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Maternal Vascular Malperfusion and Adverse Perinatal Outcomes in Low-Risk Nulliparous Women

Wright, Emily MD; Audette, Melanie C. MD, PhD; Ye, Xiang Y. BSc, MSc; Keating, Sarah MD, MSc; Hoffman, Barry PhD; Lye, Stephen J. PhD; Shah, Prakesh S. MD, MSc; Kingdom, John C. MD

doi: 10.1097/AOG.0000000000002264
Contents: Original Research

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.

Prediction of maternal vascular malperfusion of the placenta in healthy nulliparous women achieves only moderate precision; however, the majority of adverse perinatal outcomes are not explained by this disease.

Department of Obstetrics & Gynaecology, Maternal-Fetal Medicine Division, the Lunenfeld-Tanenbaum Research Institute, the Maternal-Infant Care Research Centre, the Department of Pediatrics, and the Department of Pathology and Laboratory Medicine at Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

Corresponding author: John C. Kingdom, MD, Department Obstetrics & Gynaecology, Mount Sinai Hospital, Ontario Power Generation Building, 700 University Avenue, Room 3-904, Toronto, ON, Canada M5G 1Z5; email:

Supported by the Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario (MSU-11-021) from University Health Network, Toronto (to Dr. Kingdom) and the Rose Torno Chair (to Dr. Kingdom) from Mount Sinai Hospital. Dr. Shah holds an Applied Research Chair in Reproductive and Child Health Services and Policy Research awarded by the CIHR (APR-126340).

Financial Disclosure The authors did not report any potential conflicts of interest.

Presented as a poster presentation at the 5th International Fetal Growth Meeting, November 17–19, 2016, Toronto, Ontario, Canada.

The authors thank all of the women who participated in the Placental Health Study; Natasha Milligan, MSc, for study coordination and data entry; Viji Ayyathurai, RDMS, for performing the placental ultrasound examinations; and Roche Canada, who subsidized the cost of the placental growth factor and soluble fms-like tyrosine kinase-1 reagents used for the study.

Each author has indicated that he or she has met the journal's requirements for authorship.

© 2017 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.