The review found that HIV-exposed children had slight delays in acquiring language and motor skills

A meta-analysis of eight studies found that children of HIV-infected mothers who remained HIV-free were more likely to have mild deficiencies in expressive language and gross motor function at age two compared to children not exposed to HIV.

The meta-analysis was published in Lancet Children & Adolescent HealthIt found no evidence that exposure to certain antiretroviral drugs or the mother’s or infant’s regimen increases the risk of any developmental impairment in children.

Approximately 15.4 million children of HIV-positive mothers worldwide are born without HIV infection. In some countries with a high burden of HIV, up to 20% of all deliveries each year may be in HIV-infected women. As the use of three-drug antiretroviral therapy during and after pregnancy has expanded over the past decade, the proportion of children born to HIV-positive mothers who were exposed to antiretroviral drugs during pregnancy or early in life has increased.

glossary of terms

dimensional analysis

When statistical data from all studies that relate to a particular research question and correspond to pre-specified selection criteria are collected and analyzed.

exclusion criteria

Determines who cannot participate in a research study. Eligibility criteria may include disease type and stage, other medical conditions, previous treatment history, age, and gender. For example, many trials exclude pregnant women, to avoid any potential risk to the baby, or people who are taking a medication that may interact with the treatment under study.

systematic review

A review of the results of all studies that relate to a specific research question and that meet pre-specified selection criteria.

q value

The result of a statistical test that tells us whether the results of a study are likely to be due to chance and will not be confirmed if the study is repeated. All p values ​​are between 0 and 1; The most reliable studies have p-values ​​very close to 0. A p-value of 0.001 means that there is a 1 in 1,000 chance that the results are due to chance and do not reflect a true difference. A p-value of 0.05 means that there is a 1 in 20 chance that the results are due to chance. When the p-value is 0.05 or less, the result is considered ‘statistically significant’. Confidence intervals give information similar to p-values ​​but are easy to interpret.

The control group

A group of participants in a trial who receives a standard treatment, or no treatment at all, rather than the experimental treatment being tested. Also known as joystick.

Despite this growth, there is still a lack of clarity regarding the impact of maternal HIV and ARV exposure on the development of children who remain HIV-free. Brain and nervous system development is strongly influenced by events in pregnancy and early life, but studies have produced contradictory results regarding the consequences of ARV exposure.

Researchers at the University of Cape Town in South Africa conducted a systematic review of studies that looked at neurodevelopment in HIV-exposed children who were not infected with HIV. Studies were eligible for inclusion if they compared HIV-exposed children with non-HIV-exposed children and if the HIV-exposed group excluded HIV-acquired children. Studies that compared exposure to ART in children who remained HIV-free by drug class or no exposure were also eligible.

The review identified 24 studies that looked at exposure to HIV and 13 studies that looked at exposure to antiretrovirals. Of the 24 studies that examined the effect of exposure to HIV, 12 reported poorer neurodevelopmental outcomes for HIV-exposed children compared to non-exposed children.

Then the researchers performed a meta-analysis. Sixteen studies were excluded from the meta-analysis on the basis of quality—either because the study population was unrepresentative, lacked a control group from the same population or did not use proven results—leaving eight studies including 1,856 HIV exposures and 3,067 HIV exposures. Human immunity is not exposed. children. All but one of the studies were conducted in sub-Saharan Africa and 75% of HIV-exposed children were also exposed to three antiretroviral drugs (the rest were exposed to zidovudine only).

The analysis looked at neurodevelopmental outcomes at age 2 years. HIV-exposed children had significantly weaker expressive language scores (effect size -0.17, P = 0.0013) and gross motor scores (effect size -0.07, P < 0.0001) compared to non-HIV-exposed children but did not show significant differences. Statistical significance in cognitive development, receptive to language development or fine motor development. Expressive language outcomes were only significantly different at 2 years of age while a significant difference in gross motor outcomes was already evident by 1 year of age.

Studies on the effect of exposure to antiretrovirals have not demonstrated a clear relationship between specific antiretrovirals and neurodevelopmental outcomes. In 13 studies that investigated the relationship between antiretroviral exposure and neurodevelopment as a primary outcome, only two studies demonstrated relationships between a specific drug (atazanavir or efavirenz) and poor language score. There were not enough high-quality studies to perform a meta-analysis.

What were the growth delays associated with HIV in this study?

Expressive language refers to all the ways in which children express themselves, including non-verbal ways such as pointing, gesturing, and smiling as well as speaking, acquiring words, and other language skills.

Children with poor expressive language development may have difficulty constructing sentences, naming things, or making themselves understood and likely to become frustrated if others do not understand what they are trying to say. In addition to affecting educational performance, poor expressive language development may also affect a child’s social skills and integration with peers.

Gross motor development refers to major physical activities that require whole-body movement such as crawling, standing, walking, and running. A child with poor gross motor development will be slower to reach each of these milestones and will have difficulties playing and interacting with other children.

Implications for the study results

The study investigators say their findings are consistent with studies conducted prior to the introduction of antiretroviral therapy. They say HIV-exposed but uninfected children have slight developmental delays – showing “a subtle but clear identification of differences in abilities” – and that in places where other factors such as malnutrition may also affect development, “support may lead to These children to thrive require interventions focused on expressive language and gross motor skills in early childhood.”

They concluded that long-term follow-up of children exposed to HIV is needed to assess the consequences of developmental delays in later life. For example, it is unclear whether delays in acquiring expressive language skills at age two affect learning in school-aged children, or if children catch up with it later.

The investigators say that while the lack of indication regarding the negative impact of ARV exposure on development is good news, more research is needed to determine whether certain ARV regimens are associated with better development outcomes. These studies should take into account other factors influencing the child’s neurodevelopment, such as premature birth and low birth weight, when selecting and analyzing the study population.

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