Proton Pump Inhibitors updated on 08-09-2023

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.
S14451
R57333		 Breddels, 2022 Preterm birth (birth < 37 weeks of gestation) 2nd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 1.58 [1.40;1.78] -/-   -/- - -
ref
S4444
R10544		 Cluver - Esomeprazole, 2018 Instantaneous hazard of delivery 29-37 weeks late pregnancy randomized controlled trial unexposed, sick Adjustment: Randomisation 1.07 [0.68;1.68] -/59   -/60 - 59
ref
S4515
R11139		 Saleh, 2017 Prematurity (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Matched 0.74 [0.35;1.58] C 19/40   44/80 63 40
ref
S4446
R10573		 Matok, 2012 Preterm delivery (< 37 weeks) 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.86 [0.62;1.19] 38/666   7,105/108,878 7,143 666
ref
S4428
R10468		 Diav-Citrin, 2005 Preterm birth (≤ 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No 1.36 [0.93;1.98] C 49/324   86/741 135 324
ref
S4359
R10257		 Nielsen, 1999 Preterm deliveries (< 37 weeks) (Exposure at any time) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 1.72 [0.68;4.34] C 5/51   793/13,327 798 51
ref
S4861
R12586		 Ruigomez - Omeprazole (Controls exposed to other treatment, sick), 1999 Preterm offspring (<37 weeks) 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 1.05 [0.53;2.09] C
excluded (control group) 		11/139   43/567 54 139
ref
S4276
R10001		 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Preterm offspring (<37 weeks) 1st trimester retrospective cohort unexposed (general population or NOS) Adjustment: No 1.09 [0.57;2.08] C 11/139   115/1,575 126 139
ref
S4293
R10018		 Lalkin - Omeprazole (Controls exposed to other treatment, sick), 1998 Preterm (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick excluded Adjustment: No Matched 0.56 [0.23;1.38] C
excluded (control group) 		8/84   16/101 24 84
ref
S4407
R10426		 Lalkin - Omeprazole (Controls unexposed NOS), 1998 Preterm (< 37 weeks) during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No Matched 1.20 [0.43;3.34] C 8/84   8/99 16 84
ref
Total 8 studies 1.18 [0.93;1.51] 8,281 1,363
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 Breddels, 2022Breddels, 2022 1.58[1.40; 1.78]--25%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Cluver - Esomeprazole, 2018Cluver - Esomeprazole, 2018 1.07[0.68; 1.68]-5914%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Saleh, 2017Saleh, 2017 0.74[0.35; 1.58]63407%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Matok, 2012Matok, 2012 0.86[0.62; 1.19]7,14366618%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Diav-Citrin, 2005Diav-Citrin, 2005 1.36[0.93; 1.98]13532416%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Nielsen, 1999Nielsen, 1999 1.72[0.68; 4.34]798516%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Ruigomez - Omeprazole (Controls unexposed NOS), 1999Ruigomez - Omeprazole, 1999 1 1.09[0.57; 2.08]1261399%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Lalkin - Omeprazole (Controls unexposed NOS), 1998Lalkin - Omeprazole, 1998 2 1.20[0.43; 3.34]16845%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Total (8 studies) I2 = 60% 1.18[0.93; 1.51]8,2811,3630.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed NOS; 2: Controls unexposed NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.20[0.91; 1.58]8,2811,30462%NABreddels, 2022 Saleh, 2017 Matok, 2012 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Lalkin - Omeprazole (Controls unexposed NOS), 1998 7 case control studiescase control studies 0 RCTRCT 1.07[0.68; 1.68]-59 -NACluver - Esomeprazole, 2018 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.26[0.96; 1.66]8,2181,26461%NABreddels, 2022 Matok, 2012 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Lalkin - Omeprazole (Controls unexposed NOS), 1998 6 unexposed, sickunexposed, sick 0.97[0.66; 1.43]63990%NACluver - Esomeprazole, 2018 Saleh, 2017 2 Tags Adjustment   - No  - No 1.22[0.93; 1.61]1,1386380%NASaleh, 2017 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Lalkin - Omeprazole (Controls unexposed NOS), 1998 5   - Randomisation  - Randomisation 1.07[0.68; 1.68]-59 -NACluver - Esomeprazole, 2018 1   - Yes  - Yes 1.19[0.66; 2.16]7,14366692%NABreddels, 2022 Matok, 2012 2 MatchedMatched 0.88[0.48; 1.62]791240%NASaleh, 2017 Lalkin - Omeprazole (Controls unexposed NOS), 1998 2 All studiesAll studies 1.18[0.93; 1.51]8,2811,36360%NABreddels, 2022 Cluver - Esomeprazole, 2018 Saleh, 2017 Matok, 2012 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Lalkin - Omeprazole (Controls unexposed NOS), 1998 80.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.21.40.6280.000Breddels, 2022Cluver - Esomeprazole, 2018Saleh, 2017Matok, 2012Diav-Citrin, 2005Nielsen, 1999Ruigomez - Omeprazole (Controls unexposed NOS), 1999Lalkin - Omeprazole (Controls unexposed NOS), 1998

Asymetry test p-value = 0.0938 (by Egger's regression)

slope=0.5029 (0.1055); intercept=-1.4315 (0.7195); t=1.9896; p=0.0938

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 4293, 4861

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.26[0.96; 1.66]8,2181,26461%NABreddels, 2022 Matok, 2012 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Lalkin - Omeprazole (Controls unexposed NOS), 1998 6 unexposed, sick controlsunexposed, sick controls 0.97[0.66; 1.43]63990%NACluver - Esomeprazole, 2018 Saleh, 2017 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.82[0.45; 1.49]7822315%NARuigomez - Omeprazole (Controls exposed to other treatment, sick), 1999 Lalkin - Omeprazole (Controls exposed to other treatment, sick), 1998 20.510.01.0