Calcium channel blockers (versus unexposed)

All congenital malformations (majors, minors, majors and minors, or unspecified)

id	Study   Auto Ishikawa - Amlodipine (Controls unexposed, disease free), 2023Ishikawa - Amlodipine (Controls unexposed, sick), 2023Mito - Amlodipine, 2019Van Gelder - Calcium blockers, 2015Vasilakis-Scaramozza - Calcium blockers, 2013Nakhai-Pour - Calcium blockers, 2010Weber-Schoendorfer - Calcium blockers, 2008Sorensen - Calcium blockers, 2001Parazzini - Nifedipine, 1998Magee - Calcium blockers, 1996	Lib. in paper	Exposition period  Auto during pregnancy (anytime or not specified)1st trimester2nd trimester3rd trimester2nd and/or 3rd trimesterthroughout pregnancyearly pregnancydays before deliverylate pregnancypreconception-onlypericonceptionalpreconceptional for kinetic reasonat least 1st trimester3 months (or more) before pregnancy or during pregnancy1st and 2nd trimester3 months or more before pregnancy or1st trimester	Study type  All studies Case control excluded Only case control	Control type    Auto unexposed (general population or NOS)unexposed, sickunexposed, disease freeexposed to other treatment, sicknot specifiedsiblingwhatever (meta-analysis)	Tags	OR 95%CI	x1/n1 x0/n0	no cases	no exposed	ROB	Ref.
S14091 R56263	Ishikawa - Amlodipine (Controls unexposed, disease free), 2023	Major congenital malformations	1st trimester	retrospective cohort (claims database)	unexposed, disease free excluded	Adjustment: No Indications Antihypertensive: Only chronic hypertension indication	1.98 [0.78;5.02] C excluded (control group)	5/44   4,519/74,213	4,524	44		ref
S14090 R56264	Ishikawa - Amlodipine (Controls unexposed, sick), 2023	Major congenital malformations	1st trimester	retrospective cohort (claims database)	unexposed, sick	Adjustment: No Indications Antihypertensive: Only chronic hypertension indication	1.69 [0.65;4.42] C	5/44   71/1,007	76	44		ref
S13387 R56273	Mito - Amlodipine, 2019	Major anomalies _ morphologic abnormalities	at least 1st trimester	retrospective cohort	unexposed, sick	Adjustment: No Indications Antihypertensive: Only chronic hypertension indication	0.89 [0.17;4.57]	2/48   6/129	8	48		ref
S13805 R56295	Van Gelder - Calcium blockers, 2015	Selected major birth defects (heart defects, CNS malformations, cleft lip with or without cleft palate, small intestinal atresia/stenosis, hypospadias, ...)	1st trimester	case control	unexposed (general population or NOS)	Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified	1.20 [0.60;2.50]	14/29   5,554/12,792	5,568	29		ref
S13937 R56300	Vasilakis-Scaramozza - Calcium blockers, 2013	Any anomaly, excluding minor and chromosomal anomalies	1st trimester	retrospective cohort	unexposed (general population or NOS)	Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified	0.60 [0.10;4.80]	1/55   16/682	17	55		ref
S13469 R56279	Nakhai-Pour - Calcium blockers, 2010	Major malformations	1st trimester	nested case control	unexposed (general population or NOS)	Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified	3.30 [0.70;15.56] C	2/10   4,153/59,023	4,155	10		ref
S13987 R54925	Weber-Schoendorfer - Calcium blockers, 2008	All birth defects	at least 1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified	1.58 [0.81;3.07]	15/229   33/724	48	229		ref
S13996 R56303	Sorensen - Calcium blockers, 2001	All congenital abnormality	1st trimester	case control	unexposed (general population or NOS)	Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified	1.40 [0.90;2.20]	40/89   22,825/60,927	22,865	89		ref
S13969 R54759	Parazzini - Nifedipine, 1998	Congenital malformations	2nd and/or 3rd trimester excluded	randomized controlled trial	unexposed, sick	Adjustment: Randomisation Indications Antihypertensive: All hypertensions, any indications or not specified	1.98 [0.18;22.16] C excluded (exposition period)	2/129   1/127	3	129		ref
S13988 R56270	Magee - Calcium blockers, 1996	Birth defects (major malformations)	at least 1st trimester	prospective cohort	unexposed (general population or NOS)	Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified Matched	5.63 [0.27;119.49] C	2/66   0/72	2	66		ref
					Total	8 studies	1.44 [1.07;1.93]		32,739	570
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

Sensitivity analysis

Publication bias and p-hacking diagnosis

Sub-groups analysis using all included studies

excluded 14091