Background
Methods
Study design and populations (Fig. 1)
Register-based data
Exposure to maternal thyroid disorder
Cases of cerebral palsy
Covariates
Statistical analyses
Results
Characteristics of the study populations
Danish register-based study population No = 1,270,079 | MOBAND study population No = 192,918 | |||
---|---|---|---|---|
Characteristics | Exposed to maternal thyroid disorder No = 23,625 | Unexposed No = 1,246,454 | Exposed to maternal thyroid disorder No = 3042 | Unexposed No = 189,876 |
No (%) | No (%) | No (%) | No (%) | |
Maternal age | ||||
≥ 30 years | 13,921 (58.9) | 544,852 (43.7) | 1997 (65.6) | 103,084 (54.3) |
Missing | 0 (−) | 0 (−) | 0 (−) | 0 (−) |
Maternal occupational statusa | ||||
Unemployed/ receiving benefits or pension | – | – | 310 (10.2) | 6816 (3.6) |
Missing | – | – | 50 (1.6) | 2055 (1.1) |
Maternal educational levelb | ||||
Basic | 4781 (20.2) | 280,337 (22.5) | – | – |
Missing | 694 (2.9) | 93,414 (7.5) | – | – |
Maternal diabetes | ||||
Diabetes type 1 or 2 | 518 (2.2) | 6362 (<1) | 61 (2.0) | 855 (<1) |
Missing | 0 (−) | 0 (−) | 0 (−) | 0 (−) |
Smoking in pregnancy | ||||
≥ 1 cigarettes/day | – | – | 293 (9.6) | 23,009 (12.1) |
Missing | – | – | 18 (<1) | 900 (<1) |
Alcohol consumption in pregnancy | ||||
≥ 0.5 units/week | – | – | 529 (17.4) | 50,510 (26.6) |
Missing | – | – | 206 (6.8) | 10,129 (5.3) |
Child’s sex | ||||
Male | 11,690 (49.5) | 606,514 (48.7) | 1572 (51.7) | 97,265 (51.2) |
Missing | 5 (<1) | 864 (<1) | 0 (−) | 2 (< 1) |
Gestational age | ||||
< 37 weeks (preterm) | 1796 (7.6) | 72,204 (5.8) | 233 (7.7) | 11,691 (6.2) |
Missing | 0 (−) | 5 (< 1) | 12 (< 1) | 423 (<1) |
Maternal thyroid disorder and risk of cerebral palsy
Danish register-based study population
| ||||||||||
Maternal thyroid disordera | All CP (No = 2798) | Unilateral Spastic CP (No = 912) | Bilateral Spastic CP (No = 1490) | |||||||
No | No | ORb (95% CI) | ORc (95% CI) | No | ORb (95% CI) | ORc (95% CI) | No | ORb (95% CI) | ORc (95% CI) | |
No thyroid disorder | 1,246,454 | 2748 | 1 (ref.) | 1 (ref.) | 894 | 1 (ref.) | 1 (ref.) | 1465 | 1 (ref.) | 1 (ref.) |
Thyroid disorderd | 23,625 | 50 | 0.96 (0.73–1.27) | 0.99 (0.74–1.31) | 18 | 1.06 (0.67–1.69) | 0.93 (0.58–1.48) | 25 | 0.90 (0.61–1.34) | 1.03 (0.69–1.53) |
Hypothyroidism | 12,929 | 26 | 0.91 (0.62–1.34) | 0.95 (0.64–1.39) | 9 | 0.97 (0.50–1.87) | 0.83 (0.43–1.61) | 13 | 0.86 (0.50–1.48) | 1.01 (0.58–1.74) |
Hyperthyroidism | 9943 | 24 | 1.10 (0.73–1.64) | 1.11 (0.94–1.66) | 9 | 1.26 (0.65–2.43) | 1.13 (0.59–2.18) | 12 | 1.03 (0.58–1.81) | 1.13 (0.64–1.99) |
Identification of thyroid disorder | ||||||||||
No | 1,246,454 | 2748 | 1 (ref.) | 1 (ref.) | 894 | 1 (ref.) | 1 (ref.) | 1465 | 1 (ref.) | 1 (ref.) |
Before pregnancy | 9622 | 20 | 0.94 (0.61–1.46) | 0.97 (0.62–1.50) | 7 | 1.01 (0.48–2.13) | 0.86 (0.41–1.81) | 11 | 0.97 (0.54–1.76) | 1.13 (0.62–2.04) |
In pregnancy | 1551 | 7 | 2.05 (0.98–4.32) | 2.00 (0.95–4.21) | 4 | 3.60 (1.35–9.63) | 3.14 (1.17–8.42) | <4f | NE | NE |
≤ 5 years after pregnancy | 12,452 | 23 | 0.84 (0.56–1.26) | 0.87 (0.58–1.31) | 7 | 0.78 (0.37–1.65) | 0.70 (0.33–1.48) | 12 | 0.82 (0.46–1.45) | 0.94 (0.53–1.66) |
MOBAND study population
| ||||||||||
Maternal thyroid disorder in pregnancy | All CP (No = 402) | |||||||||
No | No | ORb (95% CI) | ORc (95% CI) | ORe (95% CI) | ||||||
No thyroid disorder | 189,876 | 394 | 1 (ref.) | 1 (Ref.) | 1 (ref.) | |||||
Thyroid disorder | 3042 | 8 | 1.27 (0.63–2.55) | 1.18 (0.58–2.39) | 1.17 (0.58–2.38) | |||||
No medicationg | 534 | 3 | 2.71 (0.87–8.46) | 2.54 (0.81–7.94) | 2.54 (0.81–7.93) | |||||
Use of medicationg | 2229 | 4 | 0.86 (0.32–2.30) | 0.82 (0.30–2.19) | 0.82 (0.30–2.19) |
Assessment of bias
Agreement between sources of maternal thyroid disorder in 90,088 danish children included in both the danish register-based study population and MOBAND study population | |||||
---|---|---|---|---|---|
Register-based information
a
|
Self-report
| ||||
Unexposed | Hypothyroidism | Hyperthyroidism | Unclassifiable | Total | |
Unexposed |
88,841
| 110 | 48 | 158 | 89,157 |
Hypothyroidism | 164 |
240
| 17 | 68 | 489 |
Hyperthyroidism | 213 | 21 |
147
| 21 | 402 |
Unclassifiable | 19 | 14 | 4 |
3
| 40 |
Total | 89,237 | 385 | 216 | 250 | 90,088 |
Observed proportionate agreement | |||||
Proportion of positive agreement
| 0.60 | ||||
Proportion of negative agreement | 0.99 | ||||
Kappa | 0.60, p < 0.001 | ||||
Bias-adjusted estimates of thyroid disorder and risk of cerebral palsy
| |||||
All CP | Unilateral spastic CP | Bilateral spastic CP | |||
Bias-adjusted ORb (study error)c in register-based study population | 0.89 (0.40–1.21) | 1.20 (0.72–3.83) | 0.77 (0.24–1.22) |