Consequences of Antiangiogenic Factors Involved in Preeclampsia on Intra-uterine Growth Restricted Preterm Newborn

Overview

Preeclampsia complicates about 2-7% of pregnancies and is a major contributor to maternal and neonatal morbidity and mortality worldwide. Imbalance between circulating angiogenic and antiangiogenic factors has emerged as a potential key pathway in the pathophysiology of preeclampsia. Patients with preeclampsia have a higher circulating concentration of antiangiogenic factors (ie, soluble vascular endothelial growth factor receptor-1 \[sVEGFR- 1\], also called soluble fms-like tyrosine kinase 1 \[sFlt1\]) and soluble endoglin (sEng)\] and a lower maternal circulating concentration of free angiogenic factors (ie, vascular endothelial growth factor \[VEGF\] and placental growth factor \[PlGF\]) than patients with a normal pregnancy. Bronchopulmonary dysplasia is the main respiratory sequelae of preterm birth. Its rate increased in preterm infants born from mother with preeclampsia. Recent studies showed that bronchopulmonary dysplasia is consistently accompanied by a reduction in the number of small arteries and on abnormal distribution of vessels within the distal lungs. This is associated with reduced lung VEGF expression. The main objective of this population-based study, ie in intra uterine growth restricted preterm babies born before 30 weeks of gestational age, was to examine whether levels of sFlt1 at birth in maternal and umbilical cord blood and in the amniotic fluid is associated with an increased risk of BPD.

Preeclampsia complicates about 2-7% of pregnancies and is a major contributor to maternal and neonatal morbidity and mortality worldwide. Preeclampsia is the main cause of intra-uterine growth restriction and could lead to a preterm delivery for fetal or maternal indication. Imbalance between circulating angiogenic and antiangiogenic factors has emerged as a potential key pathway in the pathophysiology of preeclampsia. Patients with preeclampsia have a higher circulating concentration of antiangiogenic factors (ie, soluble vascular endothelial growth factor receptor-1 \[sVEGFR- 1\], also called soluble fms-like tyrosine kinase 1 \[sFlt1\]) and soluble endoglin (sEng)\] and a lower maternal circulating concentration of free angiogenic factors (ie, vascular endothelial growth factor \[VEGF\] and placental growth factor \[PlGF\]) than patients with a normal pregnancy. Bronchopulmonary dysplasia is the main respiratory sequelae of preterm birth. Its rate increased in preterm infants born from mother with preeclampsia. Recent studies showed that bronchopulmonary dysplasia is consistently accompanied by a reduction in the number of small arteries and on abnormal distribution of vessels within the distal lungs. This is associated with reduced lung VEGF expression. Infants with maternal preeclampsia had higher cord blood sFlt-1 but lower PlGF and VEGF circulating levels. There was a significantly positive relationship between birth weight and cord blood sFlt-1 levels, witness of consequences of these antiangiogenic factors on fetuses. However, no study to date has shown a correlation between the level of angiogenic and antiangiogenic factors and the main complications of preterm birth. The main objective of this population-based study, ie in 24 intra uterine growth restricted preterm babies born before 30 weeks of gestational age from mother with preeclampsia, was to examine whether levels of sFlt1 at birth in maternal and umbilical cord blood and in the amniotic fluid is associated with an increased risk of BPD at 36 weeks of gestational age. The second objectives are to explore the link between the levels of angiogenic and antiangiogenic factors and the main complications of preterm birth, ie, necrotizing enterocolitis, intra-ventricular hemorrhage, periventricular leukomalacia or infection.