Use of the angiogenic biomarker profile to risk stratify patients with fetal growth restriction

Gabriel A Arenas, Nga Y Tang, Ariel Mueller, Joana Lopes Perdigao, Harjot Kaur, Jacques S Abramowicz, Kathryn Mussatt, Kiang-Teck J Yeo, Sarosh Rana
American journal of obstetrics & gynecology MFM 2021 May 12, : 100394

BACKGROUND: Novel angiogenic biomarker profiles have demonstrated emerging evidence for predicting preeclampsia onset, severity, and adverse outcomes. Limited data exists in screening patients with fetal growth restriction for preeclampsia development using angiogenic biomarkers.

OBJECTIVE: The objective of this study was to risk stratify patients with fetal growth restriction using a soluble fms-like tyrosine kinase-1 (sFlt1) to placental growth factor (PlGF) ratio. Previously published cutoff of 38 was used to predict preeclampsia development and severity as well as adverse maternal or neonatal outcomes within a two-week time period.

STUDY DESIGN: This was a prospective observational cohort study carried out in a single tertiary hospital. Patients with a singleton fetal growth restriction pregnancy between 24 and 37 weeks gestation were evaluated using serial two-week encounters from the time of enrollment until delivery. Pregnancies with proven genetic or infectious etiology of fetal growth restriction or congenital anomalies were excluded. Ultrasound growth and Doppler measurements were obtained at the start of every encounter with routine preeclampsia labs and blood pressure checks when clinically indicated. Maternal serum was collected for all serial encounters and measured for sFlt1 and PlGF after delivery in a double blinded fashion. Maternal charts were reviewed for baseline demographic characteristics, pregnancy diagnoses and outcomes, and neonatal outcomes.

RESULTS: A total of 45 patients were enrolled for a total of 77 encounters, with the median (quartile 1, quartile 3) gestational age of the study enrolled at 31.43 (28.14, 33.57) weeks. Patients were divided into low risk (ratio < 38) and high risk (ratio ≥ 38) groups. Baseline characteristics of patients did not show any significant differences, including preeclampsia labs or ultrasound parameters, between the two groups. Systolic and diastolic blood pressures upon enrollment were statistically elevated when sFlt1/PlGF ≥ 38 (p = 0.02 and p = 0.01, respectively). Compared to patients with a low ratio, patients with a high ratio had a greater proportion of preeclampsia diagnosis, higher rates of preterm delivery under 34 and 37 weeks of gestation, smaller neonatal birthweight, and a smaller time to delivery from testing to delivery.

CONCLUSIONS: Among patients with fetal growth restriction, the sFlt1/PlGF ratio may serve as a potential biomarker for identifying at risk patients for developing preeclampsia and subsequently preterm delivery.

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