Positive impacts of universal newborn screening on the outcome of children with sickle cell disease in the province of Quebec: A retrospective cohort study

Abstract

A universal newborn screening program for sickle cell disease (uNS-SCD) was implemented in the province of Québec (Qc) in November 2013, close in time to the recommendation of early initiation of hydroxyurea (HU) therapy for children. This retrospective cohort study evaluated the impact of such a program on children first seen between January 2000 and December 2019. Cohorts pre-SCD-uNS in Qc (pre-QcNS) (n = 253) and post-QcNS (n = 157) for patients seen prior to or after Nov 2013 were compared. Kaplan-Meier curves, Poisson regression, and logistic regressions were used for statistical analysis, using Software R version 4.2.1. Median age at first visit decreased significantly from 14.4 [interquartile range: 2.4-72.0] to 1.2 months [1.2-57.6] (p < 0.001). The percentage of children born in Qc undiagnosed at birth and referred after a first SCD-related complication dropped from 42.6% to 0.0% (p < 0.0001). The median age of HU introduction for patients with SS/Sβ°-thalassemia decreased from 56.4 [31.2-96.0] to 9.0 months post-QcNS [8.0-12.1] (p < 0.001). Event-free survival improved significantly for any type of hospitalization as well as for vaso-occlusive crisis (VOC) (140-257 days (p < 0.001) and 1320 vs. 573 days (p < 0.002), respectively), resulting in a reduction from 2 [interquartile range: 1.0-3.0] to 1.0 hospitalizations/patient-year [0.6-1.4] (p < 0.001). Children with SS/Sβ°-thalassemia referred post-QcNS also had fewer emergency department visits for VOC (RR: 0.69, 95% confidence interval: 0.54-0.88). The Universal NS program allows early detection and referral of children with SCD to comprehensive care centers. Earlier access ensures that children benefit from essential preventive interventions, reducing disease burden. This cohort study highlights that uNS-SCD is an essential public health measure.

Keywords: hemoglobinopathies; neonatal screening; newborn screening; sickle cell anemia; sickle cell disease.

FIGURE 1

Flow diagram of our cohort.

FIGURE 2

Evolution of median age at introduction of hydroxyurea by follow‐up period as a function of Quebec universal newborn screening (QcNS).

FIGURE 3

Univariable analyses for event‐free survival (EFS); the event is defined as any cause of hospitalizations (A and C), or specifically as hospitalization for vaso‐occlusive crisis (VOC) treatment (B and D). We compared EFS for patients with SS/Sβ°thalassemia phenotype pre‐QcNS (turquoise) versus post‐QcNS (red) (A and B), as well as those who benefited from NS (yellow) versus unscreened children referred after first‐disease complication (blue) (C and D).