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

Late intrauterine deaths (> 22 weeks) / Stillbirths

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.
S17152
R71933		 Al Khalaf - Methyldopa (Controls unexposed, disease free), 2022 Stillbirth during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 1.99 [1.24;3.22] C
excluded (control group) 		17/1,952   7,631/1,739,944 7,648 1,952
ref
S17149
R71912		 Al Khalaf - Methyldopa (Controls unexposed, sick), 2022 Stillbirth during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 1.02 [0.59;1.73] C 17/1,952   67/7,809 84 1,952
ref
S13880
R54300		 Kayser - Methyldopa, 2020 Stillbirth 2nd and/or 3rd trimester prospective cohort unexposed, disease free Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 0.52 [0.03;10.95] C 0/221   2/580 2 221
ref
S13946
R54577		 Fidler - Methyldopa, 1983 Stillbirths (NOS) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 0.38 [0.02;8.02] C 0/50   2/96 2 50
ref
S14186
R55704		 Redman - Methyldopa, 1976 Stillbirths during pregnancy (anytime or not specified) randomized controlled trial unexposed, sick Adjustment: Randomisation Indications Antihypertensive: All hypertensions, any indications or not specified 1.06 [0.07;17.18] C 1/101   1/107 2 101
ref
Total 4 studies 0.97 [0.58;1.62] 90 2,324
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 Al Khalaf - Methyldopa (Controls unexposed, sick), 2022Al Khalaf - Methyldopa, 2022 1 1.02[0.59; 1.73]841,95291%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Kayser - Methyldopa, 2020Kayser - Methyldopa, 2020 0.52[0.03; 10.95]22213%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Fidler - Methyldopa, 1983Fidler - Methyldopa, 1983 0.38[0.02; 8.02]2503%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Redman - Methyldopa, 1976Redman - Methyldopa, 1976 1.06[0.07; 17.18]21013%ROB confusion: lowROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Total (4 studies) I2 = 0% 0.97[0.58; 1.62]902,3240.25.01.0ROB: 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 0.97[0.58; 1.63]882,2230%NAAl Khalaf - Methyldopa (Controls unexposed, sick), 2022 Kayser - Methyldopa, 2020 Fidler - Methyldopa, 1983 3 case control studiescase control studies 0 RCTRCT 1.06[0.07; 17.18]2101 -NARedman - Methyldopa, 1976 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.45[0.05; 3.84]42710%NAKayser - Methyldopa, 2020 Fidler - Methyldopa, 1983 2 unexposed, sickunexposed, sick 1.02[0.60; 1.72]862,0530%NAAl Khalaf - Methyldopa (Controls unexposed, sick), 2022 Redman - Methyldopa, 1976 2 Tags Adjustment   - No  - No 0.97[0.58; 1.63]882,2230%NAAl Khalaf - Methyldopa (Controls unexposed, sick), 2022 Kayser - Methyldopa, 2020 Fidler - Methyldopa, 1983 3   - Randomisation  - Randomisation 1.06[0.07; 17.18]2101 -NARedman - Methyldopa, 1976 1 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 0.62[0.11; 3.39]63720%NAKayser - Methyldopa, 2020 Fidler - Methyldopa, 1983 Redman - Methyldopa, 1976 3   - Only chronic hypertension indication  - Only chronic hypertension indication 1.02[0.59; 1.73]841,952 -NAAl Khalaf - Methyldopa (Controls unexposed, sick), 2022 1 MatchedMatched 0.38[0.02; 8.02]250 -NAFidler - Methyldopa, 1983 1 All studiesAll studies 0.97[0.58; 1.62]902,3240%NAAl Khalaf - Methyldopa (Controls unexposed, sick), 2022 Kayser - Methyldopa, 2020 Fidler - Methyldopa, 1983 Redman - Methyldopa, 1976 40.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.73.61.8710.000Al Khalaf - Methyldopa (Controls unexposed, sick), 2022Kayser - Methyldopa, 2020Fidler - Methyldopa, 1983Redman - Methyldopa, 1976

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 17152

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.86[1.17; 2.96]7,6522,2230%NAAl Khalaf - Methyldopa (Controls unexposed, disease free), 2022 Kayser - Methyldopa, 2020 Fidler - Methyldopa, 1983 3 unexposed, sick controlsunexposed, sick controls 1.02[0.60; 1.72]862,0530%NAAl Khalaf - Methyldopa (Controls unexposed, sick), 2022 Redman - Methyldopa, 1976 20.510.01.0