Risk of Neurodevelopmental Disorders in Children Exposed to HIV and Antiretrovirals In Utero: A National Cohort Study
Mathis Collier1,2, Laurent Chouchana1,2,3, Pierre Frange4,5
1Unité de Recherche clinique, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris (AP-HP).
Insights
Children exposed to HIV and ARVs in pregnancy show increased neurodevelopmental disorder risk. Further research is needed to understand the multifactorial origins of these disorders in this vulnerable population.
Area of Science:
- Pediatric Neurology
- Infectious Diseases
- Public Health
Background:
- Long-term assessment of neurological and cognitive development in children exposed but uninfected by HIV is crucial.
- Previous studies have been hampered by confounding factors, leading to contradictory data.
Purpose of the Study:
- To assess the incidence of neurodevelopmental disorders in children prenatally exposed to antiretrovirals (ARVs) due to maternal HIV.
- To evaluate the association between specific ARV combinations and neurodevelopmental outcomes.
Main Methods:
- Population-based matched cohort study using French National Health Data System (2012-2022).
- Inclusion of live-born singletons exposed prenatally to ARVs.
- Primary outcome: diagnosis of neurodevelopmental disorders (ICD-10); secondary outcome: specialized consultations.
Main Results:
- Higher incidence of neurodevelopmental disorders in ARV-exposed children compared to the general population (HR, 1.24).
- Specific ARV combination (tenofovir-emtricitabine with ritonavir-boosted darunavir) associated with increased risk of neurodevelopmental disorders and consultations.
- The distinct roles of maternal HIV infection and ARV treatment could not be separated.
Conclusions:
- Children exposed to HIV and ARVs in utero face an elevated risk of neurodevelopmental disorders.
- The origin of these disorders is multifactorial, warranting further investigation into the interplay of maternal infection and treatment.
Background:
The health of children exposed but uninfected by human immunodeficiency virus (HIV) requires long-term assessment, in particular in terms of neurological and cognitive development. Numerous confounding factors have hampered such assessment, and published data are contradictory.
Methods:
Using data from the French National Health Data System from 2012 to 2022, we conducted a population-based matched cohort study on all live-born single children, including those born to mothers with HIV, all prenatally exposed to antiretrovirals (ARVs). The primary outcome was the diagnosis of neurodevelopmental disorders according to the International Classification of Diseases, 10th Revision. The recourse to specialized consultations likely to indirectly reflect neurodevelopmental symptoms was also evaluated. Incidence was assessed using the Cox survival model.
Results:
Of 6 667 363 live-born singletons, 9035 were born to mothers with HIV, all exposed to ARVs during pregnancy. Children were followed for up to 11 years (average, 5.5 years). Overall, the incidence of neurodevelopmental disorders among exposed children was higher than in the general population, even after matching for 5 sociodemographic criteria and gestational age (hazard ratio, 1.24 [95% confidence interval, 1.04-1.47]). It was not possible to dissect the respective role of maternal infection from that of maternal treatment, as all children were coexposed to HIV and ARVs. However, among those exposed to tenofovir-emtricitabine, the ritonavir-boosted darunavir-based combination was significantly associated with a higher combined incidence of neurodevelopmental disorders and related specialized consultations than other protease inhibitors (log-rank P < .001).
Conclusions:
Children exposed to HIV and ARVs in utero have a higher risk of developing neurodevelopmental disorders of multifactorial origin.
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