Early diagnosis of major cardiac defects in chromosomally normal fetuses with increased nuchal translucency

Objective To determine the value of early ultrasound examination for prenatal diagnosis of cardiac defects in chromosomally normal fetuses with increased nuchal translucency thickness at 10–14 weeks of gestation.
Design Prospective audit. Setting Fetal Medicine Centre.
Methods Specialist fetal echocardiography was carried out in 398 chromosomally normal fetuses with a nuchal translucency measurement above the 99th centile (2 3.5 mm). In the first 75 pregnancies the cardiac scan was carried out at 17–22 weeks and the next 323 cases had one scan at 13–17 weeks and another at 20–22 weeks. Pregnancy outcome was obtained in all of the cases.
Results Major cardiac defects were present in 29 (7.3% of 398) cases and in 28 of these the diagnosis was made by antenatal echocardiography. In 27 of the 29 fetuses with major cardiac defects echocardiography was carried out at 13–17 weeks and an abnormality was suspected in 24 of the cases (88%).
Conclusions Increased nuchal translucency in chromosomally normal fetuses is associated with an increased prevalence of major cardiac defects and, as such, is an indication for specialist fetal echocardiography. Most of the cardiac abnormalities are detectable on antenatal fetal echocardiography and many can be excluded by early scanning.     

Outcome of fetuses with increased nuchal translucency

Recent reports on nuchal translucency screening in unselected patient populations show results that are comparable with those reported by the thus far largest series on screening for Down's syndrome based on maternal age and nuchal translucency measurement. Much interest is focused on the prognostic value of increased nuchal translucency in fetuses with normal chromosomes. Increased nuchal translucency is regarded as a clear sign of declining fetal health, which can be associated with fetal demise, structural anomalies, rare genetic syndromes, and in particular congenital heart defects. A clear association is demonstrated between nuchal translucency above the 99th centile and congenital cardiac defects. Such a finding should prompt specialized echocardiography. However, on the whole the sensitivity of nuchal translucency screening is too low to consider this as the sole criterion to screen for critical heart defects.     

Pregnancy outcome in fetuses with increased nuchal translucency and normal karyotype

OBJECTIVE: This study was conducted to evaluate pregnancy outcome and mid- and long-term prognosis of cases with nuchal translucency > or =4 mm and normal karyotype. METHODS: Retrospective analysis of 160 cases who presented with a nuchal translucency > or =4 mm when the CRL was between 45 and 84 mm was undertaken. Cystic hygromas were excluded. When the karyotype was normal a detailed anomaly scan was performed at 20 to 24 weeks followed by serial ultrasound examination. Clinical examination of the neonates was performed by a paediatrician. Long-term follow-up was completed through a questionnaire filled in by parents, GPs and paediatricians. RESULTS: 160 fetuses had an NT > or =4 mm. 44.3% had an abnormal karyotype. Of the 55.7% with normal karyotypes, 74 % did not show any abnormalities on follow-up ultrasound scan. Mid- and long-term outcome was known in 91% of the cases. 6.4% had a malformation diagnosed only at birth. Among the normal neonates, 11.1% are considered to have a significant neurological handicap or orthopaedic problems at 12 to 72 months of age. CONCLUSION: In an unselected population, NT > or =4 mm is associated with a high incidence of chromosomal and non chromosomal abnormalities. Even when the fetal karyotype and serial ultrasound examinations are considered to be normal, the risk of fetal malformation and developmental delay should not be underestimated.     

Pregnancy outcome in fetuses with increased nuchal translucency.

OBJECTIVE: The aim of this study was to examine fetal and neonatal outcomes in the setting of nuchal translucency (NT) > or =3 mm at routine first-trimester screening. STUDY DESIGN: A nested case-series study within a retrospective cohort of women screened for Down syndrome at 11-14 weeks of gestation. Crown-rump length, NT values and additional anomalies at first and early second trimesters were recorded. Follow-up information was obtained by a review of medical records and self-report from patients. Adverse outcomes included fetal death and termination of pregnancy due to structural or chromosomal anomalies. RESULT: A total of 1930 pregnant women were screened between 11 and 14 weeks of gestation. The prevalence of increased fetal NT (> or =3 mm) was 1.4% (n=27). Among these, 12 showed increased fetal NT as an isolated finding. In this group, 2 women experienced fetal demise (16%) and 10 delivered healthy babies. In the group with additional abnormalities (n=15), 9 (60%) were found to have chromosomal abnormalities, all of which were terminated. For all cases with increased fetal NT, total incidence of adverse outcome was 62%. CONCLUSION: At first-trimester ultrasonography, a fetal NT > or =3 mm was associated with a high incidence of chromosomal abnormalities in the presence of associated abnormalities. For cases with the increased fetal NT at first-trimester fetal assessment and follow-up is necessary to detect possible adverse outcomes.     

Submicroscopic chromosomal abnormalities in fetuses with increased nuchal translucency and normal karyotype

Objective: To investigate the submicroscopic chromosomal abnormalities in fetuses with increased nuchal translucency (NT) and normal karyotype.

Methods: Total of 296 fetuses with increased NT (≥3.0?mm) were tested by conventional karyotyping. When cytogenetic analysis showed normal chromosome, the pregnancies were then consulted for array-comparative genomic hybridization (CGH) analysis and received subsequent morphology scan between 20 and 24 weeks gestation. Submicroscopic chromosomal abnormalities were assessed and compared between the fetuses with and without structural defects.

Results: Chromosomal abnormality was identified in 19.9% (59/296) fetuses. Two hundred and twenty samples were tested by array CGH. Submicroscopic chromosomal abnormalities were detected in 9.1% (20/220) fetuses. For the fetuses with abnormal morphology scan, the detection rate of submicroscopic chromosomal abnormalities was higher than those with normal morphology scan (26.9% versus 6.7%, p?Conclusions: Submicroscopic chromosomal abnormalities should be accessed when the fetus was found to be with increased NT and normal karyotype, especially when the structural defects were found at second or third trimester.     

Male-to-female gender ratio in fetuses with increased nuchal translucency

Objective: To describe gender distribution in fetuses with increased nuchal translucency (NT) measurements. Methods: All fetuses with mild (2.5–2.9?mm) and moderate (3.0–3.5?mm) NT enlargement at 12.0–12.6 weeks gestation were studied. The Z test for proportions was used to compare the gender distribution of this study group to that of all babies born at Roosevelt Hospital in 2008, and to compare the gender distributions of the subgroups. Results: 5109 patients received screening at 12.0–12.6 weeks gestation. 44 fetuses had mild and 28 had moderate enlargement, with a male-to-female ratio of 3.8:1.0, much higher than the 1.06:1.0 ratio among total births at Roosevelt Hospital in 2008 (p < 0.0001). Male-to-female ratio was 7.8:1.0 in fetuses with mild and 1.8:1.0 with moderate NT enlargement (p = 0.03). Among fetuses with mild NT enlargement, 3 males had aneuploidy; among those with moderate enlargement, 6 fetuses had aneuploidy, 3 males and 3 females. Seven pregnancies with aneuploidy were voluntarily terminated. All pregnancies carried to term were healthy. Conclusions: More males than females had mild NT enlargement on first-trimester screening, but unless aneuploidy was detected they had normal birth outcomes. A slightly larger NT may be normal in males, while indicating possible fetal abnormalities in females.     

Pregnancy outcome and prognosis in fetuses with increased first-trimester nuchal translucency.

OBJECTIVE: One of the concerns of prenatal diagnosis is to find sensitive markers to screen for chromosome abnormalities, such as serum assays or nuchal translucency (NT). This study reports our experience with NT measurement during the first trimester of pregnancy. MATERIALS: The study was performed prospectively on 252 fetuses with either NT > or =3 mm or cystic hygroma. RESULTS: We observed 50 abnormal karyotypes, i.e. 19.8%. The incidence of chromosome abnormalities increased with increasing maternal age and increasing NT thickness. For the 202 fetuses with normal karyotypes, outcome was unfavourable in 32 cases: 23 elective terminations of pregnancy, 8 spontaneous abortions and 1 neonatal death. Outcome was favourable in 141 cases. Twenty-nine pregnancies were lost to follow-up. CONCLUSION: Measurement of NT at 12 weeks' gestation seems to be a good marker for chromosome abnormalities. When the karyotype is normal, the pregnancy outcome remains correlated with the degree of NT thickness. The finding of NT >3 mm between 10 and 14 weeks' gestation dictates rigorous ultrasound monitoring and caution when predicting pregnancy outcome.     

Fetal cardiac defects and increased nuchal translucency thickness: a prospective study

OBJECTIVE: The purpose of this study was to examine prospectively the association between increased nuchal translucency thickness and major cardiac defects in chromosomally normal fetuses. STUDY DESIGN: A prospective cohort study of 263 chromosomally normal fetuses with an increased nuchal translucency thickness at 11 to 14 weeks of gestation at a tertiary referral center was performed. The incidence of major cardiac defects was examined in relation to the fetal nuchal translucency thickness at the 11 to 14 week ultrasound examination. RESULTS: The nuchal translucency thickness measurements ranged from 2.2 to 8.0 mm (median, 3.1 mm). There were 13 cases of major cardiac defects in this cohort, which gave a prevalence of 49.4 of every 1000 fetuses. With the use of the 99th percentile of nuchal translucency thickness, the prevalence rose to 106.7 of every 1000 fetuses. CONCLUSION: In this population of chromosomally normal fetuses with an increased nuchal translucency thickness, the incidence of cardiac defects was high, which suggests that fetal echocardiography is indicated in this group.     

早孕期颈项透明层增厚伴或不伴颈部淋巴水囊瘤胎儿的产前诊断结果及妊娠结局分析

目的比较早孕期颈项透明层(nuchal translucency,NT)≥5 mm伴或不伴颈部淋巴水囊瘤(cystic hygroma,CH)胎儿的产前诊断结果及妊娠结局。方法回顾性分析2017年7月至2020年12月在广州市妇女儿童医疗中心就诊的NT≥5 mm且接受介入性产前诊断的131例胎儿资料,按照囊肿内是否存在分隔将所有病例分为NT增厚不伴CH组(囊肿内未发现分隔,74例)和NT增厚伴CH组(囊肿内可见分隔,57例)。比较2组胎儿遗传学检测结果、胎儿超声结构畸形发生率以及出生后健康存活率。采用χ²检验、Fisher精确概率法或非参数检验进行统计学分析。结果NT增厚不伴CH组与NT增厚伴CH组胎儿遗传学检测结果异常发生率[67.6%(50/74)与61.4%(35/57),χ²=0.54,P=0.464]、超声结构异常发生率[21.6%(16/74)与33.3%(19/57),χ²=2.26,P=0.133]、健康存活率(12/14与3/8,Fisher精确概率法,P=0.052)比较,差异均无统计学意义。结论NT增厚伴或不伴CH胎儿,虽然两者疾病谱不同,但合并染色体异常及结构畸形发生率均高,出生后都有一定的健康存活率。     

Ductus venosus flow velocities in relation to the cardiac defects in first-trimester fetuses with enlarged nuchal translucency

OBJECTIVE: Our aim is to study first-trimester ductus venosus (DV) velocities in relation to cardiac abnormalities. STUDY DESIGN: Ultrasound examination was performed in 85 normal fetuses and 45 fetuses with a nuchal translucency (NT) >95th percentile. Pulsatility index for veins (PIV) and velocity during late diastole (a-V) of the DV were measured and compared with the use of multilevel analysis, between fetuses with a heart defect and those without. RESULTS: Compared with 85 normal fetuses, the a-V and PIV of the fetuses with NT>95th percentile and normal hearts were decreased and increased, respectively. The a-V and PIV of 11 fetuses with NT>95th percentile and cardiac defects were decreased and increased compared with the 25 fetuses with normal hearts, irrespective of the karyotype. The most common cardiac malformations were septal defects. CONCLUSION: Fetuses with NT >95th percentile and cardiac defects show markedly changed DV velocities. Because the type of cardiac defects cannot always explain the hemodynamic changes found in these fetuses, some other mechanisms seem to be involved.     

Screening performance of first-trimester nuchal translucency for major cardiac defects: a meta-analysis

OBJECTIVE: The purpose of this study was to evaluate the screening performance of increased first-trimester nuchal translucency for the detection of major congenital heart defects. STUDY DESIGN: A meta-analysis based on MEDLINE and EMBASE searches (up to June 2002) that assessed the diagnostic performance of increased nuchal translucency for congenital heart defect detection. Weighted sensitivity and specificity estimates (random effects) and summary receiver-operating characteristic curves were obtained. RESULTS: Eight independent studies with 58,492 pregnant women were analyzed. There was significant heterogeneity among the studies. Nuchal translucency above the 99th percentile had a sensitivity of 31% and specificity of 98.7% (random effects calculations), with a positive likelihood ratio of 24. Summary receiver-operating characteristic estimates were consistent with these values. The ability of nuchal translucency measurements above this threshold to detect cardiac malformations varied nonsignificantly (P=.64) for different congenital heart defects types (sensitivity range, 25%-55%). CONCLUSION: Nuchal translucency screening is a modestly efficient strategy for congenital heart defect detection; the use of the 99th percentile threshold may capture approximately 30% of congenital heart defects.     

Pregnancy outcome and nuchal translucency measurements in fetuses with a normal karyotype

The aim of this study was to examine the relationship between nuchal translucency thickness and pregnancy and fetal outcome in fetuses with a normal karyotype and without structural malformations. Fetal nuchal translucency measurements were performed in 2088 chromosomally and structurally normal fetuses. In all fetuses the karyotype and pregnancy outcome were known. Likelihood ratios for different outcome measures were calculated. Spontaneous abortion, intra-uterine and neonatal death occurred in 2.4, 1.1 and 0.5 per cent respectively. The incidence of immature delivery was 1.1 per cent and of premature delivery 6.0 per cent. The only adverse pregnancy outcome recorded that was associated with increased nuchal translucency was spontaneous abortion. The likelihood ratio for the occurrence of a spontaneous abortion was 3.1 for measurements between 3.0 and 3.9 mm, and 6.8 for measurements>/=4 mm. Increased lethality in fetuses with enlarged nuchal translucency and normal chromosomes may provide evidence that the same insult causing excessive fluid collection in the nuchal region may also be responsible for fetal demise.     

Changes in nuchal translucency thickness in normal and abnormal karyotype fetuses

Objective To investigate the dynamic trend of the nuchal translucency thickness between fetuses with normal and abnormal karyotype.
Design Prospective observational study.
Setting Ospedale Microcitemico, Cagliari, Italy.
Population A cohort of 305 first trimester fetuses.
Methods Fetuses with a nuchal translucency greater than or equal to the 95th centile were invited for a second nuchal translucency measurement. The finding of an 'increased or unchanged' or 'diminished' thickness was compared in fetuses with normal and abnormal karyotype.
Main outcome measures Nuchal translucency and karyotype.
Results Median maternal age was 35 years (min 17, max 44) and median crown–rump length at first visit was 50 mm (min 38, max 80). A second nuchal translucency measurement was carried out in 292 fetuses, resulting in increased or unchanged values in 95 cases and decreased nuchal translucency in 197 cases. Two hundred and twenty-six (77.4%) fetuses had normal karyotype and 66 (22.6%) had abnormal karyotype (44 trisomies 21, 10 trisomies 18, 5 trisomies 13, 4 cases of 45 X0, 1 case of 47,XXY, 1 case of 47,XXX and 1 translocation). In the 66 chromosomally abnormal fetuses, the second nuchal translucency measurement was enlarged or unchanged in 37 (56%), and diminished in 29 (44%), while in the 226 normal fetuses the second nuchal translucency measurement was enlarged or unchanged in 58 cases (25%) and diminished in 168 (75%) (relative risk 2.6, 95% confidence interval 1.7–4.0).
Conclusion In fetuses with abnormal karyotype, the second nuchal translucency measurement tends to be increased or unchanged, while in normal cases the size of nuchal translucency is generally reduced.