Fetal Nuchal Translucency Thickness Research Articles

The value of combined detailed first-trimester ultrasound-biochemical analysis for screening fetal aneuploidy in the era of non-invasive prenatal testing.

This study aimed to investigate the performance, cost-effectiveness and additional findings of combined detailed ultrasound and biochemical screening for risks of major fetal trisomies in the first-trimester. This is a retrospective analysis study, we estimated the risk of trisomies 21, 18 and 13 based on maternal age, fetal nuchal translucency thickness, nasal bone, ductus venosus pulsatility index velocity, tricuspid regurgitation, fetal heart rate, free beta-human chorionic gonadotropin, and pregnancy-associated plasma protein A in singleton pregnant women, and performed non-invasive prenatal testing for women with risks of trisomy 21 between 1:500 and 1:300. Invasive diagnostic testing was performed for women with positive or failed non-invasive prenatal testing result and in the high-risk group of this screening method. The direct costs were compared between this strategy and the non-invasive prenatal testing which alone used as first-line screening for all pregnant women. Among 25,155 singleton pregnant women who underwent screening, 24,361 were available for analysis, of these, 194 cases underwent non-invasive prenatal testing. Among the 24,361 women, 39, 19, and 7 had trisomies 21, 18 and 13, respectively. The use of this strategy could potentially detect approximately 94.87% of trisomy 21 cases, 100% of trisomy 18 cases, and 100% of trisomy 13 cases, with false-positive rates of 2.49%, 0.41%, and 0.49%, respectively. The overall detection rate and overall false-positive rates were 96.92% and 2.52%, respectively. The detection rate was 100% in the advanced age group and 94.12% in the general age group. Additionally, structural abnormalities were detected in 137 fetuses, and 44 fetuses had other chromosomal abnormalities. The total cost of this strategy was $3,730,843.30, and the cost per person tested was $153.15. The total cost of using non-invasive prenatal testing as the first-line strategy would be $6,813,387.04 and the cost per person tested was $279.68. Our strategy is an efficient and cost-effective approach for detecting major trisomies and identifying more fetuses with a potential abnormality. Therefore, this strategy is a valuable screening method and highly feasible in the clinical setting.

Are Fetal Nuchal Translucency Thickness and Crown-rump Length Associated with Maternal Hematological and Biochemical Profile?

Background: Nuchal translucency (NT) and crown-rump length (CRL) measurements are useful fetal screening tests. The extent to which maternal hematological and biochemical profiles may impact these markers has not been evaluated. This study is designed to address this issue. Methods: Data from the first-trimester screening for aneuploidy and maternal laboratory results, including maternal fasting blood sugar (FBS), thyroid stimulating hormone (TSH), hemoglobin, hematocrit, vitamin D3, and ferritin, were collected at 11 - 13 weeks of gestational age. The association between NT/CRL and maternal laboratory tests was analyzed and reported. Results: 258 women with a mean ± SD age of 32.6 ± 5.2 years participated in the study. NT and CRL values were not correlated with maternal laboratory variables. Otherwise, CRL was positively correlated with increasing maternal age, and NT was associated with increasing gestational age. Conclusions: The results of this study indicate that NT and CRL values at 11 - 13 weeks of gestation are independent of maternal hemoglobin, FBS, vitamin D3, and ferritin status.

Atypicality index: avoiding false reassurance in prenatal screening.

To demonstrate the application of the atypicality index as an adjunct to first-trimester risk assessment for major trisomies by the combined test. This was a study of 123 998 Danish women with a singleton pregnancy who underwent routine first-trimester screening, including risk assessment for major trisomies. An atypicality index, which is a measure of the degree to which a profile is atypical, was produced for measurements of fetal nuchal translucency thickness and maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein-A. The incidence of adverse pregnancy outcome, including miscarriage, intrauterine death and termination of pregnancy, was tabulated according to the screening result and atypicality index. In pregnancies with low risk and those with high risk for major trisomies according to the combined screening test, the incidence of adverse pregnancy outcome increased with increasing atypicality index. In pregnancies with a low risk for trisomies and atypicality index of ≥ 99%, the incidence of adverse outcome was 5.1 (95% CI, 3.4-7.6) times higher compared with that in low-risk pregnancies with a typical measurement profile, reflected by an atypicality index of < 80%. Similarly, in high-risk pregnancies, the incidence of adverse outcome was 7.9 (95% CI, 4.4-14.5) times higher in those with an atypicality index of ≥ 99% compared to those with an atypicality index of < 80%. Using individual profile plots, we were able to demonstrate a transparent and intuitive method for visualization of multiple variables, which can help interpret the individual combination of measurements and level of atypicality. In pregnancies undergoing first-trimester combined screening and classified as being at low risk for major trisomies, profiles that are typical of pregnancies with normal outcome provide additional reassurance, whereas those with an atypical profile may warrant further investigation. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Sonographic Dimension of Fetal Nuchal Translucency in Kano Metropolis: A single Center Study

Background: Nuchal Translucency Thickness (NTT) is a hypo-echoic region of subcutaneous fluid accumulation in the posterior neck region at the level of the cervical spine between the skin and soft tissues and is mostly found at 11–13 weeks of fetal gestation. It is visualised with a mid-sagittal ultrasound view of the fetus in a neutral position. The NTT provides a risk assessment for chromosomal abnormalities which has been used as a marker of possible fetal abnormalities. Hence, the justification to conduct the present study.&#x0D; Aim: To establish the mean fetal nuchal translucency thickness with corresponding gestational age (GA) and to assess the correlation between Crown Rump Length (CRL), GA, and NTT among apparently healthy pregnant women.&#x0D; Methods: A cross-sectional study was conducted among 150 apparently normal consenting pregnant women in their late first trimester in the Radiology department of Muhammad Abdullahi Wase Teaching Hospital, Kano from February 2021 to May 2021. Ultrasonographic measurements of the crown-rump length (CRL), gestational age (GA), and NTT were performed on pregnancies within 11 to 13 weeks of gestation. Their 2.5th, 25th, median and 97.5th percentiles of the NTT, GA, and CRL were determined using SPSS version 23 (IBM, 2017). Indicate correlation… as part of the analysis.&#x0D; Results: Median NTT at 11-13+6 weeks of gestation was found as 3.0±0.10mm. The NT thickness increased with increasing CRL and gestational week in the first trimester. The correlation coefficient between NTT and CRL as well as GA were 0.472 and 0.451, respectively.&#x0D; Conclusion: The overall mean NTT in Kano fetuses was determined. These should be useful for first-trimester screening in ruling out potential fetal chromosomal abnormalities in Kano, Nigeria.

Role of Ultrasound in Early Detection of Molar Pregnancy

OBJECTIVES The objective of this study was to investigate the role of ultrasound in the detection of early pregnancies presenting with placental molar changes. METHODOLOGY This retrospective study was carried out at Radiology department of Hayatabad Medical Complex, Peshawar, between Aug 2020 and July 2021. All cases suspected of molar changes were evaluated from 10-14 weeks of gestation. The patient were referred to our department because of fetal abnormality, maternal disease or age and family or previous pregnancy history or were identified from an ongoing ultrasound screening study for aneuploidy by measurement of fetal nuchal translucency thickness. Transabdominal or transvaginal sonography was used to examine the fetus and placenta. RESULTS Total 85 patients of molar pregnancies were enrolled in the study. Age ranged between 20-45 years with a mean age of 32.5 years. There were 60(70.6%) complete moles (CM) and 25(27.4%) partial moles (PM) were suspected on ultrasound. In case of complete mole coexisting with a normal singleton or twin pregnancy, the molar placenta was clearly separated from the normal placenta, whereas with partial moles the molar structures were dispersed inside the placental mass. CONCLUSION Ultrasound detection of molar pregnancy remains a diagnostic challenge. Data suggest that there has been an increase in both the predictive value and the sensitivity of ultrasound over time; however, the diagnostic criteria remain ill defined. Prior to managing a miscarriage, being aware of the possibility of molar pregnancy will guide treatment and allow for adequate follow-up.

Genome-Wide Copy Number Variant and High-Throughput Transcriptomics Analyses of Placental Tissues Underscore Persisting Child Susceptibility in At-Risk Pregnancies Cleared in Standard Genetic Testing.

Several studies have shown that children from pregnancies with estimated first-trimester risk based on fetal nuchal translucency thickness and abnormal maternal serum pregnancy protein and hormone levels maintain a higher likelihood of adverse outcomes, even if initial testing for known genetic conditions is negative. We used the Finnish InTraUterine cohort (ITU), which is a comprehensively characterized perinatal cohort consisting of 943 mothers and their babies followed throughout pregnancy and 18 months postnatally, including mothers shortlisted for prenatal genetic testing but cleared for major aneuploidies (cases: n = 544, 57.7%) and control pregnancies (n = 399, 42.3%). Using genome-wide genotyping and RNA sequencing of first-trimester and term placental tissue, combined with medical information from registry data and maternal self-report data, we investigated potential negative medical outcomes and genetic susceptibility to disease and their correlates in placenta gene expression. Case mothers did not present with higher levels of depression, perceived stress, or anxiety during pregnancy. Case children were significantly diagnosed more often with congenital malformations of the circulatory system (4.12 (95% CI [1.22–13.93]) higher hazard) and presented with significantly more copy number duplications as compared to controls (burden analysis, based on all copy number variants (CNVs) with at most 10% frequency, 823 called duplications in 297 cases versus 626 called duplications in 277 controls, p = 0.01). Fifteen genes showed differential gene expression (FDR < 0.1) in association with congenital malformations in first-trimester but not term placenta. These were significantly enriched for genes associated with placental dysfunction. In spite of normal routine follow-up prenatal testing results in early pregnancy, case children presented with an increased likelihood of negative outcomes, which should prompt vigilance in follow-up during pregnancy and after birth.

Observation on the Effect of Fetal Nuchal Translucency Thickness and Mid-pregnancy Four-dimensional Color Doppler Ultrasound in the Diagnosis of Fetal Malformation

Observation on the Effect of Fetal Nuchal Translucency Thickness and Mid-pregnancy Four-dimensional Color Doppler Ultrasound in the Diagnosis of Fetal Malformation

Reappraising the Value of Fetal First-Trimester Ultrasonography

Abstract In the last few years, the introduction of cell-free DNA has rapidly altered prenatal screening regimens and is increasingly offered as the second- or, at times, even the first-tier screening test. Should an early anomaly scan also be part of an up-to-date screening policy? This paper reappraises the value of fetal first-trimester ultrasonography. The primary aims of the first-trimester scan are to establish gestational age based on the measurement of fetal crown-rump length, to detect multiple pregnancy and chorionicity, and to measure fetal nuchal translucency thickness as part of a combined screening test for chromosomal abnormalities. With recent advancements in ultrasound technology, there is compelling evidence that a majority of fetuses with major structural abnormalities and almost half of them without chromosomal abnormalities can be detected in the first trimester. We focused on the first-trimester screening of fetal major defects, especially including fetal congenital heart disease and cleft lip and palate by ultrasound markers and views. Moreover, it is critical to highlight that after a detailed anomaly scan in the first trimester without major structural anomalies and positive genetic tests, the residual chance of favorable outcome in fetuses with isolated increased nuchal translucency is relatively high. The discussion on the role of cell-free DNA in prenatal screening is still ongoing. Even in the event of it becoming a first-line screening test for aneuploidies, the importance of a first-trimester fetal scan, including assessment of markers for other anomalies, remains undisputed.

Relation Between Increased Fetal Nuchal Translucency Thickness and Chromosomal Defects in Northern Vietnam.

ObjectiveTo examine the prevalence of all chromosomal defects amongst fetuses with increased nuchal translucency thickness (NT).MethodsThis is a retrospective study amongst pregnant women indicated for amniocentesis by nuchal translucency above 3.0 mm and consent to the study. A total of 2,720 cases were recruited during the six-year period from 2015 to 2020. All singleton pregnancies were offered fetal karyotype when the fetal nuchal translucency was ≥2.5 mm. The prevalence of chromosomal defects was divided into five NT categories: 2.5-3.4 mm, 3.5-4.4 mm, 4.5-5.4 mm, 5.5-6.4 mm, ≥6.5 mm.ResultsThe study identified 2,720 amniocentesis for increased NT. The mean maternal age was 29.19 (range 17-46) years, and the mean fetal crown-rump length was 66.9 (range 45-84) mm. The fetal karyotype was abnormal in 560 (20.6%) participants. The most frequent chromosomal disorders were trisomy 21 (55%), trisomy 18 (11.2%), trisomy 13 (3.9%), 45,XO (2.7%). The prevalence of chromosomal aberrations was ranged from 17.9% (NT between 2.5-3.4 mm) to 29.7% (NT≥6.5 mm). A majority of fetuses with trisomy 13, 18, or 21 has NT measurement lower than 5.5 mm. In those with Turner syndrome, there was no difference between the group with NT <5.5 mm and the group with NT ≥5.5 mm. Increased maternal age is a risk factor for chromosomal aberrations with the rate increased from 17.6% at the youngest maternal age of 30-34 to 34% at maternal age of 35-39 and to 50% at maternal age of ≥40.ConclusionIn fetuses with increased NT, more than a half of the chromosomal abnormalities were affected by defects other than trisomy 21. The distribution of NT was different between Turner syndrome and trisomy 13, 18, 21 syndromes. Women aged 35 years or older had a higher risk of chromosomal aberrations.

VP30.11: Relation between increased fetal nuchal translucency thickness and chromosomal defects in north of Vietnam

VP30.11: Relation between increased fetal nuchal translucency thickness and chromosomal defects in north of Vietnam

Application of an individualized nomogram in first-trimester screening for trisomy 21.

ABSTRACTObjectivesTo develop and validate a nomogram based on fetal nuchal translucency thickness (NT) and ultrasonographic facial markers for screening for trisomy 21 in the first trimester of pregnancy.MethodsThis was a retrospective case–control study using stored two‐dimensional midsagittal fetal profile images captured at 11 + 0 to 13 + 6 weeks' gestation in singleton pregnancies. We included images from 302 trisomy‐21 pregnancies and 322 euploid pregnancies. Cases were divided into a training set (200 euploid + 200 with trisomy 21) and a validation set (122 euploid + 102 with trisomy 21) at a ratio of approximately 2:1. For each, the maternal age, gestational age, fetal NT and karyotype were noted, and 12 ultrasonographic fetal facial markers were measured. The least absolute shrinkage and selection operator (LASSO) method and multivariable analysis were used to select automatically the discriminative markers. Logistic regression was used to develop a LASSO model, based on the selected markers, to screen for trisomy 21 in the first trimester of pregnancy. Furthermore, 60 of the 624 images were selected randomly as a retest set to evaluate the model's robustness. The predictive performance of screening for trisomy 21 of a model based on fetal NT and maternal age and of the LASSO model was assessed using the area under the receiver‐operating‐characteristics curve (AUC). A nomogram was developed as an individualized tool to predict patient‐specific probability for trisomy 21, which is a more visual presentation of the LASSO model. The performance of the nomogram was assessed using the C‐index and calibration curve.ResultsInto the LASSO model were incorporated eight markers, including fetal NT, prenasal‐thickness‐to‐nasal‐bone‐length ratio, facial profile line, frontomaxillary facial angle, frontonasal facial angle, mandibulomaxillary facial angle, maxilla‐nasion‐mandible angle and d2 (distance between the anterior edge of the prefrontal skin and the mandibulomaxillary line) (all P < 0.05). The AUCs of the LASSO model for screening for trisomy 21 were 0.983 (95% CI, 0.971–0.994) in the training set and 0.979 (95% CI, 0.966–0.993) in the validation set, and these were higher than the AUCs of all eight individual ultrasonographic markers included in the model. The AUC of the LASSO model in the retest set was 0.997 (95% CI, 0.990–1.000), indicating good robustness of the LASSO model. The AUC of the LASSO model was significantly higher than that of the model based on fetal NT and maternal age in both training and validation sets (P < 0.001 for both). The nomogram of the LASSO model showed good discrimination of trisomy 21, with C‐indices of 0.983 in the training set and 0.981 in the validation set.ConclusionsWe present an individualized nomogram which incorporates fetal NT and a series of ultrasonographic facial profile markers selected by the LASSO method and multivariable analysis. This nomogram can potentially be utilized as a convenient and effective tool in screening for trisomy 21 in the first trimester of pregnancy. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Fetal loss after chorionic villus sampling in twin pregnancy.

To estimate the chorionic villus sampling (CVS)-related risk of fetal loss in twin pregnancy after adjustment for chorionicity, nuchal translucency thickness (NT), intertwin discordance in crown-rump length (CRL), maternal demographic characteristics and serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (β-hCG). This was a multicenter study from eight fetal medicine units in which the leadership were trained at the Harris Birthright Research Centre for Fetal Medicine in London, UK, and in which the protocols for screening, invasive testing and pregnancy management are similar. Data were obtained prospectively from women with twin pregnancy undergoing routine ultrasound examination at 11-13 weeks' gestation. Multivariable logistic regression analysis with backward stepwise elimination was used to examine whether CVS provided a significant independent contribution to the prediction of risk of fetal loss after adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free β-hCG and PAPP-A multiples of the median. Similarly, within the CVS group, multivariable logistic regression analysis was used to investigate the effect of the number of intrauterine needle insertions and size of the needle on the risk of fetal loss. The study population of 8581 twin pregnancies undergoing ultrasound examination at 11-13 weeks' gestation included 316 dichorionic and 129 monochorionic twins that had CVS. First, in twin pregnancies undergoing CVS, compared to those not undergoing CVS, there was a 2-fold increased risk of fetal loss at < 24 weeks' gestation and of loss at any stage in pregnancy. Second, the factors providing a significant independent contribution to the prediction of miscarriage or fetal loss in twin pregnancy were increased maternal weight, black racial origin, monochorionicity, and more so monoamnionicity, large intertwin discordance in CRL and increased fetal NT, and, in the case of fetal loss at any stage, there was also a contribution from assisted conception and low serum PAPP-A. Third, after adjustment for maternal and pregnancy characteristics, CVS did not provide a significant contribution to the risk of fetal loss. Fourth, in twin pregnancies that had CVS, there was no significant contribution to fetal loss from the number of intrauterine needle insertions or needle size. The 2-fold increased risk of fetal loss following CVS in twin pregnancy can, to a great extent, be explained by maternal and pregnancy characteristics rather than the invasive procedure itself. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Neurodevelopmental outcome at 2 years of corrected age in fetuses with increased nuchal translucency thickness and normal karyotype compared with matched controls.

ABSTRACTObjectivesIncreased nuchal translucency (NT) thickness is an antenatal marker of aneuploidy or malformation that can lead to termination of pregnancy. This study assessed the long‐term neurodevelopmental prognosis of infants who had isolated increased NT in utero.MethodsThis was a prospective cohort study of infants with a NT thickness > 95th percentile in the first trimester, but with a normal karyotype and no major anomalies, and controls with normal NT matched for birth weight, Apgar score, place of birth, parity and gestational age at birth. At 2 years of corrected age, all infants underwent the psychometric Brunet–Lézine test to evaluate their developmental quotient (DQ), overall (global) and specifically for the areas of posture, language, coordination and sociability.ResultsA total of 203 chromosomally normal infants were included in the increased‐NT group and 208 in the control group. The mean global DQ was significantly lower in the increased‐NT group than in the control group (108.6 ± 9.7 vs 112.8 ± 8.3; P < 0.0001), but it was within the normal range expected for that age in both groups. Similarly, the mean DQs for coordination, sociability and language, but not for posture, were significantly lower in infants with increased NT than in controls. Only one case with increased NT had a DQ < 70 (defined as severe neurodevelopmental impairment), compared with none in the control group. The difference between the two groups remained significant for a NT threshold ≥ 99th percentile and when the data were adjusted for NT thickness, the infant's sex and the mother's educational level. In the increased‐NT group, NT thickness was < 3.5 mm in over half (56%) of the infants, between 3.5 mm and 5 mm in 33% and > 5 mm in 11%, with a mean global DQ of 108.4, 110.1 and 109.7, respectively.ConclusionsInfants who had isolated increased fetal NT in the first trimester had a significantly lower, but normal, DQ at a corrected age of 2 years, when compared with controls. The findings were independent of the infant's sex, fetal NT thickness and the mother's educational level. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Distribution of nuchal translucency thickness at 11 to 14 weeks of gestation in a normal Turkish population

Background/aimThe aim of this study was to determine fetal nuchal translucency (NT) thickness nomogram values in first trimester in a Turkish population and compare them with previously reported European and Asian nomogram data.Material and methodsUltrasonographic measurements of crown-rump length (CRL) and NT thicknesses were obtained from 11 to 14 weeks of gestation in a normal Turkish population. Pregnant women with singleton pregnancy and fetal CRL between 45 and 84 mm were included in the study. The mean 1st, 3rd, 5th, 50th, 90th, 95th, 97th, and 99th percentiles and fixed cut off values of ≥ 2.5 mm, ≥ 3 mm, ≥ 3.5 mm NT thicknesses for a CRL between 45 and 84 mm were determined.ResultsA total of 1605 healthy fetuses were enrolled in the study. The sonographic measurements were performed on 1541 (%94) fetuses transabdominally and on 99 cases (%4) by the transvaginal route. The mean NT thickness for CRL between 45 and 84 mm was 1.57 ± 074 mm, and the mean 95th, 97th, and 99th percentiles of these values were 2.82 mm, 3.17, and 4.75 mm, respectively. The incidence of NT thicknesses at fixed points of ≥ 2.5 mm, ≥ 3 mm, and ≥ 3.5 mm in normal fetuses were 6.7%, 4.1%, and 2.1%, respectively.ConclusionThe present study demonstrated the nomogram data of fetal NT thickness in a Turkish population. We think that this report will be useful for further research related to NT thickness values on the prenatal diagnosis for the first trimester chromosomal abnormalities in Turkish populations.

The effect of maternal alcohol and drug abuse on first trimester screening analytes: a retrospective cohort study

BackgroundThe purpose of this study was to determine whether first trimester trisomy screening (FTS) parameters are affected by alcohol and drug use.MethodsA routine combined FTS including measurements of maternal serum levels of free β-human chorionic gonadotropin subunit (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) were measured at 9–11 weeks of gestation, and fetal nuchal translucency thickness (NTT) at 11–13 weeks of gestation. In total 544 women with singleton pregnancies [71 alcohol and drug abusers, 88 smokers, 168 non-smokers delivering a small for gestational age (SGA) child, and 217 unexposed control women] were assessed.ResultsFree β-hCG levels were higher in alcohol and drug abusing than in unexposed pregnant women [mean 1.5 vs. 1.2 multiples of medians (MoM); P = 0.013]. However, stepwise multiple linear regression analyses suggested that smoking could explain increased free β-hCG. Additionally, we observed lower PAPP-A levels in the smoking mothers (0.9 vs. 1.2 MoM; P = 0.045) and in those giving birth to an SGA child compared to the controls (1.1 vs.. 1.2 MoM; P < 0.001). Fetal NTT did not differ significantly between any of the groups.ConclusionsThe present study shows increased free β-hCG levels in alcohol and drug abusers, but maternal smoking may explain the result. Maternal serum PAPP-A levels were lower in smoking than non-smoking mothers, and in mothers delivering an SGA child. However, FTS parameters (PAPP-A, free β-hCG and NTT) seem not to be applicable for the use as alcohol biomarkers because of their clear overlap between alcohol abusers and healthy controls.

Analysis of copy number variation by sequencing in fetuses with nuchal translucency thickening.

ObjectiveCopy number variation sequencing (CNV‐seq) technique was used to analyze the genetic etiology of fetuses with increased nuchal translucency (NT).MethodsA total of 139 women with gestational 11‐14 weeks whose fetuses were detected with increased NT (NT ≥ 2.5 mm) in our hospital from July 2016 to December 2018 were selected. Fetal specimens were performed for karyotyping analysis and CNV sequencing.ResultsAccording to the nuchal translucency thickness, 2.5‐3.4, 3.5‐4.4, 4.5‐5.4, and more than 5.5 mm, the rates of chromosomal abnormalities were 22.8% (13/57), 30.8% (12/39), 42.1% (8/19), and 62.5% (15/24), respectively. There was significant difference among the incidences of chromosomal abnormalities in four groups (χ2 = 37.69, P < .01) and the incidences increased with fetal NT thickness. Among 139 cases, there were 36 cases (25.9%) with abnormal chromosome karyotypes. Meanwhile, there were 45 cases (32.3%) with abnormal CNV. In the 12 cases with abnormal CNV and normal chromosome karyotypes, there were 2 cases of pathogenic CNV, 7 cases of CNV with unknown clinical significance, and 3 cases of possibly benign CNV. There was no significant difference in CNV between pregnant women in advanced maternal age and those in normal maternal age (χ2 = 1.389, P = .239). In the fetus who showed abnormalities in NT and ultrasonography (χ2 = 5.13, P < .05) and the fetus aborted (χ2 = 113.19, P < .05), the abnormal rate of CNV was higher with statistically significant difference.ConclusionCNV‐seq combined karyotype analysis should be performed simultaneously in fetuses with increased NT, providing a basis for genetic counseling, which is of great significance for prenatal diagnosis.

First-trimester screening for trisomies in pregnancies with vanishing twin.

To examine multiples of the median (MoM) values of serum free beta-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) in a large series of pregnancies with a vanishing twin, determine the association of these values with the interval between embryonic death and blood sampling, and develop a model that would allow incorporation of these metabolites in first-trimester combined screening for trisomy. This was a retrospective study comparing maternal serum free β-hCG and PAPP-A levels at 11-13 weeks' gestation in 528 dichorionic pregnancies with a vanishing twin, including 194 (36.7%) with an empty gestational sac and 334 (63.3%) with a dead embryo, with those in 5280 normal singleton pregnancies matched for method of conception and date of examination. In vanishing-twin pregnancies with a dead embryo, marker levels were examined in relation to the estimated time between embryonic death and maternal blood sampling. First, in pregnancies with a vanishing twin, median free β-hCG MoM was not significantly different from that in normal singleton pregnancies (1.000; 95% CI, 0.985-1.016 vs 0.995; 95% CI, 0.948-1.044; P = 0.849). Second, PAPP-A MoM was higher in vanishing-twin pregnancies than in normal singleton pregnancies (1.000; 95% CI, 0.985-1.015), both in the group with an empty gestational sac (1.165; 95% CI, 1.080-1.256; P = 0.0001) and in that with a dead embryo (1.175; 95% CI, 1.105-1.249; P < 0.0001). Third, in vanishing-twin pregnancies with a dead embryo, PAPP-A MoM was related inversely to the interval between estimated gestational age at embryonic demise and blood sampling (P < 0.0001). Fourth, in first-trimester screening for trisomy 21 in singleton pregnancies, the estimated detection rate, at a 5% false-positive rate, was 82% in screening by a combination of maternal age and fetal nuchal translucency thickness, and this increased to 86% with the addition of serum free β-hCG and to 91% with the addition of serum PAPP-A. Fifth, similar performance of screening can be achieved in pregnancies with a vanishing twin, provided the appropriate adjustments are made to the level of PAPP-A for the interval between estimated gestational age at embryonic demise and blood sampling. First-trimester screening for trisomy in pregnancies with a vanishing twin should rely on a combination of maternal age, fetal nuchal translucency thickness and serum free β-hCG, as in singleton pregnancy, without the use of serum PAPP-A. Alternatively, PAPP-A can be included but only after appropriate adjustment for the interval between estimated gestational age at fetal demise and blood sampling. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Prenatal diagnosis of maternal partial trisomy 9p23p24.3 and 14q11.2q21.3 in a fetus: a case report

ObjectiveThis study aimed to report a fetus with maternal partial trisomy 9p and 14q and the phenotype detected in ultrasound.MethodsThe chromosome rearrangements in the fetus were characterized by G-banding and chromosome microarray analysis based on single nucleotide polymorphism (SNP) array of cultured amniocytes and compared with the parents’ karyotypes.ResultsThe fetal abnormal karyotype was 47,XY,+der(14)(9;14)(p23;q22). The SNP array revealed a duplicate 11.8-Mb 9p23-p24.3 fragment and a duplicate 29.6-Mb 14q11.2-q21.3 fragment. The peripheral blood karyotype of the mother was 46,XX,t(9;14)(p23;q22), while the father’s was normal at the level of 300~400 bands. A high-resolution karyotype analysis conformed the same abnormality of the mother at the level of 550~650 bands. These results indicated that the fetal chromosomal abnormality probably derived from the mother. The fetal nuchal translucency thickness was 3.5 mm, and the fetal heart was detected with around 1.0-mm ventricular defect by the ultrasound examination at 12-week gestation. The couple decided to terminate the pregnancy. They opted for in vitro fertilization and embryo transfer for the fourth pregnancy, which was successful.ConclusionsThe SNP array combined with cytogenetic analysis was particularly effective in identifying abnormal chromosomal rearrangements. These methods combined with the existing database information and fetal ultrasonography might provide a comprehensive and efficient way for the prenatal assessment of fetal situations. Preimplantation genetic diagnosis might effectively assist those women with an adverse pregnancy history in their next pregnancy.

Routine First-Trimester Screening for Fetal Trisomies in Twin Pregnancy: Cell-free DNA Test Contingent on Results From Combined Test

(Abstracted from Ultrasound Obstet Gynecol 2019;53(2):208–213) In singleton pregnancies, screening for the major trisomies using a combination of fetal nuchal translucency (NT) thickness, serum β-human chorionic gonadotropin, and pregnancy-associated plasma protein A can detect approximately 90% of cases of trisomy 13, 18, or 21, at a false-positive rate of 5%. In twin pregnancies, use of the combined test can achieve a similar detection rate (DR) for trisomy 21, but with a higher false-positive rate of about 6%.

First trimester combined screening in patients with systemic lupus erythematosus: impact of pre-analytical variables on risk assessment

BackgroundPrenatal diagnosis of fetal trisomy 21 and other chromosomal abnormalities is based on invasive tests, such as amniocentesis and chorionic villus sampling, which are carried out in women identified through screening as being at high risk for these abnormalities. The most widely used method of screening is the first-trimester combined test which utilizes maternal age, and measurements of fetal nuchal translucency thickness (NT) and maternal serum pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (hCG).ObjectivesTo assess the influence of SLE on the levels of NT, PAPP-A, and β-hCG and whether any alterations in such levels may increase the rate of false positives and the subsequent number of invasive tests.MethodThis was a prospective first-trimester screening study for trisomies 21, 18, and 13 by a combination of maternal age, fetal nuchal translucency thickness, and serum PAPP-A and β-hCG at King’s College Hospital, London, between March 2006 and February 2011. The study population included 47 cases with maternal SLE and 45,493 without SLE. The results of biomarkers in the SLE and non-SLE groups were compared.ResultsIn the SLE group, compared to the non-SLE group, there were no significant differences in median maternal age, fetal NT, or serum PAPP-A MoM, but serum free β-hCG MoM was increased (1.402, IQR 0.872–2.290 vs 0.994, IQR 0.676–1.508).ConclusionIn first trimester screening for trisomies, the measured value of free ß-hCG should be adjusted for maternal SLE to avoid false positive results and overuse of invasive tests.