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Unexpected Relationship between Plasma Homocysteine and Intrauterine Growth Restriction

¹ Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montréal, Province of Québec, H3A 1A3 Canada.

² Research Centre,
³ Division of Hematology and Oncology, Department of Pediatrics, and
⁴ Department of Obstetrics, Centre Hospitalier Universitaire Mère-Enfant (CHUME), Hôpital Sainte-Justine, Université de Montréal, Montréal, H3T 1C5 Canada.

^aAddress correspondence to this author at: Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, 1130 Pine Ave. West, Montréal, Province of Québec, H3A 1A3 Canada. Fax 514-398-7435; e-mail claire.infante-rivard{at}mcgill.ca.

Background: Moderate hyperhomocysteinemia is considered a risk factor for thrombosis and atherosclerosis. We hypothesized that higher maternal and newborn homocysteine concentrations in plasma would increase the risk of intrauterine growth restriction through placental thrombosis.

Methods: We carried out a case-control study that included all cases born at our institution over a 2-year period whose birthweight was below the 10th percentiles for gestational age and sex according to Canadian norms; controls were born at the same period and institution at or above the 10th percentiles and were matched on gestational age, race, and sex. Homocysteine was measured in cord and maternal blood. The analysis included 483 case and 468 control mothers and 409 case and 438 control newborns.

Results: Homocysteine values were largely <15 µmol/L. Contrary to expectation, within that range of values, increased plasma homocysteine, particularly in the mother, was protective against intrauterine growth restriction. With the case/control status as the outcome, the estimated odds ratio was 0.37 (95% confidence interval, 0.24–0.58) for a 5 µmol/L unit difference on the maternal homocysteine scale. With birthweight as the outcome, the estimated increase was 178.1 g (95% confidence interval, 92.5–263.7 g) for every 5 µmol/L unit increase in maternal homocysteine. Results were similar using newborn homocysteine concentrations.

Conclusions: The data suggest that, in contrast to the proposed hypothesis, mothers with small babies have lower homocysteine concentrations than those giving birth to larger ones.

The following articles in journals at HighWire Press have cited this article:

				L. Dodds, D. B. Fell, K. C. Dooley, B. A. Armson, A. C. Allen, B. A. Nassar, S. Perkins, and K.S. Joseph Effect of Homocysteine Concentration in Early Pregnancy on Gestational Hypertensive Disorders and Other Pregnancy Outcomes Clin. Chem., February 1, 2008; 54(2): 326 - 334. [Abstract] [Full Text] [PDF]

				T. Tamura and M. F. Picciano Folate and human reproduction Am. J. Clinical Nutrition, May 1, 2006; 83(5): 993 - 1016. [Abstract] [Full Text] [PDF]

				P. M. Ueland and S. E. Vollset Homocysteine and Folate in Pregnancy Clin. Chem., August 1, 2004; 50(8): 1293 - 1295. [Full Text] [PDF]

				M. M. Murphy, J. M. Scott, V. Arija, A. M. Molloy, and J. D. Fernandez-Ballart Maternal Homocysteine before Conception and throughout Pregnancy Predicts Fetal Homocysteine and Birth Weight Clin. Chem., August 1, 2004; 50(8): 1406 - 1412. [Abstract] [Full Text] [PDF]

				C. Infante-Rivard and G.-E. Rivard Unexpected Relationship between Plasma Homocysteine and Intrauterine Growth Restriction: Response Clin. Chem., April 1, 2004; 50(4): 784 - 785. [Full Text] [PDF]

				M. Y. Moridani Unexpected Relationship between Plasma Homocysteine and Intrauterine Growth Restriction Clin. Chem., April 1, 2004; 50(4): 782 - 784. [Full Text] [PDF]

				M. Cattaneo Homocysteine and the Risk of Intrauterine Growth Retardation Clin. Chem., September 1, 2003; 49(9): 1432 - 1433. [Full Text] [PDF]

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