neurodevelopment of hiv - exposed but uninfected infants...
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Neurodevelopment of HIV-exposed but uninfected infants at age 12 months Christopher Goodenough1, Anand Selvam2, Jennifer
Makin3, Irina Buhimschi4, Brian Forsyth4
1Tulane University, 2Boston University, 3University of Pretoria, 4Yale University
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HEU Children Increased morbidity
Increased mortality
Growth delay
Developmental delay
Filteau, S. The HIV-exposed, uninfected African Child. Trop Med and Intl Health. 2009;14(3):276–287
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HEU Neurodevelopment Drotar 1997 3 arms – HIV-infected, HEU and NE Found differences based on HIV status, not exposure Pediatrics. 1997 Jul;100(1):E5
Van Rie 2008 3 arms – HIV-infected, HEU and NE Analyzed delay as a categorical, not continuous variable, Found higher rates of delay in HIV-infected and HEU
arms Pediatrics. 2008 July ; 122(1): e123–e128
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HEU Neurodevelopment Alimenti 2006 Used BSID and Vineland scales to assess HAART safety Found no differences after controlling for maternal substance
use Pediatrics 2006;118;e1139
Williams 2010 Large, retrospective study of ARV effect on development, using
BSID, 2nd edition ARV usage showed no effects on development Secondary analysis showed potential differences caused by
HIV status Pediatrics. 2010 February ; 125(2): e250–e260
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HEU Neurodevelopment
Springer 2012 Small sample size (17 HEU; 20 NE) Researchers concluded no difference between groups S Afr J CH 2012;6(2):51-55
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Aims
To assess whether HIV-exposed but uninfected infants are developmentally delayed compared to non-exposed infants
To identify other factors occurring in the first year of life that may affect development in HIV-exposed but uninfected infants
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Methods Longitudinal study HEU infants followed to age 12 months
Derived from the cohort of a larger, PMTCT study in Pretoria, South Africa Enrolled at birth and followed to 3 months
Neurodevelopment study Infants born between September 1st 2010 – April 30th 2011 Follow-up at 3 and 12 months based on time of enrollment All infants confirmed HIV negative by PCR testing
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Enrollment 1351
Eligible infants
275 Invited for 12 mo
assessment
238 Assessed with
BSID and Vineland
1076 Not invited
20 Refused follow up
17 Assessed with
Vineland, but not BSID
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Data Collection Enrollment Socio-demographic characteristics
3 Months Maternal psychological measures Depression (CES-D) Self-efficacy
Infant feeding
12 Months Child Development (Bayley III) Child Adaptive Functioning (Vineland II) Hemoglobin by HemoCue (Anemia: Hb <10g/dL)
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Data Analyses Comparison of group characteristics Socio-demographics Psychological well-being
Comparison of infant development and adaptive outcomes
Multivariate model Control for baseline differences between study groups Repeated with inclusion of intervening variables that
potentially affect development
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Baseline Characteristics
Characteristic NE HEU
p Value (N = 146) (N = 92)
Maternal Age (SD) 25.6 (5.8) 28.7 (5.1) < 0.001
Married 31 (19.7%) 33 (33.7%) 0.017
First-born child 62 (39.5%) 17 (17.3%) < 0.001
Employment 55 (35.3%) 39 (41.9%) 0.34
Maternal school level attained 0.71
Primary 14 (9.0%) 11 (11.5%)
Secondary 130 (83.9%) 80 (83.3%)
Tertiary 11 (7.1%) 5 (5.2%)
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Baseline Characteristics
Characteristic NE HEU
p Value (N = 146) (N = 92)
Maternal Age (SD) 25.6 (5.8) 28.7 (5.1) < 0.001
Married 31 (19.7%) 33 (33.7%) 0.017
First-born child 62 (39.5%) 17 (17.3%) < 0.001
Employment 55 (35.3%) 39 (41.9%) 0.34
Maternal school level attained 0.71
Primary 14 (9.0%) 11 (11.5%)
Secondary 130 (83.9%) 80 (83.3%)
Tertiary 11 (7.1%) 5 (5.2%)
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Developmental Outcomes at 12 Months
Characteristic NE HEU p Value
Bayley Scales of Infant Development (N = 146) (N = 92)
Cognitive Score (SD) 100.4 (15.8) 94.5 (12.6) 0.003
Language Composite Score (SD) 91.6 (12.2) 91.6 (10.5) 0.97
Motor Composite Score (SD) 95.4 (9.5) 94.9 (9.1) 0.69
Vineland Adaptive Behavior Scales (N = 152) (N = 94)
Communication (SD) 107.3 (7.4) 107.4 (8.4) 0.95
Daily Living Skills (SD) 104.0 (10.3) 101.6 (8.8) 0.13
Socialization (SD) 103.4 (11.8) 103.3 (11.1) 0.95
Motor (SD) 96.9 (11.2) 94.4 (11.9) 0.11
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Developmental Outcomes at 12 Months
Characteristic NE HEU p Value
Bayley Scales of Infant Development (N = 146) (N = 92)
Cognitive Score (SD) 100.4 (15.8) 94.5 (12.6) 0.003
Language Composite Score (SD) 91.6 (12.2) 91.6 (10.5) 0.97
Motor Composite Score (SD) 95.4 (9.5) 94.9 (9.1) 0.69
Vineland Adaptive Behavior Scales (N = 152) (N = 94)
Communication (SD) 107.3 (7.4) 107.4 (8.4) 0.95
Daily Living Skills (SD) 104.0 (10.3) 101.6 (8.8) 0.13
Socialization (SD) 103.4 (11.8) 103.3 (11.1) 0.95
Motor (SD) 96.9 (11.2) 94.4 (11.9) 0.11
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Multiple Regression: Factors associated with cognitive development
Beta t p-value
Maternal HIV Status -0.165 -2.412 0.017
Maternal Age -0.023 -0.301 0.84
Married -0.080 -1.158 0.29
First-born child -0.005 -0.063 0.79
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Multiple Regression: Factors associated with cognitive development
Beta t p-value
Maternal HIV Status -0.165 -2.412 0.017
Maternal Age -0.023 -0.301 0.84
Married -0.080 -1.158 0.29
First-born child -0.005 -0.063 0.79
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Intervening Variables
Characteristic NE (N = 146)
HEU (N = 92) p Value
Depressed at 3 months 32 (25.4%) 16 (19.5%) 0.40
Self efficacy at 3 months (SD) 3.9 (1.7) 4.5 (1.5) 0.013
Ever breast fed 149 (96.1%) 71 (72.4%) < 0.001
Infant anemia at 12 months 64 (51.6%) 36 (43.4%) 0.26
Infant hospitalization 15 (9.6%) 13 (13.3%) 0.41
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Intervening Variables
Characteristic NE (N = 146)
HEU (N = 92) p Value
Depressed at 3 months 32 (25.4%) 16 (19.5%) 0.40
Self efficacy at 3 months (SD) 3.9 (1.7) 4.5 (1.5) 0.013
Ever breast fed 149 (96.1%) 71 (72.4%) < 0.001
Infant anemia at 12 months 64 (51.6%) 36 (43.4%) 0.26
Infant hospitalization 15 (9.6%) 13 (13.3%) 0.41
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Multiple Regression: Factors associated with cognitive development
Beta t p-value
Maternal HIV Status -0.163 -1.97 0.050
Maternal age -0.059 0.60 0.55
Married -0.171 -2.12 0.036
First-born child -0.081 -0.91 0.37
Maternal depression at 3 months -0.001 -0.012 0.99
Self-efficacy -0.081 -0.93 0.35
Ever breast fed -0.112 -1.44 0.15
Infant anemia -0.183 -2.41 0.017
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Multiple Regression: Factors associated with cognitive development
Beta t p-value
Maternal HIV Status -0.163 -1.97 0.050
Maternal age -0.059 0.60 0.55
Married -0.171 -2.12 0.036
First-born child -0.081 -0.91 0.37
Maternal depression at 3 months -0.001 -0.012 0.99
Self-efficacy -0.081 -0.93 0.35
Ever breast fed -0.112 -1.44 0.15
Infant anemia -0.183 -2.41 0.017
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Multiple Regression: Factors associated with cognitive development
Beta t p-value
Maternal HIV Status -0.163 -1.97 0.050
Maternal age -0.059 0.60 0.55
Married -0.171 -2.12 0.036
First-born child -0.081 -0.91 0.37
Maternal depression at 3 months -0.001 -0.012 0.99
Self-efficacy -0.081 -0.93 0.35
Ever breast fed -0.112 -1.44 0.15
Infant anemia -0.183 -2.41 0.017
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Summary HIV exposed but uninfected infants have significant
cognitive delay when compared with non-exposed infants from the same community
The effect of maternal HIV disease remained at borderline significance when controlling for other differences between groups
There were no differences in language or motor development or adaptive functioning
Other factors related to cognitive development included marital status and infant anemia
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Future Work
We plan to follow this cohort and to reassess development and adaptive functioning at 21 and 30 months
Published data suggests that differences in cognitive development become more marked in the second year of life
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Acknowledgements Special thanks to: Doris Duke Charitable Foundation for funding this
research project Drs. Brian Forsyth and Jennifer Makin for their
mentorship Yale University and University of Pretoria faculty and staff
for their help and support