Tenofovir (all routes except local)

Small for gestational age (weight)

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
R13534		 Dadabhai, 2019 Small for gestational age (body weight <10th percentile of gestational age) 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 1.02 [0.75;1.41] 105/614   126/685 231 614
ref
S5152
R13436		 Ejigu, 2019 Small-for-gestational-age 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 1.09 [0.78;1.52] 344/1,004   120/379 464 1,004
ref
S5189
R13504		 The EPPICC study group, 2019 Small for gestational age (<10th percentile according to Intergrowth standards) 2nd and/or 3rd trimester cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine/lamivudine-based Exposed group: TDF (mix or unspecified regimens) Indication: HIV 0.70 [0.53;0.93] 94/1,099   591/5,045 685 1,099
ref
S5145
R13414		 Caniglia, 2018 Small for gestational age (<10th percentile) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine/lamivudine/nevirapine Exposed group: TDF/emtracitabine/efavirenz Indication: HIV 0.51 [0.43;0.61] 198/1,096   204/622 402 1,096
ref
S5144
R13445		 Chetty, 2018 Small-for-gestational age (birthweight below 10th percentile of expected weight for gestational age) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine Exposed group: TDF/(emtracitabine or lamivudine)/efavirenz Indication: HIV 1.12 [0.68;1.89] 95/959   56/528 151 959
ref
S5134
R13386		 Floridia, 2018 Small by gestational age (birthweight < 10th) 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 1.23 [0.73;2.08] 63/528   21/212 84 528
ref
S5321
R13793		 Lin, 2018 Limited fetal growth 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
S5211
R13518		 Malaba, 2017 Small for gestational age (weights <10th percentile for gestational age) 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 0.91 [0.58;1.43] 112/1,208   31/277 143 1,208
ref
S5258
R13592		 Zash (Controls exposed to other treatments), 2017 Small for gestational age (<10th percentile of weight for gestational age) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: No Control group: zidovudine/lamivudine-based Exposed group: TDF (mix or unspecified regimens) Indication: HIV 0.64 [0.56;0.74] C 672/3,463   419/1,532 1,091 3,463
ref
S5136
R13403		 Moodley (Controls exposed to other treatments), 2016 Small for gestational age (below 10th percentile) 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 1.07 [0.80;1.44] C
excluded (control group) 		133/1,666   73/974 206 1,666
ref
S5138
R13408		 Moodley (Controls unexposed, sick), 2016 Small for gestational age (below 10th percentile) during pregnancy (anytime or not specified) retrospective cohort unexposed, sick Adjustment: Yes Control group: Unexposed, sick Exposed group: TDF/emtracitabine/efavirenz Indication: HIV 0.25 [0.07;0.87] 133/1,666   15/148 148 1,666
ref
S5259
R13600		 Pan, 2016 Fetal growth retardation late pregnancy randomized controlled trial unexposed, sick Adjustment: Randomisation Control group: Unexposed, sick Exposed group: TDF (only) Indication: CHB 1.03 [0.06;16.72] C 1/97   1/100 2 97
ref
S5140
R13449		 Zash, 2016 Small for gestational age (below the 10th percentile of birthweight by GA, Botswana norms) during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: Yes Control group: non-TDF (mix or unspecified regimens) Exposed group: TDF/emtracitabine/efavirenz Indication: HIV 0.40 [0.30;0.60] 125/1,054   459/2,172 584 1,054
ref
S5239
R13539		 Bagkeris, 2015 Small for gestational age (birthweight for gestational age < 3rd percentile of the overall study population) 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 1.15 [0.66;2.02] -/123   -/2,204 - 123
ref
S5160
R13453		 Pintye, 2015 6-week z-scores for weight-for-age (WAZ) < −2 SD during pregnancy (anytime or not specified) retrospective cohort exposed to other treatment, sick Adjustment: Yes Control group: zidovudine/lamivudine/nevirapine Exposed group: TDF/lamivudine-based Indication: HIV 1.86 [0.54;6.35] 6/51   7/104 13 51
ref
S5291
R13653		 Calitri, 2014 Small for gestational age (NOS) 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 0.30 [0.03;3.41] C 1/12   3/13 4 12
ref
S5127
R13312		 Ransom, 2013 Low birth weight (age and sex adjusted z- score <10th percentile) during pregnancy (anytime or not specified) prospective 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 1.09 [0.77;1.52] 72/630   153/1,395 225 630
ref
S5124
R13303		 Siberry, 2012 Small for gestational age (birth weight less than the 10th percentile for gestational age) 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 0.96 [0.60;1.52] 35/426   99/1,156 134 426
ref
Total 17 studies 0.81 [0.67;0.99] 4,361 14,089
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 1.02[0.75; 1.41]2316149%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Ejigu, 2019Ejigu, 2019 1.09[0.78; 1.52]4641,0048%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA The EPPICC study group, 2019The EPPICC study group, 2019 0.70[0.53; 0.93]6851,0999%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Caniglia, 2018Caniglia, 2018 0.51[0.43; 0.61]4021,09610%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Chetty, 2018Chetty, 2018 1.12[0.68; 1.89]1519596%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Floridia, 2018Floridia, 2018 1.23[0.73; 2.08]845286%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Lin, 2018Lin, 2018 0.88[0.02; 45.17]0590%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Malaba, 2017Malaba, 2017 0.91[0.58; 1.43]1431,2087%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Zash (Controls exposed to other treatments), 2017Zash, 2017 1 0.64[0.56; 0.74]1,0913,46310%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Moodley (Controls unexposed, sick), 2016Moodley, 2016 2 0.25[0.07; 0.87]1481,6662%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Pan, 2016Pan, 2016 1.03[0.06; 16.72]2970%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Zash, 2016Zash, 2016 0.40[0.30; 0.60]5841,0548%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Bagkeris, 2015Bagkeris, 2015 1.15[0.66; 2.02]-1236%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Pintye, 2015Pintye, 2015 1.86[0.54; 6.35]13512%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Calitri, 2014Calitri, 2014 0.30[0.03; 3.41]4121%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Ransom, 2013Ransom, 2013 1.09[0.77; 1.52]2256308%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Siberry, 2012Siberry, 2012 0.96[0.60; 1.52]1344267%ROB confusion: NAROB selection: NAROB classification: NAROB missing: NAROB mesure: NAROB reporting: NA Total (17 studies) I2 = 74% 0.81[0.67; 0.99]4,36114,0890.25.01.0ROB: A: confusion, B: selection, C: classification, D: missing, E: measurement, F: reportinglow,moderate,serious,critical,unclear,

1: Controls exposed to other treatments; 2: Controls unexposed, sick;

Sensitivity analysis

SubsetTE95% CIn casesn exposedkI2 Type of studies cohort studiescohort studies 0.81[0.66; 0.99]4,35913,93378%NADadabhai, 2019 Ejigu, 2019 The EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Floridia, 2018 Malaba, 2017 Zash (Controls exposed to other treatments), 2017 Moodley (Controls unexposed, sick), 2016 Zash, 2016 Bagkeris, 2015 Pintye, 2015 Calitri, 2014 Ransom, 2013 Siberry, 2012 15 case control studiescase control studies 0 RCTRCT 0.98[0.10; 9.51]21560%NALin, 2018 Pan, 2016 2 Type of controls unexposed (disease free or unspecified)unexposed (disease free or unspecified) 0.98[0.76; 1.27]3741,8220%NADadabhai, 2019 Malaba, 2017 2 unexposed, sickunexposed, sick 0.34[0.11; 1.04]1501,8220%NALin, 2018 Moodley (Controls unexposed, sick), 2016 Pan, 2016 3 exposed to other treatment, sickexposed to other treatment, sick 0.81[0.65; 1.01]3,83710,44579%NAEjigu, 2019 The EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Floridia, 2018 Zash (Controls exposed to other treatments), 2017 Zash, 2016 Bagkeris, 2015 Pintye, 2015 Calitri, 2014 Ransom, 2013 Siberry, 2012 12 Tags Adjustment   - No  - No 0.80[0.45; 1.41]1,1794,00367%NAFloridia, 2018 Zash (Controls exposed to other treatments), 2017 Calitri, 2014 3   - Randomisation  - Randomisation 0.98[0.10; 9.51]21560%NALin, 2018 Pan, 2016 2   - Yes  - Yes 0.82[0.64; 1.06]3,1809,93080%NADadabhai, 2019 Ejigu, 2019 The EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Malaba, 2017 Moodley (Controls unexposed, sick), 2016 Zash, 2016 Bagkeris, 2015 Pintye, 2015 Ransom, 2013 Siberry, 2012 12 Control group   - Abacavir/Lamivudine-based  - Abacavir/Lamivudine-based 1.23[0.73; 2.08]84528 -NAFloridia, 2018 1   - non-TDF (mix or unspecified regimens)  - non-TDF (mix or unspecified regimens) 0.71[0.38; 1.33]9472,12284%NAZash, 2016 Calitri, 2014 Ransom, 2013 Siberry, 2012 4   - Unexposed, disease free  - Unexposed, disease free 0.98[0.76; 1.27]3741,8220%NADadabhai, 2019 Malaba, 2017 2   - Unexposed, sick  - Unexposed, sick 0.34[0.11; 1.04]1501,8220%NALin, 2018 Moodley (Controls unexposed, sick), 2016 Pan, 2016 3   - zidovudine  - zidovudine 1.12[0.67; 1.87]151959 -NAChetty, 2018 1   - zidovudine or lamiduvine-based  - zidovudine or lamiduvine-based 1.15[0.66; 2.01]-123 -NABagkeris, 2015 1   - zidovudine/lamivudine/nevirapine  - zidovudine/lamivudine/nevirapine 0.84[0.24; 2.88]4151,14776%NACaniglia, 2018 Pintye, 2015 2   - zidovudine/lamivudine-based  - zidovudine/lamivudine-based 0.65[0.57; 0.74]1,7764,5620%NAThe EPPICC study group, 2019 Zash (Controls exposed to other treatments), 2017 2   - zidovudine-based  - zidovudine-based 1.09[0.78; 1.52]4641,004 -NAEjigu, 2019 1 Exposed group   - TDF (mix or unspecified regimens)  - TDF (mix or unspecified regimens) 0.87[0.68; 1.10]2,6036,75768%NAEjigu, 2019 The EPPICC study group, 2019 Zash (Controls exposed to other treatments), 2017 Bagkeris, 2015 Calitri, 2014 Ransom, 2013 Siberry, 2012 7   - TDF (only)  - TDF (only) 0.98[0.10; 9.51]21560%NALin, 2018 Pan, 2016 2   - TDF/(emtracitabine or lamivudine)/e ...  - TDF/(emtracitabine or lamivudine)/efavirenz 1.12[0.67; 1.87]151959 -NAChetty, 2018 1   - TDF/emtracitabine/efavirenz  - TDF/emtracitabine/efavirenz 0.47[0.37; 0.58]1,1343,81622%NACaniglia, 2018 Moodley (Controls unexposed, sick), 2016 Zash, 2016 3   - TDF/emtricitabine-based  - TDF/emtricitabine-based 1.04[0.74; 1.46]2271,7360%NAFloridia, 2018 Malaba, 2017 2   - TDF/lamivudine/efavirenz  - TDF/lamivudine/efavirenz 1.02[0.74; 1.40]231614 -NADadabhai, 2019 1   - TDF/lamivudine-based  - TDF/lamivudine-based 1.86[0.54; 6.38]1351 -NAPintye, 2015 1 Indication   - CHB  - CHB 0.98[0.10; 9.51]21560%NALin, 2018 Pan, 2016 2   - HIV  - HIV 0.81[0.66; 0.99]4,35913,93378%NADadabhai, 2019 Ejigu, 2019 The EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Floridia, 2018 Malaba, 2017 Zash (Controls exposed to other treatments), 2017 Moodley (Controls unexposed, sick), 2016 Zash, 2016 Bagkeris, 2015 Pintye, 2015 Calitri, 2014 Ransom, 2013 Siberry, 2012 15 All studiesAll studies 0.81[0.67; 0.99]4,36114,08974%NADadabhai, 2019 Ejigu, 2019 The EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Floridia, 2018 Lin, 2018 Malaba, 2017 Zash (Controls exposed to other treatments), 2017 Moodley (Controls unexposed, sick), 2016 Pan, 2016 Zash, 2016 Bagkeris, 2015 Pintye, 2015 Calitri, 2014 Ransom, 2013 Siberry, 2012 170.15.01.0

Publication bias and p-hacking diagnosis

funnel plot
0.0-4.74.52.4110.000Dadabhai, 2019Ejigu, 2019The EPPICC study group, 2019Caniglia, 2018Chetty, 2018Floridia, 2018Lin, 2018Malaba, 2017Zash (Controls exposed to other treatments), 2017Moodley (Controls unexposed, sick), 2016Pan, 2016Zash, 2016Bagkeris, 2015Pintye, 2015Calitri, 2014Ransom, 2013Siberry, 2012

Asymetry test p-value = 0.1400 (by Egger's regression)

slope=-0.5188 (0.1303); intercept=1.1976 (0.7685); t=1.5583; p=0.1400

p values plot
0.01.00.01.0

Sub-groups analysis using all included studies

excluded 5136

Sub-groupsTE95% CIn casesn exposedkI2ROB type of controls unexposed controls (disease free or unspecified)unexposed controls (disease free or unspecified) 0.98[0.76; 1.27]3741,8220%NADadabhai, 2019 Malaba, 2017 2 unexposed, sick controlsunexposed, sick controls Out of scale0.34[0.11; 1.04]1501,8220%NALin, 2018 Moodley (Controls unexposed, sick), 2016 Pan, 2016 3 exposed to other treatment, sick controlsexposed to other treatment, sick controls 0.83[0.67; 1.03]4,04312,11180%NAEjigu, 2019 The EPPICC study group, 2019 Caniglia, 2018 Chetty, 2018 Floridia, 2018 Zash (Controls exposed to other treatments), 2017 Moodley (Controls exposed to other treatments), 2016 Zash, 2016 Bagkeris, 2015 Pintye, 2015 Calitri, 2014 Ransom, 2013 Siberry, 2012 130.510.01.0