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.     

Nuchal translucency as a predictor of adverse pregnancy outcome.

BACKGROUND: Thickened nuchal translucency (NT) has been related to fetal genetic syndromes, structural abnormalities, and other diseases. The aim of this research was to evaluate the association of NT with adverse pregnancy outcomes. STUDY DESIGN: In the period 2002-2004 in 2104 pregnant women between 10+6 and 13+5 weeks' gestation, NT was evaluated as a parameter for aneuploidy screening: out of these, 734 singleton pregnant women that underwent 2nd trimester amniocentesis and whose pregnancy outcome were known were selected. NT was statistically correlated to pregnancy and neonatal outcome. RESULTS: Median gestational age (GA) at NT evaluation was 11+2 weeks' gestation. NT median was 1.1 mm (0.9-1.4 mm, 25th-75th centile, range 0.5-4.0 mm). After multiple logistic regressions, the variables significantly associated to NT values were: threatened preterm labor (p<0.008) and preterm labor (p<0.02). The best diagnostic accuracy point was NT>95th centile and >1.5 MoM for the prediction of threatened preterm labor. CONCLUSION: In this series, increased NT values were associated to threatened preterm labor and preterm labor in euploid fetuses: this finding may have clinical consequences in the management of such pregnancies.     

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.     

Elevated first-trimester nuchal translucency increases the risk of congenital heart defects

OBJECTIVE: We sought to evaluate the association between first trimester nuchal translucency measurement and the risk for major congenital heart defect in chromosomally normal fetuses. STUDY DESIGN: First trimester (10 weeks 4 days of gestation to 13 weeks 6 days of gestation) nuchal translucency was obtained in a large prospective multicenter National Institute of Child Health and Human Development study for Down syndrome prediction. The study, which was conducted between May 1998 and December 2000, was restricted to singleton pregnancies. Gestational age was determined by crown rump length measurements. Perinatal outcomes were determined and included the frequency of major congenital heart defect, which was defined as those cases that potentially could require surgery, intensive medical therapy, or prolonged follow-up time. Logistic regression analysis was used to determine whether nuchal translucency was a significant predictor of congenital heart defect. RESULTS: There were 8167 chromosomally normal pregnancies, of which 21 cases of major congenital heart defect were identified at follow-up examination (incidence, 2.6/1000 pregnancies). The risk of congenital heart defect rose with increasing nuchal translucency measurements. The mean nuchal translucency value for the normal and congenital heart defect groups were 1.5 mm and 1.9 mm, respectively (P = .05). With a nuchal translucency measurement of < 2.0 mm, the incidence of congenital heart defect was 13 of 6757 pregnancies (1.9 of every 1000 pregnancies). At 2.0 to 2.4 mm, the incidence was 5 of 1032 pregnancies (4.8 of every 1000 pregnancies). At 2.5 to 3.4 mm, the incidence was 2 of 335 pregnancies (6.0 of every 1000 pregnancies). At > or = 3.5 mm, the incidence was 1 of 43 pregnancies (23 of every 1000 pregnancies). Logistic regression analysis confirmed that nuchal translucency was associated significantly with congenital heart defect (odds ratio, 2.1; 95% CI, 1.4-3.1; P = .0004). CONCLUSION: Increased first trimester nuchal translucency measurement was associated with a higher risk of major congenital heart defect in chromosomally normal pregnancies. The practical implications of our findings are that patients with unexplained elevations of nuchal translucency may need referral for a fetal echocardiogram.     

Fetal nuchal translucency and skinfold to screen for fetal aneuploidy

Nuchal translucency (NT) is defined as the accumulation of subcutaneous fluid in the nuchal region of the fetus at 11-14 weeks. Its measurement in order to modify the previous background risk has been proved to be able to detect around 70% of trisomy 21 pregnancies (for a 5% fixed positive rate). When affected fetuses dying before 20 weeks are excluded, detection rate may decrease to 60%. Given that appropriate training of sonographers and adherence to a standard technique for the measurement of NT is of paramount importance to reduce variability, the Fetal Medicine Foundation has established a certification process. Fetal nuchal edema displayed at 15-20 weeks was described as enlarged nuchal skinfold, and is a less sensitive but more specific marker than nuchal translucency. Webbing of the neck in infants with trisomy 21 may be envisaged as the remainder of nuchal distension.     

Nuchal translucency and cardiac abnormalities in euploid singleton pregnancies

Abstract

Objective: To investigate different cut-off levels of nuchal translucency (NT) to predict abnormal cardiac findings (ACF) in second trimester ultrasound examination and confirmed postnatal congenital heart defects (CHD) in euploid pregnancies.

Methods: A retrospective analysis was performed on singleton pregnancies examined in our ultrasound units from 2006 to 2011. Fetuses with an abnormal karyotype were excluded. Different cut-off levels of NT thickness were analyzed to evaluate its performance to detect the ACF on second trimester ultrasound (2nd US) examination and also the CHD detected in neonatal follow-up evaluation of ACF cases.

Results: Of the 12?840 cases, a total number of 8541 euploid pregnancies were included in the study. Thirty-three had ACFs detected by 2nd US (3.86/1000). The mean NT thickness was found to be higher in fetuses with ACFs (p?<?0.0001). Of 33 ACFs, 17 (52%, 1.99/1000) had major CHDs in neonatal follow-up. The area under the ROC curves for NT thickness to predict ACFs and CHDs were 0.67 and 0.65, respectively.

Conclusions: Higher NT thickness is associated with higher risk of ACF. NT is a weak predictor of ACF and major CHD; however, fetuses with an unexplained increase in NT measurement should be referred for further cardiac investigations.     

Prenatal course and pregnancy outcome of fetuses with a transient nuchal translucency.

OBJECTIVES: This study was designed to correlate fetuses in a normal prenatal population who exhibited transient nuchal translucency (NT) with both prenatal course and pregnancy outcome. METHODS: The fetuses with abnormal NT were followed by ultrasonography at 1-2-week intervals during their prenatal course. Fetuses with NT who exhibited no detectable congenital malformations were defined as the NTO group; fetuses with abnormal NT and structural malformations but no chromosomal abnormalities were placed in the SM group; and fetuses with abnormal NT, structural malformations, and chromosomal abnormalities were categorized as the CA group. The groups were compared by: maternal age, weeks of gestation by ultrasound and the NT value at the initial exam, the maximum NT value, and the duration of abnormal NT. RESULTS: During the study period, 92 fetuses with abnormal NT were found, monochorionic twins excluded. Of the 92 fetuses, 80 were in the NTO group, 10 were in the SM group, and two were in the CA group. The maternal age and the gestational weeks at the initial diagnosis were not significantly different in the NTO and the SM groups. However, the NT value at the initial diagnosis, maximum NT value, and the duration of abnormal NT were significantly greater in the SM group than those values in the NTO group. CONCLUSIONS: Fetuses with transient nuchal translucency commonly had structural malformations, particularly fetuses with significant and large persistent NT.     

Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities

There is extensive evidence that effective screening for major chromosomal abnormalities can be provided in the first trimester of pregnancy. Prospective studies in a total of 200,868 pregnancies, including 871 fetuses with trisomy 21, have demonstrated that increased nuchal translucency can identify 76.8% of fetuses with trisomy 21, which represents a false-positive rate of 4.2%. When fetal nuchal translucency was combined with maternal serum free-beta-human chorionic gonadotropin and pregnancy-associated plasma protein-A in prospective studies in a total of 44,613 pregnancies, including 215 fetuses with trisomy 21, the detection rate was 87.0% for a false-positive rate of 5.0%. Studies from specialist centers with 15,822 pregnancies, which included 397 fetuses with trisomy 21, have demonstrated that the absence of the nasal bone can identify 69.0% of trisomy 21 fetuses, which represents a false-positive rate of 1.4%. It has been estimated that first-trimester screening by a combination of sonography and maternal serum testing can identify 97% of trisomy 21 fetuses, which represents a false-positive rate of 5%, or that the detection rate can be 91%, which represents a false-positive rate of 0.5%. In addition to increased nuchal translucency, important sonographic markers for chromosomal abnormalities, include fetal growth restriction, tachycardia, abnormal flow in the ductus venosus, megacystis, exomphalos and single umbilical artery. Most pregnant women prefer screening in the first, rather than in the second, trimester. As with all aspects of good clinical practice, those care givers who perform first-trimester screening should be trained appropriately, and their results should be subjected to external quality assurance.     

Predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities

Objective.?The study aimed to estimate the incidence of increased nuchal translucency in the first trimester ultrasound scan results (cut-off limit 2.5 mm) and to evaluate the predictive value of increased nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities.

Methods.?We used the ultrasound scan results of nuchal translucency evaluation and the results of chromosomal analysis of the invasive prenatal control performed as a result of increased nuchal translucency.

Results.?We collected 2183 nuchal translucency ultrasound scans in which we detected 21 embryos with a pathologic value (0.96%). We collected the data of 168 cases of invasive prenatal control due to increased nuchal translucency from which 122 cases were found. A total of 122 cases of pregnant women undergone an invasive prenatal diagnostic method due to increased nuchal translucency, of which 11 fetuses were found with trisomy 21 (Down syndrome) (9%), 3 fetuses with trisomy 13 (Patau syndrome) (2.45%), 3 fetuses with monosomy 45XO (Turner syndrome) (2.45%) and 1 fetus with translocation (0.8%).

Conclusions.?The positive predictive value of the increased fetal nuchal translucency as a screening test for the detection of fetal chromosomal abnormalities based on the results of the chromosomal-genetic analysis of the invasive prenatal diagnostic procedures is 14.8%.     

Early resolution of increased nuchal translucency in a fetus with trisomy 18

The normal timing for first-trimester nuchal translucency screening of aneuploidies is 10 to 14 weeks' gestation. We describe a fetus with trisomy 18 that presented at 11 weeks with increased nuchal thickness. Reevaluation at 12 and 13 weeks showed early return to normal of the increased nuchal measurement.     

Quality assurance of nuchal translucency for prenatal fetal Down syndrome screening

Objective: To assess the quality of nuchal translucency, (NT) measurements were performed at four public institutions performing routine first trimester combined prenatal screening for Down syndrome. Methods: The median of the NT-MoM distribution and standard deviation (SD) of the log₁₀ NT-MoM were determined. Sonographers and screening centres distributions were assessed for measures of central tendency (median) and dispersion (log₁₀ SD). Cumulative Sum (CUSUM) charts were created to assess whether screening centres and individual sonographers who had performed at least 30 NT measurements exhibited any systematic bias by checking whether their CUSUM scores exceeded predefined upper and lower control limits. Results: Of the 36 sonographers, only 67% (n?=?24) had performed 30 or more scans. The median NT-MOM at each screening centre ranged from 1.02 to 1.09. Screening centre standard deviations ranged from 0.073 to 0.099. CUSUM charts indicated that only one screening centre remained within the predefined control limits throughout the assessment period. Analysis of variance indicated that a statistically significant difference existed between the log NT-MoM distributions of the individual sonographers (F?=?10.7; p <0.0001). Inspection of the individual sonographer CUSUM charts indicated that 11 (45%) of the 24, with more than 30 NT measurements were either under or over measuring the NT. Conclusion: Prospective monitoring and feedback of quality assurance assessment results of sonographers and screening centres should be routinely reported as both are responsible, if equity of screening performance is to be maintained.     

Evaluation of fetal nuchal translucency in 98 pregnancies at risk for severe spinal muscular atrophy: possible relevance of the SMN2 copy number

Objective: To study fetal nuchal translucency (NT) thickness as a possible early marker in fetuses at risk for severe spinal muscular atrophy (SMA). To investigate the significance of the survival motor neuron (SMN) 2 gene copy number in affected fetuses. Methods: We performed 2D-ultrasound in 98 pregnancies at risk for SMA, all of which underwent prenatal molecular testing of the SMN1 gene. Crown-rump length (CRL) and NT measurements were obtained in all cases before chorionic villus sampling. Fetuses were diagnosed as healthy, carriers or affected according to the SMN1 molecular testing results. SMN2 copies were also tested in all affected fetuses. Results: Nineteen fetuses were predicted to be affected due to the absence of the SMN1 gene, 18 of which had two SMN2 copies. Mean CRL and NT values did not differ between healthy, carrier and affected fetuses. In the remaining affected case who had only one SMN2 copy, the ultrasound examination showed a NT value of 4.98?mm and findings compatible with hypoplastic left heart. Conclusions: Most affected SMA fetuses have normal NT values. Our findings support the idea that SMN2 copy number in SMA fetuses is relevant for the development of congenital heart defects and increased NT values.     

妊娠早期胎儿颈部透明层厚度与胎儿预后的前瞻性队列研究

目的探讨妊娠早期胎儿颈部透明层(NT)厚度与胎儿预后的关系。方法收集2015年12月至2018年12月于南京大学医学院附属鼓楼医院行妊娠早期胎儿NT厚度测量的单胎孕妇,共4958例建立前瞻性研究队列,进行妊娠早期胎儿结构超声筛查、妊娠早期血清学筛查、妊娠中期超声筛查及对新生儿出生后28 d的体格检查。根据妊娠早期超声筛查的结果,分为胎儿NT增厚(≥3.0 mm)者167例与NT厚度正常者4791例;将胎儿NT增厚的孕妇,分为胎儿单纯NT增厚者86例与NT增厚合并结构异常者81例。分析不同NT厚度胎儿的预后,并重点对单纯NT增厚与NT增厚合并结构异常胎儿的妊娠结局进行分析。妊娠早期超声筛查发现胎儿结构异常或血清学筛查结果为高风险的孕妇,经绒毛穿刺取样术行染色体微阵列分析(CMA)检测以明确产前诊断。结果(1)胎儿NT厚度正常孕妇的妊娠结局:共4791例孕妇,包括胎儿NT厚度正常且无结构异常者4726例,其中妊娠中期及产后新诊断结构异常83例,4688例活产;胎儿NT厚度正常但结构异常的孕妇65例,其中61例孕妇终止妊娠,4例活产。(2)胎儿单纯NT增厚孕妇的妊娠结局:86例孕妇中,66例(76.7%,66/86)行CMA检测,3例胎儿诊断为21三体综合征;除7例孕妇选择终止妊娠外,余79例行妊娠中期超声检查、新生儿出生后28 d体格检查、新生儿电话随访至6~21个月均未发现发育异常。(3)胎儿NT增厚合并结构异常孕妇的妊娠结局:81例孕妇中,73例(90.1%,73/81)行CMA检测,其中32例的胎儿为染色体非整倍体异常。70例选择终止妊娠,2例妊娠中期自然流产,9例活产。(4)NT增厚是否合并结构异常胎儿的产前诊断结果及预后比较:单纯NT增厚的胎儿染色体非整倍体的发生率为3.5%(3/86),合并结构异常者为39.5%(32/81),两者比较,差异有统计学意义(χ2=32.7,P<0.01);胎儿单纯NT增厚孕妇的健康新生儿存活率为91.9%(79/86),合并结构异常者为9.9%(8/81),两者比较,差异有统计学意义(χ2=112.3,P<0.01)。结论妊娠早期,超声筛查胎儿NT及结构,能提高出生缺陷的产前筛查率。单纯NT增厚胎儿的染色体非整倍体的发生率较低,新生儿健康存活率较高。     

Diagnosis of fetal acrania during the first trimester nuchal translucency screening for Down syndrome.

OBJECTIVES: Prenatal screening during the first-trimester using fetal nuchal translucency (NT) measurement and maternal serum levels of free beta-human chorionic gonadotropin (hCG) and pregnancy-associated plasma protein-A (PAPP-A) has become an established method for the detection of fetal Down syndrome. Increasing evidence has shown that some of the fetal structural abnormalities could be identified during NT scanning. Second trimester maternal serum alpha-fetoprotein (MSAFP) measurements and ultrasound scans have been widely used in clinical practice to identify fetal neural tube defects (NTDs). In this study, we evaluated the effectiveness of early diagnosis of fetal acrania during NT scanning. METHODS: We reviewed the medical records of 5890 pregnancies that were delivered in our hospital between January 1, 1999 and January 31, 2001. Among them, 3600 pregnant women received NT-based Down syndrome screening at 10-13 weeks' gestation. Pregnancies with fetal NTDs were evaluated and their maternal serum levels of free beta-hCG and PAPP-A were compared with those of the normal control pregnancies. RESULTS: Seven of the 3600 pregnancies were identified with fetal acrania and all of them were detected during first-trimester NT scanning. Among the seven cases, five had measurements of maternal serum concentration free beta-hCG and PAPP-A concentration, yet there were not significant difference between the pregnancies with fetal acrania and those of the control pregnancies (PAPP-A, 1.13 vs. 0.96; free beta-hCG, 1.10 vs. 1.06; P>0.05). Two of the seven affected patients did not have maternal serum biochemical measurements due to the immediate termination of pregnancies. CONCLUSIONS: We demonstrated that pregnancies with fetal acrania could be easily identified at the time of NT scanning. Careful ultrasound inspection of fetal structure during NT measurements at 10-13 weeks of gestation provides an encouraging advantage for early diagnosis of fetal acrania.     

Persistently elevated nuchal translucency and the fetal heart

Objective: To describe the outcome of fifteen cases with an elevated nuchal translucency (NT) which persisted into the second trimester as nuchal edema (NE) >6?mm whom underwent fetal echocardiography.

Materials and methods: Cases were identified following retrospective review of cardiac and genetic findings in fetuses with NE.

Results: Minor congenital heart disease was identified in 3/15 by the second trimester. Agenesis of the ductus venosus was evident in four. Pulmonary valve stenosis was diagnosed in one fetus at the 20-week scan and hypertrophic cardiomyopathy in one. However, hypertrophic cardiomyopathy or pulmonary valve stenosis was present after birth in all surviving cases by 3 months of age. On the basis of intention to treat, 11/12 survived to delivery and 9/12 survived to 28 days. There were 6 deaths before 14 months of age as a result of severe hypertrophic cardiomyopathy. Noonan syndrome was confirmed with genetic testing in 11/15 cases.

Conclusions: All fetuses with NT and NE had evidence of congenital heart disease at birth, and therefore, late gestation and postnatal review is recommended even when second trimester echocardiogram is considered normal. There is a high prevalence of Noonan syndrome and targeted genetic analysis should be considered. The outcome in these cases is poor.     

Conotruncal anomalies in fetal life: Accuracy of diagnosis, associated defects and outcome

Objectives

To assess the accuracy of prenatal echocardiography, associated anomalies, and outcome of fetuses with conotruncal anomalies (CTA).

Study design

We searched our database for CTA prenatally diagnosed between 1990 and 2005. We included tetralogy of Fallot (TOF), transposition of the great arteries (TGA), double-outlet right ventricle (DORV), truncus arteriosus (TA), pulmonary atresia with ventricular septal defect (PA-VSD) and posterior malalignment type VSD with aortic arch obstruction (pmtVSD-AAO). Data of 144 fetuses with complete follow-up were retrieved and analyzed.

Results

The main reason for referral was suspected heart defect on a routine obstetric scan (72%). Most cases were detected ≤22 weeks (55%). The presence of a CTA was confirmed postnatally in 143 cases (99%), and the diagnosis of the first fetal echocardiography was correct in 126 (87.5%). Most diagnosis of TOF (33/36, 91.7%), TGA (34/38, 89.5%) and DORV (34/38, 89.5%) were proved correct. Inadequate assessment of the interventricular septum, the distal aortic arch and/or the severity of the right outflow tract obstruction accounted for most errors. The accuracy rate was lower in TA (11/14, 78.6%) and PA-VSD (4/7, 57.1%), with evaluation of the branch pulmonary arteries as the main source of discrepancies. In 7/18 incorrect cases subsequent scans allowed to obtain a correct diagnosis. Most fetuses (64%) had an isolated CTA. Thirty-seven had chromosomal anomalies (26%) but none were found in TGA. 22q11 deletion affected 8.7% of the tested patients. Nuchal translucency (NT) was above 95th centile in 19/104 cases (18%) in which NT were measured. Fifty cases were interrupted. The overall one-year survival rate was 71%, with differences between cases with and without associated defects (9/25, 36% vs. 57/68, 83.8%; p < 0.01). The uncomplicated forms of TGA and TOF had the best survival rates (100%).

Conclusions

Most CTA can be diagnosed by fetal echocardiography with a high degree of accuracy. Chromosomal defects should always be ruled out, except for simple TGA. Current survival figures in many isolated CTA, especially simple TGA and TOF, support a change in the “classical” concept that congenital heart defects detected prenatally often have the worst outlook.

Condensation

Most CTA can be diagnosed by fetal echocardiography with a high degree of accuracy. Isolated CTA are more common and most of these may have a favourable outcome.     

Effects of Period of Gestation and Position of Fetal Neck on Nuchal Translucency Measurement

Objective

The aim of this study was to determine the effects of period of gestation and position of fetal neck on nuchal translucency measurement.

Materials and Methods

Nuchal translucency was measured in the mid-sagittal plane, with the fetal neck in the flexed, neutral, and extended positions in 100 pregnant women between 11 and 13⁺⁶ weeks. Mean nuchal translucency measurements at different periods of gestation were compared. Differences between the extended and neutral positions (Δ extended nuchal translucency) and those between the flexed and neutral positions (Δ flexed nuchal translucency) were calculated. The repeatability coefficients for the measurements in all the three positions were computed. Statistical analysis was also done.

Results

Nuchal translucency values were 1.050 ± 0.282 mm in the 11th week, 1.243 ± 0.348 mm in the 12th week, and 1.823 ± 0.357 mm in the 13th week (r = 0.747, p < 0.0001). The mean Δ flexed value was 0.233 ± 0.133 mm lesser than the neutral value (p < 0.0001). The mean Δ extended nuchal translucency was 0.305 ± 0.155 mm greater than the neutral value (p < 0.0001). The repeatability coefficient was the lowest in the neutral position (0.17 mm in the neutral position, 0.28 in the flexed position and 0.41 mm in the extended position).

Conclusion

We concluded that the period of gestation and fetal neck position can make a significant difference to nuchal translucency measurement. Repeatability of measurement is more accurate with the fetal neck in the neutral position. These findings have important implications for clinicians using nuchal translucency to screen the obstetric population for Down’s syndrome.     

Early fetal echocardiography: a new challenge in prenatal diagnosis

During the past decade, an increasing number of reports concerning the diagnosis of most major congenital heart defects (CHDs) using early fetal echocardiography (before the 18th week of gestation) have been reported in both low- and high-risk populations for CHD. The finding of increased nuchal translucency seems to be the strongest predictor of CHD during the first trimester. Although some malformations are detected as early as 11 weeks' gestation, the optimal gestational age to perform the early scan is at least 13 weeks' gestation. Transvaginal ultrasound is the preferred approach, although most authors agree that results can be improved if transabdominal ultrasound is also incorporated. The further application of color Doppler enhances visualization. The sensitivity and specificity for the detection of CHD are of an acceptable level, compared with mid-gestational echocardiography. CHDs diagnosed early in pregnancy tend to be more complex than those detected later, with a higher incidence of associated structural malformations, chromosomal abnormalities and spontaneous abortions. The neonate follow-up or postmortem examination in the case of termination of pregnancy is essential to assess the actual role of early fetal echocardiography.     

Routine screening with fetal echocardiography for prenatal diagnosis of congenital heart disease

Congenital cardiac anomalies are the most common congenital anomalies, occurring in approximately eight of 1000 live births. Proper perinatal and neonatal management is dependent upon accurate prenatal diagnosis. Approximately 10% of fetuses with cardiac abnormalities have identified risk factors; hence, most of the anomalies occur in pregnancies without prenatal risk factors. The application of detailed fetal echocardiography for prenatal screening, at present reserved mainly for high-risk cases, requires further evaluation before being recommended for the general population.

This article presents our experience of evaluating the accuracy of fetal echocardiography as a screening method in detecting cardiac anomalies in the general population of Singapore. We reviewed data from 39 808 pregnant women who received antenatal care at the National University Hospital, Singapore, between January 1986 and December 1994, and who underwent routine fetal echocardiography at 21-22 weeks of gestation. We identified 294 cases of congenital heart defects by fetal echocardiography. We obtained a sensitivity of 85.4% for the detection of congenital heart disease, and a specificity of 99.9% to rule out such anomalies. Our positive and negative predictive rates were 87.7% and 99.9%, respectively.

We recommend routine screening by echocardiography of all pregnancies at 21-22 weeks of gestation, irrespective of risk stratifcation, for the prenatal detection of cardiac anomalies, in order to improve perinatal management.     

First trimester combined screening biochemistry in detection of congenital heart defects

Objective: To evaluate the performance of first trimester biochemical markers, pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (fβ-hCG), and nuchal translucency (NT) in detection of severe congenital heart defects (CHDs).

Methods: During the study period from 1 January 2008 to 31 December 2011, biochemical markers and NT were measured in 31,144 women as part of voluntary first trimester screening program for Down’s syndrome in Northern Finland. Data for 71 severe CHD cases and 762 controls were obtained from the hospital records and from the National Medical Birth Register, which records the birth of all liveborn and stillborn infants, and from the National Register of Congenital Malformations that receives information about all the CHD cases diagnosed in Finland.

Results: Both PAPP-A and fβ-hCG multiple of median (MoM) values were decreased in all severe CHDs: 0.71 and 0.69 in ventricular septal defects (VSDs), 0.58 and 0.88 in tetralogy of Fallot cases (TOFs), 0.82 and 0.89 in hypoplastic left heart syndromes (HLHSs), and 0.88 and 0.96 in multiple defects, respectively. NT was increased in all study groups except of VSD group. ROC AUC was 0.72 for VSD when combining prior risk with PAPP-A and fβ-hCG. Adding NT did not improve the detection rate. With normal NT but decreased (<0.5 MoM) PAPP-A and fβ-hCG odds ratios for VSD and HLHS were 19.5 and 25.6, respectively.

Conclusions: Maternal serum biochemistry improves the detection of CHDs compared to NT measurement only. In cases with normal NT measurement but low concentrations of both PAPP-A and fβ-hCG, an alert for possible CHD, especially VSD, could be given with thorough examination of fetal heart in later ultrasound scans.