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Maternal serum uric acid as predictor of fetal acidemia
International Journal of Gynecology & Obstetrics 77 Ž2002. 35᎐36
Brief communication
Maternal serum uric acid as predictor of fetal acidemia M.M. AnceschiU , J.J. Piazze, L. Maranghi, A. Ruozi-Berretta, E.V. Cosmi 2nd Institute of Obstetrics and Gynecology, Uni¨ ersity ‘La Sapienza’, Rome I-00161, Italy Received 14 August 2001; received in revised form 5 November 2001; accepted 7 November 2001
Keywords: Maternal uric acid; Fetal Doppler analysis; Fetal heart rate; Neonatal acidemia
An association between hypertension and increased serum levels of uric acid in pregnancy has long been known w1x, and a correlation between uric acid levels and neonatal morbidity has also been established w2,3x. We conducted this study to evaluate the association between maternal serum levels of uric acid, decreased fetal blood flow, and fetal acidemia in pregnancy-induced hypertension ŽPIH.. Eighty-four pregnant women, 39 with a diagnosis of PIH and 45 normotensive, who were evaluated for uric acid level also had Doppler velocimetry and computerized cardiotocography ŽcCTG. investigations. Cases and controls were all delivered by elective cesarean section. Umbilical artery ŽUA. pH was assessed at birth and neonatal acidemia was defined as a pH value of F 7.15 andror a pCO 2 value of G 60 mmHg. U
Corresponding author. Tel.: q39-06-446-0484; fax: q3906-446-9128. E-mail address: [email protected] ŽM.M. Anceschi..
Serum uric acid levels were higher in women with PIH than in controls Ž5.6" 1.7 mgrdl vs. 4.5" 1.4 mgrdl, Ps 0.01.. In women with PIH, serum uric acid levels were positively correlated to the ratio between umbilical artery pulsatility and middle cerebral artery pulsatility Ž r s 0.38, P- 0.05., and inversely correlated to cCTG accelerations greater than 15 beatsrmin Ž r s y0.32, P- 0.05.. When maternal uric acid levels were correlated with fetal acid᎐base status parameters, a negative correlation was found for UA pH Ž r s y0.48, Ž r s y0.52, P- 0.001., UA HCOy 3 P- 0.004., and UA base excess values Ž r s y0.57, P- 0.0004. ŽTable 1.. We determined by receiver operator curve analysis that maternal serum uric acid values G 7.1 mgrdl were able to predict an umbilical artery pH value of F 7.15 or a pCO 2 value of G 60 mmHg at birth, with a sensitivity of 42.9%, a specificity of 92.6%, and a positive likelihood ratio of 5.79. During hypoxia, adenine monophosphate, which cannot be reconverted into ATP because of a lack of oxygen, is degraded into adenosine, hypoxan-
0020-7292r02r$20.00 䊚 2002 International Federation of Gynecology and Obstetrics. Published by Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 0 - 7 2 9 2 Ž 0 1 . 0 0 5 8 4 - 7
M.M. Anceschi et al. r International Journal of Gynecology & Obstetrics 77 (2002) 35᎐36
36
Table 1 Linear regression analysis of maternal uric acid levels Žas independent variable. and feto-neonatal indices in PIH patients and in controls Dependent variable
UArMCA ratio Acc 15 beatsrmin UA pH UA HCO3 y Žmmolrl. UA Becf Žmmolrl. 1 min Apgar 5 min Apgar
PIH Ž n s 39.
Controls Ž n s 45.
r
P
r
P
0.38 y0.32 y0.52 y0.48 y0.57 y0.41 y0.48
0.05 0.05 0.001 0.004 0.004 0.01 0.003
0.12 y0.11 y0.11 y0.19 y0.15 y0.11 y0.12
0.39 0.28 0.93 0.15 0.24 0.33 0.31
UA, umbilical artery; MCA, middle cerebral artery; Acc 15, accelerations ) 15 bpm at cCTG.
thine, and finally uric acid. ATP degradation and cell damage are therefore sources of uric acid. In addition, hypoxia and ischemia induce the expression of xanthine oxidase, the rate-limiting enzyme for the production of uric acid. One may speculate that a fetus under hypoxic conditions may be the source of an increased uric acid level in the mother. Reduced placental blood flow decreases the delivery of nutrients and oxygen to the fetus, with subsequent hypoxia. Hypoxanthine levels are found to be elevated in hypoxic fetuses w3x and neonates w2x. Hypoxanthine can cross the placenta, providing further substrate for xanthine oxidase. Markers other than hypoxanthine or xanthine have also been found to be predictors of perinatal asphyxia Že.g. the ratio of uric acid to creatinine in urine.. The increased UA pulsatility index observed in PIH suggest an obliteration of placental vessels and thus an increased breakdown of placental products. These may represent an important source of additional purine substrates for xanthine oxidase and, consequently, of increased uric acid levels and protein metabolites. Uric acid may act as an antioxidant. In unpub-
lished in vitro experiments, we observed that uric acid levels strongly correlate with the oxidability of isolated LDL, and LDL oxidability was previously shown to be increased in PIH w4x. In conclusion, an increased uric acid level is a marker for reduced fetoplacental blood flow and may be useful as a predictor of fetal acidemia. Acknowledgements Supported by MIUR and CNR. References w1x Lim KH, Friedman SA, Eckere JL, Kao L, Kilpatrick SJ. The clinical utility of serum uric acid measurement in hypertensive disease of pregnancy. Am J Obstet Gynecol 1998;178:1067᎐1071. w2x Saugstad OD. Hypoxanthine as a measurement of hypoxia. Pediatr Res 1975;9:158᎐161. w3x Breborowicz GH, Szczapa-Krenz H, Szymankiewicz M, Gadzinowski J. Determination of uric acid ŽUA. in umbilical blood in diagnosis of intrauterine hypoxia. Thai J Obstet Gynaecol 2001;13ŽSuppl 1.:82. w4x Pierucci F, Piazze JJ, Cosmi EV, Anceschi MM. Oxidability of low-density lipoproteins in pregnancy induced hypertension. Br J Obstet Gynaecol 1996;103:1159᎐1161.
Brief communication
Maternal serum uric acid as predictor of fetal acidemia M.M. AnceschiU , J.J. Piazze, L. Maranghi, A. Ruozi-Berretta, E.V. Cosmi 2nd Institute of Obstetrics and Gynecology, Uni¨ ersity ‘La Sapienza’, Rome I-00161, Italy Received 14 August 2001; received in revised form 5 November 2001; accepted 7 November 2001
Keywords: Maternal uric acid; Fetal Doppler analysis; Fetal heart rate; Neonatal acidemia
An association between hypertension and increased serum levels of uric acid in pregnancy has long been known w1x, and a correlation between uric acid levels and neonatal morbidity has also been established w2,3x. We conducted this study to evaluate the association between maternal serum levels of uric acid, decreased fetal blood flow, and fetal acidemia in pregnancy-induced hypertension ŽPIH.. Eighty-four pregnant women, 39 with a diagnosis of PIH and 45 normotensive, who were evaluated for uric acid level also had Doppler velocimetry and computerized cardiotocography ŽcCTG. investigations. Cases and controls were all delivered by elective cesarean section. Umbilical artery ŽUA. pH was assessed at birth and neonatal acidemia was defined as a pH value of F 7.15 andror a pCO 2 value of G 60 mmHg. U
Corresponding author. Tel.: q39-06-446-0484; fax: q3906-446-9128. E-mail address: [email protected] ŽM.M. Anceschi..
Serum uric acid levels were higher in women with PIH than in controls Ž5.6" 1.7 mgrdl vs. 4.5" 1.4 mgrdl, Ps 0.01.. In women with PIH, serum uric acid levels were positively correlated to the ratio between umbilical artery pulsatility and middle cerebral artery pulsatility Ž r s 0.38, P- 0.05., and inversely correlated to cCTG accelerations greater than 15 beatsrmin Ž r s y0.32, P- 0.05.. When maternal uric acid levels were correlated with fetal acid᎐base status parameters, a negative correlation was found for UA pH Ž r s y0.48, Ž r s y0.52, P- 0.001., UA HCOy 3 P- 0.004., and UA base excess values Ž r s y0.57, P- 0.0004. ŽTable 1.. We determined by receiver operator curve analysis that maternal serum uric acid values G 7.1 mgrdl were able to predict an umbilical artery pH value of F 7.15 or a pCO 2 value of G 60 mmHg at birth, with a sensitivity of 42.9%, a specificity of 92.6%, and a positive likelihood ratio of 5.79. During hypoxia, adenine monophosphate, which cannot be reconverted into ATP because of a lack of oxygen, is degraded into adenosine, hypoxan-
0020-7292r02r$20.00 䊚 2002 International Federation of Gynecology and Obstetrics. Published by Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 0 2 0 - 7 2 9 2 Ž 0 1 . 0 0 5 8 4 - 7
M.M. Anceschi et al. r International Journal of Gynecology & Obstetrics 77 (2002) 35᎐36
36
Table 1 Linear regression analysis of maternal uric acid levels Žas independent variable. and feto-neonatal indices in PIH patients and in controls Dependent variable
UArMCA ratio Acc 15 beatsrmin UA pH UA HCO3 y Žmmolrl. UA Becf Žmmolrl. 1 min Apgar 5 min Apgar
PIH Ž n s 39.
Controls Ž n s 45.
r
P
r
P
0.38 y0.32 y0.52 y0.48 y0.57 y0.41 y0.48
0.05 0.05 0.001 0.004 0.004 0.01 0.003
0.12 y0.11 y0.11 y0.19 y0.15 y0.11 y0.12
0.39 0.28 0.93 0.15 0.24 0.33 0.31
UA, umbilical artery; MCA, middle cerebral artery; Acc 15, accelerations ) 15 bpm at cCTG.
thine, and finally uric acid. ATP degradation and cell damage are therefore sources of uric acid. In addition, hypoxia and ischemia induce the expression of xanthine oxidase, the rate-limiting enzyme for the production of uric acid. One may speculate that a fetus under hypoxic conditions may be the source of an increased uric acid level in the mother. Reduced placental blood flow decreases the delivery of nutrients and oxygen to the fetus, with subsequent hypoxia. Hypoxanthine levels are found to be elevated in hypoxic fetuses w3x and neonates w2x. Hypoxanthine can cross the placenta, providing further substrate for xanthine oxidase. Markers other than hypoxanthine or xanthine have also been found to be predictors of perinatal asphyxia Že.g. the ratio of uric acid to creatinine in urine.. The increased UA pulsatility index observed in PIH suggest an obliteration of placental vessels and thus an increased breakdown of placental products. These may represent an important source of additional purine substrates for xanthine oxidase and, consequently, of increased uric acid levels and protein metabolites. Uric acid may act as an antioxidant. In unpub-
lished in vitro experiments, we observed that uric acid levels strongly correlate with the oxidability of isolated LDL, and LDL oxidability was previously shown to be increased in PIH w4x. In conclusion, an increased uric acid level is a marker for reduced fetoplacental blood flow and may be useful as a predictor of fetal acidemia. Acknowledgements Supported by MIUR and CNR. References w1x Lim KH, Friedman SA, Eckere JL, Kao L, Kilpatrick SJ. The clinical utility of serum uric acid measurement in hypertensive disease of pregnancy. Am J Obstet Gynecol 1998;178:1067᎐1071. w2x Saugstad OD. Hypoxanthine as a measurement of hypoxia. Pediatr Res 1975;9:158᎐161. w3x Breborowicz GH, Szczapa-Krenz H, Szymankiewicz M, Gadzinowski J. Determination of uric acid ŽUA. in umbilical blood in diagnosis of intrauterine hypoxia. Thai J Obstet Gynaecol 2001;13ŽSuppl 1.:82. w4x Pierucci F, Piazze JJ, Cosmi EV, Anceschi MM. Oxidability of low-density lipoproteins in pregnancy induced hypertension. Br J Obstet Gynaecol 1996;103:1159᎐1161.