Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A

Objectives 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. Setting 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 α fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin and its free β 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 (α 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 &dollar;31 (ranging from &dollar;16 to &dollar;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.

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Second Trimester Levels of Maternal Serum Inhibi A, Total Inhibin, α Inhibin Precursor, and Activin in Down's Syndrome Pregnancy

Journal of Medical Screening ◽

10.1177/096914139600300202 ◽

1996 ◽

Vol 3 (2) ◽

pp. 58-62 ◽

Cited By ~ 49

Author(s):

G M Lambert-Messerlian ◽

J A Canick ◽

G E Palomaki ◽

A L Schneyer ◽

G M Lambert-Messerlian

Keyword(s):

Down's Syndrome ◽

Down’S Syndrome ◽

Serum Marker ◽

Maternal Serum ◽

Serum Samples ◽

Significant Group ◽

Inhibin A ◽

Clinical Assay ◽

Placental Protein ◽

And Control

Objective –To determine the levels of various biochemical forms of the placental protein, inhibin (total inhibin, inhibin A, and α inhibin precursor) and activin in maternal serum samples from fetal Down's syndrome, and to determine which of these analytes most effectively identifies samples from affected pregnancies. Methods –Maternal serum samples were collected from 100 unaffected pregnancies and 20 cases of fetal Down's syndrome during gestational weeks 15–20 for routine triple marker screening, and were stored frozen after clinical assay. Levels of inhibin A, total inhibin, α inhibin precursor (pro-αC), and activin were compared retrospectively in the Down's syndrome cases and control samples. Results –There was no association of the inhibin or activin levels with gestational age or length of freezer storage, and therefore single median values were determined for the unaffected pregnancies for each analyte. Multiples of the unaffected median (MoM) values were calculated for all cases, showing that inhibin A (1.95 MoM) provided the best discrimination between cases and controls, followed by total inhibin (1.37 MoM). Mann-Whitney U analysis showed significant group differences in inhibin A (P = 0.0001) and total inhibin (P = 0.0005). In contrast, α inhibin precursor (0.81 MoM) and activin (1.16 MoM) levels in Down's syndrome cases were not significantly different from those in unaffected patients. Conclusions —Levels of inhibin A and total inhibin, but not α inhibin precursor or activin, are significantly raised in maternal serum from cases of fetal Down's syndrome. These data, taken together, indicate that inhibin A levels are specifically raised in Down's syndrome pregnancy. 45% of the inhibin A levels in the Down's syndrome samples were above the 90th centile of unaffected levels, indicating that inhibin A may be as good a marker as human chorionic gonadotrophin, the most informative serum marker currently in use.

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