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Multicenter Study
. 2025 Feb 17;20(1):76.
doi: 10.1186/s13023-025-03594-7.

Health outcomes and drug utilisation in children with Noonan syndrome: a European cohort study

Michele Santoro  1 , Ingeborg Barisic  2 , Alessio Coi  3 , Joachim Tan  4   5 , Ester Garne  6 , Maria Loane  7 , Ljubica Odak  8 , Maria Valentina Abate  3 , Elisa Ballardini  9 , Clara Cavero-Carbonell  10 , Miriam Gatt  11 , Mika Gissler  12   13   14 , Kari Klungsøyr  15   16 , Nathalie Lelong  17 , David Tucker  18 , Diana Wellesley  19 , Joan K Morris  5
Affiliations
Multicenter Study

Health outcomes and drug utilisation in children with Noonan syndrome: a European cohort study

Michele Santoro et al. Orphanet J Rare Dis. .

Abstract

Background: Noonan Syndrome (NS) is a rare multisystemic disorder with heterogeneous phenotypic manifestations. The aim of this study was to analyse rates of survival, hospitalisation, surgeries and prescriptions in children born with NS in the first 10 years of life.

Methods: This is a multi-centre population-based cohort study. Data on 175 liveborn children diagnosed with NS from 11 EUROCAT congenital anomaly registries were linked to healthcare databases. Each registry applied a common data model to standardise data and run common syntax scripts to produce aggregated results which were pooled using random effects meta-analyses.

Results: Mortality rates were high in the first year of life with 5.4% (95%CI 1.5%-10.1%) of children dying before the age of 1 year with a further 2% dying up to age 5. In the first year, 87.9% (95%CI 75.3%-94.3%) of children were hospitalized and the median Length Of hospital Stay (LOS) was 15.3 days (95%CI 9.3-21.2). After the first year, the proportion of children hospitalized remained higher than 70%, but the LOS decreased to 1.3 days per year. In the first 5 years, 65.2% of children underwent a median of two surgical procedures. The median age at first surgery was 29 weeks. The proportion of children with an antibiotic prescription increased from 53.6% at age 1 to 62.4% yearly until 4 years of age.

Conclusions: Children with NS have high mortality and morbidity not only in the first year of life but also up to five years of age. This study evaluated the health burden of NS and provided information for clinicians, health-care providers and families.

Keywords: Cohort; Hospitalization; Noonan syndrome; Prescriptions; Surgeries; Survival.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: All EUROCAT registries contributing data to the EUROlinkCAT project obtained ethical, governance and other permissions for the data linkage according to their national legislations and arrangements. University of Ulster obtained Ethics permission for the Central Results Repository on 15 September 2017 (Institute of Nursing and Health Research Ethics Filter Committee, number FCNUR-17–000). Consent for publication: The work described has not been submitted elsewhere for publication, in whole or in part, and all the authors listed have approved the manuscript for publication. Competing interests: The authors have no conflicts of interest relevant to this article to disclose.

Figures

Fig. 1
Fig. 1
Percentage hospitalised (with 95% CIs) children with Noonan syndrome, children with any congenital anomaly (‘Any CA’) and children without a congenital anomaly (‘Reference’), by age, 1995–2014
See this image and copyright information in PMC

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