Villous trophoblast abnormalities in extremely preterm deliveries with elevated second trimester maternal serum hCG or inhibin-A

Elevated levels of the maternal prenatal screening markers hCG and inhibin-A, measured at 15-20 weeks gestation, increase the subsequent risk of severe pre-eclampsia and intra-uterine growth restriction (IUGR). Since both markers are produced by syncytiotrophoblast, we tested the hypothesis that these elevations were due to accelerated differentiation of the villous trophoblast compartment. We performed a retrospective study of 12 cases from our Placenta Clinic with total hCG and/or inhibin-A levels of >= 3.0 multiples of the median that subsequently delivered by 28 weeks gestation and compared their placental pathology findings with 24 gestational age-matched controls. Morphometric analysis demonstrated a 41% reduction in the volume ratio of Ki67 positive cytotrophoblast nuclei to total trophoblast in cases vs controls (Student's T-test; p = 0.028). Distal villous hypoplasia (DVH) was significantly more common in cases (10/12) than controls (4/24); Fisher's exact test, p = 0.002. Wave-like syncytial knot (WLSK) formation was significantly more common in cases (9/12) than controls (1/24); Fisher's exact test, p < 0.0001. WLSK formation was associated with DVH and resulted from accumulation of senescent/apoptotic syncytiotrophoblast nuclei along inherent lines of syncytial nuclear organization. Our data support the hypothesis that elevated second trimester maternal serum levels of total hCG and/or inhibin-A may result from premature accelerated differentiation of the villous cytotrophoblasts. The subsequent pathologic findings in the syncytiotrophoblast could render the pregnancy at risk of severe preeclampsia and IUGR. (C) 2011 Published by Elsevier Ltd.