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. Author manuscript; available in PMC: 2018 Apr 17.
Published in final edited form as: Epidemiology. 2014 Nov;25(6):811–822. doi: 10.1097/EDE.0000000000000141

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



No.
Controls
No.
Cases
Model 1d Model 2e No.
Controls
No.
Cases
Model 1d Model 2e No.
Controls
No.
Cases
Model 1d Model 2e







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)
a

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.

b

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)

c

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

d

Pooled OR adjusted adjusted for age, sex, ethnicity, and parental education

e

Pooled OR adjusted for age, sex, ethnicity, parental education, and study

f

Refererence category