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.

Persistent low-level elevation of serum human chorionic gonadotropin after termination of pregnancy: a rare case of peritoneal trophoblastic implant

Peritoneal trophoblastic implant can occur after treatment of ectopic pregnancy. Similarly, after termination of intrauterine pregnancy, trophoblastic implants are rare but can be a complication of perforation during dilatation and curettage. We report an extremely rare case of trophoblastic implant on the myometrium, ovarian surface, and peritoneal wall 4 months after uncomplicated dilatation and curettage. To the best of our knowledge, this is the first case of peritoneal trophoblastic implant following dilatation and curettage without uterine perforation. Knowledge of this case is useful for the management of patients with persistent low-level elevation of serum human chorionic gonadotropin after termination of pregnancy.

Serum β-hCG concentration is a predictive factor for successful early medical abortion with vaginal misoprostol within 24 hours

OBJECTIVE: To evaluate the predictive factors associated with the success of medical abortion by misoprostol monotherapy within 24 hours in the first trimester of pregnancy. METHODS: The records of 228 women with miscarriage up to 11 weeks of gestational age who underwent medical abortion by intravaginal misoprostol monotherapy were reviewed. Success of abortion was defined as complete expulsion of the conceptus without the need for surgical intervention. Outcomes of interest were success of abortion within 24 hours following administration of misoprostol. RESULTS: Among 222 women who continued the process of medical abortion for 24 hours, 209 (94.1%) had a successfully completed abortion. Multivariate logistic regression showed that serum β-human chorionic gonadotropin (β-hCG) above 40,000 mIU/mL is significantly associated with failed medical abortion within 24 hours (odds ratio [OR], 7.13; 95% confidence interval [CI], 1.60–37.32; P=0.011). The area under the receiver operating characteristic curve of β-hCG level associated with successful abortion within 24 hours was 0.705 (95% CI, 0.63–0.77; P=0.007). Previous vaginal delivery seems to be significantly associated with successful abortion within 24 hours on univariate analysis (P=0.037), but the association was lost in multivariate analysis. CONCLUSION: Misoprostol monotherapy has a high success rate for first trimester abortion. Women with serum β-hCG less than 40,000 mIU/mL are likely to achieve a successful abortion within 24 hours after intravaginal administration of misoprostol.

Fetal heart rate monitoring: from Doppler to computerized analysis

The monitoring of fetal heart rate (FHR) status is an important method to check well-being of the baby during labor. Since the electronic FHR monitoring was introduced 40 years ago, it has been expected to be an innovative screening test to detect fetuses who are becoming hypoxic and who may benefit from cesarean delivery or operative vaginal delivery. However, several randomized controlled trials have failed to prove that electronic FHR monitoring had any benefit of reducing the perinatal mortality and morbidity. Also it is now clear that the FHR monitoring had high intra- and interobserver disagreements and increased the rate of cesarean delivery. Despite such limitations, the FHR monitoring is still one of the most important obstetric procedures in clinical practice, and the cardiotocogram is the most-used equipment. To supplement cardiotocogram, new methods of computerized FHR analysis and electrocardiogram have been developed, and several clinical researches have been currently performed. Computerized equipment makes us to analyze beat-to-beat variability and short term heart rate patterns. Furthermore, researches about multiparameters of FHR variability will be ongoing.

Prevalence of Low Bone Mineral Density and Associated Risk Factors in Korean Puerperal Women

Although pregnancy is a medical condition that contributes to bone loss, little information is available regarding bone mineral density (BMD) in puerperal women. This cross sectional study aimed to evaluate the prevalence of low BMD in puerperal women and to identify associated risk factors. We surveyed all puerperal women who had BMD measurements taken 4–6 weeks after delivery in a tertiary university hospital, and did not have any bone loss-related comorbidities. Among the 1,561 Korean puerperal women, 566 (36.3%) had low BMD at the lumbar spine, total hip, femoral neck, and/or trochanter. Multivariate analysis revealed that underweight women had a significantly higher risk of low BMD compared with obese women at pre-pregnancy (adjusted odds ratio [aOR], 3.21; 95% confidence interval [CI], 1.83–5.63). Also, women with inadequate gestational weight gain (GWG) were 1.4 times more likely to have low BMD than women with excessive GWG (aOR, 1.42; 95% CI, 1.04–1.94). One-way ANOVA showed that BMDs at the lumbar spine and total hip were significantly different between the 4 BMI groups (both P < 0.001) and also between the 3 GWG groups (both P < 0.001). In conclusion, this study identifies a high prevalence of low BMD in puerperal women and thus suggests the need for further evaluation about the change of BMD in pregnancy and postpartum period.

Korean-Specific Parameter Models for Calculating the Risk of Down Syndrome in the Second Trimester of Pregnancy

The purpose of the current study was to propose a Korean-specific parameter set for calculating the risk of Down syndrome in the second trimester of pregnancy and to determine the screening performances of triple and quadruple tests in Korean women. Using the data on triple or quadruple screening from three hospitals in Korea during 7 yr, we re-converted the concentrations of four serum markers to multiple of median values according to gestational age and maternal weight. After re-calculating the risk of Down syndrome in each pregnancy by multiplying maternal age-specific risk by the likelihood ratio values for the serum markers, screening performances and optimal cut-off values of triple and quadruple tests were analyzed. Among 16,077 pregnancies, 23 cases had Down syndrome (1.4/1,000 deliveries). Compared to the previous program, the tests with new parameters had improved screening performance. The triple and quadruple tests had detection rates of 65.2% and 72.7%, respectively, at a false-positive rate of 5%. The optimal cut-off value for the quadruple and triple tests was 1:250. We have presented a Korean-specific parameter set for Down syndrome screening. The proposed screening test using this parameter set may improve the performance of Down syndrome screening for Korean women.

Angular pregnancy complicated with preterm labor at 25 gestational weeks of pregnancy / 대한산부인과학회지

Angular pregnancy refers to implantation of the embryo just medial to uterotubal junction in the lateral angle of the uterine cavity. This is differentiated from interstitial pregnancy in which the gestational sac is located within intramural portion of the tube. Angular pregnancy is categorized as intrauterine pregnancy and the outcome is known favorable. However, there have been few reports about adverse perinatal complications such as abortion, retained placenta, placenta accreta, placenta percreta and uterine rupture. We report a case of angular pregnancy complicated with preterm labor at 25 gestational weeks, placenta accreta and postpartum endometritis. This case suggests that angular pregnancy should be differentiated from normal intrauterine pregnancy because of its potential risk of adverse outcome.

Factors influencing on perinatal outcomes in pregnancy with IgA nephropathy / 대한산부인과학회지

OBJECTIVE: The aim of this study is to evaluate factors influencing on perinatal outcomes of pregnancy with IgA nephropathy and the effect of pregnancy on the prognosis of IgA nephropathy. METHODS: We retrospectively reviewed clinical and laboratory findings of 28 pregnancies in 25 pregnant women with biopsy-proven IgA nephropathy at six hospitals of Catholic Medical Center throughout the period of January 1999 to December 2009. They are divided into two groups by presence or absence of perinatal complications such as preeclampsia and preterm labor and then compared. The prognosis of IgA nephropathy was determined by serum creatinine level and diagnosis of end stage renal disease (ESRD) until 3 years after delivery. Fisher exact test and Mann-Witney U test were used for statistical analysis. RESULTS: The factors that related perinatal complications included high blood pressure (P=0.019), low glomerular filtration rate (less than 50 mL/min) (P=0.029), and high creatinine level (more than 2.0 mg/dL) (P=0.005). Especially, hypertension and high creatinine level (more than 2.0 mg/dL) increased risk of not only preterm birth (P=0.017, P=0.026, respectively) but also preeclampsia (P=0.008, P=0.001, respectively). The factors that increased risk of ESRD within 2 years after delivery included high creatinine level (more than 2.0 mg/dL) (P=0.018) and preeclampsia (P=0.018). CONCLUSION: Our results indicate that hypertension and poor renal function could be predictors of poor perinatal outcomes, and when pregnancies with IgA nephropathy are complicated by preeclampsia or high creatinine level (more than 2.0 mg/dL), the prognosis of IgA nephropathy might be poor.

A Case Report of Acute Hepatitis A Infection in Pregnancy / 대한주산의학회잡지

Hepatitis A virus infection is the most common cause of acute hepatitis but is rarely reported during pregnancy. We report a case of acute hepatitis A in a 28-year old pregnant woman at 40 weeks of gestation. Her initial complaint was fever. Three days after, she developed spontaneous labor and delivered a healthy baby vaginally. Her laboratory examination showed thrombocytopenia, elevated D-dimer and decreased Fibrinogen level as well as markedly elevated liver enzymes. In addition, oliguria and pulmonary effusion were also noted. Hepatitis A infection during pregnancy may be associated with development of labor. And the differential diagnosis with preeclampsia and acute fatty liver of pregnancy is very important for the management.

Clinical significance of oligohydramnios in intrauterine growth restriction / 대한산부인과학회지

OBJECTIVE: This study was performed to prove the significance of the oligohydramnios in the intrauterine growth restriction. METHODS: Eighty two patients were identified to have intrauterine growth restriction with oligohydramnios (Group of IUGR+Oligihydramnios) and fifty six patients were identified to have intrauterine growth restriction without oligohydramnios (Group of IUGR) on ultrasound examination from January 1st, 2005 to December 31st, 2007 at St. Vincent Hospital of Catholic University of Korea. Perinatal outcomes were compared between two groups. RESULTS: Statistically significant differences were not shown between two groups in the maternal characteristics and fetal clinical features except amniotic fluid index and the duration between diagnosis and delivery. The incidence of hyperbilirubinemia and complications in the urogenital system were significantly increased in the group of IUGR+ Oligihydramnios. The other complications were not shown significant difference between two groups. CONCLUSION: Oligohydramnios may not seem to be significant predictor of adverse neonatal outcome of IUGR except the development of hyperbilirubinemia and urogenital complications.

A case of unruptured rudimentary uterine horn pregnancy at 28 weeks of gestation diagnosed by MRI / 대한산부인과학회지

Pregnancy in rudimentary horn is rare. Rupture tends to occur in the second trimester. Only a few cases of the diagnosis of unruptured third-trimester rudimentary horn pregnancy have been reported. We experienced a case of unruptured rudimentary horn pregnancy at 28+3 weeks gestation confirmed by MRI. Successful delivery of a live male fetus weighing 955g by cesarean section and excision of the rudimentary horn with ipsilateral salpinx were carried.

Interpretation of antenatal screening methods / 대한산부인과학회지

For definitive antenatal diagnosis of fetal aneuploidy, invasive tests such as chorionic villous sampling, amniocentesis and cordocentesis are required for chromosome analysis. However, to reduce the risk of miscarriage associated with procedural complications, it is important to detect pregnant women with high risk of fetal aneuploidy. Recently, there have been advances in maternal serum and sonographic markers for screening of chromosomal defects in the first and second trimester. The serum screening methods include first trimester screening with nuchal translucency and second trimester multi marker screening. Particularly, combining first and second trimester results can increase the detection rate of Down syndrome with lower false-positive rates. In addition to biochemical markers, second trimester sonogram to detect major and minor sonographic markers for chromosomal defects is important to identify the high risk pregnancy. To detect the fetal aneuploidy with high specificity and sensitivity, we need to interpret the maternal age, the results of first and second trimester serum markers and genetic sonographic findings all together.

Perinatal Outcomes according to the Types of Fetal Acidosis in Term Newborns with Umbilical Artery Acidosis / 대한주산의학회잡지

PURPOSE:To investigate the significance of umbilical artery acidosis and compare perinatal outcomes according to the types of acidosis for a tertiary hospital population delivered at term. METHODS:We reviewed maternal and neonatal medical records of all term liveborn infants with an umbilical artery pH or =20 mEq/L) and high pCO2 (> or =20 mmHg) were significantly associated with low pH value, the perinatal outcomes were not significantly different according to the level of base deficit or pCO2. CONCLUSION:The mixed acidemia was more associated with pathologic fetal acidemia than pure respiratory or metabolic acidosis. The ability to predict not only metabolic but also respiratory component of fetal acidemia may help in safe management of delivery leading to reduce the fetal acidemia.

Prenatal Diagnosis of Pallister-Killian Syndrome Associated with Pulmonary Stenosis and Right Ventricular Dilatation / 대한진단검사의학회지

Pallister-Killian syndrome (PKS) is a rare disorder characterized cytogenetically by tetrasomy 12p for isochromosome of the short arm of chromosome 12. PKS is diagnosed by prenatal genetic analysis through chorionic villous sampling, genetic amniocentesis, and cordocentesis, or by chromosomal analysis of skin fibroblasts, but is not usually detected by chromosomal analysis of peripheral blood cells. Herein, we report a case of a gravida at 23 weeks gestation with pulmonary stenosis and right ventricular dilation of the heart which were detected by sonography. Fluorescence in situ hybridization and a multicolor banding technique were performed to verify the diagnosis as 47,XX, +mar.ish i(12)(p10)(TEL++)[16]/46,XX[4], and an autopsy confirmed the cardiac anomalies detected on antenatal sonography.

Perinatal outcome of term pregnancies with meconium-stained amniotic fluid / 대한주산의학회잡지

PURPOSE: The purpose of this study was to compare the obstetric and perinatal outcome between two groups with or without meconium staining of amniotic fluid (MSAF) at term birth in one-year consecutive population at our delivery unit. METHODS: Pregnancy complication including nonreassuring fetal heart rate pattern, intrauterine growth retardation, oligohydramnios, hydramnios and preeclampsia between the two groups were retrospectively documented by review of medical record. To evaluate the perinatal outcome, apgar score at 1min and 5min, and umbilical artery blood gas analysis were also analyzed. Student T test and chi square test were used for statistic analysis. RESULTS: The study population consisted of 687 full-term neonates with presence (n=89) and absence (n=598) of MSAF. Gestational age at delivery was significantly higher in the MSAF group (p12.0 mEq/L) was not increased. The incidence of non reassuring fetal heart rate pattern was also increased in the MSAF group (4.5% vs 1.0%, p=0.03). However there was no significant difference in 1 min and 5 min Apgar score. CONCLUSION: Although MSAF is associated with the risk of non reassuring fetal heart rate pattern and fetal acidemia, the metabolic acidemia and low apgar score at 5minutes was not significantly increased compared with clear amniotic fluid group. Delivery of pregnancy with MSAF should be managed under the careful fetal heart rate monitoring.

Congenital depression of the neonatal skull unassociated with birth trauma / 대한주산의학회잡지

In spite of the fact that there is general consensus that neonatal depressed skull fractures are caused largely by instrumental extraction, there are a few reports regarding congenital depression of the skull unrelated to external trauma. In the case herein, the mother did not have any history of abdominal trauma during pregnancy and the neonate was delivered vaginally without the use of instruments, yet a round depression was noted in the left parietal bone of the neonate at the time of delivery. Computed tomography with three dimensional reconstruction images was performed and a congenital depression of the neonatal skull without fracture was diagnosed. We describe this case with a brief review of the literature.

Umbilical cord artery blood pH analysis at term pregnancy / 대한주산의학회잡지

OBJECTIVE: To assess the gestational age adjusted values of umbilical cord artery blood pH in term pregnancy METHODS: We retrospectively analyzed umbilical arterial blood pH values and obstetric data of 1,918 term singleton deliveries without maternal medical disease, pregnancy induced hypertension and fetal distress during labor periods at Kangnam St. Mary's Hospital, Catholic University medical college between January 2004 and December 2006. Low pH was defined as less than 7.10 as a stationary cutoff value, whereas pH less than (mean -2 standard deviations [SDs]) was used when gestational age was considered. We evaluated the risk of 5 minute Apgar score of less than 7 and meconium staining more than grade II at low pH. RESULTS: A significant negative correlation was found between gestational age and umbilical artery pH (p=0.000). We evaluated the umbilical artery pH value in different delivery mode. Vaginal delivery cases showed negative correlation (p=0.000), but elective cesarean section cases didnt. Low pH patients defined by both criteria of pH less than 7.10 and pH less than (mean -2SD) showed significantly increased risk of 5 minutes Apgar score of less than 7 (pH less than 7.10: p=0. 000, pH less than (mean -2SD): p=0.001) and meconium staining more than grade II (pH less than 7.10: p=0. 001, pH less than (mean -2SD): p=0.001). CONCLUSION: Our results suggest that umbilical cord pH has a negative relation with gestational age during term period.

A case of abdominal pregnancy implanted on uterosacral ligament / 대한산부인과학회지

Abdominal pregnancy, a rare type of ectopic pregnancy is difficult to be suspected at its first presentation. The diagnosis of this rare disease may often be delayed, since early symptoms are usually non-specific. In some cases, delayed diagnosis of abdominal preganacy can be associated with catastrophic hemorrhage secondary to placental separation. A 24-year old woman visited our emergency unit, presenting with a sudden-onset low abdominal pain. She had undergone uterine curettage 3 weeks before. Transvaginal sonogram of the cul-de-sac revealed complex fluid consistent with blood. On diagnostic laparoscopic operation, we found a ruptured cystic, conception-like structure near the right uterosacral ligament. Histology of the resected structure finally showed chorionic villi consistent with abdominal pregnancy. In this report, we present an unusual case of abdominal pregnancy. This case underscores the careful ultrasonic determination of gestational location at early pregnancy.

Impact of Maternal Age of 40 Years or Older on Pregnancy Outcomes / 대한주산의학회잡지

OBJECTIVE: The aim of this study was to examine the effects of maternal age on perinatal and obstetric outcomes with respect to maternal age older than 40 years. METHODS: A retrospective review of maternal and newborn medical records of women who delivered their babies in the hospitals of the Catholic University of Korea between January 1, 2000 and July 1, 2005 was conducted to compare pregnancy complications and perinatal outcomes in three age groups; women aged 25~29 years (group A; n=214), those aged 35~39 years (group B; n=276), and those aged 40 years and older (group C; n=347). RESULTS: The incidences of GDM (gestational diabetes mellitus), preterm birth and cesarean section in group C were by far the greatest among the three groups. The incidence of postterm delivery in group A was the highest among the three groups. Previous cesarean section and elderly gravida were the most frequent causes of cesarean section in group C. The incidences of low birth weight (<2,500 g) and the NMICU(neonatal medical intensive care unit) admission rate in group C were higher than those in group B, but not significantly different from those in group A. CONCLUSION: Maternal ages of 35~39 years do not appear to be associated with adverse perinatal and obstetrical outcomes. Maternal ages of over 40 years influence the incidences of PIH (pregnancy induced hypertension), GDM, preterm birth, cesarean section, placenta previa, low birth weight and NMICU admission.