Neonatal nephrotic syndrome associated with placental transmission of proinflammatory cytokines

Abstract

Although there are clinical data suggesting a direct relationship between neonatal nephrotic syndrome and placental transfer of proinflammatory cytokines from mothers with HELLP syndrome, there is no direct evidence that these inflammatory cytokines are pathogenic. Here, the first human model of placental transfer of proinflammatory cytokines from a mother with HELLP syndrome to a newborn, resulting in neonatal nephrotic syndrome is described. Forty-eight hours after delivery, the neonate developed nephrotic syndrome and abnormalities in renal function which resolved completely during the 5 days following the initiation of therapy with hydrocortisone, albumin, and furosemide. The newborn’s cord blood showed increased concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha that were identical to those found in the mother’s serum. Hydrocortisone therapy was discontinued after a 2-week course. Clinical and laboratory improvements were associated with a marked decline in serum cytokine levels, indicating that the proinflammatory cytokines were pathogenic. The neonate remained in remission with no recurrence of nephrotic syndrome during 12 months of follow-up. These findings demonstrate that the placental transmission of circulating cytokines causing HELLP syndrome occurred during pregnancy and may have resulted in nephrotic syndrome in the neonate.