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Unexpected relationship between plasma homocysteine and intrauterine growth restriction
Claire Infante-Rivard1, Georges-Etienne Rivard, Robert Gauthier
1Department of Epidemiology, Biostatistics, and Occupational Health, Faculty of Medicine, McGill University, Montréal, Province of Québec, H3A 1A3 Canada. claire.infante-rivard@mcgill.ca
Insights
Higher maternal homocysteine levels appear protective against intrauterine growth restriction, contrary to previous hypotheses. This study found lower homocysteine concentrations in mothers of smaller babies, suggesting a protective role.
Area of Science:
- Obstetrics and Gynecology
- Perinatal Medicine
- Biochemistry
Background:
- Moderate hyperhomocysteinemia is a known risk factor for thrombosis and atherosclerosis.
- Previous hypotheses suggested elevated maternal and newborn homocysteine increase the risk of intrauterine growth restriction (IUGR) via placental thrombosis.
Purpose of the Study:
- To investigate the association between maternal and newborn homocysteine concentrations and the risk of intrauterine growth restriction.
- To test the hypothesis that higher homocysteine levels increase IUGR risk.
Main Methods:
- A case-control study involving 483 case mothers and 468 control mothers, with matched newborns.
- Homocysteine levels were measured in maternal and cord blood.
- Cases were defined as birthweight below the 10th percentile for gestational age and sex.
Main Results:
- Contrary to expectations, increased plasma homocysteine, particularly maternal homocysteine, was found to be protective against IUGR.
- A 5 micromol/L increase in maternal homocysteine was associated with a reduced odds of IUGR (OR=0.37).
- Higher maternal homocysteine correlated with increased birthweight (178.1 g per 5 micromol/L increase).
Conclusions:
- Maternal homocysteine concentrations are lower in mothers delivering smaller babies, contradicting the initial hypothesis.
- The findings suggest a protective role for homocysteine against intrauterine growth restriction, particularly at maternal levels below 15 micromol/L.
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 micromol/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 micromol/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 micromol/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.