title: Clinical and haematological risk factors for cerebral macrovasculopathy in a sickle cell disease newborn cohort: a prospective study.
abstract: Children with sickle cell disease (SCD) have a significant vascular morbidity, especially cerebral macrovasculopathy (CV), detectable by transcranial Doppler. This study aimed to identify risk factors for CV using longitudinal biological and clinical data in a SCD newborn cohort followed at the Robert Debre Reference centre (n = 375 SS/Sβ(0) ). Median follow-up was 6·8 years (2677 patient-years). Among the 59 children presenting with CV, seven had a stroke. Overall, the incidence of CV was 2·20/100 patient-years [95% confidence interval (95% CI): 1·64-2·76] and the incidence of stroke was 0·26/100 patient-years (95% CI: 0·07-0·46). The cumulative risk of CV by age 14 years was 26·0% (95% CI: 20·0-33·3%). Risk factors for CV were assessed by a Cox model encompassing linear multivariate modelling of longitudinal quantitative variables. Years per upper-airway obstruction [Hazard ratio (HR) = 1·47; 95% CI: 1·05-2·06] or bronchial obstruction (HR = 1·76; 95% CI: 1·49-2·08) and reticulocyte count (HR = 1·82 per 50 × 10(9) /l increase; 95% CI: 1·10-3·01) were independent risk factors whereas fetal haemoglobin level (HR = 0·68 per 5% increase; 95% CI: 0·48-0·96) was protective. Alpha-thalassaemia was not protective in multivariate analysis (ancillary analysis n = 209). Specific treatment for upper or lower-airway obstruction and indirect targeting of fetal haemoglobin and reticulocyte count by hydroxycarbamide could potentially reduce the risk of CV.
authors.affiliation: U 1123, ECEVE, Hôpital Robert-Debré, INSERM, Paris, France.|UMR-S 1123, ECEVE, Sorbonne Paris Cité, Univ Paris Diderot, Paris, France.|Hôpital Robert-Debré, Unité d'Epidémiologie Clinique, AP-HP, Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Sommet
authors.affiliation: U 1123, ECEVE, Hôpital Robert-Debré, INSERM, Paris, France.|UMR-S 1123, ECEVE, Sorbonne Paris Cité, Univ Paris Diderot, Paris, France.|Hôpital Robert-Debré, Unité d'Epidémiologie Clinique, AP-HP, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Alberti
authors.affiliation: Hôpital Robert-Debré, UF de Génétique Moléculaire, AP-HP, Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Couque
authors.affiliation: Hôpital Robert-Debré, Service de Radiologie, AP-HP, Paris, France.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Verlhac
authors.affiliation: Hôpital Robert-Debré, Service d'Hématologie, AP-HP, Paris, France.|Hôpital Robert-Debré, Centre de Référence de la Drépanocytose, AP-HP, Paris, France.
authors.forename: Zinedine
authors.initials: Z
authors.lastname: Haouari
authors.affiliation: Hôpital Robert-Debré, Unité d'Epidémiologie Clinique, AP-HP, Paris, France.
authors.forename: Damir
authors.initials: D
authors.lastname: Mohamed
authors.affiliation: Hôpital Robert-Debré, Service d'ORL, AP-HP, Paris, France.
authors.forename: Martine
authors.initials: M
authors.lastname: François
authors.affiliation: Hôpital Robert-Debré, Service d'Hématologie, AP-HP, Paris, France.|Hôpital Robert-Debré, Centre de Référence de la Drépanocytose, AP-HP, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Missud
authors.affiliation: Hôpital Robert-Debré, Service d'Hématologie, AP-HP, Paris, France.|Hôpital Robert-Debré, Centre de Référence de la Drépanocytose, AP-HP, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Holvoet
authors.affiliation: Hôpital Robert-Debré, Service de Radiologie, AP-HP, Paris, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Elmaleh
authors.affiliation: Hôpital Robert-Debré, Service d'Hématologie, AP-HP, Paris, France.|Hôpital Robert-Debré, Centre de Référence de la Drépanocytose, AP-HP, Paris, France.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Ithier
authors.affiliation: Hôpital Robert-Debré, Service de Physiologie, AP-HP, Paris, France.|UMR 1141, Sorbonne Paris Cité, Univ Paris Diderot, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Denjean
authors.affiliation: Hôpital Robert-Debré, UF de Génétique Moléculaire, AP-HP, Paris, France.|UMR-S 1134, Laboratoire d'Excellence GR-Ex, INSERM, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Elion
authors.affiliation: Hôpital Robert-Debré, Service d'Hématologie, AP-HP, Paris, France.|Institut Universitaire d'Hématologie EA3518, Hôpital Saint Louis, Univ Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Baruchel
authors.affiliation: U 1123, ECEVE, Hôpital Robert-Debré, INSERM, Paris, France.|UMR-S 1123, ECEVE, Sorbonne Paris Cité, Univ Paris Diderot, Paris, France.|Hôpital Robert-Debré, Service d'Hématologie, AP-HP, Paris, France.|Hôpital Robert-Debré, Centre de Référence de la Drépanocytose, AP-HP, Paris, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Benkerrou
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications* / Q000628:therapy; D002539:Cerebral Arterial Diseases / Q000000981:diagnostic imaging / Q000209:etiology* / Q000517:prevention & control; D017707:Erythrocyte Transfusion; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D008173:Lung Diseases, Obstructive / Q000150:complications / Q000628:therapy; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control; D017585:Ultrasonography, Doppler, Transcranial / Q000379:methods; D017085:alpha-Thalassemia / Q000150:complications
chemical_list: D005319:Fetal Hemoglobin
keywords: cerebral vasculopathy; children; cohort; respiratory abnormalities; sickle cell disease; transcranial doppler