First-trimester serum analytes, biophysical tests and the association with pathological morphometry in the placenta of pregnancies with preeclampsia and fetal growth restriction

Objective: We test the hypothesis that first-trimester serum analytes, 4-D power Doppler placental vascular indices and uterine artery Doppler (UAD) predicts abnormal placental morphometry in pregnancies with preeclampsia (PE) and fetal growth restriction (FGR). Study design: Maternal serum analytes (PAPP-A, hCG, ADAM12s, and PP13), bilateral UADs, and placental vascular indices were measured at 11-14 weeks in a nested-case control study within a prospective cohort of women followed from the first-trimester to delivery. Vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were obtained from 4-D power Doppler histograms. Serum analytes were measured using immunofluorometric assays and values converted to multiples of the median (MoM) for gestational age. Morphometric analysis was performed on placentas from pregnancies complicated by PE (n = 13), gestational hypertension (HBP, n = 7) and FGR (defined as fetal weight <10th percentile with abnormal umbilical artery Doppler: n = 7); and 20 uncomplicated pregnancies. Two pregnancies had both FGR and PE. Each placenta was weighed and random samples taken, and fixed in formalin within 1 h of delivery. Hematoxylin & Eosin stained slides were analyzed by design-based stereology to quantify linear dimensions, surface areas and volumes of placental components. Paired t-test and ANOVA with adjustments for multiple comparisons were used. Results: The surface areas of terminal and intermediate villi as well as the volume of terminal villi were significantly smaller in placentas from pregnancies complicated by FGR and PE. Compared with the control group the mean PAPP-A (MoM) was lower in the pregnancies with abnormal placenta morphometry (1.1 ± 0.5 versus 0.7 ± 0.5, P = 0.03). The morphometric indices were lower in those pregnancies with low PAPP-A and IUGR compared with preeclampsia. Conclusion: First-trimester PAPP-A levels are associated with abnormal placental morphometry at delivery in pregnancies with PE and IUGR. These findings may explain the association between adverse pregnancy outcomes and first-trimester PAPP-A.