Proton Pump Inhibitors updated on 08-08-2023

Low birth weight (< 2500g)

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
R80066		 Hongoh - Lansoprazole, 2025 Low birth weight infants (<2500 g) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.28 [0.60;2.70] C 8/96   111/1,668 119 96
ref
S18407
R77684		 Choi b (Controls unexposed, sibling), 2023 Low birth weight (< 2500g) during pregnancy (anytime or not specified) retrospective cohort (claims database) sibling excluded Adjustment: Yes 0.87 [0.76;1.00]
excluded (control group) 		522/13,678   27,854/754,382 28,376 13,678
ref
S15108
R62070		 Choi b (Controls unexposed, sick), 2023 Low birth weight (perinatal weight <2.5 kg) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: Yes 0.95 [0.91;1.00] 2,357/41,664   104,056/2,121,323 106,413 41,664
ref
S18824
R80110		 Van Gelder, 2023 Low birth weight 3rd trimester prospective cohort unexposed (general population or NOS) Adjustment: No Matched 2.00 [1.20;3.60] -/-   -/- - -
ref
S4515
R11144		 Saleh, 2017 Neonatal (birth) weight <10th percentile according to Perinatal Registration The Netherlands during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Matched 0.64 [0.24;1.66] C 7/40   20/80 27 40
ref
S4446
R10575		 Matok, 2012 Low birth weight (< 2500 g) 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.70 [0.48;1.03] 40/666   8,988/108,878 9,028 666
ref
S4459
R10585		 Källén - Omeprazole, 2001 Low birth weight (< 2500g) 2nd and/or 3rd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: No 1.20 [0.49;2.91] -/-   -/- - -
ref
S4359
R10241		 Nielsen, 1999 Low birth weight (< 2500 g) 2nd and/or 3rd trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.52 [0.20;11.40] 3/39   657/13,327 660 39
ref
Total 7 studies 1.02 [0.78;1.33] 116,247 42,505
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 1.28[0.60; 2.70]1199610%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: critical Choi b (Controls unexposed, sick), 2023Choi b, 2023 1 0.95[0.91; 1.00]106,41341,66438%ROB confusion: moderateROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Van Gelder, 2023Van Gelder, 2023 2.00[1.20; 3.60]--15%ROB confusion: unclearROB selection: unclearROB classification: unclearROB missing: unclearROB mesure: unclearROB reporting: critical Saleh, 2017Saleh, 2017 0.64[0.24; 1.66]27406%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Matok, 2012Matok, 2012 0.70[0.48; 1.03]9,02866622%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Källén - Omeprazole, 2001Källén - Omeprazole, 2001 1.20[0.49; 2.91]--7%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Nielsen, 1999Nielsen, 1999 1.52[0.20; 11.40]660392%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (7 studies) I2 = 47% 1.02[0.78; 1.33]116,24742,5050.25.01.0ROB: A: confounding, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.02[0.78; 1.33]116,24742,50547%NAHongoh - Lansoprazole, 2025 Choi b (Controls unexposed, sick), 2023 Van Gelder, 2023 Saleh, 2017 Matok, 2012 Källén - Omeprazole, 2001 Nielsen, 1999 7 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.19[0.72; 1.98]9,80780160%NAHongoh - Lansoprazole, 2025 Van Gelder, 2023 Matok, 2012 Källén - Omeprazole, 2001 Nielsen, 1999 5 unexposed, sickunexposed, sick 0.95[0.91; 0.99]106,44041,7040%NAChoi b (Controls unexposed, sick), 2023 Saleh, 2017 2 Tags Adjustment   - No  - No 1.32[0.83; 2.08]14613632%NAHongoh - Lansoprazole, 2025 Van Gelder, 2023 Saleh, 2017 Källén - Omeprazole, 2001 4   - Yes  - Yes 0.90[0.74; 1.09]116,10142,36924%NAChoi b (Controls unexposed, sick), 2023 Matok, 2012 Nielsen, 1999 3 MatchedMatched 1.21[0.40; 3.69]274076%NAVan Gelder, 2023 Saleh, 2017 2 All studiesAll studies 1.02[0.78; 1.33]116,24742,50547%NAHongoh - Lansoprazole, 2025 Choi b (Controls unexposed, sick), 2023 Van Gelder, 2023 Saleh, 2017 Matok, 2012 Källén - Omeprazole, 2001 Nielsen, 1999 70.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.41.2380.000Hongoh - Lansoprazole, 2025Choi b (Controls unexposed, sick), 2023Van Gelder, 2023Saleh, 2017Matok, 2012Källén - Omeprazole, 2001Nielsen, 1999

Asymetry test p-value = 0.5873 (by Egger's regression)

slope=-0.0615 (0.0402); intercept=0.3723 (0.6423); t=0.5796; p=0.5873

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 18407

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.19[0.72; 1.98]9,80780160%NAHongoh - Lansoprazole, 2025 Van Gelder, 2023 Matok, 2012 Källén - Omeprazole, 2001 Nielsen, 1999 5 unexposed, sick controlsunexposed, sick controls 0.95[0.91; 0.99]106,44041,7040%NAChoi b (Controls unexposed, sick), 2023 Saleh, 2017 2 siblingssiblings 0.87[0.76; 1.00]28,37613,678 -NAChoi b (Controls unexposed, sibling), 2023 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Samji (Low birth weight (<2500gm))Samji (Low birth weight (<2500gm)) 0.60[0.50; 0.89]-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 1.02[0.78; 1.33]47%42,505----Hongoh - Lansoprazole, 2025 Choi b (Controls unexposed, sick), 2023 Van Gelder, 2023 Saleh, 2017 Matok, 2012 Källén - Omeprazole, 2001 Nielsen, 1999 70.510.01.0