Neurodevelopmental outcomes in HIV-exposed-uninfected children versus those not exposed to HIV

Abstract

Human immunodeficiency virus (HIV)-negative children born to HIV-infected mothers may exhibit differences in neurodevelopment (ND) compared to age- and gender-matched controls whose lives have not been affected by HIV. This could occur due to exposure to HIV and antiretroviral agents in utero and perinatally, or differences in the environment in which they grow up. This study assessed neurodevelopmental outcomes in HIV-exposed uninfected (HEU) and HIV-unexposed uninfected (HUU) children enrolled as controls in a multicenter ND study from Thailand and Cambodia. One hundred sixty HEU and 167 HUU children completed a neurodevelopmental assessment using the Beery Visual Motor Integration (VMI) test, Color Trails, Perdue Pegboard, and Child Behavior Checklist (CBCL). Thai children (n = 202) also completed the Wechsler Intelligence Scale (IQ) and Stanford-Binet II memory tests. In analyses adjusted for caregiver education, parent as caregiver, household income, age, and ethnicity, statistically significant lower scores were seen on verbal IQ (VIQ), full-scale IQ (FSIQ), and Binet Bead Memory among HEU compared to HUU. The mean (95% CI) differences were −6.13 (−10.3 to −1.96), p = 0.004; −4.57 (−8.80 to −0.35), p = 0.03; and −3.72 (−6.57 to −0.88), p = 0.01 for VIQ, FSIQ, and Binet Bead Memory, respectively. We observed no significant differences in performance IQ, other Binet memory domains, Color Trail, Perdue Pegboard, Beery VMI, or CBCL test scores. We conclude that HEU children evidence reductions in some neurodevelopmental outcomes compared to HUU; however, these differences are small and it remains unclear to what extent they have immediate and long-term clinical significance.

Brain Imaging and Neurodevelopment in HIV-uninfected Thai Children Born to HIV-infected Mothers

“…This study complements prior reports of no detectable differences in neurodevelopment between HEU and HUU children 13 . Our previous findings in the full sample (not only imaged children) demonstrated small, although statistically significant group differences in neuropsychological test performance 14, 15 ; our current study mapping the neuropsychiatric scores across the brain enables us to observe the neuroanatomical pathways where these group differences may reside. However, the clinical significance of our previous findings remains unclear.…”

“…School attendance was unavailable for two children (1 HEU and 1 HUU), caregivers’ education level was unavailable for three children (2 HEU and 1 HUU), and caregiver income was unavailable for two children (1 HEU and 1 HUU). All children completed age-appropriate neuropsychological assessments as previously described 14, 15 . The battery included: the Wechsler Preschool and Primary Scale of Intelligence-III (WPPSI-III, ages 2 to 6 years) and the Wechsler Intelligence Scale for Children (WISC-III, ages 6 to 17 years).…”

“…One study noted a greater frequency of mental, motor and language expression developmental delays in HEU (and other children in affected households) than HUU 12 . Another failed to identify neurodevelopment differences in the first two years of life 13 , while yet others find subtle differences 14, 15 for which the clinical meaning is unclear. A further evaluation into the neuroanatomical mechanisms potentially affected is therefore needed.…”

Disclosing in utero HIV/ARV exposure to the HIV‐exposed uninfected adolescent: is it necessary?

“…A more recent study within PHACS also evaluated cognitive outcomes in older HEU children and did not find associations between any perinatal ART class regimens and cognitive and academic scores [84]. One study from Thailand reported small reductions in Wechsler Intelligence Scale testing comparing HEU to HUU children but acknowledged the uncertainty around the long-term clinical significance of these findings [108]. …”

Effect of Caregiver Training on the Neurodevelopment of HIV-Exposed Uninfected Children and Caregiver Mental Health: A Ugandan Cluster-Randomized Controlled Trial

“…In addition, HEU children were found to be more likely to experience motor impairment (14%), delays in expressive language, and fine motor problems. 16 These impairments could be due to perinatal exposure to the HIV virus or antiretroviral therapy (ART), 17, 18 For instance antenatal HIV-exposure (without infection) may compromise HEU children’s cognitive development, when maternal immune activation negatively affects the developing fetal brain. 19 …”