Neurodevelopment of HIV - exposed but uninfected infants ...regist2.virology-education.com/2012/4HIVped/docs/... · Neurodevelopment of HIV - exposed but uninfected infants at age

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

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

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

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

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

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

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

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

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)

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

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%)

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%)

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

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

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


Beta t p-value


Maternal Age -0.023 -0.301 0.84

Married -0.080 -1.158 0.29


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

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


Beta t p-value


Maternal age -0.059 0.60 0.55

Married -0.171 -2.12 0.036


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


Beta t p-value


Maternal age -0.059 0.60 0.55

Married -0.171 -2.12 0.036



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


Beta t p-value


Maternal age -0.059 0.60 0.55

Married -0.171 -2.12 0.036



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

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

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

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

Documents

Neurodevelopment of HIV - exposed but uninfected infants ...regist2.virology-education.com/2012/4HIVped/docs/... · Neurodevelopment of HIV - exposed but uninfected infants at age