Carbamazepine (Epilepsy)

Microcephaly / Small head circumference for gestational age

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.
S5511
R17498		 Pennell (Carbamazepine), 2012 Microcephaly at birth (head circumference < 3 percentile) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 2.51 [0.90;7.05] C 13/69   6/71 19 69
ref
S7181
R20260		 Kini (Carbamazepine) (Controls unexposed, sick), 2006 Head circumference in children aged between 6 months and 16 years <3rd centile during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No 0.42 [0.08;2.21] C 2/94   5/101 7 94
ref
S5863
R14570		 Holmes (Carbamazepine) (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 2.31 [0.48;11.18] C
excluded (control group) 		2/56   8/508 10 56
ref
S5864
R14578		 Holmes (Carbamazepine) (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 1.74 [0.24;12.71] C 2/56   2/96 4 56
ref
S315
R17689		 Battino (Carbamazepine), 1999 Small head circumferences (at birth < 10th percentile) throughout pregnancy prospective cohort unexposed, sick Adjustment: Yes 0.50 [0.11;2.00] 7/128   3/30 10 128
ref
S5701
R19088		 Díaz-Romero (Carbamazepine), 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 0.29 [0.01;16.12] C 0/26   0/8 0 26
ref
Total 5 studies 1.02 [0.43;2.44] 40 373
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 Pennell (Carbamazepine), 2012Pennell, 2012 1 2.51[0.90; 7.05]196936%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kini (Carbamazepine) (Controls unexposed, sick), 2006Kini, 2006 2 0.42[0.08; 2.21]79420%ROB confusion: criticalROB selection: criticalROB classification: lowROB missing: unclearROB mesure: moderateROB reporting: moderate Holmes (Carbamazepine) (Controls unexposed, sick), 2001Holmes, 2001 3 1.74[0.24; 12.71]45615%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Battino (Carbamazepine), 1999Battino, 1999 4 0.50[0.11; 2.00]1012824%ROB confusion: moderateROB selection: lowROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Díaz-Romero (Carbamazepine), 1999Díaz-Romero, 1999 5 0.29[0.01; 16.12]0264%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 27% 1.02[0.43; 2.44]403730.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Carbamazepine; 2: Carbamazepine) (Controls unexposed, sick; 3: Carbamazepine) (Controls unexposed, sick; 4: Carbamazepine; 5: Carbamazepine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.02[0.43; 2.44]4037327%NAPennell (Carbamazepine), 2012 Kini (Carbamazepine) (Controls unexposed, sick), 2006 Holmes (Carbamazepine) (Controls unexposed, sick), 2001 Battino (Carbamazepine), 1999 Díaz-Romero (Carbamazepine), 1999 5 case control studiescase control studies 0 Type of controls unexposed, sickunexposed, sick 0.60[0.24; 1.53]213040%NAKini (Carbamazepine) (Controls unexposed, sick), 2006 Holmes (Carbamazepine) (Controls unexposed, sick), 2001 Battino (Carbamazepine), 1999 Díaz-Romero (Carbamazepine), 1999 4 exposed to other treatment, sickexposed to other treatment, sick 2.51[0.90; 7.05]1969 -NAPennell (Carbamazepine), 2012 1 Tags Adjustment   - No  - No 1.29[0.48; 3.46]3024523%NAPennell (Carbamazepine), 2012 Kini (Carbamazepine) (Controls unexposed, sick), 2006 Holmes (Carbamazepine) (Controls unexposed, sick), 2001 Díaz-Romero (Carbamazepine), 1999 4   - Yes  - Yes 0.50[0.12; 2.13]10128 -NABattino (Carbamazepine), 1999 1 All studiesAll studies 1.02[0.43; 2.44]4037327%NAPennell (Carbamazepine), 2012 Kini (Carbamazepine) (Controls unexposed, sick), 2006 Holmes (Carbamazepine) (Controls unexposed, sick), 2001 Battino (Carbamazepine), 1999 Díaz-Romero (Carbamazepine), 1999 50.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.84.82.4510.000Pennell (Carbamazepine), 2012Kini (Carbamazepine) (Controls unexposed, sick), 2006Holmes (Carbamazepine) (Controls unexposed, sick), 2001Battino (Carbamazepine), 1999Díaz-Romero (Carbamazepine), 1999

Asymetry test p-value = 0.3243 (by Egger's regression)

slope=1.3288 (1.0878); intercept=-1.6224 (1.3792); t=1.1764; p=0.3243

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5863

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.31[0.48; 11.18]1056 -NAHolmes (Carbamazepine) (Controls unexposed, disease free), 2001 1 unexposed, sick controlsunexposed, sick controls 0.60[0.24; 1.53]213040%NAKini (Carbamazepine) (Controls unexposed, sick), 2006 Holmes (Carbamazepine) (Controls unexposed, sick), 2001 Battino (Carbamazepine), 1999 Díaz-Romero (Carbamazepine), 1999 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 2.51[0.90; 7.05]1969 -NAPennell (Carbamazepine), 2012 10.510.01.0