Calcium channel blockers (versus unexposed)

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.
S17153
R71943		 Al Khalaf - Calcium channel blockers (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 4.06 [2.63;6.28] C
excluded (control group) 		22/289   34,584/1,739,944 34,606 289
ref
S17150
R71922		 Al Khalaf - Calcium channel blockers (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 1.85 [1.13;3.03] C 18/289   270/7,809 288 289
ref
S13513
R52200		 Fitton - Calcium blockers (Controls unexposed, disease free), 2020 Small for gestational age (birth weight below the 10th percentile) 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 1.24 [0.64;2.39]
excluded (control group) 		18/167   24,121/250,693 24,139 167
ref
S14422
R57252		 Fitton - Calcium blockers (Controls unexposed, sick), 2020 Small for gestational age (birth weight below the 10th percentile) during pregnancy (anytime or not specified) retrospective cohort (claims database) unexposed, sick Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 0.79 [0.48;1.29] C 18/167   1,059/7,971 1,077 167
ref
S13922
R54506		 Fisher b - Calcium inhibitors (Controls unexposed, disease free), 2018 Small for gestational age (birthweight < 10th percentile for a given gestational age in weeks, sex, race/ethnicity, and parity) during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free excluded Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 1.98 [0.37;7.01]
excluded (control group) 		3/18   923/9,219 926 18
ref
S13923
R54507		 Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018 Small for gestational age (birthweight < 10th percentile for a given gestational age in weeks, sex, race/ethnicity, and parity) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 1.46 [0.42;5.14] C 3/18   101/839 104 18
ref
S13449
R51812		 Su - Calcium blockers (Controls unexposed, disease free), 2013 Small for gestational age (<10th percentile for gestational age and gender) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, disease free excluded Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 1.79 [1.37;2.34] C
excluded (control group) 		74/303   1,250/8,181 1,324 303
ref
S13443
R51794		 Su - Calcium blockers (Controls unexposed, sick), 2013 Small for gestational age (<10th percentile for gestational age and gender) during pregnancy (anytime or not specified) population based cohort retrospective unexposed, sick Adjustment: Yes Indications Antihypertensive: Only chronic hypertension indication 1.45 [1.06;1.97] 74/303   184/1,006 258 303
ref
S13469
R51950		 Nakhai-Pour - Calcium blockers, 2010 Small for gestational age (a birth weight less than the 10th percentile for that gestational age and gender) 2nd and/or 3rd trimester nested case control unexposed (general population or NOS) Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 2.19 [0.09;53.74] C 0/1   7,445/56,333 7,445 1
ref
S13789
R54071		 Bayliss - Calcium blockers, 2002 Small for gestational age (birth weight for gestation on or below the 10th percentile using Gairdner– Pearson growth charts) throughout pregnancy retrospective cohort unexposed, sick Adjustment: No Indications Antihypertensive: Only chronic hypertension indication 0.68 [0.18;2.54] C 3/14   49/171 52 14
ref
S13988
R54962		 Magee - Calcium blockers, 1996 Small for gestational age (NOS) at least 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched 4.49 [0.49;41.36] C 4/61   1/65 5 61
ref
Total 7 studies 1.31 [0.94;1.82] 9,229 853
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 - Calcium channel blockers (Controls unexposed, sick), 2022Al Khalaf - Calcium channel b..., 2022 1 1.85[1.13; 3.03]28828924%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: moderateROB reporting: moderate Fitton - Calcium blockers (Controls unexposed, sick), 2020Fitton - Calcium blockers, 2020 2 0.79[0.48; 1.29]1,07716724%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: moderateROB mesure: moderateROB reporting: moderate Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018Fisher b - Calcium inhibitors, 2018 3 1.46[0.42; 5.14]104186%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Su - Calcium blockers (Controls unexposed, sick), 2013Su - Calcium blockers, 2013 4 1.45[1.06; 1.97]25830336%ROB confusion: seriousROB selection: lowROB classification: moderateROB missing: unclearROB mesure: moderateROB reporting: moderate Nakhai-Pour - Calcium blockers, 2010Nakhai-Pour - Calcium blockers, 2010 2.19[0.09; 53.74]7,44511%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Bayliss - Calcium blockers, 2002Bayliss - Calcium blockers, 2002 0.68[0.18; 2.54]52146%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Magee - Calcium blockers, 1996Magee - Calcium blockers, 1996 4.49[0.49; 41.36]5612%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: moderateROB mesure: criticalROB reporting: moderate Total (7 studies) I2 = 30% 1.31[0.94; 1.82]9,2298530.210.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick; 3: Controls unexposed, sick; 4: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.30[0.91; 1.86]1,78485241%NAAl Khalaf - Calcium channel blockers (Controls unexposed, sick), 2022 Fitton - Calcium blockers (Controls unexposed, sick), 2020 Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018 Su - Calcium blockers (Controls unexposed, sick), 2013 Bayliss - Calcium blockers, 2002 Magee - Calcium blockers, 1996 6 case control studiescase control studies 2.19[0.09; 53.74]7,4451 -NANakhai-Pour - Calcium blockers, 2010 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 3.56[0.57; 22.04]7,450620%NANakhai-Pour - Calcium blockers, 2010 Magee - Calcium blockers, 1996 2 unexposed, sickunexposed, sick 1.26[0.88; 1.81]1,77979146%NAAl Khalaf - Calcium channel blockers (Controls unexposed, sick), 2022 Fitton - Calcium blockers (Controls unexposed, sick), 2020 Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018 Su - Calcium blockers (Controls unexposed, sick), 2013 Bayliss - Calcium blockers, 2002 5 Tags Adjustment   - No  - No 1.25[0.75; 2.07]8,97155038%NAAl Khalaf - Calcium channel blockers (Controls unexposed, sick), 2022 Fitton - Calcium blockers (Controls unexposed, sick), 2020 Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018 Nakhai-Pour - Calcium blockers, 2010 Bayliss - Calcium blockers, 2002 Magee - Calcium blockers, 1996 6   - Yes  - Yes 1.45[1.06; 1.98]258303 -NASu - Calcium blockers (Controls unexposed, sick), 2013 1 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 0.97[0.59; 1.60]8,6312474%NAFitton - Calcium blockers (Controls unexposed, sick), 2020 Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018 Nakhai-Pour - Calcium blockers, 2010 Magee - Calcium blockers, 1996 4   - Only chronic hypertension indication  - Only chronic hypertension indication 1.51[1.14; 1.99]5986067%NAAl Khalaf - Calcium channel blockers (Controls unexposed, sick), 2022 Su - Calcium blockers (Controls unexposed, sick), 2013 Bayliss - Calcium blockers, 2002 3 MatchedMatched 4.49[0.49; 41.36]561 -NAMagee - Calcium blockers, 1996 1 All studiesAll studies 1.31[0.94; 1.82]9,22985330%NAAl Khalaf - Calcium channel blockers (Controls unexposed, sick), 2022 Fitton - Calcium blockers (Controls unexposed, sick), 2020 Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018 Su - Calcium blockers (Controls unexposed, sick), 2013 Nakhai-Pour - Calcium blockers, 2010 Bayliss - Calcium blockers, 2002 Magee - Calcium blockers, 1996 70.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-3.84.11.9600.000Al Khalaf - Calcium channel blockers (Controls unexposed, sick), 2022Fitton - Calcium blockers (Controls unexposed, sick), 2020Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018Su - Calcium blockers (Controls unexposed, sick), 2013Nakhai-Pour - Calcium blockers, 2010Bayliss - Calcium blockers, 2002Magee - Calcium blockers, 1996

Asymetry test p-value = 0.9132 (by Egger's regression)

slope=0.2663 (0.2533); intercept=0.0966 (0.8424); t=0.1147; p=0.9132

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 13449, 13922, 13513, 17153

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 2.20[1.34; 3.63]68,44583962%NAAl Khalaf - Calcium channel blockers (Controls unexposed, disease free), 2022 Fitton - Calcium blockers (Controls unexposed, disease free), 2020 Fisher b - Calcium inhibitors (Controls unexposed, disease free), 2018 Su - Calcium blockers (Controls unexposed, disease free), 2013 Nakhai-Pour - Calcium blockers, 2010 Magee - Calcium blockers, 1996 6 unexposed, sick controlsunexposed, sick controls 1.26[0.88; 1.81]1,77979146%NAAl Khalaf - Calcium channel blockers (Controls unexposed, sick), 2022 Fitton - Calcium blockers (Controls unexposed, sick), 2020 Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018 Su - Calcium blockers (Controls unexposed, sick), 2013 Bayliss - Calcium blockers, 2002 50.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Bellos - Amlodipine (Small for gestational ag ...Bellos - Amlodipine (Small for gestational age (Randomized controlled trial and Cohort studies)) 0.65[0.25; 1.64]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bellos - Nifedipine (Small for gestational ag ...Bellos - Nifedipine (Small for gestational age (Randomized controlled trial and Cohort studies)) 1.85[0.93; 3.67]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) 0.85[0.46; 1.56]22%-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 Labetalol)) 1.06[0.34; 3.19]33%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bone - GESTATIONAL HYPERTENSION (Small for ge ...Bone - GESTATIONAL HYPERTENSION (Small for gestational age infants (versus methyldopa)) Out of scale0.36[0.03; 2.85]34%-Eexposed to other treatment, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bellos - Amlodipine (Small-for-gestational ag ...Bellos - Amlodipine (Small-for-gestational age (Randomized controlled trial only)) 2.00[0.17; 24.07]NA-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT-9 Bellos - Nifedipine (Small-for-gestational ag ...Bellos - Nifedipine (Small-for-gestational age (Randomized controlled trial only)) 1.28[0.79; 2.09]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)) 0.83[0.60; 1.16]0%-U,Sunexposed, sickAnyduring pregnancy (anytime or not specified)studies TTT3 metaPregmetaPreg 1.31[0.94; 1.82]30%853----Al Khalaf - Calcium channel blockers (Controls unexposed, sick), 2022 Fitton - Calcium blockers (Controls unexposed, sick), 2020 Fisher b - Calcium inhibitors (Controls unexposed, sick), 2018 Su - Calcium blockers (Controls unexposed, sick), 2013 Nakhai-Pour - Calcium blockers, 2010 Bayliss - Calcium blockers, 2002 Magee - Calcium blockers, 1996 70.510.01.0