Thromb Haemost 2006; 95(04): 625-628
DOI: 10.1160/TH05-06-0427
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Homocysteine levels in amniotic fluid

Relationship with birth-weight
Elvira Grandone
1   I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni R. (FG) and University of Foggia, Italy
,
Donatella Colaizzo
1   I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni R. (FG) and University of Foggia, Italy
,
Gennaro Vecchione
1   I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni R. (FG) and University of Foggia, Italy
,
Natale Sciannamè
1   I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni R. (FG) and University of Foggia, Italy
,
Angelo Notarangelo
1   I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni R. (FG) and University of Foggia, Italy
,
Anna Irma Croce
1   I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni R. (FG) and University of Foggia, Italy
,
Maurizio Margaglione
1   I.R.C.C.S. Casa Sollievo della Sofferenza, S. Giovanni R. (FG) and University of Foggia, Italy
› Author Affiliations
Further Information

Publication History

Received 17 June 2005

Accepted after revision 07 February 2006

Publication Date:
30 November 2017 (online)

Summary

Hyperhomocysteinemia could playa similar role in the placenta to that played in adults at risk of thrombosis. Moreover, hyperhomocysteinemia in women is described to be associated with the birth of small for gestational age (SGA) newborns, although there are discrepancies on this issue. To date, there is no biochemical marker predictive of SGA in a given pregnancy. We verified the presence of a relationship between homocysteine in amniotic fluid at mid-pregnancy and birth-weight. Amniotic fluid was obtained from 459 healthy women undergoing midtrimester amniocentesis (17.1 ± 1.2 weeks) because of maternal age. Homocysteine levels were measured in 434 (10 twin) pregnancies. In addition, femur length (FL) and biparietal diameter (BPD) were measured. Outcome of pregnancy was recorded. 233 (53.7%) foetuses were males,201 (46.3%) females. The mean homocysteine concentration was 1.04 ± 0.72 µM, (95% C.I. 0.43–2.41). An univariate analysis showed the presence of an association with gestational age, FL, BPD. A multiple linear regression showed that homocysteine levels were significantly associated with FL (p<0.001) and BPD (p=0.011). After excluding twin pregnancies, 31 newborns (7.3%) were classified as SGA. Mean birth-weight was 2390 g in SGA, where as it was 3360 g in 393 adequate for gestational age (AGA) newborns (p<0.001).The adjusted mean level of homocysteine was significantly lower in AGA (1.01 µM; 95%CI: 0.94–1.08) than that recorded in pregnancies resulting in a SGA (1.29 µM; 95%CI: 1.05–1.51; p=0.03). In a large setting, these data provide reference values for homocysteine in amniotic fluids. Moreover, they suggest that homocysteine levels in amniotic fluids may be higher in pregnancies with a SGA newborn.

 
  • References

  • 1 D’ Angelo A, Selhub J. Homocysteine and thrombotic disease. Blood 1997; 90: 1-11.
  • 2 Ueland PM, Refsum H, Male R. et al. Disposition of endogenous homocysteine by mouse fibroblast C3H/10T1/2 CI 8 and the chemically transformed C3H/10T1/2 MCA CI 16 cells following methotrexate exposure. J Natl Cancer Inst 1986; 77: 283-9.
  • 3 Christensen B, Refsum H, Vintermyr O. et al. Homocysteine export from cells cultured in the presence of physiological or superfluous levels of methionine: methionine loading of nontransin formed, transformed, proliferating, and quiescent cells in culture. JCell Physiol 1991; 146: 52-62.
  • 4 Mudd SH, Levy HL, Skovby F. Disorders of transsulfuration. Scriver CR, Beaudet AL, Sly WS, Valle D. eds. The metabolic and molecular basis of inherited disease. McGraw-Hill; New York: 1995: 1279-327.
  • 5 McCully KS. Homocysteine and vascular disease. Nat Med 1996; 02: 386-9.
  • 6 Magera MJ, Lacey JM, Casetta B. et al. Method for the determination of total homocysteine in plasma and urine by stable isotope dilution and electrospray tandem mass spectrometry. Clin Chem 1999; 45: 1517-22.
  • 7 Zittoun J, Zittoun R. Modern clinical testing strategies in cobalamin and folate deficiency. Semin Hematol 1999; 36: 35-46.
  • 8 Danesh J, Lewington S. Plasma homocysteine and coronary heart disease: systematic review of published epidemiological studies. J Cardiovasc Risk 1998; 05: 229-32.
  • 9 Fermo I, DeVecchi E, Arcelloni C. et al. Methodological aspects of total plasma homocysteine measurement. Haematologica 1997; 82: 246-50.
  • 10 Minniti G, Piana A, Armani U. et al. Determination of plasma and serum homocysteine by high-performance liquid chromatography with fluorescence detection. J Chromatogr 1998; 828: 401-5.
  • 11 Vilaseca MA, Moyano D, Ferrer I. et al. Total homocysteine in pediatric patients. Clin Chem 1997; 43: 690-2.
  • 12 Mandsager NT, Bendon R, Mostello D. et al. Maternal floor infarction of the placenta: prenatal diagnosis and clinical significance. Obstet Gynecol 1994; 83: 750-4.
  • 13 Ronnenberg AG, Goldman MB, Chen D. et al. Preconception homocysteine and B vitamin status and birth outcomes in Chinese women. Am J Clin Nutr. 2002; 76: 1385-91.
  • 14 D’Anna R, Baviera G, Corrado F. et al. Plasma homocysteine in early and late pregnancies complicated with preeclampsia and isolated intrauterine growth restriction. Acta Obstet Gynecol Scand 2004; 83: 155-8.
  • 15 Steegers-Theunissen RP, Wathen NC, Eskes TK. et al. Maternal and fetal levels of methionine and homocysteine in early human pregnancy. Br J Obstet Gynaecol 1997; 104: 20-4.
  • 16 Rabier D, Chadefaux-Vekemans B, Oury JF. et al. Gestational age-related reference values for amniotic fluid amino acids : a useful tool for prenatal diagnosis of aminoacidopathies. Prenat Diagn 1996; 16: 623-8.
  • 17 Battaglia FC, Lubchenco LO. A practical classification of newborn infants by weight and gestational age. J Pediat 1968; 71: 159.
  • 18 Jauniaux E, Gulbis B, Gerlo E. Free amino acid in human fetal liver and fluids at 12–17 weeks of gestation. Hum Reprod 1999; 14: 1638-41.
  • 19 Kang SS, Wong PW, Zhou JM. et al. Total homocyst(e)ine in plasma and amniotic fluid of pregnant women. Metabolism 1986; 35: 889-91.
  • 20 van Hove JL, Chace DH, Kahler SG. et al. Acylcarnitines in amniotic fluid: application to the prenatal diagnosis of propionic acidaemia. J Inherit Metab Dis 1993; 16: 361-7.
  • 21 Glowinska B, Urban M, Koput A. et al. New atherosclerosis risk factors in obese, hypertensive and diabetic children and adolescents. Atherosclerosis 2003; 167: 275-86.
  • 22 Wenstrom KD, Johanning GL, Johnston KE. et al. Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malformations. Am J Obstet Gynecol 2001; 184: 806-12.
  • 23 Wenstrom KD, Johanning GL, Owen J. et al. Role of amniotic fluid homocysteine level and of fetal 5,10– Methylenetetrahydrafolate reductase genotype in the etiology of neural tube defects. Am J Med Genet 2000; 90: 12-6.