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. 2023 Aug 8;118(3):720–728. doi: 10.1016/j.ajcnut.2023.05.034

TABLE 4.

Crude associations between methyl donors and other micronutrients involved in one-carbon metabolism and spina bifida stratified by infant sex,1 National Birth Defects Prevention Study (1999–2011)

Females n = 3851
Males n = 3948
Cases n = 331 Cont N = 3520 cOR (95% CI) Cases n = 380 Cont N = 3568 cOR (95% CI)
Individual nutrients2
Vitamin B6 <1.45 mg 7 72 1.0 13 76 1.0
≥1.45 mg 324 3448 0.91 (0.42, 2.0) 367 3492 0.60 (0.33, 1.1)
Vitamin B12 <3.5 μg 19 165 1.0 27 169 1.0
≥3.5 μg 312 3355 0.79 (0.49, 1.3) 353 3399 0.64 (0.42, 0.97)
Betaine <88 mg 181 1724 1.0 202 1828 1.0
≥88 mg 150 1796 0.80 (0.64, 1.0) 178 1740 0.93 (0.75, 1.1)
Choline <200 mg 24 184 1.0 16 190 1.0
≥200 mg 307 3336 0.69 (0.45, 1.1) 364 3378 1.2 (0.74, 2.1)
Methionine <2.5 g 324 3461 1.0 378 3506 1.0
≥2.5 g 7 59 1.3 (0.62, 2.9) 2 62 NC
Riboflavin <2.4 mg 232 2326 1.0 262 2344 1.0
≥2.4 mg 99 1194 0.83 (0.65, 1.1) 118 1224 0.86 (0.69, 1.1)
Thiamine <2.34 mg 325 3387 1.0 363 3442 1.0
≥2.34 mg 6 133 0.51 (0.23, 1.1) 17 126 1.3 (0.78, 2.2)
Zinc ≤15 mg 280 2985 1.0 328 2983 1.0
>15 mg 51 535 1.0 (0.75, 1.4) 52 585 0.81 (0.60, 1.1)
Number of micronutrients with higher intake2
0–1 8 34 1.0 8 39 1.0
2–3 127 1222 0.42 (0.19, 0.93) 153 1243 0.57 (0.27, 1.2)
≥4 196 2264 0.35 (0.16, 0.76) 219 2286 0.45 (0.21, 0.96)

Cont, controls; cOR, crude OR; NC, not calculated.

1

Excludes n = 66 participants where sex was unknown or ambiguous.

2

To categorize each micronutrient intake (higher or lower intake), we used a combination of information from diet and supplements. Excluding supplementers, we regressed case-control status on the energy-adjusted dietary estimate of a given methyl donor, using restricted cubic splines with ≤5 knots controlling for estimated dietary folate equivalents as a model covariate, and identified a cut point where the OR comparing higher compared with lower intake was maximized. Subsequently, we grouped the supplementers into the respective higher intake category if the typical content of the supplement was expected to be greater than the identified dietary cutoff (refer to Table 1).