| id | Study | Lib. in paper | Exposition period | Study type |
Control type |
Tags | OR 95%CI | x1/n1 x0/n0 | no cases | no exposed | ROB | Ref. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| S18035 R75981 |
Hao (Lamotrigine) (Epilepsy), 2025 | Major congenital malformation (MCM) | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 0.81 [0.26;2.52] | 3/84 10/261 | 13 | 84 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S18701 R79551 |
Mazzone (Lamotrigine) (Mixed indications), 2025 | Congenital conditions (ICD-10 codes Q00-Q99) | during pregnancy (anytime or not specified) excluded | population based cohort retrospective | unexposed (general population or NOS) | Adjustment: Yes |
0.76 [0.48;1.20] excluded (exposition period) |
38/1,469 14,967/624,794 | 15,005 | 1,469 |
|
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| S18754 R79765 |
Moore (Lamotrigine) (Mixed indications), 2025 | Congenital conditions (any major structural congenital condition with no known associated/underlying genetic condition, as defined by EUROCAT) | during pregnancy (anytime or not specified) excluded | population based cohort retrospective | unexposed (general population or NOS) | Adjustment: Yes Matched |
1.05 [0.73;1.51] excluded (exposition period) |
39/1,470 294/14,414 | 333 | 1,470 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S16174 R67108 |
The NAAED (Indications NOS), 2025 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, disease free | Adjustment: No | 1.82 [1.02;3.25] C | 52/2,587 15/1,346 | 67 | 2,587 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S18065 R76052 |
Vajda (Epilepsy), 2025 | Fetal malformations | at least 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 1.37 [0.60;3.16] | 22/490 7/214 | 29 | 490 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17498 R73567 |
Wiggs (Epilepsy) (Lamotrigine), 2024 | Major birth defects | early pregnancy | population based cohort retrospective | unexposed, sick | Adjustment: Yes | 0.95 [0.67;1.33] | -/1,412 -/9,364 | - | 1,412 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S15218 R62396 |
Bromley (Lamotrigine) (Epilepsy), 2023 | Any congenital anomaly | during pregnancy (anytime or not specified) excluded | prospective cohort | unexposed, sick | Adjustment: No |
2.20 [0.67;7.18] C excluded (exposition period) |
11/106 4/80 | 15 | 106 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S15197 R62376 |
Cohen (Lamotrigine) (Mixed indications), 2023 | Major congenital malformations (excluding genetic/chromosomal) | 1st trimester | population based cohort retrospective | unexposed (general population or NOS) | Adjustment: Yes Partial overlapping | 0.97 [0.87;1.08] | 314/8,339 147,928/4,866,362 | 148,242 | 8,339 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S15263 R62763 |
Li (Lamotrigine) (Epilepsy), 2023 | Major congenital malformation | during pregnancy (anytime or not specified) excluded | prospective cohort | unexposed, sick | Adjustment: No |
0.44 [0.02;7.80] C excluded (exposition period) |
0/38 7/253 | 7 | 38 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S15213 R62387 |
Pekoz (Lamotrigine) (Epilepsy), 2023 | Congenital malformations (major and minor) | during pregnancy (anytime or not specified) excluded | prospective cohort | unexposed, sick | Adjustment: No |
0.91 [0.09;9.01] C excluded (exposition period) |
3/141 1/43 | 4 | 141 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12678 R48016 |
Alsfouk (Lamotrigine), 2021 | Major congenital malformation | during pregnancy (anytime or not specified) excluded | retrospective cohort | unexposed, sick | Adjustment: No |
4.46 [0.37;53.71] C excluded (exposition period) |
2/15 1/30 | 3 | 15 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12677 R47911 |
Hosny, 2021 | Major birth defects | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 2.60 [0.08;82.80] C | 0/3 1/21 | 1 | 3 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8923 R30162 |
Thomas (Lamotrigine) (Controls unexposed, disease free), 2021 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, disease free excluded | Adjustment: No |
0.76 [0.10;5.75] excluded (control group) |
1/38 11/319 | 12 | 38 |
|
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| S8924 R48247 |
Thomas (Lamotrigine) (Controls unexposed, sick), 2021 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, sick | Adjustment: Yes | 0.50 [0.10;3.70] | 1/50 16/340 | 17 | 50 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S16152 R67029 |
Alsaadi (Lamotrigine) (Epilepsy) (Controls unexposed sick), 2020 | All congenital malformations (majors and minors) | 1st trimester | retrospective cohort | unexposed, sick | Adjustment: No | 3.18 [0.18;55.20] C | 1/12 1/36 | 2 | 12 |
|
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| S8901 R30054 |
AlSheikh (Lamotrigine), 2020 | Fetal/neonatal malformation | during pregnancy (anytime or not specified) excluded | prospective cohort | unexposed, sick | Adjustment: No |
0.11 [0.00;3.08] C excluded (exposition period) |
0/20 1/8 | 1 | 20 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8904 R30086 |
Aydin (Lamotrigine), 2020 | Congenital chromosomal/structural anomalies | throughout pregnancy | retrospective cohort | unexposed, sick | Adjustment: No | 3.31 [0.06;183.69] C | 0/7 0/22 | 0 | 7 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8911 R30116 |
Meador (Lamotrigine) (Controls unexposed, disease free), 2020 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, disease free excluded | Adjustment: No |
2.48 [0.47;13.05] C excluded (control group) |
5/110 2/106 | 7 | 110 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8912 R30120 |
Meador (Lamotrigine) (Controls unexposed, sick), 2020 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 0.67 [0.07;6.13] C | 5/110 1/15 | 6 | 110 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12464 R46886 |
Kernizan, 2019 | Malformation | during pregnancy (anytime or not specified) excluded | retrospective cohort | unexposed, sick | Adjustment: No |
0.75 [0.09;6.21] C excluded (exposition period) |
1/13 14/140 | 15 | 13 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S10208 R37659 |
Petersen (Lamotrigine) (Controls unexposed NOS), 2017 | Major congenital malformation | 1st trimester | retrospective cohort (claims database) | unexposed (general population or NOS) excluded | Adjustment: Yes |
0.95 [0.51;1.79] excluded (control group) |
10/357 5,315/239,151 | 5,325 | 357 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S10209 R37660 |
Petersen (Lamotrigine) (Controls unexposed, sick), 2017 | Major congenital malformation | 1st trimester | retrospective cohort (claims database) | unexposed, sick | Adjustment: Yes | 0.88 [0.44;1.75] | 9/344 86/2,844 | 95 | 344 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8926 R30167 |
Vanya (Lamotrigine) (Controls unexposed, sick), 2015 | Major congenital malformations | throughout pregnancy | retrospective cohort | unexposed, sick | Adjustment: No | 3.55 [0.06;199.99] C | 0/6 0/20 | 0 | 6 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8917 R30139 |
Campbell (Lamotrigine), 2014 | Major malformations | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 0.97 [0.52;1.80] C | 49/2,098 13/541 | 62 | 2,098 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8964 R30361 |
Veiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014 | Major malformations | throughout pregnancy | population based cohort retrospective | unexposed, disease free excluded | Adjustment: Yes Partial overlapping |
1.26 [0.87;1.84] excluded (control group) |
28/833 22,371/771,412 | 22,399 | 833 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8965 R30364 |
Veiby (Lamotrigine) (Controls unexposed, sick) (Mixed indications), 2014 | Major malformations | throughout pregnancy | population based cohort retrospective | unexposed, sick | Adjustment: No Controls: epilepsy indication Partial overlapping | 1.20 [0.79;1.84] C | 28/833 106/3,773 | 134 | 833 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8966 R30366 |
Cassina (Lamotrigine) (Mixed indications), 2013 | Major congenital anomalies | 1st trimester | prospective cohort | unexposed, disease free | Adjustment: No | 0.34 [0.02;5.59] C | 0/46 25/803 | 25 | 46 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8952 R30268 |
Rihtman (Lamotrigine), 2013 | Children: born with congenital deformation | at least 1st trimester | prospective cohort | unexposed (general population or NOS) | Adjustment: No | 6.52 [0.30;139.67] C | 2/42 0/52 | 2 | 42 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8905 R30091 |
Charlton (Lamotrigine), 2011 | Major congenital malformations | 1st trimester | retrospective cohort (claims database) | unexposed, sick | Adjustment: No | 1.26 [0.38;4.17] | 3/98 22/902 | 25 | 98 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8909 R30110 |
Mawer (Lamotrigine) (Controls unexposed, disease free), 2010 | Major malformations | 1st trimester | prospective cohort | unexposed, disease free excluded | Adjustment: No Matched |
2.66 [0.52;13.68] excluded (control group) |
2/37 6/285 | 8 | 37 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8910 R30112 |
Mawer (Lamotrigine) (Controls unexposed, sick), 2010 | Major malformations | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 2.29 [0.20;26.30] C | 2/37 1/41 | 3 | 37 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S8919 R30145 |
Dean (Lamotrigine), 2007 | Major malformation | during pregnancy (anytime or not specified) excluded | retrospective cohort | unexposed, sick | Adjustment: No |
1.73 [0.07;40.78] C excluded (exposition period) |
0/4 3/46 | 3 | 4 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Total | 18 studies | 1.00 [0.91;1.10] | 148,723 | 16,598 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| x1: number of endpoints among exposed, n1: number of exposed; x0: number of endpoints among non exposed, n0: number of non exposed; C: calculated odds ratio from numbers of events and effectives | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1: Lamotrigine) (Epilepsy; 2: Indications NOS; 3: Epilepsy; 4: Epilepsy) (Lamotrigine; 5: Lamotrigine) (Mixed indications; 6: Lamotrigine) (Controls unexposed, sick; 7: Lamotrigine) (Epilepsy) (Controls unexposed sick; 8: Lamotrigine; 9: Lamotrigine) (Controls unexposed, sick; 10: Lamotrigine) (Controls unexposed, sick; 11: Lamotrigine) (Controls unexposed, sick; 12: Lamotrigine; 13: Lamotrigine) (Controls unexposed, sick) (Mixed indications; 14: Lamotrigine) (Mixed indications; 15: Lamotrigine; 16: Lamotrigine; 17: Lamotrigine) (Controls unexposed, sick;
Asymetry test p-value = 0.0877 (by Egger's regression)
slope=-0.0443 (0.0443); intercept=0.3935 (0.2164); t=1.8186; p=0.0877
excluded 8909, 8964, 10208, 8911, 8923