Medical Problems of Mothers of Children with Fetal-Neonatal Alloimmune Thrombocytopenia (FNAIT): Autoimmunity and Psychological Symptoms

Introduction: Fetal/neonatal alloimmune thrombocytopenia (FNAIT) results from parental platelet antigen incompatibility with subsequent maternal alloimmunization and may result in intracranial hemorrhage (ICH). We wondered if, based on HLA similarities, autoimmune disease might overlap with FNAIT: HLA-DRB3*0101 occurs in >95% of mothers with hi-titer anti-HPA-1a antibodies and B8DR3 is associated with many autoimmune diseases, e.g. insulin-dependent diabetes (IDDM), rheumatoid arthritis (RA), psoriasis, immune thrombocytopenia (ITP), and thyroiditis. This association, in addition to anecdotal comments from FNAIT-affected mothers, led us to explore if autoimmunity occurs at an increased frequency in women with FNAIT secondary to anti-HPA-1a.

Methods: A de-identified survey on Qualtrics was sent to members of NAITbabies, an FNAIT mothers' group. Mothers were queried about their personal history of FNAIT including their children and review of systems including autoimmunity. 3 women with inconclusive responses to autoimmunity were omitted. Outcomes with and without maternal autoimmunity were compared for maternal psychological problems and in first born infants neonatal incidence of ICH, survival of ICH, and low birthweight (<2.5 kg). No statistical analyses were performed; results were reported as frequencies.

Results: 364 women with at least 1 FNAIT-affected newborn completed the questionnaire. 52 mothers (14.3%) self-reported autoimmune diagnoses: 25/364 with thyroid disease (6.9%), 6 with psoriasis (1.6%), 4 with RA (1.1%), 4 with IDDM (1.1%), 3 with ITP (0.8%), and 21 with “other” autoimmune conditions. 14 mothers reported >1 autoimmune condition. Unexpectedly, 125/232 (54%) who answered the question reported psychological problems (e.g. anxiety, depression, forgetfulness) of at least 6-weeks duration. Timing, severity, medication use, and other relevant clinical factors related to psychological problems were unavailable since it was unanticipated. Among women with autoimmunity, there was NOT an increased incidence of ICH (20% vs 21%) or reduced birthweight (24% vs 20%). While the 54% of women with psychological problems (125/232) did not have an increased incidence of ICH among their neonates, there was an increased rate of psychological problems among women whose fetus/neonate did not survive their ICH (74%) compared to those whose fetus survived (51%). Mothers with more FNAIT-affected children reported psychological problems more frequently: 51% with 1 FNAIT-affected child, 55% with 2 FNAIT-affected children, and 62% of mothers with 3 FNAIT-affected children reported psychological symptoms. Women with autoimmune disease (61%) had slightly more frequent psychological problems than women without autoimmune disease (52%).

Discussion:This study demonstrates novel findings in HPA-1a incompatible FNAIT regarding maternal health and well-being. Most women with an FNAIT-affected child appear to have major psychological problems of at least 6 weeks duration. An ongoing survey is extending study of this finding with a more comprehensive investigation of mothers with FNAIT, including the type of problem (e.g., caregiver burden, depression, anxiety, post-traumatic stress disorder), demographic overview, and pertinent medical history. Even in first-time mothers, FNAIT's traumatic unexpected nature had psychological effects which then increased further with additional FNAIT-affected children. This study and the ongoing second survey study again highlight the need for routine platelet antigen screening and prophylaxis to identify at risk mothers to prevent FNAIT and avoid not only bleeding but also maternal psychological problems. The prevalence of maternal autoimmunity in mothers with FNAIT appears increased, albeit primarily thyroid disorders, but did not seem related to the severity of FNAIT; the near universal presence of B8DR3 in HPA-1a incompatible FNAIT might be responsible for the increased prevalence of autoimmunity.

Conclusion: This study expands the spectrum of disease in HPA-1a incompatible FNAIT by highlighting maternal psychological problems and autoimmunity. These findings of maternal issues add to the other non-hemorrhagic now well-described fetal/neonatal complications of FNAIT-affected pregnancies: placental inflammation, reduced birthweights, and especially impaired neurodevelopment in children.

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