Routing kinetics of human immunoglobulin-G after transamniotic fetal immunotherapy (TRAFIT) in a rodent model

Abstract

PurposeThe transamniotic route was recently discovered as a minimally invasive means of fetal immunoglobulin administration, however by unclear mechanisms. We sought to examine IgG routing after intra-amniotic delivery. MethodsSprague-Dawley fetuses (n = 78) received intra-amniotic injections of 15 mg/mL of human IgG on gestational-day 18 (E18; term=21 and 22 days). Amniotic fluid, amnion, chorion, placenta, fetal serum, liver, and stomach-aspirate samples were procured on E19, E20, and E21 for IgG quantification by ELISA. Statistical analysis was by median regression with Bonferroni-adjusted significance at p < 0.017. ResultsHuman IgG was detected at all sampled sites across all time points, though at significantly higher levels in the gestational membranes and fetal serum than in the stomach aspirate and liver (p < 0.001 for both). Gestational membranes showed a daily decrease after injection, stabilizing by E20 and E21 (p = 0.792 to < 0.001). Placental levels were significantly lower at E21 than E19 (p = 0.010). Fetal serum showed the highest human IgG levels at term. ConclusionsThe chronology of exogenous IgG kinetics after intra-amniotic injection is suggestive of direct placental transport leading to consistently high fetal serum levels, possibly combined with some fetal ingestion. Transamniotic fetal immunotherapy (TRAFIT) may become a practicable strategy for the prenatal treatment of select alloimmune disorders and infections. Level of evidenceN/A (Animal and Laboratory study). Type of studyAnimal and Laboratory Study.