Predicting risk of preterm delivery by second-trimester measurement of maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations.
OBJECTIVE
Many women who have preterm labor have abnormally high plasma concentrations of the placental peptide corticotropin-releasing hormone and the fetal product alpha-fetoprotein in early pregnancy. This study was designed to evaluate the ability of these biochemical tests and a clinical risk factor score to prospectively discriminate pregnancies at high risk for preterm delivery.


METHODS
Eight hundred sixty women were studied prospectively from the early second trimester until delivery. A risk factor score for preterm delivery was calculated from the clinical history and maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations were measured by radioimmunoassay between 17 and 30 weeks' gestation. The risk factor score, corticotropin-releasing hormone concentration, and alpha-fetoprotein concentration for each woman were expressed as individual odds or likelihood ratios for preterm delivery and as a combined risk estimate derived from the 3 tests.


RESULTS
Sixty women had preterm deliveries (n = 37 spontaneous labor, n = 23 planned deliveries), and these women had significantly higher concentrations of corticotropin-releasing hormone (median 1.92 multiples of the median) and alpha-fetoprotein (median 1.32 multiples of the median) than did women with term deliveries (median 1.00 multiples of the median, P <.001 for both tests), with these abnormalities being evident from early in the second trimester. The risk factor score was >/=10 in 28% of women with preterm delivery and 7% of women with term delivery. The combination of all 3 markers resulted in a higher detection rate and a higher positive predictive value than the risk factor score, corticotropin-releasing hormone concentration, or alpha-fetoprotein concentration alone, correctly discriminating 37% of women who would have preterm deliveries with a false-positive rate of 5%. The positive predictive value was also 37% (odds of being affected given a positive result were 1:1.7).


CONCLUSIONS
The combination of measurement of maternal plasma corticotropin-releasing hormone and alpha-fetoprotein concentrations in the second trimester with risk factor scoring provides a more accurate indicator of the risk of preterm delivery than does risk factor scoring alone. This method of risk assessment may therefore be of use in targeting prevention strategies.
Maternal Health Research Centre, John Hunter Hospital and University of Newcastle, Australia.
M
M
McLean
A
A
Bisits
J
J
Davies
W
W
Walters
A
A
Hackshaw
K
K
De Voss
R
R
Smith
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D003346:Corticotropin-Releasing Hormone / Q000097:blood*; D005260:Female; D006801:Humans; D007752:Obstetric Labor, Premature / Q000175:diagnosis* / Q000517:prevention & control; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011446:Prospective Studies; D011863:Radioimmunoassay; D012307:Risk Factors; D000509:alpha-Fetoproteins / Q000378:metabolism*
D015415:Biomarkers; D000509:alpha-Fetoproteins; D003346:Corticotropin-Releasing Hormone