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.

Spinal Accessory Neuropathy Secondary to Diffuse Large B-Cell Lymphoma

Spinal accessory neuropathy (SAN) is commonly caused by an iatrogenic procedure, and that caused by tumors is very rare. We present a case of a 49-year-old man suffering from weakness in the right trapezius and sternocleidomastoid muscle. An electrophysiology study confirmed proximal SAN. Fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) revealed a diffuse large B-cell lymphoma compressing the right spinal accessory nerve. Ultrasonography showed definite atrophy on the trapezius and sternocleidomastoid muscles. In addition, post-chemotherapy FDG-PET/CT showed increased FDG uptake in the right upper trapezius, suggestive of denervation. This is the first report of SAN caused by direct compression by a diffuse large B-cell lymphoma, comprehensively assessed by an electrophysiology study, ultrasonography, and FDG-PET/CT.

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.

Quantitative Analysis of Swallowing Function Between Dysphagia Patients and Healthy Subjects Using High-Resolution Manometry

OBJECTIVE: To compare swallowing function between healthy subjects and patients with pharyngeal dysphagia using high resolution manometry (HRM) and to evaluate the usefulness of HRM for detecting pharyngeal dysphagia. METHODS: Seventy-five patients with dysphagia and 28 healthy subjects were included in this study. Diagnosis of dysphagia was confirmed by a videofluoroscopy. HRM was performed to measure pressure and timing information at the velopharynx (VP), tongue base (TB), and upper esophageal sphincter (UES). HRM parameters were compared between dysphagia and healthy groups. Optimal threshold values of significant HRM parameters for dysphagia were determined. RESULTS: VP maximal pressure, TB maximal pressure, UES relaxation duration, and UES resting pressure were lower in the dysphagia group than those in healthy group. UES minimal pressure was higher in dysphagia group than in the healthy group. Receiver operating characteristic (ROC) analyses were conducted to validate optimal threshold values for significant HRM parameters to identify patients with pharyngeal dysphagia. With maximal VP pressure at a threshold value of 144.0 mmHg, dysphagia was identified with 96.4% sensitivity and 74.7% specificity. With maximal TB pressure at a threshold value of 158.0 mmHg, dysphagia was identified with 96.4% sensitivity and 77.3% specificity. At a threshold value of 2.0 mmHg for UES minimal pressure, dysphagia was diagnosed at 74.7% sensitivity and 60.7% specificity. Lastly, UES relaxation duration of <0.58 seconds had 85.7% sensitivity and 65.3% specificity, and UES resting pressure of <75.0 mmHg had 89.3% sensitivity and 90.7% specificity for identifying dysphagia. CONCLUSION: We present evidence that HRM could be a useful evaluation tool for detecting pharyngeal dysphagia.

Non-invasive prenatal test using cell free DNA

Although conventional prenatal screening tests for Down syndrome have been developed over the past 20 years, the positive predictive value of these tests is around 5%. Through these tests, many pregnant women have taken invasive tests including chorionic villi sampling and amniocentesis for confirming Down syndrome. Invasive test carries the risk of fetal loss at a low but significant rate. There is a large amount of evidence that non-invasive prenatal test (NIPT) using cell free DNA in maternal serum is more sensitive and specific than conventional maternal serum and/or ultrasound screening. Therefore implementing NIPT will increase aneuploidy detection rate and concurrently decrease fetal loss rate accompanying invasive test. More than 1,000,000 NIPT were performed globally since 2011. The uptake rate of NIPT is expected to increase more rapidly in the future. Moreover, as a molecular genetic technique advances, NIPT can be used for not only common aneuploidy screening but single gene disorder, microdeletion, and whole fetal genome sequencing. In this review, I will focus on the NIPT for common aneuploidies such as trisomy 13, 18, and 21.

2014 First-trimester ultrasound forum from the Korean Society of Ultrasound in Obstetrics and Gynecology

A first-trimester ultrasound scan has become an essential part of antenatal care. The Korean Society of Ultrasound in Obstetrics and Gynecology held a first-trimester ultrasound forum on April 5, 2014. The forum aimed to present an updated review of the literature on the topic of first-trimester ultrasound in specific lectures and to host a panel discussion on several important issues regarding first-trimester scans. The forum provided evidence- and consensus-based best practice patterns for obstetricians in Korea. Here, we report the review and checklists presented from the forum.

Advantages of the single nucleotide polymorphism-based noninvasive prenatal test

Down syndrome screening with cell-free DNA (cfDNA) in the maternal plasma has recently received much attention in the prenatal diagnostic field. Indeed, a large amount of evidence has already accumulated to show that screening tests with cfDNA are more sensitive and specific than conventional maternal serum and/or ultrasound screening. Globally, more than 1,000,000 of these noninvasive prenatal tests (NIPTs) have been performed to date. There are several different methods for NIPTs that are currently commercially available, including shotgun massively parallel sequencing, targeted massively parallel sequencing, and single nucleotide polymorphism (SNP)-based methods. All of these methods have their own advantages and disadvantages. In this review, I will focus specifically on the SNP-based NIPT.

The practice patterns of second trimester fetal ultrasonography: A questionnaire survey and an analysis of checklists

OBJECTIVE: To analyze practice patterns and checklists of second trimester ultrasonography, and to investigate management plans when soft markers are detected among Korean Society of Ultrasound in Obstetrics and Gynecology (KSUOG) members. METHODS: An internet-based self-administered questionnaire survey was designed. KSUOG members were invited to the survey. Checklists of the second trimester ultrasonography were also requested. In the questionnaire survey, general practice patterns of the second trimester ultrasonography and management schemes of soft markers were asked. In the checklists analysis, the number of items were counted and also compared with those recommended by other medical societies. RESULTS: A total of 101 members responded. Eighty-seven percent routinely recommended second trimester fetal anatomic surveillance. Most (91.1%) performed it between 20+0 and 23+6 weeks of gestation. Written informed consents were given by 15.8% of respondents. Nearly 60% recommended genetic counseling when multiple soft markers and/or advanced maternal age were found. Similar tendencies were found in the managements of individual soft markers. However, practice patterns were very diverse and sometimes conflicting. Forty-eight checklists were analyzed in context with the number and content of the items. The median item number was 46.5 (range, 17 to 109). Of 49 items of checklists recommended by International Society of Ultrasound in Obstetrics and Gynecology and/or American Congress of Obstetricians and Gynecologists, 14 items (28.6%) were found in less than 50% of the checklists analyzed in this study. CONCLUSION: Although general practice patterns were similar among KSUOG members, some of which were conflicting, and there is a need for standardization of the practice patterns and checklists of second trimester ultrasonography, which also have very wide range of spectrum.

Event-Related Potentials During the Visual Go/NoGo Task in Drug-Naive Boys with Attention-Deficit/Hyperactivity Disorder

OBJECTIVES: The purpose of this study was to examine the performance and electrophysiological characteristics of drug-naive children with attention-deficit/hyperactivity disorder (ADHD) during the Go/NoGo task. METHODS: Twenty-three boys with ADHD and 18 age-matched normal boys were recruited at a child psychiatric outpatient clinic in Seoul. All subjects were assessed by the Kiddie Schedules for Affective Disorders and Schizophrenia -Present and Lifetime version. The investigator also assessed all subjects using the ADHD Rating Scale-IV (ADHDRS). Event-related potentials were recorded from 8 scalp electrodes during the visual Go/NoGo task. RESULTS: Children with ADHD showed a larger mean of standard deviation of response time during the Go/NoGo task than normal children. The temporal N200 and P300 amplitudes were larger in children with ADHD relative to controls. The parietal N200 and P300 latencies were more prolonged in children with ADHD compared to normal controls. CONCLUSION: These results suggest that psychotropic-naive children with ADHD may have more variable performance ability, more difficulty in discriminating visual stimuli, and slower information processing speed than their normal agematched counterparts.

Association of the Symptoms of Parental Attention-Deficit Hyperactivity Disorder and the Parental Personality Patterns with the Symptoms of Boys with Attention-Deficit Hyperactivity Disorder

OBJECTIVES: This study was conducted to investigate the association between the symptoms of boys with attentiondeficit hyperactivity disorder (ADHD) and the attention-deficit hyperactivity symptoms, temperament and character patterns of their parents. METHODS: Forty-five boys with ADHD and who met the DSM-IV criteria were evaluated by using the ADHD rating scale (ADHD-RS), and their parents completed the Korean Adult ADHD scale (K-AADHDS) and the Temperament and Character Inventory (TCI). RESULTS: The parental K-AADHDS scores were not associated with the ADHD-RS total score and the subscale scores of their siblings. The most potent variable related to the ADHD-RS total score was the maternal self-directedness, and the second was the maternal persistence. The maternal self-directedness was the variable that was most correlated with the hyperactivity/impulsivity subscale scores of the ADHD-RS. CONCLUSIONS: The results suggest that the paternal ADHD symptoms may not be related to the ADHD symptoms of boys with ADHD. Higher maternal self-directedness and persistence may decrease overall the ADHD symptoms of these boys, and higher maternal self-directedness itself may predict lower hyperactivity/impulsivity symptoms of the boys with ADHD.

Normal Development and Common Psychiatric Illnesses in Adolescence / 신경정신의학

OBJECTIVES: I reviewed the fundamental knowledge about normal development and common psychiatric illnesses in adolescence to provide with a lecture note for resident training seminar. METHODS: Three textbooks were reviewed and summarized. RESULTS: Adolescence is a bridge period between childhood and adulthood. Through adolescence, the development and achievement of interpersonal relationship, character pattern, learning and occupational capabilities occur. In adolescence, lots of both physical and psychological changes are observed. Also the requirement of social role and duty increased. Because of them, many psychiatric illnesses and adaptive problems are developed and exert negative influences on the quality of life of adolescents and their family. CONCLUSION: Adolescence is important period in human development and many psychiatric disabilities are developed and aggravated in this period.

Maternal Parenting Stress and Sense of Competence in Children with Seizure Disorders / 신경정신의학

OBJECTIVES: While parents who foster children with epilepsy would have considerable parenting difficulties, the parenting stress and sense of competence have not been investigated. We investigated maternal parenting stress, parenting satisfaction and sense of parenting competence in children with seizure disorders, and the associations with seizure-related variables. METHODS: Mothers of 79 children with seizure disorders (41 boys, 38 girls; mean age, 9.9+/-2.3 years) and 79 healthy comparison subjects matched for age and sex were recruited for this study. The Korean version of the Parenting Stress Index (K-PSI-SF) and the Parenting Sense of Competence (K-PSOC) were used to assess parenting stress, parenting satisfaction and parenting efficacy. RESULTS: Mothers of children with seizure disorders showed higher scores on stress related to difficult child and child learning and parenting anxiety compared to mothers of healthy children. In addition, scores on stress related to parental-child interaction and child learning were significantly associated with parental economic status. Scores on stress from parental-child interaction was also correlated with seizure severity, and stress from child learning was correlated with seizure type. Sense of parenting competence and anxiety scores were correlated with paternal educational status, respectively. CONCLUSION: These findings suggest that mothers of children with epilepsy have greater parenting stress and anxiety and social and seizure-associated factors may affect the parenting stress and anxiety.