Download PDF
Am J Perinatol 2024; 41(12): 1673-1679
DOI: 10.1055/a-2249-1671
Original Article

Early Echocardiographic Predictors of Eventual Need for Patent Ductus Arteriosus Treatment: A Retrospective Study

Jenny Koo
1   Department of Neonatology, Sharp Mary Birch Hospital for Women and Newborns, Sharp Neonatal Research Institute, San Diego, California
,
Nohemi Torres
2   Department of Pediatric Cardiology, Sharp Mary Birch Hospital for Women and Newborns, San Diego, California
,
Anup Katheria
1   Department of Neonatology, Sharp Mary Birch Hospital for Women and Newborns, Sharp Neonatal Research Institute, San Diego, California
› Author Affiliations Funding The parent studies from which data were derived include:
• PREMOD2 (NCT03019367)—1R01HD088646-01
• DOXIE (NCT04413097)—1R03HD105224, TRF01357, NRP Young Investigator Award
› Further Information
Also available at
    Permissions and Reprints

Abstract

Objective Hemodynamically significant patent ductus arteriosus (hsPDA) in preterm neonates is associated with end-organ injury including intraventricular hemorrhage. Early treatment may reduce morbidities but may result in overtreatment. This study aimed to examine the association between commonly obtained echocardiographic markers within the first 12 hours of life and eventual treatment of an hsPDA.

Study Design Patients with <32 weeks' gestational age had blinded echocardiograms done within the first 12 hours of life as part of research protocols. Subsequent treatment of the patent ductus arteriosus (PDA) was determined by the clinical team independent of echocardiogram results. t-tests and chi-square tests were done for continuous data and categorical outcomes. A receiver operating curve was created to optimize cutoff values.

Results Among 199 neonates studied (mean time of echocardiogram 6.7 h after birth), those needing PDA treatment had higher left ventricular output (LVO), right ventricular output (RVO), and superior vena cava (SVC) flow (p-values 0.007, 0.044, and 0.012, respectively). Cutoffs for predicting PDA treatment were LVO > 204 mL/kg/min (63% sensitivity, 66% specificity), RVO > 221 mL/kg/min or SVC flow > 99 mL/kg/min (sensitivities 70 and 43%, specificities 48 and 73%, respectively).

Conclusion Preterm neonates with higher markers of cardiac output in the first 12 hours of birth later required PDA treatment. These data are the first to use standard cardiac output measures in the first 12 hours of life to predict the need for future PDA treatment. Further prospective studies will need to be performed to corroborate these associations between echocardiographic markers and clinical outcomes/morbidities.

Key Points

  • Early diagnosis of hsPDA may prevent severe morbidity and death.

  • There are echocardiographic markers beyond duct size and flow direction that may aid early diagnosis.

  • Cardiac output markers within the first 12 hours of life may predict need for treatment of hsPDA.

Keywords

neonatology - hemodynamics - preterm neonates - cardiac output - pulmonary hemorrhage - intraventricular hemorrhage

Authors' Contributions

The study design and data analysis were undertaken by J.K. and A.K., while data acquisition was a collaborative effort involving J.K. and N.T. The initial draft of the manuscript, including the creation of figures and artwork, was primarily conducted by J.K. Subsequent revisions to the manuscript involved contributions from J.K., A.K., and N.T.




Publication History

Received: 22 August 2023

Accepted: 12 January 2024

Accepted Manuscript online:
18 January 2024

Article published online:
08 February 2024

© 2024. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Hamrick SEG, Sallmon H, Rose AT. et al. Patent ductus arteriosus of the preterm infant. Pediatrics 2020; 146 (05) e20201209
    CrossrefPubMedGoogle Scholar
  • 2 Semberova J, Sirc J, Miletin J. et al. Spontaneous closure of patent ductus arteriosus in infants ≤1500 g. Pediatrics 2017; 140 (02) e20164258
    CrossrefPubMedGoogle Scholar
  • 3 Smith A, El-Khuffash A. Patent ductus arteriosus clinical trials: lessons learned and future directions. Children (Basel) 2021; 8 (01) 47
    PubMedGoogle Scholar
  • 4 Mirza H, Garcia J, McKinley G. et al. Duration of significant patent ductus arteriosus and bronchopulmonary dysplasia in extremely preterm infants. J Perinatol 2019; 39 (12) 1648-1655
    CrossrefPubMedGoogle Scholar
  • 5 Clyman RI, Hills NK, Cambonie G. et al. Patent ductus arteriosus, tracheal ventilation, and the risk of bronchopulmonary dysplasia. Pediatr Res 2022; 91 (03) 652-658
    CrossrefPubMedGoogle Scholar
  • 6 Gentle SJ, Travers CP, Clark M, Carlo WA, Ambalavanan N. patent ductus arteriosus and development of bronchopulmonary dysplasia-associated pulmonary hypertension. Am J Respir Crit Care Med 2023; 207 (07) 921-928
    CrossrefPubMedGoogle Scholar
  • 7 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 (12) CD013278
    PubMedGoogle Scholar
  • 8 Backes CH, Hill KD, Shelton EL. et al. Patent ductus arteriosus: a contemporary perspective for the pediatric and adult cardiac care provider. J Am Heart Assoc 2022; 11 (17) e025784
    CrossrefPubMedGoogle Scholar
  • 9 Ment LR, Oh W, Ehrenkranz RA. et al. Low-dose indomethacin and prevention of intraventricular hemorrhage: a multicenter randomized trial. Pediatrics 1994; 93 (04) 543-550
    CrossrefPubMedGoogle Scholar
  • 10 Schmidt B, Davis P, Moddemann D. et al; Trial of Indomethacin Prophylaxis in Preterms Investigators. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants. N Engl J Med 2001; 344 (26) 1966-1972
    CrossrefPubMedGoogle Scholar
  • 11 Hundscheid T, Onland W, Kooi EMW. et al; BeNeDuctus Trial Investigators. Expectant management or early ibuprofen for patent ductus arteriosus. N Engl J Med 2023; 388 (11) 980-990
    CrossrefPubMedGoogle Scholar
  • 12 Clyman RI, Liebowitz M, Kaempf J. et al; PDA-TOLERATE (PDA: TO LEave it alone or Respond And Treat Early) Trial Investigators. 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
    CrossrefPubMedGoogle Scholar
  • 13 Mitra S, Florez ID, Tamayo ME. et al. Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. JAMA 2018; 319 (12) 1221-1238
    CrossrefPubMedGoogle Scholar
  • 14 Ohlsson A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst Rev 2020; 1 (01) CD010061
    PubMedGoogle Scholar
  • 15 Pavlek LR, Slaughter JL, Berman DP, Backes CH. Catheter-based closure of the patent ductus arteriosus in lower weight infants. Semin Perinatol 2018; 42 (04) 262-268
    CrossrefPubMedGoogle Scholar
  • 16 Scerbo D, Cua CL, Rivera BK. et al. Percutaneous closure of the patent ductus arteriosus in very-low-weight infants. Neoreviews 2020; 21 (07) e469-e478
    CrossrefPubMedGoogle Scholar
  • 17 Kluckow M, Jeffery M, Gill A, Evans N. A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed 2014; 99 (02) F99-F104
    CrossrefPubMedGoogle Scholar
  • 18 de Boode WP, Kluckow M, McNamara PJ, Gupta S. Role of neonatologist-performed echocardiography in the assessment and management of patent ductus arteriosus physiology in the newborn. Semin Fetal Neonatal Med 2018; 23 (04) 292-297
    CrossrefPubMedGoogle Scholar
  • 19 Rozé JC, Cambonie G, Marchand-Martin L. et al; Hemodynamic EPIPAGE 2 Study Group. Association between early screening for patent ductus arteriosus and in-hospital mortality among extremely preterm infants. JAMA 2015; 313 (24) 2441-2448
    CrossrefPubMedGoogle Scholar
  • 20 Lee JH, Greenberg RG, Quek BH. et al. Association between early echocardiography, therapy for patent ductus arteriosus, and outcomes in very low birth weight infants. Cardiol Young 2017; 27 (09) 1732-1739
    CrossrefPubMedGoogle Scholar
  • 21 Saha AK, Sardar SK, Majhi B, Chatterjee S. Clinical and echocardiographic characteristics associated with evolution of patent ductus arteriosus in preterm neonates: a prospective cohort study. J Neonatal Perinatal Med 2022; 15 (03) 537-544
    CrossrefPubMedGoogle Scholar
  • 22 Katheria AC, Truong G, Cousins L, Oshiro B, Finer NN. Umbilical cord milking versus delayed cord clamping in preterm infants. Pediatrics 2015; 136 (01) 61-69
    CrossrefPubMedGoogle Scholar
  • 23 Katheria AC, Leone TA, Woelkers D, Garey DM, Rich W, Finer NN. The effects of umbilical cord milking on hemodynamics and neonatal outcomes in premature neonates. J Pediatr 2014; 164 (05) 1045-1050.e1
    CrossrefPubMedGoogle Scholar
  • 24 Katheria A, Reister F, Essers J. et al. Association of umbilical cord milking vs delayed umbilical cord clamping with death or severe intraventricular hemorrhage among preterm infants. JAMA 2019; 322 (19) 1877-1886
    CrossrefPubMedGoogle Scholar
  • 25 Mitra S, Rønnestad A, Holmstrøm H. Management of patent ductus arteriosus in preterm infants–where do we stand?. Congenit Heart Dis 2013; 8 (06) 500-512
    CrossrefPubMedGoogle Scholar
  • 26 Alverson DC, Eldridge MW, Johnson JD. et al. Effect of patent ductus arteriosus on left ventricular output in premature infants. J Pediatr 1983; 102 (05) 754-757
    CrossrefPubMedGoogle Scholar
  • 27 Lindner W, Seidel M, Versmold HT, Döhlemann C, Riegel KP. Stroke volume and left ventricular output in preterm infants with patent ductus arteriosus. Pediatr Res 1990; 27 (03) 278-281
    CrossrefPubMedGoogle Scholar
  • 28 Walther FJ, Kim DH, Ebrahimi M, Siassi B. Pulsed Doppler measurement of left ventricular output as early predictor of symptomatic patent ductus arteriosus in very preterm infants. Biol Neonate 1989; 56 (03) 121-128
    CrossrefPubMedGoogle Scholar
  • 29 Clyman RI, Hills NK, Liebowitz M, Johng S. Relationship between duration of infant exposure to a moderate-to-large patent ductus arteriosus shunt and the risk of developing bronchopulmonary dysplasia or death before 36 weeks. Am J Perinatol 2020; 37 (02) 216-223
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Jain A, Shah PS. Diagnosis, evaluation, and management of patent ductus arteriosus in preterm neonates. JAMA Pediatr 2015; 169 (09) 863-872
    CrossrefPubMedGoogle Scholar
  • 31 Sallmon H, Koehne P, Hansmann G. Recent advances in the treatment of preterm newborn infants with patent ductus arteriosus. Clin Perinatol 2016; 43 (01) 113-129
    CrossrefPubMedGoogle Scholar
  • 32 Su BH, Lin HY, Chiu HY, Tsai ML, Chen YT, Lu IC. Therapeutic strategy of patent ductus arteriosus in extremely preterm infants. Pediatr Neonatol 2020; 61 (02) 133-141
    CrossrefPubMedGoogle Scholar
  • 33 Paudel G, Joshi V. Echocardiography of the patent ductus arteriosus in premature infant. Congenit Heart Dis 2019; 14 (01) 42-45
    CrossrefPubMedGoogle Scholar
  • 34 Heuchan AM, Young D. Early color Doppler duct diameter and symptomatic patent ductus arteriosus in a cyclo-oxygenase inhibitor naïve population. Acta Paediatr 2013; 102 (03) 254-257
    CrossrefPubMedGoogle Scholar
  • 35 Pees C, Walch E, Obladen M, Koehne P. Echocardiography predicts closure of patent ductus arteriosus in response to ibuprofen in infants less than 28 week gestational age. Early Hum Dev 2010; 86 (08) 503-508
    CrossrefPubMedGoogle Scholar
  • 36 Olsson KW, Jonzon A, Sindelar R. A high ductal flow velocity is associated with successful pharmacological closure of patent ductus arteriosus in infants 22-27 weeks gestational age. Crit Care Res Pract 2012; 2012: 715265
    PubMedGoogle Scholar
  • 37 Su BH, Watanabe T, Shimizu M, Yanagisawa M. Echocardiographic assessment of patent ductus arteriosus shunt flow pattern in premature infants. Arch Dis Child Fetal Neonatal Ed 1997; 77 (01) F36-F40
    CrossrefPubMedGoogle Scholar
  • 38 Su BH, Peng CT, Tsai CH. Echocardiographic flow pattern of patent ductus arteriosus: a guide to indomethacin treatment in premature infants. Arch Dis Child Fetal Neonatal Ed 1999; 81 (03) F197-F200
    CrossrefPubMedGoogle Scholar
  • 39 van Laere D, van Overmeire B, Gupta S. et al; European Special Interest Group 'Neonatologist Performed Echocardiography' (NPE). Application of NPE in the assessment of a patent ductus arteriosus. Pediatr Res 2018; 84 (Suppl. 01) 46-56
    CrossrefPubMedGoogle Scholar
  • 40 Jain A, El-Khuffash AF, Kuipers BCW. et al. Left ventricular function in healthy term neonates during the transitional period. J Pediatr 2017; 182: 197-203.e2
    CrossrefPubMedGoogle Scholar
  • 41 Tsai-Goodman B, Martin RP, Marlow N, Skinner JR. The repeatability of echocardiographic determination of right ventricular output in the newborn. Cardiol Young 2001; 11 (02) 188-194
    CrossrefPubMedGoogle Scholar
  • 42 Bischoff AR, Giesinger RE, Stanford AH, Ashwath R, McNamara PJ. Assessment of superior vena cava flow and cardiac output in different patterns of patent ductus arteriosus shunt. Echocardiography 2021; 38 (09) 1524-1533
    CrossrefPubMedGoogle Scholar
  • 43 Sloot SC, de Waal KA, van der Lee JH, van Kaam AH. Central blood flow measurements in stable preterm infants after the transitional period. Arch Dis Child Fetal Neonatal Ed 2010; 95 (05) F369-F372
    CrossrefPubMedGoogle Scholar
  • 44 Jain A, Mohamed A, El-Khuffash A. et al. A comprehensive echocardiographic protocol for assessing neonatal right ventricular dimensions and function in the transitional period: normative data and z scores. J Am Soc Echocardiogr 2014; 27 (12) 1293-1304
    CrossrefPubMedGoogle Scholar
  • 45 Evans N, Kluckow M. Early determinants of right and left ventricular output in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed 1996; 74 (02) F88-F94
    CrossrefPubMedGoogle Scholar
  • 46 Clark SJ, Yoxall CW, Subhedar NV. Right ventricular volume measurements in ventilated preterm neonates. Pediatr Cardiol 2004; 25 (02) 149-153
    CrossrefPubMedGoogle Scholar
  • 47 Schwarz CE, Livingstone V, O'Toole JM, Healy DB, Panaviene J, Dempsey EM. Agreement of cardiac output estimates between electrical cardiometry and transthoracic echocardiography in very preterm infants. Neonatology 2022; 119 (05) 594-601
    CrossrefPubMedGoogle Scholar
  • 48 El Hajjar M, Vaksmann G, Rakza T, Kongolo G, Storme L. Severity of the ductal shunt: a comparison of different markers. Arch Dis Child Fetal Neonatal Ed 2005; 90 (05) F419-F422
    CrossrefPubMedGoogle Scholar
  • 49 Breatnach CR, Franklin O, James AT, McCallion N, El-Khuffash A. The impact of a hyperdynamic left ventricle on right ventricular function measurements in preterm infants with a patent ductus arteriosus. Arch Dis Child Fetal Neonatal Ed 2017; 102 (05) F446-F450
    CrossrefPubMedGoogle Scholar
  • 50 Kluckow M, Evans N. Early echocardiographic prediction of symptomatic patent ductus arteriosus in preterm infants undergoing mechanical ventilation. J Pediatr 1995; 127 (05) 774-779
    CrossrefPubMedGoogle Scholar
  • 51 Kwinta P, Rudziński A, Kruczek P, Kordon Z, Pietrzyk JJ. Can early echocardiographic findings predict patent ductus arteriosus?. Neonatology 2009; 95 (02) 141-148
    CrossrefPubMedGoogle Scholar
  • 52 Sehgal A, Paul E, Menahem S. Functional echocardiography in staging for ductal disease severity: role in predicting outcomes. Eur J Pediatr 2013; 172 (02) 179-184
    CrossrefPubMedGoogle Scholar