| 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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| S16067 R66678 |
Christensen (Valproate) (All indications) (Controls exposed to LTG), 2024 | Small for gestational age (a z-score for birth weight ≤10th percentile for gestational week, sex, and country (including newborns with congenital malformations)) | during pregnancy (anytime or not specified) | population based cohort retrospective | exposed to other treatment, sick excluded | Adjustment: No |
1.18 [1.03;1.35] C excluded (control group) |
325/2,669 920/8,756 | 1,245 | 2,669 |
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| S16022 R66510 |
Christensen (Valproate) (All indications) (Controls unexposed, general population), 2024 | Small for gestational age (a z-score for birth weight ≤10th percentile for gestational week, sex, and country (including newborns with congenital malformations)) | during pregnancy (anytime or not specified) | population based cohort retrospective | unexposed (general population or NOS) | Adjustment: Yes | 1.07 [0.95;1.21] | 325/2,669 446,267/4,467,848 | 446,592 | 2,669 |
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| S9287 R32241 |
Aydin (Valproate) (Controls exposed to Lamotrigine, sick), 2020 | Small for gestational age (birth weight) | throughout pregnancy | retrospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
0.62 [0.01;35.19] C excluded (control group) |
0/11 0/7 | 0 | 11 |
|
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| S9288 R32251 |
Aydin (Valproate) (Controls unexposed, sick), 2020 | Small for gestational age (birth weight) | throughout pregnancy | retrospective cohort | unexposed, sick | Adjustment: No | 2.05 [0.04;110.56] C | 0/11 0/22 | 0 | 11 |
|
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| S9392 R32894 |
Coste (Valproate) (Controls unexposed, NOS), 2020 | Small for gestational age (weight) | during pregnancy (anytime or not specified) | retrospective cohort (claims database) | unexposed (general population or NOS) | Adjustment: No | 1.63 [1.37;1.94] C | 149/991 167,376/1,710,441 | 167,525 | 991 |
|
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| S9315 R32455 |
Cohen (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 | Small for gestational age (ICD-9 656.5, 764.0, 764.1, 764.9) | early pregnancy | retrospective cohort (claims database) | exposed to other treatment, sick excluded | Adjustment: Yes |
1.37 [0.99;1.89] excluded (control group) |
88/2,398 106/2,682 | 194 | 2,398 |
|
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| S9316 R32462 |
Cohen (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 | Small for gestational age (ICD-9 656.5, 764.0, 764.1, 764.9) | early pregnancy | retrospective cohort (claims database) | unexposed (general population or NOS) | Adjustment: Yes | 0.86 [0.69;1.07] | 88/2,398 41,653/1,440,631 | 41,741 | 2,398 |
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| S18027 R75966 |
Margulis (Valproate) (Mixed indications), 2019 | Small for gestational age (defined within the Medical Birth Register from standard growth curves based on ultra- sound-derived fetal weights for singletons only) | during pregnancy (anytime or not specified) | population based cohort retrospective | exposed to other treatment, sick | Adjustment: Yes | 1.90 [1.20;3.20] | -/876 -/1,808 | - | 876 |
|
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| S9324 R32501 |
Putignano (Valproate), 2019 | Small for gestational age (SGA) (weight) | during pregnancy (anytime or not specified) | retrospective cohort | unexposed (general population or NOS) | Adjustment: No Matched | 2.27 [1.35;3.79] C | 22/131 75/917 | 97 | 131 |
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| S9314 R32446 |
Bank (Valproate) (Mixed indications), 2017 | Small for Gestational Age birthweight (<10th percentile) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick | Adjustment: No | 5.50 [0.70;43.52] C | 2/6 3/36 | 5 | 6 |
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| S9424 R33071 |
Veiby (Valproate) (Controls exposed to Lamotrigine, sick) b, 2013 | Small for gestational age (SGA) birth weight | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
1.03 [0.19;5.55] C excluded (control group) |
2/40 5/103 | 7 | 40 |
|
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| S9426 R33089 |
Veiby (Valproate) (Controls unexposed, disease free) b, 2013 | Small for gestational age (SGA) birth weight | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free excluded | Adjustment: Yes |
0.90 [0.20;3.70] excluded (control group) |
2/40 8,017/106,899 | 8,019 | 40 |
|
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| S9427 R33103 |
Veiby (Valproate) (Controls unexposed, sick) b, 2013 | Small for gestational age (SGA) birth weight | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No | 0.60 [0.14;2.62] C | 2/40 31/386 | 33 | 40 |
|
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| S9323 R32486 |
Pennell (Valproate), 2012 | Small for gestational age (SGA) (at birth) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick | Adjustment: Yes | 4.08 [1.11;14.96] | 9/62 4/98 | 13 | 62 |
|
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| S9290 R32263 |
Burja (Valproate) (Controls unexposed, disease free), 2006 | Small for date (NOS) | during pregnancy (anytime or not specified) | retrospective cohort (registry) | unexposed, disease free excluded | Adjustment: No |
8.17 [0.49;135.15] C excluded (control group) |
1/2 23/211 | 24 | 2 |
|
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| S9292 R32273 |
Burja (Valproate) (Controls unexposed, sick), 2006 | Small for date (NOS) | during pregnancy (anytime or not specified) | retrospective cohort (registry) | unexposed, sick | Adjustment: No | 31.00 [1.02;941.06] C | 1/2 1/32 | 2 | 2 |
|
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| S9300 R32373 |
Endo (Valproate) (Controls unexposed, disease free), 2004 | Intrauterine growth retardation (NOS) | at least 1st trimester | retrospective cohort | unexposed, disease free excluded | Adjustment: No |
2.00 [0.11;37.93] C excluded (control group) |
0/5 34/656 | 34 | 5 |
|
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| S9301 R32388 |
Endo (Valproate) (Controls unexposed, sick), 2004 | Intrauterine growth retardation (NOS) | throughout pregnancy | retrospective cohort | unexposed, sick | Adjustment: No | 0.11 [0.00;14.76] C | 0/5 0/1 | 0 | 5 |
|
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| Total | 11 studies | 1.46 [1.08;1.97] | 656,008 | 7,191 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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) (All indications) (Controls unexposed, general population; 2: Valproate) (Controls unexposed, sick; 3: Valproate) (Controls unexposed, NOS; 4: Valproate) (Controls unexposed NOS) (Mixed indications; 5: Valproate) (Mixed indications; 6: Valproate; 7: Valproate) (Mixed indications; 8: Valproate) (Controls unexposed, sick) ; 9: Valproate; 10: Valproate) (Controls unexposed, sick; 11: Valproate) (Controls unexposed, sick;
Asymetry test p-value = 0.2566 (by Egger's regression)
slope=0.0889 (0.1223); intercept=1.0034 (0.8284); t=1.2113; p=0.2566
excluded 9300, 9290, 9424, 9426, 9315, 9287, 16067