Methyldopa (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.
S17246
R72172		 Vaclavik, 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
S17243
R72157		 Al Khalaf (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
S17244
R72164		 Al Khalaf (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
S14346
R56770		 Kayser, 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
S14364
R56875		 Orbach, 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
Total 4 studies 2.28 [1.71;3.03] 8,983 3,748
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, 2024Vaclavik, 2024 1.93[1.82; 2.05]-1,23130%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: unclear Al Khalaf (Controls unexposed, sick), 2022Al Khalaf, 2022 1 1.85[1.60; 2.15]9691,95228%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Kayser, 2020Kayser, 2020 1.81[1.15; 2.84]9222517%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Orbach, 2013Orbach, 2013 4.19[3.22; 5.45]7,92234024%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 91% 2.28[1.71; 3.03]8,9833,7480.510.01.0ROB: 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 2.28[1.71; 3.03]8,9833,74891%NAVaclavik, 2024 Al Khalaf (Controls unexposed, sick), 2022 Kayser, 2020 Orbach, 2013 4 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, 2024 Kayser, 2020 Orbach, 2013 3 unexposed, sickunexposed, sick 1.85[1.60; 2.15]9691,952 -NAAl Khalaf (Controls unexposed, sick), 2022 1 Tags Adjustment   - No  - No 1.92[1.82; 2.03]1,0613,4080%NAVaclavik, 2024 Al Khalaf (Controls unexposed, sick), 2022 Kayser, 2020 3   - Yes  - Yes 4.19[3.22; 5.45]7,922340 -NAOrbach, 2013 1 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 2.46[1.42; 4.26]8,0141,79694%NAVaclavik, 2024 Kayser, 2020 Orbach, 2013 3   - Only chronic hypertension indication  - Only chronic hypertension indication 1.85[1.60; 2.15]9691,952 -NAAl Khalaf (Controls unexposed, sick), 2022 1 All studiesAll studies 2.28[1.71; 3.03]8,9833,74891%NAVaclavik, 2024 Al Khalaf (Controls unexposed, sick), 2022 Kayser, 2020 Orbach, 2013 40.510.01.0

Publication bias and p-hacking diagnosis

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

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

not enought points

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 17243

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.90[1.63; 5.18]71,7663,74898%NAVaclavik, 2024 Al Khalaf (Controls unexposed, disease free), 2022 Kayser, 2020 Orbach, 2013 4 unexposed, sick controlsunexposed, sick controls 1.85[1.60; 2.15]9691,952 -NAAl Khalaf (Controls unexposed, sick), 2022 10.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Bone - GESTATIONAL HYPERTENSION (Preterm birth)Bone - 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 (Preterm birth (Randomized controlled ...Bellos (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 (Preterm birth (Randomized controlled ...Bellos (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 - GESTATIONAL HYPERTENSION (Preterm birt ...Bone - 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 2.28[1.71; 3.03]91%3,748----Vaclavik, 2024 Al Khalaf (Controls unexposed, sick), 2022 Kayser, 2020 Orbach, 2013 40.510.01.0