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.

Short-Term Prediction of Adverse Outcomes Using the sFlt-1 (Soluble fms-Like Tyrosine Kinase 1)/PlGF (Placental Growth Factor) Ratio in Asian Women With Suspected Preeclampsia.

Current diagnostic criteria have limited clinical value for prediction of preeclampsia and fetal adverse outcomes. The prediction of short-term outcome in pregnant women with suspected preeclampsia study in Asia (PROGNOSIS Asia) was a prospective, multicenter study designed to investigate the value of the sFlt-1 (soluble fms-like tyrosine kinase 1)/PlGF (placental growth factor) ratio for predicting adverse outcomes in pregnant Asian women with suspected preeclampsia. Seven hundred sixty-four pregnant women at gestational week 20+0 days (18+0 days in Japan) to 36+6 days were enrolled at 25 sites in Asia. The primary objectives were to demonstrate the value of the sFlt-1/PlGF ratio for ruling out preeclampsia within 1 week and ruling in preeclampsia within 4 weeks. The value of the ratio for predicting fetal adverse outcomes was also assessed. Seven hundred patients were evaluable for primary end point analysis. The prevalence of preeclampsia was 14.4%. An sFlt-1/PlGF ratio of ≤38 had a negative predictive value of 98.6% (95% CI, 97.2%-99.4%) for ruling out preeclampsia within 1 week, with 76.5% sensitivity and 82.1% specificity. The positive predictive value of a ratio of >38 for ruling in preeclampsia within 4 weeks was 30.3% (95% CI, 23.0%-38.5%), with 62.0% sensitivity and 83.9% specificity. An sFlt-1/PlGF ratio of ≤38 had a negative predictive value of 98.9% (95% CI, 97.6%-99.6%) for ruling out fetal adverse outcomes within 1 week and a ratio of >38 had a positive predictive value of 53.5% (95% CI, 45.0%-61.8%) for ruling in fetal adverse outcomes within 4 weeks. The sFlt-1/PlGF ratio cutoff of 38 demonstrated clinical value for the short-term prediction of preeclampsia in Asian women with suspected preeclampsia, potentially helping to prevent unnecessary hospitalization and intervention.

Umbilical cord-derived mesenchymal stem cell extracts ameliorate atopic dermatitis in mice by reducing the T cell responses.

Mesenchymal stem cells derived from Wharton's jelly of the umbilical cord (UC-MSCs) have immunomodulatory properties. The aim of this study was to explore whether extracts of MSCs (MSC-Ex) could augment the low therapeutic efficacy of the whole cells in an Aspergillus fumigatus (Af)-induced atopic dermatitis (AD) model. LPS- or TNF-α/IFN-γ-stimulated keratinocytes (HaCaT cells) were treated with MSC-Ex, and the Af-induced AD model was established in BALB/c mice. In HaCaT cells, MSC-Ex treatment significantly reduced the inflammatory cytokine (IL-6, IL-1ß, IL-4, IL-5 and TNF-α), iNOS and NF-κB levels, and upregulated the anti-inflammatory cytokines (IL-10 and TGF-ß1). In the AD mice, the MSC-Ex group showed greatly reduced dermatitis, and lower clinical symptom scores and IgE levels. The histological dermatitis scores were also markedly lower in the MSC-Ex-treated animals compared with the MSC-treated group. Decreased levels of IFN-γ (Th1) and IL-17 (Th17), IL-4 and IL-13 (Th2) were detected in T cells and the skin tissue from the MSC-Ex treated AD mice. The therapeutic capacity of MSC-Ex was preserved after lyophilization and reconstitution. MSC-Ex treatment reproducibly suppresses dermatitis and inhibits the induction of inflammatory cytokines in the skin of AD mice. MSC-Ex is therefore a potential new treatment agent for AD.

Efficacy and safety of ferric carboxymaltose versus ferrous sulfate for iron deficiency anemia during pregnancy: subgroup analysis of Korean women.

BACKGROUND: We performed a post-hoc subgroup analysis in Korean women who participated in the Phase III FER-ASAP (FERric carboxymaltose-Assessment of SAfety and efficacy in Pregnancy) study to compare the efficacy and safety of ferric carboxymaltose (FCM) with oral ferrous sulfate (FS). METHODS: Pregnant Korean women (gestational weeks 16-33) with iron-deficiency anemia (IDA) were randomized 1:1 to FCM (n = 46; 1000-1500 mg iron) or FS (n = 44; 200 mg iron/day) group for 12 weeks. The primary objective was to compare the mean hemoglobin (Hb) increase at week 3; secondary objectives included change in iron parameters, quality of life (QoL), and safety. RESULTS: Baseline characteristics of the Korean subgroup were consistent with those of non-Korean FER-ASAP population except for lower body-mass index and higher maternal age. Hb level increases were comparable between the two treatment groups in Korean women at week 3 (FCM 1.23 ± 0.89 g/dL vs FS 1.14 ± 1.72 g/dL). Iron parameters improved over time as secondary endpoints were significantly in favor of FCM. In terms of QoL, FCM treatment significantly improved the mental and physical components as well as vitality prior to delivery. Both treatments were well tolerated. CONCLUSIONS: FCM provided significantly greater improvements in iron parameters and QoL compared to FS in the Korean subgroup. FCM may be a preferable alternative to currently available treatments for IDA during pregnancy.

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.

Previous uterine artery embolization increases the rate of repeat embolization in a subsequent pregnancy.

This study aimed to determine the rate of repeat uterine artery embolization (UAE) in women with a previous UAE. Study data were collected from the Korea National Health Insurance Claims Database of the Health Insurance Review and Assessment Service for 2009-2013. We enrolled women who had a first delivery in 2009 and a second delivery between 2010 and 2013. Among 226,408 women who had a first delivery in 2009, 296 underwent UAE. A total of 127,506 women had a second delivery between 2010 and 2013. Of 296 women who underwent UAE after the first delivery, 94 had a second delivery between 2010 and 2013. Women with a previous UAE had a higher rate of UAE at the second delivery than women without a previous UAE. Multivariate adjusted analysis showed that a UAE at the first delivery increased the rate of UAE at the second delivery (odds ratio 25.56, 95% confidence interval 9.86-66.23). Women with a previous UAE should be appropriately counseled and monitored for the need for a repeat UAE.

Umbilical cord-derived mesenchymal stem cell extracts reduce colitis in mice by re-polarizing intestinal macrophages.

Human umbilical cord mesenchymal stem cells (hUC-MSCs), originating in Wharton's jelly, are multipotent stem cells that home to damaged tissues and can modulate the immune system. We examined whether administering extracts of MSCs (MSC-Ex) instead of MSCs could augment the beneficial effects of MSC therapy by overcoming the low homing efficiency of MSCs systemically administered in inflammatory bowel diseases (IBD). Dextran sodium sulfate-induced colitis model was established in C57BL/6 mice, and MSC-Ex was administered intraperitoneally. MSC-Ex reduced colitis, disease activity index (DAI), and histological colitis scores, and increased the body weight. Treatment with MSC-Ex completely blocked the induction of inflammatory cytokines, which were strongly detected in mice with colitis. MSC-Ex shifted the macrophage functional phenotype from M1 to M2 by decreasing the levels of MCP1, CXCL9, and iNOS, but increasing the levels of IL-10, LIGHT, CCL1, and Arg-1. MSC-Ex recovered the destruction of the epithelial barrier in the differentiated Caco-2 cells in vitro. Treatment with MSC-Ex was more potent than that with MSC in reducing DAI, the histological score, and nitrite levels. These data strongly support that MSC-Ex treatment can be a potent approach to overcome severe refractory IBD.

Medical emergency team may reduce obstetric intensive care unit admissions.

AIM: Some recent studies have reported that early intervention by a medical emergency team (MET) for clinical deterioration before intensive care unit (ICU) admission was associated with a survival benefit in critically ill cancer patients. We hypothesized that early MET intervention for an obstetric crisis in the general wards would be related to favorable outcomes in critically ill obstetric patients. METHODS: Data of obstetric patients who were managed by a MET were collected retrospectively from 1 March 2008 to 30 April 2015. A total of 69 obstetric patients were enrolled. Among them, 48 (69.6%) were treated successfully in the general wards and 21 (30.4%) were transferred to the ICU. RESULTS: Major causes of MET activation were pulmonary edema (n = 23, 33.3%), hypovolemic shock (n = 19, 27.5%), and septic shock (n = 8, 11.6%). Compared with the patients treated in the general ward, the patients transferred to the ICU had significantly higher severity of illness score. Sequential Organ Failure Assessment score was the most useful for prediction of ICU admission of obstetric patients (AUC, 0.810, P < 0.001), and the ideal cut-off was 4 (sensitivity, 81%; specificity, 60%). During the study period, in-hospital mortality of the obstetric patients was 2.9% (2/69). CONCLUSION: After MET activation many obstetric patients could be successfully treated in the general wards without mortality. Therefore, MET may reduce ICU admissions in critically ill obstetric patients.

Fetal left modified myocardial performance index measured by the Auto Mod-MPI system: development of reference values and application to recipients of twin-to-twin transfusion syndrome.

OBJECTIVES: To establish normal reference ranges for the fetal left modified myocardial performance index (Mod-MPI) measured by the Auto Mod-MPI system and evaluate Mod-MPI changes in recipients of twin-to-twin transfusion syndrome (TTTS) before and after fetoscopic laser coagulation. METHODS: This was a prospective longitudinal study of normal singleton fetuses from 12.0 to 40.0 weeks of gestation. TTTS cases treated by laser coagulation were reviewed for Mod-MPI measurements of recipients. All measurements were performed using the Auto Mod-MPI system by a single experienced operator. RESULTS: Among a total 447 examinations from 222 fetuses, we were unable to measure the Mod-MPI in two cases, and therefore, 445 examinations were analyzed. The median Mod-MPI consistently increased from 0.44 to 0.56 throughout gestation. The median isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT) also increased with advancing gestational age. The ejection time (ET) increased until 27 weeks of gestation and decreased thereafter. In the 30 recipients, Mod-MPI, ICT, and IRT increased before laser coagulation and significantly decreased after laser coagulation. CONCLUSION: Normal reference values for left Mod-MPI were established using the Auto Mod-MPI system, and these might be useful for assessing cardiac function in TTTS. © 2016 John Wiley & Sons, Ltd.

Unusual prenatal sonographic findings without an elevated maternal serum alpha-fetoprotein level in a fetus with epidermolysis bullosa.

A 31-year-old pregnant woman was referred to us at 34.6 weeks' menstrual age for sonographic evaluation of a fetal left lower limb abnormality. Sonographic findings revealed shortening of the left tibia and dorsal hyperflexion of the left foot. There was no family history of genetic disease, and the maternal serum alpha-fetoprotein concentration was normal. A male infant was born with extensive skin peeling, mainly on his left leg, associated with muscular dystrophy. Epidermolysis bullosa was confirmed on a skin biopsy; the neonate died 53 days after birth as a result of severe sepsis. Although cutaneous epidermolysis bullosa is difficult to diagnose prenatally, shortening and deformity of extremities may provide a clue to the diagnosis, even when the maternal alpha-fetoprotein concentration is normal. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:319-321, 2016.

Umbilical cord mesenchymal stromal cells affected by gestational diabetes mellitus display premature aging and mitochondrial dysfunction.

Human umbilical cord mesenchymal stromal cells (hUC-MSCs) of Wharton's jelly origin undergo adipogenic, osteogenic, and chondrogenic differentiation in vitro. Recent studies have consistently shown their therapeutic potential in various human disease models. However, the biological effects of major pregnancy complications on the cellular properties of hUC-MSCs remain to be studied. In this study, we compared the basic properties of hUC-MSCs obtained from gestational diabetes mellitus (GDM) patients (GDM-UC-MSCs) and normal pregnant women (N-UC-MSCs). Assessments of cumulative cell growth, MSC marker expression, cellular senescence, and mitochondrial function-related gene expression were performed using a cell count assay, senescence-associated ß-galactosidase staining, quantitative real-time reverse transcription-polymerase chain reaction, immunoblotting, and cell-based mitochondrial functional assay system. When compared with N-UC-MSCs, GDM-UC-MSCs showed decreased cell growth and earlier cellular senescence with accumulation of p16 and p53, even though they expressed similar levels of CD105, CD90, and CD73 MSC marker proteins. GDM-UC-MSCs also displayed significantly lower osteogenic and adipogenic differentiation potentials than N-UC-MSCs. Furthermore, GDM-UC-MSCs exhibited a low mitochondrial activity and significantly reduced expression of the mitochondrial function regulatory genes ND2, ND9, COX1, PGC-1α, and TFAM. Here, we report intriguing and novel evidence that maternal metabolic derangement during gestation affects the biological properties of fetal cells, which may be a component of fetal programming. Our findings also underscore the importance of the critical assessment of the biological impact of maternal-fetal conditions in biological studies and clinical applications of hUC-MSCs.

Diffuse decidual leucocytoclastic necrosis and NK cell aggregates: two distinct features of miscarriage.

AIMS: Primary histopathology of miscarriage remains undetermined in the majority of cases. This study was conducted to determine histological characteristics pertinent to miscarriage. METHODS: The study groups were composed of elective abortions (n=29) and miscarriages (n=45) comprised of chromosomally normal (n=15) and abnormal cases (n=30). Immunohistochemistry was done against CD3, CD8, TIA-1 and CD56. RESULTS: Two histological features--diffuse decidual leucocytoclastic necrosis (DDLN) and decidual natural killer cell aggregates (NKCA)--were relatively common in miscarriages. The frequencies of DDLN and NKCA were different between the groups (p<0.05 and p<0.05, respectively). DDLN was found in 13.8% (4/29) of elective abortions, while it was observed in 60.0% (9/15) and 23.3% (7/30) of chromosomally normal and abnormal miscarriages, respectively. DDLN was more frequent in chromosomally normal miscarriages than in elective abortions (p=0.004). NKCA was present in 13.8% (4/29) of elective abortions, while being found in 33.3% (5/15) and 43.3% (13/30) of chromosomally normal and abnormal miscarriages, respectively. NKCA was more frequent in chromosomally abnormal miscarriages than in elective abortions (p=0.020). CONCLUSIONS: The findings strongly suggest that defective placentation and abnormal maternal immune response are associated with miscarriage. DDLN and NKCA seem to have diagnostic values in the pathological evaluation of miscarriage.

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.

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.

Massive perivillous fibrin deposition in the placenta and uterine metastasis of gastric adenocarcinoma during pregnancy.

The prognosis of gastric cancer during pregnancy is unfavorable because of delayed diagnosis and advanced stage. We present a case of gastric carcinoma metastasized to the placenta and uterus during pregnancy. Pathological examination revealed a poorly differentiated adenocarcinoma of the stomach with lymph node metastasis. After counseling, the patient decided to terminate the pregnancy and begin immediate treatment for gastric cancer. Hysterectomy and subtotal hysterectomy were performed because medical termination of the pregnancy was unsuccessful. Pathological examination of the placenta and uterus revealed metastases of gastric adenocarcinoma. All the uterine vessels were packed with tumor cells and the myometrium showed extensive coagulative necrosis. Moreover, microscopic findings of the placenta were consistent with massive perivillous fibrin deposition. Our case clearly suggests that massive perivillous fibrin deposition in the placenta can be associated with malignancy during pregnancy and that uterine metastasis of maternal malignancy may result in myometrial dysfunction unresponsive to uterotonics.

Measurement of intracranial translucency using three-dimensional ultrasound and Volume IT™.

OBJECTIVES: To establish the reference range of intracranial translucency (IT) in the Korean population, and to evaluate whether Volume IT™ is a reliable technique for measuring IT. METHODS: We retrospectively analyzed the IT of 93 singleton fetuses at 10.5 to 12.6 weeks of gestation using previously obtained three-dimensional volume data. The IT was measured manually and automatically using Volume IT™ in each fetus by one experienced and one beginner operator. We measured the IT values according to the crown-rump length and evaluated whether Volume IT™ can successfully measure the IT. Inter-observer agreement and intra-observer reproducibility were analyzed using the intraclass correlation coefficients (ICC), and the IT measurements obtained by the experienced operator using the manual and automated methods were then compared using the Bland-Altman plot and ICC. RESULTS: Among 93 cases, 2 were lost to follow-up after the first trimester scan and were excluded from further evaluation. Both operators identified the fourth ventricle in all 91 cases using Volume IT™. The experienced and beginner operators were able to measure the IT in 89 (98%) fetuses, with 4 and 13, respectively, requiring adjustments. The IT values increased with gestational age (correlation coefficient, r=0.491, P <0.0001). Inter-operator agreement was moderate (ICC=0.580 for automated and 0.546 for manual measurements), and intra-operator reproducibility was highest for automated measurements by the experienced operator (ICC=0.944). Agreement of the IT values between the manual and automated methods was high (ICC=0.950). CONCLUSIONS: Our results provide the reference range of IT in the Korean population. The Volume IT™ may be a reliable technique for measuring IT.