Baseline characteristics according to AED use during pregnancy
| Lamotrigine | Carbamazepine | Clonazepam | Gabapentin | Levetiracetam | ||||||
| Number of exposed pregnancies | 2916 | 502 | 1246 | 378 | 621 | |||||
| Median follow-up (years) (IQR) | 3.5 (2.7 to 4.5) | 3.8 (2.8 to 4.7) | 4.8 (4.1 to 5.3) | 3.4 (2.5 to 4.3) | 3.4 (2.6 to 4.4) | |||||
| Maternal age at birth (years) | <25 | 431 (14.8) | 51 (10.2) | *** | 118 (9.5) | *** | 32 (8.5) | *** | 119 (19.2) | ** |
| 25–30 | 927 (31.8) | 119 (23.7) | 302 (24.2) | 90 (23.8) | 212 (34.1) | |||||
| 30–35 | 980 (33.6) | 168 (33.5) | 380 (30.5) | 125 (33.1) | 181 (29.1) | |||||
| ≥35 | 578 (19.8) | 164 (32.7) | 446 (35.8) | 131 (34.7) | 109 (17.6) | |||||
| Eligibility for CMU-C | 461 (15.8) | 98 (19.5) | * | 303 (24.3) | *** | 82 (21.7) | ** | 134 (21.6) | *** | |
| History of mental and behavioural disorders | 368 (12.6) | 104 (20.7) | *** | 216 (17.3) | *** | 43 (11.4) | NS | 51 (8.2) | ** | |
| Proxy for alcohol intake | 35 (1.2) | 7 (1.4) | NS | 35 (2.8) | *** | 6 (1.6) | NS | 13 (2.1) | NS | |
| Proxy for smoking | 311 (10.7) | 59 (11.8) | NS | 165 (13.2) | * | 66 (17.5) | *** | 69 (11.1) | NS | |
| Folic acid supplementation | 2026 (69.5) | 281 (56.0) | *** | 360 (28.9) | *** | 139 (36.8) | *** | 396 (63.8) | ** | |
| SSRIs during pregnancy | 210 (7.2) | 42 (8.4) | NS | 201 (16.1) | *** | 42 (11.1) | ** | 23 (3.7) | ** | |
| History of antipsychotic use | 227 (7.8) | 64 (12.7) | *** | 123 (9.9) | * | 24 (6.3) | NS | 15 (2.4) | *** | |
| Number of psychiatric medications† | 0 | 1641 (56.3) | 265 (52.8) | * | 492 (39.5) | *** | 157 (41.5) | *** | 366 (58.9) | NS |
| 1 | 669 (22.9) | 107 (21.3) | 283 (22.7) | 91 (24.1) | 138 (22.2) | |||||
| 2 | 258 (8.8) | 42 (8.4) | 149 (12.0) | 49 (13.0) | 54 (8.7) | |||||
| 3–4 | 211 (7.2) | 52 (10.4) | 183 (14.7) | 54 (14.3) | 39 (6.3) | |||||
| ≥5 | 137 (4.7) | 36 (7.2) | 139 (11.2) | 27 (7.1) | 24 (3.9) | |||||
| Gestational age (weeks after LMP) | <32 | 11 (0.4) | 3 (0.6) | NS | 10 (0.8) | NS | 2 (0.5) | *** | 7 (1.1) | NS |
| 32–35 | 42 (1.4) | 8 (1.6) | 28 (2.2) | 23 (6.1) | 11 (1.8) | |||||
| 35–37 | 129 (4.4) | 14 (2.8) | 55 (4.4) | 21 (5.6) | 33 (5.3) | |||||
| ≥37 | 2734 (93.8) | 477 (95.0) | 1153 (92.5) | 332 (87.8) | 570 (91.8) | |||||
| Gender (male) | 1524 (52.3) | 265 (52.8) | NS | 597 (47.9) | * | 206 (54.5) | NS | 292 (47.0) | * | |
| Birth weight | <2500 | 179 (6.1) | 35 (7.0) | NS | 105 (8.4) | * | 47 (12.4) | *** | 60 (9.7) | *** |
| 2500–3000 | 630 (21.6) | 110 (21.9) | 278 (22.3) | 73 (19.3) | 152 (24.5) | |||||
| 3000–3500 | 1196 (41.0) | 182 (36.3) | 485 (38.9) | 140 (37.0) | 251 (40.4) | |||||
| ≥3500 | 911 (31.2) | 175 (34.9) | 378 (30.3) | 118 (31.2) | 158 (25.4) | |||||
| Oxcarbazepine | Pregabalin | Topiramate | Valproic acid | ||||||
| Number of exposed pregnancies | 143 | 1627 | 477 | 991 | |||||
| Median follow-up (years) (IQR) | 4.0 (2.7 to 4.8) | 3.3 (2.5 to 4.3) | 3.6 (2.6 to 4.6) | 3.9 (2.8 to 4.8) | |||||
| Maternal age at birth (years) | <25 | 23 (16.1) | NS | 139 (8.5) | *** | 66 (13.8) | NS | 137 (13.8) | *** |
| 25–30 | 32 (22.4) | 414 (25.4) | 144 (30.2) | 259 (26.1) | |||||
| 30–35 | 52 (36.4) | 495 (30.4) | 153 (32.1) | 310 (31.3) | |||||
| ≥35 | 36 (25.2) | 579 (35.6) | 114 (23.9) | 285 (28.8) | |||||
| Eligibility for CMU-C | 36 (25.2) | ** | 404 (24.8) | *** | 79 (16.6) | NS | 311 (31.4) | *** | |
| History of mental and behavioural disorders | 36 (25.2) | *** | 169 (10.4) | * | 54 (11.3) | NS | 96 (9.7) | * | |
| Proxy for alcohol intake | 1 (0.7) | NS | 21 (1.3) | NS | 7 (1.5) | NS | 22 (2.2) | * | |
| Proxy for smoking | 13 (9.1) | NS | 257 (15.8) | *** | 43 (9.0) | NS | 136 (13.7) | ** | |
| Folic acid supplementation | 89 (62.2) | NS | 440 (27.0) | *** | 179 (37.5) | *** | 525 (53.0) | *** | |
| SSRIs during pregnancy | 22 (15.4) | *** | 172 (10.6) | *** | 55 (11.5) | ** | 33 (3.3) | *** | |
| History of antipsychotic use | 31 (21.7) | *** | 79 (4.9) | *** | 30 (6.3) | NS | 49 (4.9) | ** | |
| Number of psychiatric medications† | 0 | 65 (45.5) | *** | 701 (43.1) | *** | 217 (45.5) | *** | 653 (65.9) | *** |
| 1 | 33 (23.1) | 355 (21.8) | 92 (19.3) | 180 (18.2) | |||||
| 2 | 14 (9.8) | 227 (14.0) | 69 (14.5) | 67 (6.8) | |||||
| 3–4 | 9 (6.3) | 216 (13.3) | 68 (14.3) | 45 (4.5) | |||||
| ≥5 | 22 (15.4) | 128 (7.9) | 31 (6.5) | 46 (4.6) | |||||
| Gestational age (weeks after LMP) | <32 | 1 (0.7) | NS | 12 (0.7) | * | 7 (1.5) | * | 7 (0.7) | NS |
| 32–35 | 3 (2.1) | 37 (2.3) | 10 (2.1) | 19 (1.9) | |||||
| 35–37 | 6 (4.2) | 61 (3.7) | 19 (4.0) | 45 (4.5) | |||||
| ≥37 | 133 (93.0) | 1517 (93.2) | 441 (92.5) | 920 (92.8) | |||||
| Gender (male) | 65 (45.5) | NS | 847 (52.1) | NS | 254 (53.2) | NS | 496 (50.1) | NS | |
| Birth weight | <2500 | 12 (8.4) | NS | 118 (7.3) | NS | 32 (6.7) | NS | 88 (8.9) | * |
| 2500–3000 | 30 (21.0) | 324 (19.9) | 90 (18.9) | 227 (22.9) | |||||
| 3000–3500 | 60 (42.0) | 630 (38.7) | 203 (42.6) | 389 (39.3) | |||||
| ≥3500 | 41 (28.7) | 555 (34.1) | 152 (31.9) | 287 (29.0) | |||||
Figures are N (%).
*P<0.05, **p<0.01, ***p<0.001.
†Number of fifth-level ATC classes of psychiatric medications to whom mothers were exposed in the year before pregnancy.
AED, antiepileptic drug; ATC, Anatomical Therapeutic Chemical; CMU- C, complementary universal health insurance for low-income people; IQR, interquartile range; LMP, last menstrual period; NS, not significant; SSRIs, selective serotonin reuptake inhibitors.