Calcium channel blockers (versus unexposed)

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.
S13513
R52198		 Fitton - Calcium blockers (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 4.73 [2.90;7.71]
excluded (control group) 		39/167   12,622/250,693 12,661 167
ref
S14422
R57250		 Fitton - Calcium blockers (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 3.00 [2.08;4.32] C 39/167   736/7,971 775 167
ref
S13387
R52258		 Mito - Amlodipine, 2019 Preterm birth (<37 wks) at least 1st trimester retrospective cohort unexposed, sick Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 0.56 [0.26;1.24] C 10/48   41/129 51 48
ref
S13449
R51810		 Su - Calcium blockers (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 2.66 [1.92;3.67] C
excluded (control group) 		47/303   529/8,181 576 303
ref
S13443
R51792		 Su - Calcium blockers (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 2.11 [1.43;3.10] 47/303   84/1,006 131 303
ref
S13987
R54924		 Weber-Schoendorfer - Calcium blockers, 2008 Preterm children (<37 weeks) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified 4.63 [2.94;7.27] 54/227   47/722 101 227
ref
S13969
R54749		 Parazzini - Nifedipine, 1998 Preterm delivery (< 37 weeks of gestation) 2nd and/or 3rd trimester randomized controlled trial unexposed, sick Adjustment: Randomisation Indications Antihypertensive: All hypertensions, any indications or not specified 1.26 [0.77;2.07] C 58/129   50/127 108 129
ref
S13988
R54961		 Magee - Calcium blockers, 1996 Delivery < 37 weeks at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 4.01 [1.03;15.62] 18/64   6/71 24 64
ref
Total 6 studies 2.08 [1.23;3.53] 1,190 938
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 Fitton - Calcium blockers (Controls unexposed, sick), 2020Fitton - Calcium blockers, 2020 1 3.00[2.08; 4.32]77516720%ROB confusion: criticalROB selection: lowROB classification: moderateROB missing: moderateROB mesure: moderateROB reporting: moderate Mito - Amlodipine, 2019Mito - Amlodipine, 2019 0.56[0.26; 1.24]514815%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Su - Calcium blockers (Controls unexposed, sick), 2013Su - Calcium blockers, 2013 2 2.11[1.43; 3.10]13130320%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Weber-Schoendorfer - Calcium blockers, 2008Weber-Schoendorfer - Calcium blockers, 2008 4.63[2.94; 7.27]10122719%ROB confusion: seriousROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: unclearROB reporting: moderate Parazzini - Nifedipine, 1998Parazzini - Nifedipine, 1998 1.26[0.77; 2.07]10812918%ROB confusion: lowROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Magee - Calcium blockers, 1996Magee - Calcium blockers, 1996 4.01[1.03; 15.62]24649%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Total (6 studies) I2 = 83% 2.08[1.23; 3.53]1,1909380.210.01.0ROB: 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 2.33[1.31; 4.15]1,08280982%NAFitton - Calcium blockers (Controls unexposed, sick), 2020 Mito - Amlodipine, 2019 Su - Calcium blockers (Controls unexposed, sick), 2013 Weber-Schoendorfer - Calcium blockers, 2008 Magee - Calcium blockers, 1996 5 case control studiescase control studies 0 RCTRCT 1.26[0.77; 2.07]108129 -NAParazzini - Nifedipine, 1998 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 4.56[2.97; 7.01]1252910%NAWeber-Schoendorfer - Calcium blockers, 2008 Magee - Calcium blockers, 1996 2 unexposed, sickunexposed, sick 1.57[0.88; 2.81]1,06564783%NAFitton - Calcium blockers (Controls unexposed, sick), 2020 Mito - Amlodipine, 2019 Su - Calcium blockers (Controls unexposed, sick), 2013 Parazzini - Nifedipine, 1998 4 Tags Adjustment   - No  - No 1.82[0.54; 6.13]85027986%NAFitton - Calcium blockers (Controls unexposed, sick), 2020 Mito - Amlodipine, 2019 Magee - Calcium blockers, 1996 3   - Randomisation  - Randomisation 1.26[0.77; 2.07]108129 -NAParazzini - Nifedipine, 1998 1   - Yes  - Yes 3.10[1.43; 6.69]23253085%NASu - Calcium blockers (Controls unexposed, sick), 2013 Weber-Schoendorfer - Calcium blockers, 2008 2 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 2.77[1.51; 5.08]1,00858780%NAFitton - Calcium blockers (Controls unexposed, sick), 2020 Weber-Schoendorfer - Calcium blockers, 2008 Parazzini - Nifedipine, 1998 Magee - Calcium blockers, 1996 4   - Only chronic hypertension indication  - Only chronic hypertension indication 1.14[0.32; 4.15]18235188%NAMito - Amlodipine, 2019 Su - Calcium blockers (Controls unexposed, sick), 2013 2 MatchedMatched 4.01[1.03; 15.62]2464 -NAMagee - Calcium blockers, 1996 1 All studiesAll studies 2.08[1.23; 3.53]1,19093883%NAFitton - Calcium blockers (Controls unexposed, sick), 2020 Mito - Amlodipine, 2019 Su - Calcium blockers (Controls unexposed, sick), 2013 Weber-Schoendorfer - Calcium blockers, 2008 Parazzini - Nifedipine, 1998 Magee - Calcium blockers, 1996 60.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.82.40.8320.000Fitton - Calcium blockers (Controls unexposed, sick), 2020Mito - Amlodipine, 2019Su - Calcium blockers (Controls unexposed, sick), 2013Weber-Schoendorfer - Calcium blockers, 2008Parazzini - Nifedipine, 1998Magee - Calcium blockers, 1996

Asymetry test p-value = 0.5521 (by Egger's regression)

slope=1.3131 (0.7627); intercept=-1.9866 (3.0638); t=0.6484; p=0.5521

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 13449, 13513

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 3.74[2.62; 5.33]13,36276148%NAFitton - Calcium blockers (Controls unexposed, disease free), 2020 Su - Calcium blockers (Controls unexposed, disease free), 2013 Weber-Schoendorfer - Calcium blockers, 2008 Magee - Calcium blockers, 1996 4 unexposed, sick controlsunexposed, sick controls 1.57[0.88; 2.81]1,06564783%NAFitton - Calcium blockers (Controls unexposed, sick), 2020 Mito - Amlodipine, 2019 Su - Calcium blockers (Controls unexposed, sick), 2013 Parazzini - Nifedipine, 1998 40.510.01.0

Umbrella review (other published meta-analyses)

Published MATE95% CIn exposedkI2Control groupExposition period AbalosAbalos 1.01[0.86; 1.18]0%-unexposed, sickduring pregnancy (anytime or not specified)studies4 Bellos - AmlodipineBellos - Amlodipine 1.50[0.19; 11.56]NA-unexposed, sickduring pregnancy (anytime or not specified)studies-9 Bellos - AmlodipineBellos - Amlodipine 0.75[0.22; 2.51]NA-unexposed, sickduring pregnancy (anytime or not specified)studies-9 Bellos - NifedipineBellos - Nifedipine 1.06[0.50; 2.27]NA-unexposed, sickduring pregnancy (anytime or not specified)studies-9 Bellos - NifedipineBellos - Nifedipine 1.50[0.52; 4.32]NA-unexposed, sickduring pregnancy (anytime or not specified)studies-9 Bone - GESTATIONAL HYPERTENSIONBone - GESTATIONAL HYPERTENSION 1.06[0.76; 1.50]20%-unexposed, sickduring pregnancy (anytime or not specified)studies-9 Bone - GESTATIONAL HYPERTENSIONBone - GESTATIONAL HYPERTENSION 0.51[0.15; 1.82]31%-exposed to other treatment, sickduring pregnancy (anytime or not specified)studies-9 Bone - GESTATIONAL HYPERTENSIONBone - GESTATIONAL HYPERTENSION 1.64[0.69; 4.01]33%-exposed to other treatment, sickduring pregnancy (anytime or not specified)studies-9 Bone - GESTATIONAL HYPERTENSIONBone - GESTATIONAL HYPERTENSION 1.36[0.45; 4.27]33%-exposed to other treatment, sickduring pregnancy (anytime or not specified)studies-9 metaPregmetaPreg 2.08[1.23; 3.53]83%938--Fitton - Calcium blockers (Controls unexposed, sick), 2020 Mito - Amlodipine, 2019 Su - Calcium blockers (Controls unexposed, sick), 2013 Weber-Schoendorfer - Calcium blockers, 2008 Parazzini - Nifedipine, 1998 Magee - Calcium blockers, 1996 60.510.01.0