Osteoprotegerin and RANKL serum concentrations in neonates of mothers with early-onset pre-eclampsia: comparison with neonates of normotensive mothers

Abstract

BackgroundPre-eclampsia is a known risk factor for long-term cardiovascular complications. Osteoprotegerin (OPG) and the receptor activator of nuclear factor κB ligand (RANKL) have been implicated in the pathogenesis of cardiovascular disease. The OPG-RANKL axis function is also altered in pregnant women with pre-eclampsia, but there is lack of data regarding OPG and RANKL concentrations in their neonates. AimsTo examine the effects of early-onset pre-eclampsia on OPG and RANKL serum concentrations at birth, taking into account the influence of various perinatal factors. Study designOPG and RANKL serum concentrations were measured in 28 premature newborns of mothers with early onset pre-eclampsia, and in 28 preterm and 28 full-term neonates of normotensive mothers (control groups). ResultsNeonates of pre-eclamptic mothers had higher OPG and lower RANKL levels compared to both control groups (Kruskal-Wallis P < 0.0001 and P = 0.014, respectively). Regression analysis showed that pre-eclampsia (P < 0.0001), birth weight z-score (P = 0.048) and antenatal steroid administration (P = 0.034) were significant determinants of OPG levels. Multivariable regression analysis also showed that pre-eclampsia was an independent predictor of increased diastolic and mean blood pressure in these neonates. ConclusionsEarly-onset pre-eclampsia affects OPG concentrations at birth and is an independent predictor of increased blood pressure in the offspring. Our findings suggest that altered OPG-RANKL axis function may be one of the mechanisms of cardiovascular ‘programming’ in fetuses exposed to pre-eclampsia.