Centrally acting antiadrenergic (versus unexposed) updated on 03-11-2025

Preterm (< 37 weeks)

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.
S17154
R71945		 Vaclavik - Methyldopa, 2024 Preterm delivery during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 1.93 [1.82;2.05] -/1,231   -/71,860 - 1,231
ref
S17152
R71934		 Al Khalaf - Methyldopa (Controls unexposed, disease free), 2022 Preterm birth (less than 37 weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 4.65 [4.10;5.26] C
excluded (control group) 		292/1,952   63,460/1,739,944 63,752 1,952
ref
S17149
R71913		 Al Khalaf - Methyldopa (Controls unexposed, sick), 2022 Preterm birth (less than 37 weeks) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 1.85 [1.60;2.15] C 292/1,952   677/7,809 969 1,952
ref
S13508
R52187		 Fitton - Centrally acting (Controls unexposed, disease free), 2020 Preterm birth (birth on or before 36 weeks gestation). 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 3.11 [1.70;5.72]
excluded (control group) 		26/136   12,622/250,693 12,648 136
ref
S14423
R57253		 Fitton - Centrally acting (Controls unexposed, sick), 2020 Preterm birth (birth on or before 36 weeks gestation) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 2.32 [1.51;3.59] C 26/136   736/7,971 762 136
ref
S13880
R54301		 Kayser - Methyldopa, 2020 Preterm birth (delivery before 37 completed gestational weeks) 2nd and/or 3rd trimester prospective cohort unexposed, disease free Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 1.81 [1.15;2.84] C 36/225   56/588 92 225
ref
S13479
R51990		 Orbach - Methyldopa, 2013 Preterm delivery (< 37 weeks of gestation) 3rd trimester retrospective cohort (claims database) unexposed, disease free Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified 4.19 [3.22;5.45] 86/340   7,836/97,820 7,922 340
ref
S13450
R51813		 Su - Centrally acting (Controls unexposed, disease free), 2013 Preterm birth (< 37 completed weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 3.72 [2.56;5.39] C
excluded (control group) 		37/181   529/8,181 566 181
ref
S13444
R51795		 Su - Centrally acting (Controls unexposed, sick), 2013 Preterm birth (< 37 completed weeks) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Indications Antihypertensive: Only chronic hypertension indication 2.87 [1.87;4.40] 37/181   84/1,006 121 181
ref
Total 6 studies 2.35 [1.86;2.97] 9,866 4,065
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 Vaclavik - Methyldopa, 2024Vaclavik - Methyldopa, 2024 1.93[1.82; 2.05]-1,23123%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: unclear Al Khalaf - Methyldopa (Controls unexposed, sick), 2022Al Khalaf - Methyldopa, 2022 1 1.85[1.60; 2.15]9691,95221%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Fitton - Centrally acting (Controls unexposed, sick), 2020Fitton - Centrally acting, 2020 2 2.32[1.51; 3.59]76213613%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Kayser - Methyldopa, 2020Kayser - Methyldopa, 2020 1.81[1.15; 2.84]9222512%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Orbach - Methyldopa, 2013Orbach - Methyldopa, 2013 4.19[3.22; 5.45]7,92234018%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Su - Centrally acting (Controls unexposed, sick), 2013Su - Centrally acting, 2013 3 2.87[1.87; 4.40]12118113%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (6 studies) I2 = 86% 2.35[1.86; 2.97]9,8664,0650.510.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick; 3: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 2.35[1.86; 2.97]9,8664,06586%NAVaclavik - Methyldopa, 2024 Al Khalaf - Methyldopa (Controls unexposed, sick), 2022 Fitton - Centrally acting (Controls unexposed, sick), 2020 Kayser - Methyldopa, 2020 Orbach - Methyldopa, 2013 Su - Centrally acting (Controls unexposed, sick), 2013 6 case control studiescase control studies 0 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 2.46[1.42; 4.26]8,0141,79694%NAVaclavik - Methyldopa, 2024 Kayser - Methyldopa, 2020 Orbach - Methyldopa, 2013 3 unexposed, sickunexposed, sick 2.17[1.66; 2.85]1,8522,26952%NAAl Khalaf - Methyldopa (Controls unexposed, sick), 2022 Fitton - Centrally acting (Controls unexposed, sick), 2020 Su - Centrally acting (Controls unexposed, sick), 2013 3 Tags Adjustment   - No  - No 1.92[1.82; 2.03]1,8233,5440%NAVaclavik - Methyldopa, 2024 Al Khalaf - Methyldopa (Controls unexposed, sick), 2022 Fitton - Centrally acting (Controls unexposed, sick), 2020 Kayser - Methyldopa, 2020 4   - Yes  - Yes 3.61[2.51; 5.18]8,04352154%NAOrbach - Methyldopa, 2013 Su - Centrally acting (Controls unexposed, sick), 2013 2 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 2.43[1.58; 3.74]8,7761,93291%NAVaclavik - Methyldopa, 2024 Fitton - Centrally acting (Controls unexposed, sick), 2020 Kayser - Methyldopa, 2020 Orbach - Methyldopa, 2013 4   - Only chronic hypertension indication  - Only chronic hypertension indication 2.20[1.45; 3.34]1,0902,13372%NAAl Khalaf - Methyldopa (Controls unexposed, sick), 2022 Su - Centrally acting (Controls unexposed, sick), 2013 2 All studiesAll studies 2.35[1.86; 2.97]9,8664,06586%NAVaclavik - Methyldopa, 2024 Al Khalaf - Methyldopa (Controls unexposed, sick), 2022 Fitton - Centrally acting (Controls unexposed, sick), 2020 Kayser - Methyldopa, 2020 Orbach - Methyldopa, 2013 Su - Centrally acting (Controls unexposed, sick), 2013 60.510.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.71.70.2760.000Vaclavik - Methyldopa, 2024Al Khalaf - Methyldopa (Controls unexposed, sick), 2022Fitton - Centrally acting (Controls unexposed, sick), 2020Kayser - Methyldopa, 2020Orbach - Methyldopa, 2013Su - Centrally acting (Controls unexposed, sick), 2013

Asymetry test p-value = 0.2719 (by Egger's regression)

slope=0.5962 (0.1013); intercept=1.9548 (1.5351); t=1.2734; p=0.2719

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 13450, 13508, 17152

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.05[1.92; 4.86]84,9804,06597%NAVaclavik - Methyldopa, 2024 Al Khalaf - Methyldopa (Controls unexposed, disease free), 2022 Fitton - Centrally acting (Controls unexposed, disease free), 2020 Kayser - Methyldopa, 2020 Orbach - Methyldopa, 2013 Su - Centrally acting (Controls unexposed, disease free), 2013 6 unexposed, sick controlsunexposed, sick controls 2.17[1.66; 2.85]1,8522,26952%NAAl Khalaf - Methyldopa (Controls unexposed, sick), 2022 Fitton - Centrally acting (Controls unexposed, sick), 2020 Su - Centrally acting (Controls unexposed, sick), 2013 30.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Bone - Methyldopa - GESTATIONAL HYPERTENSION ...Bone - Methyldopa - GESTATIONAL HYPERTENSION (Preterm birth) 1.04[0.61; 1.83]28%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Abalos (Preterm birth (< 37 weeks) (RCT versu ...Abalos (Preterm birth (< 37 weeks) (RCT versus no antihypertensive drugs/placebo)) 1.61[0.73; 3.57]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 Bellos - Methyldopa (Preterm birth (Randomize ...Bellos - Methyldopa (Preterm birth (Randomized controlled trial and Cohort studies)) 0.98[0.42; 2.29]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bellos - Methyldopa (Preterm birth (Randomize ...Bellos - Methyldopa (Preterm birth (Randomized controlled trial only)) 0.70[0.35; 1.42]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bone - Methyldopa - GESTATIONAL HYPERTENSION ...Bone - Methyldopa - GESTATIONAL HYPERTENSION (Preterm birth (versus beta-blockers)) 1.20[0.56; 2.70]34%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 metaPregmetaPreg 2.35[1.86; 2.97]86%4,065----Vaclavik - Methyldopa, 2024 Al Khalaf - Methyldopa (Controls unexposed, sick), 2022 Fitton - Centrally acting (Controls unexposed, sick), 2020 Kayser - Methyldopa, 2020 Orbach - Methyldopa, 2013 Su - Centrally acting (Controls unexposed, sick), 2013 60.510.01.0