Placental size and the prediction of severe early-onset intrauterine growth restriction in women with low pregnancy-associated plasma protein-A.
OBJECTIVE
Screening studies for trisomy 21 demonstrate that low maternal serum pregnancy-associated plasma protein-A (PAPP-A) at 11-13 weeks' gestation is associated with stillbirth, intrauterine growth restriction (IUGR) and pre-eclampsia in chromosomally normal fetuses. However, the strength of these associations is too weak to justify screening for these placental insufficiency syndromes. Our objective was to evaluate placental size and uterine artery (UtA) Doppler imaging as second-stage screening tests for women with low PAPP-A.


METHODS
We prospectively studied 90 normal singleton pregnancies with first-trimester PAPP-A </= 0.30 multiples of the median. Maternal serum alpha-fetoprotein (AFP) at 15-18 weeks' gestation, and second-trimester placental size and UtA Doppler indices were assessed as predictors of pregnancy outcome.


RESULTS
The risks of IUGR, preterm delivery before 32 weeks' gestation and stillbirth were significantly associated with small placental size (relative risk (RR), 3.96; 95% CI, 2.21-5.98; RR, 3.96; 95% CI, 2.21-5.98; and RR, 6.44, 95% CI, 2.74-14.54, respectively) and elevated AFP (RR, 3.67; 95% CI, 1.78-7.71; RR, 2.48; 95% CI, 1.23-4.94; and RR, 5.14; 95% CI, 1.66-16.85, respectively), but not with abnormal UtA Doppler indices. The combination of elevated AFP and small placental size further increased the risk of IUGR (RR, 4.88; 95% CI, 2.88-5.31), delivery before 32 weeks' gestation (RR, 4.25; 95% CI, 2.38-4.98) and stillbirth (RR, 7.44; 95% CI, 3.04-3.75).


CONCLUSIONS
Small placental size and elevated AFP, but not UtA Doppler indices, identify women with low PAPP-A at high risk of IUGR, extreme preterm delivery and stillbirth. These additional screening tests may directly improve perinatal outcomes in women with low PAPP-A.
Proctor
L K
LK
Placenta Clinic, Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada.
Toal
M
M
Keating
S
S
Chitayat
D
D
Okun
N
N
Windrim
R C
RC
Smith
G C S
GC
Kingdom
J C P
JC
D000328:Adult; D015415:Biomarkers / Q000097:blood; D005260:Female; D005317:Fetal Growth Retardation / Q000175:diagnosis*; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D009929:Organ Size; D010920:Placenta / Q000033:anatomy & histology / Q000000981:diagnostic imaging*; D010927:Placental Insufficiency / Q000000981:diagnostic imaging*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D047928:Premature Birth; D012307:Risk Factors; D050497:Stillbirth; D014463:Ultrasonography; D055988:Uterine Artery / Q000000981:diagnostic imaging*
D015415:Biomarkers; D011266:Pregnancy-Associated Plasma Protein-A