Integrated Screening for Down’s Syndrome Based on Tests Performed During the First and Second Trimesters

Wald, NJ; Watt, Hilary; Hackshaw, Allan

doi:10.1097/00006254-200001000-00006

Cited by 139 publications

(186 citation statements)

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“…Ongoing studies may develop the ability to integrate these and other tests to derive a single estimation of risk in the future. 19 Other women may be determined to undergo invasive testing to exclude the possibility of Down syndrome but may use nuchal translucency to assist them in choosing between CVS and amniocentesis. Although it is not clear that CVS, when performed by an experienced operator, has a significantly higher complication rate than amniocentesis, there is some evidence to suggest slightly higher miscarriage rates with CVS.…”

Section: Beneficence-based Dimensions Of Firsttrimester Ultrasonograpmentioning

confidence: 99%

Prenatal informed consent for sonogram: the time for first‐trimester nuchal translucency has come.

Chasen¹,

Skupski²,

McCullough³

et al. 2001

J of Ultrasound Medicine

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ltrasonographic screening in pregnancy has been and continues to be a matter of controversy. For the past 20 years, second-trimester ultrasonographic screening has been debated. Even today, the American College of Obstetricians and Gynecologists does not endorse this as a standard of care. Nonetheless, secondtrimester ultrasonography is widely offered. In 1989, two of us (F.A.C. and L.B.M.) made the argument that "the standard of care demands that prenatal informed consent for sonogram be accepted as an indication for the prudent use of obstetric ultrasonography performed by qualified personnel." 1 The purpose of this editorial is to extend that argument to first-trimester ultrasonographic screening for aneuploidy using nuchal translucency determination. Reliability of First-Trimester Ultrasonographic Screening for AneuploidyThe term nuchal translucency refers to the ultrasonographic measurement of nuchal skin late in the first trimester. A specific feature of neonates with Down syndrome is redundant nuchal skin. This has also been noted with other autosomal trisomies as well as Turner syndrome. 2 Nuchal edema occurs in the fetus as well, and varying degrees of this are visible ultrasonographically. These range from slight thickening of nuchal skin to cystic hygromas, which are congenital malformations in which dilated lymphatic channels form a soft tissue mass, typically in the posterior neck.Benacerraf et al 3 reported an association between increased nuchal skin fold thickness in the second trimester and Down syndrome in 1985. Although this is a useful second-trimester marker for Down syndrome, only approximately 20% to 30% of fetuses with Down syndrome will have increased nuchal skin fold thickness. 4 Nicolaides et al 5 described an association with first-trimester nuchal edema and aneuploidy in 1992. Subsequently, numerous studies described increased nuchal translucency in most fetuses with Down syndrome and other forms of aneuploidy between 10 and 14 weeks. Most early studies defined increased nuchal translucency using a single cutoff, usually 3.0 mm. 6 A problem with using a single cutoff in defining abnormal nuchal translucency is the fact that nuchal translucency increases with gestational age in fetuses without abnorAbbreviations CVS, chorionic villus sampling; FMF, Fetal Medicine Foundation

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Section: Beneficence-based Dimensions Of Firsttrimester Ultrasonograpmentioning

confidence: 99%

Prenatal informed consent for sonogram: the time for first‐trimester nuchal translucency has come.

Chasen¹,

Skupski²,

McCullough³

et al. 2001

J of Ultrasound Medicine

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“…Second-trimester markers are also offered as part of integrated screening (Wald et al, 1999a) and contingent (Christiansen and Larsen, 2002;Benn et al, 2005) and sequential screening programes (Benn, 2002;Benn et al, 2005). The identification of new second-trimester markers will make it possible to reduce the false positive rate of screening, and thus, the number of invasive procedures associated with a 1% risk of aborting an otherwise healthy fetus (Tabor et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

ADAM 12 as a second‐trimester maternal serum marker in screening for Down syndrome

et al. 2007

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Background ADAM 12 is a placenta-derived glycoprotein that is involved in growth and differentiation. The maternal serum concentration of ADAM 12 is a potential first-trimester maternal serum marker of Down syndrome (DS). Here we examine the potential of ADAM 12 as a second-trimester maternal serum marker of DS. Materials and MethodsThe concentration of ADAM 12 was determined in gestational week 14-19 in 88 DS pregnancies and 341 matched control pregnancies. Medians of normal pregnancies were established by polynomial regression and the distribution of log 10 MoM ADAM 12 values in DS pregnancies and controls determined. Correlations with alpha-fetoprotein (AFP) and free β-human chorionic gonadotrophin (free β-hCG) were established and used to model the performance of maternal serum screening with ADAM 12 in combination with other second-trimester serum markers. ResultsThe ADAM 12 maternal serum concentration was significantly increased with a median MoM of 1.85 and a mean log 10 MoM (SD) of 0.268 (0.2678) compared to a mean log 10 MoM (SD) of 0.013 (0.4318) in controls. ADAM 12 correlated with maternal weight and ethnicity (with the serum concentration increased in Afro-Caribbeans), but neither with maternal age nor gestational age, and only marginally with AFP (r(DS) = 0.078, r(controls) = 0.093) and free β-hCG (r(DS) = 0.073, r(controls) = 0.144. The increase in detection rate-for a false positive rate of 5%-by adding ADAM 12 to the double test (AFP + free β-hCG) was 4%, similar to that of adding uE3 to the double test.Conclusion ADAM 12 is an efficient second-trimester marker for DS. Further studies should be conducted to determine whether it may be a useful additonal or alternative marker to those currently used in the secondtrimester.

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“…Recently a combination of maternal age, nuchal translucency and first and second trimester biochemical markers has been proposed as a highly effective test that could achieve a detection rate of 85% for 1% screen positive rate 7 . However, this was based on statistical calculations from past studies in different populations.…”

Section: Introductionmentioning

confidence: 99%

The use of nuchal translucency measurement and second trimester biochemical markers in screening for Down's Syndrome

Michailidis

Spencer

Economides

2001

BJOG

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Objective To assess the effectiveness of antenatal screening for trisomy 21 by first trimester sonography followed by second trimester biochemical screening. Design Retrospective five-year review.Setting Maternity unit of a university hospital.Population An unselected group of 7447 pregnant women who had a first trimester scan and nuchal translucency measurement in our unit after January 1995 and had an estimated date of delivery before 1 January 2000. 11.9% were $ 37 years old. A subgroup (n ¼ 4864) also had second trimester biochemical testing by alphafetoprotein and free b-human chorionic gonadotrophin. Main outcome measures Prenatal and postnatal diagnosis of trisomy 21.Results There were 23 fetuses affected with trisomy 21. The overall prenatal detection rate was 87% (20/23; 95% CI 66% to 97%) and we performed invasive procedures in 8.5% of our population. First trimester sonography identified 74% (95% CI 51.6% to 89.8%) of affected fetuses. Second trimester biochemical screening detected half of the fetuses with trisomy 21 which were missed by first trimester screening, increasing the sensitivity to 90.5% (19/21; 95% CI 69.6% to 98.8%) for an invasive procedure rate of 4.2% performed in screened positive women. However, the positive predictive value of the biochemical test was very low (0.5%). In screen negative women, karyotyping for advanced maternal age did not detect any affected fetuses. Conclusion First trimester nuchal translucency measurement is an effective screening test for the prenatal detection of fetuses with Down's Syndrome. Although the measurement of biochemical markers in the second trimester can detect additional affected fetuses this may be outweighed by the delay in diagnosis, the extra visits and cost so that the right time for biochemical screening is most likely to be in the first trimester.

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Integrated Screening for Down’s Syndrome Based on Tests Performed During the First and Second Trimesters

Cited by 139 publications

References 0 publications

Prenatal informed consent for sonogram: the time for first‐trimester nuchal translucency has come.

Prenatal informed consent for sonogram: the time for first‐trimester nuchal translucency has come.

ADAM 12 as a second‐trimester maternal serum marker in screening for Down syndrome

The use of nuchal translucency measurement and second trimester biochemical markers in screening for Down's Syndrome

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