| 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S16067 R66679 |
Christensen (Valproate) (All indications) (Controls exposed to LTG), 2024 | Microcephaly (z-score for head circumference ≤3rd 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 |
1.17 [0.92;1.48] C excluded (control group) |
97/2,669 274/8,756 | 371 | 2,669 |
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| S16022 R66511 |
Christensen (Valproate) (All indications) (Controls unexposed, general population), 2024 | Microcephaly (z-score for head circumference ≤3rd 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 | 1.08 [0.85;1.37] | 97/2,669 134,023/4,467,848 | 134,120 | 2,669 |
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| S10174 R37203 |
Blotière (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 | Microcephaly (until 24 months of age, identifiable by: Q02; brain MRI; according to the EUROCAT definition) | 1st trimester | retrospective cohort (claims database) | exposed to other treatment, sick excluded | Adjustment: No |
1.09 [0.04;26.89] C excluded (control group) |
0/913 1/2,997 | 1 | 913 |
|
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| S10051 R36477 |
Blotière (Valproate) (Controls unexposed NOS) (Mixed indications), 2019 | Microcephaly (until 24 months of age, identifiable by: Q02; brain MRI; according to the EUROCAT definition) | 1st trimester | retrospective cohort (claims database) | unexposed (general population or NOS) | Adjustment: No | 2.34 [0.15;37.55] C | 0/913 438/1,875,733 | 438 | 913 |
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| S18027 R75967 |
Margulis (Valproate) (Mixed indications), 2019 | Microcephaly (a head circumference of two or more SDs below the mean for gestational age at birth, using a local standard) | during pregnancy (anytime or not specified) | population based cohort retrospective | exposed to other treatment, sick | Adjustment: Yes | 1.80 [1.00;3.20] | -/824 -/1,767 | - | 824 |
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| S9323 R32490 |
Pennell (Valproate), 2012 | Microcephaly at birth (head circumference < 3 percentile) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick | Adjustment: No | 1.27 [0.34;4.83] C | 4/38 6/71 | 10 | 38 |
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| S9346 R32602 |
Kini (Valproate) (Controls unexposed, sick), 2006 | Head circumference in children aged between 6 months and 16 years <3rd centile | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, sick | Adjustment: No | 1.66 [0.46;5.96] C | 5/63 5/101 | 10 | 63 |
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| S9369 R32758 |
Battino (Valproate), 1999 | Small head circumferences (at birth < 10th percentile) | throughout pregnancy | prospective cohort | unexposed, sick | Adjustment: No | 0.68 [0.14;3.26] C | 4/57 3/30 | 7 | 57 |
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| S9370 R32759 |
Díaz-Romero (Valproate), 1999 | Head circumference <2 SD at birth (measured by a physician and correlated with sex and with gestational age) | during pregnancy (anytime or not specified) | cohort | unexposed, sick | Adjustment: No | 0.79 [0.01;44.65] C | 0/10 0/8 | 0 | 10 |
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| S9341 R32589 |
Dravet (Valproate), 1992 | Isolated microcephaly at birth (head circumference >2 SD lower than those given in the reference tables adjusted for gestational age at birth) | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 3.12 [0.34;28.74] C | 6/31 1/14 | 7 | 31 |
|
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| Total | 8 studies | 1.18 [0.95;1.46] | 134,592 | 4,605 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 NOS) (Mixed indications; 3: Valproate) (Mixed indications; 4: Valproate; 5: Valproate) (Controls unexposed, sick; 6: Valproate; 7: Valproate; 8: Valproate;
Asymetry test p-value = 0.3026 (by Egger's regression)
slope=0.0776 (0.1133); intercept=0.4198 (0.3723); t=1.1274; p=0.3026
excluded 10174, 16067