Table 3. Association of Different Doses of Prenatal Exposure to Valproate and Other ASMs With Childhood Epilepsya.
| ASM monotherapy exposure, mg/d | Children of mothers with epilepsy | Incidence rate, per 10 000 person-years (95% CI) | AHR (95% CI) | Cumulative incidence, age 10 y, % (95% CI) | ||
|---|---|---|---|---|---|---|
| Total No. (N = 38 663) | With epilepsy, No. | |||||
| Basic adjustedb | Fully adjustedc | |||||
| No ASM | 22 207 | 390 | 26.5 (24.0-29.2) | 1 [Reference] | 1 [Reference] | 2.5 (2.2-2.8) |
| Valproate | ||||||
| <750 | 774 | 48 | 63.5 (47.8-84.2) | 2.24 (1.62-3.09) | 2.18 (1.58-3.02) | 6.0 (4.3-8.1) |
| 750-1499 | 888 | 55 | 62.4 (47.9-81.2) | 2.11 (1.53-2.92) | 2.19 (1.58-3.02) | 5.6 (4.1-7.5) |
| ≥1500 | 290 | 19 | 62.4 (39.8-97.9) | 2.04 (1.24-3.33) | 2.14 (1.30-3.50) | 6.7 (4.0-10.2) |
| Lamotrigine | ||||||
| <150 | 1480 | 29 | 26.7 (18.6-38.4) | 1.04 (0.71-1.52) | 1.01 (0.69-1.48) | 2.9 (1.9-4.2) |
| 150-299 | 1617 | 38 | 35.7 (26.0-49.0) | 1.36 (0.97-1.91) | 1.44 (1.03-2.03) | 3.3 (2.3-4.7) |
| ≥300 | 2192 | 37 | 29.1 (21.1-40.2) | 1.07 (0.76-1.51) | 1.12 (0.79-1.58) | 3.0 (2.0-4.3) |
| Levetiracetam | ||||||
| <750 | 225 | 5 | 54.1 (22.5-129.9) | 1.93 (0.79-4.73) | 1.86 (0.75-4.57) | NA |
| 750-1499 | 330 | 5 | 36.8 (15.3-88.3) | 1.38 (0.57-3.37) | 1.38 (0.56-3.36) | NA |
| ≥1500 | 506 | 6 | 26.1 (11.7-58.1) | 0.93 (0.41-2.10) | 0.98 (0.43-2.21) | NA |
| Carbamazepine | ||||||
| <500 | 800 | 27 | 35.0 (24.0-51.0) | 1.18 (0.78-1.79) | 1.21 (0.79-1.83) | 2.7 (1.6-4.1) |
| 500-999 | 1270 | 34 | 25.2 (18.0-35.3) | 0.85 (0.58-1.26) | 0.95 (0.64-1.40) | 2.7 (1.9-3.9) |
| ≥1000 | 594 | 20 | 36.5 (23.6-56.6) | 1.29 (0.81-2.05) | 1.42 (0.89-2.28) | 3.7 (2.1-6.1) |
| Oxcarbazepine | ||||||
| <500 | 232 | <5d | NA | NA | NA | NA |
| ≥500 | 1228 | 20d | 19.8 (13.3-29.6) | 0.70 (0.44-1.11) | 0.73 (0.46-1.17) | 1.6 (0.9-2.6) |
| Topiramate | ||||||
| <150 | 188 | <5d | NA | NA | NA | NA |
| ≥150 | 102 | 10d | 139.7 (72.7-268.5) | 4.79 (2.44-9.39) | 4.88 (2.47-9.62) | NA |
| Clonazepam | ||||||
| <4 | 292 | 13 | 41.5 (24.1-71.4) | 1.61 (0.92-2.84) | 1.61 (0.91-2.85) | 3.0 (1.4-5.7) |
| ≥4 | 47 | 5 | 97.2 (40.4-233.4) | 3.43 (1.39-8.49) | 3.66 (1.48-9.05) | NA |
Abbreviations: AHR, adjusted hazard ratio; ASM, antiseizure medication; NA, not analyzed due to low numbers or insufficient follow-up time.
a
Based on 5 Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) from 1996 to 2017.
b
Adjusted for year of birth, sex of the child, and country of birth.
c
Additionally adjusted for maternal age, parity, educational level, smoking in pregnancy, use of antidepressants in pregnancy, and maternal psychiatric comorbidity.
d
Rounded for data privacy reasons.