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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S9200 R31923 |
The NAAED (Controls exposed to Lamotrigine, sick) (Indications NOS), 2022 | Major congenital malformations | 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
1.52 [0.80;2.90] C excluded (control group) |
12/423 44/2,333 | 56 | 423 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9201 R31925 |
The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, disease free | Adjustment: No | 2.89 [1.29;6.49] C | 12/423 12/1,201 | 24 | 423 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S12697 R48801 |
Alsfouk (Phenytoin) (Controls exposed to Lamotrigine, sick), 2021 | Major congenital malformation | during pregnancy (anytime or not specified) | retrospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
5.00 [0.08;316.71] C excluded (control group) |
0/1 2/15 | 2 | 1 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S12699 R48802 |
Alsfouk (Phenytoin) (Controls unexposed, sick), 2021 | Major congenital malformation | during pregnancy (anytime or not specified) excluded | retrospective cohort | unexposed, sick | Adjustment: No |
19.00 [0.27;1331.97] C excluded (exposition period) |
0/1 1/30 | 1 | 1 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S12850 R48451 |
Thomas (Phenytoin) (Controls exposed to Lamotrigine, sick), 2021 | Major congenital malformations | 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
3.06 [0.37;25.57] C excluded (control group) |
7/119 1/50 | 8 | 119 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S12851 R48459 |
Thomas (Phenytoin) (Controls unexposed, disease free), 2021 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, disease free excluded | Adjustment: No |
1.64 [0.62;4.33] excluded (control group) |
6/106 11/319 | 17 | 106 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S12852 R48463 |
Thomas (Phenytoin) (Controls unexposed, sick), 2021 | Major congenital malformations | 1st trimester | prospective cohort | unexposed, sick | Adjustment: Yes | 1.27 [0.51;3.16] C | 7/119 16/340 | 23 | 119 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9192 R31826 |
Aydin (Phenytoin) (Controls exposed to Lamotrigine, sick), 2020 | Congenital chromosomal/structural anomalies | throughout pregnancy | retrospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
13.00 [0.10;1680.94] C excluded (control group) |
0/1 0/7 | 0 | 1 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9193 R31836 |
Aydin (Phenytoin) (Controls unexposed, sick), 2020 | Congenital chromosomal/structural anomalies | throughout pregnancy | retrospective cohort | unexposed, sick | Adjustment: No | 43.00 [0.35;5328.22] C | 0/1 0/22 | 0 | 1 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9247 R35159 |
Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2019 | Fetal malformations | at least 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
0.45 [0.06;3.43] C excluded (control group) |
1/44 20/406 | 21 | 44 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9248 R35160 |
Vajda (Phenytoin) (Controls unexposed, sick), 2019 | Fetal malformations | at least 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 0.80 [0.10;6.61] | 1/44 5/176 | 6 | 44 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9246 R32086 |
Tomson (Phenytoin), 2018 | Major congenital malformation | at least 1st trimester | prospective cohort | exposed to other treatment, sick | Adjustment: No | 2.25 [1.06;4.79] C | 8/125 74/2,514 | 82 | 125 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9272 R32156 |
Bank (Phenytoin) (Mixed indications), 2017 | Major Malformation | during pregnancy (anytime or not specified) excluded | prospective cohort | exposed to other treatment, sick | Adjustment: No |
14.20 [0.23;878.06] C excluded (exposition period) |
0/3 0/36 | 0 | 3 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9198 R31915 |
He (Phenytoin) (Controls exposed to Lamotrigine, sick), 2017 | Congenital malformations | during pregnancy (anytime or not specified) | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
2.14 [0.03;131.94] C excluded (control group) |
0/4 0/8 | 0 | 4 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9199 R31917 |
He (Phenytoin) (Controls unexposed, sick), 2017 | Congenital malformations | during pregnancy (anytime or not specified) excluded | prospective cohort | unexposed, sick | Adjustment: No |
8.71 [0.15;511.85] C excluded (exposition period) |
0/4 0/31 | 0 | 4 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9186 R31769 |
Arkilo (Phenytoin), 2015 | Major malformations | during pregnancy (anytime or not specified) excluded | retrospective cohort | exposed to other treatment, sick | Adjustment: No |
5.22 [0.09;299.04] C excluded (exposition period) |
0/5 0/24 | 0 | 5 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9206 R31949 |
Källén (Phenytoin) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 | Relatively severe malformations | early pregnancy | population based cohort retrospective | exposed to other treatment, sick excluded | Adjustment: No |
2.65 [1.35;5.22] C excluded (control group) |
12/140 37/1,084 | 49 | 140 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9207 R31951 |
Källén (Phenytoin) (Controls unexposed, NOS) (Indications NOS), 2013 | Relatively severe malformations | early pregnancy | population based cohort retrospective | unexposed (general population or NOS) | Adjustment: Yes | 1.84 [0.95;3.21] | 12/140 49,499/1,575,847 | 49,511 | 140 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9191 R31818 |
Arteaga-Vázquez (Phenytoin), 2012 | Congenital malformations | 1st trimester | case control | unexposed, sick | Adjustment: No | 2.01 [0.83;4.84] C | 19/43 13/46 | 32 | 43 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9225 R35123 |
Bànhidy (Phenytoin), 2011 | Total congenital abnormalities | throughout pregnancy | case control | unexposed, sick | Adjustment: No Matched | 0.61 [0.21;1.82] C | 14/33 12/22 | 26 | 33 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9209 R31954 |
Mawer (Phenytoin) (Controls exposed to Lamotrigine, sick), 2010 | Major malformations | 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
1.06 [0.05;24.77] C excluded (control group) |
0/7 2/37 | 2 | 7 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9210 R31956 |
Mawer (Phenytoin) (Controls unexposed, disease free), 2010 | Major malformations | 1st trimester | prospective cohort | unexposed, disease free excluded | Adjustment: No Matched |
3.30 [0.17;64.87] C excluded (control group) |
0/7 6/285 | 6 | 7 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9211 R31958 |
Mawer (Phenytoin) (Controls unexposed, sick), 2010 | Major malformations | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 2.03 [0.07;55.28] C | 0/7 1/41 | 1 | 7 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9235 R32051 |
Kini (Phenytoin) (Controls unexposed, sick), 2006 | Major malformations | during pregnancy (anytime or not specified) excluded | retrospective cohort | unexposed, sick | Adjustment: No |
0.97 [0.10;9.07] excluded (exposition period) |
1/26 4/101 | 5 | 26 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9212 R31962 |
Meador (Phenytoin), 2006 | Congenital malformations | during pregnancy (anytime or not specified) excluded | prospective cohort | exposed to other treatment, sick | Adjustment: No |
7.46 [0.81;68.50] C excluded (exposition period) |
4/56 1/98 | 5 | 56 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9238 R32063 |
Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 | Major congenital malformation | 1st trimester | prospective cohort | exposed to other treatment, sick excluded | Adjustment: No |
1.13 [0.33;3.88] C excluded (control group) |
3/82 21/647 | 24 | 82 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9239 R32065 |
Morrow (Phenytoin) (Controls unexposed, sick), 2006 | Major congenital malformation | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 1.04 [0.27;4.02] C | 3/82 8/227 | 11 | 82 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9220 R31995 |
Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006 | Major malformations | throughout pregnancy | prospective cohort | unexposed, sick | Adjustment: No | 34.33 [0.49;2389.88] C | 0/2 0/52 | 0 | 2 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9224 R32001 |
Artama (Phenytoin), 2005 | Malformations | 1st trimester | retrospective cohort (registry) | unexposed, sick | Adjustment: No | 0.95 [0.02;6.11] | 1/38 26/939 | 27 | 38 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9231 R32036 |
Kaaja (Phenytoin), 2003 | Major malformation | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 2.94 [0.48;17.82] C | 3/124 2/239 | 5 | 124 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9196 R31912 |
Dean (Phenytoin), 2002 | Congenital malformations (major and minor) | at least 1st trimester | retrospective cohort | unexposed, sick | Adjustment: No | 4.80 [1.54;14.93] C | 13/25 7/38 | 20 | 25 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9202 R31934 |
Holmes (Phenytoin) (Controls unexposed, disease free), 2001 | Major malformations | during pregnancy (anytime or not specified) | retrospective cohort | unexposed, disease free excluded | Adjustment: Yes |
1.90 [0.30;9.20] excluded (control group) |
3/87 9/508 | 12 | 87 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9203 R31943 |
Holmes (Phenytoin) (Controls unexposed, sick), 2001 | Major malformations | during pregnancy (anytime or not specified) excluded | retrospective cohort | unexposed, sick | Adjustment: No |
8.17 [0.42;160.54] C excluded (exposition period) |
3/87 0/98 | 3 | 87 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9204 R31945 |
Hvas (Phenytoin) (Controls unexposed, disease free), 2000 | Major congenital malformations | 1st trimester | retrospective cohort | unexposed, disease free excluded | Adjustment: No |
83.94 [1.66;4238.34] C excluded (control group) |
0/1 280/23,827 | 280 | 1 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9205 R31947 |
Hvas (Phenytoin) (Controls unexposed, sick), 2000 | Major congenital malformations | 1st trimester | retrospective cohort | unexposed, sick | Adjustment: No | 211.00 [1.73;25761.82] C | 0/1 0/106 | 0 | 1 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9185 R31762 |
Al Bunyan (Phenytoin), 1999 | Congenital malformations | during pregnancy (anytime or not specified) excluded | retrospective cohort | unexposed, sick | Adjustment: No |
1.12 [0.02;62.74] C excluded (exposition period) |
0/9 0/10 | 0 | 9 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9227 R32029 |
Canger (Phenytoin), 1999 | All type of malformation | 1st trimester | prospective cohort | unexposed, sick | Adjustment: No | 6.24 [0.31;126.88] C | 3/31 0/25 | 3 | 31 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9232 R32037 |
Kaneko (Phenytoin), 1999 | Malformations | throughout pregnancy | prospective cohort | unexposed, sick | Adjustment: No | 3.17 [0.87;11.54] C | 12/132 3/98 | 15 | 132 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9240 R32067 |
Samrén (Phenytoin), 1999 | Major congential abnormalities | at least 1st trimester | retrospective cohort | unexposed, disease free | Adjustment: No Matched | 0.50 [0.10;3.40] | 1/151 29/2,000 | 30 | 151 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9273 R37354 |
Nulman (Phenytoin) (Controls unexposed, NOS) (Mixed indications), 1997 | Malformations (major) | at least 1st trimester | prospective cohort | unexposed (general population or NOS) | Adjustment: No Matched | 1.55 [0.24;9.91] C | 3/34 2/34 | 5 | 34 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9241 R32069 |
Steegers-Theunissen (Phenytoin), 1994 | Major malformations (ICD9 British Paediatric Association System) | during pregnancy (anytime or not specified) excluded | prospective cohort | unexposed, disease free | Adjustment: No |
2.76 [0.12;62.85] C excluded (exposition period) |
0/8 2/106 | 2 | 8 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9194 R31839 |
D'Souza (Phenytoin) (Controls unexposed, disease free), 1991 | Congenital anomalies | throughout pregnancy | prospective cohort | unexposed, disease free excluded | Adjustment: No Matched |
161.84 [8.83;2965.43] C excluded (control group) |
12/22 0/62 | 12 | 22 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9195 R31868 |
D'Souza (Phenytoin) (Controls unexposed, sick), 1991 | Congenital anomalies | throughout pregnancy | prospective cohort | unexposed, sick | Adjustment: No | 8.40 [0.88;80.27] C | 12/22 1/8 | 13 | 22 |
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ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9233 R32044 |
Kelly (Phenytoin), 1984 | Major abnormality | during pregnancy (anytime or not specified) excluded | prospective cohort | unexposed, sick | Adjustment: No |
0.50 [0.03;8.42] C excluded (exposition period) |
1/41 1/21 | 2 | 41 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9236 R32052 |
Lowe (Phenytoin) (Controls unexposed, disease free), 1973 | Malformations | 1st trimester | population based cohort retrospective | unexposed, disease free excluded | Adjustment: No |
10.16 [2.11;48.99] C excluded (control group) |
2/9 865/31,632 | 867 | 9 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
S9237 R32054 |
Lowe (Phenytoin) (Controls unexposed, sick), 1973 | Malformations | 1st trimester | population based cohort retrospective | unexposed, sick | Adjustment: No | 10.29 [1.47;71.98] C | 2/9 3/111 | 5 | 9 |
|
ref | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Total | 21 studies | 2.08 [1.48;2.92] | 49,839 | 1,586 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: Controls unexposed, disease free) (Indications NOS; 2: Phenytoin) (Controls unexposed, sick; 3: Phenytoin) (Controls unexposed, sick; 4: Phenytoin) (Controls unexposed, sick; 5: Phenytoin; 6: Phenytoin) (Controls unexposed, NOS) (Indications NOS; 7: Phenytoin; 8: Phenytoin; 9: Phenytoin) (Controls unexposed, sick; 10: Phenytoin) (Controls unexposed, sick; 11: Phenytoin) (Controls unexposed, sick) ; 12: Phenytoin; 13: Phenytoin; 14: Phenytoin; 15: Phenytoin) (Controls unexposed, sick; 16: Phenytoin; 17: Phenytoin; 18: Phenytoin; 19: Phenytoin) (Controls unexposed, NOS) (Mixed indications; 20: Phenytoin) (Controls unexposed, sick; 21: Phenytoin) (Controls unexposed, sick;
Asymetry test p-value = 0.1312 (by Egger's regression)
slope=0.2957 (0.3040); intercept=0.7488 (0.4747); t=1.5774; p=0.1312
excluded 9236, 9194, 9204, 9202, 9238, 9209, 9210, 9206, 9198, 9247, 9192, 12697, 12850, 12851, 9200