Objective: Many biochemical observations have shown that nitric oxide (NO) is involved in the vascular angiogenic activity of the fetoplacental unit. The aim of this study was to determine whether NO is implicated in the pathogenesis of intrauterine growth restriction (IUGR).
Methods: We retrospectively assessed amniotic fluid NO from second-trimester amniocentesis of 20 healthy normotensive women who subsequently developed IUGR and 20 controls. The same women were re-assessed at the third trimester when IUGR had developed and when the same 20 controls had shown normal pregnancy. Amniotic fluid NO was detected by discontinuous spectrophotometry and the Griess reaction.
Results: At the second trimester, NO levels in women with subsequent IUGR were significantly lower than in controls (4.1 +/- 0.2 microg/mg creatinine vs. 6.02 +/- 1.57 microg/mg creatinine, p < 0.001). At the third trimester, in women with IUGR, NO levels were significantly higher than in normal pregnancies (7.4 +/- 1.5 vs. 5.02 +/- 0.9 microg/mg creatinine, p < 0.001), and directly correlated with gestational age when growth restriction was diagnosed (r = 0.69, p < 0.001).
Conclusions: Low levels of NO during the early second trimester may represent an impaired stimulus to vascular formation and endothelial regulation, inducing placental disease and subsequent fetal growth restriction. High levels of amniotic fluid NO during the third trimester may represent a compensation factor for maintaining adequate uteroplacental perfusion in pregnancies with IUGR.