Neonatal cholestasis: new insights pathophysiology and strategies to improve patient diagnosis and prognosis

Ermelinda Santos Silva

Ermelinda Santos Silva, a specialist in Pediatrics, integrates the Gastroenterology Unit of the Department of Pediatrics of Centro Materno-Infantil do Norte, CHUPorto.
She got her Ph.D. in Medical Sciences at ICBAS-UP in March 2022, under the supervision of Professor Ana Isabel Lopes and co-supervision of Professors Alice Santos Silva and Esmeralda Martins.


What is neonatal cholestasis?

Neonatal cholestasis (NC) is a rare syndrome (incidence of 1/2500) but with great relevance due to the high associated morbidity and mortality (mortality ~10% at 12 months of life), with the survival of many patients depending on liver transplantation. NC remains a relevant clinical challenge due to the significant prevalence of late diagnoses among newborns (NB) and infants with jaundice and to the challenging diagnostic approach related to the great variability of underlying etiologies, some of which rare and requiring specific treatment.


What was the primary study objective?

The main aim of this thesis was to contribute to improving the diagnosis and prognosis of patients with NC. It included five original studies (three retrospective and two cross-sectional, one of which with prospective recruitment), a clinical report with deion of two clinical s, and a letter to the editor.


What were the main study results?

A study with healthcare professionals (physicians and nurses) showed that the specialization in Pediatrics was the only independent variable significantly associated with a better ability to recognize pale stools (one of the clinical signs of cholestasis).
The retrospective study, which included a cohort of 154 Portuguese patients, showed significant epidemiological changes over the last decades. It also showed that despite a considerable reduction in the age of recognition of NC, overall and native liver survival rates did not improve significantly. The deion of two clinical s of a rare entity innovatively treated with replacement enzyme was included as an example.
The analysis of clinical and biochemical parameters at the time of hospital admission of patients in this cohort allowed to identify some with diagnostic and predictive prognostic value, as well as to develop innovative diagnostic models for some underlying entities and predictors of unfavorable prognosis. Based on these predictive models, personal experience, and evidence available in the literature, two diagnostic algorithms were developed.
Finally, the cross-sectional study with prospective recruitment of healthy 2-month-old infants innovatively suggested that the plasma bile acid pro in early postnatal life may influence the regulation of the redox state (and/or vice versa) and erythrocyte turnover. It also suggested that exclusive breastfeeding in humans may be associated with delayed maturation of the bile acid pro, potentially contributing to an improved redox state through this or other mechanisms.

What contributions to the clinical practice may come this study?

This thesis proposes several measures that can potentially be implemented in the Portuguese setting, namely the incorporation of the Taiwanese Stool Color Card in the Portuguese Child and Youth Health Book (with the permission of the Stool Color Card author and the Taiwanese Ministry of Health, already obtained).

In the future, the knowledge of the pathophysiology of NC should be deepened through lines of research involving the mother-child binomial rather than just the NB/infant with NC, towards precision and preventive medicine.

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