Proton Pump Inhibitors updated on 08-08-2023

Late intrauterine deaths (> 22 weeks) / Stillbirths

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.
S18819
R80062		 Hongoh - Lansoprazole, 2025 Stillbirths (fetal death after 22 weeks of gestation) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.34 [0.08;24.04] C 0/97   6/1,693 6 97
ref
S4515
R11147		 Saleh, 2017 Fetal death during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Matched 0.66 [0.07;6.54] C 1/40   3/80 4 40
ref
S4428
R10464		 Diav-Citrin, 2005 Stillbirth during pregnancy (anytime or not specified) prospective cohort unexposed (general population or NOS) Adjustment: No 4.26 [0.78;23.33] C 4/411   2/868 6 411
ref
S4359
R10427		 Nielsen, 1999 Stillborn (before and during birth) (Exposure at any time) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No 2.83 [0.17;46.52] C 0/51   46/13,327 46 51
ref
S4861
R12585		 Ruigomez - Omeprazole (Controls exposed to other treatment, sick), 1999 Stillbirths 1st trimester retrospective cohort exposed to other treatment, sick excluded Adjustment: No 0.37 [0.02;6.71] C
excluded (control group) 		0/139   5/567 5 139
ref
S4276
R10000		 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 Stillbirths 1st trimester retrospective cohort unexposed (general population or NOS) Adjustment: No 0.36 [0.02;6.10] C 0/139   15/1,575 15 139
ref
Total 5 studies 1.66 [0.58;4.75] 77 738
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 Hongoh - Lansoprazole, 2025Hongoh - Lansoprazole, 2025 1.34[0.08; 24.04]69713%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: critical Saleh, 2017Saleh, 2017 0.66[0.07; 6.54]44021%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Diav-Citrin, 2005Diav-Citrin, 2005 4.26[0.78; 23.33]641138%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Nielsen, 1999Nielsen, 1999 2.83[0.17; 46.52]465114%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Ruigomez - Omeprazole (Controls unexposed NOS), 1999Ruigomez - Omeprazole, 1999 1 0.36[0.02; 6.10]1513914%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 1.66[0.58; 4.75]777380.210.01.0ROB: A: confounding, 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 1.66[0.58; 4.75]777380%NAHongoh - Lansoprazole, 2025 Saleh, 2017 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.12[0.65; 6.91]736980%NAHongoh - Lansoprazole, 2025 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 4 unexposed, sickunexposed, sick 0.66[0.07; 6.54]440 -NASaleh, 2017 1 Tags Adjustment   - No  - No 1.66[0.58; 4.75]777380%NAHongoh - Lansoprazole, 2025 Saleh, 2017 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 5 MatchedMatched 0.66[0.07; 6.54]440 -NASaleh, 2017 1 All studiesAll studies 1.66[0.58; 4.75]777380%NAHongoh - Lansoprazole, 2025 Saleh, 2017 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 50.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.54.01.7660.000Hongoh - Lansoprazole, 2025Saleh, 2017Diav-Citrin, 2005Nielsen, 1999Ruigomez - Omeprazole (Controls unexposed NOS), 1999

Asymetry test p-value = 0.2465 (by Egger's regression)

slope=3.2313 (1.9416); intercept=-2.3294 (1.6222); t=1.4360; p=0.2465

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 4861

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.12[0.65; 6.91]736980%NAHongoh - Lansoprazole, 2025 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 4 unexposed, sick controlsunexposed, sick controls 0.66[0.07; 6.54]440 -NASaleh, 2017 1 exposed to other treatment, sick controlsexposed to other treatment, sick controls Out of scale0.37[0.02; 6.71]5139 -NARuigomez - Omeprazole (Controls exposed to other treatment, sick), 1999 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Samji (Stillbirths)Samji (Stillbirths) 2.20[0.57; 8.60]-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 1.66[0.58; 4.75]0%738----Hongoh - Lansoprazole, 2025 Saleh, 2017 Diav-Citrin, 2005 Nielsen, 1999 Ruigomez - Omeprazole (Controls unexposed NOS), 1999 50.510.01.0