Clomiphene

Neural Tube Defects

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
R64752		 Weller, 2017 Neural Tube Defects 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 1.12 [0.62;2.02] 14/1,861   642/98,728 656 1,861
ref
S15691
R64824		 Benedum, 2016 Neural Tube Defects preconceptional for kinetic reason case control unexposed, disease free Adjustment: Yes Clomiphene exposure: 1 month before the LMP to 1 month after the LMP Clomiphene indications: Not detailled but exclusion of ART including IVF or ICSI 2.10 [0.90;4.80] 7/76   212/4,405 219 76
ref
S15714
R64914		 Banhidy, 2008 Neural tube defects 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 4.50 [0.70;26.70] 7/103   1,195/39,250 1,202 103
ref
S15707
R64859		 Lammer, 1995 Neural Tube Defects (anencephaly and spina bifida aperta) preconceptional for kinetic reason case control unexposed (general population or NOS) Adjustment: No Clomiphene exposure: The menstrual cycle just preceding conception (all or mainly) Clomiphene indications: Ovarian stimulation for infertility (NOS) 0.87 [0.14;4.10] 3/-   286/- 289 -
ref
S15716
R64922		 Shaw, 1995 Neural Tube Defects (anencephaly, spina bifida cystica, craniorachischisis, or iniencephaly) preconceptional for kinetic reason case control unexposed (general population or NOS) Adjustment: No Clomiphene exposure: 3 months before pregnancy Clomiphene indications: Any or not specified 1.50 [0.43;6.10] 6/10   532/1,067 538 10
ref
S15717
R64923		 Milunsky, 1990 Neural tube defects preconceptional for kinetic reason prospective cohort unexposed (general population or NOS) Adjustment: No Clomiphene exposure: 3 months before pregnancy Clomiphene indications: Any or not specified 2.20 [0.60;8.60] 2/438   47/22,317 49 438
ref
Total 6 studies 1.50 [1.00;2.25] 2,953 2,488
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 1.12[0.62; 2.02]6561,86147%ROB confusion: criticalROB selection: lowROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: critical Benedum, 2016Benedum, 2016 2.10[0.90; 4.80]2197623%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Banhidy, 2008Banhidy, 2008 4.50[0.70; 26.70]1,2021035%ROB confusion: criticalROB selection: criticalROB classification: moderateROB missing: unclearROB mesure: unclearROB reporting: moderate Lammer, 1995Lammer, 1995 0.87[0.14; 4.10]289-6%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: moderateROB reporting: moderate Shaw, 1995Shaw, 1995 1.50[0.43; 6.10]538109%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: unclearROB reporting: moderate Milunsky, 1990Milunsky, 1990 2.20[0.60; 8.60]494389%ROB confusion: criticalROB selection: unclearROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Total (6 studies) I2 = 0% 1.50[1.00; 2.25]2,9532,4880.210.01.0ROB: 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 1.25[0.73; 2.15]7052,2990%NAWeller, 2017 Milunsky, 1990 2 case control studiescase control studies 1.90[1.03; 3.51]2,2481890%NABenedum, 2016 Banhidy, 2008 Lammer, 1995 Shaw, 1995 4 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.50[1.00; 2.25]2,9532,4880%NAWeller, 2017 Benedum, 2016 Banhidy, 2008 Lammer, 1995 Shaw, 1995 Milunsky, 1990 6 Tags Adjustment   - No  - No 1.53[0.67; 3.47]8764480%NALammer, 1995 Shaw, 1995 Milunsky, 1990 3   - Yes  - Yes 1.63[0.87; 3.08]2,0772,04032%NAWeller, 2017 Benedum, 2016 Banhidy, 2008 3 Clomiphene exposure   - 1 month before the LMP to 1 month a ...  - 1 month before the LMP to 1 month after the LMP 2.10[0.91; 4.85]21976 -NABenedum, 2016 1   - 2 months before conception through ...  - 2 months before conception through the first month of pregnancy 1.12[0.62; 2.02]6561,861 -NAWeller, 2017 1   - 3 months before pregnancy  - 3 months before pregnancy 1.82[0.71; 4.64]5874480%NAShaw, 1995 Milunsky, 1990 2   - Inadvertently during the first and ...  - Inadvertently during the first and second months of pregnancy. 4.50[0.73; 27.79]1,202103 -NABanhidy, 2008 1   - The menstrual cycle just preceding ...  - The menstrual cycle just preceding conception (all or mainly) 0.87[0.16; 4.71]289- -NALammer, 1995 1 Clomiphene indications   - Any or not specified  - Any or not specified 1.82[0.71; 4.64]5874480%NAShaw, 1995 Milunsky, 1990 2   - Inadvertently treated during pregnancy  - Inadvertently treated during pregnancy 4.50[0.73; 27.79]1,202103 -NABanhidy, 2008 1   - Not detailled but exclusion of ART ...  - Not detailled but exclusion of ART including IVF or ICSI 2.10[0.91; 4.85]21976 -NABenedum, 2016 1   - Not detailled but exclusion of in v ...  - Not detailled but exclusion of in vitro fertilization (IVF) treatments 1.12[0.62; 2.02]6561,861 -NAWeller, 2017 1   - Ovarian stimulation for infertility ...  - Ovarian stimulation for infertility (NOS) 0.87[0.16; 4.71]289- -NALammer, 1995 1 MatchedMatched 4.50[0.73; 27.79]1,202103 -NABanhidy, 2008 1 All studiesAll studies 1.50[1.00; 2.25]2,9532,4880%NAWeller, 2017 Benedum, 2016 Banhidy, 2008 Lammer, 1995 Shaw, 1995 Milunsky, 1990 60.210.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-2.22.61.1150.000Weller, 2017Benedum, 2016Banhidy, 2008Lammer, 1995Shaw, 1995Milunsky, 1990

Asymetry test p-value = 0.3161 (by Egger's regression)

slope=-0.0459 (0.4301); intercept=0.9715 (0.8486); t=1.1448; p=0.3161

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) 1.50[1.00; 2.25]2,9532,4880%NAWeller, 2017 Benedum, 2016 Banhidy, 2008 Lammer, 1995 Shaw, 1995 Milunsky, 1990 60.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Auffret (Neural tube defects)Auffret (Neural tube defects) 1.21[0.88; 1.66]26%-Wwhatever (meta-analysis)Peri(PK)preconceptional for kinetic reasonstudies TTT13 Greenland (Neural tube defects)Greenland (Neural tube defects) 1.08[0.76; 1.51]-Wwhatever (meta-analysis)Peripericonceptionalstudies TTT10 metaPregmetaPreg 1.50[1.00; 2.25]0%2,488----Weller, 2017 Benedum, 2016 Banhidy, 2008 Lammer, 1995 Shaw, 1995 Milunsky, 1990 60.510.01.0