Research and analysis
Table 1: Prevalence rate of Congenital Malformations for prioritised AEDs
Updated 7 January 2021
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| Carbamazepine | Gabapentin | Lamotrigine | Levetiracetam | Oxcarbazepine | Phenobarbital | Phenytoin | Pregabalin | Topiramate | Valproate | Zonisamide | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Meta-analyses | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Veroniki et al 2017a | 4.14% | 2.43% | 2.62% | 1.77% | 2.96% | 5.50% | 6.08% | - | 4.67% | 9.07% | - |
| Not set | 8437 exposures | 329 exposures | 6290 exposures | 1015 exposures | 372 exposures | 1709 exposures | 2237 exposures | Not set | 599 exposures | 4455 exposures | Not set |
| Weston et al 2016 | 3.71% (95% CI 3.19 to 4.27) | 1.47% (95% CI 0.26 to 3.64) | 2.31% (95% CI 1.87 to 2.78) | 1.77% (95% CI 0.98 to 2.79) | 2.39% | 7.10% | 5.38% | - | 4.28% | 9.09% (95% CI 8.02 to 10.23) | 0.28% |
| Not set | Not set | Not set | Not set | Not set | (95% CI 0.85 to 4.68) | (95% CI 5.36 to 9.08)) | (95% CI 4.22 to 6.67) | Not set | (95 % CI 2.65-6.29) | Not set | (95% CI 0.25 to 2.39) |
| Not set | 4.93% (95% CI 3.84 to 6.16) | RR 0.61 (0.07, 5.18) vs WWOE | RR 1.68 (0.78, 3.65) vs WWOE | RR 2.16 (0.76, 6.17) vs WWOE | Not set | Not set | Not set | Not set | Not set | 10.93% (95% CI 8.91 to 13.13) | Not set |
| Not set | Random effects modelling* | Not set | Not set | Not set | RR 1.94 (0.53, 7.15) vs WWOE | RR 2.84 (1,57, 5.13) vs WWOE | 6.26% | Not set | RR 3.69 (1.36, 10.07) vs WWOE | Random effects modelling* | RR 0.44 (0.02, 7.93) vs WWOE |
| Not set | Not set | RR 1.50 (1.16, 0.23, 5.93) vs WWE | RR 1.07 (.064, 1.77) vs WWE | RR 0.32 (0.10, 1.07) vs WWE | Not set | RR 1.95 (0.97, 3.93) vs WWE | (95% CI 4.37 to 8.47) | Not set | RR 1.99 (0.65, 6.08) vs WWE | Not set | Not set |
| Not set | RR 2.01 (1.20, 3.36) vs WWOE | Not set | Not set | Not set | RR 2.75 (0.53, 14.43) vs WWE | Not set | Random effects modelling | Not set | Not set | RR 5.69 (3.33, 9.73) vs WWOE | 90 exposures |
| Not set | Not set | Not set | Not set | Not set | Not set | 709 exposures | Not set | Not set | 473 exposures | RR 3.13 (2.16, 4.54) vs WWE | Not set |
| Not set | RR 1.50 (1.03, 2.19) vs WWE | 190 exposures | 4195 exposures | 817 exposures | Not set | Not set | RR 2.38 (1.12, 5.03) vs WWOE | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | 238 exposures | Not set | RR 2.40 (1,42, 4.08) vs WWE | Not set | Not set | 2565 exposures | Not set |
| Not set | 4666 exposures | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | 1279 exposures | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Meador et al 2008 | 4.62% | - | 2.91% (95% CI 2.00 to 3.82) LMT mono | - | - | 4.91% (95% CI 3.22 to 6.59) PHB mono | 7.36% | - | - | 10.73% | - |
| Not set | (95% CI 3.48 to 5.76) CBZ mono | Not set | Not set | Not set | Not set | Not set | (95% CI 3.60 to 11.11) | Not set | Not set | (95% CI 8.16 to 13.29) | Not set |
| Not set | Not set | Not set | 5.59% (95% CI 1.11 to 10.08) LMT dual | Not set | Not set | 9.19% (95% CI 5.88 to 12.50) PHB dual | PHT mono | Not set | Not set | VPA mono | Not set |
| Not set | 7.10% (95% CI 3.71 to 10.49) CBZ dual | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | 14.57% (95% CI 8.81 to 20.33) PHB poly | 11.47% | Not set | Not set | 9.79% | Not set |
| Not set | 8.57 (95% CI 1.99 to 15.16) CBZ poly | Not set | 1337 mono and | Not set | Not set | Not set | (95% CI 6.65 to 16.30) | Not set | Not set | (95% CI 7.57 to 12.02) | Not set |
| Not set | Not set | Not set | 599 dual exposures | Not set | Not set | Not set | PHT dual | Not set | Not set | VPA dual | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | 945 PHB mono exposures | Not set | Not set | Not set | Not set | Not set |
| Not set | 4411 mono | Not set | Not set | Not set | Not set | Not set | 14.27% | Not set | Not set | 25.00% | Not set |
| Not set | 942 dual and | Not set | Not set | Not set | Not set | Not set | (95% CI 8.95 to 19.60) | Not set | Not set | (95% CI 5.97 to 44.03) | Not set |
| Not set | 70 poly exposures | Not set | Not set | Not set | Not set | Not set | PHT poly | Not set | Not set | VPA poly | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | 1198 mono | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | 720 dual and | Not set | Not set | 2097 mono | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | 276 poly exposures | Not set | Not set | 694 dual and | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | 20 poly exposures | Not set |
| Pregnancy Registries | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| UK and Ireland Pregnancy Registry (UKEPR) | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| UKEPR | 2.60% | Not set | 2.30% | Not set | Not set | Not set | Not set | Not set | Not set | 6.70% | Not set |
| ? Campbell et al 2014 | (95% CI 1.9 to 3.5) | Not set | (95% CI 1.8 to 3.1) | Not set | Not set | Not set | Not set | Not set | Not set | (95% CI 5.5 to 8.3) | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | 1657 exposures | Not set | 2098 exposures | Not set | Not set | Not set | Not set | Not set | Not set | 1220 VPA exposures | Not set |
| ? UKEPR Morrow et al 2006 | 2.2% (95% CI 1.4 to 3.4) | 3.20% | 3.2% (95% 2.1 to 4.9) | 0.0% (95% CI 0.0 to 14.9) | Not set | Not set | 3.70% | Not set | 7.10% | 6.2% (95% CI 4.6 to 8.2) | Not set |
| Not set | Not set | (95% CI 0.6 to 16.2) | Not set | Not set | Not set | Not set | (95% CI 1.3 to 10.2) | Not set | (95% CI 2.0-22.6) | Not set | Not set |
| Not set | 927 exposures | Not set | 647 exposures | 26 exposures | Not set | Not set | Not set | Not set | Not set | 762 exposures | Not set |
| Not set | Not set | 31 exposures | Not set | Not set | Not set | Not set | 82 exposures | Not set | 28 exposures | Not set | Not set |
| ? Hunt et al 2008 | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | 4.80% | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | (95% CI 5.6-14.1) | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | 70 TPM mono exposures | Not set | Not set |
| European Pregnancy Registry (EURAP) | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Tomson et al 2018 | 5.50% | Not set | 2.90% | 2.80% | 3.00% | 6.50% | 6.40% | Not set | 3.90% | 10.30% | Not set |
| Not set | (95% CI 4.5 to 6.6) | Not set | (95% CI 2.3 to 3.7) | (95% CI 1.7 to 4.5) | (95% CI 1.4 to 5.4) | (95% CI 4.2 to 9.9) | (95% CI 2.8 to 12.2) | Not set | (95% CI 1.5-8.4) | (95% CI 8.8 to 12.0 | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | 1957 exposures | Not set | 2154 exposures | 599 exposures | 333 exposures | 294 exposures | 125 exposures | Not set | 152 exposures | 1381exposures | Not set |
| North American Antiepileptic Drug Pregnancy Registry (NAAEDPR) | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | 2.90% | 1.5% (95% CI 0.37 to 3.9) | 2.30% | 2.3% (95% CI 1.5 to 3.4) | 1.90% | 5.60% | 2.60% | - | 5.10% | 9.30% | 1.20% |
| Published on NAAEDPR website - 2019 | (95% CI 2.0 to 4.0%) | Not set | (95% CI 1.7 to 2.9) | Not set | (95 % CI 0.7 to 4.1%) | (95% CI 3.0 to 9.6%) | (95% CI 1.4 to 4.4) | Not set | (95% CI 3.4 to 7.4) | (95% CI 6.5 to 12.7%) | (95% CI 0.2 to 3.9%) |
| Not set | Not set | 207 exposures | Not set | 1029 exposures | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | 1110 exposures | Not set | 2179 exposures | Not set | 265 exposures | 195 exposures | 431 exposures | Not set | 489 exposures | 335 exposures | 166 exposures |
| ? Hernandez-Diaz et al 2012 | 3.00% | 0.7% (95% 0.02 to 3.8) | 2.00% | 2.40% | 2.20% | 5.50% | 2.90% | Not set | 4.20% | 9.30% | 0 malformations |
| Not set | (95% CI 2.1 to 4.2) | Not set | (95% CI 1.4 to 2.8) | (95% CI 1.2 to 4.3) | (95% CI 0.6 to 5.5) | (95% CI 2.8 to 9.7) | (95% CI 1.5 to 5.0) | Not set | (95% CI 2.4 to 6.8) | (6.4 to 13.0 | Not set |
| Not set | Not set | 145 exposures | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | 90 exposures |
| Not set | 1033 exposures | Not set | 1562 exposures | 450 exposures | 182 exposures | 199 exposures | 416 exposures | Not set | 359 exposures | 323 exposures | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Australian Pregnancy Registry (APR) | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Vajda et al 2019 | 5.90% | Not set | 4.90% | 3.60% | 5.30% | Not set | 2.30% | Not set | 1.90% | 14.80% | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | 409 exposures | Not set | 406 exposures | 139 exposures | 19 exposures | Not set | Not set | Not set | 53 exposures | 290 exposures | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | 44 exposures | Not set | Not set | Not set | Not set |
| ? Vajda et al 2014 | 5.50% | Not set | 4.60% | 2.40% | 5.90% | Not set | 2.40% | Not set | 2.40% | 13.80% | Not set |
| Not set | 346 exposure | Not set | 307 exposures | 82 exposures | 17 exposures | Not set | 41 exposures | Not set | 42 exposures | 253 exposures | Not set |
| Prospective studies | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Patorno et al 2017 | Not set | Not set | Not set | Not set | Not set | Not set | Not set | 5.90% | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Prospective cohort study | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | 477 exposures | Not set | Not set | Not set |
| Petersen et al 2017 | 3.29% | Not set | 2.80% | Not set | Not set | Not set | Not set | Not set | Not set | 6.55% | Not set |
| Not set | (95% CI 1.66 to 5.82) | Not set | (95% CI 1.35 to 5.09) | Not set | Not set | Not set | Not set | Not set | Not set | (95% CI 3.71 to 10.57) | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | 334 exposures | Not set | 357 exposures | Not set | Not set | Not set | Not set | Not set | Not set | 229 exposures | Not set |
| Winterfeld et al 2016 | Not set | Not set | Not set | Not set | Not set | Not set | Not set | 9.60% | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Prospective cohort study | Not set | Not set | Not set | Not set | Not set | Not set | Not set | 164 total | Not set | Not set | Not set |
| Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | 116 1st trimester (19 mono) | Not set | Not set | Not set |
| ? Veiby et al 2014? | 2.90% | Not set | 3.40% | 1.70% | 1.80% | 7.40% | Not set | 3.30% | 4.20% | 6.30% | Not set |
| Not set | 685 exposures | Not set | 833 exposures | 118 exposures | 57 exposures | 27 exposures | Not set | 30 exposures | 48 exposures | 333 exposures | Not set |
| ? Fujii et al 2013 | Not set | 4.10% | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| Not set | Not set | 223 exposures | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| ? Kallen et al 2013 | 3.40% | 1.40% | 2.77% | 0.66% | 6.90% | 7.14% | 6.94% | 1.56% | 5.88% | 7.19% | 14.28% |
| Not set | 1706 total and 1511 mono exposures | 143 total and 119 mono exposures | 1337 total and 1084 mono exposures | 151 total 57 mono exposures | 58 total and 40 mono exposures | 28 total and 17 mono exposures | 173 total and 140 mono exposures | 128 total and 111 mono exposures | 102 total and 49 mono exposures | 862 total and 697 mono exposures | 7 total and 3 mono exposures |
| ? Kaaja et al 2003 | 3.96% | Not set | Not set | Not set | 11% | 4.54% | 3.30% | Not set | Not set | 6.35% | Not set |
| Not set | 363 exposures | Not set | Not set | Not set | 9 exposures | 5 exposures | 124 exposures | Not set | Not set | 61 exposures | Not set |
| *Conducted due to significant variance | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |
| ? These studies were included in the Weston et al 2016 and/or the Veroniki et al 2017a meta-analyses and therefore for the purposes of the public assessment report these data will not be presented separately. | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set | Not set |