Amniotic fluid nitric oxide metabolites, cyclic guanosine 3 ',5 ' monophosphate and dimethylarginine in alloimmunized pregnancies

Objective: To determine the relationship between gestational age or the Lil ey index (the severity of fetal hemolysis) and the amniotic fluid total nit rite (NOx), cyclic guanosine 3',5 'monophosphate (cGMP) and dimethylarginin e (DMA) concentrations. We hypothesized that the concentrations of these co mponents change because of fetal growth or adaptation to fetal anemia. Stud y Design: Amniotic fluids (n=64) were obtained between 23 and 37 weeks from fifty-three patients at risk for alloimmunization. Amniotic fluids from th e pregnancies with a Liley index=1 were considered as controls (n=17). Crea tinine (C, mu Mol) was determined with the Jaffe reagent, nitrite (NOx, mu Mol) with the Griess reagent, cGMP (nMol) by an enzyme immunoassay and DMA (mu Mol) after HPLC. Multiple regression analysis was used for separating t he effects of growth and the estimated degree of anemia. Results: The conce ntration of NOx, cGMP and DMA was not related to the Liley index or whether or not the fetuses needed blood transfusions. The concentrations of creati nine (C), NOx and cGMP increased during pregnancy (in weeks;W) (C=-69.2+6.2 8W; r(2)=0.532; P<0.0001, NOx=-17.6+1.29W; r(2)=0.106; P=0.01, cGMP=-20.9+1 .05W; r(2)=0.414; P<0.0001). The DMA concentration (3.8+/-0.8(SD) and the N Ox/creatinine ratio (181+/-110 mM/M) did not change with gestational age. T he cGMP/creatinine ratios (mu M/M) increased (cGMP/C= 41.8+4.31W; r(2)=0.13 4; P=0.007) whereas the DMA/creatinine ratio (mM/M) declined during pregnan cy (DMA/C=73.1-1.34W; r(2)=0.278; P=0.0002). Consequently, the NOx/DMA and cGMP/DMA ratios increased (NOx/DMA=-6.96+0.43W; r(2)=0.105; P=0.02, cGMP/DM A=-5.9+0.29W; r(2)=0.391; P<0.0001). Conclusions: The concentrations in amn iotic fluid of cGMP and NOX, but not of DMA increase during gestation. The cGMP/creatinine ratio increases also whereas that of DMA decreases. The cha nges in products of the NO-cGMP pathway are independent of mild to moderate fetal hemolysis and may result from fetal growth as well as from reduced i nhibition of NO synthase by DMA. Gestational age related effects should be taken into account when analyzing nitric oxide metabolites in amniotic flui ds. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.