Unexpected Relationship between Plasma Homocysteine and Intrauterine Growth Restriction

Abstract 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.