Second Trimester Placental Growth Factor Levels and Placental Histopathology in Low-Risk Nulliparous Pregnancies

Objective: Placental growth factor (PlGF) levels are lower at delivery in pregnancies with preeclampsia or fetuses small for gestational age (SGA). These obstetrical complications are typically mediated by placental dysfunction, most commonly related to the specific placental phenotype termed placental maternal vascular malperfusion (MVM). The objective of this study was to determine the relationship between PlGF levels in the second trimester and the development of placental diseases that underlie adverse perinatal outcomes. Methods: We performed a secondary analysis of the prospective Placental Health Study in unselected healthy nulliparous women (n = 773). Maternal demographic data, Doppler ultrasound measurements, and plasma PlGF levels at 15 to 18 weeks gestation were analyzed for association with pregnancy outcomes and placental pathology following delivery. Results: Low PlGF levels in the second trimester (<10th percentile; <72 pg/mL) was associated with preterm delivery (<37 weeks; 26% vs. 6%, P < 0.001; unadjusted odds ratio (OR) 5.75, 95% CI 3.2-10.5), reduced mean birth weight (2998 vs. 3320 g, P < 0.001), SGA deliveries (25% vs. 11%, P = 0.001; OR 2.6, 95% CI 1.5-4.6), and preeclampsia (7% vs. 2%, P = 0.02; OR 4.3, 95% CI 1.5-12.8) relative to normal PlGF levels (>10th percentile; >72 pg/mL). Low PlGF was associated with lower mean placental weight (447 vs. 471 g, P = 0.01), aberrant cord insertion (25% vs. 12%, P = 0.001) and a pathologic diagnosis of MVM (18% vs. 11%, P = 0.04; OR 1.9, 95% CI 1.01-3.55) but not with other placental pathologies. Conclusion: MVM placental pathology and related adverse perinatal outcomes are associated with low PlGF in the early second trimester for healthy nulliparous women.