Tenofovir (all routes except local)

Intrauterine deaths (as a whole 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.
S5175
R13488		 Liu (Controls exposed to LDT), 2019 Threatened abortion 3rd trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Control group: telbivudine Exposed group: TDF (only) Indication: CHB 1.04 [0.72;1.52] C
excluded (control group) 		62/325   73/396 135 325
ref
S5174
R13480		 Liu (Controls unexposed, sick), 2019 Threatened abortion 3rd trimester prospective cohort unexposed, sick Adjustment: No Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 1.05 [0.63;1.75] C 62/325   25/136 87 325
ref
S5134
R13372		 Floridia, 2018 Pregnancy not ending in a live birth during pregnancy (anytime or not specified) cohort exposed to other treatment, sick Adjustment: No Control group: Abacavir/Lamivudine-based Exposed group: TDF/emtricitabine-based Indication: HIV 1.18 [0.76;1.84] 83/442   33/202 116 442
ref
S5154
R13472		 Heffron, 2018 Pregnancy loss during pregnancy (anytime or not specified) prospective cohort unexposed, sick Adjustment: Yes Control group: Unexposed, sick Exposed group: TDF (mix or unspecified regimens) Indication: PrEP 0.59 [0.15;2.23] 5/30   20/96 25 30
ref
S5153
R13437		 Pintye, 2017 Any pregnancy loss at least 1st trimester prospective cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine/lamivudine-based Exposed group: TDF/lamivudine-based Indication: PrEP 1.19 [0.35;4.08] 17/-   7/- 24 -
ref
S5265
R13631		 Mugo, 2014 Pregnancy losses early pregnancy randomized controlled trial unexposed, sick Adjustment: Randomisation Control group: Unexposed, sick Exposed group: TDF (only) Indication: PrEP 0.92 [0.54;1.57] C 53/174   31/96 84 174
ref
Total 5 studies 1.04 [0.79;1.37] 336 971
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 Liu (Controls unexposed, sick), 2019Liu, 2019 1 1.05[0.63; 1.75]8732528%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Floridia, 2018Floridia, 2018 1.18[0.76; 1.84]11644238%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Heffron, 2018Heffron, 2018 0.59[0.15; 2.23]25304%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Pintye, 2017Pintye, 2017 1.19[0.35; 4.08]24-5%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Mugo, 2014Mugo, 2014 0.92[0.54; 1.57]8417426%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 1.04[0.79; 1.37]3369710.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 1.09[0.79; 1.49]2527970%NALiu (Controls unexposed, sick), 2019 Floridia, 2018 Heffron, 2018 Pintye, 2017 4 case control studiescase control studies 0 RCTRCT 0.92[0.54; 1.57]84174 -NAMugo, 2014 1 Type of controls unexposed, sickunexposed, sick 0.95[0.66; 1.36]1965290%NALiu (Controls unexposed, sick), 2019 Heffron, 2018 Mugo, 2014 3 exposed to other treatment, sickexposed to other treatment, sick 1.18[0.78; 1.80]1404420%NAFloridia, 2018 Pintye, 2017 2 Tags Adjustment   - No  - No 1.12[0.80; 1.57]2037670%NALiu (Controls unexposed, sick), 2019 Floridia, 2018 2   - Randomisation  - Randomisation 0.92[0.54; 1.57]84174 -NAMugo, 2014 1   - Yes  - Yes 0.87[0.35; 2.15]49300%NAHeffron, 2018 Pintye, 2017 2 Control group   - Abacavir/Lamivudine-based  - Abacavir/Lamivudine-based 1.18[0.76; 1.84]116442 -NAFloridia, 2018 1   - Unexposed, sick  - Unexposed, sick 0.95[0.66; 1.36]1965290%NALiu (Controls unexposed, sick), 2019 Heffron, 2018 Mugo, 2014 3   - zidovudine/lamivudine-based  - zidovudine/lamivudine-based 1.19[0.35; 4.06]24- -NAPintye, 2017 1 Exposed group   - TDF (mix or unspecified regimens)  - TDF (mix or unspecified regimens) 0.59[0.15; 2.27]2530 -NAHeffron, 2018 1   - TDF (only)  - TDF (only) 0.98[0.68; 1.42]1714990%NALiu (Controls unexposed, sick), 2019 Mugo, 2014 2   - TDF/emtricitabine-based  - TDF/emtricitabine-based 1.18[0.76; 1.84]116442 -NAFloridia, 2018 1   - TDF/lamivudine-based  - TDF/lamivudine-based 1.19[0.35; 4.06]24- -NAPintye, 2017 1 Indication   - CHB  - CHB 1.05[0.63; 1.75]87325 -NALiu (Controls unexposed, sick), 2019 1   - HIV  - HIV 1.18[0.76; 1.84]116442 -NAFloridia, 2018 1   - PrEP  - PrEP 0.90[0.57; 1.44]1332040%NAHeffron, 2018 Pintye, 2017 Mugo, 2014 3 All studiesAll studies 1.04[0.79; 1.37]3369710%NALiu (Controls unexposed, sick), 2019 Floridia, 2018 Heffron, 2018 Pintye, 2017 Mugo, 2014 50.25.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-1.61.70.8260.000Liu (Controls unexposed, sick), 2019Floridia, 2018Heffron, 2018Pintye, 2017Mugo, 2014

Asymetry test p-value = 0.3653 (by Egger's regression)

slope=0.2403 (0.2020); intercept=-0.6938 (0.6519); t=1.0642; p=0.3653

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5175

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 0.95[0.66; 1.36]1965290%NALiu (Controls unexposed, sick), 2019 Heffron, 2018 Mugo, 2014 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 1.10[0.84; 1.46]2757670%NALiu (Controls exposed to LDT), 2019 Floridia, 2018 Pintye, 2017 30.510.01.0