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| |  SMFM: Smoking in Pregnancy Places Foetus at Risk for Neural Tube Defects By Cameron Johnston Special to DG News NEW ORLEANS, LA -- January 22, 2002 -- Smoking during pregnancy seems to result in reduced levels of serum and red blood cell folate, which could potentially place the developing foetus at risk for neural tube defects, according to a cross-sectional study. Investigators at the University of Ottawa, in Ottawa, Ontario, Canada, found that low folate levels may represent a new risk factor to the mother to be for development of atherosclerosis and stroke. In a presentation at the 22nd annual meeting of the Society for Maternal-Fetal Medicine (SMFM), in New Orleans, Louisiana, United States, they reported that folate levels have been inextricably linked to -- and inversely proportional to -- homocysteine levels. Therefore, reduced folate levels may in turn result in increased homocysteine levels, which would lead to an increased risk of atherosclerosis and stroke. Therefore, the objective of the present study was to determine whether serum and red blood cell folate levels were decreased in pregnant smokers and whether total plasma homocysteine levels were elevated. "In the non-pregnant population, we know that homocysteine is associated with a variety of significant disease states, including venous thromboembolism [VTE], stroke and coronary artery disease," said Dr. Sarah McDonald of the department of obstetrics and gynecology at University of Ottawa. "During pregnancy, high levels of homocysteine have also been associated with the same pregnancy outcomes associated with smoking -- namely, low birth weight, spontaneous abortions, still births, [placental] abruption, foetal anomalies, and venous thromboembolism." In Dr. McDonald’s study, patients who had all reached six to 16 weeks’ gestation with singleton pregnancies were identified through a maternal health clinic and divided into smokers and non-smokers (controls). There were 40 patients in each group. Patients were excluded if that had had chronic hypertension, VTE, pre-term labour or premature rupture of membranes, or if they were deficient in vitamins B6, B12 or folate. Demographically, and in terms of patient make-up, there were no differences in age, parity, history of previous spontaneous or induced abortions, miscarriage, gestational age or any other relevant factors. The researchers found significant differences between smokers and controls with respect to both serum folate and red blood cell folate levels. Serum folate levels were 22.7 nmol/L in the smoking group versus 29.4 nmol/L in the control group (p=0.001). Red blood cell folate levels were 766 nmol/L and 900 nmol/L in each group, respectively; (p=0.038). Both measures were statistically significant, but Dr. McDonald pointed out that they were also clinically significant, in that a folate level <900 nmol/L is generally accepted to put the developing foetus at risk for neural tube defects. The study also looked at a particular genotype of folate synthesis, the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), which is important in the conversion of homocysteine to methionine, thereby lessening the risk of cardiovascular disease that high levels of homocysteine might represent. The enzyme exists in three forms -- wild-type, heterozygous and mutant. For each MTHFR genotype, serum folate levels were lower in smokers. The lowest folate levels were seen in the homozygous MTHFR 677TT genotype (18.6 nmol/L in smokers vs. 24.2 nmol/L in controls). This finding could suggest that smoking might be more harmful in some smokers than in others, according to Dr. McDonald. Also, the homocysteine levels were not associated with folate status among either group. Nonetheless, she said, it still appears that smoking may be considered a co-variant, which compounds the risk of developing complications as well as increasing the well-known risk for neural tube defects in some infants. A gene-environment interaction between MTHFR gene activity and tobacco exposure on serum folate levels is present. Dr. McDonald further speculated that it might be advisable to recommend additional folate supplements for women who smoke during pregnancy as a means of safeguarding against lower folate levels.
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