Objective: To evaluate the disease burden of placental maternal vascular malperfusion pathology in a low-risk nulliparous population and test the hypothesis that a multiparameter model in the second trimester can predict maternal vascular malperfusion with high precision.
Methods: A single-center, prospective cohort study was conducted in healthy nulliparous women. Maternal vascular malperfusion disease burden was estimated by incidence, relative risk (RR), and population-attributable risk percent. Maternal risk factors, serum biomarkers, Doppler, and placental morphologic ultrasonography were examined in isolation and in combination for prediction of this placental pathology.
Results: The incidence of maternal vascular malperfusion pathology was 8.4% (72/856). Women with pathology had higher risk of preeclampsia (8.33% compared with 1.79%; RR 4.67, 95% CI 1.85-11.77%; population-attributable risk 23.6%, 95% CI 16.9-31.6%), small for gestational age (SGA) (47.22% compared with 9.45%; RR 5.00, 95% CI 3.6-6.93%; population-attributable risk 25.2%, 95% CI 22.1-28.5%), and the composite of adverse outcomes (defined as SGA or preeclampsia) (47.22% compared with 10.59%; RR 4.46, 95% CI 3.25-6.13; population-attributable risk 22.5%, 95% CI 19.8-25.5%). The combination of parameters was superior to individual modalities alone in predicting maternal vascular malperfusion, but achieved only moderate precision (area under the curve 0.77, 95% CI 0.71-0.84).
Conclusion: One in 12 healthy nulliparous women develop maternal vascular malperfusion placental pathology, and these pregnancies had a 4.5 times higher risk of developing preeclampsia or delivering a SGA neonate compared with those without this pathology. A multiparameter model achieved modest precision to predict placental maternal vascular malperfusion. Importantly, in low-risk pregnancies, maternal vascular malperfusion accounts for one fourth of pregnancy outcomes with SGA or preeclampsia. The low population-attributable risk of this placental pathology for SGA and preeclampsia illustrates the importance of discovering novel associations to reduce the disease burden of these pregnancy complications.