Neurodevelopment of HIV-Exposed Uninfected Infants Born to Women With Perinatally Acquired HIV in the United States

Jennifer Jao, Deborah Kacanek, Wendy Yu, Paige L Williams, Kunjal Patel, Sandra Burchett, Gwendolyn Scott, Elaine J Abrams, Rhoda S Sperling, Russell B Van Dyke, Renee Smith, Kathleen Malee, Pediatric HIV/AIDS Cohort Study, Jennifer Jao, Deborah Kacanek, Wendy Yu, Paige L Williams, Kunjal Patel, Sandra Burchett, Gwendolyn Scott, Elaine J Abrams, Rhoda S Sperling, Russell B Van Dyke, Renee Smith, Kathleen Malee, Pediatric HIV/AIDS Cohort Study

Abstract

Background: Lifelong HIV and antiretroviral therapy may confer neurodevelopmental risk on the children of women with perinatally acquired HIV infection (PHIV).

Setting: We analyzed data from HIV-exposed uninfected (HEU) infants born to women with PHIV vs. non-perinatally acquired HIV (NPHIV) enrolled in the Surveillance Monitoring for Antiretroviral Therapy Toxicities (SMARTT) study.

Methods: Using the Bayley Scales of Infant and Toddler Development, third Ed. (Bayley-III), we compared neurodevelopmental outcomes at the age of 1 year in HEU infants born to women with PHIV vs. NPHIV. Those with valid Bayley-III data at the age of 1 year and a mother born after 1982 were included. Cognitive, language, and motor domains were assessed as continuous composite scores. Linear mixed effects models were fit to estimate the mean difference in Bayley-III scores between groups, adjusting for confounders.

Results: Five hundred fifty women with HIV gave birth to 678 HEU children (125 and 553 born to women with PHIV and NPHIV, respectively). Mean scores for each of the Bayley-III domains were not significantly different between infants born to women with PHIV vs. NPHIV in unadjusted models. After adjustment, infants of women with PHIV had lower language (91.9 vs. 94.8, P = 0.05) and motor (93.7 vs. 96.8, P = 0.03) composite scores, but no differences in cognitive composite scores.

Conclusions: Cognitive domain outcomes of infants born to women with PHIV vs. NPHIV are reassuring. Differences in early language and motor functioning, while of modest clinical significance, highlight the importance of long-term monitoring of neurodevelopment in children of women with PHIV.

Conflict of interest statement

Declaration of Interests

The authors have no financial disclosures to report.

Figures

Figure 1.. Study Population Derivation
Figure 1.. Study Population Derivation
SMARTT=Surveillance Monitoring of ART Toxicities; HEU-PHIV=HIV-exposed uninfected infant born to woman with perinatally acquired HIV; HEU-NPHIV=HIV-exposed uninfected infant born to woman with non-perinatally acquired HIV

References

    1. Van Rie A, Mupuala A, Dow A. Impact of the HIV/AIDS epidemic on the neurodevelopment of preschool-aged children in Kinshasa, Democratic Republic of the Congo. Pediatrics. 2008;122(1):e123–128.
    1. McHenry MS, McAteer CI, Oyungu E, et al. Neurodevelopment in Young Children Born to HIV-Infected Mothers: A Meta-analysis. Pediatrics. 2018;141(2).
    1. Gomez C, Archila ME, Rugeles C, Carrizosa J, Rugeles MT, Cornejo JW. [A prospective study of neurodevelopment of uninfected children born to human immunodeficiency virus type 1 positive mothers]. Rev Neurol. 2009;48(6):287–291.
    1. le Roux SM, Donald KA, Brittain K, et al. Neurodevelopment of breastfed HIV-exposed uninfected and HIV-unexposed children in South Africa. AIDS. 2018;32(13):1781–1791.
    1. Kerr SJ, Puthanakit T, Vibol U, et al. Neurodevelopmental outcomes in HIV-exposed-uninfected children versus those not exposed to HIV. AIDS Care. 2014;26(11):1327–1335.
    1. Nozyce ML, Huo Y, Williams PL, et al. Safety of In Utero and Neonatal Antiretroviral Exposure: Cognitive and Academic Outcomes in HIV-exposed, Uninfected Children 5–13 Years of Age. Pediatr Infect Dis J. 2014;33(11):1128–1133.
    1. Rice ML, Zeldow B, Siberry GK, et al. Evaluation of risk for late language emergence after in utero antiretroviral drug exposure in HIV-exposed uninfected infants. Pediatr Infect Dis J. 2013;32(10):e406–413.
    1. le Roux SM, Donald KA, Kroon M, et al. HIV Viremia During Pregnancy and Neurodevelopment of HIV-Exposed Uninfected Children in the Context of Universal Antiretroviral Therapy and Breastfeeding: A Prospective Study. Pediatr Infect Dis J. 2018.
    1. Badell ML, Kachikis A, Haddad LB, Nguyen ML, Lindsay M. Comparison of pregnancies between perinatally and sexually HIV-infected women: an observational study at an urban hospital. Infectious diseases in obstetrics and gynecology. 2013;2013:301763.
    1. Jao J, Kacanek D, Williams PL, et al. Birth Weight and Preterm Delivery Outcomes of Perinatally vs. non-Perinatally HIV-infected Pregnant Women in the U.S.: Results from the PHACS SMARTT Study and IMPAACT P1025 Protocol. Clin Infect Dis. 2017.
    1. Munjal I, Dobroszycki J, Fakioglu E, et al. Impact of HIV-1 infection and pregnancy on maternal health: comparison between perinatally and behaviorally infected young women. Adolesc Health Med Ther. 2013;4:51–58.
    1. Connors SL, Levitt P, Matthews SG, et al. Fetal mechanisms in neurodevelopmental disorders. Pediatr Neurol. 2008;38(3):163–176.
    1. Bourgeois JP. Synaptogenesis, heterochrony and epigenesis in the mammalian neocortex. Acta Paediatr Suppl. 1997;422:27–33.
    1. Van Dyke RB, Chadwick EG, Hazra R, Williams PL, Seage GR 3rd. The PHACS SMARTT Study: Assessment of the Safety of In Utero Exposure to Antiretroviral Drugs. Front Immunol. 2016;7:199.
    1. Sirois PA, Huo Y, Williams PL, et al. Safety of perinatal exposure to antiretroviral medications: developmental outcomes in infants. Pediatr Infect Dis J. 2013;32(6):648–655.
    1. Bayley N. Bayley Scales of Infant and Toddler Development–Third Edition. San Antonio, TX: Harcourt Assessment; 2006.
    1. Wechsler D. Wechsler Abbreviated Scale of Intelligence. San Antonio: The Psychological Corporation; 1999.
    1. Aidala AHJ, Mellins CA, Dodds S, Whetten K, Martin D, Gillis L, & Ko P. Development and validation of the Client Diagnostic Questionnaire (CDQ): a mental health screening tool for use in HIV/AIDS service settings. Psychology, Health & Medicine. 2004;9(3):362–380.
    1. Whitehead N, Potterton J, Coovadia A. The neurodevelopment of HIV-infected infants on HAART compared to HIV-exposed but uninfected infants. AIDS Care. 2014;26(4):497–504.
    1. Truong HM, Sim MS, Dillon M, et al. Correlation of immune activation during late pregnancy and early postpartum with increases in plasma HIV RNA, CD4/CD8 T cells, and serum activation markers. Clin Vaccine Immunol. 2010;17(12):2024–2028.
    1. Goeden N, Velasquez J, Arnold KA, et al. Maternal Inflammation Disrupts Fetal Neurodevelopment via Increased Placental Output of Serotonin to the Fetal Brain. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2016;36(22):6041–6049.
    1. Langridge AT, Glasson EJ, Nassar N, et al. Maternal conditions and perinatal characteristics associated with autism spectrum disorder and intellectual disability. PLoS One. 2013;8(1):e50963.
    1. Hoare J, Fouche JP, Phillips N, et al. Structural brain changes in perinatally HIV-infected young adolescents in South Africa. AIDS. 2018;32(18):2707–2718.
    1. Wood SM, Shah SS, Steenhoff AP, Rutstein RM. The impact of AIDS diagnoses on long-term neurocognitive and psychiatric outcomes of surviving adolescents with perinatally acquired HIV. AIDS. 2009;23(14):1859–1865.
    1. Smith R, Chernoff M, Williams PL, et al. Impact of HIV severity on cognitive and adaptive functioning during childhood and adolescence. Pediatr Infect Dis J. 2012;31(6):592–598.
    1. Nachman S, Chernoff M, Williams P, Hodge J, Heston J, Gadow KD. Human immunodeficiency virus disease severity, psychiatric symptoms, and functional outcomes in perinatally infected youth. Arch Pediatr Adolesc Med. 2012;166(6):528–535.
    1. Koekkoek S, de Sonneville LM, Wolfs TF, Licht R, Geelen SP. Neurocognitive function profile in HIV-infected school-age children. Eur J Paediatr Neurol. 2008;12(4):290–297.
    1. Sirois PA, Chernoff MC, Malee KM, et al. Associations of Memory and Executive Functioning With Academic and Adaptive Functioning Among Youth With Perinatal HIV Exposure and/or Infection. J Pediatric Infect Dis Soc. 2016;5(suppl 1):S24–S32.
    1. Nichols SL, Chernoff MC, Malee KM, et al. Executive Functioning in Children and Adolescents With Perinatal HIV Infection and Perinatal HIV Exposure. J Pediatric Infect Dis Soc. 2016;5(suppl 1):S15–S23.
    1. Danese A, McEwen BS. Adverse childhood experiences, allostasis, allostatic load, and age-related disease. Physiol Behav. 2012;106(1):29–39.
    1. Malee KM, Mellins CA, Huo Y, et al. Prevalence, incidence, and persistence of psychiatric and substance use disorders among mothers living with HIV. J Acquir Immune Defic Syndr. 2014;65(5):526–534.
    1. Vesga-Lopez O, Blanco C, Keyes K, Olfson M, Grant BF, Hasin DS. Psychiatric disorders in pregnant and postpartum women in the United States. Arch Gen Psychiatry. 2008;65(7):805–815.
    1. Kessler RC, Chiu WT, Demler O, Merikangas KR, Walters EE. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617–627.
    1. Aylward GP. Continuing issues with the Bayley-III: where to go from here. J Dev Behav Pediatr. 2013;34(9):697–701.
    1. Anderson PJ, De Luca CR, Hutchinson E, Roberts G, Doyle LW, Victorian Infant Collaborative G. Underestimation of developmental delay by the new Bayley-III Scale. Arch Pediatr Adolesc Med. 2010;164(4):352–356.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir