Association of serum angiogenic factors with bronchopulmonary dysplasia. The ANGIODYS cohort study

Objectives: Angiogenic factors may be involved in lung development. To evaluate the relations between maternal and cord blood angiogenic factors (sFlt-1, placental growth factor [PlGF], soluble endogline [sEng], transforming growth factor beta [TGF-beta]) and their association with moderate and severe bronchopulmonary dysplasia (BPD) in very preterm growth-restricted infants. Study design: Prospective monocentric cohort study. Twenty-four mother-child dyads featuring antepartum preeclampsia, intra-uterine growth restriction (IUGR) and birth before 30 weeks' gestation were included. This ensured a 80% power to test whether sFlt-1 maternal levels would be twice as high in cases of BPD as in the absence of BPD. Main outcome measures: Four pro/anti-angiogenic factors from two pathways (sFlt-1, PlGF and sEng, TGFbeta) were measured in maternal serum before delivery (at the time of hospitalization or the day of birth) and in neonates' cord blood. Neonatal outcome was moderate to severe BPD, defined as oxygen requirement for at least 28 days and persistent need for oxygen or ventilatory support at 36 weeks' postmenstrual age. Results: sFlt-1 levels were positively correlated in maternal serum and cord blood (r(s) = 0.83, p < .001) but levels of PlGF and TGF-beta and its receptor sEng were not. Among all the factors studied in cord and maternal blood, none was associated with BPD. Conclusions: In IUGR preterm babies born before 30 weeks' gestation from preeclamptic mothers, serum sFlt-1, PlGF and sEng, TGF-beta levels were not correlated with BPD. The increased BPD risk in preterm neonates born from preeclamptic mothers cannot be related to high sFlt-1 levels.