Early diagnosis of preeclampsia using placental growth factor: An operational pilot study in Maputo, Mozambique

Highlights

• In Mozambique, introducing PlGF to assess risks was associated with increased referrals to higher levels of care.

• Low PlGF (<100 pg/ml) identifies women at increased risk of adverse maternal and perinatal events.

• Stillbirth complicates preeclampsia pregnancies approximately one-third of the time when PlGF < 50 pg/ml.

• All women in the study were hypertensive with suspected preeclampsia.

• PlGF values were revealed to the clinical staff as an element of clinical assessment.

Abstract

In well-resourced settings, reduced circulating maternal free placental growth factor (PlGF) aids in either predicting or confirming the diagnosis of preeclampsia, fetal growth restriction, stillbirth, preterm birth, and delivery within 14 days of testing when pre-eclampsia is suspected. This operational pilot implementation of maternal plasma PlGF in women with suspected preeclampsia was conducted in six antenatal clinics in Maputo, Mozambique (six control clinics for comparison). The primary outcome was transfer to higher levels of care, following the informative PlGF assay. Of antenatal visits, 133/31,993 (0.42%) and 20/33,841 (0.06%) resulted in pre-eclampsia-related transfers of care for women attending intervention and control clinics, respectively (p < .0001). The clinic-to-delivery for women with low PlGF (<100 pg/ml) interval was shorter, (vs normal PlGF (median 10 days [IQR 1–25] vs 36 [11–83], p < .0001)). Low PlGF was associated with younger maternal age, higher blood pressure, earlier delivery, more therapeutic interventions, preterm birth, lower birth weight, and perinatal loss. In addition, one-third of hypertensive women with PlGF < 50 pg/ml suffered a stillbirth. In urban Mozambican women with symptoms and/or signs suggestive of preeclampsia, low maternal plasma PlGF concentrations are associated with increased risks of adverse pregnancy outcomes, especially early delivery and stillbirth. Therefore, introducing PlGF into the clinical care of women with suspected preeclampsia was associated with increased transfers to higher levels of care; low PlGF (<100 pg/ml) was associated with increased maternal and perinatal risks. PlGF < 50 pg/ml is particularly associated with stillbirth in women with suspected preeclampsia.

Introduction

Pregnancy hypertension, especially preeclampsia, remains a significant contributor to adverse maternal and perinatal events in sub-Saharan Africa [1], [2]. Some women whose pregnancies are complicated by preeclampsia have evidence of angiogenic factor imbalance, with a surfeit of antiangiogenic factors (e.g., soluble fms-like tyrosine kinase-1 (sFlt-1)) and reduced proangiogenic factors (e.g., placental growth factor (PlGF)) [3], [4], [5], [6], [7].

Previously, we have confirmed the diagnostic performance of masked plasma PlGF in identifying women at increased risk of imminent delivery in clinics in Maputo, Mozambique [8]; through the identification of pregnancy complications beyond preeclampsia, such as fetal growth restriction of placental origin [9]. Therefore, we have proposed that PlGF should improve the provision of precision medicine to individual women and improve pregnancy outcomes for those with preeclampsia or related placenta-mediated complications in all settings. Thereby, clinicians in all settings may be better able to triage women with suspected complications to optimize the care of those most at risk within stretched health systems.

After completion of this technical evaluation study, we designed and conducted a pilot implementation study in health centers to assess the impact of PlGF in aiding the diagnosis and time-of-disease risk stratification of preeclampsia, and, thereby, improving appropriate interventions for, and timely care of women with preeclampsia. In contrast to clinical research methods, which typically focus on the health effects of an evidence-based practice, implementation studies typically focus on rates and quality of use of evidence-based practices rather than their effects [10].