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

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.
S17123
R71692
Van der Zande - ACE-Is and/or ARBs, 2024 Stillbirths (foetal death beyond 20 weeks of pregnancy) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indications Antihypertensive: Only cardiac indications other than hypertension (long QT syndrome, structural heart disease, ...) Renin angiotensin: ARBs and/or ACEIs (Angiotensin II receptor blockers and/or Angiotensin-converting enzyme inhibitors) 1.93 [0.26;14.25] C 1/42   71/5,697 72 42
ref
S14147
R55484
Hoeltzenbein a - ARBs, 2018 Stillbirth early pregnancy prospective cohort unexposed, disease free Adjustment: No Indications Antihypertensive: Only chronic hypertension indication Matched Renin angiotensin: ARBs (Angiotensin II receptor blockers) 24.25 [1.25;471.94] C 3/165   0/560 3 165
ref
S14149
R55512
Hoeltzenbein b - ACEi, 2018 Stillbirth early pregnancy prospective cohort unexposed, disease free Adjustment: No Indications Antihypertensive: Only chronic hypertension indication Matched Renin angiotensin: ACEIs (Angiotensin-converting enzyme inhibitors) 0.99 [0.09;11.00] C 1/329   2/654 3 329
ref
S14158
R55561
Moretti - ACEi/ARBs, 2012 Fetal death 1st trimester prospective cohort unexposed, disease free Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched Renin angiotensin: ARBs and/or ACEIs (Angiotensin II receptor blockers and/or Angiotensin-converting enzyme inhibitors) 0.99 [0.02;50.39] C 0/139   0/138 0 139
ref
S14145
R55545
Diav-Citrin - ACEi/ARB, 2011 Stillbirth early pregnancy prospective cohort unexposed (general population or NOS) Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Renin angiotensin: ARBs and/or ACEIs (Angiotensin II receptor blockers and/or Angiotensin-converting enzyme inhibitors) 1.48 [0.33;6.66] C 3/252   4/495 7 252
ref
S14146
R55479
Cournot - ACEi, 2006 Late fetal deaths 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched Renin angiotensin: ACEIs (Angiotensin-converting enzyme inhibitors) 5.06 [0.24;106.33] C 2/159   0/159 2 159
ref
Total 6 studies 2.13 [0.84;5.42] 87 1,086
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 Van der Zande - ACE-Is and/or ARBs, 2024Van der Zande - ACE-Is and/or ARBs, 2024 1.93[0.26; 14.25]724222%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Hoeltzenbein a - ARBs, 2018Hoeltzenbein a - ARBs, 2018 24.25[1.25; 471.94]316510%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Hoeltzenbein b - ACEi, 2018Hoeltzenbein b - ACEi, 2018 0.99[0.09; 11.00]332915%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Moretti - ACEi/ARBs, 2012Moretti - ACEi/ARBs, 2012 0.99[0.02; 50.39]01396%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Diav-Citrin - ACEi/ARB, 2011Diav-Citrin - ACEi/ARB, 2011 1.48[0.33; 6.66]725238%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Cournot - ACEi, 2006Cournot - ACEi, 2006 5.06[0.24; 106.33]21599%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Total (6 studies) I2 = 0% 2.13[0.84; 5.42]871,0860.250.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.13[0.84; 5.42]871,0860%NAVan der Zande - ACE-Is and/or ARBs, 2024 Hoeltzenbein a - ARBs, 2018 Hoeltzenbein b - ACEi, 2018 Moretti - ACEi/ARBs, 2012 Diav-Citrin - ACEi/ARB, 2011 Cournot - ACEi, 2006 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.19[0.77; 6.29]151,0440%NAHoeltzenbein a - ARBs, 2018 Hoeltzenbein b - ACEi, 2018 Moretti - ACEi/ARBs, 2012 Diav-Citrin - ACEi/ARB, 2011 Cournot - ACEi, 2006 5 unexposed, sickunexposed, sick 1.93[0.26; 14.25]7242 -NAVan der Zande - ACE-Is and/or ARBs, 2024 1 Tags Adjustment   - No  - No 2.13[0.84; 5.42]871,0860%NAVan der Zande - ACE-Is and/or ARBs, 2024 Hoeltzenbein a - ARBs, 2018 Hoeltzenbein b - ACEi, 2018 Moretti - ACEi/ARBs, 2012 Diav-Citrin - ACEi/ARB, 2011 Cournot - ACEi, 2006 6 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 1.76[0.49; 6.30]95500%NAMoretti - ACEi/ARBs, 2012 Diav-Citrin - ACEi/ARB, 2011 Cournot - ACEi, 2006 3   - Only cardiac indications other than ...  - Only cardiac indications other than hypertension (long QT syndrome, structural heart disease, ...) 1.93[0.26; 14.25]7242 -NAVan der Zande - ACE-Is and/or ARBs, 2024 1   - Only chronic hypertension indication  - Only chronic hypertension indication 4.34[0.19; 98.39]649463%NAHoeltzenbein a - ARBs, 2018 Hoeltzenbein b - ACEi, 2018 2 MatchedMatched 3.23[0.71; 14.63]87924%NAHoeltzenbein a - ARBs, 2018 Hoeltzenbein b - ACEi, 2018 Moretti - ACEi/ARBs, 2012 Cournot - ACEi, 2006 4 Renin angiotensin   - ACEIs (Angiotensin-converting enzym ...  - ACEIs (Angiotensin-converting enzyme inhibitors) 1.86[0.28; 12.26]54880%NAHoeltzenbein b - ACEi, 2018 Cournot - ACEi, 2006 2   - ARBs (Angiotensin II receptor blockers)  - ARBs (Angiotensin II receptor blockers) 24.25[1.25; 471.94]3165 -NAHoeltzenbein a - ARBs, 2018 1   - ARBs and/or ACEIs (Angiotensin II r ...  - ARBs and/or ACEIs (Angiotensin II receptor blockers and/or Angiotensin-converting enzyme inhibitors) 1.56[0.49; 4.93]794330%NAVan der Zande - ACE-Is and/or ARBs, 2024 Moretti - ACEi/ARBs, 2012 Diav-Citrin - ACEi/ARB, 2011 3 All studiesAll studies 2.13[0.84; 5.42]871,0860%NAVan der Zande - ACE-Is and/or ARBs, 2024 Hoeltzenbein a - ARBs, 2018 Hoeltzenbein b - ACEi, 2018 Moretti - ACEi/ARBs, 2012 Diav-Citrin - ACEi/ARB, 2011 Cournot - ACEi, 2006 60.250.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.75.52.4040.000Van der Zande - ACE-Is and/or ARBs, 2024Hoeltzenbein a - ARBs, 2018Hoeltzenbein b - ACEi, 2018Moretti - ACEi/ARBs, 2012Diav-Citrin - ACEi/ARB, 2011Cournot - ACEi, 2006

Asymetry test p-value = 0.4291 (by Egger's regression)

slope=-0.3732 (1.3533); intercept=1.0211 (1.1620); t=0.8788; p=0.4291

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.19[0.77; 6.29]151,0440%NAHoeltzenbein a - ARBs, 2018 Hoeltzenbein b - ACEi, 2018 Moretti - ACEi/ARBs, 2012 Diav-Citrin - ACEi/ARB, 2011 Cournot - ACEi, 2006 5 unexposed, sick controlsunexposed, sick controls 1.93[0.26; 14.25]7242 -NAVan der Zande - ACE-Is and/or ARBs, 2024 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Buawangpong (ACEi/ARBs) (Stillbirth)Buawangpong (ACEi/ARBs) (Stillbirth) 2.36[1.17; 4.76]0%-Wwhatever (meta-analysis)T11st trimesterstudies TTT8 Buawangpong (ACEi/ARBs) (Stillbirth)Buawangpong (ACEi/ARBs) (Stillbirth) 2.36[1.17; 4.76]0%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT8 Fu (ACEi/ARBs) (Stillbirth (versus exposed to ...Fu (ACEi/ARBs) (Stillbirth (versus exposed to other oral antihypertensives)) 1.38[0.22; 8.77]25%-Eexposed to other treatment, sickT1+at least 1st trimesterstudies TTT4 Fu (ACEi/ARBs) (Stillbirth (versus non‐expose ...Fu (ACEi/ARBs) (Stillbirth (versus non‐exposed controls)) 1.75[1.21; 2.53]0%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT4 metaPregmetaPreg 2.13[0.84; 5.42]0%1,086----Van der Zande - ACE-Is and/or ARBs, 2024 Hoeltzenbein a - ARBs, 2018 Hoeltzenbein b - ACEi, 2018 Moretti - ACEi/ARBs, 2012 Diav-Citrin - ACEi/ARB, 2011 Cournot - ACEi, 2006 60.510.01.0