Proton Pump Inhibitors updated on 08-09-2023

Infant asthma

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.
S14452
R57347		 Noh, 2023 Asthma in infant during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Matched 0.96 [0.94;0.99] -/36,529   -/146,116 - 36,529
ref
S12489
R47105		 Malaeb, 2021 Diagnosed asthma (mean age 10.3 years old) during pregnancy (anytime or not specified) case control unexposed (general population or NOS) Adjustment: Yes 3.50 [1.36;9.02] 26/151   81/849 107 151
ref
S4436
R10497		 Cea Soriano, 2016 Asthma during pregnancy (anytime or not specified) retrospective cohort (registry) unexposed (general population or NOS) Adjustment: Yes Matched 1.03 [0.76;1.40] -/808   -/7,596 - 808
ref
S4439
R10504		 Yitshak-Sade, 2016 Asthma during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.10 [0.98;1.22] -/2,336   -/86,403 - 2,336
ref
S4417
R10455		 Mulder, 2014 Asthma during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.35 [0.94;1.94] 39/319   3,630/33,047 3,669 319
ref
S4437
R10503		 Hak, 2013 Childhood asthma during pregnancy (anytime or not specified) nested case control unexposed (general population or NOS) Adjustment: Yes Matched 2.76 [0.93;8.17] 13/20   1,861/3,728 1,874 20
ref
S4406
R10422		 Andersen (Controls exposed to other treatment, sick), 2012 Asthma during pregnancy (anytime or not specified) retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: No 0.84 [0.71;0.99] C
excluded (control group) 		381/2,238   315/1,605 696 2,238
ref
S4358
R10234		 Andersen (Controls unexposed NOS), 2012 Asthma during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.41 [1.27;1.56] 381/2,238   24,125/194,822 24,506 2,238
ref
Total 7 studies 1.23 [1.01;1.49] 30,156 42,401
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 Noh, 2023Noh, 2023 0.96[0.94; 0.99]-36,52923%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Malaeb, 2021Malaeb, 2021 3.50[1.36; 9.02]1071514%ROB confusion: moderateROB selection: criticalROB classification: criticalROB missing: moderateROB mesure: criticalROB reporting: moderate Cea Soriano, 2016Cea Soriano, 2016 1.03[0.76; 1.40]-80815%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Yitshak-Sade, 2016Yitshak-Sade, 2016 1.10[0.98; 1.22]-2,33621%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Mulder, 2014Mulder, 2014 1.35[0.94; 1.94]3,66931913%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Hak, 2013Hak, 2013 2.76[0.93; 8.17]1,874203%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Andersen (Controls unexposed NOS), 2012Andersen, 2012 1 1.41[1.27; 1.56]24,5062,23822%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (7 studies) I2 = 91% 1.23[1.01; 1.49]30,15642,4010.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.15[0.95; 1.39]28,17542,23093%NANoh, 2023 Cea Soriano, 2016 Yitshak-Sade, 2016 Mulder, 2014 Andersen (Controls unexposed NOS), 2012 5 case control studiescase control studies 3.16[1.55; 6.45]1,9811710%NAMalaeb, 2021 Hak, 2013 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.30[1.07; 1.58]30,1565,87273%NAMalaeb, 2021 Cea Soriano, 2016 Yitshak-Sade, 2016 Mulder, 2014 Hak, 2013 Andersen (Controls unexposed NOS), 2012 6 unexposed, sickunexposed, sick 0.96[0.94; 0.99]-36,529 -NANoh, 2023 1 Tags Adjustment   - Yes  - Yes 1.30[1.07; 1.58]30,1565,87273%NAMalaeb, 2021 Cea Soriano, 2016 Yitshak-Sade, 2016 Mulder, 2014 Hak, 2013 Andersen (Controls unexposed NOS), 2012 6 MatchedMatched 1.02[0.82; 1.29]1,87437,35748%NANoh, 2023 Cea Soriano, 2016 Hak, 2013 3 All studiesAll studies 1.23[1.01; 1.49]30,15642,40191%NANoh, 2023 Malaeb, 2021 Cea Soriano, 2016 Yitshak-Sade, 2016 Mulder, 2014 Hak, 2013 Andersen (Controls unexposed NOS), 2012 70.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.51.50.6650.000Noh, 2023Malaeb, 2021Cea Soriano, 2016Yitshak-Sade, 2016Mulder, 2014Hak, 2013Andersen (Controls unexposed NOS), 2012

Asymetry test p-value = 0.0653 (by Egger's regression)

slope=-0.0650 (0.0394); intercept=2.8199 (1.1986); t=2.3527; p=0.0653

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 4406

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.30[1.07; 1.58]30,1565,87273%NAMalaeb, 2021 Cea Soriano, 2016 Yitshak-Sade, 2016 Mulder, 2014 Hak, 2013 Andersen (Controls unexposed NOS), 2012 6 unexposed, sick controlsunexposed, sick controls 0.96[0.94; 0.99]-36,529 -NANoh, 2023 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.84[0.71; 0.99]6962,238 -NAAndersen (Controls exposed to other treatment, sick), 2012 10.510.01.0