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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Cuckle
Howard S
HS
Reproductive Epidemiology, University of Leeds, Leeds, UK. h.s.cuckle@leeds.ac.uk
Spencer
K
K
Nicolaides
K H
KH
D000328:Adult; D000465:Algorithms; D000782:Aneuploidy; D015415:Biomarkers / Q000097:blood*; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood; D004314:Down Syndrome / Q000097:blood* / Q000175:diagnosis* / Q000517:prevention & control; D005260:Female; D006801:Humans; D008403:Mass Screening / Q000379:methods; D011247:Pregnancy; D018566:Pregnancy, High-Risk / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis; D011296:Prenatal Diagnosis / Q000379:methods*; D018570:Risk Assessment
D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A