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Tenofovir (all routes except local)
Overall results
Study description
Excluded studies
Table
Graphic
auto
during pregnancy (anytime or not specified)
1st trimester
2nd trimester
3rd trimester
2nd and/or 3rd trimester
throughout pregnancy
early pregnancy
days before delivery
late pregnancy
preconception-only
periconceptional
preconceptional for kinetic reason
at least 1st trimester
3 months (or more) before pregnancy or during pregnancy
1st and 2nd trimester
3 months or more before pregnancy or1st trimester
Whatever the period exposition
individual studies
Outcome
TE
95% CI
n cases
n exposed
k
Pub. bias
Congenital malformations
All congenital malformations (majors, minors, majors and minors, or unspecified)
Watts, 2004 Brogly, 2010 Gibb, 2012 Knapp, 2012 Floridia, 2013 Sibiude, 2014 Prieto (Controls unexposed, sick), 2014 Phiri, 2014 Mugo, 2014 Williams, 2015 Bérard (Controls unexposed, sick), 2017 Mehta, 2019
12
0.99
[
0.81
; 1.21]
1,423
2,364
low
Major congenital malformations
Watts, 2004 Brogly, 2010 Gibb, 2012 Floridia, 2013 Phiri, 2014 Prieto (Controls unexposed, sick), 2014 Williams, 2015 Bérard (Controls unexposed, sick), 2017 Mehta, 2019
9
1.14
[
0.85
; 1.54]
449
1,284
not evaluable
Congenital heart defects
Floridia, 2013 Sibiude, 2014
2
0.85
[
0.47
; 1.55]
7
996
not evaluable
Limb defects
Floridia, 2013 Sibiude, 2014
2
0.89
[
0.44
; 1.78]
4
996
not evaluable
Microcephaly / Small head circumference for gestational age
Siberry, 2012 Pintye, 2015 Williams, 2020
3
0.98
[
0.71
; 1.37]
152
1,171
not evaluable
Nervous system anomalies
Floridia, 2013 Sibiude, 2014
2
1.96
[
0.38
; 10.03]
1
996
not evaluable
Abdominal wall defects
Floridia, 2013
1
1.08
[
0.04
; 26.66]
1
173
not evaluable
Chromosomal abnormalities
Floridia, 2013
1
1.08
[
0.11
; 10.46]
4
173
not evaluable
Eye, ear, face and neck malformations
Floridia, 2013 Sibiude, 2014
2
1.42
[
0.37
; 5.52]
-
996
not evaluable
Genital anomalies
Floridia, 2013
1
1.63
[
0.15
; 18.03]
3
173
not evaluable
Urinary malformations
Floridia, 2013 Sibiude, 2014
2
1.00
[
0.38
; 2.63]
3
996
not evaluable
Hypospadias
0
-
-
-
-
-
Minor congenital malformations
0
-
-
-
-
-
Growth parameters and prematurity
Preterm (< 37 weeks)
Gibb, 2012 Ransom, 2013 Mugo, 2014 Calitri, 2014 Greenup (Controls unexposed, sick), 2014 Bagkeris, 2015 Moodley (Controls unexposed, sick), 2016 Zash, 2016 Pan, 2016 Samadi Kochaksaraei, 2016 Kolgelier, 2016 Fowler, 2016 Zash (Controls exposed to other treatments), 2017 Malaba, 2017 Pintye, 2017 Floridia, 2018 Rough, 2018 Wakano (Controls unexposed, sick), 2018 Chetty, 2018 Caniglia, 2018 Jourdain a, 2018 Heffron, 2018 Lin, 2018 Liu (Controls unexposed, sick), 2019 Chang, 2019 The EPPICC study group, 2019 Dadabhai, 2019 Ejigu, 2019 Seidel, 2020
29
0.89
[
0.78
; 1.02]
5,305
16,149
low
Low birth weight (< 2500g)
Vigano, 2011 Gibb, 2012 Siberry, 2012 Celen, 2013 Calitri, 2014 Bagkeris, 2015 Pintye, 2015 Fowler, 2016 Moodley (Controls unexposed, sick), 2016 Kolgelier, 2016 Malaba, 2017 Floridia, 2018 Chetty, 2018 Rough, 2018 Wakano (Controls unexposed, sick), 2018 Dadabhai, 2019 Ejigu, 2019 Liu (Controls unexposed, sick), 2019
18
0.97
[
0.80
; 1.17]
2,069
8,480
low
Small for gestational age (weight)
Siberry, 2012 Ransom, 2013 Calitri, 2014 Bagkeris, 2015 Pintye, 2015 Moodley (Controls unexposed, sick), 2016 Zash, 2016 Pan, 2016 Zash (Controls exposed to other treatments), 2017 Malaba, 2017 Chetty, 2018 Caniglia, 2018 Lin, 2018 Floridia, 2018 Dadabhai, 2019 Ejigu, 2019 The EPPICC study group, 2019
17
0.81
[
0.67
; 0.99]
4,361
14,089
probable
Very preterm (28 to 32 weeks)
Fowler, 2016 Malaba, 2017 Zash (Controls exposed to other treatments), 2017 Caniglia, 2018 Rough, 2018 Floridia, 2018 Chetty, 2018 The EPPICC study group, 2019
8
0.93
[
0.61
; 1.42]
758
9,791
not evaluable
Very low birth weight (< 1500g)
Fowler, 2016 Malaba, 2017 Floridia, 2018 Rough, 2018
4
0.93
[
0.48
; 1.81]
110
3,067
not evaluable
Small for gestational age (length)
Vigano, 2011 Siberry, 2012 Pintye, 2015
3
1.09
[
0.72
; 1.64]
142
377
not evaluable
Large for gestational age (weight)
Malaba, 2017 Floridia, 2018
2
0.80
[
0.55
; 1.17]
198
1,736
not evaluable
Macrosomia (> 4000g)
Vigano, 2011 Pan, 2016
2
2.66
[
0.34
; 20.58]
5
130
not evaluable
Large for gestational age (length)
Vigano, 2011
1
2.19
[
0.19
; 25.40]
3
33
not evaluable
Maternal consequences
Caesarean
Gibb, 2012 Greenup (Controls unexposed, sick), 2014 Colbers, 2015 Samadi Kochaksaraei, 2016 Wakano (Controls unexposed, sick), 2018 Seo, 2018 Jourdain a, 2018 Lin, 2018 Floridia, 2018 Liu (Controls unexposed, sick), 2019 Chang, 2019 Zeng (Controls unexposed, sick), 2019 Seidel, 2020
13
1.10
[
0.92
; 1.33]
870
1,617
low
Maternal liver disorder / failure during pregnancy
Chen, 2015 Pan, 2016 Seo, 2018 Jourdain a, 2018 Lin, 2018 Floridia, 2018 Sibiude, 2019
7
1.05
[
0.71
; 1.55]
153
1,044
not evaluable
Postpartum hemorrhage
Greenup (Controls unexposed, sick), 2014 Pan, 2016 Lin, 2018 Zeng (Controls unexposed, sick), 2019 Liu (Controls unexposed, sick), 2019
5
0.79
[
0.38
; 1.67]
30
610
not evaluable
Preeclampsia
Ransom, 2013 Pan, 2016 Lin, 2018 Floridia, 2018
4
0.77
[
0.40
; 1.48]
124
1,447
not evaluable
Amniotic fluid problems (polyhydramnios and/or oligohydramnios)
Greenup (Controls unexposed, sick), 2014
1
1.04
[
0.04
; 26.49]
1
58
not evaluable
Maternal consequences (as a whole)
Jourdain a, 2018 Zeng (Controls unexposed, sick), 2019
2
0.89
[
0.56
; 1.43]
93
239
not evaluable
Gestational diabetes
Ransom, 2013 Floridia, 2018
2
0.95
[
0.50
; 1.80]
141
1,291
not evaluable
Oligohydramnios
Greenup (Controls unexposed, sick), 2014
1
1.04
[
0.04
; 26.49]
1
58
not evaluable
Placenta previa
0
-
-
-
-
-
Assisted deliveries (forceps, vacuum, ...)
Samadi Kochaksaraei, 2016
1
1.57
[
0.53
; 4.66]
27
23
not evaluable
Polyhydramnios
Greenup (Controls unexposed, sick), 2014
1
0.34
[
0.01
; 17.67]
-
58
not evaluable
Neonatal disorders
Low Apgar score (< 7) (at 1 min)
Greenup (Controls unexposed, sick), 2014 Lin, 2018 Jourdain a, 2018 Liu (Controls unexposed, sick), 2019
4
1.42
[
0.50
; 4.07]
22
603
not evaluable
Neonatal death (< 28 days of life)
Fowler, 2016 Zash (Controls exposed to other treatments), 2017 Pintye, 2017 Floridia, 2018
4
1.07
[
0.36
; 3.16]
113
4,390
not evaluable
Hearing loss / Auditory deficit
Celen, 2013 Torre, 2016
2
0.80
[
0.41
; 1.54]
-
623
not evaluable
Low Apgar score (< 7) (at 5 min)
Greenup (Controls unexposed, sick), 2014
1
0.11
[
0.00
; 2.75]
1
58
not evaluable
Metabolic disorders in neonate/infant
Celen, 2013 Williams, 2016
2
0.71
[
0.48
; 1.06]
-
21
not evaluable
Neonatal disorders (as a whole)
Chi, 2007 Jourdain a, 2018
2
1.04
[
0.70
; 1.54]
124
359
not evaluable
Very low Apgar score (< 5) (at 1 min)
Jourdain a, 2018 Lin, 2018
2
1.59
[
0.20
; 12.44]
3
220
not evaluable
Bone fractures / bone mineralisation anomalies
Gibb, 2012
1
0.56
[
0.01
; 28.40]
-
111
not evaluable
Hypothyroidism (fetal/neonatal)
Celen, 2013
1
1.10
[
0.02
; 57.89]
-
21
not evaluable
Jaundice / Icterus
Pan, 2016
1
1.87
[
0.17
; 21.00]
3
95
not evaluable
Mitochondrial abnormalities
Crain, 2011
1
1.85
[
0.96
; 3.55]
51
299
not evaluable
Neonatal infections
Pan, 2016
1
1.87
[
0.17
; 21.00]
3
95
not evaluable
Long term consequences
Child/Infant head circumference abnormalities (> 1 year)
Siberry, 2012 Pintye, 2015 Williams, 2020
3
1.10
[
0.80
; 1.51]
186
1,082
not evaluable
Child/Infant weight abnormalities (> 1 year)
Siberry, 2012 Ransom, 2013 Pintye, 2015
3
1.35
[
0.95
; 1.94]
138
712
not evaluable
Child/Infant death (> 28 days of life)
Gibb, 2012 Mugo, 2014
2
0.49
[
0.18
; 1.35]
18
192
not evaluable
Child/Infant lenght abnormalities (> 1 year)
Siberry, 2012 Pintye, 2015
2
1.26
[
0.65
; 2.44]
83
255
not evaluable
Intrauterine deaths
Late intrauterine deaths (> 22 weeks)
Gibb, 2012 Mugo, 2014 Zash, 2016 Pan, 2016 Fowler, 2016 Moodley (Controls unexposed, sick), 2016 Pintye, 2017 Zash (Controls exposed to other treatments), 2017 Caniglia, 2018 Jourdain a, 2018 Favarato, 2019
11
0.70
[
0.43
; 1.14]
496
11,431
critical
Intrauterine deaths (as a whole or unspecified)
Mugo, 2014 Pintye, 2017 Floridia, 2018 Heffron, 2018 Liu (Controls unexposed, sick), 2019
5
1.04
[
0.79
; 1.37]
336
971
not evaluable
Early intrauterine death (< 22 weeks)
Gibb, 2012 Mugo, 2014 Pintye, 2017
3
1.01
[
0.72
; 1.43]
226
425
not evaluable
Elective/induced termination of pregnancy
Mugo, 2014 Floridia, 2018
2
1.28
[
0.77
; 2.14]
79
616
not evaluable
0.0
100.0
1.0