448 - The influence of prostaglandin pathway gene polymorphisms on the development PDA and results of hsPDA treatment in infants born before 32 weeks of gestation - pilot study

Publication Number: 3433.448

Dawid Szpecht, Department of Neonatology Poznan University of Medical Sciences, Poznan, Wielkopolskie, Poland; Marcin Minta, Department of Neonatology, Karol Marcinkowski University of Medical Sciences in Poznan, ul. Polna 33, 60-535 Poznań, Poland;, Poznan, Wielkopolskie, Poland; Grazyna Kurzawinska, Poznan University of Medical Sciences, Poznan, Wielkopolskie, Poland; Agnieszka Seremak Mrozikiewicz, Poznań University of Medical Sciences, Poznań, Wielkopolskie, Poland

Background: The management of patent ductus arteriosus (PDA) in preterm infants continues to pose a major clinical challenge. With the advent of novel diagnostic approaches, growing attention has been directed toward the genetic determinants of various neonatal conditions. Genetic variability has been extensively documented as a factor influencing drug metabolism, thereby modulating dose-dependent responses and resistance to standard pharmacological interventions.

Objective: The aim of the study was to assess the potential impact of polymorphisms in genes associated with the prostaglandin pathway on the response to pharmacological treatment of hemodynamically significant PDA (HsPDA) in infants born before 32 weeks of gestation.

Design/Methods: Blood necessary for genetic testing was collected during blood collection for standard tests (0,5ml). Genomic DNA was isolated from nucleated blood cells using the QIAamp DNA Mini Kit (QIAGEN, Hilden, Germany). The single-nucleotide polymorphisms listed in Table 1 were genotyped by PCR-RFLP.
PDA was diagnosed by transthoracic echocardiography on postnatal day 2 and repeated at 24 h intervals until ductal closure. Hemodynamic significance was adjudicated according to the guidelines of the Polish Neonatal Society. The efficacy of pharmacological treatment was defined as complete PDA closure confirmed by echocardiographic examination.
Ethics approval was granted by the Bioethics Committee of the Poznan University of Medical Sciences (No. 96/22).
Funding was provided by the National Science Centre, Poland, grant No. 2021/05/X/NZ5/01430.

Results: The study cohort comprised 99 neonates born at 24-32 weeks' gestation (median, 30 weeks). PDA was diagnosed in 36 infants (36.4%), of whom 21 (21.2%) had HsPDA.
Patients with HsPDA were treated with ibuprofen (n = 3; 3.03%), paracetamol (n = 14; 14.14%), and both (n = 4; 4.04%).
Analysis of the studied polymorphisms revealed an increased frequency of PDA among carriers of the rs1051931 polymorphism. We noticed a statistically significant influence of rs4613763 in the codominant variant on the success of the applied pharmacological therapy. All results are presented in Tables 2 and 3.

Conclusion(s): Our study indicates that specific polymorphisms may contribute to the development of PDA and respond to treatment. Knowing and understanding it will give us a tool for more adequate treatment and will allow us to avoid adverse effects resulting from the use of drugs to which the response may be unsatisfactory. Further advancement of research in this field is expected to facilitate the development of more effective treatment strategies.

The following single-nucleotide polymorphisms (SNPs) were analyzed.


Association of Individual SNPs with Successful Pharmacologic Ductal Closure.


Drug-specific effects were observed, with evidence of SNP-by-treatment interaction for paracetamol versus ibuprofen in relation to pharmacologic closure.