Analysis of Screening for Autism Spectrum Disorders in Children Affected By Fnait with and without Intra-Cranial Hemorrhage

Background: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) results from parental platelet antigen incompatibility and maternal sensitization, causing thrombocytopenia which may be complicated by intra-cranial hemorrhage (ICH). Previous studies of FNAIT have focused on platelet counts and bleeding; limited investigation of neurodevelopmental outcomes have been performed (De Vos, J Peds 2023). The De Vos study identified increased neurodevelopmental issues in at least 1 of 5, 6 to 14 year old children with FNAIT without ICH. Members of NAITbabies, a mothers-with-FNAIT group, believed autism might be increased in FNAIT-affected children. Our survey evaluated neurodevelopmental issues (autism) in FNAIT-affected children, with and without a history of ICH.

Methods: De-identified questionnaires comprising our FNAIT survey were distributed via Qualtrics to members of NAITbabies, a group of mothers affected by FNAIT. The survey completed by mothers assessed neurodevelopmental behavior of their children using 4 age-specific autism screening scales to identify FNAIT-affected children at high risk: Q-CHAT-10 for children 18-24 months; M-CHAT 2-4 years; AQ10-Child 4 -11 years; and AQ10-Adolescent for >12 years with 20, 61, 173, and 70 children in each group. Mothers were asked if a diagnosis of autism was known prior to completing the autism screening. Screening responses were scored as at risk based on standard algorithms for each scale. Analyses explored the prevalence of risk of autism in screening among each of the 4 age groups, Differences among age groups and between children with and without ICH were compared.

Results: The study cohort included responses describing 324 children across the 4 age groups, with 55 having experienced ICH and 269 not (newborns not surviving ICH were excluded). There was a higher prevalence of autism diagnosis in the ICH group than the non-ICH group across all age groups, except in the 18-24-month group which had no reported autism diagnoses. In the 18-24-month-olds, 3/5 children with ICH “screened” at risk for autism, compared to 0/15 without ICH. In the 2-4yr olds, 1 child with ICH was previously diagnosed with autism, with screening identifying 2/12 (16.6%) at risk; none of the 49 children without ICH reported a diagnosis or were identified as at risk for autism. In the 4-11yr-olds, reported autism diagnosis was similar between those with ICH (7.4%) and those without ICH (6.8%); however, screening showed 33% with ICH and 13% without ICH at high risk. The highest levels in reported diagnosis (and screening) were in the 12+ age group: 4 /11 (36.4%) with ICH compared to 7/59 (11.8%) of those without ICH; screening identified high autism risk in 45% with ICH and 37% of without ICH in this 12+ age group. Overall, in the ICH group, there was a substantial increase in positive screening (high risk) results compared to pre-reported autism diagnoses across all four age groups, but the screening total for high risk never exceeded 45% of ICH cases. In the non-ICH groups, increased positive screening results compared to pre-reported autism diagnoses was only seen in the 2 older age groups; the most striking finding was that more than one third of the oldest (12+) age group screened at high risk.

Discussion: The results demonstrate that autism, and probably other neurodevelopmental issues, may become more apparent with age in both the ICH and no ICH groups. It is also important to realize that this screening questionnaire is intended to trigger further evaluation rather than being a specific diagnostic test for autism. It also identifies non-specific neurologic damage that may not be autism.

Conclusions: Children affected by FNAIT, especially adolescents, are at risk for “autism” even without having had an ICH. This likely is because of now well-described perinatal placental inflammation. Surprisingly, even those who had had an ICH tested remarkably well in over half the cases. These screening results indicate the need for screening, which may need to be repeated at intervals, for autism in particular and neurologic damage in general in children affected by FNAIT independent of whether an ICH occurred.

Bussel:RallyBio: Consultancy, Research Funding; Argenx: Consultancy; Janssens: Consultancy; Alpine-Vertex: Consultancy; UCB: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy.