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

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

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.
S17121
R75073		 Van der Zande - Diuretics, 2024 Total foetal and neonatal congenital anomalies (composite of the incidence of foetal or neonatal congenital anomalies, that corresponds to major malformations according to the other publication) 1st trimester prospective cohort unexposed, sick Adjustment: Yes Indications Antihypertensive: Only cardiac indications other than hypertension (long QT syndrome, structural heart disease, ...) 1.30 [0.66;2.55] 11/191   276/5,357 287 191
ref
S13806
R56297		 Van Gelder - Diuretics, 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 1.00 [0.50;2.30] 11/25   5,557/12,796 5,568 25
ref
S13473
R56281		 Nakhai-Pour - Diuretics, 2010 Major malformations 1st trimester nested case control unexposed (general population or NOS) Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 3.15 [1.19;8.35] C 5/26   4,150/59,007 4,155 26
ref
S14087
R55437		 Olesen_Denmark - Diuretics, 2001 Malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: No Indications Antihypertensive: All hypertensions, any indications or not specified 1.90 [0.90;4.30] 7/-   2,235/46,998 2,242 -
ref
S17837
R75315		 Czeizel - Furosemide, 1999 Congenital malformations 1st trimester case control unexposed (general population or NOS) Adjustment: Yes Indications Antihypertensive: All hypertensions, any indications or not specified Matched 1.60 [0.80;3.30] 14/29   22,851/60,987 22,865 29
ref
Total 5 studies 1.55 [1.10;2.18] 35,117 271
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 Van der Zande - Diuretics, 2024Van der Zande - Diuretics, 2024 1.30[0.66; 2.55]28719126%ROB confusion: seriousROB selection: lowROB classification: unclearROB missing: unclearROB mesure: criticalROB reporting: moderate Van Gelder - Diuretics, 2015Van Gelder - Diuretics, 2015 1.00[0.50; 2.30]5,5682520%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Nakhai-Pour - Diuretics, 2010Nakhai-Pour - Diuretics, 2010 3.15[1.19; 8.35]4,1552612%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Olesen_Denmark - Diuretics, 2001Olesen_Denmark - Diuretics, 2001 1.90[0.90; 4.30]2,242-19%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Czeizel - Furosemide, 1999Czeizel - Furosemide, 1999 1.60[0.80; 3.30]22,8652923%ROB confusion: unclearROB selection: criticalROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Total (5 studies) I2 = 0% 1.55[1.10; 2.18]35,1172710.510.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.53[0.92; 2.55]2,5291910%NAVan der Zande - Diuretics, 2024 Olesen_Denmark - Diuretics, 2001 2 case control studiescase control studies 1.61[0.89; 2.93]32,5888039%NAVan Gelder - Diuretics, 2015 Nakhai-Pour - Diuretics, 2010 Czeizel - Furosemide, 1999 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.66[1.08; 2.54]34,8308014%NAVan Gelder - Diuretics, 2015 Nakhai-Pour - Diuretics, 2010 Olesen_Denmark - Diuretics, 2001 Czeizel - Furosemide, 1999 4 unexposed, sickunexposed, sick 1.30[0.66; 2.56]287191 -NAVan der Zande - Diuretics, 2024 1 Tags Adjustment   - No  - No 1.72[0.92; 3.25]11,9655142%NAVan Gelder - Diuretics, 2015 Nakhai-Pour - Diuretics, 2010 Olesen_Denmark - Diuretics, 2001 3   - Yes  - Yes 1.44[0.88; 2.34]23,1522200%NAVan der Zande - Diuretics, 2024 Czeizel - Furosemide, 1999 2 Indications Antihypertensive   - All hypertensions, any indications ...  - All hypertensions, any indications or not specified 1.66[1.08; 2.54]34,8308014%NAVan Gelder - Diuretics, 2015 Nakhai-Pour - Diuretics, 2010 Olesen_Denmark - Diuretics, 2001 Czeizel - Furosemide, 1999 4   - Only cardiac indications other than ...  - Only cardiac indications other than hypertension (long QT syndrome, structural heart disease, ...) 1.30[0.66; 2.56]287191 -NAVan der Zande - Diuretics, 2024 1 MatchedMatched 1.60[0.79; 3.25]22,86529 -NACzeizel - Furosemide, 1999 1 All studiesAll studies 1.55[1.10; 2.18]35,1172710%NAVan der Zande - Diuretics, 2024 Van Gelder - Diuretics, 2015 Nakhai-Pour - Diuretics, 2010 Olesen_Denmark - Diuretics, 2001 Czeizel - Furosemide, 1999 50.510.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.41.60.5970.000Van der Zande - Diuretics, 2024Van Gelder - Diuretics, 2015Nakhai-Pour - Diuretics, 2010Olesen_Denmark - Diuretics, 2001Czeizel - Furosemide, 1999

Asymetry test p-value = 0.1565 (by Egger's regression)

slope=-1.6554 (1.1209); intercept=5.4158 (2.8787); t=1.8814; p=0.1565

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.66[1.08; 2.54]34,8308014%NAVan Gelder - Diuretics, 2015 Nakhai-Pour - Diuretics, 2010 Olesen_Denmark - Diuretics, 2001 Czeizel - Furosemide, 1999 4 unexposed, sick controlsunexposed, sick controls 1.30[0.66; 2.56]287191 -NAVan der Zande - Diuretics, 2024 10.510.01.0