Renin-angiotensin system (ACEIs and/or ARBs) (versus unexposed) updated on 03-11-2025

Nervous system anomalies

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.
S13793
R54098		 Bateman - ACE inhibitor (Controls unexposed, NOS), 2017 Central nervous system malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) excluded Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Renin angiotensin: ACEIs (Angiotensin-converting enzyme inhibitors) 1.46 [0.81;2.64]
excluded (control group) 		11/4,107   2,433/1,329,517 2,444 4,107
ref
S13794
R54101		 Bateman - ACE inhibitor (Controls unexposed, sick), 2017 Central nervous system malformations 1st trimester retrospective cohort (claims database) unexposed, sick Adjustment: Yes Indications Antihypertensive: Only chronic hypertension indication Renin angiotensin: ACEIs (Angiotensin-converting enzyme inhibitors) 0.54 [0.26;1.11] -/2,631   45/15,884 - 2,631
ref
S14144
R55535		 Cooper - ACEi, 2006 Central nervous system malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified Renin angiotensin: ACEIs (Angiotensin-converting enzyme inhibitors) 4.39 [1.37;14.02] 3/209   80/29,096 83 209
ref
Total 2 studies 1.46 [0.19;11.38] 83 2,840
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 Bateman - ACE inhibitor (Controls unexposed, sick), 2017Bateman - ACE inhibitor, 2017 1 0.54[0.26; 1.11]-2,63152%ROB confusion: moderateROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Cooper - ACEi, 2006Cooper - ACEi, 2006 4.39[1.37; 14.02]8320948%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (2 studies) I2 = 89% 1.46[0.19; 11.38]832,8400.210.01.0ROB: A: confusion, 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 1.46[0.19; 11.38]832,84089%NABateman - ACE inhibitor (Controls unexposed, sick), 2017 Cooper - ACEi, 2006 2 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 4.39[1.37; 14.04]83209 -NACooper - ACEi, 2006 1 unexposed, sickunexposed, sick 0.54[0.26; 1.12]-2,631 -NABateman - ACE inhibitor (Controls unexposed, sick), 2017 1 Tags Adjustment   - Yes  - Yes 1.46[0.19; 11.38]832,84089%NABateman - ACE inhibitor (Controls unexposed, sick), 2017 Cooper - ACEi, 2006 2 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 4.39[1.37; 14.04]83209 -NACooper - ACEi, 2006 1   - Only chronic hypertension indication  - Only chronic hypertension indication 0.54[0.26; 1.12]-2,631 -NABateman - ACE inhibitor (Controls unexposed, sick), 2017 1 Renin angiotensin   - ACEIs (Angiotensin-converting enzym ...  - ACEIs (Angiotensin-converting enzyme inhibitors) 1.46[0.19; 11.38]832,84089%NABateman - ACE inhibitor (Controls unexposed, sick), 2017 Cooper - ACEi, 2006 2 All studiesAll studies 1.46[0.19; 11.38]832,84089%NABateman - ACE inhibitor (Controls unexposed, sick), 2017 Cooper - ACEi, 2006 20.210.01.0

Publication bias and p-hacking diagnosis

funnel plot

Funnel plot not drawn. Less than 3 points.

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

not enought points

p values plot

Funnel plot not drawn. Less than 3 points.

Sub-groups analysis using all included studies

excluded 13793

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.25[0.78; 6.45]2,5274,31663%NABateman - ACE inhibitor (Controls unexposed, NOS), 2017 Cooper - ACEi, 2006 2 unexposed, sick controlsunexposed, sick controls 0.54[0.26; 1.12]362,631 -NABateman - ACE inhibitor (Controls unexposed, sick), 2017 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Buawangpong (ACEi/ARBs) (Central nervous syst ...Buawangpong (ACEi/ARBs) (Central nervous system malformations) 1.88[0.73; 4.83]61%-Wwhatever (meta-analysis)T11st trimesterstudies TTT3 Buawangpong (ACEi/ARBs) (Central nervous syst ...Buawangpong (ACEi/ARBs) (Central nervous system malformations) 2.02[1.08; 3.78]49%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 Vial (ACEi) (Central nervous system malformations)Vial (ACEi) (Central nervous system malformations) 1.67[0.84; 3.29]51%-U,DFunexposed, disease freeT11st trimesterstudies TTT3 metaPregmetaPreg 1.46[0.19; 11.38]89%2,840----Bateman - ACE inhibitor (Controls unexposed, sick), 2017 Cooper - ACEi, 2006 20.510.01.0