First trimester screening for structural fetal abnormalities: Nuchal translucency sonography

Nuchal translucency refers to the normal subcutaneous space, observed on first trimester ultrasound examination, between the skin and the cervical spine in the fetus. Increased nuchal translucency is known to be associated with an increased risk of aneuploidy, particularly Down syndrome. In addition to this association with aneuploidy, multiple studies have now identified increased nuchal translucency as a nonspecific marker of a wide range of fetal structural abnormalities, to include congenital diaphragmatic hernia, cardiac defects, and various genetic syndromes. The degree of nuchal translucency is directly related to the prevalence of fetal anomalies and may have prognostic significance, especially when found in association with other anomalies. The pathophysiology of increased nuchal translucency is uncertain but may be the result of cardiac failure or alterations in lymphatic drainage. Increased nuchal translucency may identify pregnancies that require further assessment, to include additional sonographic evaluation and possible fetal echocardiography. Further evaluation is required to assess the role of nuchal translucency screening in the general population.     

First trimester screening for aneuploidy: Serum biochemical markers

The article reviews screening for Down syndrome in the first trimester (8-13 gestational weeks) with maternal serum analytes. In the first trimester, 2 serum markers stand out: pregnancy-associated plasma protein-A, a large glycoprotein tetramer, and free beta-human chorionic gonadotropin (beta-hCG), 1 of the 2 subunits of the glycoprotein hormone hCG. Some data indicate that hCG itself may be as effective as free beta-hCG in the first trimester. Maternal serum levels of pregnancy-associated plasma protein-A are low and free beta-hCG are high (consensus multiple of the medians, 0.4 and 1.8, respectively) in Down syndrome pregnancy. The consensus estimate of screening performance by using pregnancy-associated plasma protein-A and free beta-hCG in combination with maternal age is 60% detection rate at a 5% false positive rate. This is similar to the screening performance of second trimester double markers, but not as good as the screening performance of second trimester triple or quad markers. For this reason, first trimester screening with serum markers alone cannot be recommended except in cases in which second trimester screening cannot be done.     

Nuchal translucency and first trimester biochemical markers for down syndrome screening: a cost-effectiveness analysis

OBJECTIVE: The purpose of this study was to perform a cost-effectiveness analysis that compared the first- and second- trimester screening tools for Down syndrome. STUDY DESIGN: A decision tree was designed that compared four possible screens for Down syndrome: (1) current second- trimester expanded maternal serum alpha-fetoprotein test (AFP), (2) first-trimester nuchal translucency screen, (3) first-trimester serum screen, and (4) combined first-trimester screen with both nuchal translucency screen and a serum screen. Incremental cost-benefit and cost-effectiveness ratios were calculated that compared the first-trimester screens with expanded alpha-fetoprotein. RESULTS: The combined screen (nuchal translucency screen + first-trimester serum screen) identified 3,833 Down syndrome fetuses, the nuchal translucency alone identified 3,413 Down syndrome fetuses, and the first- trimester serum screen identified 2,993 Down syndrome fetuses. Each of these screens was an improvement over the current expanded AFP screen, which diagnosed 2,446 Down syndrome fetuses. It would cost $98,381 for each additional Down syndrome case that would be identified by nuchal translucency alone, with a benefit-to-cost ratio of 4.85. The addition of the first-trimester serum screen is still cost-effective compared with expanded AFP; the cost would be $319,934 for each additional Down syndrome fetus who was identified, which would be a benefit-to-cost ratio of 1.57. CONCLUSION: First-trimester screening for Down syndrome with nuchal translucency screening alone or with serum markers is more clinically effective and cost-effective than the current expanded AFP screen that is being used.     

First trimester aneuploidy screening combining biochemical and ultrasound markers

The different strategies applied for Down syndrome (DS) screening in a single center are presented and the results are analyzed taking into account the number of invasive procedures needed for the diagnosis of one affected pregnancy. The use of advanced maternal age as a single criterion, from 1980 to 1992 proved to be poorly effective since 102 amniocentesis are needed to diagnose one DS affected pregnancy (1:102) or 52 to diagnose any aneuploidy (1:52) With the use of second trimester screening with serum markers (AFP and hCG) at 14-18 weeks in 8711 women less than 38 years, from 1993 to 1999 the ratios were improved to 1:82 and 1:47 respectively. With the introduction of the combined test in 1999 using free hCG, PAPP-A (sampling at 9-10 weeks) and NT (measured at 12 weeks) in 3644 women under 38 years, and gestational weeks adjusted by US in 3644 singleton pregnancies with complete follow-up, the ratios were substantially improved to 1:16 procedures for DS or 1:8 for any aneuploidy. The detection rate achieved was 90% for a false positive rate of 3.4%. Comparing the different strategies applied in our Unit it is clear that the combined test applied in the first trimester provides a substantial improvement in detection rates and reduction of unnecessary invasive testing.     

孕妇超声下胎儿颈项透明层筛查的临床分析

目的分析孕妇妊娠11~14周胎儿颈项透明层(nuchal translucency,NT)超声筛查的临床意义。方法收集2012年1月至2012年12月在北京妇产医院妊娠11~14周进行超声NT筛查的孕妇共10 982例,以NT≥2.5mm为临界值。结果①10 982例孕妇中≥2.5mm者173例,随访到结局者165例,染色体异常者12例,21-三体5例,18-三体5例,13-三体1例,45XO 1例;胎儿外观畸形而染色体正常者9例;②对临床资料判断胎儿染色体正常者153例(通过孕期产检及分娩后新生儿查体随访,并非有染色体核型分析者)及染色体异常者12例的NT厚度进行完全随机两样本均数的比较,得出结论 (t<0.05),差异有统计学意义;③染色体正常者中对有无胎儿外观畸形进行NT厚度完全随机两样本均数的比较,结果 (P<0.05),差异有统计学意义。结论对妊娠11~14周孕妇进行NT超声筛查有很重要意义,可以尽早筛出胎儿染色体异常及外观畸形胎儿,降低大孕周引产风险。     

Nuchal translucency measurement--non invasive ultrasound screening for fetal abnormalities. Part I

OBJECTIVE: Fetal abnormalities are the most common cause of perinatal and postnatal death and infant handicap. In the last years came into being many diagnostic methods making possible--precise and accurate diagnosis of fetal malformation. DESIGN: Estimation the value of the screening test for fetal abnormalities based on the nuchal translucency measurement between 10-14th week of pregnancy. MATERIAL AND METHODS: A group of 675 women with singleton pregnancies undergoing first trimester nuchal translucency measurement. Nuchal translucency thickness was measured by transvaginal ultrasound examination according to Nicolaides. Derived risks were then calculated. RESULTS: When we used a risk of 1:250 as the cutoff to define a positive result on the screening test, the rate of detection of fetal abnormalities was 100%, with a false positive rate of 1.3%. CONCLUSION: First trimester nuchal translucency measurement is an effective method of screening for fetal abnormalities (obstetrical high-risk group).     

First trimester screening for preeclampsia

PURPOSE OF REVIEW: Aspirin therapy from the first trimester of pregnancy may benefit women at high risk for preeclampsia. We review publications from the past year that examine first-trimester screening studies for preeclampsia. RECENT FINDINGS: For a false positive rate of 5%, first-trimester uterine artery Doppler studies will detect 50-65% of women who will develop severe preeclampsia (i.e. needing delivery before 35 weeks). Measurement of placental volume with three-dimensional ultrasound at 11-14 weeks detected 20% for a false positive rate of 10% in one study and further evaluation of this technique is needed. Maternal serum placental growth factor, vascular endothelial growth factor and soluble fms-like tyrosine kinase-1 have shown initial promise, but recent studies have shown no improvement in screening compared with using uterine artery Doppler alone. Placental protein 13 is the most promising serum marker and in combination with uterine Doppler may predict up to 90% of cases of severe preeclampsia for a false positive rate of 9%. SUMMARY: First-trimester uterine artery Doppler can identify over half of women who will develop preeclampsia. Detection rates may be increased by a combination of uterine artery Doppler with first-trimester maternal serum markers, especially placental protein 13. Such high-risk women may be the most likely to benefit from pharmacological intervention in future trials.     

First trimester screening

Screening for aneuploidy has traditionally been reserved for women of advanced maternal age. More recent advances in serum screening and ultrasound technology have allowed women of all ages to be offered screening in the second and even first trimester. These methods and their effectiveness are discussed.     

Nuchal translucency measurement--non invasive ultrasound screening for fetal abnormalities. Part II

OBJECTIVE: There is well established association between increased nuchal translucency and chromosomal abnormality. DESIGN: To investigate a new method of screening for fetal abnormalities on the basis of maternal age and fetal nuchal translucency thickness in the first and second term of pregnancy. METHODS: A group of 650 pregnant women from the 10th week of pregnancy until childbirth has been put under examination. Nuchal translucency thickness was measured by transvaginal ultrasound examination according to Nicolaides in the first trimester of pregnancy and by transabdominal ultrasound examination between 15-19th week of pregnancy. Derived risk were then calculated. RESULTS: There were 8 chromosomal and 1 structural defects. When we used a risk of 1:250 as the cutoff to define a positive result on the screening test, the rate of detection of fetal abnormalities was 100%, with a false positive rate 0.7%. CONCLUSION: This study suggests a benefit in combining maternal age-related risk together with NT measurement in the first and second trimester of pregnancy. Such kind of test could also be helpful in twin pregnancies.     

Nuchal translucency thickness and outcome in chromosome translocation diagnosed in the first trimester

In order to determine the significance of nuchal translucency thickness on the subsequent natural history of first-trimester fetuses with a chromosome translocation, seven consecutive cases diagnosed between 11 and 13 weeks of gestation were reviewed. Nuchal translucency measurements were successfully obtained before chorionic villus sampling (CVS) in all cases. Three fetuses had an unbalanced translocation and all were associated with increased nuchal translucency and multiple anomalies at the detailed second-trimester scan. There were no survivors in this group. The remaining four fetuses had a balanced translocation; all had normal nuchal translucency thickness and no structural anomalies were detected in the second trimester. Three of these fetuses were born at > or =35 weeks of gestation and were phenotypically normal. However, an unexpected single fetal demise occurred in a dichorionic twin pregnancy at 28 weeks of gestation. It is concluded that nuchal translucency measurements provide important prognostic information on pregnancy outcome in first-trimester fetuses with a chromosome translocation. In parents with a known balanced translocation, the detection of increased nuchal translucency at 11-14 weeks of gestation is associated with unbalanced translocations, structural anomalies and poor pregnancy outcome.