Objective: To investigate the status of the fetal renin-angiotensin system (RAS) in pregnancies complicated by severe intrauterine growth retardation (IUGR), and its possible relationship to elevated fetoplacental vascular resistance as indicated by abnormal umbilical artery Doppler flow velocity waveforms (FVW).
Design: Prospective survey of pregnancies falling into predefined categories and presenting at the Queen Mothers Hospital, Glasgow, over the study period.
Subjects: Effects of mode of delivery and gestational age were investigated using uncomplicated term pregnancies delivered vaginally (SVD group, n = 15) or by elective caesarean section (ECS group, n = 9), and normal pregnancies with spontaneous preterm onset of labour (PREM group, n = 6; normal birthweight for gestational age (31 weeks)). These groups were used as controls for the 13 IUGR cases delivered preterm (31 weeks) by caesarean section in the fetal interest.
Main outcomes measures: Umbilical artery FVW, birthweight, cord venous angiotensin II concentration ([cv ANG II]), fetoplacental vascular ANG II receptor concentration.
Results: Cord venous angiotensin II concentration was similar to maternal values in the ECS group (31-101 pmol/l, 95% CI), but was elevated (81-288 pmol/l, P = 0.03) after vaginal delivery. The concentration of ANG II receptors (type AT1, dissociation equilibrium constant, 1.27 nmol/l) in placental primary/secondary stem vascular tissue was lower in the SVD group (18-44 fmol/mg membrane protein, 95% CI), compared with the ECS group (29-122 fmol/mg, P = 0.03) consistent with acute receptor down-regulation by the elevated ANG II levels. No effect of gestational age on receptor number was demonstrable (P = 0.13, PREM (premature delivery) vs ECS group). In the IUGR group, [cv ANG II] (94-378 pmol/l) was markedly elevated compared with the ECS controls (P = 0.001) but receptor concentration (28-84 fmol/mg) was not significantly altered (P = 0.13). No relationships between [cv ANG II] or receptor number and umbilical artery FVW could be identified. No changes in receptor affinity were observed.
Conclusion: These results indicate activation of the fetal RAS in IUGR and suggest that responsiveness of the fetoplacental vasculature to the peptide is not diminished as would be expected from the elevated plasma ANG II levels. ANG II may contribute to the increased fetoplacental vascular resistance observed in this disorder, but does not apparently account for the abnormal umbilical artery FVW that is observed in a proportion of IUGR cases.