<p>Neonatal presentation of cystic fibrosis (CF), particularly meconium ileus, has historically been associated with severe disease and poor prognosis. However, its impact on long-term outcomes in the era of newborn screening and CFTR modulators remains unclear. We aimed to compare long-term clinical outcomes between patients with and without neonatal presentation of CF. We conducted a retrospective observational study including all patients with CF followed at a tertiary reference center in Lisbon, Portugal, between 2013 and March 2025. Neonatal presentation was defined by meconium ileus, neonatal cholestasis, poor weight gain, respiratory symptoms, or exocrine pancreatic insufficiency within the first 28&#xa0;days of life. Demographic, genetic, nutritional, pulmonary, and clinical outcome data were analyzed. Among 61 patients with CF, 16 (26.2%) had neonatal presentation, predominantly meconium ileus. This group was more frequently F508del homozygous than the non-neonatal group (75.0% vs. 37.8%, <i>p</i> = 0.019). Nutritional outcomes were comparable between groups, with overlapping BMI z-score trajectories across follow-up. Lung function in patients with neonatal presentation showed a trend toward greater decline in FEV₁ during adolescence. Patients without neonatal presentation exhibited a higher burden and broader spectrum of chronic complications. Mortality was low in both groups.</p><p><i>Conclusion</i>: Neonatal presentation in CF no longer confers a uniformly adverse long-term prognosis under contemporary care. Although associated with significant early disease burden, nutritional outcomes and survival remain preserved. However, the observed trend toward greater pulmonary decline during adolescence suggests persistent respiratory vulnerability requiring long-term surveillance.</p><p><Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> <p><b>What is Known:</b></p> <p>• <i>Neonatal CF presentation (e.g., meconium ileus) has historically been associated with severe disease and poor prognosis.</i></p> <p>• <i>Newborn screening and CFTR modulators have substantially improved CF outcomes.</i></p> </entry> </row> <row> <entry align="left" nameend="c2" namest="c1"> <p><b>What is New:</b></p> <p>• <i>Despite significant early morbidity, neonatal CF presentation was associated with preserved nutritional outcomes and survival, but a trend toward greater pulmonary decline in adolescence.</i></p> <p>• <i>Neonatal presentation may represent a risk-modifying rather than deterministic phenotype in the modern CF era.</i></p> </entry> </row> </tbody> </tgroup> </Table></p>

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Long-term clinical outcomes of neonatal cystic fibrosis presentation: a single-center retrospective study

  • Ema Freitas,
  • Carolina Simão,
  • Raquel Lopes de Bragança,
  • Susana Castanhinha

摘要

Neonatal presentation of cystic fibrosis (CF), particularly meconium ileus, has historically been associated with severe disease and poor prognosis. However, its impact on long-term outcomes in the era of newborn screening and CFTR modulators remains unclear. We aimed to compare long-term clinical outcomes between patients with and without neonatal presentation of CF. We conducted a retrospective observational study including all patients with CF followed at a tertiary reference center in Lisbon, Portugal, between 2013 and March 2025. Neonatal presentation was defined by meconium ileus, neonatal cholestasis, poor weight gain, respiratory symptoms, or exocrine pancreatic insufficiency within the first 28 days of life. Demographic, genetic, nutritional, pulmonary, and clinical outcome data were analyzed. Among 61 patients with CF, 16 (26.2%) had neonatal presentation, predominantly meconium ileus. This group was more frequently F508del homozygous than the non-neonatal group (75.0% vs. 37.8%, p = 0.019). Nutritional outcomes were comparable between groups, with overlapping BMI z-score trajectories across follow-up. Lung function in patients with neonatal presentation showed a trend toward greater decline in FEV₁ during adolescence. Patients without neonatal presentation exhibited a higher burden and broader spectrum of chronic complications. Mortality was low in both groups.

Conclusion: Neonatal presentation in CF no longer confers a uniformly adverse long-term prognosis under contemporary care. Although associated with significant early disease burden, nutritional outcomes and survival remain preserved. However, the observed trend toward greater pulmonary decline during adolescence suggests persistent respiratory vulnerability requiring long-term surveillance.

What is Known:

Neonatal CF presentation (e.g., meconium ileus) has historically been associated with severe disease and poor prognosis.

Newborn screening and CFTR modulators have substantially improved CF outcomes.

What is New:

Despite significant early morbidity, neonatal CF presentation was associated with preserved nutritional outcomes and survival, but a trend toward greater pulmonary decline in adolescence.

Neonatal presentation may represent a risk-modifying rather than deterministic phenotype in the modern CF era.