Placental Growth Factor as a Predictor of Adverse Pregnancy Outcomes in Preeclamptic Women in Abakaliki

INTRODUCTION Despite advances in care, preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality worldwide and its syndromic nature makes diagnosis and management difficult.1 Preeclampsia (PE) is a pregnancy-specific syndrome, defined by new onset hypertension and proteinuria after 20 weeks of gestation.2 It complicates 2-8% of pregnancies and accounts for more than 50,000 maternal death annually.2,3 In developing countries, where lack of access to appropriate maternal care is a major problem, maternal death rates are as high as 15% as compared with 0% to 1.8% in industrialized countries.1 A 10-year review of maternal mortality in Ebonyi state University Teaching Hospital showed that PE and eclampsia accounted for 6.1% of maternal death.4 Preeclampsia affects multiple organ systems and can lead to severe maternal and fetal complications.5-10 Maternal and perinatal morbidity and mortality resulting from PE are due to its complications.6-8 Maternal complications include eclampsia, cerebrovascular accident, placental abruption, disseminated intravascular coagulation, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, liver hemorrhage or rupture, pulmonary edema, adult respiratory distress syndrome, acute renal failure, and death. Perinatal consequences include stillbirth, preterm delivery, fetal growth restriction (FGR), and neonatal death.5-10 The only curative treatment for PE is delivery of the placenta.9-13 The challenge in caring for women with PE is to identify those who are at increased risk of complications so that appropriate and timely delivery can be offered.14 Most of the symptoms associated with PE are common and nonspecific, which can lead to poor predictability of adverse outcomes.15 Moreover, the capacity to predict adverse maternal and perinatal outcomes remains poor.15 Recognition of those patients at risk of adverse outcomes related to PE can reduce or avert maternal and perinatal morbidity and mortality associated with the condition.16 Currently available biochemical makers such as proteinuria and uric acid have been shown to be poor predictors of adverse pregnancy outcomes in preeclamptic women.16-20 This suggests that a clinical diagnostic test able to predict maternal and fetal risk could be useful. Among biochemical markers, attention has recently focused on angiogenic factors, such as PlGF. Placental growth factor is an angiogenic growth factor related to vascular endothelial growth factor that is exclusively produced by the trophoblast.18 A growing body of evidence suggests that an imbalance of angiogenic/anti-angiogenic factors are involved in the pathophysiology of PE.18 Studies on the pathogenesis of PE support the hypothesis of a pathogenetic model of defective placentation resulting from reduced concentrations of angiogenic growth factors (free PlGF) and increased concentrations of anti-angiogenic factors such as soluble Fms-like tyrosine kinase-1 (sFlt-1).16-24 The majority of studies of PlGF testing have focused on either prediction of PE or confirmation of the diagnosis once PE is suspected. Even though this biomarker has excellent predictive value for PE, a major issue is that there is no clear intervention that can prevent the subsequent development of the disease. Several preventive measures such as supplementation with vitamin C and vitamin E, aspirin, or calcium fail to consistently prevent subsequent development of PE.19 Thus, the value remains either a "research procedure" or a method of risk assessment to identify patients who may benefit from more intensive surveillance. Currently studies are focused on evaluating the role of plasma angiogenic and anti-angiogenic factors in predicting the outcome of patients with PE. Studies have shown a positive correlation between low maternal serum PlGF levels and adverse maternal and fetal outcomes.21 These findings have led to speculation that PlGF might be useful in both the prediction of PE and prognosis with respect to the occurrence of related adverse outcomes.

Considering the contribution of PE to maternal morbidity and mortality in Abakaliki and poor predictive accuracy of available biochemical markers on adverse pregnancy outcomes and the search for better predictive maker of adverse outcomes among preeclamptic women, a study on PlGF as a predictor of outcomes among preeclamptic women in Abakaliki is important.

1.1 JUSTIFICATION FOR THE STUDY Preeclampsia has remained among the leading causes of maternal morbidity and mortality worldwide.22 Maternal deaths resulting from PE are due to complications associated with the condition.20-25 Clinical prediction of disease complications may facilitate initiation of timely management to prevent morbidity and mortality in the mother and baby. The studies on current predictive biomarkers (proteinuria or uric acid) of adverse outcomes among preeclamptic women have shown poor predictive results.24 Hence there is a need for identification of highly specific and sensitive biomarkers that would allow early identification of patients at risk and for prediction of adverse outcomes for women who developed the condition and thus help in providing proper prenatal care. Placental growth factor appears to be a promising tool in this regard. Literature search showed that this study has not been done in Abakaliki. Hence, the outcome of this study will help to make evidence based recommendations on the role of maternal serum level of PlGF in the management of preeclamptic women in Abakaliki.

3.0 AIM AND OBJECTIVES AND RESEARCH QUESTION 3.1 AIM The aim of the study is to test the predictive accuracy of maternal free PlGF concentration for pregnancy adverse outcomes in patients with preeclampsia based on a single assay at the time of admission.

3.2 SPECIFIC OBJECTIVES To compare the mean serum level of PlGF among preeclamptic women with and without adverse pregnancy outcomes.