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Introduction: Invasive prenatal testing with chromosomal microarray analysis after first-trimester screening is a relevant option but there is still debate regarding the indications. Therefore, we evaluated the prevalence of numerical chromosomal aberrations detected by classic karyotype and clinically relevant copy number variants (CNVs) in prenatal samples using array comparative genomic hybridization (aCGH) stratified to NT thickness: 4.5 mm, and by the presence/absence of associated structural anomalies detected by ultrasonography. Materials and Methods: Retrospective cohort study carried out at two tertiary Polish centers for prenatal diagnosis (national healthcare system) in central and south regions from January 2018 to December 2021. A total of 1746 prenatal samples were received. Indications for invasive prenatal testing included high risk of Down syndrome in the first-trimester combined test (n = 1484) and advanced maternal age (n = 69), and, in 193 cases, other reasons, such as parental request, family history of congenital defects, and genetic mutation carrier, were given. DNA was extracted directly from amniotic fluid (n = 1582) cells and chorionic villus samples (n = 164), and examined with classic karyotype and aCGH. Results: Of the entire cohort of 1746 fetuses, classical karyotype revealed numerical chromosomal aberrations in 334 fetuses (19.1%), and aCGH detected CNV in 5% (n = 87). The frequency of numerical chromosomal aberrations increased with NT thickness from 5.9% for fetuses with NT < p95th to 43.3% for those with NT > 4.5 mm. The highest rate of numerical aberrations was observed in fetuses with NT > 4.5 mm having at least one structural anomaly (50.2%). CNVs stratified by NT thickness were detected in 2.9%, 2.9%, 3.5%, 4.3%, 12.2%, and 9.0% of fetuses with NT < 95th percentile, 95th percentile–2.9 mm, 3.0–3.4 mm, 3.5–3.9 mm, 4.0–4.5 mm, and >4.5 mm, respectively. After exclusion of fetuses with structural anomalies and numerical aberrations, aCGH revealed CNVs in 2.0% of fetuses with NT < 95th percentile, 1.5% with NTp95–2.9 mm, 1.3% with NT 3.0–3.4 mm, 5.4% with NT 3.5–3.9 mm, 19.0% with NT 4.0–4.5 mm, and 14.8% with NT > 4.5 mm. Conclusions: In conclusion, our study indicates that performing aCGH in samples referred to invasive prenatal testing after first-trimester screening provides additional clinically valuable information over conventional karyotyping, even in cases with normal NT and anatomy. [ABSTRACT FROM AUTHOR]

Objective: Our aim is to evaluate the role of the ratio of first-trimester CRL (crown rump length) measurement to NT (nuchal translucency) measurements in predicting early-onset fetal growth restriction (FGR) and to contribute to the existing literature. Methods: In the present case-control study, fetuses with early-onset FGR were compared with a gestational age-matched low-risk control group. This study was conducted in the perinatology clinic of Ankara Bilkent City Hospital between 2020 and 2023. Maternal age, gravidity, parity, crown-rump length (CRL), and nuchal translucency (NT) measurements were compared between pregnant women with early onset FGR (n=39) and pregnant women without FGR (n=50). Results: The mean age of pregnant women with FGR who participated in the study was 27.1±0.8, and the mean age of pregnant women without FGR was 26.3±0.6, and no statistically significant difference was found between the two groups (p=0.4)). Mean CRL was 54.98±1.08 mm in the group with FGR and 56.99±1.11 mm in the group without FGR; there was no significant difference between the two groups (p=0.2). The mean NT value was 1.11 ± 0.04 mm in the FGR group and 1.13 ± 0.02 mm in the without FGR group, there was no significant difference between the two groups (p=0.73). The mean CRL/NT ratio was 52.00±2.33 in the group with early onset FGR and 51.46±1.48 in the group without FGR and there was no statistically significant difference between the two groups (p=0.83). When the early developing FGR group is evaluated within itself, the mean gestational age at diagnosis was 31.7±0.3 weeks. The mean estimated fetal weight (EFW) percentile at diagnosis was 4.5±0.6 and AC percentile was 2.9±0.4. The mean umbilical artery systole/diastole ratio (UA-SD) was 2.9±0.16 and the mean umbilical artery pulsatility index (UA-PI) was 1.02±0.05. Conclusion: Crown-rump length to nuchal translucency ratio is not clinically useful to predict early-onset FGR. [ABSTRACT FROM AUTHOR]

Background: Since non-invasive prenatal testing (NIPT) in maternal blood became available, we evaluated which chromosome aberrations found in our cohort of fetuses with an enlarged NT in the first trimester of pregnancy (tested with SNP microarray) could be detected by NIPT as well. Method: 362 fetuses were referred for cytogenetic testing due to an enlarged NT (≥3.5 mm). Chromosome aberrations were investigated using QF-PCR, karyotyping and whole genome SNP array. Results: After invasive testing a chromosomal abnormality was detected in 137/362 (38 %) fetuses. 100/362 (28 %) cases concerned trisomy 21, 18 or 13, 25/362 (7 %) an aneuploidy of sex chromosomes and 3/362 (0.8 %) triploidy. In 6/362 (1.6 %) a pathogenic structural unbalanced chromosome aberration was seen and in 3/362 (0.8 %) a susceptibility locus for neurodevelopmental disorders was found. We estimated that in 2-10 % of fetuses with enlarged NT a chromosome aberration would be missed by current NIPT approaches. Conclusion: Based on our cohort of fetuses with enlarged NT we may conclude that NIPT, depending on the approach, will miss chromosome aberrations in a significant percentage of pregnancies. Moreover all abnormal NIPT results require confirmatory studies with invasive testing, which will delay definitive diagnosis in ca. 30 % of patients. These figures are important for pretest counseling enabling pregnant women to make informed choices on the prenatal test. Larger cohorts of fetuses with an enlarged NT should be investigated to assess the additional diagnostic value of high resolution array testing for this indication. [ABSTRACT FROM AUTHOR]

ABSTRACT Objectives To determine the effect of different ultrasound machine-probe combinations on nuchal translucency ( NT) measurements and to assess how this impacts on the accuracy of the NT-derived component of first-trimester screening for trisomy 21. Methods Sixteen different ultrasound machine-probe combinations were used for axial measurement of 2.0-, 3.0- and 4.0-mm spaced targets in an ultrasound phantom. Differences between the measured and known values were determined. The mean of the axial measurements was used to calculate adjusted risks for trisomy 21, given specific clinical scenarios. Results Differences observed using different machine-probe combinations for the 2.0-mm target ranged from 1.8-2.2 mm; for the 3.0-mm target, 2.7-3.2 mm; and for the 4-mm target, 3.7-4.3 mm, and exceeded those due to intraobserver variability. For a fetal crown-rump length of 50.0 mm and NT measurement of 2.0 mm, the maximum/minimum measurements in the fetus of a 40-year-old woman led to derived risks ranging from 1 in 32 ( NT, 2.2 mm) to 1 in 189 ( NT, 1.8 mm) and in the fetus of a 20-year-old with an NT of 3.0 mm these ranged from 1 in 102 ( NT, 3.2 mm) to 1 in 160 ( NT, 2.7 mm). Conclusions We have described the effect of machine-probe combinations on small but very precise ultrasound measurements. Such machine-probe combinations led to greater variability than those ascribed to intraobserver differences, and significantly affected the screening risk for the same fixed measurement. This finding has implications for Down syndrome screening algorithms and audit of ultrasound operators. Furthermore, most ultrasound machines are neither calibrated nor specified for measurements of tenths of a mm. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To study the outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency thickness (NT), with respect to fetal loss, structural defects and genetic syndromes with developmental delay, and to provide information that would be helpful for parental counseling on the residual risk of adverse outcome when ultrasound findings are normal. Methods: We reviewed the outcome of all pregnancies presenting at the Academic Medical Centre in Amsterdam with increased NT between January 1994 and March 2005. Fetal karyotyping and two-step ultrasound investigation at 13-18 and 20-24 weeks' gestation were offered in all cases. Particular attention was paid to the relationship between normal karyotype, ultrasound findings at the 20-24-week scan and subsequent pregnancy outcome. An adverse outcome was defined as miscarriage, intrauterine death, termination of pregnancy at parental request or the finding of one or more structural defects or genetic disorders. Results: A total of 675 fetuses with increased NT, known karyotype and known pregnancy outcome was analyzed. A chromosomal anomaly was detected in 224 (33%) fetuses. In 451 (67%) fetuses, the karyotype was normal. The overall incidence of an adverse pregnancy outcome in this group was 19% and, when analyzed according to the initial degree of increase in NT, the likelihood of an adverse outcome increased with increasing NT, ranging from 8% to 80%. 425 fetuses underwent a detailed second-trimester ultrasound scan. Anomalies were detected, at the time of ultrasound or after birth, in 54 (13%) of these fetuses (17 isolated cardiac defects, 14 other structural defects and 23 genetic disorders). An adverse pregnancy outcome was recorded in 4% of cases in which there were normal findings at the 20-week scan. Seven of these cases were classified as 'potentially amenable' to ultrasound detection. With exclusion of these cases, the chance of a healthy baby, if the 20-week scan was completely normal, was 98%. Genetic syndromes with dysmorphic features and neurodevelopmental delay occurred in seven (1.6%) of the fetuses with normal karyotype. In three of these pregnancies, non-specific suspicious ultrasound findings (nuchal edema, mild pyelectasis, pericardial effusion) were observed at the mid-trimester scan and in two others, subtle cardiac defects were detected after delivery. In the remaining two cases (0.5%) the mid-trimester scan was completely normal and no structural defects were observed after delivery. Conclusion: After exclusion of chromosomal anomalies, one out of five fetuses with increased NT has an adverse pregnancy outcome. The chance of an uneventful pregnancy outcome depends on the initial degree of increase in NT. However, if the detailed ultrasound examination at around 20 weeks is normal, a favorable outcome can be expected with confidence, irrespective of initially increased NT. [ABSTRACT FROM AUTHOR]