(1199) Second trimester placental proteins are associated with maternal vascular malperfusion among patients with adverse outcomes

Objective: Adverse pregnancy outcomes (APO) are known to be heterogenous in etiology; many are linked to maternal vascular malperfusion (MVM) of the placenta.  Second trimester placental proteins have poor prediction of APO. Placental proteins may have a greater association with APO related to a specific underlying mechanism such as MVM.  The objective of this study is to evaluate levels of second trimester placental proteins and placental MVM among patients with an APO.

Study Design:

This is a secondary analysis of a prospective cohort study of 9,289 low risk nulliparous patients with singleton gestation (nuMom2b). For this analysis, participants who met the following criteria were included: 1. APO defined as preterm birth (< 37 weeks), preeclampsia/eclampsia, small for gestational age infant, or stillbirth; 2. Maternal serum placental proteins (sFlt-1, Adam-1, VEGF, endoglin, bHcg, AFP, PlGF, Inhibin A, Papp-A, sFlt/PlGF) collected between 16 and 21 weeks gestational age; 3. Placental pathology data. A single perinatal pathologist (LE) manually reviewed all placental data (lesions and additional comments included in the publicly available data set) to categorize participants as MVM absent or present. Placental protein levels were compared by MVM category using Wilcoxon rank sum.

Results: Of the 9,289 participants in the parent study, 2,091 (24%) had APO. Of these, 510 patients were eligible for inclusion, of which 216 (42%) had any presence of MVM.  There was a significantly higher level of inhibin-A and sFlt-1/PlGF ratio and lower levels of VEGF and PlGF among those with MVM compared to those without (Table). A trend towards increase in sFlt-1, ADAM-12, and endoglin was additionally seen in MVM related APO.

Conclusion:

Among individuals with APO, MVM is associated with significant differences in second trimester maternal serum placental proteins, especially those related to angiogenesis.  Over half of APO were unrelated to MVM in this cohort. Classifying APO by placental pathology may lead to improvement in use and development of predictive biomarkers, given the underlying heterogeneity of APO.