Phenobarbital (Epilepsy)

All congenital malformations (majors, minors, majors and minors, or unspecified)

R analysis
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.
S12834
R48342		 Thomas (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2021 Major congenital malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 3.04 [0.37;24.93] C
excluded (control group) 		8/137   1/50 9 137
ref
S7550
R26952		 Thomas (Phenobarbital) (Controls unexposed, disease free), 2021 Major congenital malformations 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 1.57 [0.62;3.97]
excluded (control group) 		7/129   11/319 18 129
ref
S12835
R48352		 Thomas (Phenobarbital) (Controls unexposed, sick), 2021 Major congenital malformations 1st trimester prospective cohort unexposed, sick Adjustment: Yes 1.20 [0.50;2.70] 8/137   16/340 24 137
ref
S7786
R35181		 Vajda (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2019 Fetal malformations at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 6.27 [0.25;158.67] C
excluded (control group) 		0/2   20/406 20 2
ref
S7787
R35182		 Vajda (Phenobarbital) (Controls unexposed, sick), 2019 Fetal malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 10.33 [0.38;283.37] C 0/2   5/176 5 2
ref
S7660
R26954		 Tomson (Phenobarbital), 2018 Major congenital malformation at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 2.28 [1.36;3.83] C 19/294   74/2,514 93 294
ref
S6723
R30020		 Barroso (Phenobarbital), 2015 Major anomalies during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, disease free Adjustment: No 2.11 [0.68;6.62] C
excluded (exposition period) 		4/32   20/316 24 32
ref
S6321
R26955		 Veiby (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2014 Major malformations throughout pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.69 [0.04;11.87] C
excluded (control group) 		0/18   23/593 23 18
ref
S6322
R26956		 Veiby (Phenobarbital) (Controls unexposed, disease free), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, disease free excluded Adjustment: No 0.96 [0.06;15.91] C
excluded (control group) 		0/18   22,371/771,412 22,371 18
ref
S6323
R26957		 Veiby (Phenobarbital) (Controls unexposed, sick), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, sick Adjustment: No 0.98 [0.06;16.47] C 0/18   106/3,773 106 18
ref
S5941
R26941		 Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012 Major congenital malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Controls: mixed indications 2.50 [0.90;6.80]
excluded (control group) 		-/-   -/- - -
ref
S7936
R26942		 Hernández-Díaz (Phenobarbital) (Controls unexposed, disease free), 2012 Major congenital malformations 1st trimester prospective cohort unexposed, disease free Adjustment: No 5.10 [1.80;14.90] 11/199   5/442 16 199
ref
S6500
R35122		 Bànhidy (Phenobarbital), 2011 Total congenital abnormalities throughout pregnancy case control unexposed, sick Adjustment: No Matched 2.48 [0.09;68.14] C 1/1   12/22 13 1
ref
S6624
R18204		 Burja (Phenobarbital) (Controls unexposed, disease free), 2006 Congenital malformation during pregnancy (anytime or not specified) retrospective cohort (registry) unexposed, disease free excluded Adjustment: No 37.36 [0.68;2061.38] C
excluded (control group) 		0/1   5/211 5 1
ref
S6620
R18184		 Burja (Phenobarbital) (Controls unexposed, sick), 2006 Congenital malformation during pregnancy (anytime or not specified) excluded retrospective cohort (registry) unexposed, sick Adjustment: No 63.00 [0.51;7760.63] C
excluded (exposition period) 		0/1   0/32 0 1
ref
S5590
R19021		 Endo (Phenobarbital) (Controls unexposed, disease free), 2004 Congenital malformations throughout pregnancy retrospective cohort unexposed, disease free excluded Adjustment: No 1.20 [0.07;21.20] C
excluded (control group) 		0/10   27/656 27 10
ref
S8225
R25803		 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Congenital malformations throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 0.05 [0.00;6.68] C 0/10   0/1 0 10
ref
S6139
R26945		 Kaaja (Phenobarbital), 2003 Major malformation 1st trimester prospective cohort unexposed, sick Adjustment: No 10.51 [0.44;251.86] C 0/5   2/239 2 5
ref
S6678
R18495		 Dean (Phenobarbital), 2002 Congenital malformations (major and minor) at least 1st trimester retrospective cohort unexposed, sick Adjustment: No 4.01 [1.53;10.50] C 29/61   7/38 36 61
ref
S5865
R26943		 Holmes (Phenobarbital) (Controls unexposed, disease free), 2001 Major malformations during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free excluded Adjustment: Yes 2.70 [0.60;16.40]
excluded (control group) 		3/64   9/508 12 64
ref
S5866
R26944		 Holmes (Phenobarbital) (Controls unexposed, sick), 2001 Major malformations during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, sick Adjustment: No 11.28 [0.57;222.22] C
excluded (exposition period) 		3/64   0/98 3 64
ref
S8351
R26465		 Al Bunyan (Phenobarbital), 1999 Congenital malformations during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, sick Adjustment: No 6.33 [0.09;458.24] C
excluded (exposition period) 		0/2   0/10 0 2
ref
S7171
R26576		 Canger (Phenobarbital), 1999 All type of malformation 1st trimester prospective cohort unexposed, sick Adjustment: No 2.81 [0.15;54.03] C 4/83   0/25 4 83
ref
S6440
R17694		 Kaneko (Phenobarbital), 1999 Malformations throughout pregnancy prospective cohort unexposed, sick Adjustment: No 1.58 [0.34;7.28] C 4/84   3/98 7 84
ref
S5515
R26949		 Samrén (Phenobarbital), 1999 Major congential abnormalities at least 1st trimester retrospective cohort unexposed, disease free Adjustment: No Matched 1.96 [0.75;5.14] C 5/178   29/2,000 34 178
ref
S6708
R26950		 Steegers-Theunissen (Phenobarbital), 1994 Major malformations (ICD9 British Paediatric Association System) during pregnancy (anytime or not specified) excluded prospective cohort unexposed, disease free Adjustment: No 1.80 [0.08;39.83] C
excluded (exposition period) 		0/12   2/106 2 12
ref
S6686
R18608		 D'Souza (Phenobarbital) (Controls unexposed, disease free), 1991 Congenital anomalies throughout pregnancy prospective cohort unexposed, disease free excluded Adjustment: No Matched 73.80 [2.36;2304.87] C
excluded (control group) 		1/4   0/62 1 4
ref
S6694
R18769		 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Congenital anomalies throughout pregnancy prospective cohort unexposed, sick Adjustment: No 2.33 [0.11;50.99] C 1/4   1/8 2 4
ref
S5514
R16406		 Robert (Phenobarbital), 1986 Congenital malformations (minor and major) 1st trimester retrospective cohort unexposed, sick Adjustment: No 1.37 [0.35;5.31] C 6/40   4/35 10 40
ref
S6953
R26948		 Kelly (Phenobarbital), 1984 Major abnormality during pregnancy (anytime or not specified) excluded prospective cohort unexposed, sick Adjustment: No 0.52 [0.02;13.80] C
excluded (exposition period) 		0/13   1/21 1 13
ref
S6586
R18064		 Lowe (Phenobarbital) (Controls unexposed, disease free), 1973 Malformations 1st trimester population based cohort retrospective unexposed, disease free excluded Adjustment: No 0.68 [0.09;4.95] C
excluded (control group) 		1/53   865/31,632 866 53
ref
S6589
R18070		 Lowe (Phenobarbital) (Controls unexposed, sick), 1973 Malformations 1st trimester population based cohort retrospective unexposed, sick Adjustment: No 0.69 [0.07;6.82] C 1/53   3/111 4 53
ref
Total 15 studies 2.20 [1.61;3.02] 356 1,169
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

Forest plot

StudyTE95% CIn casesn exposedweightROBABCDEF Thomas (Phenobarbital) (Controls unexposed, sick), 2021Thomas, 2021 1 1.20[0.50; 2.70]2413714%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Vajda (Phenobarbital) (Controls unexposed, sick), 2019Vajda, 2019 2 10.33[0.38; 283.37]521%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Tomson (Phenobarbital), 2018Tomson, 2018 3 2.28[1.36; 3.83]9329437%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Veiby (Phenobarbital) (Controls unexposed, sick), 2014Veiby, 2014 4 0.98[0.06; 16.47]106181%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Hernández-Díaz (Phenobarbital) (Controls unexposed, disease free), 2012Hernández-Díaz, 2012 5 5.10[1.80; 14.90]161999%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Bànhidy (Phenobarbital), 2011Bànhidy, 2011 6 2.48[0.09; 68.14]1311%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Endo (Phenobarbital) (Controls unexposed, sick), 2004Endo, 2004 7 0.05[0.00; 6.68]0100%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kaaja (Phenobarbital), 2003Kaaja, 2003 8 10.51[0.44; 251.86]251%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Dean (Phenobarbital), 2002Dean, 2002 9 4.01[1.53; 10.50]366111%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Canger (Phenobarbital), 1999Canger, 1999 10 2.81[0.15; 54.03]4831%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kaneko (Phenobarbital), 1999Kaneko, 1999 11 1.58[0.34; 7.28]7844%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Samrén (Phenobarbital), 1999Samrén, 1999 12 1.96[0.75; 5.14]3417811%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA D'Souza (Phenobarbital) (Controls unexposed, sick), 1991D'Souza, 1991 13 2.33[0.11; 50.99]241%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Robert (Phenobarbital), 1986Robert, 1986 14 1.37[0.35; 5.31]10405%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Lowe (Phenobarbital) (Controls unexposed, sick), 1973Lowe, 1973 15 0.69[0.07; 6.82]4532%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (15 studies) I2 = 0% 2.20[1.61; 3.02]3561,1690.050.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Phenobarbital) (Controls unexposed, sick; 2: Phenobarbital) (Controls unexposed, sick; 3: Phenobarbital; 4: Phenobarbital) (Controls unexposed, sick; 5: Phenobarbital) (Controls unexposed, disease free; 6: Phenobarbital; 7: Phenobarbital) (Controls unexposed, sick; 8: Phenobarbital; 9: Phenobarbital; 10: Phenobarbital; 11: Phenobarbital; 12: Phenobarbital; 13: Phenobarbital) (Controls unexposed, sick; 14: Phenobarbital; 15: Phenobarbital) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.20[1.60; 3.02]3431,1680%NAThomas (Phenobarbital) (Controls unexposed, sick), 2021 Vajda (Phenobarbital) (Controls unexposed, sick), 2019 Tomson (Phenobarbital), 2018 Veiby (Phenobarbital) (Controls unexposed, sick), 2014 Hernández-Díaz (Phenobarbital) (Controls unexposed, disease free), 2012 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Kaaja (Phenobarbital), 2003 Dean (Phenobarbital), 2002 Canger (Phenobarbital), 1999 Kaneko (Phenobarbital), 1999 Samrén (Phenobarbital), 1999 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Robert (Phenobarbital), 1986 Lowe (Phenobarbital) (Controls unexposed, sick), 1973 14 case control studiescase control studies 2.48[0.09; 68.14]131 -NABànhidy (Phenobarbital), 2011 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.08[1.21; 7.84]5037742%NAHernández-Díaz (Phenobarbital) (Controls unexposed, disease free), 2012 Samrén (Phenobarbital), 1999 2 unexposed, sickunexposed, sick 1.85[1.15; 3.00]2134980%NAThomas (Phenobarbital) (Controls unexposed, sick), 2021 Vajda (Phenobarbital) (Controls unexposed, sick), 2019 Veiby (Phenobarbital) (Controls unexposed, sick), 2014 Bànhidy (Phenobarbital), 2011 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Kaaja (Phenobarbital), 2003 Dean (Phenobarbital), 2002 Canger (Phenobarbital), 1999 Kaneko (Phenobarbital), 1999 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Robert (Phenobarbital), 1986 Lowe (Phenobarbital) (Controls unexposed, sick), 1973 12 exposed to other treatment, sickexposed to other treatment, sick 2.28[1.36; 3.83]93294 -NATomson (Phenobarbital), 2018 1 Tags Adjustment   - No  - No 2.43[1.73; 3.42]3321,0320%NAVajda (Phenobarbital) (Controls unexposed, sick), 2019 Tomson (Phenobarbital), 2018 Veiby (Phenobarbital) (Controls unexposed, sick), 2014 Hernández-Díaz (Phenobarbital) (Controls unexposed, disease free), 2012 Bànhidy (Phenobarbital), 2011 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Kaaja (Phenobarbital), 2003 Dean (Phenobarbital), 2002 Canger (Phenobarbital), 1999 Kaneko (Phenobarbital), 1999 Samrén (Phenobarbital), 1999 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Robert (Phenobarbital), 1986 Lowe (Phenobarbital) (Controls unexposed, sick), 1973 14   - Yes  - Yes 1.20[0.52; 2.79]24137 -NAThomas (Phenobarbital) (Controls unexposed, sick), 2021 1 MatchedMatched 2.00[0.79; 5.04]471790%NABànhidy (Phenobarbital), 2011 Samrén (Phenobarbital), 1999 2 All studiesAll studies 2.20[1.61; 3.02]3561,1690%NAThomas (Phenobarbital) (Controls unexposed, sick), 2021 Vajda (Phenobarbital) (Controls unexposed, sick), 2019 Tomson (Phenobarbital), 2018 Veiby (Phenobarbital) (Controls unexposed, sick), 2014 Hernández-Díaz (Phenobarbital) (Controls unexposed, disease free), 2012 Bànhidy (Phenobarbital), 2011 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Kaaja (Phenobarbital), 2003 Dean (Phenobarbital), 2002 Canger (Phenobarbital), 1999 Kaneko (Phenobarbital), 1999 Samrén (Phenobarbital), 1999 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Robert (Phenobarbital), 1986 Lowe (Phenobarbital) (Controls unexposed, sick), 1973 150.050.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.86.62.9650.000Thomas (Phenobarbital) (Controls unexposed, sick), 2021Vajda (Phenobarbital) (Controls unexposed, sick), 2019Tomson (Phenobarbital), 2018Veiby (Phenobarbital) (Controls unexposed, sick), 2014Hernández-Díaz (Phenobarbital) (Controls unexposed, disease free), 2012Bànhidy (Phenobarbital), 2011Endo (Phenobarbital) (Controls unexposed, sick), 2004Kaaja (Phenobarbital), 2003Dean (Phenobarbital), 2002Canger (Phenobarbital), 1999Kaneko (Phenobarbital), 1999Samrén (Phenobarbital), 1999D'Souza (Phenobarbital) (Controls unexposed, sick), 1991Robert (Phenobarbital), 1986Lowe (Phenobarbital) (Controls unexposed, sick), 1973

Asymetry test p-value = 0.7162 (by Egger's regression)

slope=0.8738 (0.2731); intercept=-0.1624 (0.4372); t=0.3715; p=0.7162

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6586, 6686, 5865, 5590, 6624, 5941, 6321, 6322, 7786, 12834, 7550

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.24[1.11; 4.52]23,33359132%NAThomas (Phenobarbital) (Controls unexposed, disease free), 2021 Veiby (Phenobarbital) (Controls unexposed, disease free), 2014 Hernández-Díaz (Phenobarbital) (Controls unexposed, disease free), 2012 Endo (Phenobarbital) (Controls unexposed, disease free), 2004 Samrén (Phenobarbital), 1999 D'Souza (Phenobarbital) (Controls unexposed, disease free), 1991 Lowe (Phenobarbital) (Controls unexposed, disease free), 1973 7 unexposed, sick controlsunexposed, sick controls 1.85[1.15; 3.00]2134980%NAThomas (Phenobarbital) (Controls unexposed, sick), 2021 Vajda (Phenobarbital) (Controls unexposed, sick), 2019 Veiby (Phenobarbital) (Controls unexposed, sick), 2014 Bànhidy (Phenobarbital), 2011 Endo (Phenobarbital) (Controls unexposed, sick), 2004 Kaaja (Phenobarbital), 2003 Dean (Phenobarbital), 2002 Canger (Phenobarbital), 1999 Kaneko (Phenobarbital), 1999 D'Souza (Phenobarbital) (Controls unexposed, sick), 1991 Robert (Phenobarbital), 1986 Lowe (Phenobarbital) (Controls unexposed, sick), 1973 12 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.33[1.50; 3.62]1454510%NAThomas (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2021 Vajda (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2019 Tomson (Phenobarbital), 2018 Veiby (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2014 Hernández-Díaz (Phenobarbital) (Controls exposed to Lamotrigine, sick), 2012 50.510.01.0