Levetiracetam (All indications) updated on 04-22-2025

Preterm (< 37 weeks)

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.
S16096
R66789		 Hoeltzenbein (Levetiracetam), 2024 Preterm birth (birth before completed gestational week 37) at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: Yes 1.47 [0.74;2.93] 21/197   30/432 51 197
ref
S15220
R62418		 Bromley (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Preterm birth (gestational age < 37 weeks) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No 0.67 [0.26;1.75] C
excluded (control group) 		7/70   15/106 22 70
ref
S15219
R62405		 Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 Preterm birth (gestational age < 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No 0.70 [0.25;1.91] C 7/70   11/80 18 70
ref
S12618
R47567		 Van Marter (Levetiracetam) (Controls unexposed, disease free), 2021 Premature (≤36 wk) at least 1st trimester prospective cohort unexposed, disease free excluded Adjustment: No 1.10 [0.46;2.68] C
excluded (control group) 		11/97   11/106 22 97
ref
S12615
R47549		 Van Marter (Levetiracetam) (Controls unexposed, sick), 2021 Premature (≤36 wk) at least 1st trimester prospective cohort unexposed, sick Adjustment: No 1.79 [0.21;14.97] C 11/97   1/15 12 97
ref
S8986
R30511		 Aydin (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Preterm delivery (before 37 weeks of gestation) throughout pregnancy retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.68 [0.01;39.07] C
excluded (control group) 		0/10   0/7 0 10
ref
S8987
R30521		 Aydin (Levetiracetam) (Controls unexposed, sick), 2020 Preterm delivery (before 37 weeks of gestation) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No 0.41 [0.02;9.43] C 0/10   2/22 2 10
ref
S10071
R36651		 Coste (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Gestational age at birth (< 37 WA) during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.35 [0.96;1.89] C
excluded (control group) 		51/621   131/2,108 182 621
ref
S9020
R30708		 Coste (Levetiracetam) (Controls unexposed, NOS), 2020 Gestational age at birth (< 37 WA) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.59 [1.19;2.11] C 51/621   91,255/1,710,441 91,306 621
ref
S18026
R75962		 Margulis (Levetiracetam) (Epilepsy), 2019 Preterm birth (delivery before 37 completed weeks) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick Adjustment: Yes 1.40 [0.70;2.80] -/126   -/1,787 - 126
ref
S9029
R30779		 Bank (Levetiracetam) (Mixed indications), 2017 Premature (<37 weeks gestation) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No 1.77 [0.06;48.38] C 0/7   1/36 1 7
ref
S8982
R30469		 Arkilo (Levetiracetam), 2015 Premature delivery during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No 1.56 [0.22;10.96] C 2/11   3/24 5 11
ref
S9030
R30788		 Kilic (Levetiracetam) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.38 [0.05;2.87] C
excluded (control group) 		1/26   83/880 84 26
ref
S9031
R30791		 Kilic (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) excluded Adjustment: No 0.76 [0.10;5.59] C
excluded (control group) 		1/26   33,974/676,834 33,975 26
ref
S9032
R30794		 Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 Preterm (< 37 weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 0.51 [0.07;3.80] C 1/26   383/5,296 384 26
ref
S8983
R30482		 Artama (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2013 Preterm birth (<37 gestational weeks) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 3.75 [0.71;19.83] C
excluded (control group) 		2/13   8/173 10 13
ref
S8984
R30494		 Artama (Levetiracetam) (Controls unexposed, disease free), 2013 Preterm birth (<37 gestational weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: Yes 3.54 [0.77;16.36]
excluded (control group) 		2/13   30,027/719,509 30,029 13
ref
S8985
R30506		 Artama (Levetiracetam) (Controls unexposed, sick), 2013 Preterm birth (<37 gestational weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes 3.33 [0.67;16.56] 2/13   85/1,793 87 13
ref
Total 10 studies 1.48 [1.17;1.86] 91,866 1,178
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 Hoeltzenbein (Levetiracetam), 2024Hoeltzenbein, 2024 1 1.47[0.74; 2.93]5119711%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: critical Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Bromley, 2023 2 0.70[0.25; 1.91]18705%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: low Van Marter (Levetiracetam) (Controls unexposed, sick), 2021Van Marter, 2021 3 1.79[0.21; 14.97]12971%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: low Aydin (Levetiracetam) (Controls unexposed, sick), 2020Aydin, 2020 4 0.41[0.02; 9.43]2101%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Coste (Levetiracetam) (Controls unexposed, NOS), 2020Coste, 2020 5 1.59[1.19; 2.11]91,30662165%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Margulis (Levetiracetam) (Epilepsy), 2019Margulis, 2019 6 1.40[0.70; 2.80]-12611%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Bank (Levetiracetam) (Mixed indications), 2017Bank, 2017 7 1.77[0.06; 48.38]170%ROB confusion: criticalROB selection: lowROB classification: lowROB missing: lowROB mesure: moderateROB reporting: moderate Arkilo (Levetiracetam), 2015Arkilo, 2015 8 1.56[0.22; 10.96]5111%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014Kilic, 2014 9 0.51[0.07; 3.80]384261%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Artama (Levetiracetam) (Controls unexposed, sick), 2013Artama, 2013 10 3.33[0.67; 16.56]87132%ROB confusion: moderateROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Total (10 studies) I2 = 0% 1.48[1.17; 1.86]91,8661,1780.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Levetiracetam; 2: Levetiracetam) (Epilepsy) (Controls unexposed, sick; 3: Levetiracetam) (Controls unexposed, sick; 4: Levetiracetam) (Controls unexposed, sick; 5: Levetiracetam) (Controls unexposed, NOS; 6: Levetiracetam) (Epilepsy; 7: Levetiracetam) (Mixed indications; 8: Levetiracetam; 9: Levetiracetam) (Controls unexposed, sick) (Mixed indications; 10: Levetiracetam) (Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.48[1.17; 1.86]91,8661,1780%NAHoeltzenbein (Levetiracetam), 2024 Bromley (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 Margulis (Levetiracetam) (Epilepsy), 2019 Bank (Levetiracetam) (Mixed indications), 2017 Arkilo (Levetiracetam), 2015 Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 Artama (Levetiracetam) (Controls unexposed, sick), 2013 10 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.59[1.19; 2.11]91,306621 -NACoste (Levetiracetam) (Controls unexposed, NOS), 2020 1 unexposed, sickunexposed, sick 0.99[0.48; 2.03]5032160%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 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 5 exposed to other treatment, sickexposed to other treatment, sick 1.45[0.91; 2.31]573410%NAHoeltzenbein (Levetiracetam), 2024 Margulis (Levetiracetam) (Epilepsy), 2019 Bank (Levetiracetam) (Mixed indications), 2017 Arkilo (Levetiracetam), 2015 4 Tags Adjustment   - No  - No 1.46[1.12; 1.90]91,7288420%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 Arkilo (Levetiracetam), 2015 Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 7   - Yes  - Yes 1.54[0.97; 2.46]1383360%NAHoeltzenbein (Levetiracetam), 2024 Margulis (Levetiracetam) (Epilepsy), 2019 Artama (Levetiracetam) (Controls unexposed, sick), 2013 3 Controls   - epilepsy indication  - epilepsy indication 0.51[0.07; 3.80]38426 -NAKilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 1 All studiesAll studies 1.48[1.17; 1.86]91,8661,1780%NAHoeltzenbein (Levetiracetam), 2024 Bromley (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 Margulis (Levetiracetam) (Epilepsy), 2019 Bank (Levetiracetam) (Mixed indications), 2017 Arkilo (Levetiracetam), 2015 Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 Artama (Levetiracetam) (Controls unexposed, sick), 2013 100.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.04.42.0260.000Hoeltzenbein (Levetiracetam), 2024Bromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023Van Marter (Levetiracetam) (Controls unexposed, sick), 2021Aydin (Levetiracetam) (Controls unexposed, sick), 2020Coste (Levetiracetam) (Controls unexposed, NOS), 2020Margulis (Levetiracetam) (Epilepsy), 2019Bank (Levetiracetam) (Mixed indications), 2017Arkilo (Levetiracetam), 2015Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014Artama (Levetiracetam) (Controls unexposed, sick), 2013

Asymetry test p-value = 0.3336 (by Egger's regression)

slope=0.4913 (0.1322); intercept=-0.3645 (0.3542); t=1.0290; p=0.3336

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8983, 8984, 9030, 9031, 8986, 10071, 12618, 15220

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.55[1.19; 2.03]155,3327570%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 0.99[0.48; 2.03]5032160%NABromley (Levetiracetam) (Epilepsy) (Controls unexposed, sick), 2023 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 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.31[1.01; 1.70]3551,0810%NAHoeltzenbein (Levetiracetam), 2024 Bromley (Levetiracetam) (Epilepsy) (Controls exposed to LTG), 2023 Aydin (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Coste (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2020 Margulis (Levetiracetam) (Epilepsy), 2019 Bank (Levetiracetam) (Mixed indications), 2017 Arkilo (Levetiracetam), 2015 Kilic (Levetiracetam) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Artama (Levetiracetam) (Controls exposed to Lamotrigine, sick), 2013 90.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Veroniki a (NMA) (All indications) (Preterm birth)Veroniki a (NMA) (All indications) (Preterm birth) 0.87[0.31; 2.04]NA-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 1.48[1.17; 1.86]0%1,178----Hoeltzenbein (Levetiracetam), 2024 Bromley (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 Margulis (Levetiracetam) (Epilepsy), 2019 Bank (Levetiracetam) (Mixed indications), 2017 Arkilo (Levetiracetam), 2015 Kilic (Levetiracetam) (Controls unexposed, sick) (Mixed indications), 2014 Artama (Levetiracetam) (Controls unexposed, sick), 2013 100.510.01.0