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

Neonatal bradycardia

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.
S13853
R54281		 Kayser - Metoprolol/bisoprolol, 2020 Neonatal bradycardia days before delivery prospective cohort unexposed, disease free Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified 1.80 [0.50;7.20] 5/252   5/588 10 252
ref
S13863
R54238		 Mazkereth - Beta-blockers, 2019 Neonatal bradycardia (< 100 beats per minute) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 13.53 [0.76;242.38] C 6/153   0/153 6 153
ref
S13795
R54102		 Bateman - Beta-blockers, 2016 Neonatal bradycardia (ICD-9 779.81) late pregnancy retrospective cohort (claims database) unexposed, sick Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified 1.29 [1.07;1.55] 165/10,561   385/31,683 550 10,561
ref
S14183
R55596		 Yassen - Acebutolol, 1992 Neonatal bradycardia (< 100beats /min) with cyanosis during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 21.00 [0.97;453.94] C 5/11   0/11 5 11
ref
S13947
R54585		 Fidler - Oxprenolol, 1983 Abnormal intrapartum cardiotocograms (mainly Bradycardia) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 2.22 [1.09;4.51] C 24/49   29/96 53 49
ref
Total 5 studies 1.94 [1.06;3.55] 624 11,026
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 Kayser - Metoprolol/bisoprolol, 2020Kayser - Metoprolol/bisoprolol, 2020 1.80[0.50; 7.20]1025215%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Mazkereth - Beta-blockers, 2019Mazkereth - Beta-blockers, 2019 13.53[0.76; 242.38]61534%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Bateman - Beta-blockers, 2016Bateman - Beta-blockers, 2016 1.29[1.07; 1.55]55010,56148%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Yassen - Acebutolol, 1992Yassen - Acebutolol, 1992 21.00[0.97; 453.94]5114%ROB confusion: criticalROB selection: unclearROB classification: unclearROB missing: lowROB mesure: moderateROB reporting: moderate Fidler - Oxprenolol, 1983Fidler - Oxprenolol, 1983 2.22[1.09; 4.51]534930%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 49% 1.94[1.06; 3.55]62411,0260.550.01.0ROB: 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 1.94[1.06; 3.55]62411,02649%NAKayser - Metoprolol/bisoprolol, 2020 Mazkereth - Beta-blockers, 2019 Bateman - Beta-blockers, 2016 Yassen - Acebutolol, 1992 Fidler - Oxprenolol, 1983 5 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.35[1.20; 4.59]683126%NAKayser - Metoprolol/bisoprolol, 2020 Yassen - Acebutolol, 1992 Fidler - Oxprenolol, 1983 3 unexposed, sickunexposed, sick 2.64[0.32; 22.00]55610,71461%NAMazkereth - Beta-blockers, 2019 Bateman - Beta-blockers, 2016 2 Tags Adjustment   - No  - No 4.64[1.07; 20.11]6421338%NAMazkereth - Beta-blockers, 2019 Yassen - Acebutolol, 1992 Fidler - Oxprenolol, 1983 3   - Yes  - Yes 1.30[1.08; 1.56]56010,8130%NAKayser - Metoprolol/bisoprolol, 2020 Bateman - Beta-blockers, 2016 2 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 1.94[1.06; 3.55]62411,02649%NAKayser - Metoprolol/bisoprolol, 2020 Mazkereth - Beta-blockers, 2019 Bateman - Beta-blockers, 2016 Yassen - Acebutolol, 1992 Fidler - Oxprenolol, 1983 5 MatchedMatched 4.64[1.07; 20.11]6421338%NAMazkereth - Beta-blockers, 2019 Yassen - Acebutolol, 1992 Fidler - Oxprenolol, 1983 3 All studiesAll studies 1.94[1.06; 3.55]62411,02649%NAKayser - Metoprolol/bisoprolol, 2020 Mazkereth - Beta-blockers, 2019 Bateman - Beta-blockers, 2016 Yassen - Acebutolol, 1992 Fidler - Oxprenolol, 1983 50.550.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.74.31.8820.000Kayser - Metoprolol/bisoprolol, 2020Mazkereth - Beta-blockers, 2019Bateman - Beta-blockers, 2016Yassen - Acebutolol, 1992Fidler - Oxprenolol, 1983

Asymetry test p-value = 0.0192 (by Egger's regression)

slope=0.1097 (0.0675); intercept=1.5399 (0.3340); t=4.6111; p=0.0192

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) 2.35[1.20; 4.59]683126%NAKayser - Metoprolol/bisoprolol, 2020 Yassen - Acebutolol, 1992 Fidler - Oxprenolol, 1983 3 unexposed, sick controlsunexposed, sick controls 2.64[0.32; 22.00]55610,71461%NAMazkereth - Beta-blockers, 2019 Bateman - Beta-blockers, 2016 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Magee (Neonatal bradycardia)Magee (Neonatal bradycardia) 1.93[1.05; 3.53]69%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT3 Magee (Neonatal bradycardia)Magee (Neonatal bradycardia) Out of scale-9.00[-9.00; -9.00]NA-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT2 De Bruin (Neonatal bradycardia (Case control ...De Bruin (Neonatal bradycardia (Case control studies)) 1.86[0.31; 11.19]82%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT5 De Bruin (Neonatal bradycardia (Cohort studies))De Bruin (Neonatal bradycardia (Cohort studies)) 2.10[0.97; 4.55]58%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT3 De Bruin (Neonatal bradycardia (RCT studies))De Bruin (Neonatal bradycardia (RCT studies)) 2.36[1.33; 4.18]38%-Wwhatever (meta-analysis)Anyduring pregnancy (anytime or not specified)studies TTT11 Abalos (Neonatal bradycardia (RCT versus no a ...Abalos (Neonatal bradycardia (RCT versus no antihypertensive drugs/placebo)) 2.20[0.68; 7.16]57%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 metaPregmetaPreg 1.94[1.06; 3.55]49%11,026----Kayser - Metoprolol/bisoprolol, 2020 Mazkereth - Beta-blockers, 2019 Bateman - Beta-blockers, 2016 Yassen - Acebutolol, 1992 Fidler - Oxprenolol, 1983 50.510.01.0