TY - JOUR
T1 - The natural course of pregnancies in women with primary atypical haemolytic uraemic syndrome and asymptomatic relatives
AU - Timmermans, Sjoerd A. M. E. G.
AU - Werion, Alexis
AU - Spaanderman, Marc E. A.
AU - Reutelingsperger, Chris P.
AU - Damoiseaux, Jan G. M. C.
AU - Morelle, Johann
AU - Paassen, Pieter
N1 - Funding Information:
We gratefully thank the nephrologists affiliated with the Limburg Renal Registry and the members of the multidisciplinary TMA/HUS team at the Cliniques Universitaires Saint‐Luc and the UCLouvain Kidney Disease Network for the recruitment and excellent care of patients. Furthermore, we acknowledge N. Bijnens, E. Geelkens, H. van Rie and R. Theunissen (Maastricht University Medical Center) for their excellent technical assistance and S. Druart and Y. Cnops for the management of the biobank (Cliniques Universitaires Saint‐Luc). This work was supported in part by funding from the Fondation Saint‐Luc (J.M), the National Fund for Scientific Research (J.M.), the Fonds de Recherche des Cliniques Universitaires Saint‐Luc (J.M.) and the Association pour l’Information et la Recherche sur les Maladies Rénales Génétiques (J.M.).
Funding Information:
We gratefully thank the nephrologists affiliated with the Limburg Renal Registry and the members of the multidisciplinary TMA/HUS team at the Cliniques Universitaires Saint-Luc and the UCLouvain Kidney Disease Network for the recruitment and excellent care of patients. Furthermore, we acknowledge N. Bijnens, E. Geelkens, H. van Rie and R. Theunissen (Maastricht University Medical Center) for their excellent technical assistance and S. Druart and Y. Cnops for the management of the biobank (Cliniques Universitaires Saint-Luc). This work was supported in part by funding from the Fondation Saint-Luc (J.M), the National Fund for Scientific Research (J.M.), the Fonds de Recherche des Cliniques Universitaires Saint-Luc (J.M.) and the Association pour l?Information et la Recherche sur les Maladies R?nales G?n?tiques (J.M.).
Publisher Copyright:
© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd
PY - 2020/8
Y1 - 2020/8
N2 - Pregnancy has been linked to various microangiopathies, including primary atypical haemolytic uraemic syndrome (aHUS). Complement dysregulation, often linked to rare variants in complement genes, is key for primary aHUS to manifest and may play a role in pregnancy complications of the mother and fetus. The burden of such complications is unknown, making counselling of women with primary aHUS and asymptomatic relatives difficult. We analyzed the maternal and fetal outcomes of 39 pregnancies from 17 women with primary aHUS and two asymptomatic relatives. Seven out of 39 pregnancies were complicated by pregnancy-associated aHUS. Five out of 32 pregnancies not linked to pregnancy-associated aHUS were complicated by pre-eclampsia or HELLP. Rare genetic variants were identified in 10 women (asymptomatic relatives, n = 2) who had a total of 14 pregnancies, including 10 uncomplicated pregnancies. Thirty-five out of 39 pregnancies resulted in live birth. Eight out of 19 women had progressed to end-stage kidney disease, with an incidence of 2·95 (95% confidence interval, 1·37–5·61) per 100 person-years after the first pregnancy. Thus, we emphasized the frequency of successful pregnancies in women with primary aHUS and asymptomatic relatives. Pregnancies should be monitored closely. Rare genetic variants cannot predict the risk of a given pregnancy.
AB - Pregnancy has been linked to various microangiopathies, including primary atypical haemolytic uraemic syndrome (aHUS). Complement dysregulation, often linked to rare variants in complement genes, is key for primary aHUS to manifest and may play a role in pregnancy complications of the mother and fetus. The burden of such complications is unknown, making counselling of women with primary aHUS and asymptomatic relatives difficult. We analyzed the maternal and fetal outcomes of 39 pregnancies from 17 women with primary aHUS and two asymptomatic relatives. Seven out of 39 pregnancies were complicated by pregnancy-associated aHUS. Five out of 32 pregnancies not linked to pregnancy-associated aHUS were complicated by pre-eclampsia or HELLP. Rare genetic variants were identified in 10 women (asymptomatic relatives, n = 2) who had a total of 14 pregnancies, including 10 uncomplicated pregnancies. Thirty-five out of 39 pregnancies resulted in live birth. Eight out of 19 women had progressed to end-stage kidney disease, with an incidence of 2·95 (95% confidence interval, 1·37–5·61) per 100 person-years after the first pregnancy. Thus, we emphasized the frequency of successful pregnancies in women with primary aHUS and asymptomatic relatives. Pregnancies should be monitored closely. Rare genetic variants cannot predict the risk of a given pregnancy.
KW - primary atypical haemolytic uraemic syndrome
KW - thrombotic microangiopathy
KW - pregnancy
KW - complement
KW - genetics
KW - COMPLEMENT INHIBITOR ECULIZUMAB
KW - MEMBRANE COFACTOR PROTEIN
KW - THROMBOTIC MICROANGIOPATHIES
KW - FACTOR-H
KW - HYPERTENSION
KW - VARIANTS
KW - OUTCOMES
KW - DISEASE
KW - AHUS
U2 - 10.1111/bjh.16626
DO - 10.1111/bjh.16626
M3 - Article
C2 - 32342491
SN - 0007-1048
VL - 190
SP - 442
EP - 449
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 3
ER -