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TABLE 2

Meta-analyses of 30 studies investigating the association between maternal age and type 1 diabetes before and after adjustments for recorded confounders and in subgroups defined by study type and quality

Maternal age (years)Case subjects (n)Combined OR (95% CI)PHeterogeneity
χ2 (P)I2
Overall (n = 30 studies)      
    <20 764 0.88 (0.74−1.04) 0.12 81.4 (<0.001) 64 
    20–25 3,919 0.95 (0.89−1.00) 0.05 36.1 (0.17) 20 
    25–30 5,433 1.00 (ref.)    
    30–35 3,274 1.05 (0.97−1.13) 0.28 59.1 (0.001) 51 
    ≥35 1,334 1.10 (1.01−1.20) 0.03 36.4 (0.16) 20 
    Per 5-year increase 14,724 1.05 (1.02−1.09) 0.006 97.7 (<0.001) 70 
Adjusted for gestational age, birth weight, and birth order*(n = 20 studies)      
    <20 403 0.95 (0.77−1.17) 0.65 42.7 (0.001) 56 
    20–25 1,846 0.90 (0.84−0.97) 0.003 20.9 (0.34) 
    25–30 2,826 1.00 (ref.)    
    30–35 1,709 1.05 (0.93−1.19) 0.40 46.4 (<0.001) 59 
    ≥35 737 1.12 (0.97−1.29) 0.14 33.0 (0.024) 42 
    Per 5-year increase 7,521 1.06 (1.00−1.12) 0.05 66.5 (<0.001) 71 
Adjusted for all available confounders as shown in Table 1 (n = 30 studies)      
    <20 736 0.89 (0.74−1.07) 0.22 88.9 (<0.001) 67 
    20–25 3,715 0.93 (0.87−0.99) 0.02 36.2 (0.17) 20 
    25–30 5,147 1.00 (ref.)    
    30–35 3,105 1.08 (0.99−1.18) 0.10 62.4 (<0.001) 54 
    ≥35 1,251 1.12 (1.02−1.24) 0.02 39.9 (0.09) 27 
    Per 5-year increase 13,954 1.06 (1.01−1.11) 0.01 116.9 (<0.001) 75 
Cohort studies (n = 5 studies)      
    <20 269 0.80 (0.65−0.99) 0.04 9.3 (0.06) 57 
    20–25 1,105 0.89 (0.82−0.96) 0.003 3.8 (0.43) 
    25–30 1,681 1.00 (ref.)    
    30–35 1,057 0.99 (0.88−1.12) 0.93 8.7 (0.07) 54 
    ≥35 468 1.08 (0.96−1.22) 0.21 5.2 (0.26) 23 
    Per 5-year increase 4,580 1.06 (1.01−1.11) 0.03 12.7 (0.01) 69 
Case-control studies (n = 25 studies)      
    <20 495 0.91 (0.73−1.14) 0.41 71.5 (<0.001) 66 
    20–25 2,814 0.97 (0.91−1.05) 0.47 28.9 (0.22) 17 
    25–30 3,752 1.00 (ref.)    
    30–35 2,217 1.07 (0.97−1.19) 0.20 49.6 (0.002) 52 
    ≥35 866 1.12 (0.99−1.25) 0.07 30.9 (0.16) 22 
    Per 5-year increase 10,144 1.05 (1.00−1.11) 0.04 84.6 (<0.001) 72 
Studies with a low risk of bias (n = 14 studies)      
    <20 518 0.81 (0.70−0.94) 0.005 20.8 (0.08) 38 
    20–25 2,547 0.90 (0.86−0.96) <0.001 9.3 (0.75) 
    25–30 3,648 1.00 (ref.)    
    30–35 2,195 1.08 (0.99−1.18) 0.10 23.8 (0.03) 45 
    ≥35 904 1.18 (1.06−1.32) 0.003 18.3 (0.14) 29 
    Per 5-year increase 9,812 1.10 (1.06−1.14) <0.001 27.6 (0.01) 53 
Maternal age (years)Case subjects (n)Combined OR (95% CI)PHeterogeneity
χ2 (P)I2
Overall (n = 30 studies)      
    <20 764 0.88 (0.74−1.04) 0.12 81.4 (<0.001) 64 
    20–25 3,919 0.95 (0.89−1.00) 0.05 36.1 (0.17) 20 
    25–30 5,433 1.00 (ref.)    
    30–35 3,274 1.05 (0.97−1.13) 0.28 59.1 (0.001) 51 
    ≥35 1,334 1.10 (1.01−1.20) 0.03 36.4 (0.16) 20 
    Per 5-year increase 14,724 1.05 (1.02−1.09) 0.006 97.7 (<0.001) 70 
Adjusted for gestational age, birth weight, and birth order*(n = 20 studies)      
    <20 403 0.95 (0.77−1.17) 0.65 42.7 (0.001) 56 
    20–25 1,846 0.90 (0.84−0.97) 0.003 20.9 (0.34) 
    25–30 2,826 1.00 (ref.)    
    30–35 1,709 1.05 (0.93−1.19) 0.40 46.4 (<0.001) 59 
    ≥35 737 1.12 (0.97−1.29) 0.14 33.0 (0.024) 42 
    Per 5-year increase 7,521 1.06 (1.00−1.12) 0.05 66.5 (<0.001) 71 
Adjusted for all available confounders as shown in Table 1 (n = 30 studies)      
    <20 736 0.89 (0.74−1.07) 0.22 88.9 (<0.001) 67 
    20–25 3,715 0.93 (0.87−0.99) 0.02 36.2 (0.17) 20 
    25–30 5,147 1.00 (ref.)    
    30–35 3,105 1.08 (0.99−1.18) 0.10 62.4 (<0.001) 54 
    ≥35 1,251 1.12 (1.02−1.24) 0.02 39.9 (0.09) 27 
    Per 5-year increase 13,954 1.06 (1.01−1.11) 0.01 116.9 (<0.001) 75 
Cohort studies (n = 5 studies)      
    <20 269 0.80 (0.65−0.99) 0.04 9.3 (0.06) 57 
    20–25 1,105 0.89 (0.82−0.96) 0.003 3.8 (0.43) 
    25–30 1,681 1.00 (ref.)    
    30–35 1,057 0.99 (0.88−1.12) 0.93 8.7 (0.07) 54 
    ≥35 468 1.08 (0.96−1.22) 0.21 5.2 (0.26) 23 
    Per 5-year increase 4,580 1.06 (1.01−1.11) 0.03 12.7 (0.01) 69 
Case-control studies (n = 25 studies)      
    <20 495 0.91 (0.73−1.14) 0.41 71.5 (<0.001) 66 
    20–25 2,814 0.97 (0.91−1.05) 0.47 28.9 (0.22) 17 
    25–30 3,752 1.00 (ref.)    
    30–35 2,217 1.07 (0.97−1.19) 0.20 49.6 (0.002) 52 
    ≥35 866 1.12 (0.99−1.25) 0.07 30.9 (0.16) 22 
    Per 5-year increase 10,144 1.05 (1.00−1.11) 0.04 84.6 (<0.001) 72 
Studies with a low risk of bias (n = 14 studies)      
    <20 518 0.81 (0.70−0.94) 0.005 20.8 (0.08) 38 
    20–25 2,547 0.90 (0.86−0.96) <0.001 9.3 (0.75) 
    25–30 3,648 1.00 (ref.)    
    30–35 2,195 1.08 (0.99−1.18) 0.10 23.8 (0.03) 45 
    ≥35 904 1.18 (1.06−1.32) 0.003 18.3 (0.14) 29 
    Per 5-year increase 9,812 1.10 (1.06−1.14) <0.001 27.6 (0.01) 53 

*Includes only studies for which adjustments for birth weight (in categories <2.5, 2.5−3, 3−3.5, 2−4.5, >4.5 kg), gestational age (in categories ≤ 37, 38−41, ≥42 weeks), and birth order (in categories first, second, or third born or later) could be made.

†Excluding case-control studies that have control subjects who were not randomly selected (or population based) or studies in which the response rate in either the case or control subjects was less than 80% (or unknown) as shown in Table 1.

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