Lipid Peroxidation, Antioxidant Defence and Acid-Base Status in Cord Blood at Birth: The Influence of Diabetes

Pregnancy complicated by poor control of diabetes is associated with a higher risk of embryopathies, spontaneous abortions and perinatal mortality. A number of authors suggest an involvement of reactive oxygen species (ROS) in diabetic pregnancy. Determining lipid peroxidation products (LP), scavenging enzyme activities and the umbilical cord blood’s acid-base balance may contribute to an adequate diagnosis of the neonate at birth. Nevertheless, such measurements seem to have limited value in practical clinical routine. The present study evaluates LP, antioxidant defence and acid-base status related to diabetic pregnancy. Twenty- eight women with type 1 diabetes (PGDM), 19 with gestational diabetes (GDM) and 13 control cases were investigated. An additional control group consisted of 15 healthy patients with negative diabetic history; all women underwent vaginal delivery. Immediately after delivery cord blood samples and placental tissue were collected for malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) determination. Additionally, pH, pCO₂, pO₂ and base excess were measured in both vessels and compared to identify and exclude double venous samples. MDA levels in both cord blood and placental homogenates were significantly higher in both pregestational and gestational diabetic groups, but SOD activity was significantly diminished. Cord blood GSH was markedly elevated in PGDM and GDM. We have also shown significant differences in acid-base parameters in infants of PGDM group. Statistical analysis was performed using the Mann-Whitney U-test.

These findings indicate an excessive oxidative stress in pregnancy complicated by diabetes mellitus. Evaluating LP products and scavenging enzyme activities may be valuable, sensitive indexes of fetal/neonatal threat in diabetic pregnancy in humans. Since oxidative stress is an important pathway for fetal injury, we believe that obtaining adequate measurements at the time of birth would contribute to clarifying the fetal/neonatal status in a medical and legal context and might be of value in altering therapy in newborn infants.

Key words:

Pregnancy - Diabetes Mellitus - Oxidative Stress - Lipid Peroxidation - Acid-Base Status

References

• 1 Baker L, Piddington R. Diabetic embryopathy: a selective review of recent trends.  J Diabetes Complications. 1993;  7 204-212
• 2 Coustan D R, Imarah J. Prophylactic insulin treatment of gestational diabetes reduces the incidence of macrosomia, operative delivery and birth trauma.  Am J Obstet Gynecol. 1984;  150 836-840
• 3 Reece E A, Gabrielli S, Abballa M. Prevention of diabetes - associated birth defect.  Semin Perinatol. 1987;  12 292-296
• 4 Sadler T W, Hunter E S, Wynn R E, Philips L S. Evidence of multifactorial origin of diabetes induced embryopathies.  Diabetes. 1989;  38 70-74
• 5 Kitzmiller J L, Cloherty J P, Younger M D. Diabetic pregnancy and perinatal morbidity.  Am J Obstet Gynecol. 1978;  131 560-580
• 6 Saugstad O D. Mechanisms of tissue injury by oxygen radicals: implications for neonatal disease.  Acta Paediatr. 1996;  85 1-4
• 7 Almaas R, Sundar T B, Rootwelt T, Øyasæter S, Saugstad O D. Plasma hypoxanthine reacts more abruptly to changes in oxygenation than base deficit and uric acid in newborn piglets.  J Perinat Med. 1997;  25 353-360
• 8 Halliwell B. Free Radicals and Antioxidants: A personal view.  Nutrition Reviews. 1994;  52 No 8 253-265
• 9 Gutteridge J MC. Lipid peroxidation and antioxidants as biomarkers of tissue damage.  Clin Chem. 1995;  41/12 1819-1828
• 10 Kato H, Yoneyama Y, Araki T. Fetal plasma lipid peroxide levels in pregnancies complicated by preeclampsia.  Gynecol Obstet Invest. 1997;  43 158-161
• 11 Pryor W A, Godber S S. Noninvasive measures of oxidative stress status in humans.  Free Radic Bio Med. 1991;  10 177-184
• 12 Wang W, Pang C CP, Rogers M S, Chang A MZ. Lipid peroxidation in cord blood at birth.  Am J Obstet Gynecol. 1996;  174 62-65
• 13 Do¿browski A, Chwiecko M. Oxygen radicals mediate depletion of pancreatic sulfhydryl compounds in rats with cerulein-induced acute pancreatitis.  Digestion. 1990;  47 15-19
• 14 Lowry O H, Rosebrough N J, Farr A L, Randal R J. Protein measurement with the Folin phenol reagent.  J Biol Chem. 1951;  193 265-275
• 15 Richards D S, Jonson J WC. The practical implications of cord blood acid-base studies.  Clin Obstet Gynecol. 1993;  36 91-104
• 16 Westgate J, Garibaldi J M, Greene K R. Umbilical cord blood gas analysis at delivery: a time for quality data.  Br J Obstet Gynaecol. 1994;  101 1054-1063
• 17 Perlman J M, Risser R. Severe Fetal Acidemia: Neonatal Neurologic Features and Short-term Outcome.  Pediatr Neurol. 1993;  9 277-282
• 18 Marinari U M, Traverso N, Maloberti G, Pronzato M A. Free radicals and fetal pathology.  J Perinat Med. 1994;  22 Suppl. 1 39-41
• 19 Eriksson U J, Borg L AH. Protection by free oxygen radical scavenging enzymes against glucose-induced embryonic malformations in vitro.  Diabetes. 1991;  34 325-331
• 20 Viana M, Herrera E, Bonet B. Teratogenic effects of diabetes mellitus in the rat. Prevention by vitamin E.  Diabetes. 1996;  39 1041-1046
• 21 Speroff L, Reece E A (eds). Diabetes and Development.  In: Seminars in Reproductive Endocrinology.  New York, Stuttgart:; Thieme, 1999 17, no. 2: 117-194
• 22 Weber G F. The Pathophysiology of reactive oxygen intermediates in the central nervous system.  Medical Hypotheses. 1994;  43 223-230
• 23 Goldman A S, Baker L, Pididington R. Hyperglycemia induced teratogenesis is mediated by functional deficiency in arachidonic acid.  Proc Natl Acad Sci USA. 1985;  82 277-286
• 24 Hennig B, Chow C K. Lipid peroxidation and endothelial cell injury: implications in atherosclerosis.  Free Radic Biol Med. 1988;  4 99-106
• 25 Warso M A, Lands W E. Lipid peroxidation in relation to prostacyclin and thromboxane physiology and pathophysiology.  Br Med Bull. 1983;  39 277-280
• 26 Kinalski M, Śledziewski A, Telejko B, Zarzycki W, Kinalska I. Antioxidant therapy and streptozotocin-induced diabetes in pregnant rats.  Acta Diabetol. 1999;  36 113-117
• 27 Sivan E, Reece E A, Wu Y K, Homko C J, Polansky M, Borenstein M. Dietary vitamin E prophylaxis and diabetic embryopathy: morphologic and biochemical analysis.  Am J Obstet Gynecol. 1996;  175 793-799
• 28 Xu L, Badr M Z. Enhanced potential for oxidative stress in hyperinsulinemic rats: imbalance between hepatic peroxisomal hydrogen peroxide production and the composition due to hyperinsulinemia.  Horm Metab Res. 1999;  31: 4 278-282
• 29 Rogers M S, Mongelli J M, Tsang K H, Wang C C, Law K P. Lipid peroxidation in cord blood at birth: the effect of labour.  Br J Obstet Gynecol. 1998;  105 739-744