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were higher in women with a normal pregnancy than in women carrying a fetus with an NTD (Kirke et al., 1993; Laurence et al., 1981; Smithells et al., 1976) or with a fetus having another type of malformation (Bunduki et al., 1995). This difference was not found in one study with only eight NTD cases (Economides et al., 1992).

In a case-control study in three maternity hospitals in Dublin, Ireland, from 1986 to 1990, erythrocyte folate values were measured in frozen samples taken at a median gestational age of 15 weeks (Daly et al., 1995; Kirke et al., 1993). The percentage of women using folate supplements was 5 percent. A negative apparently nonlinear association was observed between NTD risk and erythrocyte folate concentration (Table 8-10). It is not known whether the risk would continue to decrease as erythrocyte folate values increased to higher than 1,241 nmol/L (570 ng/mL), which was the mean erythrocyte concentration of the controls who had concentrations in the highest category in Table 8-10. However, the population studied had a relatively high incidence of NTD, around 2 per 1,000 births. Extrapolation of results should be made with great care because the NTD risk in the U.S. population could be lower at every level of erythrocyte folate.

Determinants of Erythrocyte Folate. In a recent study in women aged 22 to 35 years in the Minneapolis-St. Paul area, folate supplements and folate-fortified cereals were found to be independent predic

TABLE 8-10 Distribution of Cases and Controls and Risks of Neural Tube Defect (NTD) by Erythrocyte Folate Concentration

Erythrocyte Folate nmol/L (ng/mL)a

N (%) of Cases

N (%) of Controls

Risk of NTD per 1,000 Birthsb

95% Confidence Interval

0–339 (0–149)

11 (13.1)

10 (3.8)

6.6

3.3–11.7

340–452 (150–199)

13 (15.5)

24 (9.0)

3.2

1.7–5.5

453–679 (200–299)

29 (34.5)

75 (28.2)

2.3

1.6–3.3

680–903 (300–399)

20 (23.8)

77 (29.0)

1.6

1.0–2.4

≥ 906 (400)

11 (13.1)

80 (30.0)

0.8

0.4–1.5

Total

84 (100.0)

266 (100.0)

1.9

1.5–2.3

a 1 ng/mL = 2.27 nmol/L, as reported in the original study. This conversion factor differs from that used in the rest of this report.

b Absolute NTD risk has been extrapolated from the odds ratio computed in a case-control study.

SOURCE: Adapted from Daly et al. (1995).



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