Metronidazole (all routes except local only) updated on 01-29-2025

Major congenital malformations

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.
S17594
R74251		 Muanda a (Controls exposed to penicillins), 2017 Major congenital malformations 1st trimester retrospective cohort (claims database) exposed to other treatment, sick excluded Adjustment: Yes 1.15 [0.84;1.57]
excluded (control group) 		47/412   894/9,106 941 412
ref
S17595
R74265		 Muanda a (Controls unexposed, NOS), 2017 Major congenital malformations 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.10 [0.81;1.49] 47/412   12,225/124,469 12,272 412
ref
S17586
R74211		 Zagorodnikova, 2017 Major malformation during pregnancy (anytime or not specified) excluded cohort unexposed, sick Adjustment: No 1.00 [0.42;2.38] C
excluded (exposition period) 		7/200   22/629 29 200
ref
S17582
R74194		 Koss, 2012 Congenital anomalies (excluding the non major) 1st trimester retrospective cohort unexposed, disease free Adjustment: Yes 0.88 [0.30;2.56] 4/348   38/1,907 42 348
ref
S17590
R74241		 Diav-Citrin, 2001 Major anomalies (including ETOP Elective termination of pregnancy) 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.47 [0.48;4.50] 4/131   12/579 16 131
ref
S17589
R74217		 Czeizel, 1998 Congenital abnormality 1st trimester case control unexposed (general population or NOS) Adjustment: Yes 1.14 [0.89;1.46] 107/269   17,193/47,664 17,300 269
ref
S17596
R74281		 Piper, 1993 Any birth defects (minor abnormalities not considered) 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 1.20 [0.90;1.60] 96/1,318   80/1,320 176 1,318
ref
S17583
R74202		 Morgan, 1978 Major congenital abnormalities during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, sick Adjustment: No 0.66 [0.21;2.10] C
excluded (exposition period) 		7/597   5/283 12 597
ref
S17591
R74247		 Heinonen (Controls exposed to penicillins), 1977 Malformations Showing Uniform Rates by Hospital 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 1.53 [0.36;6.47] C
excluded (control group) 		2/31   153/3,546 155 31
ref
S17592
R74249		 Heinonen (Controls unexposed, NOS), 1977 Malformations Showing Uniform Rates by Hospital 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 1.45 [0.35;6.10] C 2/31   2,275/50,251 2,277 31
ref
Total 6 studies 1.15 [0.98;1.34] 32,083 2,509
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 Muanda a (Controls unexposed, NOS), 2017Muanda a, 2017 1 1.10[0.81; 1.49]12,27241226%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Koss, 2012Koss, 2012 0.88[0.30; 2.56]423482%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Diav-Citrin, 2001Diav-Citrin, 2001 1.47[0.48; 4.50]161312%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: criticalROB mesure: criticalROB reporting: moderate Czeizel, 1998Czeizel, 1998 1.14[0.89; 1.46]17,30026940%ROB confusion: unclearROB selection: criticalROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Piper, 1993Piper, 1993 1.20[0.90; 1.60]1761,31829%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Heinonen (Controls unexposed, NOS), 1977Heinonen, 1977 2 1.45[0.35; 6.10]2,277311%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: critical Total (6 studies) I2 = 0% 1.15[0.98; 1.34]32,0832,5090.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, NOS; 2: Controls unexposed, NOS;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.16[0.95; 1.41]14,7832,2400%NAMuanda a (Controls unexposed, NOS), 2017 Koss, 2012 Diav-Citrin, 2001 Piper, 1993 Heinonen (Controls unexposed, NOS), 1977 5 case control studiescase control studies 1.14[0.89; 1.46]17,300269 -NACzeizel, 1998 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.15[0.98; 1.34]32,0832,5090%NAMuanda a (Controls unexposed, NOS), 2017 Koss, 2012 Diav-Citrin, 2001 Czeizel, 1998 Piper, 1993 Heinonen (Controls unexposed, NOS), 1977 6 Tags Adjustment   - No  - No 1.46[0.61; 3.54]2,2931620%NADiav-Citrin, 2001 Heinonen (Controls unexposed, NOS), 1977 2   - Yes  - Yes 1.14[0.97; 1.34]29,7902,3470%NAMuanda a (Controls unexposed, NOS), 2017 Koss, 2012 Czeizel, 1998 Piper, 1993 4 All studiesAll studies 1.15[0.98; 1.34]32,0832,5090%NAMuanda a (Controls unexposed, NOS), 2017 Koss, 2012 Diav-Citrin, 2001 Czeizel, 1998 Piper, 1993 Heinonen (Controls unexposed, NOS), 1977 60.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.71.90.8780.000Muanda a (Controls unexposed, NOS), 2017Koss, 2012Diav-Citrin, 2001Czeizel, 1998Piper, 1993Heinonen (Controls unexposed, NOS), 1977

Asymetry test p-value = 0.7078 (by Egger's regression)

slope=0.1183 (0.0609); intercept=0.1262 (0.3135); t=0.4026; p=0.7078

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 17591, 17594

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.15[0.98; 1.34]32,0832,5090%NAMuanda a (Controls unexposed, NOS), 2017 Koss, 2012 Diav-Citrin, 2001 Czeizel, 1998 Piper, 1993 Heinonen (Controls unexposed, NOS), 1977 6 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.16[0.86; 1.58]1,0964430%NAMuanda a (Controls exposed to penicillins), 2017 Heinonen (Controls exposed to penicillins), 1977 20.510.01.0

Umbrella review (other published meta-analyses)

Published MAControlPeriodTE95% CIn exposedkI2 Burtin (Birth defects in live-born infants (m ...Burtin (Birth defects in live-born infants (major)) 0.93[0.73; 1.18]-T11st trimesterstudies TTT7 Ajiji (Major congenital malformations)Ajiji (Major congenital malformations) 1.15[0.98; 1.34]25%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT12 Ajiji (Major congenital malformations (local ...Ajiji (Major congenital malformations (local route)) 1.19[0.88; 1.62]NA-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT1 Ajiji (Major congenital malformations (system ...Ajiji (Major congenital malformations (systemic route)) 1.05[0.77; 1.43]52%-Wwhatever (meta-analysis)T1+at least 1st trimesterstudies TTT4 Ajiji (Major congenital malformations (vs une ...Ajiji (Major congenital malformations (vs unexposed disease free)) 1.25[0.98; 1.61]30%-U,DFunexposed, disease freeT1+at least 1st trimesterstudies TTT4 Ajiji (Major congenital malformations (vs une ...Ajiji (Major congenital malformations (vs unexposed not specified)) 1.08[0.88; 1.32]20%-U,GPunexposed (general population or NOS)T1+at least 1st trimesterstudies TTT8 metaPregmetaPreg 1.15[0.98; 1.34]0%2,509----Muanda a (Controls unexposed, NOS), 2017 Koss, 2012 Diav-Citrin, 2001 Czeizel, 1998 Piper, 1993 Heinonen (Controls unexposed, NOS), 1977 60.510.01.0