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Clonazepam (Psy and Mixed indications)
Overall results
Study description
Excluded studies
Table
Graphic
auto
during pregnancy (anytime or not specified)
1st trimester
2nd trimester
3rd trimester
2nd and/or 3rd trimester
throughout pregnancy
early pregnancy
days before delivery
late pregnancy
preconception-only
periconceptional
preconceptional for kinetic reason
at least 1st trimester
3 months (or more) before pregnancy or during pregnancy
1st and 2nd trimester
3 months or more before pregnancy or1st trimester
Whatever the period exposition
individual studies
Outcome
TE
95% CI
n cases
n exposed
k
Pub. bias
Congenital malformations
All congenital malformations (majors, minors, majors and minors, or unspecified)
Källén (Indications NOS), 2013 Veiby (Mixed indications), 2014 Noh (Mixed indications), 2022 The NAAED (Indications NOS), 2023
4
1.04
[
0.85
; 1.27]
228,884
1,793
not evaluable
Major congenital malformations
Källén (Indications NOS), 2013 Veiby (Mixed indications), 2014 Noh (Mixed indications), 2022 The NAAED (Indications NOS), 2023
4
1.04
[
0.85
; 1.27]
228,884
1,793
not evaluable
Microcephaly / Small head circumference for gestational age
Eros (Indications NOS), 2002 Blotière (Indications other than epilepsy), 2019 Christensen (Indications other than epilepsy), 2024
3
3.19
[
0.47
; 21.76]
133,817
1,999
not evaluable
Ano-rectal atresia and stenosis
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
1.16
[
0.32
; 4.18]
1,610
1,003
not evaluable
Cleft lip with or without cleft palate
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
0.95
[
0.39
; 2.30]
4,723
1,007
not evaluable
Cleft palate
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
1.60
[
0.67
; 3.84]
2,757
1,006
not evaluable
Congenital heart defects
Tinker (Mixed indications), 2019 Noh (Mixed indications), 2022
2
1.03
[
0.80
; 1.33]
95,840
1,498
not evaluable
Gastroschisis
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
1.12
[
0.30
; 4.14]
1,643
1,003
not evaluable
Hypospadias
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
0.83
[
0.29
; 2.37]
5,913
-
not evaluable
Oesophageal atresia with or without tracheo-oesophageal fistula
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
1.45
[
0.24
; 8.75]
1,146
1,002
not evaluable
Atrial septal defect
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
0.82
[
0.30
; 2.21]
6,295
1,005
not evaluable
Atrioventricular septal defect
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
2.68
[
0.74
; 9.72]
898
1,003
not evaluable
Bilateral renal agenesis including Potter syndrome
Blotière (Indications other than epilepsy), 2019
1
12.68
[
0.79
; 204.77]
75
980
not evaluable
Club foot / Talipes equinovarus
Blotière (Indications other than epilepsy), 2019
1
1.14
[
0.16
; 8.12]
1,678
980
not evaluable
Coarctation of aorta
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
0.66
[
0.13
; 3.35]
1,932
1,002
not evaluable
Craniosynostosis
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
1.04
[
0.34
; 3.19]
2,345
1,004
not evaluable
Diaphragmatic hernia
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
1.02
[
0.20
; 5.18]
1,245
1,002
not evaluable
Hydrocephaly
Tinker (Mixed indications), 2019
1
1.07
[
0.14
; 7.98]
513
22
not evaluable
Neural Tube Defects
Tinker (Mixed indications), 2019
1
1.30
[
0.48
; 3.49]
2,105
26
not evaluable
Omphalocele
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
1.54
[
0.21
; 11.07]
700
1,001
not evaluable
Spina bifida
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
1.34
[
0.44
; 4.02]
1,857
1,004
not evaluable
Tetralogy of Fallot
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
1.94
[
0.78
; 4.78]
1,781
1,006
not evaluable
Ventricular septal defect
Tinker (Mixed indications), 2019 Blotière (Indications other than epilepsy), 2019
2
1.46
[
0.67
; 3.16]
6,295
1,005
not evaluable
Anophthalmos/micropthalmos
Tinker (Mixed indications), 2019
1
1.22
[
0.07
; 20.20]
230
21
not evaluable
Anotia
Tinker (Mixed indications), 2019
1
2.40
[
0.71
; 8.16]
685
24
not evaluable
Aortic valve atresia/stenosis
Tinker (Mixed indications), 2019
1
1.08
[
0.14
; 8.02]
510
22
not evaluable
Atresia or stenosis of other parts of small intestine
0
-
-
-
-
-
Bladder exstrophy and/or epispadia
Blotière (Indications other than epilepsy), 2019
1
11.61
[
0.72
; 187.25]
82
980
not evaluable
Cardiac septal defects
Tinker (Mixed indications), 2019
1
1.10
[
0.51
; 2.36]
4,673
31
not evaluable
Ear malformations
0
-
-
-
-
-
Ebstein's anomaly
Blotière (Indications other than epilepsy), 2019
1
18.96
[
1.17
; 307.53]
50
980
not evaluable
Eye defects
0
-
-
-
-
-
Genital anomalies
0
-
-
-
-
-
Hypoplastic left heart (HLH/HLHS)
Blotière (Indications other than epilepsy), 2019
1
4.42
[
0.28
; 70.98]
216
980
not evaluable
Hypoplastic right heart (HRH/HRHS)
Blotière (Indications other than epilepsy), 2019
1
14.40
[
0.89
; 232.77]
66
980
not evaluable
Limb reduction defects (LRD)
0
-
-
-
-
-
Oro-facial clefts
Blotière (Indications other than epilepsy), 2019
1
0.68
[
0.10
; 4.83]
2,816
980
not evaluable
Polydactyly
0
-
-
-
-
-
Pulmonary valve atresia
Blotière (Indications other than epilepsy), 2019
1
6.28
[
0.39
; 100.91]
152
980
not evaluable
Pulmonary valve stenosis
Tinker (Mixed indications), 2019
1
1.20
[
0.46
; 3.13]
1,532
26
not evaluable
Transposition of the great vessels
Tinker (Mixed indications), 2019
1
1.44
[
0.34
; 6.14]
765
23
not evaluable
Growth parameters and prematurity
Low birth weight (< 2500g)
Coste (Indications other than epilepsy), 2020 Christensen (Indications other than epilepsy), 2024
2
1.26
[
0.75
; 2.12]
232,055
2,265
not evaluable
Small for gestational age (weight)
Coste (Indications other than epilepsy), 2020 Christensen (Indications other than epilepsy), 2024
2
1.29
[
1.14
; 1.45]
611,550
2,265
not evaluable
Preterm (< 37 weeks)
Kilic (Mixed indications), 2014 Coste (Indications other than epilepsy), 2020
2
1.46
[
1.21
; 1.77]
125,345
1,508
not evaluable
Extremely preterm (< 28 weeks)
Coste (Indications other than epilepsy), 2020
1
0.67
[
0.09
; 4.78]
2,042
1,246
not evaluable
Macrosomia (> 4000g)
Coste (Indications other than epilepsy), 2020
1
0.86
[
0.76
; 0.97]
577,475
1,246
not evaluable
Very preterm (28 to 32 weeks)
Coste (Indications other than epilepsy), 2020
1
1.44
[
0.75
; 2.78]
8,593
1,246
not evaluable
Maternal consequences
Caesarean
Oberlander (Controls unexposed, sick) (Indications other than epilepsy), 2004
1
0.92
[
0.19
; 4.43]
8
18
not evaluable
Neonatal disorders
Neonatal medical care
Oberlander (Controls unexposed, sick) (Indications other than epilepsy), 2004
1
1.91
[
0.53
; 6.84]
14
18
not evaluable
Low Apgar score (< 7) (at 5 min)
Christensen (Mixed indications), 2015
1
1.47
[
0.62
; 3.50]
8,802
260
not evaluable
Neonatal disorders (as a whole)
Coste (Indications other than epilepsy), 2020
1
1.26
[
1.08
; 1.46]
222,398
1,246
not evaluable
Long term consequences
Child/Infant death (> 28 days of life)
Coste (Indications other than epilepsy), 2020
1
0.58
[
0.15
; 2.34]
4,697
1,246
not evaluable
Intrauterine deaths
Early intrauterine deaths (< 22 weeks) / Spontaneous abortions
Bech (Indications other than epilepsy), 2014 Sheehy (Indications NOS), 2019
2
1.86
[
1.56
; 2.22]
135,482
439
not evaluable
Neuro-developmental disorders
ASD (Autism spectrum disorder): Diagnosis
Coste (Indications other than epilepsy), 2020 Bjørk (Mixed indications), 2022
2
1.34
[
0.95
; 1.90]
42,750
2,428
not evaluable
ASD (Autism spectrum disorder): Diagnosis/Risk
Coste (Indications other than epilepsy), 2020 Bjørk (Mixed indications), 2022
2
1.34
[
0.95
; 1.90]
42,750
2,428
not evaluable
Cognitive developmental disorders/delay (< 3 years old)
Oberlander (Controls unexposed, sick) (Indications other than epilepsy), 2004
1
2.96
[
0.99
; 8.88]
-
18
not evaluable
Cognitive developmental disorders/delay (> 6 years old)
Bjørk (Mixed indications), 2022
1
1.76
[
1.06
; 2.92]
16,399
1,182
not evaluable
Neuro-developmental disorders (as a whole)
Coste (Indications other than epilepsy), 2020 Bjørk (Mixed indications), 2022
2
1.31
[
1.03
; 1.66]
78,371
2,428
not evaluable
Psychomotor developmental disorders/delay
Oberlander (Controls unexposed, sick) (Indications other than epilepsy), 2004
1
0.73
[
0.25
; 2.14]
-
18
not evaluable
Severe cognitive developmental delay (Mental retardation) (> 6 years old)
Bjørk (Mixed indications), 2022
1
1.76
[
1.06
; 2.92]
16,399
1,182
not evaluable
ADHD (Attention deficit hyperactivity disorder): Diagnosis
Christensen (Indications NOS), 2019
1
1.43
[
0.95
; 2.16]
28,777
314
not evaluable
ADHD (Attention deficit hyperactivity disorder): Diagnosis/Risk
Christensen (Indications NOS), 2019
1
1.43
[
0.95
; 2.16]
27,857
314
not evaluable
Childhood autism (F84.0)
Christensen (Indications NOS), 2013
1
0.90
[
0.11
; 7.37]
2,065
269
not evaluable
Cognitive developmental disorders/delay (3-6 years old)
Coste (Indications other than epilepsy), 2020
1
0.60
[
0.19
; 1.85]
3,401
1,246
not evaluable
Language disorders/delay
Coste (Indications other than epilepsy), 2020
1
0.90
[
0.72
; 1.13]
72,109
1,246
not evaluable
Learning disorders
Elkjaer (Indications, NOS), 2018
1
1.14
[
1.00
; 1.29]
-
101
not evaluable
Severe cognitive developmental delay (Mental retardation) (3-6 years old)
Coste (Indications other than epilepsy), 2020
1
0.60
[
0.19
; 1.85]
3,401
1,246
not evaluable
0.0
100.0
1.0