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Background As the most common chronic lung disease (CLD) related to premature birth, bronchopulmonary dysplasia (BPD) is associated with long-term lung disease along with cardiovascular and neurodevelopmental disorders. However, data on the incidence and predictors of BPD in Qatar are lacking. Objectives In this study, we aimed to determine the incidence of BPD among infants born at ≤ 32 weeks gestational age (GA) at our neonatal unit, and identify risk factors for the development of BPD and moderate-severe BPD. Methods This was a retrospective observational cohort study conducted at a single site: a level-III neonatal intensive care unit (NICU) in Qatar. We included 1539 neonates born at ≤ 32 weeks of gestation with birth weights of ≤ 1500 grams who were admitted to the NICU between 2017 and 2020. Univariate and multivariate logistic regression analyses were performed to identify potential factors and predictors and their possible associations with the development of BPD and moderate-severe BPD. We also applied BPD classifications to determine the variability in the incidence of BPD in our cohort according to various definitions (2001 National Institute of Child Health and Human Development (NICHD) Diagnostic Criteria, 2016 Revisions of NICHD Criteria, and 2019 Neonatal Research Network Jensen Grading). Results A total of 451 infants (29.3%) had BPD (BPD group) while 1088 (70.7%) did not (non-BPD group), and the overall incidence of BPD was 29.3%. The most relevant risk factors associated with a higher risk of developing BPD identified in the multivariate logistic regression analysis were appropriate weight for gestational age (adjusted OR (aOR) 3.67, 95%CI 2.02-6.67, P < 0.001), presence of patent ductus arteriosus (PDA) (aOR 2.61, 95%CI 1.86-3.66, P < 0.001), late-onset sepsis (aOR 2.16; 95%CI 1.29-3.62; P = 0.003), and use of invasive ventilation (aOR 1.90; 95%CI 1.35-2.69; P < 0.001). The most relevant independent risk factors associated with a higher risk for developing moderate-severe BDP were postnatal steroids (aOR 7.12, 95%CI 3.77-13.44, P < 0.001), use of inhaled nitric oxide (aOR 3.65, 95%CI 1.48-9.01, P = 0.005), use of invasive ventilation (aOR 2.13, 95%CI 1.13-4.00, P = 0.019), late-onset sepsis (aOR 2.07, 95%CI 1.10-3.91, P = 0.025), and male sex (aOR 2.04, 95%CI 1.24-3.36, P = 0.005). The difference in the distribution of BPD severity across the three different definitions of NICHD was significant (P < 0.001). Conclusion The results of this study showed that the incidence of BPD remained high in infants born at ≤ 32 weeks of gestational age and birth weight <1500 g with appropriate weight for gestational age. The presence of PDA at birth or first echocardiography, late-onset sepsis, and use of invasive ventilation were significant risk factors for the incidence of BPD. The identification of risk factors will contribute to the implementation of lung-protective strategies for at-risk infants who may benefit from potential preventive therapy.
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Background: Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease characterized by defective FAS signaling, which results in chronic, nonmalignant lymphoproliferation and autoimmunity accompanied by increased numbers of "double-negative" T-cells (DNTs) (T-cell receptor αß+ CD4-CD8-) and an increased risk of developing malignancies later in life. Case presentation: We herein report a case of a newborn boy with a novel germline homozygous variant identified in the FAS gene, exon 9, c.775del, which was considered pathogenic. The consequence of this sequence change was the creation of a premature translational stop signal p.(lle259*), associated with a severe clinical phenotype of ALPS-FAS. The elder brother of the proband was also affected by ALPS and has been found to have the same FAS homozygous variant associated with a severe clinical phenotype of ALPS-FAS, whereas the unaffected parents are heterozygous carriers of this variant. This new variant has not previously been described in population databases (gnomAD and ExAC) or in patients with FAS-related conditions. Treatment with sirolimus effectively improved the patient clinical manifestations with obvious reduction in the percentage of DNTs. Conclusion: We described a new ALPS-FAS clinical phenotype-associated germline FAS homozygous pathogenic variant, exon 9, c.775del, that produces a premature translational stop signal p.(lle259*). Sirolimus significantly reduced DNTs and substantially relieved the patient's clinical symptoms.