Maternal and Fetal Outcomes of Pregnancies in Women with Atypical Hemolytic Uremic Syndrome

J Am Soc Nephrol. 2018 Mar;29(3):1020-1029. doi: 10.1681/ASN.2016090995. Epub 2017 Dec 27.

Abstract

Atypical HUS (aHUS) is a disorder most commonly caused by inherited defects of the alternative pathway of complement, or the proteins that regulate this pathway, and life-threatening episodes of aHUS can be provoked by pregnancy. We retrospectively and prospectively investigated 27 maternal and fetal pregnancy outcomes in 14 women with aHUS from the Vienna Thrombotic Microangiopathy Cohort. Seven pregnancies (26%) were complicated by pregnancy-associated aHUS (p-aHUS), of which three appeared to be provoked by infection, bleeding, and curettage, and three individuals were considered to have preeclampsia/HELLP syndrome before the definitive diagnosis of p-aHUS was made. Mutations in genes that encode the complement alternative pathway proteins or the molecules that regulate this pathway were detected in 71% of the women, with no relationship to pregnancy outcome. Twenty-one pregnancies (78%) resulted in a live birth, two preterm infants were stillborn, and four pregnancies resulted in early spontaneous abortions. Although short-term renal outcome was good in most women, long-term renal outcome was poor; among the 14 women, four had CKD stage 1-4, five had received a renal allograft, and three were dialysis-dependent at study end. We prospectively followed nine pregnancies of four women and treated six of these pregnancies with prophylactic plasma infusions (one pregnancy resulted in p-aHUS, one intrauterine fetal death occurred, and seven pregancies were uneventful). Our study emphasizes the frequency of successful pregnancies in women with aHUS. Close monitoring of such pregnancies for episodes of thrombotic microangiopathy is essential but, the best strategy to prevent these episodes remains unclear.

Keywords: TMA; aHUS; atypical hemolytic uremic syndrome; complement-mediated; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / etiology
  • Adult
  • Atypical Hemolytic Uremic Syndrome / complications*
  • Atypical Hemolytic Uremic Syndrome / genetics
  • Atypical Hemolytic Uremic Syndrome / physiopathology*
  • Atypical Hemolytic Uremic Syndrome / therapy
  • Complement Pathway, Alternative / genetics
  • Disease Progression
  • Female
  • Fetal Death / etiology
  • Humans
  • Infant, Newborn
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / physiopathology*
  • Kidney Failure, Chronic / therapy
  • Live Birth
  • Male
  • Middle Aged
  • Mutation
  • Plasma
  • Pregnancy
  • Pregnancy Complications / etiology*
  • Pregnancy Complications / genetics
  • Pregnancy Complications / therapy
  • Prospective Studies
  • Retrospective Studies
  • Stillbirth
  • Thrombotic Microangiopathies / etiology*
  • Young Adult