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

Neonatal medical care

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
R54283		 Kayser - Metoprolol/bisoprolol, 2020 Postnatal respiratory disorder days before delivery prospective cohort unexposed, disease free Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified 1.50 [0.70;3.30] 22/252   32/588 54 252
ref
S14051
R55688		 Xiang - Labetalol, 2020 Admission to Neonatal Intensive Care Unit during pregnancy (anytime or not specified) randomized controlled trial unexposed, sick Adjustment: Randomisation Indications Antihypertensive: Only chronic hypertension indication 2.23 [1.21;4.12] C 38/124   20/121 58 124
ref
S13863
R54241		 Mazkereth - Beta-blockers, 2019 Neonatal intensive care unit hospitalization during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 0.11 [0.01;2.03] C 0/153   4/153 4 153
ref
S13883
R54317		 Thewissen - Labetalol (Controls unexposed, disease free), 2017 Mechanical ventilation during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 1.75 [0.52;5.84] C
excluded (control group) 		14/22   11/22 25 22
ref
S13866
R54314		 Thewissen - Labetalol (Controls unexposed, sick), 2017 Mechanical ventilation during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 1.46 [0.44;4.88] C 14/22   12/22 26 22
ref
S13392
R54165		 Ray - Beta-blockers, 2001 Neonatal intensive care unit admission during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified 2.40 [1.60;3.50] 208/428   269/980 477 428
ref
Total 5 studies 1.94 [1.31;2.88] 619 979
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 1.50[0.70; 3.30]5425219%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Xiang - Labetalol, 2020Xiang - Labetalol, 2020 2.23[1.21; 4.12]5812427%ROB confusion: lowROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Mazkereth - Beta-blockers, 2019Mazkereth - Beta-blockers, 2019 0.11[0.01; 2.03]41532%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Thewissen - Labetalol (Controls unexposed, sick), 2017Thewissen - Labetalol, 2017 1 1.46[0.44; 4.88]26229%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Ray - Beta-blockers, 2001Ray - Beta-blockers, 2001 2.40[1.60; 3.50]47742843%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 27% 1.94[1.31; 2.88]6199790.05.01.0ROB: 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 1.68[0.91; 3.09]56185545%NAKayser - Metoprolol/bisoprolol, 2020 Mazkereth - Beta-blockers, 2019 Thewissen - Labetalol (Controls unexposed, sick), 2017 Ray - Beta-blockers, 2001 4 case control studiescase control studies 0 RCTRCT 2.23[1.21; 4.12]58124 -NAXiang - Labetalol, 2020 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.50[0.69; 3.26]54252 -NAKayser - Metoprolol/bisoprolol, 2020 1 unexposed, sickunexposed, sick 2.01[1.23; 3.30]56572736%NAXiang - Labetalol, 2020 Mazkereth - Beta-blockers, 2019 Thewissen - Labetalol (Controls unexposed, sick), 2017 Ray - Beta-blockers, 2001 4 Tags Adjustment   - No  - No 0.57[0.05; 6.58]3017561%NAMazkereth - Beta-blockers, 2019 Thewissen - Labetalol (Controls unexposed, sick), 2017 2   - Randomisation  - Randomisation 2.23[1.21; 4.12]58124 -NAXiang - Labetalol, 2020 1   - Yes  - Yes 2.15[1.45; 3.18]53168011%NAKayser - Metoprolol/bisoprolol, 2020 Ray - Beta-blockers, 2001 2 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 1.68[0.91; 3.09]56185545%NAKayser - Metoprolol/bisoprolol, 2020 Mazkereth - Beta-blockers, 2019 Thewissen - Labetalol (Controls unexposed, sick), 2017 Ray - Beta-blockers, 2001 4   - Only chronic hypertension indication  - Only chronic hypertension indication 2.23[1.21; 4.12]58124 -NAXiang - Labetalol, 2020 1 MatchedMatched 0.57[0.05; 6.58]3017561%NAMazkereth - Beta-blockers, 2019 Thewissen - Labetalol (Controls unexposed, sick), 2017 2 All studiesAll studies 1.94[1.31; 2.88]61997927%NAKayser - Metoprolol/bisoprolol, 2020 Xiang - Labetalol, 2020 Mazkereth - Beta-blockers, 2019 Thewissen - Labetalol (Controls unexposed, sick), 2017 Ray - Beta-blockers, 2001 50.05.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.54.21.7940.000Kayser - Metoprolol/bisoprolol, 2020Xiang - Labetalol, 2020Mazkereth - Beta-blockers, 2019Thewissen - Labetalol (Controls unexposed, sick), 2017Ray - Beta-blockers, 2001

Asymetry test p-value = 0.0169 (by Egger's regression)

slope=1.3145 (0.1385); intercept=-2.0040 (0.4145); t=4.8343; p=0.0169

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 13883

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.57[0.82; 3.01]792740%NAKayser - Metoprolol/bisoprolol, 2020 Thewissen - Labetalol (Controls unexposed, disease free), 2017 2 unexposed, sick controlsunexposed, sick controls 2.01[1.23; 3.30]56572736%NAXiang - Labetalol, 2020 Mazkereth - Beta-blockers, 2019 Thewissen - Labetalol (Controls unexposed, sick), 2017 Ray - Beta-blockers, 2001 40.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Firoz (Labetalol) (Admission to Neonatal inte ...Firoz (Labetalol) (Admission to Neonatal intensive care unit (Labetalol iv versus Nifedipine)) 1.00[0.18; 5.56]NA-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT1 Firoz (Labetalol) (Admission to Neonatal inte ...Firoz (Labetalol) (Admission to Neonatal intensive care unit (Labetalol versus Methyldopa)) 1.06[0.66; 1.72]NA-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT1 Abalos (Admission to neonatal or intensive ca ...Abalos (Admission to neonatal or intensive care nursery (RCT versus no antihypertensive drugs/placebo)) 1.07[0.82; 1.41]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT3 Magee (Admission to special care baby unit)Magee (Admission to special care baby unit) 0.97[0.76; 1.24]8%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT4 Magee (Admission to special care baby unit)Magee (Admission to special care baby unit) 0.99[0.75; 1.29]0%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT4 Bone - GESTATIONAL HYPERTENSION (Neonatal car ...Bone - GESTATIONAL HYPERTENSION (Neonatal care unit admission (versus calcium channel inhibitors)) 1.48[0.32; 7.59]33%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bone - GESTATIONAL HYPERTENSION (Neonatal car ...Bone - GESTATIONAL HYPERTENSION (Neonatal care unit admission (versus methyldopa)) 0.72[0.27; 1.81]33%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Shekhar (Intravenous labetalol) - GESTATIONAL ...Shekhar (Intravenous labetalol) - GESTATIONAL HYPERTENSION (Neonatal intensive care unit (NICU) admission) 1.30[0.88; 1.96]NA-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT5 Shi (Intravenous Labetalol) - GESTATIONAL HYP ...Shi (Intravenous Labetalol) - GESTATIONAL HYPERTENSION (Neonatal Intensive Care Unit admission (versus oral nifedipine)) 0.99[0.62; 1.59]0%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT3 metaPregmetaPreg 1.94[1.31; 2.88]27%979----Kayser - Metoprolol/bisoprolol, 2020 Xiang - Labetalol, 2020 Mazkereth - Beta-blockers, 2019 Thewissen - Labetalol (Controls unexposed, sick), 2017 Ray - Beta-blockers, 2001 50.510.01.0