Association of extreme first-trimester free human chorionic gonadotropin-beta, pregnancy-associated plasma protein A, and nuchal translucency with intrauterine growth restriction and other adverse pregnancy outcomes.
OBJECTIVE
The purpose of this study was to determine the association between first-trimester trisomy 21 screening markers (free human chorionic gonadotropin-beta [hCG], pregnancy-associated plasma protein A [PAPP-A], and nuchal translucency) and adverse pregnancy outcome.


METHODS
This was a cohort study of 8012 patients enrolled in a National Institute of Child Health and Human Development-sponsored study of first-trimester trisomy 21 and 18 screening. Trisomy 21 and 18 risk results and individual marker levels in unaffected pregnancies and pregnancies with adverse outcomes were evaluated.


RESULTS
PAPP-A <1st percentile (OR 5.4, 95% CI 2.8-10.3) and PAPP-A <5th percentile (OR 2.7, 95% CI 1.9-3.9) and free beta-hCG <1st percentile (OR 2.7, 95% CI 1.3-5.9) were associated with increased risk of intrauterine growth restriction (IUGR) with positive predictive values of 24.1%, 14.1%, and 14.3%, respectively. PAPP-A <5th percentile (OR 2.3 95% CI 1.1-4.7) and nuchal translucency >99th percentile (OR 3.5, 95% CI 1.1-11.3) were associated with increased risk of preterm delivery before 34 weeks. Increased risk at screening for trisomy 21 and 18 identified 16 of the 29 other chromosomal abnormalities (55%). Low free beta-hCG, low PAPP-A, and increased nuchal translucency were all associated with an increased rate of fetal abnormality.


CONCLUSIONS
Extreme values of first-trimester free beta-hCG, PAPP-A, and nuchal translucency are all associated with adverse outcomes. The especially high predictive value for IUGR of PAPP-A levels below the 1st percentile suggests that patients within this group may benefit from increased surveillance for this condition.
Krantz
David
D
NTD Laboratories Inc., 403 Oakwood Road, Huntington Station, NY 11746, USA. dakrantz@ntdlabs.com
Goetzl
Laura
L
Simpson
Joe Leigh
JL
Thom
Elizabeth
E
Zachary
Julia
J
Hallahan
Terrence W
TW
Silver
Richard
R
Pergament
Eugene
E
Platt
Lawrence D
LD
Filkins
Karen
K
Johnson
Anthony
A
Mahoney
Maurice
M
Hogge
W Allen
WA
Wilson
R Douglas
RD
Mohide
Patrick
P
Hershey
Douglas
D
Wapner
Ronald
R
D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000097:blood*; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood*; D006801:Humans; D048208:Nuchal Translucency Measurement; D016017:Odds Ratio; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First / Q000097:blood*; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D011446:Prospective Studies; D012680:Sensitivity and Specificity
D018997:Chorionic Gonadotropin, beta Subunit, Human; D011266:Pregnancy-Associated Plasma Protein-A