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) . | P . | Heterogeneity . | |
|---|---|---|---|---|---|
| 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) | 9 |
| 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) | 0 |
| 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) | 0 |
| 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) . | P . | Heterogeneity . | |
|---|---|---|---|---|---|
| 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) | 9 |
| 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) | 0 |
| 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) | 0 |
| 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.