Abstract
Objective
Assess if unit-level PDA management correlates with neurodevelopmental impairment (NDI) at 18–24 months corrected postnatal age (CPA) in extremely preterm infants.
Study design
Retrospective analysis of infants born at <29 weeks (2014–2017) across two units having distinct PDA strategies. Site 1 utilized an echocardiography-based treatment strategy aiming for accelerated closure (control). Site 2 followed a conservative approach. Primary endpoint: NDI, characterized by cerebral palsy, any Bayley-III composite score <85, sensorineural/mixed hearing loss, or at least unilateral visual impairment.
Results
377 infants were evaluated. PDA treatment rates remained unchanged in Site 1 but eventually reached 0% in Site 2. Comparable rates of any/significant NDI were seen across both sites (any NDI: 38% vs 36%; significant NDI: 13% vs 10% for Site 1 and 2, respectively). After adjustments, NDI rates remained similar.
Conclusion
PDA management strategies in extremely preterm newborns showed no significant impact on neurodevelopment outcomes at 18–24 months CPA.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Data availability
Data for this study cannot be shared publicly as it is bound by confidentiality agreements governed by hospital offices. Aggregate data may be made available from the corresponding author (GA) on reasonable request.
References
de Carvalho Nunes G, Wutthigate P, Simoneau J, Beltempo M, Sant’Anna GM, Altit G. Natural evolution of the patent ductus arteriosus in the extremely premature newborn and respiratory outcomes. J Perinatol. 2022;42:642–8.
Sung SI, Chang YS, Kim J, Choi JH, Ahn SY, Park WS. Natural evolution of ductus arteriosus with noninterventional conservative management in extremely preterm infants born at 23-28 weeks of gestation. PLoS One. 2019;14:1–11.
Parkerson S, Philip R, Talati A, Sathanandam S. Management of patent ductus arteriosus in premature infants in 2020. Front Pediatr. 2021;8:590578.
Ruoss JL, Bazacliu C, Giesinger RE, McNamara PJ. Patent ductus arteriosus and cerebral, cardiac, and gut hemodynamics in premature neonates. Semin Fetal Neonatal Med. 2020;25:101120.
Weir FJ, Ohlsson A, Myhr TL, Fong K, Ryan ML. A patent ductus arteriosus is associated with reduced middle cerebral artery blood flow velocity. Eur J Pediatr. 1999;158:484–7.
Rozé JC, Cambonie G, Le Thuaut A, Debillon T, Ligi I, Gascoin G, et al. Effect of early targeted treatment of ductus arteriosus with ibuprofen on survival without cerebral palsy at 2 years in infants with extreme prematurity: a randomized clinical trial. J Pediatr. 2021;233:33–42.e2.
Hundscheid T, Onland W, Kooi EMW, Vijlbrief DC, de Vries WB, Dijkman KP, et al. Expectant management or early ibuprofen for patent ductus arteriosus. N. Engl J Med. 2023;388:980–90.
Mitra S, Scrivens A, von Kursell AM, Disher T. Early treatment versus expectant management of hemodynamically significant patent ductus arteriosus for preterm infants. Cochrane Database Syst Rev. 2020;12:CD013278.
Sung SI, Chang YS, Ahn SY, Jo HS, Yang M, Park WS. Conservative non-intervention approach for hemodynamically significant patent ductus arteriosus in extremely preterm infants. Front Pediatr. 2020;8:605134.
Yanowitz TD, Yao AC, Werner JC, Pettigrew KD, Oh W, Stonestreet BS. Effects of prophylactic low-dose indomethacin on hemodynamics in very low birth weight infants. J Pediatr. 1998;132:28–34.
Stark MJ, Crawford TM, Ziegler NM, Hall A, Andersen CC. Differential effects of ibuprofen and indomethacin on cerebral oxygen kinetics in the very preterm baby. Front Pediatr. 2022;10:979112.
Benitz WE. Patent ductus arteriosus in preterm infants. Pediatrics. 2016;137:e20153730.
Ngo S, Profit J, Gould JB, Lee HC. Trends in patent ductus arteriosus diagnosis and management for very low birth weight infants. Pediatrics. 2017;139:e20162390.
Hagadorn JI, Brownell EA, Trzaski JM, Johnson KR, Lainwala S, Campbell BT, et al. Trends and variation in management and outcomes of very low-birth-weight infants with patent ductus arteriosus. Pediatr Res. 2016;80:785–92.
Lokku A, Mirea L, Lee SK, Shah PS. Trends and outcomes of patent ductus arteriosus treatment in very preterm infants in Canada. Am J Perinatol. 2017;34:441–50.
Park J, Yoon SJ, Han J, Song IG, Lim J, Shin JE, et al. Patent ductus arteriosus treatment trends and associated morbidities in neonates. Sci Rep. 2021;11:10689.
Hagadorn JI, Bennett MV, Brownell EA, Payton KSE, Benitz WE, Lee HC. Covariation of neonatal intensive care unit-level patent ductus arteriosus management and in-neonatal intensive care unit outcomes following preterm birth. J Pediatr. 2018;203:225–233.e1.
Shah PS, Seidlitz W, Chan P, Yeh S, Musrap N, Lee SK. Internal audit of the Canadian neonatal network data collection system. Am J Perinatol. 2017;34:1241–9.
Shennan AT, Dunn MS, Ohlsson A, Lennox K, Hoskins EM. Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics. 1988;82:527–32.
Papile L-A, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978;92:529–34.
Joseph Volpe, Terrie Inder, Basil Darras, Linda de Vries, Adre du Plessis, Jeffrey Neil, et al. Volpe’s Neurology of the Newborn. 6th ed. Elsevier; 484–99 p. (2017).
Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978;187:1–7.
Tita ATN, Andrews WW. Diagnosis and management of clinical chorioamnionitis. Clin Perinatol. 2010;37:339–54.
Soraisham AS, Singhal N, McMillan DD, Sauve RS, Lee SK. A multicenter study on the clinical outcome of chorioamnionitis in preterm infants. Am J Obstet Gynecol. 2009;200:372.e1–6.
International Committee for the Classification of Retinopathy of Prematurity. The international classification of retinopathy of prematurity revisited. Arch Ophthalmol. 2005;123:991–9.
Kramer MS, Platt RW, Wen SW, Joseph KS, Allen A, Abrahamowicz M, et al. A new and improved population-based Canadian reference for birth weight for gestational age. Pediatrics. 2001;108:e35.
Hornik CP, Fort P, Clark RH, Watt K, Benjamin DK, Smith PB, et al. Early and late onset sepsis in very-low-birth-weight infants from a large group of neonatal intensive care units. Early Hum Dev. 2012;88:S69–74.
Gunel MK, Mutlu A, Tarsuslu T, Livanelioglu A. Relationship among the manual ability classification system (MACS), the gross motor function classification system (GMFCS), and the functional status (WeeFIM) in children with spastic cerebral palsy. Eur J Pediatr. 2009;168:477–85.
Busque AA, Jabbour E, Patel S, Couture É, Garfinkle J, Khairy M, et al. Incidence and risk factors for autism spectrum disorder among infants born <29 weeks’ gestation. Paediatr Child Health (Can). 2022;27:346–52.
Sankar MN, Benitz WE. Does crossover treatment of control subjects invalidate results of randomized trials of patent ductus arteriosus treatment? J Perinatol. 2020;40:1863–70.
Dani C, Lista G, Bianchi S, Mosca F, Schena F, Ramenghi L, et al. Intravenous paracetamol in comparison with ibuprofen for the treatment of patent ductus arteriosus in preterm infants: a randomized controlled trial. Eur J Pediatr. 2021;180:807–16.
Mari G, Moise KJ, Deter RL, Kirshon B, Huhta JC, Carpenter RJ, et al. Doppler assessment of the pulsatility index of the middle cerebral artery during constriction of the fetal ductus arteriosus after indomethacin therapy. Am J Obstet Gynecol. 1989;161:1528–31.
Chen X, Han D, Wang X, Huang X, Huang Z, Liu Y, et al. Vascular and pulmonary effects of ibuprofen on neonatal lung development. Respir Res. 2023;24:39.
Ohlsson A, Walia R, Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev. 2015;2015:1–143.
Jansen EJS, Hundscheid T, Onland W, Kooi EMW, Andriessen P, de Boode WP. Factors associated with benefit of treatment of patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. Front Pediatr. 2021;9:626262.
Kabra NS, Schmidt B, Roberts RS, Doyle LW, Papile L, Fanaroff A. Neurosensory impairment after surgical closure of patent ductus arteriosus in extremely low birth weight infants: results from the trial of indomethacin prophylaxis in preterms. J Pediatrics. 2007;150:229–234.e1.
Barcroft M, McKee C, Berman DP, Taylor RA, Rivera BK, Smith CV, et al. Percutaneous closure of patent ductus arteriosus. Clin Perinatol. 2022;49:149–66.
Kaga M, Sanjo M, Sato T, Miura Y, Ono T. Safety of conservative approach for persistent patent ductus arteriosus in preterm infants: Neurodevelopmental outcomes at 5 years of age. Tohoku J Exp Med. 2019;249:155–61.
Collins RT, Lyle RE, Rettiganti M, Gossett JM, Robbins JM, Casey PH. Long-term neurodevelopment of low-birthweight, preterm infants with patent ductus arteriosus. J Pediatr. 2018;203:170–6.
Aldecoa-Bilbao V, García-Catalán MJ, Gaixa M, Clotet Caba J, Teodoro S, Figaró Voltà C. Neurodevelopmental impairment at two years in premature infants with prolonged patency of ductus arteriosus after a conservative approach. Am J Perinatol. 2021;38:449–55.
Oncel MY, Eras Z, Uras N, Canpolat FE, Erdeve O, Oguz SS. Neurodevelopmental outcomes of preterm infants treated with oral paracetamol versus ibuprofen for patent ductus arteriosus. Am J Perinatol. 2017;34:1185–9.
Weisz DE, Mirea L, Rosenberg E, Jang M, Ly L, Church PT, et al. Association of patent ductus arteriosus ligation with death or neurodevelopmental impairment among extremely preterm infants. JAMA Pediatr. 2017;171:443–9.
Janz-Robinson EM, Badawi N, Walker K, Bajuk B, Abdel-Latif ME, Bowen J, et al. Neurodevelopmental outcomes of premature infants treated for patent ductus arteriosus: a population-based Cohort Study. J Pediatrics. 2015;167:1025–1032.e3.
Gudmundsdottir A, Broström L, Skiöld B, Källén K, Serenius F, Norman M, et al. The type and timing of patent ductus arteriosus treatment was associated with neurodevelopment when extremely preterm infants reached 6.5 years. Acta Paediatr, Int J Paediatr. 2021;110:510–20.
Wickremasinghe AC, Rogers EE, Piecuch RE, Johnson BC, Golden S, Moon-Grady AJ, et al. Neurodevelopmental outcomes following two different treatment approaches (early ligation and selective ligation) for patent ductus arteriosus. J Pediatr. 2012;161:1065–72.
de Waal K, Phad N, Stubbs M, Chen Y, Kluckow M. A randomized placebo-controlled pilot trial of early targeted nonsteroidal anti-inflammatory drugs in preterm infants with a patent ductus arteriosus. J Pediatr. 2021;228:82–86.e2.
Schindler T, Smyth J, Bolisetty S, Michalowski J, Mallitt KA, Singla A, et al. Early PARacetamol (EPAR) trial: a randomized controlled trial of early paracetamol to promote closure of the ductus arteriosus in preterm infants. Neonatology. 2021;118:274–81.
Clyman RI, Liebowitz M, Kaempf J, Erdeve O, Bulbul A, Håkansson S, et al. PDA-TOLERATE Trial: an exploratory randomized controlled trial of treatment of moderate-to-large patent ductus arteriosus at 1 week of age. J Pediatr. 2019;205:41–48.e6.
EL-Khuffash A, Bussmann N, Breatnach CR, Smith A, Tully E, Griffin J, et al. A pilot randomized controlled trial of early targeted patent ductus arteriosus treatment using a risk based severity score (The PDA RCT). J Pediatr. 2021;229:127–33.
Giesinger RE, Hobson AA, Bischoff AR, Klein JM, McNamara PJ. Impact of early screening echocardiography and targeted PDA treatment on neonatal outcomes in “22-23” week and “24-26” infants. Semin Perinatol. 2023;47:151721.
Kristman V, Manno M, Côté P. Loss to follow-up in cohort studies: How much is too much? Eur J Epidemiol. 2004;19:751–60.
Acknowledgements
We thank the Canadian Neonatal Network and the Canadian Neonatal Follow Up Network who provided the local database of the 2 centers with the standardized definitions.
Funding
This project was supported by the Neonatology divisions of Centre Hospitalier Universitaire Sainte-Justine and McGill University Health Centre. The NeoCardioLab and its platforms were funded by the Department of Pediatrics of McGill University, the Just for Kids Foundation, the Foundation of Stars, as well as the Grand Defi Pierre Lavoie.
Author information
Authors and Affiliations
Contributions
TML, MB, AG, SS, OB, MC interpreted the results and critically reviewed the manuscript for important intellectual content. ST, AL conceptualized and designed the study, interpreted the results, supervised the student work and reviewed and revised all manuscript drafts for important intellectual content. GA conceptualized and designed the study, conducted the analyses interpreted the results, and reviewed and revised all manuscript drafts for important intellectual content. SBC conceptualized the study, conducted the analyses, interpreted the results and wrote the paper. All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Cervera, S.B., Saeed, S., Luu, T.M. et al. Evaluation of the association between patent ductus arteriosus approach and neurodevelopment in extremely preterm infants. J Perinatol 44, 388–395 (2024). https://doi.org/10.1038/s41372-024-01877-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41372-024-01877-8