Tenofovir (all routes except local)

Postpartum hemorrhage

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
R13495		 Liu (Controls exposed to LDT), 2019 Post‐partum haemorrhage 3rd trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Control group: telbivudine Exposed group: TDF (only) Indication: CHB 0.41 [0.02;9.98] C
excluded (control group) 		0/325   1/396 1 325
ref
S5174
R13496		 Liu (Controls unexposed, sick), 2019 Post‐partum haemorrhage 3rd trimester prospective cohort unexposed, sick Adjustment: No Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 0.14 [0.01;3.41] C 0/325   1/136 1 325
ref
S5293
R13655		 Zeng (Controls exposed to telbivudine), 2019 Postpartum hemorrhage 2nd and/or 3rd trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Control group: telbivudine Exposed group: TDF (only) Indication: CHB 0.99 [0.37;2.66] C
excluded (control group) 		8/71   10/88 18 71
ref
S5712
R14211		 Zeng (Controls unexposed, sick), 2019 Postpartum hemorrhage 2nd and/or 3rd trimester prospective cohort unexposed, sick Adjustment: No Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 1.04 [0.32;3.40] C 8/71   5/46 13 71
ref
S5321
R13792		 Lin, 2018 Postpartum hemorrhage 3rd trimester randomized controlled trial unexposed, sick Adjustment: Randomisation Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 0.88 [0.02;45.17] C 0/59   0/52 0 59
ref
S5259
R13608		 Pan, 2016 Postpartum hemorrhage late pregnancy randomized controlled trial unexposed, sick Adjustment: Randomisation Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 1.03 [0.25;4.25] C 4/97   4/100 8 97
ref
S5244
R13562		 Greenup (Controls exposed to lamivudine), 2014 Postpartum haemorrhage 2nd and/or 3rd trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Control group: Lamivudine Exposed group: TDF (only) Indication: CHB 0.91 [0.25;3.32] C
excluded (control group) 		5/58   5/53 10 58
ref
S5243
R13552		 Greenup (Controls unexposed, sick), 2014 Postpartum haemorrhage 2nd and/or 3rd trimester prospective cohort unexposed, sick Adjustment: No Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 0.53 [0.12;2.47] C 5/58   3/20 8 58
ref
Total 5 studies 0.79 [0.38;1.67] 30 610
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 0.14[0.01; 3.41]13255%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Zeng (Controls unexposed, sick), 2019Zeng, 2019 2 1.04[0.32; 3.40]137140%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Lin, 2018Lin, 2018 0.88[0.02; 45.17]0594%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Pan, 2016Pan, 2016 1.03[0.25; 4.25]89728%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Greenup (Controls unexposed, sick), 2014Greenup, 2014 3 0.53[0.12; 2.47]85824%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (5 studies) I2 = 0% 0.79[0.38; 1.67]306100.05.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls unexposed, sick; 2: Controls unexposed, sick; 3: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.71[0.29; 1.74]224540%NALiu (Controls unexposed, sick), 2019 Zeng (Controls unexposed, sick), 2019 Greenup (Controls unexposed, sick), 2014 3 case control studiescase control studies 0 RCTRCT 1.01[0.27; 3.84]81560%NALin, 2018 Pan, 2016 2 Type of controls unexposed, sickunexposed, sick 0.79[0.38; 1.67]306100%NALiu (Controls unexposed, sick), 2019 Zeng (Controls unexposed, sick), 2019 Lin, 2018 Pan, 2016 Greenup (Controls unexposed, sick), 2014 5 Tags Adjustment   - No  - No 0.71[0.29; 1.74]224540%NALiu (Controls unexposed, sick), 2019 Zeng (Controls unexposed, sick), 2019 Greenup (Controls unexposed, sick), 2014 3   - Randomisation  - Randomisation 1.01[0.27; 3.84]81560%NALin, 2018 Pan, 2016 2 Control group   - Unexposed, sick  - Unexposed, sick 0.79[0.38; 1.67]306100%NALiu (Controls unexposed, sick), 2019 Zeng (Controls unexposed, sick), 2019 Lin, 2018 Pan, 2016 Greenup (Controls unexposed, sick), 2014 5 Exposed group   - TDF (only)  - TDF (only) 0.79[0.38; 1.67]306100%NALiu (Controls unexposed, sick), 2019 Zeng (Controls unexposed, sick), 2019 Lin, 2018 Pan, 2016 Greenup (Controls unexposed, sick), 2014 5 Indication   - CHB  - CHB 0.79[0.38; 1.67]306100%NALiu (Controls unexposed, sick), 2019 Zeng (Controls unexposed, sick), 2019 Lin, 2018 Pan, 2016 Greenup (Controls unexposed, sick), 2014 5 All studiesAll studies 0.79[0.38; 1.67]306100%NALiu (Controls unexposed, sick), 2019 Zeng (Controls unexposed, sick), 2019 Lin, 2018 Pan, 2016 Greenup (Controls unexposed, sick), 2014 50.05.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.74.52.4110.000Liu (Controls unexposed, sick), 2019Zeng (Controls unexposed, sick), 2019Lin, 2018Pan, 2016Greenup (Controls unexposed, sick), 2014

Asymetry test p-value = 0.2765 (by Egger's regression)

slope=0.4965 (0.5971); intercept=-0.9317 (0.7022); t=1.3269; p=0.2765

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5244, 5175, 5293

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed, sick controlsunexposed, sick controls 0.79[0.38; 1.67]306100%NALiu (Controls unexposed, sick), 2019 Zeng (Controls unexposed, sick), 2019 Lin, 2018 Pan, 2016 Greenup (Controls unexposed, sick), 2014 5 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.91[0.43; 1.96]294540%NALiu (Controls exposed to LDT), 2019 Zeng (Controls exposed to telbivudine), 2019 Greenup (Controls exposed to lamivudine), 2014 30.510.01.0