| 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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| S16814 R70544 |
Christensen (Phenobarbital) (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 |
1.98 [1.06;3.69] C excluded (control group) |
11/183 274/8,756 | 285 | 183 |
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| S16815 R70548 |
Christensen (Phenobarbital) (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 | 1.82 [0.96;3.47] | 11/183 134,023/4,467,848 | 134,034 | 183 |
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| S10043 R36316 |
Blotière (Phenobarbital) (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 |
12.56 [0.51;310.72] C excluded (control group) |
0/80 1/2,997 | 1 | 80 |
|
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| S10044 R36339 |
Blotière (Phenobarbital) (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 | 26.90 [1.67;434.48] C | 0/80 438/1,875,733 | 438 | 80 |
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| S9497 R33479 |
Holmes (Phenobarbital) (Controls unexposed, disease free), 2001 | Microcephaly at birth (Head circumference more than 2 SD below the mean value for the same race, sex and gestational age) | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, disease free excluded | Adjustment: No |
3.18 [0.82;12.31] C excluded (control group) |
3/62 8/508 | 11 | 62 |
|
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| S9498 R33488 |
Holmes (Phenobarbital) (Controls unexposed, sick), 2001 | Microcephaly at birth (Head circumference more than 2 SD below the mean value for the same race, sex and gestational age) | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, sick | Adjustment: No | 2.39 [0.39;14.73] C | 3/62 2/96 | 5 | 62 |
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| S9589 R33955 |
Battino (Phenobarbital or Primidone), 1999 | Small head circumferences (at birth < 10th percentile) | throughout pregnancy | prospective cohort | unexposed, sick | Adjustment: No | 2.01 [0.56;7.25] C | 21/115 3/30 | 24 | 115 |
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| S9544 R33715 |
Díaz-Romero (Phenobarbital), 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 | 5.00 [0.07;366.35] C | 0/2 0/8 | 0 | 2 |
|
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| S9519 R33608 |
Dravet (Phenobarbital), 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 | 3.55 [0.42;29.89] C | 12/56 1/14 | 13 | 56 |
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| S9522 R33613 |
Kelly (Phenobarbital), 1984 | Microcephaly at unknown age (head circumference < 5th centile) | during pregnancy (anytime or not specified) | prospective cohort | unexposed, sick | Adjustment: No | 3.64 [0.30;44.78] C | 2/13 1/21 | 3 | 13 |
|
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| Total | 7 studies | 2.24 [1.35;3.71] | 134,517 | 511 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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: Phenobarbital) (All indications) (Controls unexposed, general population; 2: Phenobarbital) (Controls unexposed NOS) (Mixed indications; 3: Phenobarbital) (Controls unexposed, sick; 4: Phenobarbital or Primidone; 5: Phenobarbital; 6: Phenobarbital; 7: Phenobarbital;
Asymetry test p-value = 0.0496 (by Egger's regression)
slope=0.2218 (0.2718); intercept=1.0242 (0.3973); t=2.5776; p=0.0496
excluded 9497, 10043, 16814