Table 4. Risk of Acute Lymphoblastic Leukemia Associated with Maternal Vitamin and Folic Acid Supplementation, Stratified by Study with Low or High Between-Study Variabilitya.
Supplement, Period |
Data Availability | All Studies | Low Between-study Variabilityb | High Between-study Variabilityc | |||||||||||||||||
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No. Controls |
No. Cases |
Model 1d | Model 2e | No. Controls |
No. Cases |
Model 1d | Model 2e | No. Controls |
No. Cases |
Model 1d | Model 2e | ||||||||||
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No. Studies |
No. Controls |
No. Cases |
OR | (95% CI) | OR | (95% CI) | OR | (95% CI) | OR | (95% CI) | OR | (95% CI) | OR | (95% CI) | |||||||
Vitamins | |||||||||||||||||||||
Any time | 12 | 11466 | 6845 | ||||||||||||||||||
nof | 4787 | 2497 | 1.00 | 1.00 | 1312 | 1108 | 1.00 | 1.00 | 3475 | 1389 | 1.00 | 1.00 | |||||||||
Yes | 6679 | 4348 | 1.21 | (1.13–1.28) | 0.85 | (0.78–0.92) | 2711 | 1909 | 0.84 | (0.76–0.93) | 0.89 | (0.80–0.99) | 3968 | 2439 | 1.46 | (1.34–1.59) | 0.80 | (0.71–0.90) | |||
Preconception | 8 | 6931 | 4566 | ||||||||||||||||||
nof | 5749 | 3834 | 1.00 | 1.00 | — | — | — | — | |||||||||||||
Yes | 1182 | 732 | 0.93 | (0.84–1.03) | 0.88 | (0.79–0.99) | |||||||||||||||
Pregnancy | 10 | 8554 | 5704 | ||||||||||||||||||
nof | 3161 | 1844 | 1.00 | 1.00 | 1051 | 873 | 1.00 | 1.00 | 2110 | 971 | 1.00 | 1.00 | |||||||||
Yes | 5393 | 3860 | 1.17 | (1.09–1.26) | 0.81 | (0.74–0.88) | 3200 | 2160 | 0.79 | (0.71–0.88) | 0.88 | (0.78–0.98) | 2193 | 1700 | 1.57 | (1.41–1.74) | 0.68 | (0.58–0.80) | |||
Folic acid | |||||||||||||||||||||
Any time | 8 | 5588 | 3002 | ||||||||||||||||||
nof | 3416 | 1769 | 1.00 | 1.00 | 1460 | 794 | 1.00 | 1.00 | 1956 | 975 | 1.00 | 1.00 | |||||||||
Yes | 2172 | 1233 | 1.09 | (0.99–1.19) | 0.80 | (0.71–0.89) | 439 | 261 | 1.08 | (0.90–1.30) | 0.92 | (0.76–1.12) | 1733 | 972 | 1.06 | (0.95–1.19) | 0.72 | (0.62–0.84) | |||
Preconception | 7 | 5011 | 2756 | ||||||||||||||||||
nof | 4313 | 2404 | 1.00 | 1.00 | — | — | — | — | |||||||||||||
Yes | 698 | 352 | 0.89 | (0.77–1.02) | 0.82 | (0.70–0.96) | |||||||||||||||
Pregnancy | 7 | 5094 | 2589 | ||||||||||||||||||
nof | 3294 | 1585 | 1.00 | 1.00 | 1317 | 597 | 1.00 | 1.00 | 1977 | 988 | 1.00 | 1.00 | |||||||||
Yes | 1800 | 1004 | 1.13 | (1.02–1.25) | 0.77 | (0.67–0.88) | 106 | 57 | 1.15 | (0.82–1.62) | 1.10 | (0.78–1.55) | 1694 | 947 | 1.06 | (0.94–1.18) | 0.72 | (0.62–0.83) |
Studies were separated into low- and high-high-variability groups, based on proportions of women taking vitamins or folic acid across each of the studies, when between-study variability contributed to more than 30% of the overall variability. Based on this criteria, studies were not stratified for the preconception time period.
Low-variability studies: Vitamins, any time: canada, Costa Rica, US NCCLS (1995–2002), greece, australia, egypt; Vitamins, pregnancy: canada, Costa Rica, Greece, Australia, US NCCLS (2003–2008), egypt; Folic acid, pregnancy: New Zealand, Brazil, US NCCLS (2003–2008)
High-variability studies: Vitamins, any time: US CCG, New Zealand, Germany, Brazil, France, US NCCLS (2003–2008); Vitamins, pregnancy: US CCG, New Zealand, Brazil, France; Folic acid, any time: Canada, Costa Rica, France, Australia; Folic acid, pregnancy: Canada, Costa Rica, France, Australia
Pooled OR adjusted adjusted for age, sex, ethnicity, and parental education
Pooled OR adjusted for age, sex, ethnicity, parental education, and study
Refererence category