| 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S17423 R73166 |
Madley-Dowd_SE (Valproate) (Controls exposed to LTG) (Mixed indications), 2024 | Attention Deficit Hyperactivity Disorder - ICD-8/9/10 codes and/or ADHD medication prescription - 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 |
1.38 [1.13;1.68] excluded (control group) |
164/1,178 243/5,035 | 407 | 1,178 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17424 R73172 |
Madley-Dowd_SE (Valproate) (Controls unexposed, general pop) (Mixed indications), 2024 | Attention Deficit Hyperactivity Disorder - ICD-8/9/10 codes and/or ADHD medication prescription - Mean 5-20 years old (according groups) | during pregnancy (anytime or not specified) | population based cohort retrospective | unexposed (general population or NOS) | Adjustment: Yes Partial overlapping | 1.18 [1.01;1.39] | 164/1,178 147,608/2,651,210 | 147,772 | 1,178 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17425 R73178 |
Madley-Dowd_SE (Valproate) (Controls unexposed, sibling) (Mixed indications), 2024 | Attention Deficit Hyperactivity Disorder - ICD-8/9/10 codes and/or ADHD medication prescription - Mean 5-20 years old (according groups) | during pregnancy (anytime or not specified) | population based cohort retrospective | sibling excluded | Adjustment: Yes Partial overlapping |
1.26 [0.81;1.96] excluded (control group) |
-/- -/- | - | - |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17286 R72378 |
Madley-Dowd_UK (Valproate) (Controls exposed to LTG) (Mixed indications), 2024 | Attention Deficit Hyperactivity Disorder - ICD10 codes and/or ADHD medication prescription - 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 |
0.90 [0.38;2.15] excluded (control group) |
10/423 14/939 | 24 | 423 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17271 R72379 |
Madley-Dowd_UK (Valproate) (Controls unexposed, general pop) (Mixed indications), 2024 | Attention Deficit Hyperactivity Disorder - ICD10 codes and/or ADHD medication prescription - 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 | 1.48 [0.71;3.07] | 10/423 4,794/514,066 | 4,804 | 423 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S17279 R72380 |
Madley-Dowd_UK (Valproate) (Controls unexposed, sibling) (Mixed indications), 2024 | Attention Deficit Hyperactivity Disorder - ICD10 codes and/or ADHD medication prescription - 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 |
4.00 [1.39;11.47] excluded (control group) |
-/- -/- | - | - |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S15237 R63068 |
Dreier (Valproate) (Epilepsy) (Controls exposed to LTG), 2023 | Attention-deficit/hyperactivity disorder (ADHD) - Corresponding ICD-10 F-chapter - Up to 22 years of age | during pregnancy (anytime or not specified) | population based cohort propective | exposed to other treatment, sick excluded | Adjustment: No |
3.14 [2.37;4.16] C excluded (control group) |
106/1,952 95/5,288 | 201 | 1,952 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S15228 R63069 |
Dreier (Valproate) (Epilepsy) (Controls unexposed, sick), 2023 | Attention-deficit/hyperactivity disorder (ADHD) - Corresponding ICD-10 F-chapter - Up to 22 years of age | during pregnancy (anytime or not specified) | population based cohort propective | unexposed, sick | Adjustment: Yes | 1.41 [1.10;1.81] | 106/1,952 528/22,203 | 634 | 1,952 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9404 R46515 |
Huber-Mollema (Valproate), 2019 | Diagnosis of ADHD | throughout pregnancy | prospective cohort | exposed to other treatment, sick | Adjustment: No | 1.38 [0.25;7.58] C | 2/26 5/88 | 7 | 26 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9416 R46518 |
Richards (Valproate) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2019 | The Strengths and Difficulties Questionnaire - parent-completed (SDQP) Hyperactivity ≥7 (at 4 years old) | during pregnancy (anytime or not specified) | population based cohort retrospective | exposed to other treatment, sick excluded | Adjustment: Yes |
0.67 [0.31;1.42] excluded (control group) |
10/161 13/149 | 23 | 161 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9417 R46519 |
Richards (Valproate) (Controls unexposed, NOS) (Indications NOS), 2019 | The Strengths and Difficulties Questionnaire - parent-completed (SDQP) Hyperactivity ≥7 (at 4 years old) | during pregnancy (anytime or not specified) | population based cohort retrospective | unexposed (general population or NOS) | Adjustment: Yes | 1.35 [0.71;2.58] | 10/161 11,841/286,966 | 11,851 | 161 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9374 R46517 |
Bromley (Valproate), 2016 | Maladaptive behavior: Attention (BASC) (5-9 years old) | during pregnancy (anytime or not specified) | retrospective cohort (registry) | unexposed, sick | Adjustment: No extrapolated (cont. endpoint) | 0.89 [0.44;1.79] | -/47 -/55 | - | 47 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9377 R46509 |
Bromley (Valproate) (Controls exposed to Lamotrigine, sick), 2013 | Attention deficit hyperactivity disorder (at 6 years old) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
0.60 [0.01;30.84] C excluded (control group) |
0/50 0/30 | 0 | 50 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9380 R46510 |
Bromley (Valproate) (Controls unexposed, disease free), 2013 | Attention deficit hyperactivity disorder (at 6 years old) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free excluded | Adjustment: No |
4.31 [0.08;220.05] C excluded (control group) |
0/50 0/214 | 0 | 50 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9383 R46511 |
Bromley (Valproate) (Controls unexposed, sick), 2013 | Attention deficit hyperactivity disorder (at 6 years old) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No | 0.52 [0.01;26.73] C | 0/50 0/26 | 0 | 50 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9390 R46514 |
Cohen (Valproate), 2013 | Children with either ADHD inattentive OR combined types > 1 SD (from the Attention Problems and Hyperactivity scales of the BASC) (Both Parent and Teacher) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick | Adjustment: No | 1.84 [0.46;7.35] C | 6/28 4/31 | 10 | 28 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9450 R46520 |
Rihtman (Valproate) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2013 | Conners’ Parent - ADHD Index (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) |
2.74 [1.13;6.67] excluded (control group) |
-/29 -/39 | - | 29 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9451 R46521 |
Rihtman (Valproate) (Controls unexposed, NOS) (Mixed indications), 2013 | Conners’ Parent - ADHD Index (mean age 4-5 years old) | at least 1st trimester | prospective cohort | unexposed (general population or NOS) | Adjustment: No extrapolated (cont. endpoint) | 3.38 [1.45;7.88] | -/29 -/52 | - | 29 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9424 R46522 |
Veiby (Valproate) (Controls exposed to Lamotrigine, sick) b, 2013 | ADHD symptoms ≥ 2SD (at 36 months) (Specific checklist) (Parent-reported) | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
0.76 [0.07;7.80] C excluded (control group) |
1/19 3/44 | 4 | 19 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9426 R46523 |
Veiby (Valproate) (Controls unexposed, disease free) b, 2013 | ADHD symptoms ≥ 2SD (at 36 months) (Specific checklist) (Parent-reported) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, disease free excluded | Adjustment: No |
1.30 [0.20;9.90] excluded (control group) |
1/19 1,743/43,571 | 1,744 | 19 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9427 R46524 |
Veiby (Valproate) (Controls unexposed, sick) b, 2013 | ADHD symptoms ≥ 2SD (at 36 months) (Specific checklist) (Parent-reported) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No | 2.08 [0.22;19.67] C | 1/19 4/154 | 5 | 19 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9428 R46525 |
Viinikainen (Valproate) b, 2006 | Conners' Teacher Rating Scale Global Index scores >1 SD | throughout pregnancy | prospective cohort | unexposed, sick | Adjustment: No Matched | 0.90 [0.10;7.78] C | 2/12 2/11 | 4 | 12 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| S9278 R46508 |
Adab (Valproate), 2004 | Attention deficit hyperactivity disorder | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, sick | Adjustment: No | 8.31 [0.39;175.93] C | 2/63 0/101 | 2 | 63 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Total | 12 studies | 1.28 [1.13;1.44] | 165,089 | 3,988 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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) (Controls unexposed, sick; 4: Valproate; 5: Valproate) (Controls unexposed, NOS) (Indications NOS; 6: Valproate; 7: Valproate) (Controls unexposed, sick; 8: Valproate; 9: Valproate) (Controls unexposed, NOS) (Mixed indications; 10: Valproate) (Controls unexposed, sick) ; 11: Valproate) ; 12: Valproate;
Asymetry test p-value = 0.2173 (by Egger's regression)
slope=0.1736 (0.0790); intercept=0.4728 (0.3591); t=1.3167; p=0.2173
excluded 9377, 9380, 9450, 9424, 9426, 9416, 15237, 17423, 17425, 17286, 17279