Clomiphene

Hypospadias

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.
S15680
R64755		 Weller, 2017 Hypospadias preconceptional for kinetic reason retrospective cohort unexposed (general population or NOS) Adjustment: Yes Clomiphene exposure: 2 months before conception through the first month of pregnancy Clomiphene indications: Not detailled but exclusion of in vitro fertilization (IVF) treatments 1.08 [0.15;7.79] 1/1,861   73/98,728 74 1,861
ref
S15679
R64744		 Lind, 2013 Isolated Second- or Third-Degree Hypospadias preconceptional for kinetic reason case control unexposed (general population or NOS) Adjustment: Yes Clomiphene exposure: 1 month before to 4 months after conception Clomiphene indications: Any or not specified 1.90 [1.20;3.00] 38/81   1,499/5,770 1,537 81
ref
S15714
R64916		 Banhidy, 2008 Hypospadias early pregnancy case control unexposed (general population or NOS) Adjustment: Yes Clomiphene exposure: Inadvertently during the first and second months of pregnancy. Clomiphene indications: Inadvertently treated during pregnancy Matched 1.70 [0.70;4.20] 10/106   3,028/41,083 3,038 106
ref
S15692
R64825		 Meijer, 2006 Hypospadias (glandular/coronary, penile, penoscrotal, or perineal), isolated or in combination with other defects (but not syndromic) preconceptional for kinetic reason case control unexposed (general population or NOS) Adjustment: No Clomiphene exposure: Prior pregnancy (not specified and/or 0-3 months) Clomiphene indications: Any or not specified 1.27 [0.58;2.79] 7/71   385/4,859 392 71
ref
S15703
R64833		 Sorensen, 2005 Hypospadias (ICD-8: 752.20, 752.21, 752.22, 752.28, 752.29; and ICD-10: Q54.0, Q54.1, Q54.2, Q54.3, Q54.4, Q54.8, Q54.9) preconceptional for kinetic reason nested case control unexposed (general population or NOS) Adjustment: Yes Clomiphene exposure: 3 months before until 3 months after conception Clomiphene indications: Any or not specified Matched 0.48 [0.15;1.54] 3/62   316/3,447 319 62
ref
Total 5 studies 1.42 [0.93;2.17] 5,360 2,181
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 Weller, 2017Weller, 2017 1.08[0.15; 7.79]741,8614%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: critical Lind, 2013Lind, 2013 1.90[1.20; 3.00]1,5378144%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Banhidy, 2008Banhidy, 2008 1.70[0.70; 4.20]3,03810618%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Meijer, 2006Meijer, 2006 1.27[0.58; 2.79]3927122%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Sorensen, 2005Sorensen, 2005 0.48[0.15; 1.54]3196212%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Total (5 studies) I2 = 21% 1.42[0.93; 2.17]5,3602,1810.25.01.0ROB: 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 1.08[0.15; 7.78]741,861 -NAWeller, 2017 1 case control studiescase control studies 1.39[0.85; 2.27]5,28632039%NALind, 2013 Banhidy, 2008 Meijer, 2006 Sorensen, 2005 4 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.42[0.93; 2.17]5,3602,18121%NAWeller, 2017 Lind, 2013 Banhidy, 2008 Meijer, 2006 Sorensen, 2005 5 Tags Adjustment   - No  - No 1.27[0.58; 2.79]39271 -NAMeijer, 2006 1   - Yes  - Yes 1.37[0.76; 2.47]4,9682,11038%NAWeller, 2017 Lind, 2013 Banhidy, 2008 Sorensen, 2005 4 Clomiphene exposure   - 1 month before to 4 months after co ...  - 1 month before to 4 months after conception 1.90[1.20; 3.00]1,53781 -NALind, 2013 1   - 2 months before conception through ...  - 2 months before conception through the first month of pregnancy 1.08[0.15; 7.78]741,861 -NAWeller, 2017 1   - 3 months before until 3 months afte ...  - 3 months before until 3 months after conception 0.48[0.15; 1.54]31962 -NASorensen, 2005 1   - Inadvertently during the first and ...  - Inadvertently during the first and second months of pregnancy. 1.70[0.69; 4.16]3,038106 -NABanhidy, 2008 1   - Prior pregnancy (not specified and/ ...  - Prior pregnancy (not specified and/or 0-3 months) 1.27[0.58; 2.79]39271 -NAMeijer, 2006 1 Clomiphene indications   - Any or not specified  - Any or not specified 1.24[0.62; 2.46]2,24821459%NALind, 2013 Meijer, 2006 Sorensen, 2005 3   - Inadvertently treated during pregnancy  - Inadvertently treated during pregnancy 1.70[0.69; 4.16]3,038106 -NABanhidy, 2008 1   - Not detailled but exclusion of in v ...  - Not detailled but exclusion of in vitro fertilization (IVF) treatments 1.08[0.15; 7.78]741,861 -NAWeller, 2017 1 MatchedMatched 0.96[0.28; 3.29]3,35716865%NABanhidy, 2008 Sorensen, 2005 2 All studiesAll studies 1.42[0.93; 2.17]5,3602,18121%NAWeller, 2017 Lind, 2013 Banhidy, 2008 Meijer, 2006 Sorensen, 2005 50.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.42.71.2090.000Weller, 2017Lind, 2013Banhidy, 2008Meijer, 2006Sorensen, 2005

Asymetry test p-value = 0.1927 (by Egger's regression)

slope=0.9898 (0.3793); intercept=-1.6348 (0.9764); t=1.6743; p=0.1927

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) 1.42[0.93; 2.17]5,3602,18121%NAWeller, 2017 Lind, 2013 Banhidy, 2008 Meijer, 2006 Sorensen, 2005 50.510.01.0