Carbamazepine (Epilepsy)

Intrauterine deaths (as a whole 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.
S7504
R22448		 Meador (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2020 Fetal loss (Spontaneous miscarriages and fetal death) 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.16 [0.06;23.67] C
excluded (control group) 		0/14   3/113 3 14
ref
S7496
R22424		 Meador (Carbamazepine) (Controls unexposed, disease free), 2020 Fetal loss (Spontaneous miscarriages and fetal death) 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 7.81 [0.15;410.24] C
excluded (control group) 		0/14   0/106 0 14
ref
S7499
R22433		 Meador (Carbamazepine) (Controls unexposed, sick), 2020 Fetal loss (Spontaneous miscarriages and fetal death) 1st trimester prospective cohort unexposed, sick Adjustment: No 1.07 [0.02;58.03] C 0/14   0/15 0 14
ref
S8063
R24569		 Trivedi (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2018 Spontaneous fetal loss (both spontaneous abortion before 20 weeks of gestation and stillbirths occurring after 20 weeks of gestation) 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.68 [0.23;2.03] C
excluded (control group) 		27/465   4/48 31 465
ref
S8057
R24563		 Trivedi (Carbamazepine) (Controls unexposed, sick), 2018 Spontaneous fetal loss (both spontaneous abortion before 20 weeks of gestation and stillbirths occurring after 20 weeks of gestation) 1st trimester prospective cohort unexposed, sick Adjustment: Yes 3.53 [1.15;10.90] 27/465   5/178 32 465
ref
S7756
R22962		 Vajda (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2018 Intrauterine foetal death throughout pregnancy prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.30 [0.64;2.63] C
excluded (control group) 		19/404   14/382 33 404
ref
S7747
R22953		 Vajda (Carbamazepine) (Controls unexposed, sick), 2018 Intrauterine foetal death throughout pregnancy prospective cohort unexposed, sick Adjustment: No 8.00 [1.08;59.25] 19/404   1/170 20 404
ref
S7415
R21826		 Miškov (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2016 Fetal loss during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.50 [0.24;9.35] C
excluded (control group) 		2/13   4/37 6 13
ref
S7043
R19883		 Miškov (Carbamazepine) (Controls unexposed, disease free), 2016 Fetal loss during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No 60.71 [2.73;1349.00] C
excluded (control group) 		2/13   0/128 2 13
ref
S7409
R21798		 Miškov (Carbamazepine) (Controls unexposed, sick), 2016 Fetal loss during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 1.67 [0.06;43.79] C 2/13   0/4 2 13
ref
S6253
R16655		 Arkilo (Carbamazepine), 2015 Unsuccessful pregnancies (miscarriages/stillbirths) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 2.36 [0.35;15.93] C 3/17   2/24 5 17
ref
S333
R16615		 Tomson (Carbamazepine), 2015 Intrauterine death at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 1.08 [0.85;1.37] C 144/1,713   150/1,910 294 1,713
ref
S6290
R16966		 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Intrauterine death 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 0.81 [0.59;1.11] C 67/1,718   105/2,198 172 1,718
ref
S6611
R18137		 Holmes (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2011 Intrauterine death as a whole 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Controls: mixed indications 1.48 [0.57;3.85] C
excluded (control group) 		8/573   9/948 17 573
ref
S5877
R14642		 Holmes (Carbamazepine) (Controls unexposed, disease free), 2011 Intrauterine death as a whole 1st trimester prospective cohort unexposed, disease free Adjustment: No 2.68 [0.33;21.54] C 8/573   1/190 9 573
ref
S5498
R17507		 Meador (Carbamazepine), 2006 Fetal death (early and late intrauterine deaths) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 8.32 [0.44;156.51] C 4/110   0/98 4 110
ref
S5578
R14505		 Diav-Citrin (Carbamazepine), 2001 Intrauterine deaths as a whole at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched 1.30 [0.68;2.47] C 18/108   28/210 46 108
ref
Total 10 studies 1.29 [0.91;1.83] 584 5,135
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 Meador (Carbamazepine) (Controls unexposed, sick), 2020Meador, 2020 1 1.07[0.02; 58.03]0141%ROB confusion: unclearROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: low Trivedi (Carbamazepine) (Controls unexposed, sick), 2018Trivedi, 2018 2 3.53[1.15; 10.90]324658%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Vajda (Carbamazepine) (Controls unexposed, sick), 2018Vajda, 2018 3 8.00[1.08; 59.25]204043%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Miškov (Carbamazepine) (Controls unexposed, sick), 2016Miškov, 2016 4 1.67[0.06; 43.79]2131%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: criticalROB mesure: moderateROB reporting: moderate Arkilo (Carbamazepine), 2015Arkilo, 2015 5 2.36[0.35; 15.93]5173%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Tomson (Carbamazepine), 2015Tomson, 2015 6 1.08[0.85; 1.37]2941,71333%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014Campbell, 2014 7 0.81[0.59; 1.11]1721,71830%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Holmes (Carbamazepine) (Controls unexposed, disease free), 2011Holmes, 2011 8 2.68[0.33; 21.54]95733%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Meador (Carbamazepine), 2006Meador, 2006 9 8.32[0.44; 156.51]41101%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Diav-Citrin (Carbamazepine), 2001Diav-Citrin, 2001 10 1.30[0.68; 2.47]4610817%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (10 studies) I2 = 40% 1.29[0.91; 1.83]5845,1350.220.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Carbamazepine) (Controls unexposed, sick; 2: Carbamazepine) (Controls unexposed, sick; 3: Carbamazepine) (Controls unexposed, sick; 4: Carbamazepine) (Controls unexposed, sick; 5: Carbamazepine; 6: Carbamazepine; 7: Carbamazepine) (Controls exposed to Lamotrigine, sick; 8: Carbamazepine) (Controls unexposed, disease free; 9: Carbamazepine; 10: Carbamazepine;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.29[0.91; 1.83]5845,13540%NAMeador (Carbamazepine) (Controls unexposed, sick), 2020 Trivedi (Carbamazepine) (Controls unexposed, sick), 2018 Vajda (Carbamazepine) (Controls unexposed, sick), 2018 Miškov (Carbamazepine) (Controls unexposed, sick), 2016 Arkilo (Carbamazepine), 2015 Tomson (Carbamazepine), 2015 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Holmes (Carbamazepine) (Controls unexposed, disease free), 2011 Meador (Carbamazepine), 2006 Diav-Citrin (Carbamazepine), 2001 10 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.38[0.75; 2.56]556810%NAHolmes (Carbamazepine) (Controls unexposed, disease free), 2011 Diav-Citrin (Carbamazepine), 2001 2 unexposed, sickunexposed, sick 3.71[1.49; 9.25]548960%NAMeador (Carbamazepine) (Controls unexposed, sick), 2020 Trivedi (Carbamazepine) (Controls unexposed, sick), 2018 Vajda (Carbamazepine) (Controls unexposed, sick), 2018 Miškov (Carbamazepine) (Controls unexposed, sick), 2016 4 exposed to other treatment, sickexposed to other treatment, sick 1.00[0.72; 1.37]4753,55839%NAArkilo (Carbamazepine), 2015 Tomson (Carbamazepine), 2015 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Meador (Carbamazepine), 2006 4 Tags Adjustment   - No  - No 1.10[0.83; 1.47]5524,67024%NAMeador (Carbamazepine) (Controls unexposed, sick), 2020 Vajda (Carbamazepine) (Controls unexposed, sick), 2018 Miškov (Carbamazepine) (Controls unexposed, sick), 2016 Arkilo (Carbamazepine), 2015 Tomson (Carbamazepine), 2015 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Holmes (Carbamazepine) (Controls unexposed, disease free), 2011 Meador (Carbamazepine), 2006 Diav-Citrin (Carbamazepine), 2001 9   - Yes  - Yes 3.53[1.15; 10.87]32465 -NATrivedi (Carbamazepine) (Controls unexposed, sick), 2018 1 MatchedMatched 1.30[0.68; 2.47]46108 -NADiav-Citrin (Carbamazepine), 2001 1 All studiesAll studies 1.29[0.91; 1.83]5845,13540%NAMeador (Carbamazepine) (Controls unexposed, sick), 2020 Trivedi (Carbamazepine) (Controls unexposed, sick), 2018 Vajda (Carbamazepine) (Controls unexposed, sick), 2018 Miškov (Carbamazepine) (Controls unexposed, sick), 2016 Arkilo (Carbamazepine), 2015 Tomson (Carbamazepine), 2015 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Holmes (Carbamazepine) (Controls unexposed, disease free), 2011 Meador (Carbamazepine), 2006 Diav-Citrin (Carbamazepine), 2001 100.220.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.02.4430.000Meador (Carbamazepine) (Controls unexposed, sick), 2020Trivedi (Carbamazepine) (Controls unexposed, sick), 2018Vajda (Carbamazepine) (Controls unexposed, sick), 2018Miškov (Carbamazepine) (Controls unexposed, sick), 2016Arkilo (Carbamazepine), 2015Tomson (Carbamazepine), 2015Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014Holmes (Carbamazepine) (Controls unexposed, disease free), 2011Meador (Carbamazepine), 2006Diav-Citrin (Carbamazepine), 2001

Asymetry test p-value = 0.0214 (by Egger's regression)

slope=-0.1681 (0.1190); intercept=1.1903 (0.4173); t=2.8526; p=0.0214

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 6611, 7415, 7043, 8063, 7756, 7504, 7496

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.68[0.78; 17.46]5770854%NAMeador (Carbamazepine) (Controls unexposed, disease free), 2020 Miškov (Carbamazepine) (Controls unexposed, disease free), 2016 Holmes (Carbamazepine) (Controls unexposed, disease free), 2011 Diav-Citrin (Carbamazepine), 2001 4 unexposed, sick controlsunexposed, sick controls 3.71[1.49; 9.25]548960%NAMeador (Carbamazepine) (Controls unexposed, sick), 2020 Trivedi (Carbamazepine) (Controls unexposed, sick), 2018 Vajda (Carbamazepine) (Controls unexposed, sick), 2018 Miškov (Carbamazepine) (Controls unexposed, sick), 2016 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.01[0.85; 1.21]5655,0270%NAMeador (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2020 Trivedi (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2018 Vajda (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2018 Miškov (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2016 Arkilo (Carbamazepine), 2015 Tomson (Carbamazepine), 2015 Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2014 Holmes (Carbamazepine) (Controls exposed to Lamotrigine, sick), 2011 Meador (Carbamazepine), 2006 90.510.01.0