Lamotrigine (All indications)

Hypospadias

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.
S15197
R62332		 Cohen (Lamotrigine) (Mixed indications), 2023 Hypospadias 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 1.01 [0.66;1.55] -/8,339   -/4,866,362 - 8,339
ref
S10035
R36163		 Blotière (Lamotrigine) (Mixed indications), 2019 Hypospadias 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.20 [0.60;2.60] 7/2,997   3,371/1,875,733 3,378 2,997
ref
S8964
R30359		 Veiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014 Hypospadias throughout pregnancy population based cohort retrospective unexposed, disease free Adjustment: No Partial overlapping 2.41 [0.90;6.44] C 4/833   1,543/771,412 1,547 833
ref
S8908
R30105		 Källén (Lamotrigine) (Indications NOS), 2013 Hypospadias early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Partial overlapping 0.87 [0.18;2.04] 3/1,084   4,552/1,575,847 4,555 1,084
ref
Total 4 studies 1.14 [0.82;1.59] 9,480 13,253
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 Cohen (Lamotrigine) (Mixed indications), 2023Cohen, 2023 1 1.01[0.66; 1.55]-8,33961%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Blotière (Lamotrigine) (Mixed indications), 2019Blotière, 2019 2 1.20[0.60; 2.60]3,3782,99721%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Veiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014Veiby, 2014 3 2.41[0.90; 6.44]1,54783311%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Källén (Lamotrigine) (Indications NOS), 2013Källén, 2013 4 0.87[0.18; 2.04]4,5551,0847%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 0% 1.14[0.82; 1.59]9,48013,2530.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Lamotrigine) (Mixed indications; 2: Lamotrigine) (Mixed indications; 3: Lamotrigine) (Controls unexposed, disease free) (Mixed indications; 4: Lamotrigine) (Indications NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.14[0.82; 1.59]9,48013,2530%NACohen (Lamotrigine) (Mixed indications), 2023 Blotière (Lamotrigine) (Mixed indications), 2019 Veiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Lamotrigine) (Indications NOS), 2013 4 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.14[0.82; 1.59]9,48013,2530%NACohen (Lamotrigine) (Mixed indications), 2023 Blotière (Lamotrigine) (Mixed indications), 2019 Veiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Lamotrigine) (Indications NOS), 2013 4 Tags Adjustment   - No  - No 2.41[0.90; 6.44]1,547833 -NAVeiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014 1   - Yes  - Yes 1.04[0.73; 1.48]7,93312,4200%NACohen (Lamotrigine) (Mixed indications), 2023 Blotière (Lamotrigine) (Mixed indications), 2019 Källén (Lamotrigine) (Indications NOS), 2013 3 Partial overlappingPartial overlapping 1.20[0.71; 2.01]6,10210,25626%NACohen (Lamotrigine) (Mixed indications), 2023 Veiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Lamotrigine) (Indications NOS), 2013 3 All studiesAll studies 1.14[0.82; 1.59]9,48013,2530%NACohen (Lamotrigine) (Mixed indications), 2023 Blotière (Lamotrigine) (Mixed indications), 2019 Veiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Lamotrigine) (Indications NOS), 2013 40.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.51.60.7430.000Cohen (Lamotrigine) (Mixed indications), 2023Blotière (Lamotrigine) (Mixed indications), 2019Veiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014Källén (Lamotrigine) (Indications NOS), 2013

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

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.14[0.82; 1.59]9,48013,2530%NACohen (Lamotrigine) (Mixed indications), 2023 Blotière (Lamotrigine) (Mixed indications), 2019 Veiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Lamotrigine) (Indications NOS), 2013 40.510.01.0

Umbrella review (other published meta-analyses)

Published MATE95% CIn exposedkI2Control groupExposition period Veroniki (NMA)Veroniki (NMA) 0.66[0.23; 2.26]-whatever (meta-analysis)during pregnancy (anytime or not specified)studies8 metaPregmetaPreg 1.14[0.82; 1.59]0%13,253--Cohen (Lamotrigine) (Mixed indications), 2023 Blotière (Lamotrigine) (Mixed indications), 2019 Veiby (Lamotrigine) (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Lamotrigine) (Indications NOS), 2013 40.510.01.0