| 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S16197 R67127 |
Hernandez-Diaz (Valproate) (Epilepsy) (Controls exposed to LTG), 2024 | Autism spectrum disorder (ASD) - At least two visits with codes for ASD - Median follow-up was 2 years | 2nd and/or 3rd trimester | retrospective cohort (claims database) | exposed to other treatment, sick excluded | Adjustment: No |
1.59 [0.95;2.68] C excluded (control group) |
24/561 38/1,392 | 62 | 561 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S16196 R67126 |
Hernandez-Diaz (Valproate) (Epilepsy) (Controls unexposed, sick), 2024 | Autism spectrum disorder (ASD) - At least two visits with codes for ASD - Median follow-up was 2 years | 2nd and/or 3rd trimester | retrospective cohort (claims database) | unexposed, sick | Adjustment: Yes | 2.96 [1.79;4.89] | 24/561 102/8,815 | 126 | 561 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17423 R73167 |
Madley-Dowd_SE (Valproate) (Controls exposed to LTG) (Mixed indications), 2024 | Autism - ICD-8/9/10 codes - Mean 5-20 years old (according groups) | during pregnancy (anytime or not specified) | population based cohort retrospective | exposed to other treatment, sick excluded | Adjustment: Yes Partial overlapping |
2.19 [1.70;2.82] excluded (control group) |
111/1,178 134/5,035 | 245 | 1,178 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17424 R73173 |
Madley-Dowd_SE (Valproate) (Controls unexposed, general pop) (Mixed indications), 2024 | Autism - ICD-8/9/10 codes - Mean 5-20 years old (according groups) | during pregnancy (anytime or not specified) | population based cohort retrospective | unexposed (general population or NOS) | Adjustment: Yes Partial overlapping | 1.82 [1.49;2.21] | 111/1,178 68,788/2,651,210 | 68,899 | 1,178 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17425 R73179 |
Madley-Dowd_SE (Valproate) (Controls unexposed, sibling) (Mixed indications), 2024 | Autism - ICD-8/9/10 codes - Mean 5-20 years old (according groups) | during pregnancy (anytime or not specified) | population based cohort retrospective | sibling excluded | Adjustment: Yes Partial overlapping |
1.13 [0.65;1.99] excluded (control group) |
-/- -/- | - | - |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17286 R72340 |
Madley-Dowd_UK (Valproate) (Controls exposed to LTG) (Mixed indications), 2024 | Autism - ICD10 codes - Median follow up 9.32 (5.54-12.83) years old | during pregnancy (anytime or not specified) | retrospective cohort (claims database) | exposed to other treatment, sick excluded | Adjustment: Yes |
1.38 [0.69;2.74] excluded (control group) |
14/423 20/939 | 34 | 423 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17271 R72297 |
Madley-Dowd_UK (Valproate) (Controls unexposed, general pop) (Mixed indications), 2024 | Autism - ICD10 codes - Median follow up 9.32 (5.54-12.83) years old | during pregnancy (anytime or not specified) | retrospective cohort (claims database) | unexposed (general population or NOS) | Adjustment: Yes | 1.51 [0.87;2.63] | 14/423 7,657/514,066 | 7,671 | 423 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17279 R72322 |
Madley-Dowd_UK (Valproate) (Controls unexposed, sibling) (Mixed indications), 2024 | Autism - ICD10 codes - Median follow up 9.32 (5.54-12.83) years old | during pregnancy (anytime or not specified) | retrospective cohort (claims database) | sibling excluded | Adjustment: Yes |
0.81 [0.28;2.31] excluded (control group) |
-/- -/- | - | - |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12708 R47947 |
Bjørk (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2022 | Diagnosis of childhood autism (F84.0), atypical autism (F84.1), and Asperger syndrome (F84.5) - Median follow up valproate 9.9 (6.0-14.3) years old | during pregnancy (anytime or not specified) | population based cohort retrospective | exposed to other treatment, sick excluded | Adjustment: No |
3.36 [2.47;4.58] C excluded (control group) |
82/2,421 82/7,950 | 164 | 2,421 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12519 R47160 |
Bjørk (Valproate) (Controls unexposed NOS) (Mixed indications), 2022 | Diagnosis of childhood autism (F84.0), atypical autism (F84.1), and Asperger syndrome (F84.5) - Median follow up valproate 9.9 (6.0-14.3) years old | during pregnancy (anytime or not specified) | population based cohort retrospective | unexposed (general population or NOS) excluded | Adjustment: Yes |
3.44 [2.77;4.28] excluded (control group) |
82/2,421 38,437/4,463,879 | 38,519 | 2,421 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S12707 R47944 |
Bjørk (Valproate) (Controls unexposed, sick) (Mixed indications), 2022 | Diagnosis of childhood autism (F84.0), atypical autism (F84.1), and Asperger syndrome (F84.5) - Median follow up valproate 9.9 (6.0-14.3) years old | during pregnancy (anytime or not specified) | population based cohort retrospective | unexposed, sick | Adjustment: No Controls: epilepsy indication | 2.81 [2.18;3.61] C | 82/2,421 267/21,634 | 349 | 2,421 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9391 R32879 |
Coste (Valproate) (Controls exposed to Lamotrigine, sick), 2020 | Diagnosis Pervasive developmental disorders (F84) (mean age of 3.7 years old) | during pregnancy (anytime or not specified) | retrospective cohort (claims database) | exposed to other treatment, sick excluded | Adjustment: Yes |
4.70 [1.90;11.40] excluded (control group) |
17/991 7/2,108 | 24 | 991 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9392 R32897 |
Coste (Valproate) (Controls unexposed, NOS), 2020 | Diagnosis Pervasive developmental disorders (F84) (mean age of 3.6 years old) | during pregnancy (anytime or not specified) | retrospective cohort (claims database) | unexposed (general population or NOS) | Adjustment: Yes | 4.60 [2.90;7.50] | 17/991 4,280/1,710,441 | 4,297 | 991 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9404 R32952 |
Huber-Mollema (Valproate), 2019 | Diagnosis of autism spectrum disorder | throughout pregnancy | prospective cohort | exposed to other treatment, sick | Adjustment: No | 2.74 [0.57;13.12] C | 3/26 4/88 | 7 | 26 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9431 R33120 |
Wood (Valproate), 2015 | Score >30 (CARS) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick | Adjustment: No | 1.04 [0.04;28.06] C | 1/26 0/9 | 1 | 26 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9377 R35213 |
Bromley (Valproate) (Controls exposed to Lamotrigine, sick), 2013 | Autistic Spectrum Disorders (at 6 years old) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
2.52 [0.27;23.69] C excluded (control group) |
4/50 1/30 | 5 | 50 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9380 R35214 |
Bromley (Valproate) (Controls unexposed, disease free), 2013 | Autistic Spectrum Disorders (at 6 years old) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free excluded | Adjustment: No |
4.57 [1.10;18.93] C excluded (control group) |
4/50 4/214 | 8 | 50 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9383 R35215 |
Bromley (Valproate) (Controls unexposed, sick), 2013 | Autistic Spectrum Disorders (at 6 years old) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No | 5.04 [0.26;97.51] C | 4/50 0/26 | 4 | 50 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9278 R32185 |
Adab (Valproate), 2004 | Asperger’s syndrome | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, sick | Adjustment: No | 4.90 [0.20;122.25] C | 1/63 0/101 | 1 | 63 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Total | 9 studies | 2.53 [1.87;3.42] | 81,355 | 5,739 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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: Valproate) (Epilepsy) (Controls unexposed, sick; 2: Valproate) (Controls unexposed, general pop) (Mixed indications; 3: Valproate) (Controls unexposed, general pop) (Mixed indications; 4: Valproate) (Controls unexposed, sick) (Mixed indications; 5: Valproate) (Controls unexposed, NOS; 6: Valproate; 7: Valproate; 8: Valproate) (Controls unexposed, sick; 9: Valproate;
Asymetry test p-value = 0.4965 (by Egger's regression)
slope=0.7403 (0.1713); intercept=0.5897 (0.8223); t=0.7171; p=0.4965
excluded 9377, 9380, 9391, 12708, 12519, 16197, 17423, 17425, 17286, 17279