Down syndrome screening marker levels in women with a previous aneuploidy pregnancy

Reproductive Epidemiology, University of Leeds, Leeds, UK.
Prenatal Diagnosis (Impact Factor: 3.27). 01/2005; 25(1):47-50. DOI: 10.1002/pd.1082
Source: PubMed


In Down syndrome screening programmes, women with a previous affected pregnancy are assumed to have the same marker distribution as those without a family history. This assumption needs to be tested.
Information on previous aneuploidy pregnancies was routinely sought on the test request forms in three centres, Leeds, Romford and the Fetal Medicine Centre, London. For each woman with a previous aneuploidy (case), five unaffected pregnancies to women without a history were selected as controls. The markers tested included maternal serum free beta-human chorionic gonadotrophin (hCG), pregnancy-associated plasma protein A (PAPP-A), alpha-fetoprotein, unconjugated estriol and ultrasound nuchal translucency thickness.
There were 375 cases: 303 with previous Down syndrome, 63 with Edwards syndrome and 9 with Patau's syndrome. There was a statistically significant difference between cases and controls, in the distribution of free beta-hCG and PAPP-A levels, adjusted for gestation. On average, free beta-hCG was increased by 10% in a subsequent pregnancy after aneuploidy (p < 0.005, Wilcoxon rank sum test) and for PAPP-A the increase was 15% (p < 0.0001). No other marker was significantly different.
Risk calculation algorithms need to be modified to take account of the increased marker levels. Until data from sufficient affected pregnancies are available for study, it would be prudent to assume that the same increase as in unaffected pregnancies applies.

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Available from: Kevin Spencer, Sep 29, 2014
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    • "Most of these confounders have such a significant influence as to require correction for. Others such as diabetes, fetal sex, previous aneuploidy history, early vaginal bleeding (Cuckle et al., 2005; Cowans et al., *Correspondence to: K. Spencer, Clinical Biochemistry Department , King George Hospital, Barley Lane, Goodmayes IG3 8YB, UK. E-mail: 2009; Spencer et al., 2000e, 2005b, 2009a,b) and previous screening result (Spencer, 2001, 2002) are either too small or too problematical to make correction for. "
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    ABSTRACT: To assess the impact of a vanishing twin on the levels of the biochemical markers used in the first trimester aneuploidy screening. A retrospective analysis of free beta-hCG and PAPP-A levels in 270 women with a normal singleton fetus with ultrasound evidence of a vanishing twin pregnancy. Marker levels (as MoM) were compared in three groups-76 women with a second empty gestational sac, 194 women with a second gestational sac containing a dead fetus with a measurable crown rump length (CRL), and 1360 matched singleton pregnancies. In women with a second empty gestational sac, the median free beta-hCG and PAPP-A MoMs (0.968 and 1.040, respectively) were not significantly different from the 1.0 MoM in singleton pregnancies. In the group with a vanished twin with a measurable-CRL-there was a significantly increased median PAPP-A MoM (1.317) but the median free beta-hCG MoM was not changed (1.024). Modelling this bias in PAPP-A MoM the detection rate for trisomy 21 would fall from 85 to 75%. First trimester screening in the presence of a vanishing twin may lead to errors in risk estimation. In such circumstances it may be advisable to restrict screening to the use of nuchal translucency (NT) alone.
    Full-text · Article · Mar 2010 · Prenatal Diagnosis
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    • "This is in agreement with our previous data (Cuckle et al., 2005). However, we could find no evidence for any elevation of free β-hCG, contrary to our earlier study in 2005 (Cuckle et al., 2005). In the earlier study, no correction of marker MoMs were made for smoking, ethnicity, parity or IVF pregnancy and whilst an attempt to adjust for parity was made by matching cases to controls of the same maternal age (and hence likely parity). "
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    ABSTRACT: To re-evaluate in a larger cohort of patients if the maternal serum biochemical markers used in first trimester aneuploidy screening have the same marker distributions in pregnancies with a previous history of aneuploidy compared with those that have no previous history. Information related to previous pregnancy history is routinely recorded as part of first trimester screening in three centres King George, Kings College and Fetal Medicine Centre, London. From the database, records were extracted for women who had a previous pregnancy diagnosed with trisomies 13, 18 or 21. For each woman with a previous aneuploidy, five unaffected pregnancies in women of the same maternal age and with no previous aneuploidy pregnancy were selected as controls. A comparison was made between the marker distributions for pregnancy associated plasma protein-A (PAPP-A) and free beta-human chronic gonadotrophin (beta-hCG) amongst the cases and controls using nonparametric statistical tests. A series of 8240 controls were compared against group of 1032 cases with a previous trisomy 21, 293 with a previous trisomy 18 and 158 with a previous trisomy 13. Cases with multiple previous trisomies were excluded. There were no significant differences in the level of free beta-hCG; however, in cases of trisomy 21 and trisomy 13 the levels of PAPP-A were increased by 5 and 16%, respectively. Risk calculation algorithms may need to take account of the increased PAPP-A levels in women with a previous trisomy 21 or trisomy 13.
    Full-text · Article · Dec 2009 · Prenatal Diagnosis

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