| 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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| S19391 R82375 |
Honybun (Controls exposed to LTG) (Valproate) (Epilepsy), 2026 | Processing Speed Index (Assesses psychomotor speed across time-based tasks) - Wechsler Intelligence Scale - Children aged 3–18 years (mean age about 10 years) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No extrapolated (cont. endpoint) |
6.48 [1.99;21.06] excluded (control group) |
-/19 -/23 | - | 19 |
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| S19387 R82335 |
Honybun (Controls unexposed, sick) (Valproate) (Epilepsy), 2026 | Processing Speed Index (Assesses psychomotor speed across time-based tasks) - Wechsler Intelligence Scale - Children aged 3–18 years (mean age about 10 years) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No extrapolated (cont. endpoint) | 10.58 [2.93;38.12] | -/19 -/19 | - | 19 |
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| S19382 R82293 |
Straub (Controls exposed to LTG) (Valproate) (Epilepsy), 2026 | Coordination disorders - ICD-10 codes: F82 - Mean follow up (full cohort): 3.4 years | during pregnancy (anytime or not specified) | retrospective cohort (claims database) | exposed to other treatment, sick excluded | Adjustment: No |
1.79 [0.93;3.46] C excluded (control group) |
13/796 30/3,273 | 43 | 796 |
|
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| S19374 R82205 |
Straub (Controls unexposed, sick) (Valproate) (Epilepsy), 2026 | Coordination disorders - ICD-10 codes: F82 - Mean follow up (full cohort): 3.4 years | during pregnancy (anytime or not specified) | retrospective cohort (claims database) | unexposed, sick | Adjustment: Yes | 1.68 [0.89;3.16] | 13/796 91/8,887 | 104 | 796 |
|
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| S19336 R82027 |
Moore (Controls exposed to LTG) (Valproate) (Indication NOS), 2025 | Gross motor disorders - Assessment offered to all children - At the 27–30 months | during pregnancy (anytime or not specified) | population based cohort retrospective | exposed to other treatment, sick excluded | Adjustment: No |
1.75 [0.91;3.37] C excluded (control group) |
13/198 36/934 | 49 | 198 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S19329 R82049 |
Moore (Controls unexposed, general pop) (Valproate) (Indication NOS), 2025 | Fine motor disorders - Assessment offered to all children - At the 27–30 months | during pregnancy (anytime or not specified) | population based cohort retrospective | unexposed (general population or NOS) | Adjustment: No Matched | 3.43 [1.84;6.38] C | 14/198 43/1,979 | 57 | 198 |
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| S16621 R69705 |
Thomas b (Valproate) (Epilepsy) (Controls exposed to LTG), 2022 | Delayed motor development quotient (< 84, i.e one SD of the mean) - The developmental assessment scale for Indian infants (DASII) - Between 12-24 months of age (mean (SD): 15.3 (3.9) months)) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
12.15 [1.61;91.52] C excluded (control group) |
69/211 1/26 | 70 | 211 |
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| S16622 R69706 |
Thomas b (Valproate) (Epilepsy) (Controls unexposed, sick), 2022 | The motor development quotient (MODQ) - The developmental assessment scale for Indian infants (DASII) - Between 12-24 months of age (mean (SD): 15.3 (3.9) months)) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No extrapolated (cont. endpoint) | 2.04 [1.34;3.12] | -/211 -/110 | - | 211 |
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| S9398 R32935 |
Deshmukh (Valproate), 2016 | Vineland-II Adaptative Behavior Scales - Low and moderately low in the motor skills domain | throughout pregnancy | prospective cohort | exposed to other treatment, sick | Adjustment: Yes | 11.11 [2.04;50.00] | 16/51 8/104 | 24 | 51 |
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| S9942 R35743 |
Videman (Valproate) (Controls exposed to Lamotrigine, sick), 2016 | Griffiths Mental Developmental Scale - Locomotor (at the age of 7 months) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No extrapolated (cont. endpoint) |
3.94 [0.47;32.94] excluded (control group) |
-/5 -/8 | - | 5 |
|
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| S9944 R35755 |
Videman (Valproate) (Controls unexposed, disease free), 2016 | Griffiths Mental Developmental Scale - Locomotor (at the age of 7 months) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free | Adjustment: No extrapolated (cont. endpoint) | 6.88 [1.27;37.31] | -/5 -/59 | - | 5 |
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| S9377 R32812 |
Bromley (Valproate) (Controls exposed to Lamotrigine, sick), 2013 | Dyspraxia (at 6 years old) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
1.21 [0.10;13.92] C excluded (control group) |
2/50 1/30 | 3 | 50 |
|
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| S9380 R32828 |
Bromley (Valproate) (Controls unexposed, disease free), 2013 | Dyspraxia (at 6 years old) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free excluded | Adjustment: No |
22.47 [1.06;475.80] C excluded (control group) |
2/50 0/214 | 2 | 50 |
|
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| S9383 R32844 |
Bromley (Valproate) (Controls unexposed, sick), 2013 | Dyspraxia (at 6 years old) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No | 2.68 [0.12;58.07] C | 2/50 0/26 | 2 | 50 |
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| S9450 R33203 |
Rihtman (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2013 | Miller Function and Participation Scales (MFUN) - Fine Motor (mean age 4-5 years old) | at least 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No Controls: epilepsy indication extrapolated (cont. endpoint) |
1.66 [0.71;3.90] excluded (control group) |
-/30 -/42 | - | 30 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9451 R33238 |
Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 | Miller Function and Participation Scales (MFUN) - Fine Motor (mean age 4-5 years old) | at least 1st trimester | prospective cohort | unexposed (general population or NOS) | Adjustment: No extrapolated (cont. endpoint) | 5.14 [2.19;12.07] | -/30 -/52 | - | 30 |
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| S9389 R32854 |
Cohen (Valproate), 2011 | Motor Index score (the Bayley Scales of Infant Development (BSID-II)) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick | Adjustment: Yes extrapolated (cont. endpoint) | 1.67 [0.80;3.48] | -/38 -/62 | - | 38 |
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| S9418 R33044 |
Shallcross (Valproate), 2011 | Locomotor (Griffiths scale) | throughout pregnancy | prospective cohort | unexposed, disease free | Adjustment: No extrapolated (cont. endpoint) | 3.08 [1.59;5.96] | -/44 -/97 | - | 44 |
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| S9428 R33104 |
Viinikainen (Valproate) b, 2006 | Touwen's test Neurological dysfunction/impairment | throughout pregnancy | prospective cohort | unexposed, sick | Adjustment: No Matched | 3.44 [0.53;22.43] C | 5/13 2/13 | 7 | 13 |
|
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| S9278 R32187 |
Adab (Valproate), 2004 | Dyspraxia | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, sick | Adjustment: No | 1.07 [0.17;6.59] C | 2/63 3/101 | 5 | 63 |
|
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| S9410 R32988 |
Koch (Valproate), 1996 | Minor neurological dysfunction (at age 6) (Touwen) | during pregnancy (anytime or not specified) | prospective cohort | unexposed (general population or NOS) | Adjustment: No Matched | 7.50 [1.32;42.51] C | 4/8 4/34 | 8 | 8 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Total | 13 studies | 3.03 [2.16;4.24] | 207 | 1,526 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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: Controls unexposed, sick) (Valproate) (Epilepsy; 2: Controls unexposed, sick) (Valproate) (Epilepsy; 3: Controls unexposed, general pop) (Valproate) (Indication NOS; 4: Valproate) (Epilepsy) (Controls unexposed, sick; 5: Valproate; 6: Valproate) (Controls unexposed, disease free; 7: Valproate) (Controls unexposed, sick; 8: Valproate) (Controls unexposed, NOS) (Mixed indications; 9: Valproate; 10: Valproate; 11: Valproate) ; 12: Valproate; 13: Valproate;
Asymetry test p-value = 0.0786 (by Egger's regression)
slope=0.5206 (0.2789); intercept=1.2664 (0.6532); t=1.9386; p=0.0786
excluded 9377, 9380, 9450, 9942, 16621, 19336, 19391, 19382