| 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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| S17423 R73170 |
Madley-Dowd_SE (Valproate) (Controls exposed to LTG) (Mixed indications), 2024 | Intellectual disability (intelligence quotient below 70) - 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 |
2.41 [1.69;3.44] excluded (control group) |
64/1,178 60/5,035 | 124 | 1,178 |
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| S17424 R73176 |
Madley-Dowd_SE (Valproate) (Controls unexposed, general pop) (Mixed indications), 2024 | Intellectual disability (intelligence quotient below 70) - 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: No Partial overlapping | 2.64 [2.02;3.44] | 64/1,178 24,323/2,651,210 | 24,387 | 1,178 |
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| S17425 R73182 |
Madley-Dowd_SE (Valproate) (Controls unexposed, sibling) (Mixed indications), 2024 | Intellectual disability (intelligence quotient below 70) - 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 |
2.23 [1.01;4.92] excluded (control group) |
-/- -/- | - | - |
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| S17286 R72355 |
Madley-Dowd_UK (Valproate) (Controls exposed to LTG) (Mixed indications), 2024 | Intellectual disability - 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 |
0.66 [0.12;3.51] excluded (control group) |
-/423 -/939 | - | 423 |
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| S17271 R72356 |
Madley-Dowd_UK (Valproate) (Controls unexposed, general pop) (Mixed indications), 2024 | Intellectual disability - 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 | 1.04 [0.25;4.34] | -/423 1,119/514,066 | - | 423 |
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| S17279 R72357 |
Madley-Dowd_UK (Valproate) (Controls unexposed, sibling) (Mixed indications), 2024 | Intellectual disability - 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 |
0.30 [0.06;1.59] excluded (control group) |
-/- -/- | - | - |
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| S16560 R69576 |
Stjerna (Valproate) (Epilepsy), 2024 | Full scale intelligence quotient (FSIQ continuous) - The Wechsler Intelligence Scale for Children (WISC-III) - At 6-7 years old | throughout pregnancy | retrospective cohort | exposed to other treatment, sick | Adjustment: Yes extrapolated (cont. endpoint) | 1.74 [0.76;3.97] | -/25 -/74 | - | 25 |
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| S12708 R53673 |
Bjørk (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2022 | Diagnosis of intellectual disability (ID): mild ID (F70), moderate ID (F71), severe ID (F72), and profound ID (F73) - 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 |
7.97 [5.07;12.52] C excluded (control group) |
64/2,421 27/7,950 | 91 | 2,421 |
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| S12519 R53674 |
Bjørk (Valproate) (Controls unexposed NOS) (Mixed indications), 2022 | Diagnosis of intellectual disability (ID): mild ID (F70), moderate ID (F71), severe ID (F72), and profound ID (F73) - 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 |
4.77 [3.73;6.10] excluded (control group) |
64/2,421 16,384/4,463,879 | 16,448 | 2,421 |
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| S12707 R53675 |
Bjørk (Valproate) (Controls unexposed, sick) (Mixed indications), 2022 | Diagnosis of intellectual disability (ID): mild ID (F70), moderate ID (F71), severe ID (F72), and profound ID (F73) - 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 | 4.20 [3.11;5.66] C | 64/2,421 139/21,634 | 203 | 2,421 |
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| S15275 R62802 |
Thomas a (Valproate), 2022 | Full-scale IQ - Wechsler Intelligence Scale for Children or Adult - Ages 13 to 21 years (mean of 16.5 ± 2.2 years) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No extrapolated (cont. endpoint) | 1.31 [0.38;4.52] | -/33 -/11 | - | 33 |
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| S9374 R53666 |
Bromley (Valproate), 2016 | Full-scale IQ <85 (Wechsler Preschool and Primary Scale of Intelligence (WPPSI) / Wechsler Intelligence Scale for Children (WISC)) (5-9 years old) | during pregnancy (anytime or not specified) | retrospective cohort (registry) | unexposed, sick | Adjustment: No | 4.11 [1.04;16.19] C | 9/47 3/55 | 12 | 47 |
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| S9371 R53663 |
Baker (Valproate) (Controls exposed to Lamotrigine, sick), 2015 | Mean child Full scale IQ - Differential ability scales (DAS) (age mean >6 years old) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No extrapolated (cont. endpoint) |
3.48 [1.49;8.14] excluded (control group) |
-/51 -/29 | - | 51 |
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| S9372 R53664 |
Baker (Valproate) (Controls unexposed, disease free), 2015 | IQ <85 - Differential ability scales (DAS) (age mean >6 years old) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free excluded | Adjustment: Yes |
6.83 [3.02;15.45] excluded (control group) |
-/51 -/210 | - | 51 |
|
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| S9373 R53665 |
Baker (Valproate) (Controls unexposed, sick), 2015 | Mean child Full scale IQ - Differential ability scales (DAS) (age mean >6 years old) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No extrapolated (cont. endpoint) | 3.76 [1.54;9.19] | -/51 -/25 | - | 51 |
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| S9414 R53670 |
Meador (Valproate), 2013 | IQ <85 (DAS) (at 6 years old) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick | Adjustment: Yes | 7.02 [1.42;34.66] C | 8/49 2/74 | 10 | 49 |
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| S9415 R53671 |
Nadebaum (Valproate), 2011 | Full-scale child's IQ (WISC) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick | Adjustment: No extrapolated (cont. endpoint) | 5.19 [1.20;22.40] | -/23 -/9 | - | 23 |
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| S9421 R53678 |
Titze (Valproate) (Controls unexposed, disease free), 2008 | Learning disability (IQ<70) (German versions of the revised Wechsler Intelligence Scales for children and for adults) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free excluded | Adjustment: No Matched |
19.40 [0.31;1195.39] C excluded (control group) |
0/3 0/49 | 0 | 3 |
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| S9422 R53679 |
Titze (Valproate) (Controls unexposed, sick), 2008 | Learning disability (IQ<70) (German versions of the revised Wechsler Intelligence Scales for children and for adults) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No | 1.53 [0.05;49.80] C | 0/3 1/13 | 1 | 3 |
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| S9428 R53672 |
Viinikainen (Valproate) b, 2006 | Full Scale IQ (FIQ) < 1SD (Wechsler Intelligence Scale for Children (WISC III)) | throughout pregnancy | prospective cohort | unexposed, sick | Adjustment: No Matched | 18.33 [0.88;380.72] C | 5/13 0/13 | 5 | 13 |
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| S9429 R53680 |
Vinten (Valproate), 2005 | IQ score <69 (Wechsler Intelligence Scale for Children (WISC III)) (Aged between 6 and 16 years) | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, sick | Adjustment: No | 3.47 [1.14;10.56] C | 9/41 6/80 | 15 | 41 |
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| S9278 R53662 |
Adab (Valproate), 2004 | Mean Full Scale IQ (Wechsler Intelligence Scale for Children (WISC)) (Aged between 6 and 16 years) | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, sick | Adjustment: No extrapolated (cont. endpoint) | 1.26 [0.64;2.50] | -/41 -/80 | - | 41 |
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| S9401 R53667 |
Gaily (Valproate) (Controls unexposed, disease free), 2004 | Full scale IQ (Wechsler Preschool and Primary Scale of Intelligence Revised (WPPSI-R) or Wechsler Intelligence Scale for Children Revised (WISC-R)) | 2nd and/or 3rd trimester | prospective cohort | unexposed, disease free excluded | Adjustment: No extrapolated (cont. endpoint) |
2.40 [0.85;6.75] excluded (control group) |
-/13 -/140 | - | 13 |
|
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| S9402 R53668 |
Gaily (Valproate) (Controls unexposed, sick), 2004 | Full scale IQ (Wechsler Preschool and Primary Scale of Intelligence Revised (WPPSI-R) or Wechsler Intelligence Scale for Children Revised (WISC-R)) | 2nd and/or 3rd trimester | prospective cohort | unexposed, sick | Adjustment: No extrapolated (cont. endpoint) | 1.82 [0.59;5.59] | -/13 -/45 | - | 13 |
|
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| Total | 14 studies | 2.69 [1.99;3.62] | 24,633 | 4,361 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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) (Controls unexposed, general pop) (Mixed indications; 2: Valproate) (Controls unexposed, general pop) (Mixed indications; 3: Valproate) (Epilepsy; 4: Valproate) (Controls unexposed, sick) (Mixed indications; 5: Valproate; 6: Valproate; 7: Valproate) (Controls unexposed, sick; 8: Valproate; 9: Valproate; 10: Valproate) (Controls unexposed, sick; 11: Valproate) ; 12: Valproate; 13: Valproate; 14: Valproate) (Controls unexposed, sick;
Asymetry test p-value = 0.6352 (by Egger's regression)
slope=1.1408 (0.1807); intercept=-0.2705 (0.5558); t=0.4867; p=0.6352
excluded 9401, 9421, 9371, 9372, 12708, 12519, 17423, 17425, 17286, 17279