1
Supplemental Table 1. Baseline characteristics comparing those who were tested (with at least one valid test) to those who were not tested for neurodevelopment outcomes among the HEU children from the Mma Bana and Tshipidi studies, Botswana 2009 - 2012
Characteristic Tested
(N=598) (N, % of total)
Not tested (N=334) (N, % of total) Study
Mma Bana 261 (43.7%) 245 (73.4%)
Tshipidi 337 (56.4%) 89 (26.7%)
Gender
Female 304 (50.8%) 166 (49.7%)
Prematurity
Yes 58 (9.8%) 73 (22.1%)
Birthweight LBW Maternal age
96 (16.1%) 78 (23.9%)
18-24 172 (28.8%) 135 (40.4%)
25-29 174 (29.1%) 95 (28.4%)
30-34 128 (21.4%) 54 (16.2%)
35-39 108 (18.1%) 40 (12.0%)
40-44 16 (2.7%) 6 (1.8%)
Maternal education
None 13 (2.2%) 9 (2.7%)
Primary 99 (16.6%) 52 (15.6%)
Secondary junior 347 (58.1%) 178 (53.3%) Secondary senior
or tertiary
138 (23.1%) 92 (27.5%) Maternal income
None 309 (51.9%) 161 (48.6%)
<P500 92 (15.5%) 18 (5.4%)
P501-P1000 106 (17.8%) 65 (19.6%)
>P1000 88 (14.8%) 52 (15.7%)
2 Supplemental Table 2. Baseline characteristics of those “Missing” versus “Not Missing”
neurodevelopmental outcomes among the HEU children with at least one valid BSID III test from the Mma Bana and Tshipidi studies, Botswana 2009 - 2012
Not missing (N, %)
Missing (N, %)
P-value (Chi-Square)
Bayley cognitive 524 (87.6%) 74 (12.4%)
Gender 0.69
Female 256 (48.9%) 38 (51.4%)
Birthweight 0.76
Low birthweight 24 (11.2%) 6 (12.8%)
Breast-fed <0.01
Ever breastfed 282 (53.8%) 26 (35.1%)
Premature 0.23
Premature 48 (9.3%) 10 (13.7%)
Maternal age 0.39
18-24 154 (29.4%) 18 (24.3%)
25-29 149 (28.4%) 25 (33.8%)
30-34 109 (20.8%) 19 (25.7%)
35-39 99 (18.9%) 9 (12.2%)
40-44 13 (2.5%) 3 (4.1%)
Maternal education 0.57
None 13 (2.5%) 0 (0%)
Primary 86 (16.4%) 13 (17.8%)
Secondary junior 303 (57.8%) 44 (60.3%)
Secondary senior or tertiary 122 (23.3%) 16 (21.9%)
Maternal income <0.01
None 284 (54.4%) 25 (34.3%)
<P500 76 (14.6%) 16 (21.9%)
P501-P1000 91 (17.4%) 15 (20.6%)
>P1000 71 (13.6%) 17 (23.3%)
Bayley gross motor
Gender 0.97
Female 255 (49.1%) 39 (49.4%)
Birthweight 0.46
Low birthweight 23 (10.8%) 7 (14.6%)
Breast-fed <0.01
Ever breastfed 278 (53.6%) 30 (38.0%)
Premature 0.36
Premature 48 (9.4%) 10 (12.7%)
Maternal age 0.09
18-24 155 (29.9%) 17 (21.5%)
25-29 147 (28.3%) 27 (34.2%)
30-34 109 (21.0%) 19 (24.1%)
3 Supplemental Table 2. (Continued)
Not missing (N, %)
Missing (N, %)
P-value (Chi-Square)
35-39 97 (18.7%) 11 (13.9%)
40-44 11 (2.1%) 5 (6.3%)
Maternal education 0.48
None 13 (2.5%) 0 (0%)
Primary 85 (16.4%) 14 (18.0%)
Secondary junior 299 (57.6%) 48 (61.5%)
Secondary senior or tertiary 122 (23.5%) 16 (20.5%)
Maternal income 0.08
None 278 (53.8%) 31 (39.7%)
<P500 75 (14.5%) 17 (21.8%)
P501-P1000 92 (17.8%) 14 (18.0%)
>P1000 72 (13.9%) 16 (20.5%)
Supplemental Table 3. Unadjusted mean Bayley neurodevelopment domain scores and univariate analysis for among the HEU children with at least one valid BSID III test from the Mma Bana and Tshipidi studies, Botswana 2009 - 2012
Cognitive Gross motor Fine motor Expressive language
Receptive language
N M
ea n
S D
p N Me
an S D
p N M
ea n
S D
p N M
e a n
S D
p N M
ea n
SD p
Total 5 2 4
55 .2
5.
9
5 1 9
53 .0
4 . 9
5 3 1
37 .9
4 . 7
5 1 7
2 6.
0 5 . 2
51 8
21 .9
3 . 8 Study
2 1 4
57 .3
7 . 8
2 1 3
53 .5
6 . 8
2 2 0
38 .7
5 . 2
2 1 2
2 7.
4 5 . 9
2 1 3
23 .0
3 . 8 Mma
Bana
<0.
01
0 . 0 6
<0.
0 1
<0.
01
<0.
01
Tshipi di
3 1 0
53 .8
3 . 4
3 0 6
52 .6
2 . 8
3 1 1
37 .3
1 . 8
3 0 5
2 5.
0 4 . 4
3 0 5
21 .1
3 . 5 Gender
2 6 8
55 .6
6 . 4
2 6 4
52 .7
5 . 7
2 7 2
38 .1
4 . 0
2 6 6
2 6.
2 5 . 4
2 6 7
22 .2
3 . 6 Femal
e
0.
0 8
0 . 1 3
0 . 1 8
0.
4 2
0.
02
Male 2 5 6
54 .7
5 . 2
2 5 5
53 .3
3 . 9
2 5 9
37 .6
3 . 3
2 5 1
2 5.
8 4 . 9
2 5 1
21 .5
3 . 9 Birthwei
ght Norm
al 4
4 2
55 .3
6 . 1
0.
2 5
4 3 9
53 .1
5 . 1
0 . 1 5
4 4 8
37 .9
3 . 9
0 . 5 3
4 3 7
2 6.
0 5 . 2
0.
7 3
4 3 7
21 .9
3 . 9
0.
54
Low 8 2
54 .5
4 . 1
8 0
52 .3
3 . 2
8 3
37 .6
2 . 0
8 0
2 5.
8 4 . 9
8 1
21 .6
3 . 1 Breastfe
d 2
8 2
53 .8
3 . 3
2 7 8
52 .7
2 . 8
2 8 3
37 .3
1 . 8
2 7 9
2 5.
0 4 . 4
2 7 8
21 .0
3 . Not 6
breastfe d
<
0.
0 1
0 . 1 4
<0.
01
<0 .0 1
<0.01
Breas tfed
2 4 2
56 .8
7 . 6
2 4 1
53 .3
6 . 5
2 4 8
38 .5
4 . 9
2 3 8
2 7.
2 5 . 8
2 4 0
22 .8
3 . 8 Prematu
rity Full- term
4 7 0
55 .4
6 . 1
0.
0 5
4 6 4
53 .1
5 . 0
0 . 0 9
4 7 6
37 .9
3 . 8
0 . 1 9
4 6 5
2 6.
1 5 . 2
0.
2 6
4 6 5
22 .0
3 . 8
0.
0 6
p* 4 Supplemental Table 3. (Continued)
Cognitive Gross motor Fine motor Expressive language
Receptive language
N M
ea n
S D
p N M
e a n
S D
p N M
e a n
S D
p N M
e a n
S D
p N M
e a n
S D
p
Mater nal age 1
5 4
55 .4
6 . 0
1 5 5
5 2.
9 4 . 2
1 5 9
3 8.
0 3 . 9
1 5 4
2 6 . 4
5 . 2
1 5 3
2 1.
9 4 . 18- 2
24
0.
27
0.
9 0
0.
4 6
0.
38
0.
46 25-
29
1 4 9
55 .5
6 . 1
1 4 7
5 3.
1 5 . 3
1 5 0
3 7.
9 3 . 9
1 4 9
2 5 . 4
5 . 3
1 4 9
2 1.
9 3 . 5 30-
34
1 0 9
54 .7
7 . 0
1 0 9
5 3.
0 6 . 1
1 1 1
3 7.
8 4 . 4
1 0 8
2 6 . 4
5 . 4
1 0 8
2 2.
0 3 . 9 35-
39
9 9
55 .0
4 . 0
9 7
5 3.
0 3 . 8
9 8
3 7.
6 1 . 8
9 5
2 6 . 2
4 . 4
9 6
2 1.
6 3 . 3 40-
44
1 3
53 .7
4 . 9
1 1
5 2.
2 3 . 1
1 3
3 8.
1 1 . 7
1 1
2 2 . 3
5 . 9
1 2
2 0.
9 2 . 7 Mater
nal Educa tion
Non e
1 3
55 .5
3 . 1
0.
21 1 3
5 1.
9 3 . 0
0.
2 5
1 3
3 7.
7 2 . 0
0.
2 7
1 3
2 5 . 5
4 . 4
0.
02 1 3
2 1.
2 2 . 6
0.
42
Prim ary
8 6
54 .5
7 . 7
8 5
5 1.
9 7 . 1
8 7
3 7.
5 4 . 7
8 4
2 4 . 5
6 . 0
8 5
2 1.
3 4 . 2 Seco
ndar y junio r
3 0 3
55 .1
5 . 0
2 9 9
5 3.
4 3 . 5
3 0 7
3 7.
9 3 . 1
2 9 9
2 6 . 3
4 . 9
2 9 9
2 2.
1 3 . 7
Seco ndar y seni or
1 2 2
55 .7
6 . 5
1 2 2
5 2.
8 5 . 8
1 2 4
3 8.
1 4 . 2
1 2 1
2 6 . 5
5 . 2
1 2 1
2 1.
7 3 . 8
Mater nal incom
Analysis of variance (ANOVA) test for categorical independent variables (sex, ever-breastfed, HAART) and ordinal independent variables (birth-weight, prematurity, maternal viral load, maternal CD4, maternal age, maternal education, maternal income, year of testing) BF-Breastfed FF-Formula
5
Supplemental Table 4. Unadjusted mean development milestones checklist neurodevelopment domain scores and univariate analysis among the HEU children with at least one valid BSID III test from the Mma Bana and Tshipidi studies, Botswana 2009 - 2012
Locomotor Fine motor Language Personal-social
N Mean SD p N Mean SD p N Mean SD p N Mean SD p
Total 593 31.9 2.6 590 18.9 2.
5
593 16.4 2.
8
590 46.1 4.
6
Study 0.01 0.04 0.95 <0.01
Mma Bana 256 31.6 3.3 254 18.7 2.
7
256 16.4 3.
0
255 47.3 5.
0
Tshipidi 337 32.2 1.8 336 19.1 2.
3
337 16.5 2.
6
335 45.1 3.
9 Sex
302 31.9 2.7 300 19.0 2.
5
302 16.6 2.
7
301 46.5 4.
Female 0.89 0.21 0.24 1 0.01
Male 291 31.9 2.4 290 18.8 2.
5
291 16.3 2.
9
289 45.6 5.
0 Birthweight
497 31.9 2.7 495 18.9 2.
5
497 16.5 2.
8
496 46.1 4.
Normal 0.60 0.85 0.18 8 0.49
Low 96 31.8 1.7 95 18.9 2.
3
96 16.1 2.
7
94 45.8 3.
0 Breastfeeding
308 32.1 1.9 307 19.1 2.
2
308 16.4 2.
6
306 45.0 4.
Not breastfed 0.12 0.04 0.66 0 <0.01
Breastfed 285 31.8 3.2 283 18.7 2.
7
285 16.5 2.
9
284 47.2 4.
8 Prematurity
Not premature 528 32.0 2.6 0.26 525 19.0 2. 0.20 528 16.5 2. 0.71 525 46.2 4. 0.06
5 9 6
Premature 58 31.6 2.8 58 18.5 2.
7
58 16.3 2.
1
58 45.0 4.
1 Maternal Viral Load
<=400 149 32.3 1.6 0.13 148 19.4 1.
9
0.19 149 16.5 2.
6
0.41 148 45.7 3.
7 0.08
400-999 43 31.9 1.5 43 18.3 2.
6
43 16.7 2.
9
43 45.6 3.
2
1000-9999 150 31.5 3.1 149 18.6 2.
8
150 16.6 2.
8
150 45.8 4.
9
>=10000 247 32.0 2.7 246 18.9 2.
5
247 16.3 2.
9
245 46.5 5.
0 Maternal CD4
<200 70 31.7 4.0 0.17 70 18.5 3.
1
0.12 70 16.0 3.
6
0.07 70 46.1 7.
5 0.91
200-349 161 31.9 2.9 160 18.8 2.
6
161 16.5 2.
9
160 46.0 4.
8
300-499 191 31.8 2.2 189 19.1 2.
2
191 16.3 2.
8
189 46.1 3.
3
>=500 168 32.2 1.9 168 19.0 2.
4
168 16.8 2.
3
168 46.1 3.
9 HAART
ZDV 210 32.1 1.9 0.15 210 18.9 2.
4
0.95 210 16.5 2.
5
0.53 209 45.3 3.
3
<0.01
ART 377 31.8 2.9 374 18.9 2.
5
377 16.4 3.
0
375 46.5 5.
1
Supplemental Table 4. (Continued)
Locomotor Fine motor Language Personal-social
N Mean SD p N Mean SD p N Mean SD p N Mean SD p
Maternal age
18-24 170 31.7 2.8 0.72 169 18.7 2.
5
0.05 170 16.4 2.
9
0.95 169 45.8 4.
6 0.59
25-29 172 31.9 3.2 171 18.7 2.
8
172 16.5 2.
8
172 46.4 4.
4
30-34 128 32.3 1.8 127 19.3 2.
2
128 16.4 2.
8
126 46.5 3.
4
35-39 107 32.0 2.0 107 19.0 2.
3
107 16.7 2.
6
107 45.3 5.
8
40-44 16 32.5 1.3 16 19.6 2.
2
16 15.4 2.
3
16 46.1 3.
6 Maternal education
None 13 31.1 2.14 0.42 13 16.9 2.
7
0.01 13 17.1 1.
6
0.09 13 46.5 3.
3 0.87
Primary 98 31.8 2.39 98 18.9 2.
5
98 16.0 2.
7
98 46.1 4.
1
Secondary junior 344 32.0 2.43 341 18.8 2.
4
344 16.4 2.
9
342 46.1 4.
7 Secondary senior or tertiary 137 31.9 3.04 137 19.3 2.
6
137 16.8 2.
7
136 46.0 4.
7 Maternal income
None 306 31.7 2.7 0.04 303 19.1 2.
4
0.20 306 16.4 2.
8
0.09 304 46.0 4.
3 0.52
<P500 91 31.7 3.6 91 18.4 3.
2
91 15.9 3.
1
91 46.0 5.
6
P501-P1000 105 32.2 2.0 105 18.9 2.
2
105 16.8 3.
0
105 45.8 5.
2
>P1000 88 32.5 1.3 88 19.1 2.
4
88 16.8 2.
1
87 46.7 2.
8 Year of testing
2009 73 32.2 2.3 0.03 72 19.1 2.
0
0.03 73 16.3 3.
2
0.59 73 47.2 3.
1
<0.01
2010 183 31.4 3.6 182 18.5 2.
9
183 16.5 3.
0
182 47.3 5.
6
2012 75 32.0 2.2 75 18.5 2.
7
75 16.0 3.
3
75 44.9 5.
6
2013 184 32.2 1.6 184 19.2 2.
2
184 16.6 2.
3
184 45.2 3.
0
2014 78 32.3 2.0 77 19.3 2.
0
78 16.6 2.
5
76 45.1 3.
9 p* Analysis of variance (ANOVA) test for categorical independent variables (sex, ever-breastfed, HAART) and ordinal independent variables
(birth-weight, prematurity, maternal viral load, maternal CD4, maternal age, maternal education, maternal income, year of testing) BF-Breastfed FF-Formula
Supplemental Table 5. Unadjusted mean Bayley neurodevelopment domain scores and univariate analysis among the HEU children with at least one valid BSID III test in Tshipidi who were formula fed only, Botswana 2009 - 2012
Cognitive Gross motor Fine motor Expressive language Receptive language
N Mean SD p N Mean SD p N Mean SD p N Mean SD p N Mean SD p
Total 282 53.8 3.3 278 52.7 2.8 282 37.3 1.8 279 25.0 4.4 278 21.0 3.6
Sex
139 54.4 3.4 136 52.5 3.0 140 37.5 1.9 138 25.0 4.6 138 21.3 3.3
Female <0.01 0.18 0.06 0.87 0.23
Male 143 53.2 3.1 142 52.9 2.6 142 37.1 1.7 141 24.9 4.2 140 20.8 3.8
Birthweight
235 53.9 3.3 232 52.9 2.7 235 37.3 1.8 232 25.1 4.3 231 21.0 3.6
Normal 0.17 0.02 0.67 0.27 0.02
Low 47 53.2 3.2 46 51.8 3.1 47 37.2 1.6 47 24.3 4.5 47 21.0 3.3
Prematurity
Full-term 242 54.0 3.4 0.09 237 52.9 2.7 <0.01 242 37.3 1.8 0.35 239 25.0 4.3 0.69 238 21.1 3.6 0.26
Premature 34 52.9 2.6 34 51.5 3.1 34 37.0 2.1 34 24.7 4.9 34 20.4 3.4
Maternal Viral Load
<=400 105 53.7 3.4 0.79 102 52.9 2.4 0.56 104 37.3 1.7 0.87 104 25.1 4.1 0.34 104 21.0 3.0 0.90
400-999 26 53.4 3.7 25 52.1 3.6 26 37.3 2.3 26 25.3 4.2 26 21.0 3.2
1000-9999 68 54.5 3.1 69 52.6 3.1 68 37.4 1.8 67 25.3 4.5 67 21.3 3.5
>=10000 80 53.5 3.1 79 52.7 2.8 81 37.3 1.7 79 24.3 4.7 78 20.8 4.3
Maternal
CD4 18 53.3 4.1 18 52.7 2.3 18 36.7 2.2 18 24.4 4.1 18 20.5 4.0
<200 0.66 0.49 0.24 0.26 0.48
200-349 66 53.7 3.1 65 52.8 3.0 67 37.3 1.6 66 25.0 4.2 65 21.1 2.9
300-499 103 54.0 3.4 102 52.8 2.5 103 37.2 1.9 102 24.5 4.7 102 20.8 4.0
>=500 95 53.8 3.2 93 52.4 3.0 94 37.4 1.8 93 256 4.1 93 21.3 3.4
HAART
ZDV 175 54.2 3.3 <0.01 174 52.6 2.9 0.60 176 37.3 1.8 0.94 173 25.1 4.5 0.80 172 21.2 3.8 0.41
ART 102 53.0 3.1 99 52.8 2.6 101 37.3 1.8 101 24.9 4.1 101 20.8 3.0
Maternal age
77 53.8 3.2 78 52.1 3.2 77 37.3 1.8 77 25.1 4.5 76 20.9 4.4
18-24 0.20 0.39 0.86 0.80 0.39
25-29 78 54.4 3.4 76 52.9 2.5 79 37.2 1.8 78 24.7 4.3 78 21.2 3.4
30-34 67 53.4 3.6 66 53.4 2.6 67 37.5 1.9 66 25.8 4.2 66 21.6 3.1
35-39 40-44
54 6
53.4 53.7
2.9 3.8
53 5
52.4 52.0
2.7 3.7
53 6
37.0 38.0
1.6 1.4
53 5
24.7 20.0
4.0 5.8
53 5
20.2 20.6
3.0 2.3 Supplemental Table 5. (Continued)
Cognitive Gross motor Fine motor Expressive language Receptive language
N Mean SD p N Mean SD p N Mean SD p N Mean SD p N Mean SD p
Wood 79 53.7 3.2 75 52.5 2.7 79 37.3 2.0 77 25.1 4.3 4 20.3 3.9
Kerosine 4 53.0 1.4 4 52.0 0.8 4 38.0 1.8 4 23.0 6.6 77 20.8 3.4
None 5 55.0 2.2 5 54.4 3.2 5 38.2 1.3 5 27.6 3.2 5 24.2 0.8
Food insecurity
None 82 53.6 3.8 0.43 81 52.9 2.6 0.10 82 37.2 1.8 0.86 82 24.9 4.5 0.75 81 20.7 3.3 0.64
Mild 56 54.2 2.9 55 52.9 2.9 56 37.4 1.6 56 25.1 4.3 56 20.8 4.7
Moderate 77 54.3 3.3 78 52.9 2.4 78 37.4 2.1 75 25.5 4.0 75 21.7 3.0
Severe 67 53.0 2.9 64 52.0 3.3 66 37.1 1.5 66 24.4 4.6 66 20.7 3.2
Depression High score
- - - 0.14 - - - 0.77 - - - 0.65 - - - 0.32 - - - 0.22
Social support
High score
- - - 0.33 - - - 0.07 - - - 0.19 - - - 0.77 - - - 0.67
Stigma High score
- - - 0.13 - - - 0.81 - - - 0.40 - - - 0.61 - - - 0.16
Alcohol use
Ever 22 53.2 3.1 0.26 22 51.9 2.6 0.50 21 37.1 1.3 0.94 22 25.1 4.2 0.40 21 20.4 3.0 0.55
Never 232 54.1 3.4 231 52.6 2.8 233 37.3 1.9 230 24.7 4.4 230 21.0 3.7
Tobacco use
Ever 4 54.5 2.6 0.58 4 52.8 1.5 0.97 4 35.8 1.3 0.18 4 26.8 3.0 0.19 4 22.8 2.5 0.20
Never 7 54.4 4.2 7 52.6 5.0 7 36.9 1.2 7 26.6 5.9 7 22.3 4.2
Year of testing
2010 67 55.3 3.2 <0.01 67 52.3 2.9 0.99 67 37.1 2.3 0.50 66 24.4 4.8 0.81 66 21.3 3.5 0.06
2012 153 53.8 3.2 152 53.1 2.5 154 53.1 2.5 153 25.4 4.1 153 21.3 3.7
2013 62 52.2 2.9 59 52.2 3.2 61 37.3 1.8 60 24.6 4.5 59 20.0 3.2
p* Analysis of variance (ANOVA) test for categorical independent variables (sex, ever-breastfed, HAART) and ordinal independent variables (birth-weight, prematurity, maternal viral load, maternal CD4, maternal age, maternal education, maternal income, year of testing) BF-Breastfed FF-Formula
Supplemental Table 6. Unadjusted mean Development Milestones Checklist neurodevelopment domain scores and univariate analysis among the HEU children with at least one valid BSID III test in Tshipidi who were formula fed only, Botswana 2009 – 2012
Locomotor Fine motor Language score Personal-social
N Mean SD p N Mean SD p N Mean SD p N Mean SD p
Total 307 32.1 1.9 306 19.1 2.2 307 16.4 2.6 305 45.0 4.0
Sex
151 32.1 2.9 150 19.3 2.2 151 16.5 2.6 150 45.7 3.2
Female 0.89 0.15 0.39 <0.01
Male 156 32.1 1.7 156 18.9 2.3 156 16.3 2.7 155 44.4 4.6
Birthweight
254 32.2 1.8 254 19.2 2.2 254 16.5 2.6 253 45.1 4.2
Normal 0.01 0.49 0.12 0.50
Low 53 31.5 2.0 52 18.9 2.3 53 15.9 2.9 52 44.7 2.9
Prematurity
Not premature 260 32.2 1.5 <0.01 259 19.2 2.2 0.06 260 16.4 2.8 0.99 258 45.1 4.0 0.30
Premature 40 31.3 3.2 40 18.5 2.8 40 16.4 1.9 40 44.4 4.5
Maternal viral load
<=400 113 32.3 1.7 0.54 112 19.4 1.9 0.57 113 16.3 2.6 0.88 112 45.2 3.7 0.79
400-999 27 31.7 1.7 27 18.2 2.1 27 16.6 3.0 27 44.8 3.5
1000-9999 75 31.8 2.2 75 18.9 2.7 75 16.8 2.2 75 44.9 3.4
>=10000 89 32.2 1.6 89 19.3 2.2 89 16.2 2.9 88 45.0 5.0
Maternal CD4
22 32.3 1.2 22 18.4 1.9 22 15.7 3.9 22 43.6 8.8
<200 0.37 0.93 0.58 0.97
200-349 73 32.3 1.6 73 19.3 2.3 73 16.7 2.5 73 45.7 2.9
300-499 112 31.9 1.8 111 19.3 2.1 112 16.2 2.8 110 45.0 2.8
>=500 100 32.1 2.2 100 19.0 2.5 100 17.0 2.1 100 44.9 4.2
HAART
ZDV 193 32.0 2.0 0.72 193 19.0 2.4 0.29 193 16.5 2.5 0.37 192 45.2 3.3 0.26
ART 108 32.1 1.7 107 19.3 2.0 108 16.2 2.9 107 44.7 5.1
Maternal age
81 31.8 1.9 81 19.0 2.3 81 16.4 2.5 81 44.8 3.2
18-24 0.90 0.45 0.34 0.33
25-29 91 32.3 1.7 91 19.0 2.2 91 16.8 2.5 91 45.7 2.7
30-34 72 32.5 1.6 71 19.6 2.0 72 16.2 2.9 70 45.5 2.8
35-39 56 31.6 2.3 56 18.9 2.4 56 16.4 2.8 56 43.5 7.0
40-44 7 32.6 1.0 7 19.4 2.6 7 14.6 2.5 7 47.3 2.4
Maternal education
None 7 31.0 2.3 0.04 7 17.1 2.0 0.01 7 17.4 1.9 0.04 7 46.0 3.1 0.54
Supplemental Table 6. (Continued)
Locomotor Fine motor Language score Personal-social
N Mean SD p N Mean SD p N Mean SD p N Mean SD p
Primary 37 31.5 2.7 37 19.3 2.4 37 15.7 2.7 37 45.0 3.9
Secondary junior 187 32.2 1.7 186 18.9 2.3 187 16.3 2.7 186 44.8 4.5
Secondary senior 75 32.2 1.6 75 19.7 1.9 75 17.1 2.4 74 45.6 2.6
Maternal income
None 171 31.9 2.1 0.10 170 19.1 2.3 0.06 171 16.4 2.6 0.21 170 44.9 3.8 0.16
<P500 21 32.1 1.5 21 18.8 2.6 21 15.5 3.0 21 44.0 4.4
P501-P1000 60 32.4 1.5 60 19.1 2.0 60 16.2 3.0 60 45.1 5.4
>P1000 53 32.4 1.4 53 19.4 2.1 53 16.9 2.2 52 46.1 2.4
Access to sanitation
Indoor 52 32.4 1.4 0.32 52 19.4 2.0 0.13 52 16.7 2.4 0.44 51 45.8 2.5 0.21
Private 208 32.0 1.7 207 19.2 2.2 208 16.3 2.9 207 44.8 4.3
Shared 46 32.0 2.7 46 18.5 2.6 46 16.7 1.7 46 45.3 4.1
Electricity
Yes 150 32.2 2.1 0.33 149 19.3 2.3 0.18 150 16.4 2.5 0.89 148 45.1 3.1 0.91
No 156 32.0 1.6 156 18.9 2.2 156 16.4 2.8 156 45.0 4.8
Source of water
Home 49 32.3 1.4 0.33 49 19.5 2.0 0.39 49 17.0 2.4 0.30 48 45.4 2.9 0.48
Yard 209 31.9 2.0 208 19.1 2.3 209 16.2 2.8 208 44.8 4.1
Communal 41 32.5 1.5 41 18.8 2.4 41 16.5 2.1 41 46.0 4.8
Other 7 31.7 2.2 7 19.0 1.9 7 16.7 2.1 7 44.8 2.7
Cooking method
Gas, electric 212 32.2 1.7 <0.01 211 19.3 2.1 <0.01 212 16.5 2.7 0.82 210 45.2 4.1 0.02
Wood 83 31.8 1.6 83 18.8 2.4 83 16.3 2.6 83 44.7 3.1
Kerosine 6 29.5 5.8 6 16.5 4.5 6 15.8 2.2 6 40.5 8.9
None 5 32.4 1.3 5 20.0 1.0 5 16.0 0.0 5 47.0 2.1
Housing
Formal 301 32.1 1.9 0.70 300 19.1 2.3 0.92 301 16.4 2.6 0.80 299 45.1 4.0 0.96
Informal 4 31.5 1.3 4 19.3 2.2 4 16.0 3.3 4 44.5 4.5
None 1 31.0 - 1 20.0 - 1 18.0 - 1 45.0 -
Food insecurity
None 88 32.0 2.2 0.71 87 19.4 2.1 0.10 88 16.5 2.9 0.59 86 45.5 3.0 0.10
Supplemental Table 6. (Continued)
Locomotor Fine motor Language score Personal-social
N Mean SD p N Mean SD p N Mean SD p N Mean SD p
Moderate 86 32.1 1.5 86 19.1 2.1 86 16.3 2.7 86 44.8 5.0
Severe 71 32.1 2.3 71 18.8 2.6 71 16.3 2.7 71 44.5 4.8
Depression
High score - - - 0.07 - - - 0.05 - - - 0.28 - - - 0.02
Social support
High score - - - 0.09 - - - 0.12 - - - 0.31 - - - 0.13
Stigma
High score - - - 0.83 - - - 0.86 - - - 0.21 - - - 0.76
Alcohol use
Ever 22 32.2 2.2 0.58 22 20.2 1.4 0.41 22 16.5 2.1 0.17 22 43.5 5.7 0.63
Never 254 32.0 1.8 253 18.9 2.3 254 16.3 3.0 252 45.0 4.6
Tobacco use
Ever 4 32.5 1.7 0.73 4 19.3 2.2 0.32 4 16.0 0.0 0.04 4 44.8 3.5 0.74
Never 7 32.1 1.7 7 20.0 2.7 7 18.9 2.0 7 45.7 2.8
Year of testing
2010 71 32.0 2.2 0.35 71 18.7 2.6 0.05 71 16.0 3.3 0.17 71 44.7 5.7 0.88
2012 170 32.1 1.6 170 19.2 2.2 170 16.5 2.3 170 45.2 3.1
2013 66 32.3 2.1 65 19.5 1.7 66 16.6 2.6 64 44.8 4.1
p* Analysis of variance (ANOVA) test for categorical independent variables (sex, ever-breastfed, HAART) and ordinal independent variables (birth-weight, prematurity, maternal viral load, maternal CD4, maternal age, maternal education, maternal income, year of testing) BF-Breastfed FF-Formula
Supplemental Table 7. Sensitivity analyses among the HEU children with at least one valid BSID III test from the Mma Bana and Tshipidi studies, Botswana 2009 - 2012
Supplemental Table 8. Sensitivity analyses univariate analysis among the HEU children with at least one valid BSID III test in Tshipidi who were formula fed only, Botswana 2009 - 2012
Adjusted difference* Further adjusted for birthweight
Further adjusted for prematurity Neurodevelopmental
assessment
Mean difference (95%
CI)
P-value Mean
difference (95% CI)
P-value Mean
difference (95% CI)
P-value
BSIDIII
Cognitive -0.3 (-1.4, 0.9) 0.64 -0.2 (-1.3, 1.0) 0.77 -0.2 (-1.4, 0.9) 0.67 Gross motor 0.8 (-0.1, 1.7) 0.08 0.9 (-0.1, 1.8) 0.09 0.7 (-0.2, 1,6) 0.10 Fine motor 0.5 (-0.2, 1.3) 0.16 0.6 (-0.2, 1.3) 0.13 0.5 (-0.2, 1.3) 0.17 Expressive language 0.7 (-0.3, 1.7) 0.19 0.8 (-0.2, 1.8) 0.13 0.6 (-0.4, 1.7) 0.23 Receptive language 0.1 (-0.7, 0.8) 0.88 0.1 (-0.7, 0.9) 0.81 0.1 (-0.7, 0.9) 0.84
DMC
Loco motor 0.0 (-0.5, 0.6) 0.86 0.0 (-0.5, 0.5) 0.91 0.1 (-0.5, 0.5) 0.85 Fine motor 0.3 (-0.3, 0.8) 0.32 0.3 (-0.3, 0.8) 0.31 0.3 (-0.2, 0.7) 0.30 Language -0.1 (-0.5, 0.4) 0.82 0.0 (-0.5, 0.5) 0.97 -0.1 (-0.5, 0.4) 0.76 Personal-social 0.2 (-0.7, 1.1) 0.69 0.2 (-0.7, 1.1) 0.63 0.2 (-0.7, 1.1) 0.72
*Bayley-III: Cognitive adjusted for year of neurodevelopmental testing. Gross Motor adjusted for maternal income, Fine Motor adjusted for maternal CD4 count and year of neurodevelopmental testing, Expressive Language adjusted for maternal education and year of neurodevelopmental testing, Receptive Language adjusted for year of
neurodevelopmental testing. DMC: Locomotor adjusted for maternal income and year of neurodevelopmental testing, Fine Motor adjusted for maternal CD4, maternal age and year of neurodevelopmental testing, language adjusted for maternal CD4 count and maternal education, Personal-Social adjusted for year of neurodevelopmental testing.
Adjusted difference* Further adjusted for birthweight
Further adjusted for prematurity Neurodevelopmental
Assessment
Mean difference (95%
CI)
P-value Mean
difference (95%
CI)
P-value Mean
difference (95%
CI)
P-value
BSIDIII
Cognitive -0.2 (-1.1, 0.7) 0.66 -0.1 (-1.0, 0.9) 0.91 -0.2 (-1.1, 0.7) 0.72 Gross motor 0.0 (-0.7, 0.7) 0.95 0.2 (-0.5, 0.9) 0.60 0.0 (-0.6, 0.7) 0.93 Fine motor -0.1 (-0.6, 0.4) 0.55 -0.1 (-0.3, 0.4) 0.60 -0.1 (-0.6, 0.3) 0.59 Expressive language -0.2 (-1.3, 0.9) 0.71 0.0 (-1.0, 1.1) 0.93 -0.3 (-1.4, 0.8) 0.63 Receptive language 0.2 (-0.8, 1.2) 0.70 0.2 (-0.8, 1.3) 0.69 0.2 (-0.8, 1.2) 0.68
DMC
Loco motor 0.1 (-0.3, 0.6) 0.66 0.2 (-0.2, 0.7) 0.29 0.2 (-0.3, 0.6) 0.47 Fine motor 0.0 (-0.6, 0.6) 0.88 0.1 (-0.5, 0.7) 0.82 0.1 (-0.5, 0.7) 0.76 Language -0.6 (-1.3, 0.1) 0.10 -0.5 (-1.2, 0.2) 0.16 -0.6 (-1.4, 0.1) 0.08 Personal-social -0.7 (-1.6, 0.3) 0.16 -0.7 (-1.7, 0.3) 0.16 -0.7 (-1.7, 0.3) 0.18
*Bayley-III: Cognitive adjusted for maternal education, depression and year of neurodevelopmental testing. Gross Motor adjusted for source of water and social score, Fine Motor adjusted for maternal education, access to sanitation and social support, Expressive Language is adjusted for maternal education and income, Receptive Language is adjusted for stigma and year of neurodevelopmental testing. DMC: Locomotor adjusted for maternal income and social support, Fine Motor adjusted for maternal education, use of alcohol during pregnancy and year of neurodevelopmental testing, Language for maternal education and year of neurodevelopmental testing. Personal- Social adjusted for depression.
Supplemental Table 9. Baseline characteristics of “at risk” (at risk or low score <1SD below domain-specific mean or invalid) versus “not at risk” (not at risk, not low score, valid) among the HEU children from the Tshipidi and Mma Bana studies, Botswana 2009 - 2012
Within normal range (N, %)
Low-invalid-at risk (N, %)
P-value (Chi-Square)
Bayley cognitive 488 (91.7%) 44 (8.3%)
Gender 0.17
Female 252 (51.6%) 18 (40.9%)
Birthweight 0.03
Low birthweight 71 (14.6%) 12 (27.3%)
Breast-fed 0.05
Ever breastfed 232 (47.5%) 14 (31.8%)
Premature 0.30
Premature 44 (9.1%) 6 (14.0%)
Maternal age 0.22
18-24 147 (30.1%) 10 (22.7%)
25-29 139 (28.5%) 12 (27.3%)
30-34 99 (20.9%) 12 (27.3%)
35-39 93 (19.1%) 7 (15.9%)
40-44 10 (2.1%) 3 (6.8%)
Maternal education 0.07
None 13 (2.7%) 0 (0%)
Primary 74 (15.2%) 13 (30.0%)
Secondary Junior 286 (58.6%) 22 (50.0%)
Secondary Senior or Tertiary 115 (23.6%) 9 (20.5%)
Maternal income 0.49
None 262 (53.9%) 28 (63.6%)
<P500 70 (14.4%) 7 (15.9%)
P501-P1000 86 (17.7%) 5 (11.4%)
>P1000 68 (14.0%) 4 (9.1%)
Bayley gross motor 479 (90.7%) 49 (9.3%)
Gender 0.69
Female 239 (49.9%) 23 (46.9%)
Birthweight 0.54
Low birthweight 72 (15.0%) 9 (18.4%)
Breast-fed 0.82
Not breastfed 223 (46.6%) 22 (44.9%)
Premature 0.02
Premature 41 (8.7%) 9 (19.2%)
Maternal age 0.64
18-24 140 (29.2%) 18 (36.7%)
25-29 138 (28.8%) 12 (24.5%)
Supplemental Table 9. (Continued)
Within normal range (N, %)
Low-invalid-at risk (N, %)
P-value (Chi-Square)
35-39 90 (18.8%) 8 (16.3%)
40-44 9 (1.9%) 2 (4.1%)
Maternal education 0.21
None 11 (2.3%) 2 (4.1%)
Primary 74 (15.5%) 12 (24.5%)
Secondary Junior 283 (59.1%) 22 (44.9%)
Secondary Senior or Tertiary 111 (23.2%) 13 (26.5%)
Maternal income 0.45
None 258 (54.1%) 27 (55.1%)
<P500 66 (13.8%) 10 (20.4%)
P501-P1000 84 (17.6%) 8 (16.3%)
>P1000 69 (14.5%) 4 (8.2%)
Bayley fine motor 509 (94.6%) 29 (5.4%)
Gender 0.50
Female 248 (48.7%) 16 (55.2%)
Birthweight 0.80
Low birthweight 79 (15.5%) 5 (17.2%)
Breast-fed 0.84
Ever breastfed 271 (53.2%) 13 (44.8%)
Premature 0.15
Premature 46 (9.2%) 5 (17.2%)
Maternal age 0.78
18-24 150 (29.5%) 11 (37.9%)
25-29 144 (28.3%) 8 (27.6%)
30-34 107 (21.0%) 6 (20.7%)
35-39 95 (18.7%) 4 (13.8%)
40-44 13 (2.6%) 0 (0%)
Maternal education 0.46
None 13 (2.6%) 0 (0%)
Primary 82 (16.1%) 6 (20.7%)
Secondary Junior 293 (57.6%) 19 (65.5%)
Secondary Senior or Tertiary 121 (23.8%) 4 (13.8%)
Maternal income 0.88
None 272 (53.7%) 17 (58.6%)
<P500 80 (15.8%) 3 (10.3%)
P501-P1000 87 (17.2%) 5 (17.2%)
>P1000 68 (13.4%) 4 (13.9%)
Bayley expressive language 438 (83.3%) 88 (16.7%)
Supplemental Table 10. Univariate predictors of low-invalid-‘at-risk’ neurodevelopment domain scores among the HEU children from the Mma Bana and Tshipidi studies, Botswana 2009 - 2012
Bayley Cognitive
P value OR (95%CI)
Gross motor P value OR (95%CI)
Fine motor P value OR (95%CI)
Expressive language P value OR (95%CI)
Receptive language P value OR (95%CI)
Gender 0.18 0.69 0.50 0.17 <0.01
Male vs. Female 1.54 (0.82, 2.89) 0.89 (0.49, 1.60) 1.30 (0.61, 2.75) 1.38 (0.87, 2.18) 2.20 (1.37, 3.51)
Birthweight 0.03 0.54 0.80 0.64 0.56
Low vs. Normal 2.20 (1.08, 4.48) 1.27 (0.59, 2.73) 1.13 (0.42, 3.06) 1.16 (0.63, 2.14) 1.20 (0.66, 2.18)
Breast-fed 0.05 0.82 0.84 <0.01 <0.01
Ever vs. Never 0.52 (0.27, 1.00) 0.94 (0.52, 1.69) 0.93 (0.44, 1.96) 0.43 (0.26, 0.71) 0.35 (0.21, 0.58)
Prematurity 0.30 0.02 0.16 0.43 0.03
Premature vs.
Full-term
1.62 (0.65, 4.05) 2.50 (1.13, 5.53) 2.07 (0.75, 5.68) 1.35 (0.65, 2.83) 2.08 (1.07, 4.06)
Maternal age 0.22 0.61 0.24 0.94 0.90
1.18 (0.91, 1.53) 0.94 (0.72, 1.21) 0.81 (0.58, 1.15) 0.99 (0.81, 1.21) 1.01 (0.83, 1.23) Maternal
education
0.27
0.79 (0.51, 1.21) 0.38
0.83 (0.55, 1.25) 0.48
0.83 (0.49, 1.40) 0.41
0.87 (0.63, 1.20) 0.86
1.03 (0.75, 1.42) Maternal income 0.15
0.80 (0.59, 1.08) 0.38
0.88 (0.67, 1.16) 0.85
0.97 (0.69, 1.36) 0.34
1.10 (0.90, 1.35) 0.04
0.80 (0.64, 0.99)
Supplemental Table 11. Multivariate predictors of low-invalid-‘at-risk’ neurodevelopment domain scores among the HEU children from the Mma Bana and Tshipidi studies, Botswana 2009 - 2012
Bayley Cognitive P value OR (95%CI)
Gross motor P value OR (95%CI)
Fine motor P value OR (95%CI)
Expressive language P value OR (95%CI)
Receptive language P value OR (95%CI)
Gender <0.01
Male vs. Female - - - - 0.46 (0.29, 0.75)
Birthweight 0.03
Low vs. Normal 2.17 (1.06, 4.43) - - - -
Breast-fed 0.05 <0.01 <0.01
Ever vs. Never 0.52 (0.27, 1.01) - - 0.43 (0.26, 0.71) 0.35 (0.21, 0.57)
Prematurity 0.02
Premature vs.
Full-term
- 2.50 (1.13,
5.53)
- - -
Maternal age
- - - - -
Maternal education
- - - - -
Maternal income 0.04
- - - - 0.79 (0.64, 0.99)