Tenofovir (all routes except local)

Low birth weight (< 2500g)

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.
S5238
R13533		 Dadabhai, 2019 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) retrospective cohort unexposed, disease free Adjustment: Yes Control group: Unexposed, disease free Exposed group: TDF/lamivudine/efavirenz Indication: HIV 1.62 [0.97;2.71] 44/614   34/685 78 614
ref
S5152
R13435		 Ejigu, 2019 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine-based Exposed group: TDF (mix or unspecified regimens) Indication: HIV 1.01 [0.70;1.45] 209/1,004   77/379 286 1,004
ref
S5175
R13492		 Liu (Controls exposed to LDT), 2019 Low birthweight infant (NOS) 3rd trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Control group: telbivudine Exposed group: TDF (only) Indication: CHB 0.88 [0.38;2.00] C
excluded (control group) 		10/325   14/400 24 325
ref
S5174
R13485		 Liu (Controls unexposed, sick), 2019 Low birthweight infant (NOS) 3rd trimester prospective cohort unexposed, sick Adjustment: No Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 2.13 [0.46;9.84] C 10/325   2/136 12 325
ref
S5144
R13446		 Chetty, 2018 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No Control group: zidovudine Exposed group: TDF/(emtracitabine or lamivudine)/efavirenz Indication: HIV 1.26 [0.88;1.82] C 103/959   46/528 149 959
ref
S5134
R13384		 Floridia, 2018 Low birth weight (< 2,500 g) 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 0.88 [0.59;1.30] 100/540   44/214 144 540
ref
S5155
R13463		 Rough, 2018 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine/lamivudine-based Exposed group: TDF/emtricitabine-based Indication: HIV 0.90 [0.73;1.11] 167/960   275/1,593 442 960
ref
S5737
R14236		 Wakano (Controls exposed to lamivudine), 2018 Low birthweight babies (<2500 g) 2nd and/or 3rd trimester prospective cohort exposed to other treatment, sick excluded Adjustment: No Control group: Lamivudine Exposed group: TDF (only) Indication: CHB 1.67 [0.02;137.36] C
excluded (control group) 		0/2   0/3 0 2
ref
S5738
R14240		 Wakano (Controls unexposed, sick), 2018 Low birthweight babies (<2500 g) 2nd and/or 3rd trimester prospective cohort unexposed, sick Adjustment: No Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 1.67 [0.02;137.36] C 0/2   0/3 0 2
ref
S5211
R13516		 Malaba, 2017 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) prospective cohort unexposed, disease free Adjustment: Yes Control group: Unexposed, disease free Exposed group: TDF/emtricitabine-based Indication: HIV 1.47 [0.90;2.40] 181/1,266   26/278 207 1,266
ref
S5131
R13340		 Fowler, 2016 Low birth weight (< 2,500 g) 2nd and/or 3rd trimester randomized controlled trial exposed to other treatment, sick Adjustment: Randomisation Control group: zidovudine/lamivudine/lopinavir–ritonavir Exposed group: TDF/emtricitabine/lopinavir–ritonavir Indication: HIV 0.80 [0.53;1.20] C 51/301   65/319 116 301
ref
S5319
R13758		 Kolgelier, 2016 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No Control group: Lamivudine Exposed group: TDF (only) Indication: CHB 0.02 [0.00;1.43] C 0/9   1/2 1 9
ref
S5136
R13401		 Moodley (Controls exposed to other treatments), 2016 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick excluded Adjustment: No Control group: zidovudine/nevirapine Exposed group: TDF/emtracitabine/efavirenz Indication: HIV 1.40 [1.09;1.81] C
excluded (control group) 		224/1,666   97/974 321 1,666
ref
S5138
R13407		 Moodley (Controls unexposed, sick), 2016 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: Yes Control group: Unexposed, sick Exposed group: TDF/emtracitabine/efavirenz Indication: HIV 0.12 [0.04;0.37] 224/1,666   34/148 258 1,666
ref
S5239
R13540		 Bagkeris, 2015 Low birthweight (< 2500 g) 2nd and/or 3rd trimester prospective cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine or lamiduvine-based Exposed group: TDF (mix or unspecified regimens) Indication: HIV 1.09 [0.65;1.82] -/123   -/2,204 - 123
ref
S5160
R13452		 Pintye, 2015 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No Control group: zidovudine/lamivudine/nevirapine Exposed group: TDF/lamivudine-based Indication: HIV 1.51 [0.62;3.69] C 9/89   13/188 22 89
ref
S5291
R13652		 Calitri, 2014 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No Control group: non-TDF (mix or unspecified regimens) Exposed group: TDF (mix or unspecified regimens) Indication: HIV 0.53 [0.10;2.98] C 3/12   5/13 8 12
ref
S5273
R13638		 Celen, 2013 Low birth weight (< 2500 g) 2nd and/or 3rd trimester retrospective cohort unexposed, sick Adjustment: No Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 1.10 [0.06;18.78] C 1/21   1/23 2 21
ref
S5122
R13297		 Gibb, 2012 Low birth weight (<2,500 g) throughout pregnancy prospective cohort exposed to other treatment, sick Adjustment: No Control group: zidovudine/lamivudine-based Exposed group: TDF/zidovudine/lamivudine Indication: HIV 0.74 [0.34;1.60] C 19/130   13/69 32 130
ref
S5124
R13302		 Siberry, 2012 Low birth weight (< 2,500 g) during pregnancy (anytime or not specified) cohort exposed to other treatment, sick Adjustment: Yes Control group: non-TDF (mix or unspecified regimens) Exposed group: TDF (mix or unspecified regimens) Indication: HIV 0.73 [0.48;1.11] 83/426   221/1,156 304 426
ref
S5121
R13269		 Vigano, 2011 Low birth weight (< 10th percentile) during pregnancy (anytime or not specified) prospective cohort exposed to other treatment, sick Adjustment: No Control group: non-TDF (mix or unspecified regimens) Exposed group: TDF (mix or unspecified regimens) Indication: HIV 1.07 [0.24;4.67] C 4/33   4/35 8 33
ref
Total 18 studies 0.97 [0.80;1.17] 2,069 8,480
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 Dadabhai, 2019Dadabhai, 2019 1.62[0.97; 2.71]786147%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Ejigu, 2019Ejigu, 2019 1.01[0.70; 1.45]2861,00410%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Liu (Controls unexposed, sick), 2019Liu, 2019 1 2.13[0.46; 9.84]123251%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Chetty, 2018Chetty, 2018 1.26[0.88; 1.82]14995910%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Floridia, 2018Floridia, 2018 0.88[0.59; 1.30]14454010%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Rough, 2018Rough, 2018 0.90[0.73; 1.11]44296013%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Wakano (Controls unexposed, sick), 2018Wakano, 2018 2 1.67[0.02; 137.36]020%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Malaba, 2017Malaba, 2017 1.47[0.90; 2.40]2071,2668%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Fowler, 2016Fowler, 2016 0.80[0.53; 1.20]1163019%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Kolgelier, 2016Kolgelier, 2016 0.02[0.00; 1.43]190%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Moodley (Controls unexposed, sick), 2016Moodley, 2016 3 0.12[0.04; 0.37]2581,6663%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Bagkeris, 2015Bagkeris, 2015 1.09[0.65; 1.82]-1237%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Pintye, 2015Pintye, 2015 1.51[0.62; 3.69]22894%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Calitri, 2014Calitri, 2014 0.53[0.10; 2.98]8121%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Celen, 2013Celen, 2013 1.10[0.06; 18.78]2210%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Gibb, 2012Gibb, 2012 0.74[0.34; 1.60]321304%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Siberry, 2012Siberry, 2012 0.73[0.48; 1.11]3044269%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Vigano, 2011Vigano, 2011 1.07[0.24; 4.67]8332%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (18 studies) I2 = 47% 0.97[0.80; 1.17]2,0698,4800.05.01.0ROB: 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 0.98[0.80; 1.22]1,9538,17948%NADadabhai, 2019 Ejigu, 2019 Liu (Controls unexposed, sick), 2019 Chetty, 2018 Floridia, 2018 Rough, 2018 Wakano (Controls unexposed, sick), 2018 Malaba, 2017 Kolgelier, 2016 Moodley (Controls unexposed, sick), 2016 Bagkeris, 2015 Pintye, 2015 Calitri, 2014 Celen, 2013 Gibb, 2012 Siberry, 2012 Vigano, 2011 17 case control studiescase control studies 0 RCTRCT 0.80[0.53; 1.20]116301 -NAFowler, 2016 1 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 1.54[1.08; 2.20]2851,8800%NADadabhai, 2019 Malaba, 2017 2 unexposed, sickunexposed, sick 0.65[0.10; 4.22]2722,01470%NALiu (Controls unexposed, sick), 2019 Wakano (Controls unexposed, sick), 2018 Moodley (Controls unexposed, sick), 2016 Celen, 2013 4 exposed to other treatment, sickexposed to other treatment, sick 0.93[0.82; 1.05]1,5124,5860%NAEjigu, 2019 Chetty, 2018 Floridia, 2018 Rough, 2018 Fowler, 2016 Kolgelier, 2016 Bagkeris, 2015 Pintye, 2015 Calitri, 2014 Gibb, 2012 Siberry, 2012 Vigano, 2011 12 Tags Adjustment   - No  - No 1.05[0.83; 1.33]3782,1200%NALiu (Controls unexposed, sick), 2019 Chetty, 2018 Floridia, 2018 Wakano (Controls unexposed, sick), 2018 Kolgelier, 2016 Pintye, 2015 Calitri, 2014 Celen, 2013 Gibb, 2012 Vigano, 2011 10   - Randomisation  - Randomisation 0.80[0.53; 1.20]116301 -NAFowler, 2016 1   - Yes  - Yes 0.94[0.68; 1.29]1,5756,05973%NADadabhai, 2019 Ejigu, 2019 Rough, 2018 Malaba, 2017 Moodley (Controls unexposed, sick), 2016 Bagkeris, 2015 Siberry, 2012 7 Control group   - Abacavir/Lamivudine-based  - Abacavir/Lamivudine-based 0.88[0.59; 1.30]144540 -NAFloridia, 2018 1   - Lamivudine  - Lamivudine 0.02[0.00; 1.43]19 -NAKolgelier, 2016 1   - non-TDF (mix or unspecified regimens)  - non-TDF (mix or unspecified regimens) 0.74[0.50; 1.09]3204710%NACalitri, 2014 Siberry, 2012 Vigano, 2011 3   - Unexposed, disease free  - Unexposed, disease free 1.54[1.08; 2.20]2851,8800%NADadabhai, 2019 Malaba, 2017 2   - Unexposed, sick  - Unexposed, sick 0.65[0.10; 4.22]2722,01470%NALiu (Controls unexposed, sick), 2019 Wakano (Controls unexposed, sick), 2018 Moodley (Controls unexposed, sick), 2016 Celen, 2013 4   - zidovudine  - zidovudine 1.26[0.88; 1.82]149959 -NAChetty, 2018 1   - zidovudine or lamiduvine-based  - zidovudine or lamiduvine-based 1.09[0.65; 1.82]-123 -NABagkeris, 2015 1   - zidovudine/lamivudine/lopinavir–rit ...  - zidovudine/lamivudine/lopinavir–ritonavir 0.80[0.53; 1.20]116301 -NAFowler, 2016 1   - zidovudine/lamivudine/nevirapine  - zidovudine/lamivudine/nevirapine 1.51[0.62; 3.69]2289 -NAPintye, 2015 1   - zidovudine/lamivudine-based  - zidovudine/lamivudine-based 0.89[0.73; 1.09]4741,0900%NARough, 2018 Gibb, 2012 2   - zidovudine-based  - zidovudine-based 1.01[0.70; 1.45]2861,004 -NAEjigu, 2019 1 Exposed group   - TDF (mix or unspecified regimens)  - TDF (mix or unspecified regimens) 0.92[0.72; 1.16]6061,5980%NAEjigu, 2019 Bagkeris, 2015 Calitri, 2014 Siberry, 2012 Vigano, 2011 5   - TDF (only)  - TDF (only) 0.96[0.18; 5.07]1535727%NALiu (Controls unexposed, sick), 2019 Wakano (Controls unexposed, sick), 2018 Kolgelier, 2016 Celen, 2013 4   - TDF/(emtracitabine or lamivudine)/e ...  - TDF/(emtracitabine or lamivudine)/efavirenz 1.26[0.88; 1.82]149959 -NAChetty, 2018 1   - TDF/emtracitabine/efavirenz  - TDF/emtracitabine/efavirenz 0.12[0.04; 0.36]2581,666 -NAMoodley (Controls unexposed, sick), 2016 1   - TDF/emtricitabine/lopinavir–ritonavir  - TDF/emtricitabine/lopinavir–ritonavir 0.80[0.53; 1.20]116301 -NAFowler, 2016 1   - TDF/emtricitabine-based  - TDF/emtricitabine-based 0.99[0.76; 1.29]7932,76642%NAFloridia, 2018 Rough, 2018 Malaba, 2017 3   - TDF/lamivudine/efavirenz  - TDF/lamivudine/efavirenz 1.62[0.97; 2.71]78614 -NADadabhai, 2019 1   - TDF/lamivudine-based  - TDF/lamivudine-based 1.51[0.62; 3.69]2289 -NAPintye, 2015 1   - TDF/zidovudine/lamivudine  - TDF/zidovudine/lamivudine 0.74[0.34; 1.60]32130 -NAGibb, 2012 1 Indication   - CHB  - CHB 0.96[0.18; 5.07]1535727%NALiu (Controls unexposed, sick), 2019 Wakano (Controls unexposed, sick), 2018 Kolgelier, 2016 Celen, 2013 4   - HIV  - HIV 0.96[0.79; 1.17]2,0548,12353%NADadabhai, 2019 Ejigu, 2019 Chetty, 2018 Floridia, 2018 Rough, 2018 Malaba, 2017 Fowler, 2016 Moodley (Controls unexposed, sick), 2016 Bagkeris, 2015 Pintye, 2015 Calitri, 2014 Gibb, 2012 Siberry, 2012 Vigano, 2011 14 All studiesAll studies 0.97[0.80; 1.17]2,0698,48047%NADadabhai, 2019 Ejigu, 2019 Liu (Controls unexposed, sick), 2019 Chetty, 2018 Floridia, 2018 Rough, 2018 Wakano (Controls unexposed, sick), 2018 Malaba, 2017 Fowler, 2016 Kolgelier, 2016 Moodley (Controls unexposed, sick), 2016 Bagkeris, 2015 Pintye, 2015 Calitri, 2014 Celen, 2013 Gibb, 2012 Siberry, 2012 Vigano, 2011 180.05.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-5.35.32.7010.000Dadabhai, 2019Ejigu, 2019Liu (Controls unexposed, sick), 2019Chetty, 2018Floridia, 2018Rough, 2018Wakano (Controls unexposed, sick), 2018Malaba, 2017Fowler, 2016Kolgelier, 2016Moodley (Controls unexposed, sick), 2016Bagkeris, 2015Pintye, 2015Calitri, 2014Celen, 2013Gibb, 2012Siberry, 2012Vigano, 2011

Asymetry test p-value = 0.5842 (by Egger's regression)

slope=0.0311 (0.1452); intercept=-0.3197 (0.5724); t=0.5585; p=0.5842

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5136, 5737, 5175

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 1.54[1.08; 2.20]2851,8800%NADadabhai, 2019 Malaba, 2017 2 unexposed, sick controlsunexposed, sick controls 0.65[0.10; 4.22]2722,01470%NALiu (Controls unexposed, sick), 2019 Wakano (Controls unexposed, sick), 2018 Moodley (Controls unexposed, sick), 2016 Celen, 2013 4 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.99[0.86; 1.15]1,8576,57925%NAEjigu, 2019 Liu (Controls exposed to LDT), 2019 Chetty, 2018 Floridia, 2018 Rough, 2018 Wakano (Controls exposed to lamivudine), 2018 Fowler, 2016 Kolgelier, 2016 Moodley (Controls exposed to other treatments), 2016 Bagkeris, 2015 Pintye, 2015 Calitri, 2014 Gibb, 2012 Siberry, 2012 Vigano, 2011 150.510.01.0