Association between congenital abnormalities among siblings and acute leukemia among children with Down syndrome
| . | Controls . | Combined cases . | . | ALL . | . | AML . | . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | n (%) . | n (%) . | OR* (95% CI) . | n (%) . | OR* (95% CI) . | n (%) . | OR* (95% CI) . | |||||||
| At least one sibling with an abnormality† | ||||||||||||||
| No | 110 (74%) | 94 (71%) | 1.00 | 60 (71%) | 1.00 | 34 (71%) | 1.00 | |||||||
| Yes | 39 (26%) | 39 (29%) | 1.23 (0.71-2.13) | 25 (29%) | 1.12 (0.60-2.09) | 14 (29%) | 1.60 (0.66-3.86) | |||||||
| Number of siblings with abnormalities‡ | ||||||||||||||
| 0 | 110 (74%) | 94 (71%) | 1.00 | 60 (71%) | 1.00 | 34 (71%) | 1.00 | |||||||
| 1 | 32 (21%) | 36 (27%) | 1.36 (0.76-2.42) | 22 (26%) | 1.23 (0.64-2.38) | 14 (29%) | 1.94 (0.78-4.80) | |||||||
| ≥2 | 7 (5%) | 3 (2%) | 0.53 (0.12-2.36) | 3 (4%) | 0.61 (0.14-2.74) | 0 (0%) | ||||||||
| Ptrend = 0.91 | Ptrend = 0.88 | Ptrend = — | ||||||||||||
| Down syndrome | ||||||||||||||
| No | 148 (99%) | 132 (99%) | 1.00 | 85 (100%) | 47 (98%) | 1.00 | ||||||||
| Yes | 1 (1%) | 1 (1%) | 0.52 (0.03-10.47) | 0 (0%) | 1 (2%) | 0.64 (0.03-12.70) | ||||||||
| Microcephaly | ||||||||||||||
| No | 149 (100%) | 131 (99%) | 84 (99%) | 47 (98%) | ||||||||||
| Yes | 0 (0%) | 2 (1%) | 1 (1%) | 1 (2%) | ||||||||||
| Cleft lip or palate | ||||||||||||||
| No | 148 (99%) | 132 (99%) | 1.00 | 84 (99%) | 1.00 | 48 (100%) | ||||||||
| Yes | 1 (1%) | 1 (1%) | 0.85 (0.05-14.31) | 1 (1%) | 1.48 (0.09-24.80) | 0 (0%) | ||||||||
| Spina bifida/other spinal defect | ||||||||||||||
| No | 149 (100%) | 131 (99%) | 84 (99%) | 47 (98%) | ||||||||||
| Yes | 0 (0%) | 2 (1%) | 1 (1%) | 1 (2%) | ||||||||||
| Hemihypertrophy | ||||||||||||||
| No | 148 (99%) | 132 (99%) | 1.00 | 84 (99%) | 1.00 | 48 (100%) | ||||||||
| Yes | 1 (1%) | 1 (1%) | 1.09 (0.06-18.49) | 1 (1%) | 1.54 (0.08-28.37) | 0 (0%) | ||||||||
| Heart defect | ||||||||||||||
| No | 139 (93%) | 125 (94%) | 1.00 | 81 (95%) | 1.00 | 44 (92%) | 1.00 | |||||||
| Yes | 10 (7%) | 8 (6%) | 0.78 (0.28-2.18) | 4 (5%) | 0.57 (0.16-2.02) | 4 (8%) | 1.29 (0.30-5.52) | |||||||
| Pancreas/digestive tract defect | ||||||||||||||
| No | 149 (100%) | 132 (99%) | 85 (100%) | 47 (98%) | ||||||||||
| Yes | 0 (0%) | 1 (1%) | 0 (0%) | 1 (2%) | ||||||||||
| Kidney/bladder/sex organ defect | ||||||||||||||
| No | 146 (98%) | 129 (97%) | 1.00 | 83 (98%) | 1.00 | 46 (96%) | 1.00 | |||||||
| Yes | 3 (2%) | 4 (3%) | 1.86 (0.39-8.87) | 2 (2%) | 1.41 (0.22-9.00) | 2 (4%) | 1.90 (0.22-16.31) | |||||||
| Hernia | ||||||||||||||
| No | 142 (95%) | 125 (94%) | 1.00 | 80 (94%) | 1.00 | 45 (94%) | 1.00 | |||||||
| Yes | 7 (5%) | 8 (6%) | 1.44 (0.49-4.20) | 5 (6%) | 1.30 (0.38-4.48) | 3 (6%) | 1.96 (0.31-12.52) | |||||||
| Deafness/hearing impairment | ||||||||||||||
| No | 149 (100%) | 132 (99%) | 84 (99%) | 48 (100%) | ||||||||||
| Yes | 0 (0%) | 1 (1%) | 1 (1%) | 0 (0%) | ||||||||||
| Blindness/vision problems | ||||||||||||||
| No | 148 (99%) | 131 (99%) | 1.00 | 83 (98%) | 1.00 | 48 (100%) | ||||||||
| Yes | 1 (1%) | 2 (1%) | 3.09 (0.25-38.28) | 2 (2%) | 2.92 (0.22-38.57) | 0 (0%) | ||||||||
| Other chromosomal abnormalities | ||||||||||||||
| No | 149 (100%) | 133 (100%) | 85 (100%) | 48 (100%) | ||||||||||
| Yes | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | ||||||||||
| Developmental delays | ||||||||||||||
| No | 145 (97%) | 127 (95%) | 1.00 | 79 (93%) | 1.00 | 48 (100%) | ||||||||
| Yes | 4 (3%) | 6 (5%) | 1.61 (0.42-6.22) | 6 (7%) | 2.21 (0.56-8.62) | 0 (0%) | ||||||||
| Large/multiple birthmarks | ||||||||||||||
| No | 131 (88%) | 120 (90%) | 1.00 | 77 (91%) | 1.00 | 43 (90%) | 1.00 | |||||||
| Yes | 18 (12%) | 13 (10%) | 0.82 (0.37-1.83) | 8 (9%) | 0.78 (0.30-2.01) | 5 (10%) | 1.02 (0.31-3.36) | |||||||
| . | Controls . | Combined cases . | . | ALL . | . | AML . | . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | n (%) . | n (%) . | OR* (95% CI) . | n (%) . | OR* (95% CI) . | n (%) . | OR* (95% CI) . | |||||||
| At least one sibling with an abnormality† | ||||||||||||||
| No | 110 (74%) | 94 (71%) | 1.00 | 60 (71%) | 1.00 | 34 (71%) | 1.00 | |||||||
| Yes | 39 (26%) | 39 (29%) | 1.23 (0.71-2.13) | 25 (29%) | 1.12 (0.60-2.09) | 14 (29%) | 1.60 (0.66-3.86) | |||||||
| Number of siblings with abnormalities‡ | ||||||||||||||
| 0 | 110 (74%) | 94 (71%) | 1.00 | 60 (71%) | 1.00 | 34 (71%) | 1.00 | |||||||
| 1 | 32 (21%) | 36 (27%) | 1.36 (0.76-2.42) | 22 (26%) | 1.23 (0.64-2.38) | 14 (29%) | 1.94 (0.78-4.80) | |||||||
| ≥2 | 7 (5%) | 3 (2%) | 0.53 (0.12-2.36) | 3 (4%) | 0.61 (0.14-2.74) | 0 (0%) | ||||||||
| Ptrend = 0.91 | Ptrend = 0.88 | Ptrend = — | ||||||||||||
| Down syndrome | ||||||||||||||
| No | 148 (99%) | 132 (99%) | 1.00 | 85 (100%) | 47 (98%) | 1.00 | ||||||||
| Yes | 1 (1%) | 1 (1%) | 0.52 (0.03-10.47) | 0 (0%) | 1 (2%) | 0.64 (0.03-12.70) | ||||||||
| Microcephaly | ||||||||||||||
| No | 149 (100%) | 131 (99%) | 84 (99%) | 47 (98%) | ||||||||||
| Yes | 0 (0%) | 2 (1%) | 1 (1%) | 1 (2%) | ||||||||||
| Cleft lip or palate | ||||||||||||||
| No | 148 (99%) | 132 (99%) | 1.00 | 84 (99%) | 1.00 | 48 (100%) | ||||||||
| Yes | 1 (1%) | 1 (1%) | 0.85 (0.05-14.31) | 1 (1%) | 1.48 (0.09-24.80) | 0 (0%) | ||||||||
| Spina bifida/other spinal defect | ||||||||||||||
| No | 149 (100%) | 131 (99%) | 84 (99%) | 47 (98%) | ||||||||||
| Yes | 0 (0%) | 2 (1%) | 1 (1%) | 1 (2%) | ||||||||||
| Hemihypertrophy | ||||||||||||||
| No | 148 (99%) | 132 (99%) | 1.00 | 84 (99%) | 1.00 | 48 (100%) | ||||||||
| Yes | 1 (1%) | 1 (1%) | 1.09 (0.06-18.49) | 1 (1%) | 1.54 (0.08-28.37) | 0 (0%) | ||||||||
| Heart defect | ||||||||||||||
| No | 139 (93%) | 125 (94%) | 1.00 | 81 (95%) | 1.00 | 44 (92%) | 1.00 | |||||||
| Yes | 10 (7%) | 8 (6%) | 0.78 (0.28-2.18) | 4 (5%) | 0.57 (0.16-2.02) | 4 (8%) | 1.29 (0.30-5.52) | |||||||
| Pancreas/digestive tract defect | ||||||||||||||
| No | 149 (100%) | 132 (99%) | 85 (100%) | 47 (98%) | ||||||||||
| Yes | 0 (0%) | 1 (1%) | 0 (0%) | 1 (2%) | ||||||||||
| Kidney/bladder/sex organ defect | ||||||||||||||
| No | 146 (98%) | 129 (97%) | 1.00 | 83 (98%) | 1.00 | 46 (96%) | 1.00 | |||||||
| Yes | 3 (2%) | 4 (3%) | 1.86 (0.39-8.87) | 2 (2%) | 1.41 (0.22-9.00) | 2 (4%) | 1.90 (0.22-16.31) | |||||||
| Hernia | ||||||||||||||
| No | 142 (95%) | 125 (94%) | 1.00 | 80 (94%) | 1.00 | 45 (94%) | 1.00 | |||||||
| Yes | 7 (5%) | 8 (6%) | 1.44 (0.49-4.20) | 5 (6%) | 1.30 (0.38-4.48) | 3 (6%) | 1.96 (0.31-12.52) | |||||||
| Deafness/hearing impairment | ||||||||||||||
| No | 149 (100%) | 132 (99%) | 84 (99%) | 48 (100%) | ||||||||||
| Yes | 0 (0%) | 1 (1%) | 1 (1%) | 0 (0%) | ||||||||||
| Blindness/vision problems | ||||||||||||||
| No | 148 (99%) | 131 (99%) | 1.00 | 83 (98%) | 1.00 | 48 (100%) | ||||||||
| Yes | 1 (1%) | 2 (1%) | 3.09 (0.25-38.28) | 2 (2%) | 2.92 (0.22-38.57) | 0 (0%) | ||||||||
| Other chromosomal abnormalities | ||||||||||||||
| No | 149 (100%) | 133 (100%) | 85 (100%) | 48 (100%) | ||||||||||
| Yes | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) | ||||||||||
| Developmental delays | ||||||||||||||
| No | 145 (97%) | 127 (95%) | 1.00 | 79 (93%) | 1.00 | 48 (100%) | ||||||||
| Yes | 4 (3%) | 6 (5%) | 1.61 (0.42-6.22) | 6 (7%) | 2.21 (0.56-8.62) | 0 (0%) | ||||||||
| Large/multiple birthmarks | ||||||||||||||
| No | 131 (88%) | 120 (90%) | 1.00 | 77 (91%) | 1.00 | 43 (90%) | 1.00 | |||||||
| Yes | 18 (12%) | 13 (10%) | 0.82 (0.37-1.83) | 8 (9%) | 0.78 (0.30-2.01) | 5 (10%) | 1.02 (0.31-3.36) | |||||||
Adjusted for child's reference age (continuous), maternal age (<35 versus ≥ 35 y), maternal race (white versus non-white), and maternal education (≤high school versus some post–high school versus college graduate).
Includes only index children with at least one sibling (ncases = 133; ncontrols = 149).
Total count of siblings with at least one birth defect (range: 0≤ number of siblings ≤12).