattern was noted in both great arteries on color Doppler imaging. Fetal hydrops was also detected. Follow-up ultrasonographic evaluation at 19 weeks demonstrated intrauterine fetal death. Postmortem autopsy revealed the absence of both aortic and pulmonary valve leaflets. To the best of our knowledge, this is the earliest diagnosed case of absent both aortic and pulmonary valves and only the second case to be diagnosed prenatally.

Practice patterns in the management of threatened preterm labor in Korea: A multicenter retrospective study

OBJECTIVE: This study aimed to examine clinical practice patterns in the management of pregnant women admitted with threatened preterm labor (TPL) in Korea. METHODS: Data from women admitted with a diagnosis of TPL were collected from 22 hospitals. TPL was defined as regular uterine contractions with or without other symptoms such as pelvic pressure, backache, increased vaginal discharge, menstrual-like cramps, bleeding/show and cervical changes. Data on general patient information, clinical characteristics at admission, use of tocolytics, antibiotics, and corticosteroids, and pregnancy outcomes were collected using an online data collections system. RESULTS: A total of 947 women with TPL were enrolled. First-line tocolysis was administered to 822 (86.8%) patients. As a first-line tocolysis, beta-agonists were used most frequently (510/822, 62.0%), followed by magnesium sulfate (183/822, 22.3%), calcium channel blockers (91/822, 11.1%), and atosiban (38/822, 4.6%). Of the 822 women with first-line tocolysis, second-line tocolysis were required in 364 (44.3%). Of 364 with second-line, 199 had third-line tocolysis (37.4%). Antibiotics were administered to 29.9% of patients (284/947) with single (215, 22.7%), dual (26, 2.7%), and triple combinations (43, 4.5%). Corticosteroids were administered to 420 (44.4%) patients. Betamethasone was administered to 298 patients (71.0%), and dexamethasone was administered to 122 patients (29.0%). CONCLUSION: Practice patterns in the management of TPL in Korea were quite various. It is needed to develop standardized practice guidelines for TPL management.

Intrauterine therapy for macrocystic congenital cystic adenomatoid malformation of the lung

OBJECTIVE: To report on our experiences with thoracoamniotic shunting and/or the injection of a sclerosing agent (OK-432) to treat fetuses diagnosed with macrocystic congenital cystic adenomatoid malformation (CCAM) of the lung. METHODS: A retrospective study was undertaken in six fetuses with macrocystic CCAM at our institute that had been confirmed by postnatal surgery between August 1999 and January 2012. RESULTS: Six fetuses that had been diagnosed with macrocystic CCAM were analyzed. The median gestational age at diagnosis was 23.5 weeks (range, 19.5-31.0 weeks), and at the time of primary treatment was 24.0 weeks (range, 20.5-31.0 weeks). The mean size of the largest cyst at the initial assessment was 42.5+/-15 mm. Four fetuses were associated with mediastinal shifting, and one also showed fetal hydrops. All fetuses underwent a shunting procedure within the cysts, one case among them was also treated with OK-432. After the completion of all procedures, the mean size of the largest cyst was all decreased (14.2+/-12 mm). The median gestational age at delivery was 38.0 weeks (range, 32.4-40.3 weeks). All of the newborns underwent the surgical resection at a median age of 6 days (range, 1-136 days) and are currently doing well without any complications. CONCLUSION: We suggest that intrauterine decompression therapy to manage fetal macrocystic CCAM is recommendable treatment for good perinatal outcome.

Thanatophoric dysplasia in a dichorionic twin confirmed by genetic analysis at the early second trimester: A case report and literature review

Thanatophoric dysplasia (TD) is caused by mutation of the gene that encodes fibroblast growth factor 3 (FGFR3). Owing to the poor prognosis for TD, prenatal diagnosis is critical to optimal perinatal management. We report here a case of TD in twin pregnancy, which was prenatally diagnosed by DNA analysis following amniocentesis at 15 weeks, and was managed by selective fetal termination. Prenatal ultrasonography and molecular analysis to detect TD-specific mutations enable accurate diagnosis of FGFR3-related TD in utero and appropriate obstetrical management at early gestation during twin pregnancy.

Variety of prenatally diagnosed congenital heart disease in 22q11.2 deletion syndrome

OBJECTIVE: To analyze the spectrum of prenatally diagnosed congenital heart disease in a Korean population with 22q11.2 deletion syndrome, and to provide guidelines for screening 22q11.2 deletion prenatally. METHODS: This retrospective study evaluated 1,137 consecutive fetuses that had prenatal genetic testing for 22q11.2 deletion because of suspected congenital heart disease between September 2002 and December 2012, at Asan Medical Center, Seoul, Korea. RESULTS: Main cardiovascular diseases in the 53 fetuses with confirmed 22q11.2 deletions were tetralogy of Fallot (n = 24, 45%), interrupted aortic arch (n = 10, 19%), ventricular septal defect (n = 5, 9%), double outlet right ventricle (n = 4, 8%), and coarctation of the aorta (n = 4, 8%). Other cardiac defects were rarely associated with 22q11.2 deletion. One fetus had persistent truncus arteriosus, one had aortic stenosis, and one had hypoplastic right heart syndrome. Two fetuses had normal intracardiac anatomy with an isolated right aortic arch, and one had an isolated bilateral superior vena cava. CONCLUSION: A variety of congenital heart diseases were seen during the prenatal period. Conotruncal cardiac defects except transposition of great arteries were strongly associated with 22q11.2 deletion. When such anomalies are diagnosed by fetal echocardiography, genetic testing for 22q11.2 deletion should be offered. Even if less frequent deletion-related cardiac defects are detected, other related anomalies, such as thymic hypoplasia or aplasia, should be evaluated to rule out a 22q11.2 deletion.

An unusual ultrasonographic manifestation of a fetal Ebstein anomaly

An Ebstein anomaly is a rare congenital heart defect defined by an inferior displacement of the septal and posterior leaflets of the tricuspid valve from the tricuspid annulus. This anomaly shows various ultrasonographic manifestations, thus making the prenatal diagnosis sometimes difficult. We here report a rare case of an Ebstein anomaly which was prenatally suspected as the absence of the tricuspid valve with functional pulmonary atresia because of non-visible tricuspid leaflets on an echocardiograph at 24 weeks of gestation. An emergency cesarean section was performed at 35 weeks of gestation as fetal hydrops were seen on a follow-up scan. Postnatal surgery confirmed Ebstein anomaly type-D which demonstrates an almost complete atrialization of the right ventricle with the exception of a small and infundibular component. Because of its rarity, prenatal findings of a type-D Ebstein anomaly have not been reported previously. We suggest from this first such case report that this anomaly should be considered as a possible diagnosis when the tricuspid leaflets are not well visualized.

Prenatal diagnosis of atrial isomerism in the Korean population

OBJECTIVE: To report our experiences in the prenatal diagnosis of atrial isomerism and postnatal outcomes. METHODS: A total of 80 fetuses prenatally diagnosed with atrial isomerism were retrospectively analyzed between 1999 and 2011 at a single institution. RESULTS: Of 43 fetuses with prenatally diagnosed right atrial isomerism (RAI), 40 cases were analyzed. The diagnostic accuracy was 93%. The main intracardiac anomalies in RAI were atrioventricular septal defect (AVSD), abnormal pulmonary venous connection, bilateral superior vena cava (BSVC), and pulmonary atresia. Among 28 live births, three infants were lost to follow up, and the overall survival rate was 60%. Of 37 fetuses with prenatally diagnosed left atrial isomerism (LAI), 35 were evaluated. The diagnostic accuracy was 97%. The main intracardiac anomalies in LAI were ventricular septal defect, BSVC, AVSD, double outlet right ventricle, and bradyarrhythmia. Among seven patients with bradyarrhythmia, only one showed a complete atrioventricular block. All fetuses had an interrupted inferior vena cava with azygous continuation. The overall survival rate was 90%. CONCLUSION: Our study confirms the previous findings of fetal atrial isomerism. We also demonstrates a much lower prevalence of AVSD and complete heart block in LAI and a better survival rate in RAI. Although the postnatal outcomes for RAI were worse than those for LAI, successful postnatal surgery with active management improved the survival rate.

Prenatal Diagnosis of der(X)t(X;Y)(p22.31;q11.22) in a Male Fetus by Using Array Comparative Genomic Hybridization

Xp/Yq translocations are rare chromosomal rearrangements, and the phe-notype of male carriers varies according to the segment of the Xp region that is deleted. In this case report, we describe a der(X)t(X;Y)(p22.31;q11.22) translocation, detected by conventional cytogenetic analysis, in a male fetus at a gestational age of 16 weeks. Chromosomal analysis of parental blood confirmed that this chromosomal aberration had been maternally inherited. Array comparative genomic hybridization (CGH) analysis of fetal blood further indicated a nullisomy of Xp22.31-pter and a breakpoint between the STS and KAL1 genes. The STS, NLGN4, ARSE, CSF2RA, and SHOX genes are present in the region that was deleted, and are known to be related to conditions such as X-linked ichthyosis, chondrodysplasia punctata, mental retardation, and facial dysmorphism in humans. Prenatal ultrasonographic findings and autopsy results were consistent with Xp22.31-pter deletion phenotypes. Genetic counseling was provided for the mother. The observations from this case study indicate that advanced molecular techniques can provide a more precise prenatal diagnosis of chromosomal anomalies than conventional cytogenetics can.