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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S15275 R62800 |
Thomas (Valproate), 2022 | Verbal IQ/Verbal comprehension index (VCI) - 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) | 1.57 [0.45;5.45] | -/33 -/11 | - | 33 |
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S9391 R32883 |
Coste (Valproate) (Controls exposed to Lamotrigine, sick), 2020 | Visits to a speech therapist (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 |
1.50 [1.10;1.90] excluded (control group) |
93/991 122/2,108 | 215 | 991 |
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S9392 R32901 |
Coste (Valproate) (Controls unexposed, NOS), 2020 | Health care utilization: Speech therapy (mean age of 3.6 years old) | during pregnancy (anytime or not specified) | retrospective cohort (claims database) | unexposed (general population or NOS) | Adjustment: Yes | 1.70 [1.40;2.10] | 93/991 72,012/1,710,441 | 72,105 | 991 |
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S9405 R32975 |
Husebye (Valproate) (Controls exposed to Lamotrigine, sick), 2020 | Language impairment age 8 years (Language 20) | during pregnancy (anytime or not specified) | population based cohort propective | exposed to other treatment, sick excluded | Adjustment: No |
1.62 [0.44;5.87] C excluded (control group) |
5/16 9/41 | 14 | 16 |
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S9406 R32977 |
Husebye (Valproate) (Controls unexposed, disease free), 2020 | Language impairment age 8 years (Language 20) | during pregnancy (anytime or not specified) | population based cohort propective | unexposed, disease free excluded | Adjustment: Yes |
2.20 [0.70;6.40] excluded (control group) |
5/16 8,250/42,550 | 8,255 | 16 |
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S9407 R32979 |
Husebye (Valproate) (Controls unexposed, sick), 2020 | Language impairment age 8 years (Language 20) | during pregnancy (anytime or not specified) | population based cohort propective | unexposed, sick | Adjustment: No | 1.49 [0.49;4.59] C | 5/16 35/150 | 40 | 16 |
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S9408 R32981 |
Kasradze (Valproate) (Controls exposed to Lamotrigine, sick), 2017 | Verbal comprehension (VCI) (WPPSI-4) (mean age 4-4.5 years old) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No extrapolated (cont. endpoint) |
0.48 [0.05;4.50] excluded (control group) |
-/18 -/3 | - | 18 |
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S9409 R32984 |
Kasradze (Valproate) (Controls unexposed, disease free), 2017 | Verbal comprehension (VCI) (WPPSI-4) (mean age 4-4.5 years old) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free | Adjustment: No extrapolated (cont. endpoint) Matched | 7.59 [2.69;21.43] | -/18 -/50 | - | 18 |
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S9374 R32781 |
Bromley (Valproate), 2016 | Verbal abilities <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 | 3.45 [1.00;11.84] C | 10/47 4/55 | 14 | 47 |
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S9398 R32934 |
Deshmukh (Valproate), 2016 | Vineland-II Adaptative Behavior Scales - Low and moderately low in the communication domain | throughout pregnancy | prospective cohort | exposed to other treatment, sick | Adjustment: Yes | 4.35 [0.79;25.00] | 9/51 8/104 | 17 | 51 |
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S9942 R35745 |
Videman (Valproate) (Controls exposed to Lamotrigine, sick), 2016 | Griffiths Mental Developmental Scale - Hearing and speech (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) |
4.00 [0.48;33.44] excluded (control group) |
-/5 -/8 | - | 5 |
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S9944 R35757 |
Videman (Valproate) (Controls unexposed, disease free), 2016 | Griffiths Mental Developmental Scale - Hearing and speech (at the age of 7 months) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free | Adjustment: No extrapolated (cont. endpoint) | 41.13 [6.91;244.94] | -/5 -/59 | - | 5 |
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S9371 R32763 |
Baker (Valproate) (Controls exposed to Lamotrigine, sick), 2015 | Mean child verbal 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) |
2.96 [1.27;6.89] excluded (control group) |
-/51 -/29 | - | 51 |
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S9372 R32768 |
Baker (Valproate) (Controls unexposed, disease free), 2015 | Mean child verbal IQ - Differential ability scales (DAS) (age mean >6 years old) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free excluded | Adjustment: No extrapolated (cont. endpoint) |
5.60 [3.16;9.96] excluded (control group) |
-/51 -/210 | - | 51 |
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S9373 R32774 |
Baker (Valproate) (Controls unexposed, sick), 2015 | Mean child verbal 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) | 3.06 [1.26;7.44] | -/51 -/25 | - | 51 |
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S9414 R33010 |
Meador (Valproate), 2013 | Verbal index score (at age 6 years old) (Created by averaging standard scores) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick | Adjustment: Yes extrapolated (cont. endpoint) | 3.77 [1.92;7.41] | -/49 -/74 | - | 49 |
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S9450 R33196 |
Rihtman (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2013 | Stanford Binet Intelligence Scales, Fifth Edition (SB5) - Verbal IQ (VIQ) (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) |
1.21 [0.51;2.87] excluded (control group) |
-/29 -/41 | - | 29 |
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S9451 R33231 |
Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 | Stanford Binet Intelligence Scales, Fifth Edition (SB5) - Verbal IQ (VIQ) (mean age 4-5 years old) | at least 1st trimester | prospective cohort | unexposed (general population or NOS) | Adjustment: No extrapolated (cont. endpoint) | 1.81 [0.79;4.15] | -/29 -/52 | - | 29 |
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S9415 R33022 |
Nadebaum (Valproate), 2011 | Total language delay (CELF-4) (core language ≤ 85) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick | Adjustment: No | 8.23 [0.42;162.35] C | 7/23 0/9 | 7 | 23 |
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S9418 R33046 |
Shallcross (Valproate), 2011 | Hearing and language (Griffiths scale) | throughout pregnancy | prospective cohort | unexposed, disease free | Adjustment: No extrapolated (cont. endpoint) | 3.01 [1.56;5.82] | -/44 -/97 | - | 44 |
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S9400 R32940 |
Eriksson (Valproate), 2005 | Mean Verbal IQ (VIQ) (Wechsler Intelligence Scale for Children (WISC III)) | throughout pregnancy | prospective cohort | unexposed, sick | Adjustment: No extrapolated (cont. endpoint) Matched | 2.94 [0.70;12.28] | -/13 -/13 | - | 13 |
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S9278 R32184 |
Adab (Valproate), 2004 | Verbal IQ (VIQ) less than low average (≤ 89) (Wechsler Intelligence Scale for Children (WISC)) | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, sick | Adjustment: No | 2.03 [0.93;4.42] C | 27/41 39/80 | 66 | 41 |
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S9401 R32942 |
Gaily (Valproate) (Controls unexposed, disease free), 2004 | Verbal IQ score (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) |
4.31 [1.46;12.73] excluded (control group) |
-/12 -/139 | - | 12 |
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S9402 R32946 |
Gaily (Valproate) (Controls unexposed, sick), 2004 | Verbal IQ score (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) | 3.22 [0.99;10.49] | -/12 -/44 | - | 12 |
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Total | 15 studies | 2.87 [2.05;4.02] | 72,249 | 1,423 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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; 2: Valproate) (Controls unexposed, NOS; 3: Valproate) (Controls unexposed, sick; 4: Valproate) (Controls unexposed, disease free; 5: Valproate; 6: Valproate; 7: Valproate) (Controls unexposed, disease free; 8: Valproate) (Controls unexposed, sick; 9: Valproate; 10: Valproate) (Controls unexposed, NOS) (Mixed indications; 11: Valproate; 12: Valproate; 13: Valproate; 14: Valproate; 15: Valproate) (Controls unexposed, sick;
Asymetry test p-value = 0.0047 (by Egger's regression)
slope=0.3935 (0.1364); intercept=1.4505 (0.4267); t=3.3996; p=0.0047
excluded 9401, 9450, 9371, 9372, 9942, 9408, 9391, 9405, 9406