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UGT1A1*28 Genotypes and Respiratory Disease in Very Preterm Infants: A Cohort Study
Jesper Padkær Petersen1, Finn Ebbesen, Mads Vilhelm Hollegaard
1Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark.
Insights
The Gilbert genotype (UGT1A1*28 allele) is linked to increased oxygen needs and bronchopulmonary dysplasia (BPD) risk in very preterm infants. This genetic factor impacts respiratory outcomes in premature newborns.
Area of Science:
- Neonatal Medicine
- Genetics
- Respiratory Medicine
Background:
- Respiratory disease is common and severe in very preterm infants.
- Bilirubin acts as both a neurotoxin and antioxidant, potentially influencing preterm respiratory disease.
- The Gilbert genotype (UGT1A1*28 allele) is a primary genetic determinant of bilirubin variation.
Purpose of the Study:
- To investigate the association between the UGT1A1*28 allele and respiratory disease in very preterm infants.
Main Methods:
- A cohort study included 1,354 very preterm infants (gestational age <32 weeks).
- Infant genotypes were sourced from the Danish Neonatal Screening Biobank.
- Clinical data on surfactant therapy, oxygen supplementation, and bronchopulmonary dysplasia (BPD) were collected.
Main Results:
- The UGT1A1*28 allele correlated with increased odds of requiring supplementary oxygen and developing BPD.
- Oxygen supplementation duration was extended by 6.38 days for infants with the UGT1A1*28 allele.
- No significant effect was found on the need for surfactant treatment.
Conclusions:
- UGT1A1*28 genotypes are associated with higher oxygen supplementation requirements and an increased risk of BPD in very preterm newborns.
- The findings suggest a genetic influence on respiratory morbidity in this vulnerable population.
Background:
Respiratory disease in the very preterm infant is frequent and often severe. Bilirubin is both a potent neurotoxin and antioxidant, and may have a clinical impact on preterm respiratory disease. The Gilbert genotype, the UGT1A1*28 allele, is the major known genetic cause of variation in bilirubin.
Objectives:
To study the association between respiratory disease in the very preterm infant and the UGT1A1*28 allele.
Methods:
This is a cohort study of 1,354 very preterm infants (gestational age <32 weeks) born in Jutland, Denmark in 1997-2011. Genotypes were obtained from the Danish Neonatal Screening Biobank, and clinical information was obtained from the databases of two tertiary neonatal intensive care units. Outcomes were the need for surfactant therapy, any need for and duration of supplementary oxygen and bronchopulmonary dysplasia (BPD).
Results:
Per UGT1A1*28 allele, odds were increased for any need of supplementary oxygen (odds ratio 1.26; 1.05-1.50) and for BPD (odds ratio 1.71; 1.23-2.39), the need of supplementary oxygen increased by 6.38 days (1.87-10.89), and chance per day of no longer needing supplementary oxygen was reduced (hazard rate 0.84; 0.76-0.93). No effect was observed for need of surfactant treatment (odds ratio 1.08; 0.91-1.28). Hardy-Weinberg equilibrium was unlikely for the cohort (p < 0.012). This could be explained by death prior to genotype sampling. In tests of robustness this failed to explain the primary results.
Conclusions:
Compared to the common genotype, UGT1A1*28 genotypes were associated with an increased need of oxygen supplementation and risk of BPD in very preterm newborns.
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