Labetalol (versus unexposed) updated on 12-17-2024

Small for gestational age (weight)

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.
S17133
R71853		 Delteil, 2024 Small for gestational age (weight) at least 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Indications Antihypertensive: Only chronic indication (hypertension or cardiac) 2.26 [1.65;3.04] 61/238   13,794/135,159 13,855 238
ref
S13510
R52195		 Fitton (Controls unexposed, disease free), 2020 Small for gestational age (birth weight below the 10th percentile) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free excluded Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified 1.92 [1.43;2.57]
excluded (control group) 		96/680   24,121/250,693 24,217 680
ref
S14424
R57256		 Fitton (Controls unexposed, sick), 2020 Small for gestational age (birth weight below the 10th percentile) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 1.07 [0.86;1.34] C 96/680   1,059/7,971 1,155 680
ref
S14403
R57205		 Xiang, 2020 Smaller than gestational age (birth weight <10 percentile, based on Waitz et al curves) during pregnancy (anytime or not specified) randomized controlled trial unexposed, sick Adjustment: Randomisation Indications Antihypertensive: Only chronic hypertension indication 2.87 [1.63;5.05] C 53/124   25/121 78 124
ref
S13912
R54428		 Duan, 2018 Small for gestational age (birth weight <10th percentile for the corresponding gestational week) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified 2.90 [2.60;3.20] 590/3,357   32,488/374,391 33,078 3,357
ref
S14341
R56741		 Thewissen (Controls unexposed, disease free), 2017 Small for gestational age during pregnancy (anytime or not specified) prospective cohort unexposed, disease free excluded Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 2.10 [0.18;25.01] C
excluded (control group) 		2/22   1/22 3 22
ref
S14342
R56744		 Thewissen (Controls unexposed, sick), 2017 Small for gestational age during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 0.27 [0.05;1.50] C 2/22   6/22 8 22
ref
S13885
R54322		 Petersen, 2012 Small for gestational age (birth weight < 10th percentile for the corresponding gestational week) 1st and 2nd trimester population based cohort retrospective unexposed (general population or NOS) Adjustment: Yes Indications Antihypertensive: Only chronic hypertension indication 2.02 [1.72;2.37] 258/1,452   93,662/909,226 93,920 1,452
ref
S14266
R56081		 Cruickshank, 1990 Intrauterine growth retardation (NOS) 3rd trimester randomized controlled trial unexposed, sick Adjustment: Randomisation Indications Antihypertensive: All hypertensions, any indications or not specified 1.30 [0.39;4.33] C 6/31   7/45 13 31
ref
Total 7 studies 1.86 [1.29;2.68] 142,107 5,904
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 Delteil, 2024Delteil, 2024 2.26[1.65; 3.04]13,85523818%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Fitton (Controls unexposed, sick), 2020Fitton, 2020 1 1.07[0.86; 1.34]1,15568019%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Xiang, 2020Xiang, 2020 2.87[1.63; 5.05]7812414%ROB confusion: lowROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Duan, 2018Duan, 2018 2.90[2.60; 3.20]33,0783,35720%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Thewissen (Controls unexposed, sick), 2017Thewissen, 2017 2 0.27[0.05; 1.50]8224%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Petersen, 2012Petersen, 2012 2.02[1.72; 2.37]93,9201,45220%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Cruickshank, 1990Cruickshank, 1990 1.30[0.39; 4.33]13316%ROB confusion: lowROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (7 studies) I2 = 92% 1.86[1.29; 2.68]142,1075,9040.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.77[1.16; 2.70]142,0165,74994%NADelteil, 2024 Fitton (Controls unexposed, sick), 2020 Duan, 2018 Thewissen (Controls unexposed, sick), 2017 Petersen, 2012 5 case control studiescase control studies 0 RCTRCT 2.33[1.18; 4.60]9115526%NAXiang, 2020 Cruickshank, 1990 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.39[1.83; 3.12]140,8535,04786%NADelteil, 2024 Duan, 2018 Petersen, 2012 3 unexposed, sickunexposed, sick 1.28[0.61; 2.66]1,25485777%NAFitton (Controls unexposed, sick), 2020 Xiang, 2020 Thewissen (Controls unexposed, sick), 2017 Cruickshank, 1990 4 Tags Adjustment   - No  - No 0.70[0.20; 2.47]1,16370259%NAFitton (Controls unexposed, sick), 2020 Thewissen (Controls unexposed, sick), 2017 2   - Randomisation  - Randomisation 2.33[1.18; 4.60]9115526%NAXiang, 2020 Cruickshank, 1990 2   - Yes  - Yes 2.39[1.83; 3.12]140,8535,04786%NADelteil, 2024 Duan, 2018 Petersen, 2012 3 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 1.30[0.58; 2.92]34,2544,09096%NAFitton (Controls unexposed, sick), 2020 Duan, 2018 Thewissen (Controls unexposed, sick), 2017 Cruickshank, 1990 4   - Only chronic hypertension indication  - Only chronic hypertension indication 2.16[1.65; 2.82]93,9981,57626%NAXiang, 2020 Petersen, 2012 2   - Only chronic indication (hypertensi ...  - Only chronic indication (hypertension or cardiac) 2.26[1.66; 3.07]13,855238 -NADelteil, 2024 1 MatchedMatched 0.27[0.05; 1.50]822 -NAThewissen (Controls unexposed, sick), 2017 1 All studiesAll studies 1.86[1.29; 2.68]142,1075,90492%NADelteil, 2024 Fitton (Controls unexposed, sick), 2020 Xiang, 2020 Duan, 2018 Thewissen (Controls unexposed, sick), 2017 Petersen, 2012 Cruickshank, 1990 70.110.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.12.71.0590.000Delteil, 2024Fitton (Controls unexposed, sick), 2020Xiang, 2020Duan, 2018Thewissen (Controls unexposed, sick), 2017Petersen, 2012Cruickshank, 1990

Asymetry test p-value = 0.2685 (by Egger's regression)

slope=1.0458 (0.2131); intercept=-2.5328 (2.0353); t=1.2444; p=0.2685

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 14341, 13510

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.28[1.81; 2.87]165,0735,74978%NADelteil, 2024 Fitton (Controls unexposed, disease free), 2020 Duan, 2018 Thewissen (Controls unexposed, disease free), 2017 Petersen, 2012 5 unexposed, sick controlsunexposed, sick controls 1.28[0.61; 2.66]1,25485777%NAFitton (Controls unexposed, sick), 2020 Xiang, 2020 Thewissen (Controls unexposed, sick), 2017 Cruickshank, 1990 40.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Bellos (Small for gestational age (Randomized ...Bellos (Small for gestational age (Randomized controlled trial and Cohort studies)) 2.44[1.36; 4.41]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bone - GESTATIONAL HYPERTENSION (Small for ge ...Bone - GESTATIONAL HYPERTENSION (Small for gestational age infants) 1.13[0.65; 1.92]42%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bone - GESTATIONAL HYPERTENSION (Small for ge ...Bone - GESTATIONAL HYPERTENSION (Small for gestational age infants) 0.77[0.38; 1.57]24%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bellos (Small-for-gestational age (Randomized ...Bellos (Small-for-gestational age (Randomized controlled trial only)) 1.17[0.58; 2.36]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 1.86[1.29; 2.68]92%5,904----Delteil, 2024 Fitton (Controls unexposed, sick), 2020 Xiang, 2020 Duan, 2018 Thewissen (Controls unexposed, sick), 2017 Petersen, 2012 Cruickshank, 1990 70.510.01.0