Beta-blockers (All routes except ocular) (versus unexposed) updated on 12-17-2024

Perinatal death

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.
S13480
R52001		 Orbach - Atenolol, 2013 Perinatal death (NOS) 3rd trimester retrospective cohort (claims database) unexposed, disease free Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 0.33 [0.02;5.28] C 0/107   1,379/97,820 1,379 107
ref
S13882
R54321		 Petersen - Beta-blockers, 2012 Perinatal mortality (death occurring within the first 28 days of life or stillbirth) 1st and 2nd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Indications Antihypertensive: Only chronic hypertension indication 1.89 [1.25;2.84] 44/2,459   6,048/909,226 6,092 2,459
ref
S13392
R54166		 Ray - Beta-blockers, 2001 Perinatal death (after 20 weeks gestation and up to 30 days after birth) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified 1.50 [0.60;3.40] 16/428   19/980 35 428
ref
S14027
R55140		 Rosenfeld - Pindolol, 1986 Perinatal mortality during pregnancy (anytime or not specified) randomized controlled trial unexposed, sick Adjustment: Randomisation Indications Antihypertensive: All hypertensions, any indications or not specified 0.96 [0.02;50.34] C 0/23   0/22 0 23
ref
S14041
R55416		 Lieberman - Propranolol, 1978 Stillbirth or neonatal death during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 7.00 [1.04;46.95] C 7/9   5/15 12 9
ref
Total 5 studies 1.84 [1.28;2.63] 7,518 3,026
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 Orbach - Atenolol, 2013Orbach - Atenolol, 2013 0.33[0.02; 5.28]1,3791072%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Petersen - Beta-blockers, 2012Petersen - Beta-blockers, 2012 1.89[1.25; 2.84]6,0922,45977%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Ray - Beta-blockers, 2001Ray - Beta-blockers, 2001 1.50[0.60; 3.40]3542817%ROB confusion: seriousROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Rosenfeld - Pindolol, 1986Rosenfeld - Pindolol, 1986 0.96[0.02; 50.34]0231%ROB confusion: lowROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Lieberman - Propranolol, 1978Lieberman - Propranolol, 1978 7.00[1.04; 46.95]1294%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: lowROB mesure: unclearROB reporting: moderate Total (5 studies) I2 = 0% 1.84[1.28; 2.63]7,5183,0260.220.01.0ROB: 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 1.84[1.12; 3.02]7,5183,00317%NAOrbach - Atenolol, 2013 Petersen - Beta-blockers, 2012 Ray - Beta-blockers, 2001 Lieberman - Propranolol, 1978 4 case control studiescase control studies 0 RCTRCT 0.96[0.02; 50.34]-23 -NARosenfeld - Pindolol, 1986 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.38[0.37; 5.15]7,4712,56633%NAOrbach - Atenolol, 2013 Petersen - Beta-blockers, 2012 2 unexposed, sickunexposed, sick 2.02[0.81; 5.01]474609%NARay - Beta-blockers, 2001 Rosenfeld - Pindolol, 1986 Lieberman - Propranolol, 1978 3 Tags Adjustment   - No  - No 1.80[0.09; 35.50]1,39111668%NAOrbach - Atenolol, 2013 Lieberman - Propranolol, 1978 2   - Randomisation  - Randomisation 0.96[0.02; 50.34]-23 -NARosenfeld - Pindolol, 1986 1   - Yes  - Yes 1.81[1.25; 2.63]6,1272,8870%NAPetersen - Beta-blockers, 2012 Ray - Beta-blockers, 2001 2 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 1.72[0.64; 4.59]1,42656717%NAOrbach - Atenolol, 2013 Ray - Beta-blockers, 2001 Rosenfeld - Pindolol, 1986 Lieberman - Propranolol, 1978 4   - Only chronic hypertension indication  - Only chronic hypertension indication 1.89[1.25; 2.85]6,0922,459 -NAPetersen - Beta-blockers, 2012 1 All studiesAll studies 1.84[1.28; 2.63]7,5183,0260%NAOrbach - Atenolol, 2013 Petersen - Beta-blockers, 2012 Ray - Beta-blockers, 2001 Rosenfeld - Pindolol, 1986 Lieberman - Propranolol, 1978 50.120.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.85.42.4270.000Orbach - Atenolol, 2013Petersen - Beta-blockers, 2012Ray - Beta-blockers, 2001Rosenfeld - Pindolol, 1986Lieberman - Propranolol, 1978

Asymetry test p-value = 0.7793 (by Egger's regression)

slope=0.6806 (0.3089); intercept=-0.2308 (0.7532); t=0.3064; p=0.7793

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) 1.38[0.37; 5.15]7,4712,56633%NAOrbach - Atenolol, 2013 Petersen - Beta-blockers, 2012 2 unexposed, sick controlsunexposed, sick controls 2.02[0.81; 5.01]474609%NARay - Beta-blockers, 2001 Rosenfeld - Pindolol, 1986 Lieberman - Propranolol, 1978 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Bone - GESTATIONAL HYPERTENSION (Perinatal death)Bone - GESTATIONAL HYPERTENSION (Perinatal death) 1.29[0.30; 6.09]30%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bellos - Labetalol (Perinatal death (Randomiz ...Bellos - Labetalol (Perinatal death (Randomized controlled trial and Cohort studies)) 1.32[0.52; 3.33]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bellos - Oxprenolol (Perinatal death (Randomi ...Bellos - Oxprenolol (Perinatal death (Randomized controlled trial and Cohort studies)) 0.80[0.04; 14.76]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bellos - Atenolol (Perinatal death (Randomize ...Bellos - Atenolol (Perinatal death (Randomized controlled trial and Cohort studies))) 1.75[0.77; 3.96]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bellos - Labetalol (Perinatal death (Randomiz ...Bellos - Labetalol (Perinatal death (Randomized controlled trial only)) 0.63[0.17; 2.39]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bellos - Oxprenolol (Perinatal death (Randomi ...Bellos - Oxprenolol (Perinatal death (Randomized controlled trial only)) 0.56[0.03; 10.47]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bone - GESTATIONAL HYPERTENSION (Perinatal de ...Bone - GESTATIONAL HYPERTENSION (Perinatal death (versus calcium channel inhibitors)) 0.87[0.03; 31.11]33%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bone - GESTATIONAL HYPERTENSION (Perinatal de ...Bone - GESTATIONAL HYPERTENSION (Perinatal death (versus methyldopa)) 0.88[0.37; 2.15]27%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Magee (Perinatal mortality)Magee (Perinatal mortality) 0.61[0.30; 1.26]0%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT14 Magee (Perinatal mortality)Magee (Perinatal mortality) 1.01[0.46; 2.22]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT12 metaPregmetaPreg 1.84[1.28; 2.63]0%3,026----Orbach - Atenolol, 2013 Petersen - Beta-blockers, 2012 Ray - Beta-blockers, 2001 Rosenfeld - Pindolol, 1986 Lieberman - Propranolol, 1978 50.510.01.0