Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A.
OBJECTIVE
To determine the second trimester Down's syndrome screening performance of maternal serum dimeric inhibin A, both alone and in combination with existing serum markers.


METHODS
A case-control set of serum samples from patients with Down's syndrome (52) and subjects with matched unaffected pregnancies obtained in a previous cohort study before second trimester amniocentesis and karyotyping. The amniocenteses were performed for reasons other than a positive serum screening test result.


METHODS
For each serum from a Down's syndrome pregnancy, five serum samples from pregnancies with a normal karyotype were matched for recruitment centre, gestational age, maternal age, and date of amniocentesis. A specific form of inhibin (dimeric inhibin A) was measured using monoclonal antibodies. Measurements of alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin and its free beta subunit were already available. Screening performance was modelled using distribution variables of the analytes coupled with the 1993 age distribution of pregnant women in the United States.


RESULTS
The median dimeric inhibin A level was 2.10 times higher in Down's syndrome pregnancies. When dimeric inhibin A was combined with maternal age and three other serum markers (alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin) the Down's syndrome detection rate increased to 75% (from 66%) at a 5% false positive rate. If dimeric inhibin A could be added for less than $31 (ranging from $16 to $39 depending on the detection rate, markers chosen, and method of dating), the cost of detecting each Down's syndrome pregnancy and the number of procedure related fetal losses would both be reduced.


CONCLUSIONS
The addition of dimeric inhibin A to prenatal screening programmes for Down's syndrome should be considered, or possibly it could be substituted for an existing serum marker. One barrier to implementation in the United States, however, is the unavailability of kits with Food and Drug Administration approval.
Haddow
J E
JE
Foundation for Blood Research, Scarborough, ME 04074, USA.
Palomaki
G E
GE
Knight
G J
GJ
Foster
D L
DL
Neveux
L M
LM
D016022:Case-Control Studies; D006063:Chorionic Gonadotropin / Q000097:blood; D003198:Computer Simulation; D003365:Costs and Cost Analysis; D004314:Down Syndrome / Q000175:diagnosis*; D004964:Estriol / Q000097:blood; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007265:Inhibins / Q000097:blood*; D008403:Mass Screening / Q000191:economics / Q000706:statistics & numerical data*; D008423:Maternal Age; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis / Q000191:economics / Q000706:statistics & numerical data*; D000509:alpha-Fetoproteins / Q000032:analysis
D006063:Chorionic Gonadotropin; D000509:alpha-Fetoproteins; D007265:Inhibins; D004964:Estriol