Pregabalin (All indications)

All congenital malformations (majors, minors, majors and minors, 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.
S16194
R67117
The NAAED (Controls exposed to LTG) (Indications NOS), 2024 Major congenital malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.54 [0.37;6.49] C
excluded (control group)
2/62   52/2,461 54 62
ref
S16184
R67118
The NAAED (Controls unexposed, disease free) (Indications NOS), 2024 Major congenital malformations 1st trimester prospective cohort unexposed, disease free Adjustment: No 2.88 [0.64;12.88] C 2/62   15/1,311 17 62
ref
S15251
R62701
Dudukina (Controls exposed to LTG) (Mixed indications), 2023 Major congenital malformations 3 months or more before pregnancy or1st trimester population based cohort retrospective exposed to other treatment, sick excluded Adjustment: Yes 1.25 [0.98;1.59]
excluded (control group)
138/2,332   351/7,005 489 2,332
ref
S15252
R62722
Dudukina (Controls unexposed, NOS) (Mixed indications), 2023 Major congenital malformations 3 months or more before pregnancy or1st trimester excluded population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.14 [0.96;1.35]
excluded (exposition period)
138/2,332   126,437/3,063,173 126,575 2,332
ref
S8530
R35199
Vajda (Controls exposed to Lamotrigine, sick), 2019 Fetal malformations at least 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 18.80 [0.36;971.86] C
excluded (control group)
0/1   20/406 20 1
ref
S8531
R35200
Vajda (Controls unexposed, sick), 2019 Fetal malformations at least 1st trimester prospective cohort unexposed, sick Adjustment: No 31.00 [0.56;1711.11] C 0/1   5/176 5 1
ref
S8529
R28290
Tomson, 2018 Malformed Offspring at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: No 4.68 [0.24;91.38] C 0/4   74/2,514 74 4
ref
S8528
R28288
Patorno_MAX and MaketScan (Other indications), 2017 Major congenital malformations (MAX and Marketscan data) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.99 [0.66;1.47] 24/471   38,116/1,750,259 38,140 471
ref
S8525
R28238
Winterfeld (Other indications), 2016 Overall major birth defects 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched 6.50 [1.70;24.70] 3/19   16/573 19 19
ref
S8534
R28300
Veiby (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Major congenital malformation throughout pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.99 [0.13;7.54] C
excluded (control group)
1/30   28/833 29 30
ref
S8535
R28302
Veiby (Controls unexposed, disease free) (Mixed indications), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, disease free excluded Adjustment: No 1.15 [0.16;8.48] C
excluded (control group)
1/30   22,371/771,412 22,372 30
ref
S8536
R28306
Veiby (Controls unexposed, sick) (Mixed indications), 2014 Major malformations throughout pregnancy population based cohort retrospective unexposed, sick Adjustment: No Controls: epilepsy indication 1.19 [0.16;8.84] C 1/30   106/3,773 107 30
ref
S8532
R28294
Källén (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 Relatively severe malformations early pregnancy population based cohort retrospective exposed to other treatment, sick excluded Adjustment: No 0.52 [0.12;2.18] C
excluded (control group)
2/111   37/1,084 39 111
ref
S8533
R28296
Källén (Controls unexposed, NOS) (Indications NOS), 2013 Relatively severe malformations early pregnancy population based cohort retrospective unexposed (general population or NOS) Adjustment: No 0.57 [0.14;2.29] C 2/111   49,499/1,575,847 49,501 111
ref
Total 7 studies 1.87 [0.83;4.23] 87,863 698
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 The NAAED (Controls unexposed, disease free) (Indications NOS), 2024The NAAED, 2024 1 2.88[0.64; 12.88]176215%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: low Vajda (Controls unexposed, sick), 2019Vajda, 2019 2 31.00[0.56; 1711.11]514%ROB confusion: criticalROB selection: moderateROB classification: lowROB missing: moderateROB mesure: moderateROB reporting: moderate Tomson, 2018Tomson, 2018 4.68[0.24; 91.38]7446%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: moderateROB mesure: lowROB reporting: low Patorno_MAX and MaketScan (Other indications), 2017Patorno_MAX and MaketScan, 2017 3 0.99[0.66; 1.47]38,14047130%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: low Winterfeld (Other indications), 2016Winterfeld, 2016 4 6.50[1.70; 24.70]191917%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: lowROB reporting: unclear Veiby (Controls unexposed, sick) (Mixed indications), 2014Veiby, 2014 5 1.19[0.16; 8.84]1073011%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Källén (Controls unexposed, NOS) (Indications NOS), 2013Källén, 2013 6 0.57[0.14; 2.29]49,50111117%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 53% 1.87[0.83; 4.23]87,8636980.2100.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, disease free) (Indications NOS; 2: Controls unexposed, sick; 3: Other indications; 4: Other indications; 5: Controls unexposed, sick) (Mixed indications; 6: Controls unexposed, NOS) (Indications NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.87[0.83; 4.23]87,86369853%NAThe NAAED (Controls unexposed, disease free) (Indications NOS), 2024 Vajda (Controls unexposed, sick), 2019 Tomson, 2018 Patorno_MAX and MaketScan (Other indications), 2017 Winterfeld (Other indications), 2016 Veiby (Controls unexposed, sick) (Mixed indications), 2014 Källén (Controls unexposed, NOS) (Indications NOS), 2013 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.65[0.63; 4.36]87,67766368%NAThe NAAED (Controls unexposed, disease free) (Indications NOS), 2024 Patorno_MAX and MaketScan (Other indications), 2017 Winterfeld (Other indications), 2016 Källén (Controls unexposed, NOS) (Indications NOS), 2013 4 unexposed, sickunexposed, sick 3.75[0.18; 79.19]1123151%NAVajda (Controls unexposed, sick), 2019 Veiby (Controls unexposed, sick) (Mixed indications), 2014 2 exposed to other treatment, sickexposed to other treatment, sick 4.68[0.24; 91.38]744 -NATomson, 2018 1 Tags Adjustment   - No  - No 2.48[0.91; 6.76]49,72322741%NAThe NAAED (Controls unexposed, disease free) (Indications NOS), 2024 Vajda (Controls unexposed, sick), 2019 Tomson, 2018 Winterfeld (Other indications), 2016 Veiby (Controls unexposed, sick) (Mixed indications), 2014 Källén (Controls unexposed, NOS) (Indications NOS), 2013 6   - Yes  - Yes 0.99[0.66; 1.47]38,140471 -NAPatorno_MAX and MaketScan (Other indications), 2017 1 Controls   - epilepsy indication  - epilepsy indication 1.19[0.16; 8.84]10730 -NAVeiby (Controls unexposed, sick) (Mixed indications), 2014 1 MatchedMatched 6.50[1.71; 24.78]1919 -NAWinterfeld (Other indications), 2016 1 All studiesAll studies 1.87[0.83; 4.23]87,86369853%NAThe NAAED (Controls unexposed, disease free) (Indications NOS), 2024 Vajda (Controls unexposed, sick), 2019 Tomson, 2018 Patorno_MAX and MaketScan (Other indications), 2017 Winterfeld (Other indications), 2016 Veiby (Controls unexposed, sick) (Mixed indications), 2014 Källén (Controls unexposed, NOS) (Indications NOS), 2013 70.2100.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.42.4560.000The NAAED (Controls unexposed, disease free) (Indications NOS), 2024Vajda (Controls unexposed, sick), 2019Tomson, 2018Patorno_MAX and MaketScan (Other indications), 2017Winterfeld (Other indications), 2016Veiby (Controls unexposed, sick) (Mixed indications), 2014Källén (Controls unexposed, NOS) (Indications NOS), 2013

Asymetry test p-value = 0.1213 (by Egger's regression)

slope=-0.2748 (0.3326); intercept=1.3174 (0.7067); t=1.8641; p=0.1213

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 8532, 8534, 8535, 8535, 8530, 15251, 16194

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.48[0.73; 3.01]132,42172347%NAThe NAAED (Controls unexposed, disease free) (Indications NOS), 2024 Patorno_MAX and MaketScan (Other indications), 2017 Winterfeld (Other indications), 2016 Veiby (Controls unexposed, disease free) (Mixed indications), 2014 Veiby (Controls unexposed, disease free) (Mixed indications), 2014 Källén (Controls unexposed, NOS) (Indications NOS), 2013 6 unexposed, sick controlsunexposed, sick controls 3.75[0.18; 79.19]1123151%NAVajda (Controls unexposed, sick), 2019 Veiby (Controls unexposed, sick) (Mixed indications), 2014 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.21[0.51; 2.90]2162083%NAThe NAAED (Controls exposed to LTG) (Indications NOS), 2024 Vajda (Controls exposed to Lamotrigine, sick), 2019 Tomson, 2018 Veiby (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 Källén (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 50.510.01.0