Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro-Caribbean populations

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.

show abstract

“…In this regard, the size of the increase in ADAM 12 in Afro-Caribbean pregnancies is very similar to that seen with PAPP-A (Spencer et al, 2005).…”

Section: Discussionsupporting

confidence: 64%

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

et al. 2007

View full text Add to dashboard Cite

show abstract

“…All biochemical markers were converted to multiple of the median (MoM) of the expected normal median for a pregnancy of the same gestational day using values established in a previous study corrected for maternal weight (Spencer et al, , 2003a, self-recorded smoking status and ethnicity (Spencer et al, , 2005a. To take account of gestational variation of foetal NT, we expressed the measured foetal NT as the difference from the normal median NT (Snijders et al, 1998;Spencer et al, 2003a) at the measured CRL, this being the delta NT.…”

Section: Methodsmentioning

confidence: 99%

“…Several recent studies have shown an association between low first-trimester maternal serum pregnancy associated plasma protein-A (PAPP-A) levels and the subsequent development of pregnancy complications, including pre-eclampsia Smith et al, 2002;Yaron et al, 2002;Tul et al, 2003;Dugoff et al, 2004;Krantz et al, 2004;Spencer et al, 2005aSpencer et al, , 2006aSpencer et al, ,b, 2007aCowans and Spencer, 2007).…”

Section: Introductionmentioning

confidence: 99%

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

Spencer

Cowans²,

Nicolaides³

2007

Prenatal Diagnosis

183

113

View full text Add to dashboard Cite

Background Low levels of pregnancy associated plasma protein-A (PAPP-A) have been previously shown to be associated with pregnancies that subsequently develop pre-eclampsia. The objective of this study was to establish the relative risk for pre-eclampsia at various PAPP-A levels as an aid to counselling and follow up of pregnancies.Methods Maternal serum PAPP-A and free ß-human chorionic gonadotropin (ß-hCG) levels at 11 to 13 weeks of gestation from 224 singleton pregnancies that subsequently developed pre-eclampsia were compared to those from 47 770 normal singleton pregnancies resulting in live births after 37 weeks with birth weight greater than or equal to the 10th centile of normal for gestation. In all cases, the measured PAPP-A and free ß-hCG levels were expressed as multiple of the median (MoM). The association between metabolite levels and the incidence of pre-eclampsia was assessed by comparing the relative incidence at a number of MoM cut-offs and at various centiles. At various marker levels, the likelihood ratio for pre-eclampsia was also calculated. ResultsIn the pre-eclampsia group the median PAPP-A MoM was significantly reduced (0.772 MoM, p < 0.0001) whilst the median free β-hCG MoM was not different from controls (0.981 MoM, p = 0.26). With decreasing levels of PAPP-A, the likelihood ratio for pre-eclampsia increased. At the 5th centile of normal (PAPP-A MoM 0.415) the odds ratio was increased 4-fold and at this cut-off 15% of cases of pre-eclampsia would be identified. ConclusionsThe graphical presentation of a likelihood ratio curve for pre-eclampsia at any PAPP-A MoM level is likely to be useful in counselling women with low levels of PAPP-A and a normal karyotype. Use of low levels of PAPP-A for selecting women for further follow-up with uterine artery Doppler may further improve the clinical discrimination.

show abstract

“…Previous studies have suggested that there is no significant difference in fetal NT between Chinese and Caucasian populations 7 . On the other hand, levels of free β-hCG and PAPP-A among Chinese women were 1.15 and 1.23 times higher than those of Caucasian women, which if taken into account might increase the screen-positive rate from 5.3% to 5.9% 6,7 .…”

Section: Discussionmentioning

confidence: 99%

“…For example, previous studies have shown that, when compared with Caucasians, Chinese women have significantly higher median values for the first-trimester biochemical markers 6,7 . The aim of this study was to report our initial experience of 2990 cases of combined first-trimester screening tests in a predominantly Chinese population.…”

Section: Introductionmentioning

confidence: 99%

First‐trimester combined screening for trisomy 21 in a predominantly Chinese population

Leung

Chan

Leung

et al. 2006

Ultrasound in Obstet & Gyne

Self Cite

View full text Add to dashboard Cite

show abstract

Ethnicity and the need for correction of biochemical and ultrasound markers of chromosomal anomalies in the first trimester: a study of Oriental, Asian and Afro-Caribbean populations

Cited by 132 publications

References 23 publications

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

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

Low levels of maternal serum PAPP‐A in the first trimester and the risk of pre‐eclampsia

First‐trimester combined screening for trisomy 21 in a predominantly Chinese population

Contact Info

Product

Resources

About