Table 1.
Maternal and neonatal characteristics by exposure group—overall study population. N (%) are shown.
| Unexposed* | Exposed to valproate | Exposed to lamotrigine | Exposed to carbamazepine | Exposed to clonazepam | Exposed to gabapentin | Exposed to levetiracetam | Exposed to oxcarbazepine | Exposed to phenobarbital | Exposed to pregabalin | Exposed to topiramate | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (N = 1,710,441) | (N = 991) | (N = 2,813) | (N = 468) | (N = 1,246) | (N = 378) | (N = 621) | (N = 143) | (N = 84) | (N = 1,627) | (N = 477) | ||
| Maternal characteristics | ||||||||||||
| Age at the end of pregnancy (years) | Mean (standard deviation) | 29.8 (5.3) | 31.0 (5.7) | 29.9 (5.1) | 31.7 (5.6) | 32.1 (5.5) | 32.2 (5.5) | 29.3 (5.3) | 30.6 (5.7) | 31.4 (6.6) | 32.3 (5.7) | 30.5 (5.3) |
| < 25 | 276,843 (16.2) | 137 (13.8) | 424 (15.1) | 50 (10.7) | 118 (9.5) | 32 (8.5) | 119 (19.2) | 23 (16.1) | 18 (21.4) | 139 (8.5) | 66 (13.8) | |
| [25–30] | 562,803 (32.9) | 259 (26.1) | 916 (32.6) | 111 (23.7) | 302 (24.2) | 90 (23.8) | 212 (34.1) | 32 (22.4) | 15 (17.9) | 414 (25.4) | 144 (30.2) | |
| [30–35] | 547,199 (32.0) | 310 (31.3) | 942 (33.5) | 156 (33.3) | 380 (30.5) | 125 (33.1) | 181 (29.1) | 52 (36.4) | 20 (23.8) | 495 (30.4) | 153 (32.1) | |
| ≥ 35 | 323,596 (18.9) | 285 (28.8) | 531 (18.9) | 151 (32.3) | 446 (35.8) | 131 (34.7) | 109 (17.6) | 36 (25.2) | 31 (36.9) | 579 (35.6) | 114 (23.9) | |
| Complementary Universal Health Insurance scheme | 270,199 (15.8) | 311 (31.4) | 446 (15.9) | 92 (19.7) | 303 (24.3) | 82 (21.7) | 134 (21.6) | 36 (25.2) | 27 (32.1) | 404 (24.8) | 79 (16.6) | |
| Salary reconstituted from the sum of maternity leave allowances | Missing data | 660,198 (38.6) | 552 (55.7) | 1,157 (41.1) | 218 (46.6) | 577 (46.3) | 162 (42.9) | 264 (42.5) | 67 (46.9) | 50 (59.5) | 701 (43.1) | 190 (39.8) |
| < €1000 ** | 75,800 (7.2) | 58 (13.2) | 161 (9.7) | 32 (12.8) | 58 (8.7) | 17 (7.9) | 43 (12.0) | 7 (9.2) | 6 (17.6) | 117 (12.6) | 27 (9.4) | |
| €1000–1499 ** | 156,470 (14.9) | 102 (23.2) | 256 (15.5) | 43 (17.2) | 126 (18.8) | 50 (23.1) | 73 (20.4) | 18 (23.7) | 9 (26.5) | 177 (19.1) | 63 (22.0) | |
| €1500–1999 ** | 349,119 (33.2) | 144 (32.8) | 612 (37.0) | 91 (36.4) | 216 (32.3) | 81 (37.5) | 118 (33.1) | 26 (34.2) | 10 (29.4) | 366 (39.5) | 103 (35.9) | |
| €2000–2499 ** | 222,451 (21.2) | 74 (16.9) | 310 (18.7) | 53 (21.2) | 135 (20.2) | 34 (15.7) | 56 (15.7) | 17 (22.4) | 7 (20.6) | 136 (14.7) | 61 (21.3) | |
| €2500–2999 ** | 118,169 (11.3) | 38 (8.7) | 160 (9.7) | 19 (7.6) | 48 (7.2) | 19 (8.8) | 37 (10.4) | 5 (6.6) | 1 (2.9) | 74 (8.0) | 16 (5.6) | |
| ≥ €3000 ** | 128,234 (12.2) | 23 (5.2) | 157 (9.5) | 12 (4.8) | 86 (12.9) | 15 (6.9) | 30 (8.4) | 3 (3.9) | 1 (2.9) | 56 (6.0) | 17 (5.9) | |
| Year of end of pregnancy | 2011 | 321,046 (18.8) | 243 (24.5) | 490 (17.4) | 121 (25.9) | 601 (48.2) | 59 (15.6) | 90 (14.5) | 32 (22.4) | 15 (17.9) | 230 (14.1) | 93 (19.5) |
| 2012 | 488,371 (28.6) | 333 (33.6) | 778 (27.7) | 134 (28.6) | 500 (40.1) | 90 (23.8) | 147 (23.7) | 50 (35.0) | 32 (38.1) | 412 (25.3) | 118 (24.7) | |
| 2013 | 471,047 (27.5) | 233 (23.5) | 793 (28.2) | 134 (28.6) | 83 (6.7) | 116 (30.7) | 202 (32.5) | 27 (18.9) | 23 (27.4) | 465 (28.6) | 128 (26.8) | |
| 2014 | 429,977 (25.1) | 182 (18.4) | 752 (26.7) | 79 (16.9) | 62 (5.0) | 113 (29.9) | 182 (29.3) | 34 (23.8) | 14 (16.7) | 520 (32.0) | 138 (28.9) | |
| Folic acid | 482,209 (28.2) | 525 (53.0) | 1,978 (70.3) | 268 (57.3) | 360 (28.9) | 139 (36.8) | 396 (63.8) | 89 (62.2) | 32 (38.1) | 440 (27.0) | 179 (37.5) | |
| Indicator of alcohol use | 5,503 (0.3) | 22 (2.2) | 27 (1.0) | 2 (0.4) | 35 (2.8) | 6 (1.6) | 13 (2.1) | 1 (0.7) | 2 (2.4) | 21 (1.3) | 7 (1.5) | |
| Indicator of tobacco use | 137,968 (8.1) | 136 (13.7) | 283 (10.1) | 53 (11.3) | 165 (13.2) | 66 (17.5) | 69 (11.1) | 13 (9.1) | 8 (9.5) | 257 (15.8) | 43 (9.0) | |
| Diagnosis of mental illness other than tobacco and alcohol use disorders | 41,553 (2.4) | 96 (9.7) | 287 (10.2) | 74 (15.8) | 216 (17.3) | 43 (11.4) | 51 (8.2) | 36 (25.2) | 15 (17.9) | 169 (10.4) | 54 (11.3) | |
| Antidepressants before pregnancy | 105,848 (6.2) | 107 (10.8) | 399 (14.2) | 84 (17.9) | 494 (39.6) | 143 (37.8) | 68 (11.0) | 37 (25.9) | 13 (15.5) | 603 (37.1) | 185 (38.8) | |
| Antidepressants during pregnancy | 38,561 (2.3) | 58 (5.9) | 239 (8.5) | 67 (14.3) | 393 (31.5) | 100 (26.5) | 30 (4.8) | 29 (20.3) | 7 (8.3) | 422 (25.9) | 113 (23.7) | |
| SSRI during pregnancy | 27,188 (1.6) | 33 (3.3) | 168 (6.0) | 36 (7.7) | 201 (16.1) | 42 (11.1) | 23 (3.7) | 22 (15.4) | 5 (6.0) | 172 (10.6) | 55 (11.5) | |
| Antipsychotics before pregnancy | 12,497 (0.7) | 49 (4.9) | 131 (4.7) | 32 (6.8) | 123 (9.9) | 24 (6.3) | 15 (2.4) | 31 (21.7) | 6 (7.1) | 79 (4.9) | 30 (6.3) | |
| Antipsychotics during pregnancy | 11,281 (0.7) | 37 (3.7) | 77 (2.7) | 24 (5.1) | 109 (8.7) | 17 (4.5) | 8 (1.3) | 24 (16.8) | 5 (6.0) | 67 (4.1) | 27 (5.7) | |
| Anxiolytics before pregnancy | 243,326 (14.2) | 284 (28.7) | 980 (34.8) | 176 (37.6) | 522 (41.9) | 150 (39.7) | 232 (37.4) | 59 (41.3) | 28 (33.3) | 659 (40.5) | 188 (39.4) | |
| Anxiolytics during pregnancy | 106,177 (6.2) | 206 (20.8) | 675 (24.0) | 120 (25.6) | 389 (31.2) | 112 (29.6) | 173 (27.9) | 50 (35.0) | 23 (27.4) | 429 (26.4) | 103 (21.6) | |
| Hypnotics before pregnancy | 69,084 (4.0) | 93 (9.4) | 246 (8.7) | 44 (9.4) | 287 (23.0) | 72 (19.0) | 57 (9.2) | 20 (14.0) | 12 (14.3) | 315 (19.4) | 71 (14.9) | |
| Hypnotics during pregnancy | 18,314 (1.1) | 46 (4.6) | 94 (3.3) | 28 (6.0) | 157 (12.6) | 32 (8.5) | 28 (4.5) | 15 (10.5) | 4 (4.8) | 149 (9.2) | 34 (7.1) | |
| Indicator of severity of psychiatric morbidity (number of ATC classes of psychotropic drugs) | 0 | 1,406,243 (82.2) | 653 (65.9) | 1,640 (58.3) | 263 (56.2) | 492 (39.5) | 157 (41.5) | 366 (58.9) | 65 (45.5) | 53 (63.1) | 701 (43.1) | 217 (45.5) |
| 1 | 184,570 (10.8) | 180 (18.2) | 658 (23.4) | 107 (22.9) | 283 (22.7) | 91 (24.1) | 138 (22.2) | 33 (23.1) | 10 (11.9) | 355 (21.8) | 92 (19.3) | |
| 2 | 67,558 (3.9) | 67 (6.8) | 247 (8.8) | 34 (7.3) | 149 (12.0) | 49 (13.0) | 54 (8.7) | 14 (9.8) | 8 (9.5) | 227 (14.0) | 69 (14.5) | |
| 3 | 27,762 (1.6) | 28 (2.8) | 106 (3.8) | 26 (5.6) | 102 (8.2) | 40 (10.6) | 28 (4.5) | 5 (3.5) | 4 (4.8) | 133 (8.2) | 36 (7.5) | |
| 4 | 12,338 (0.7) | 17 (1.7) | 71 (2.5) | 11 (2.4) | 81 (6.5) | 14 (3.7) | 11 (1.8) | 4 (2.8) | 5 (6.0) | 83 (5.1) | 32 (6.7) | |
| ≥ 5 | 11,970 (0.7) | 46 (4.6) | 91 (3.4) | 27 (5.8) | 139 (11.2) | 27 (7.2) | 24 (3.9) | 22 (15.4) | 4 (4.8) | 128 (7.9) | 31 (6.5) | |
| Neonatal characteristics | ||||||||||||
| Gestational age at birth | Mean (standard deviation) | 39.1 (1.7) | 39.0 (1.8) | 39.0 (1.7) | 39.1 (1.8) | 38.9 (1.9) | 38.6 (2.1) | 38.9 (2.0) | 38.8 (1.9) | 38.8 (2.0) | 38.9 (1.9) | 39.0 (2.1) |
| 22–26 WA | 2041 (0.1) | 1 (0.1) | 2 (0.1) | 0 (0.0) | 1 (0.1) | 0 (0.0) | 1 (0.2) | 1 (0.7) | 0 (0.0) | 3 (0.2) | 1 (0.2) | |
| 27–31 WA | 8584 (0.5) | 6 (0.6) | 9 (0.3) | 3 (0.6) | 9 (0.7) | 2 (0.5) | 6 (1.0) | 0 (0.0) | 1 (1.2) | 9 (0.6) | 6 (1.3) | |
| 32–34 WA | 20,638 (1.2) | 19 (1.9) | 40 (1.4) | 7 (1.5) | 28 (2.2) | 23 (6.1) | 11 (1.8) | 3 (2.1) | 1 (1.2) | 37 (2.3) | 10 (2.1) | |
| 35–36 WA | 59,992 (3.5) | 45 (4.5) | 124 (4.4) | 12 (2.6) | 55 (4.4) | 21 (5.6) | 33 (5.3) | 6 (4.2) | 3 (3.6) | 61 (3.7) | 19 (4.0) | |
| ≥ 37 WA | 1,619,186 (94.7) | 920 (92.8) | 2638 (93.8) | 446 (95.3) | 1153 (92.5) | 332 (87.8) | 570 (91.8) | 133 (93.0) | 79 (94.0) | 1517 (93.2) | 441 (92.5) | |
| Sex | Male | 873,972 (51.1) | 496 (50.1) | 1471 (52.3) | 243 (51.9) | 597 (47.9) | 206 (54.5) | 292 (47.0) | 65 (45.5) | 43 (51.2) | 847 (52.1) | 254 (53.2) |
| Weight at birth | Mean (standard deviation) | 3,288 (513) | 3,209 (550) | 3,262 (515) | 3,274 (542) | 3,220 (553) | 3,190 (600) | 3,152 (540) | 3,218 (597) | 3,087 (593) | 3,263 (563) | 3,257 (579) |
| < 2500 g | 91,455 (5.3) | 88 (8.9) | 172 (6.1) | 31 (6.6) | 105 (8.4) | 47 (12.4) | 60 (9.7) | 12 (8.4) | 12 (14.3) | 118 (7.3) | 32 (6.7) | |
| 2500–2999 g | 337,541 (19.7) | 227 (22.9) | 606 (21.5) | 103 (22.0) | 278 (22.3) | 73 (19.3) | 152 (24.5) | 30 (21.0) | 20 (23.8) | 324 (19.9) | 90 (18.9) | |
| 3000–3499 g | 704,348 (41.2) | 389 (39.3) | 1,156 (41.1) | 176 (37.6) | 485 (38.9) | 140 (37.0) | 251 (40.4) | 60 (42.0) | 35 (41.7) | 630 (38.7) | 203 (42.6) | |
| ≥ 3500 g | 577,097 (33.7) | 287 (29.0) | 879 (31.2) | 158 (33.8) | 378 (30.3) | 118 (31.2) | 158 (25.4) | 41 (28.7) | 17 (20.2) | 555 (34.1) | 152 (31.9) | |
| Small for gestational age | 167,376 (9.8) | 149 (15.0) | 284 (10.1) | 48 (10.3) | 159 (12.8) | 45 (11.9) | 82 (13.2) | 14 (9.8) | 17 (20.2) | 177 (10.9) | 55 (11.5) | |
| Neonatal condition | 222,201 (13.0) | 119 (12.0) | 349 (12.4) | 59 (12.6) | 197 (15.8) | 53 (14.0) | 85 (13.7) | 17 (11.9) | 9 (10.7) | 231 (14.2) | 74 (15.5) | |
*Not exposed to any antiepileptic drug during pregnancy. ** among those for whom the information was available.