Proton Pump Inhibitors updated on 10-13-2025

Cleft palate

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.
S18406
R77682		 Choi a (Controls unexposed, sibling), 2023 Cleft palate 1st trimester retrospective cohort (claims database) sibling excluded Adjustment: Yes 0.97 [0.32;2.94]
excluded (control group) 		10/16,787   17/18,567 27 16,787
ref
S14453
R57353		 Choi a (Controls unexposed, sick), 2023 Cleft palate 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes 1.02 [0.72;1.43] 38/40,540   2,281/2,655,676 2,319 40,540
ref
S4357
R10232		 Anderka, 2012 Cleft Palate 1st trimester case control unexposed, sick Adjustment: Yes 2.59 [0.88;7.63] 5/18   520/4,516 525 18
ref
S4275
R10701		 Pasternak, 2010 Cleft palate alone 1st trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes 0.79 [0.19;3.25] 2/3,651   -/- - 3,651
ref
S4861
R12551		 Ruigomez - Omeprazole (Controls exposed to other treatment, sick), 1999 Cleft palate only 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 1.36 [0.06;33.59] C
excluded (control group) 		0/139   1/567 1 139
ref
S4276
R9960		 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Cleft palate only 1st trimester retrospective cohort unexposed (general population or NOS) Adjustment: No 3.79 [0.15;93.41] C 0/139   1/1,575 1 139
ref
Total 4 studies 1.17 [0.75;1.83] 2,845 44,348
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 Choi a (Controls unexposed, sick), 2023Choi a, 2023 1 1.02[0.72; 1.43]2,31940,54074%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: NAROB reporting: NA Anderka, 2012Anderka, 2012 2.59[0.88; 7.63]5251815%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Pasternak, 2010Pasternak, 2010 0.79[0.19; 3.25]-3,6519%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Ruigomez - Omeprazole (Controls unexposed NOS), 1999Ruigomez - Omeprazole, 1999 2 3.79[0.15; 93.41]11392%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (4 studies) I2 = 11% 1.17[0.75; 1.83]2,84544,3480.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.02[0.73; 1.42]2,32044,3300%NAChoi a (Controls unexposed, sick), 2023 Pasternak, 2010 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 3 case control studiescase control studies 2.59[0.88; 7.63]52518 -NAAnderka, 2012 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.02[0.28; 3.74]13,7900%NAPasternak, 2010 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 2 unexposed, sickunexposed, sick 1.40[0.59; 3.34]2,84440,55862%NAChoi a (Controls unexposed, sick), 2023 Anderka, 2012 2 Tags Adjustment   - No  - No 3.79[0.15; 93.41]1139 -NARuigomez - Omeprazole (Controls unexposed NOS), 1999 1   - Yes  - Yes 1.19[0.69; 2.06]2,84444,20929%NAChoi a (Controls unexposed, sick), 2023 Anderka, 2012 Pasternak, 2010 3 All studiesAll studies 1.17[0.75; 1.83]2,84544,34811%NAChoi a (Controls unexposed, sick), 2023 Anderka, 2012 Pasternak, 2010 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 40.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.84.01.9620.000Choi a (Controls unexposed, sick), 2023Anderka, 2012Pasternak, 2010Ruigomez - Omeprazole (Controls unexposed NOS), 1999

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 4861, 18406

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.02[0.28; 3.74]13,7900%NAPasternak, 2010 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 2 unexposed, sick controlsunexposed, sick controls 1.40[0.59; 3.34]2,84440,55862%NAChoi a (Controls unexposed, sick), 2023 Anderka, 2012 2 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.36[0.06; 33.59]1139 -NARuigomez - Omeprazole (Controls exposed to other treatment, sick), 1999 1 siblingssiblings 0.97[0.32; 2.94]2716,787 -NAChoi a (Controls unexposed, sibling), 2023 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Peron (metaPreg) (Cleft palate)Peron (metaPreg) (Cleft palate) 1.77[0.77; 4.06]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT3 metaPregmetaPreg 1.17[0.75; 1.83]11%44,348----Choi a (Controls unexposed, sick), 2023 Anderka, 2012 Pasternak, 2010 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 40.510.01.0