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

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.
S17601
R74302		 Kamal, 2018 Congenital anomalies (NOS) 2nd and/or 3rd trimester excluded prospective cohort unexposed, disease free Adjustment: No 1.52 [0.07;32.36] C
excluded (exposition period) 		0/35   2/265 2 35
ref
S17594
R74264		 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
R74278		 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
R74214		 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
R74195		 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
S10586
R39043		 Andrews, 2003 Congenital malformations 2nd trimester excluded randomized controlled trial unexposed, sick Adjustment: Randomisation Co-administration 1.03 [0.29;3.58] C
excluded (exposition period) 		5/347   5/356 10 347
ref
S17590
R74242		 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
S17585
R74207		 Sorensen, 1999 Congenital abnormalities 1st trimester retrospective cohort (claims database) unexposed (general population or NOS) Adjustment: Yes 0.44 [0.11;1.81] 2/84   693/13,327 695 84
ref
S17589
R74234		 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
S17588
R74216		 Caro-Paton, 1997 Any malformations 1st trimester case control unexposed (general population or NOS) Adjustment: No 1.48 [0.78;2.79] 24/40   21,054/41,822 21,078 40
ref
S17596
R74290		 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
S17584
R74204		 Rosa, 1987 Birth defects 1st trimester case control unexposed (general population or NOS) Adjustment: No 0.92 [0.70;1.20] 63/1,083   6,501/103,256 6,564 1,083
ref
S17583
R74201		 Morgan, 1978 Congenital abnormalities (major and minor) during pregnancy (anytime or not specified) excluded retrospective cohort unexposed, sick Adjustment: No 0.71 [0.28;1.74] C
excluded (exposition period) 		12/597   8/283 20 597
ref
S17591
R74246		 Heinonen (Controls exposed to penicillins), 1977 Any Malformations 1st trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No 2.00 [0.70;5.78] C
excluded (control group) 		4/31   244/3,546 248 31
ref
S17592
R74248		 Heinonen (Controls unexposed, NOS), 1977 Any Malformations 1st trimester prospective cohort unexposed (general population or NOS) Adjustment: No 2.15 [0.75;6.14] C 4/31   3,244/50,251 3,248 31
ref
Total 9 studies 1.10 [0.97;1.26] 61,391 3,716
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]12,27241218%ROB confusion: seriousROB selection: moderateROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: moderate Koss, 2012Koss, 2012 0.88[0.30; 2.56]423481%ROB confusion: seriousROB selection: criticalROB classification: criticalROB missing: unclearROB mesure: criticalROB reporting: moderate Diav-Citrin, 2001Diav-Citrin, 2001 1.47[0.48; 4.50]161311%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: criticalROB mesure: criticalROB reporting: moderate Sorensen, 1999Sorensen, 1999 0.44[0.11; 1.81]695841%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: unclearROB mesure: unclearROB reporting: moderate Czeizel, 1998Czeizel, 1998 1.14[0.89; 1.46]17,30026928%ROB confusion: unclearROB selection: criticalROB classification: moderateROB missing: lowROB mesure: criticalROB reporting: moderate Caro-Paton, 1997Caro-Paton, 1997 1.48[0.78; 2.79]21,078404%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Piper, 1993Piper, 1993 1.20[0.90; 1.60]1761,31821%ROB confusion: criticalROB selection: moderateROB classification: criticalROB missing: lowROB mesure: criticalROB reporting: moderate Rosa, 1987Rosa, 1987 0.92[0.70; 1.20]6,5641,08324%ROB confusion: criticalROB selection: criticalROB classification: criticalROB missing: lowROB mesure: moderateROB reporting: critical Heinonen (Controls unexposed, NOS), 1977Heinonen, 1977 2 2.15[0.75; 6.14]3,248312%ROB confusion: criticalROB selection: moderateROB classification: moderateROB missing: unclearROB mesure: criticalROB reporting: critical Total (9 studies) I2 = 0% 1.10[0.97; 1.26]61,3913,7160.25.01.0ROB: 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 1.15[0.95; 1.40]16,4492,3240%NAMuanda a (Controls unexposed, NOS), 2017 Koss, 2012 Diav-Citrin, 2001 Sorensen, 1999 Piper, 1993 Heinonen (Controls unexposed, NOS), 1977 6 case control studiescase control studies 1.07[0.87; 1.31]44,9421,39218%NACzeizel, 1998 Caro-Paton, 1997 Rosa, 1987 3 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.10[0.97; 1.26]61,3913,7160%NAMuanda a (Controls unexposed, NOS), 2017 Koss, 2012 Diav-Citrin, 2001 Sorensen, 1999 Czeizel, 1998 Caro-Paton, 1997 Piper, 1993 Rosa, 1987 Heinonen (Controls unexposed, NOS), 1977 9 Tags Adjustment   - No  - No 1.18[0.82; 1.70]30,9061,28528%NADiav-Citrin, 2001 Caro-Paton, 1997 Rosa, 1987 Heinonen (Controls unexposed, NOS), 1977 4   - Yes  - Yes 1.13[0.96; 1.32]30,4852,4310%NAMuanda a (Controls unexposed, NOS), 2017 Koss, 2012 Sorensen, 1999 Czeizel, 1998 Piper, 1993 5 All studiesAll studies 1.10[0.97; 1.26]61,3913,7160%NAMuanda a (Controls unexposed, NOS), 2017 Koss, 2012 Diav-Citrin, 2001 Sorensen, 1999 Czeizel, 1998 Caro-Paton, 1997 Piper, 1993 Rosa, 1987 Heinonen (Controls unexposed, NOS), 1977 90.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.71.80.8570.000Muanda a (Controls unexposed, NOS), 2017Koss, 2012Diav-Citrin, 2001Sorensen, 1999Czeizel, 1998Caro-Paton, 1997Piper, 1993Rosa, 1987Heinonen (Controls unexposed, NOS), 1977

Asymetry test p-value = 0.7494 (by Egger's regression)

slope=0.0618 (0.1229); intercept=0.2041 (0.6142); t=0.3323; p=0.7494

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) 1.10[0.97; 1.26]61,3913,7160%NAMuanda a (Controls unexposed, NOS), 2017 Koss, 2012 Diav-Citrin, 2001 Sorensen, 1999 Czeizel, 1998 Caro-Paton, 1997 Piper, 1993 Rosa, 1987 Heinonen (Controls unexposed, NOS), 1977 9 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.20[0.89; 1.62]1,1894430%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 (all))Burtin (Birth defects in live-born infants (all)) 0.96[0.75; 1.22]-T11st trimesterstudies TTT7 Caro-Paton (Malformations (any or major))Caro-Paton (Malformations (any or major)) 1.08[0.90; 1.29]-Wwhatever (meta-analysis)Earlyearly pregnancystudies TTT5 metaPregmetaPreg 1.10[0.97; 1.26]0%3,716----Muanda a (Controls unexposed, NOS), 2017 Koss, 2012 Diav-Citrin, 2001 Sorensen, 1999 Czeizel, 1998 Caro-Paton, 1997 Piper, 1993 Rosa, 1987 Heinonen (Controls unexposed, NOS), 1977 90.510.01.0