Neurodevelopment in Young Children Born to HIV-Infected Mothers: A Meta-analysis

McHenry, Megan S.; McAteer, Carole I.; Oyungu, Eren; McDonald, Brenna C.; Bosma, Chris B.; Mpofu, Philani; Deathe, Andrew R.; Vreeman, Rachel C.

doi:10.1542/peds.2017-2888

“…By contrast, low maternal CD4 count did not increase the IRRs of having caries in primary teeth for the HEU children investigated in this study. This study's results are at odds with those of some previous studies , but in accordance with others . The absence of an effect of maternal CD4 count on caries might be explained by the particular characteristics of the HEU children investigated, being born to mothers who did not qualify for ARV therapy during pregnancy because of less‐advanced infection and high immune competency (i.e., CD4 count > 350 µ l −1 ).…”

Section: Discussionsupporting

confidence: 52%

Association of maternal HIV‐1 severity with dental caries: an observational study of uninfected 5‐ to 7‐yr‐old children of HIV‐1‐infected mothers without severe immune suppression

Birungi

¹

,

Engebretsen

²

,

Lie

³

et al. 2020

European J Oral Sciences

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Treatment programs to prevent perinatal and postnatal HIV‐1 transmission have become available in sub‐Saharan Africa, leading to an emerging population of HIV‐1 exposed uninfected (HEU) children. Exposure to HIV‐1 in utero and during breastfeeding may increase the risk of morbidity and mortality in HEU children. This study estimated the association of the severity of maternal HIV‐1 infection as assessed by CD4 count and viral load at baseline (7 d postpartum), with dmft count of their 5‐ to 7‐yr‐old HEU offspring. A follow‐up study was conducted of HIV‐1‐infected mother–HEU children pairs (n = 164) from the Ugandan site of the ANRS 12341‐PROMISE‐ PEP trial (ClinicalTrials.gov, number NCT00640263). HIV‐1‐infected mothers were interviewed and the HEU children were examined for caries using the World Health Organization's survey methods for field conditions and the dmft index. Directed acyclic graphs and negative binomial regression were used for analyses. The prevalence of 1 or more dmft was 48%. Negative binomial regression showed no association between the dmft count and maternal CD4 counts 7 d postpartum but a 10% lower dmft count with longer breastfeeding duration was found. Maternal CD4 count at birth was not associated with the dental caries experience in uninfected children born to women without severe immune suppression, while there appeared to be a protective effect of high viral load and breastfeeding duration.

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“…Earlier studies revealed variable rates of GDI among PHIV children. A recent meta‐analysis of neurodevelopment in PHIV and PHEU young children reported developmental impairment (−2 SD below the mean on the Bayley Scales of Infant Development) among 21% to 35% of children; however, most of these studies did not indicate onset of ART . Our study revealed that 32% of PHIV children had developmental impairment overall, yet impairment was significantly less likely among children with early initiation of ART (22%) compared to those with later initiation of ART PHIV (44%).…”

Section: Discussioncontrasting

confidence: 50%

Low risk of neurodevelopmental impairment among perinatally acquired HIV‐infected preschool children who received early antiretroviral treatment in Thailand

Jantarabenjakul

¹

,

Chonchaiya

²

,

Puthanakit

³

et al. 2019

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Introduction Antiretroviral therapy ( ART ) is recommended in perinatally HIV‐infect ed ( PHIV ) infants immediately upon diagnosis. We aimed to compare neurodevelopmental outcomes between PHIV children who initiated ART within 12 months of life and perinatally HIV‐ exposed uninfected ( PHEU ) children and to assess neurodevelopmental outcomes by timing of ART . Methods This prospective cohort study included Thai children aged 12 to 56 months who were assessed with the Mullen Scales of Early Learning ( MSEL ) at enrolment and at 48 weeks. Global Developmental Impairment ( GDI ) was defined as Early Learning Composite ( ELC ) ≤ 70 on the MSEL ; typical developmental pattern was defined as ELC > 70 at both visits. Logistic regression was used to compare prevalence of any GDI . Predictors of changing ELC scores were analysed with generalized estimating equations linear regression model. Results From 2016 to 2017, 50 PHIV (twenty‐seven early ART within three months and twenty‐three standard ART within three to twelve months) and 100 PHEU children were enrolled. Median ( IQR ) age at first assessment was 28 (19 to 41) months. PHIV children had lower age‐relevant Z scores for weight, height and head circumference compared to the PHEU group ( p < 0.05). The prevalence of overall GDI was 18% (95% CI 11 to 27) and 32% (95% CI 20 to 47) in PHEU and PHIV children respectively ( p = 0.06). In subgroup analysis, 22% (95% CI 9 to 42) of early ART PHIV children and 44% (95% CI 23 to 66) of standard ART PHIV children had overall GDI . There was a higher rate of GDI in standard ART PHIV children ( p = 0.01), but not in the early ART group ( p = 0.62) when compared with PHEU children. The standard ART PHIV group demonstrated lower typical developmental pattern than both the early ART P...

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“…For both zidovudine‐ and lamuvidine‐exposed rodents, some studies suggested that memory and learning may be impaired at early ages . More recent clinical studies with newer ART regimens have not found such deficits in young children . Fewer data are available about specific cognitive functions in older HEU children and adolescents, but studies have found a higher frequency of reading and math impairments in HEU children compared to the general population .…”

Section: Discussionmentioning

confidence: 99%

“…For the 1.4 million children born annually to mothers living with HIV, there are concerns that HIV or antiretroviral therapy (ART) exposure may negatively impact neurodevelopment, including cognition, language and motor skills . A meta‐analysis on neurodevelopment in HIV‐exposed uninfected (HEU) children highlighted the limitations in the current body of literature including the heterogeneity of the patient populations between studies, limited confounders measured and variability in ART regimens.…”

Section: Introductionmentioning

confidence: 99%

In utero exposure to HIV and/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes

McHenry

¹

,

Balogun

²

,

McDonald

³

et al. 2019

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Introducion With the increasing number of children exposed to HIV or antiretroviral therapy in utero, there are concerns that this population may have worse neurodevelopmental outcomes compared to those who are unexposed. The objective of this study was to systematically review the clinical and preclinical literature on the effects of in utero exposure to HIV and/or antiretroviral therapy ( ART ) on neurodevelopment. Methods We systematically searched OVID Medline, Psyc INFO and Embase, as well as the Cochrane Collaborative Database, Google Scholar and bibliographies of pertinent articles. Titles, abstracts, and full texts were assessed independently by two reviewers. Data from included studies were extracted. Results are summarized qualitatively. Results The search yielded 3027 unique titles. Of the 255 critically reviewed full‐text articles, 25 met inclusion criteria for the systematic review. Five articles studied human subjects and looked at brain structure and function. The remaining 20 articles were preclinical studies that mostly focused on behavioural assessments in animal models. The few clinical studies had mixed results. Some clinical studies found no difference in white matter while others noted higher fractional anisotropy and lower mean diffusivity in the brains of HIV ‐exposed uninfected children compared to HIV ‐unexposed uninfected children, correlating with abnormal neurobehavioral scores. Preclinical studies focused primarily on neurobehavioral changes resulting from monotherapy with either zidovudine or lamivudine. Various developmental and behavioural changes were noted in preclinical studies with ART exposure, including decreased grooming, decreased attention, memory deficits and fewer behaviours associated with appropriate social interaction. Conclusions While the existing literature suggests that there may be some neurobehavioral differences associated with HIV and ART exposure, limited data are available to substantially support these claims. More research is needed comparing neurobiological factors between HIV ‐exposed uninfected and HIV ‐unexposed uninfected children and using exposures consistent with current clinical care.

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Neurodevelopment in Young Children Born to HIV-Infected Mothers: A Meta-analysis

Cited by 105 publications

References 36 publications

Association of maternal HIV‐1 severity with dental caries: an observational study of uninfected 5‐ to 7‐yr‐old children of HIV‐1‐infected mothers without severe immune suppression

Association of maternal HIV‐1 severity with dental caries: an observational study of uninfected 5‐ to 7‐yr‐old children of HIV‐1‐infected mothers without severe immune suppression

Low risk of neurodevelopmental impairment among perinatally acquired HIV‐infected preschool children who received early antiretroviral treatment in Thailand

In utero exposure to HIV and/or antiretroviral therapy: a systematic review of preclinical and clinical evidence of cognitive outcomes

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