Methyldopa (versus unexposed) updated on 03-11-2025

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.
S17243
R72159		 Al Khalaf (Controls unexposed, disease free), 2022 Fetal growth restriction during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, disease free excluded Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 1.86 [1.47;2.36] C
excluded (control group) 		71/1,952   34,584/1,739,944 34,655 1,952
ref
S17244
R72166		 Al Khalaf (Controls unexposed, sick), 2022 Fetal growth restriction during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 1.05 [0.81;1.38] C 71/1,952   270/7,809 341 1,952
ref
S14346
R56768		 Kayser, 2020 Small for gestational age (birth weight < 10th percentile for gestational age and sex- 2nd and/or 3rd trimester prospective cohort unexposed, disease free Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 1.04 [0.57;1.89] C 15/147   58/587 73 147
ref
S14364
R56881		 Orbach, 2013 Small for gestational age 3rd trimester retrospective cohort (claims database) unexposed, disease free Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 1.36 [0.67;2.75] 8/340   1,704/97,820 1,712 340
ref
S14339
R56733		 Mabie, 1986 Intra-uterine growth retardation (birthweight < 10th percentile according to Lubchenco curve) during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 5.57 [1.69;18.35] C 12/54   4/82 16 54
ref
S14376
R56967		 Welt, 1981 Small for gestational age 2nd and/or 3rd trimester randomized controlled trial unexposed, sick Adjustment: Randomisation Indications Antihypertensive: Only chronic hypertension indication 3.67 [0.12;113.74] C 1/6   0/6 1 6
ref
Total 5 studies 1.36 [0.87;2.13] 2,143 2,499
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 (Controls unexposed, sick), 2022Al Khalaf, 2022 1 1.05[0.81; 1.38]3411,95240%ROB confusion: criticalROB selection: unclearROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Kayser, 2020Kayser, 2020 1.04[0.57; 1.89]7314726%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: lowROB mesure: unclearROB reporting: moderate Orbach, 2013Orbach, 2013 1.36[0.67; 2.75]1,71234022%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Mabie, 1986Mabie, 1986 5.57[1.69; 18.35]165411%ROB confusion: criticalROB selection: moderateROB classification: unclearROB missing: unclearROB mesure: moderateROB reporting: moderate Welt, 1981Welt, 1981 3.67[0.12; 113.74]162%ROB confusion: lowROB selection: unclearROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Total (5 studies) I2 = 49% 1.36[0.87; 2.13]2,1432,4990.520.01.0ROB: 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 1.35[0.84; 2.18]2,1422,49360%NAAl Khalaf (Controls unexposed, sick), 2022 Kayser, 2020 Orbach, 2013 Mabie, 1986 4 case control studiescase control studies 0 RCTRCT 3.67[0.12; 113.74]16 -NAWelt, 1981 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.16[0.74; 1.83]1,7854870%NAKayser, 2020 Orbach, 2013 2 unexposed, sickunexposed, sick 2.28[0.57; 9.10]3582,01274%NAAl Khalaf (Controls unexposed, sick), 2022 Mabie, 1986 Welt, 1981 3 Tags Adjustment   - No  - No 1.35[0.84; 2.18]2,1422,49360%NAAl Khalaf (Controls unexposed, sick), 2022 Kayser, 2020 Orbach, 2013 Mabie, 1986 4   - Randomisation  - Randomisation 3.67[0.12; 113.74]16 -NAWelt, 1981 1 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 1.16[0.74; 1.83]1,7854870%NAKayser, 2020 Orbach, 2013 2   - Only chronic hypertension indication  - Only chronic hypertension indication 2.28[0.57; 9.10]3582,01274%NAAl Khalaf (Controls unexposed, sick), 2022 Mabie, 1986 Welt, 1981 3 All studiesAll studies 1.36[0.87; 2.13]2,1432,49949%NAAl Khalaf (Controls unexposed, sick), 2022 Kayser, 2020 Orbach, 2013 Mabie, 1986 Welt, 1981 50.520.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.14.42.1030.000Al Khalaf (Controls unexposed, sick), 2022Kayser, 2020Orbach, 2013Mabie, 1986Welt, 1981

Asymetry test p-value = 0.1647 (by Egger's regression)

slope=-0.1760 (0.2156); intercept=1.5345 (0.8386); t=1.8298; p=0.1647

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) 1.51[1.04; 2.19]36,4402,43944%NAAl Khalaf (Controls unexposed, disease free), 2022 Kayser, 2020 Orbach, 2013 3 unexposed, sick controlsunexposed, sick controls 2.28[0.57; 9.10]3582,01274%NAAl Khalaf (Controls unexposed, sick), 2022 Mabie, 1986 Welt, 1981 30.510.01.0

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)) 1.62[0.97; 2.71]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) 0.81[0.40; 1.77]29%-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 (versus beta-blockers)) 0.86[0.16; 4.17]32%-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)) 1.11[0.69; 1.80]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Abalos (Small-for-gestational age (RCT versus ...Abalos (Small-for-gestational age (RCT versus no antihypertensive drugs/placebo)) 0.96[0.02; 47.65]72%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT2 metaPregmetaPreg 1.36[0.87; 2.13]49%2,499----Al Khalaf (Controls unexposed, sick), 2022 Kayser, 2020 Orbach, 2013 Mabie, 1986 Welt, 1981 50.510.01.0