Does anti-HPA-1a affect birthweight in Fetal and Neonatal Alloimmune Thrombocytopenia?

Abstract

Objective: This study tests the clinical hypothesis that FNAIT secondary to anti-HPA-1a results in smaller newborns, and the corollary hypothesis that antenatal management of FNAIT in HPA-1a-incompatible pregnancies increases birthweight by reducing the effects of anti-HPA-1a. Design: FNAIT-affected siblings, one untreated and one treated for FNAIT, were paired for the purpose of comparing their birthweights. Birthweights of FNAIT-affected and -unaffected pups in a mouse model of HPA-1a-specific-FNAIT were also analyzed. Setting: New York Presbyterian-Weill Cornell Medical Center, New York, NY; Versiti Blood Research Institute, Milwaukee, WI. Population: 270 FNAIT-affected newborns from a randomized clinical trial; responders to a NAITbabies.org; and pups in a mouse model of HPA-1a-specific-FNAIT were evaluated. Methods: Birthweight percentiles of untreated FNAIT-affected neonates were compared to those of published controls and treated FNAIT-affected siblings using one-sample, two-tailed t-tests. Body weights of FNAIT-affected and -unaffected pups in a mouse model of HPA-1a-specific-FNAIT were analyzed similarly. Main Outcome Measures: The difference in birthweight percentile between untreated and treated FNAIT-affected siblings was analyzed. Results: Untreated siblings were not small compared to normal controls. However, treated siblings in both cohorts had significantly higher birthweight percentiles compared to their untreated, affected sibling. FNAIT-affected neonatal pups had lower body weights than FNAIT-unaffected pups. Conclusions: The effect of treatment, especially high dose IVIG believed to “block” FcRn and lower maternal anti-HPA-1a levels, to increase birthweights suggests maternal anti-HPA-1a reduces birthweights. We believe this is mediated by anti-HPA-1a binding to placental syncytiotrophoblasts, resulting in placental inflammation.