Placental growth factor testing in the management of late preterm pre-eclampsia without severe features: A multi-center, randomized, controlled trial

Am J Obstet Gynecol. 2021 Apr 3;S0002-9378(21)00224-6. doi: 10.1016/j.ajog.2021.03.044. Online ahead of print.


Background: In women with late preterm pre-eclampsia the optimal time of delivery is controversial, because of the fine balance between maternal benefits from early delivery and the risks for prematurity. It remains challenging to define prognostic markers to identify women at the highest risk of complication, in which a selective planned delivery may reduce maternal and perinatal adverse outcomes.

Objective: This trial aimed to determine whether using an algorithm based on maternal levels of placental growth factor (PlGF) in women with late preterm pre-eclampsia to decide the best time of delivery reduced the progression to pre-eclampsia with severe features without increasing the adverse perinatal outcomes.

Study design: This parallel-group, open-label, multicenter, randomized controlled trial was conducted in seven maternity units across Spain. We compared selective planned delivery based on maternal levels of PlGF at admission (revealed group) and expectant management under usual care (concealed group) with individual randomization in singleton pregnancies with late preterm pre-eclampsia from 34 to 36+6 weeks gestation. The co-primary maternal outcome was the progression to pre-eclampsia with severe features. The co-primary neonatal outcome was morbidity up to infant hospital discharge with a non-inferiority hypothesis (non-inferiority margin of 10% difference in incidence). Analyses were conducted by intention-to-treat.

Results: Between January 1, 2016, and December 31, 2019, 178 women were recruited. Of those women, 88 women were assigned to the revealed group and 90 were assigned to the concealed group. The data analysis was performed before the completion of the required sample size. The proportion of women with progression to pre-eclampsia with severe features was significantly lower in the revealed group than in the concealed group (adjusted relative risk [RR], 0.5; 95% confidence interval [CI], 0.33-0.76; p=0.001). The proportion of infants with neonatal morbidity was not significantly different between groups (adjusted RR, 0.77; 95% CI, 0.39-1.53; p=0.45).

Conclusions: There is evidence to suggest that the use of an algorithm based on PlGF levels in women with late preterm pre-eclampsia results in a lower rate of progression to pre-eclampsia with severe features and reduces maternal complications, without worsening the neonatal outcomes. This trade-off should be discussed with women with late preterm pre-eclampsia to allow shared decision-making on the timing of delivery.

Keywords: Biomarkers; Blood pressure; Infant; Morbidity; Newborn; Pre-eclampsia; Prediction; Therapy.