Levetiracetam (All indications)

Small for gestational age (weight)

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.
S15220
R62419
Bromley (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Small for gestation (calculated using gender-specific scales) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.67 [0.24;1.86] C
excluded (control group)
6/70   13/106 19 70
ref
S15219
R62406
Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Small for gestation (calculated using gender-specific scales) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.48 [0.17;1.35] C 6/70   13/80 19 70
ref
S12549
R47239
Dreier (Levetiracetam), 2021 Small for gestational age (birth weight below the 10th percentile for GA, sex and country) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 1.13 [0.92;1.39] -/1,019   -/- - 1,019
ref
S12618
R47566
Van Marter (Levetiracetam) (Controls unexposed, disease free), 2021 Small for gestational age (weight for gestational age <10th percentile) at least 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 0.75 [0.26;2.19] C
excluded (control group)
6/89   9/102 15 89
ref
S12615
R47548
Van Marter (Levetiracetam) (Controls unexposed, sick), 2021 Small for gestational age (weight for gestational age <10th percentile) at least 1st trimester prospective cohort unexposed, sick Adjustment: No 2.13 [0.11;39.98] C 6/89   0/14 6 89
ref
S8986
R30513
Aydin (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Small for gestational age (birth weight) throughout pregnancy retrospective cohort exposed to other treatment, sick excluded Adjustment: No 7.00 [0.30;164.40] C
excluded (control group)
3/10   0/7 3 10
ref
S8987
R30523
Aydin (Levetiracetam) (Controls unexposed, sick), 2020 Small for gestational age (birth weight) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 23.15 [1.05;509.05] C 3/10   0/22 3 10
ref
S9020
R30711
Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Small for gestational age (weight) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.40 [1.11;1.77] C 82/621   167,376/1,710,441 167,458 621
ref
S9029
R30780
Bank (Levetiracetam) (Mixed indications), 2017 Small for Gestational Age birthweight (<10th percentile) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 1.83 [0.16;20.71] C 1/7   3/36 4 7
ref
S9030
R30787
Kilic (Levetiracetam) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Small for gestational age (birth weight <10% percentile for the gestational birth week) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 1.33 [0.39;4.54] C
excluded (control group)
3/26   78/876 81 26
ref
S9031
R30790
Kilic (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2014 Small for gestational age (birth weight <10% percentile for the gestational birth week) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: No 1.22 [0.37;4.06] C
excluded (control group)
3/26   65,118/673,844 65,121 26
ref
S9032
R30793
Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 Small for gestational age (birth weight <10% percentile for the gestational birth week) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 1.03 [0.31;3.43] C 3/26   594/5,275 597 26
ref
S8983
R30484
Artama (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2013 Small for gestational age (weight) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 2.73 [0.12;59.97] C
excluded (control group)
0/13   2/173 2 13
ref
S8984
R30496
Artama (Levetiracetam) (Controls unexposed, disease free), 2013 Small for gestational age (weight) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: No 2.00 [0.12;33.85] C
excluded (control group)
0/13   14,079/719,509 14,079 13
ref
S8985
R30508
Artama (Levetiracetam) (Controls unexposed, sick), 2013 Small for gestational age (weight) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No 1.65 [0.10;28.29] C 0/13   42/1,793 42 13
ref
Total 8 studies 1.22 [0.96;1.54] 168,129 1,855
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 Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Bromley, 2023 1 0.48[0.17; 1.35]19705%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: low Dreier (Levetiracetam), 2021Dreier, 2021 2 1.13[0.92; 1.39]-1,01946%ROB confusion: unclearROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Van Marter (Levetiracetam) (Controls unexposed, sick), 2021Van Marter, 2021 3 2.13[0.11; 39.98]6891%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: low Aydin (Levetiracetam) (Controls unexposed, sick), 2020Aydin, 2020 4 23.15[1.05; 509.05]3101%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Coste (Levetiracetam) (Controls unexposed, NOS), 2020Coste, 2020 5 1.40[1.11; 1.77]167,45862142%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Bank (Levetiracetam) (Mixed indications), 2017Bank, 2017 6 1.83[0.16; 20.71]471%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014Kilic, 2014 7 1.03[0.31; 3.43]597264%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Artama (Levetiracetam) (Controls unexposed, sick), 2013Artama, 2013 8 1.65[0.10; 28.29]42131%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (8 studies) I2 = 21% 1.22[0.96; 1.54]168,1291,8550.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Levetiracetam) (Epilepsy) (Controls unexposed, sick; 2: Levetiracetam; 3: Levetiracetam) (Controls unexposed, sick; 4: Levetiracetam) (Controls unexposed, sick; 5: Levetiracetam) (Controls unexposed, NOS; 6: Levetiracetam) (Mixed indications; 7: Levetiracetam) (Controls unexposed, sick) (Mixed indications; 8: Levetiracetam) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.22[0.96; 1.54]168,1291,85521%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Dreier (Levetiracetam), 2021 Van Marter (Levetiracetam) (Controls unexposed, sick), 2021 Aydin (Levetiracetam) (Controls unexposed, sick), 2020 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Bank (Levetiracetam) (Mixed indications), 2017 Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 Artama (Levetiracetam) (Controls unexposed, sick), 2013 8 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.40[1.11; 1.77]167,458621 -NACoste (Levetiracetam) (Controls unexposed, NOS), 2020 1 unexposed, sickunexposed, sick 1.07[0.64; 1.79]6671,22724%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Dreier (Levetiracetam), 2021 Van Marter (Levetiracetam) (Controls unexposed, sick), 2021 Aydin (Levetiracetam) (Controls unexposed, sick), 2020 Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 Artama (Levetiracetam) (Controls unexposed, sick), 2013 6 exposed to other treatment, sickexposed to other treatment, sick 1.83[0.16; 20.71]47 -NABank (Levetiracetam) (Mixed indications), 2017 1 Tags Adjustment   - No  - No 1.23[0.75; 2.03]168,12983621%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Van Marter (Levetiracetam) (Controls unexposed, sick), 2021 Aydin (Levetiracetam) (Controls unexposed, sick), 2020 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Bank (Levetiracetam) (Mixed indications), 2017 Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 Artama (Levetiracetam) (Controls unexposed, sick), 2013 7   - Yes  - Yes 1.13[0.92; 1.39]-1,019 -NADreier (Levetiracetam), 2021 1 Controls   - epilepsy indication  - epilepsy indication 1.03[0.31; 3.43]59726 -NAKilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 1 All studiesAll studies 1.22[0.96; 1.54]168,1291,85521%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Dreier (Levetiracetam), 2021 Van Marter (Levetiracetam) (Controls unexposed, sick), 2021 Aydin (Levetiracetam) (Controls unexposed, sick), 2020 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Bank (Levetiracetam) (Mixed indications), 2017 Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 Artama (Levetiracetam) (Controls unexposed, sick), 2013 80.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.83.91.8920.000Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Dreier (Levetiracetam), 2021Van Marter (Levetiracetam) (Controls unexposed, sick), 2021Aydin (Levetiracetam) (Controls unexposed, sick), 2020Coste (Levetiracetam) (Controls unexposed, NOS), 2020Bank (Levetiracetam) (Mixed indications), 2017Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014Artama (Levetiracetam) (Controls unexposed, sick), 2013

Asymetry test p-value = 0.7009 (by Egger's regression)

slope=0.1723 (0.1226); intercept=0.2275 (0.5644); t=0.4031; p=0.7009

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8983, 8984, 9030, 9031, 8986, 12618, 15220

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.36[1.09; 1.70]246,6737490%NAVan Marter (Levetiracetam) (Controls unexposed, disease free), 2021 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Kilic (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2014 Artama (Levetiracetam) (Controls unexposed, disease free), 2013 4 unexposed, sick controlsunexposed, sick controls 1.07[0.64; 1.79]6671,22724%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Dreier (Levetiracetam), 2021 Van Marter (Levetiracetam) (Controls unexposed, sick), 2021 Aydin (Levetiracetam) (Controls unexposed, sick), 2020 Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 Artama (Levetiracetam) (Controls unexposed, sick), 2013 6 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.11[0.55; 2.25]1091260%NABromley (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Aydin (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Bank (Levetiracetam) (Mixed indications), 2017 Kilic (Levetiracetam) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Artama (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2013 50.510.01.0