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

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.
S19322
R81891
Kim (Controls exposed to LTG) (Levetiracetam) (Indications NOS), 2026 Microcephaly 1st trimester population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.44 [0.05;4.25] C
excluded (control group)
1/542   3/718 4 542
ref
S19315
R81806
Kim (Controls unexposed, NOS) (Levetiracetam) (Indications NOS), 2026 Microcephaly 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.35 [0.13;14.60] 1/542   2,473/2,489,078 2,474 542
ref
S16071
R66695
Christensen (Levetiracetam) (All indications) (Controls exposed to LTG), 2024 Microcephaly (z-score for head circumference ≤3rd percentile for gestational week, sex, and country (including newborns with congenital malformations)) during pregnancy (anytime or not specified) population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.95 [0.65;1.37] C
excluded (control group)
32/1,077   274/8,756 306 1,077
ref
S16037
R66568
Christensen (Levetiracetam) (All indications) (Controls unexposed, general population), 2024 Microcephaly (z-score for head circumference ≤3rd percentile for gestational week, sex, and country (including newborns with congenital malformations)) during pregnancy (anytime or not specified) population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 0.89 [0.61;1.30] 32/1,077   134,023/4,467,848 134,055 1,077
ref
S10170
R37110
Blotière (Levetiracetam) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 Microcephaly (until 24 months of age, identifiable by: Q02; brain MRI; according to the EUROCAT definition) 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 1.73 [0.07;42.42] C
excluded (control group)
0/579   1/2,997 1 579
ref
S10037
R36195
Blotière (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2019 Microcephaly (until 24 months of age, identifiable by: Q02; brain MRI; according to the EUROCAT definition) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 3.70 [0.23;59.26] C 0/579   438/1,875,733 438 579
ref
Total 3 studies 0.92 [0.64;1.34] 136,967 2,198
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 Kim (Controls unexposed, NOS) (Levetiracetam) (Indications NOS), 2026Kim, 2026 1 1.35[0.13; 14.60]2,4745422%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Christensen (Levetiracetam) (All indications) (Controls unexposed, general population), 2024Christensen, 2024 2 0.89[0.61; 1.30]134,0551,07796%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Blotière (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2019Blotière, 2019 3 3.70[0.23; 59.26]4385792%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (3 studies) I2 = 0% 0.92[0.64; 1.34]136,9672,1980.210.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, NOS) (Levetiracetam) (Indications NOS; 2: Levetiracetam) (All indications) (Controls unexposed, general population; 3: Levetiracetam) (Controls unexposed NOS) (Mixed indications;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.92[0.64; 1.34]136,9672,1980%NAKim (Controls unexposed, NOS) (Levetiracetam) (Indications NOS), 2026 Christensen (Levetiracetam) (All indications) (Controls unexposed, general population), 2024 Blotière (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2019 3 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.92[0.64; 1.34]136,9672,1980%NAKim (Controls unexposed, NOS) (Levetiracetam) (Indications NOS), 2026 Christensen (Levetiracetam) (All indications) (Controls unexposed, general population), 2024 Blotière (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2019 3 Tags Adjustment   - No  - No 3.70[0.23; 59.26]438579 -NABlotière (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2019 1   - Yes  - Yes 0.90[0.62; 1.31]136,5291,6190%NAKim (Controls unexposed, NOS) (Levetiracetam) (Indications NOS), 2026 Christensen (Levetiracetam) (All indications) (Controls unexposed, general population), 2024 2 All studiesAll studies 0.92[0.64; 1.34]136,9672,1980%NAKim (Controls unexposed, NOS) (Levetiracetam) (Indications NOS), 2026 Christensen (Levetiracetam) (All indications) (Controls unexposed, general population), 2024 Blotière (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2019 30.210.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 10170, 16071, 19322

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.92[0.64; 1.34]136,9672,1980%NAKim (Controls unexposed, NOS) (Levetiracetam) (Indications NOS), 2026 Christensen (Levetiracetam) (All indications) (Controls unexposed, general population), 2024 Blotière (Levetiracetam) (Controls unexposed NOS) (Mixed indications), 2019 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.94[0.65; 1.35]3112,1980%NAKim (Controls exposed to LTG) (Levetiracetam) (Indications NOS), 2026 Christensen (Levetiracetam) (All indications) (Controls exposed to LTG), 2024 Blotière (Levetiracetam) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2019 30.510.01.0