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Patent ductus arteriosus and cerebral, cardiac, and gut hemodynamics in premature neonates

  • J.L. Ruoss
    Affiliations
    Division of Neonatology, Department of Pediatrics, University of Florida, 1600 SW Archer Rd, Gainesville, FL, 32608, USA
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  • C. Bazacliu
    Affiliations
    Division of Neonatology, Department of Pediatrics, University of Florida, 1600 SW Archer Rd, Gainesville, FL, 32608, USA
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  • R.E. Giesinger
    Affiliations
    Division of Neonatology, Department of Pediatrics, University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA
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  • P.J. McNamara
    Correspondence
    Corresponding author. Division of Neonatology, Department of Pediatrics and Internal Medicine, University of Iowa, 200 Hawkin's drive, Iowa city, Iowa 52242, USA.
    Affiliations
    Division of Neonatology, Department of Pediatrics, University of Iowa, 200 Hawkins Drive, Iowa City, IA, 52242, USA

    Department of Internal Medicine, University of Iowa, 8803 John Pappajohn Pavillion 200 Hawkins Drive, Iowa City, IA, 52242, USA
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      Abstract

      Patent ductus arteriosus is associated with multiple comorbidities in premature infants, however a causal link or strategy to decrease these morbidities has not been found. The association between the patent ductus arteriosus and morbidities has biologic plausibility as, like any cardiac mixing lesion, a significant systemic to pulmonic shunt may lead to pulmonary over-circulation and systemic hypoperfusion. Understanding the underlying pathophysiology of associated morbidities in the setting of a patent ductus arteriosus may aid in risk stratifying infants and offer a patient targeted approach to infants with a pathological ductal shunt. While the deleterious impact of increased pulmonary blood flow maybe easier to identify, the impact on end-organ perfusion is more challenging. In this review, we will discuss the pathophysiology of a hemodynamically significant patent ductus arteriosus in premature infants, impact on end-organ perfusion and associated morbidities, and novel modalities to assess shunt volume and effect on end-organ perfusion.

      Keywords

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      References

        • El-Khuffash A.
        • James A.T.
        • Corcoran J.D.
        • Dicker P.
        • Franklin O.
        • Elsayed Y.N.
        • Ting J.Y.
        • Sehgal A.
        • Malikiwi A.
        • Harabor A.
        • Soraisham A.S.
        • McNamara P.J.
        A patent ductus arteriosus severity score predicts chronic Lung disease or death before discharge.
        J Pediatr. 2015; 167 (e2. Epub 2015/10/18\PubMed PMID: 26474706): 1354-1361https://doi.org/10.1016/j.jpeds.2015.09.028
        • Lokku A.
        • Mirea L.
        • Lee S.K.
        • Shah P.S.
        • Canadian Neonatal N.
        Trends and outcomes of patent ductus arteriosus treatment in very preterm infants in Canada.
        Am J Perinatol. 2017; 34 (PubMed PMID: 27649293): 441-450https://doi.org/10.1055/s-0036-1593351
        • Sankar M.N.
        • Bhombal S.
        • Benitz W.E.
        PDA: to treat or not to treat.
        Congenit Heart Dis. 2019; 14 (Epub 2019/02/28, PubMed PMID: 30811796): 46-51https://doi.org/10.1111/chd.12708
        • de Boode W.P.
        • Kluckow M.
        • McNamara P.J.
        • 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 (PubMed PMID: 29551482): 292-297https://doi.org/10.1016/j.siny.2018.03.007
        • Skelton R.
        • Evans N.
        • Smythe J.
        A blinded comparison of clinical and echocardiographic evaluation of the preterm infant for patent ductus arteriosus.
        J Paediatr Child Health. 1994; 30 (Epub 1994/10/01. PubMed PMID: 7833075): 406-411
        • Koch J.
        • Hensley G.
        • Roy L.
        • Brown S.
        • Ramaciotti C.
        • Rosenfeld C.R.
        Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less.
        Pediatrics. 2006; 117 (Epub 2006/04/06, PubMed PMID: 16585305): 1113-1121https://doi.org/10.1542/peds.2005-1528
        • Semberova J.
        • Sirc J.
        • Miletin J.
        • Kucera J.
        • Berka I.
        • Sebkova S.
        • O'Sullivan S.
        • Franklin O.
        • Stranak Z.
        Spontaneous closure of patent ductus arteriosus in infants </=1500 g.
        Pediatrics. 2017; 140 (Epub 2017/07/14, PubMed PMID: 28701390)https://doi.org/10.1542/peds.2016-4258
        • Hagadorn J.I.
        • Bennett M.V.
        • Brownell E.A.
        • Payton K.S.E.
        • Benitz W.E.
        • Lee H.C.
        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 (PubMed PMID: 30243544): 225-233 e1https://doi.org/10.1016/j.jpeds.2018.07.025
        • Hagadorn J.I.
        • Brownell E.A.
        • Trzaski J.M.
        • Johnson K.R.
        • Lainwala S.
        • Campbell B.T.
        • Herbst K.W.
        Trends and variation in management and outcomes of very low-birth-weight infants with patent ductus arteriosus.
        Pediatr Res. 2016; 80 (Epub 2016/08/11, PubMed PMID: 27509008): 785-792https://doi.org/10.1038/pr.2016.166
        • Sung S.I.
        • Chang Y.S.
        • Chun J.Y.
        • Yoon S.A.
        • Yoo H.S.
        • Ahn S.Y.
        • Park W.S.
        Mandatory closure versus nonintervention for patent ductus arteriosus in very preterm infants.
        J Pediatr. 2016; 177 (e1. Epub 2016/07/28, PubMed PMID: 27453374): 66-71https://doi.org/10.1016/j.jpeds.2016.06.046
        • Roze J.C.
        • Cambonie G.
        • Marchand-Martin L.
        • Gournay V.
        • Durrmeyer X.
        • Durox M.
        • Storme L.
        • Porcher R.
        • Ancel P.Y.
        • Hemodynamic E.S.G.
        Association between early screening for patent ductus arteriosus and in-hospital mortality among extremely preterm infants.
        J Am Med Assoc. 2015; 313 (Epub 2015/06/24, PubMed PMID: 26103028): 2441-2448https://doi.org/10.1001/jama.2015.6734
        • Sellmer A.
        • Bjerre J.V.
        • Schmidt M.R.
        • McNamara P.J.
        • Hjortdal V.E.
        • Host B.
        • Bech B.H.
        • Henriksen T.B.
        Morbidity and mortality in preterm neonates with patent ductus arteriosus on day 3.
        Arch Dis Child Fetal Neonatal Ed. 2013; 98 (Epub 2013/07/31, PubMed PMID: 23893268): F505-F510https://doi.org/10.1136/archdischild-2013-303816
        • Fink D.
        • El-Khuffash A.
        • McNamara P.J.
        • Nitzan I.
        • Hammerman C.
        Tale of two patent ductus arteriosus severity scores: similarities and differences.
        Am J Perinatol. 2018; 35 (PubMed PMID: 28787748): 55-58https://doi.org/10.1055/s-0037-1605576
        • Deshpande P.
        • Baczynski M.
        • McNamara P.J.
        • Jain A.
        Patent ductus arteriosus: the physiology of transition.
        Semin Fetal Neonatal Med. 2018; 23 (PubMed PMID: 29779927): 225-231https://doi.org/10.1016/j.siny.2018.05.001
        • Weisz D.E.
        • Giesinger R.E.
        Surgical management of a patent ductus arteriosus: is this still an option?.
        Semin Fetal Neonatal Med. 2018; 23 (PubMed PMID: 29636280): 255-266https://doi.org/10.1016/j.siny.2018.03.003
        • van Laere D.
        • van Overmeire B.
        • Gupta S.
        • El-Khuffash A.
        • Savoia M.
        • McNamara P.J.
        • Schwarz C.E.
        • de Boode W.P.
        European special interest group 'neonatologist performed E. Application of NPE in the assessment of a patent ductus arteriosus.
        Pediatr Res. 2018; 84 (PubMed PMID: 30072803; PMCID: PMC6257219): 46-56https://doi.org/10.1038/s41390-018-0077-x
        • Smith A.
        • McNamara P.J.
        • El-Khuffash A.F.
        Non-pharmacological management of a hemodynamically significant patent ductus arteriosus.
        Semin Fetal Neonatal Med. 2018; 23 (PubMed PMID: 29580939): 245-249https://doi.org/10.1016/j.siny.2018.03.008
        • Jain A.
        • Shah P.S.
        Diagnosis, evaluation, and management of patent ductus arteriosus in preterm neonates.
        JAMA Pediatr. 2015; 169 (Epub 2015/07/15, PubMed PMID: 26168357): 863-872https://doi.org/10.1001/jamapediatrics.2015.0987
        • Hiedl S.
        • Schwepcke A.
        • Weber F.
        • Genzel-Boroviczeny O.
        Microcirculation in preterm infants: profound effects of patent ductus arteriosus.
        J Pediatr. 2010; 156 (Epub 2009/10/23, PubMed PMID: 19846115): 191-196https://doi.org/10.1016/j.jpeds.2009.08.034
        • van der Laan M.E.
        • Roofthooft M.T.
        • Fries M.W.
        • Berger R.M.
        • Schat T.E.
        • van Zoonen A.G.
        • Tanis J.C.
        • Bos A.F.
        • Kooi E.M.
        A hemodynamically significant patent ductus arteriosus does not affect cerebral or renal tissue oxygenation in preterm infants.
        Neonatology. 2016; 110 (Epub 2016/04/19, PubMed PMID: 27088709): 141-147https://doi.org/10.1159/000445101
        • Kluckow M.
        The pathophysiology of low systemic blood flow in the preterm infant.
        Front Pediatr. 2018; 6 (PubMed PMID: 29503814; PMCID: PMC5820306): 29https://doi.org/10.3389/fped.2018.00029
        • Laughon M.
        • Bose C.
        • Allred E.
        • O'Shea T.M.
        • Van Marter L.J.
        • Bednarek F.
        • Leviton A.
        • Investigators E.S.
        Factors associated with treatment for hypotension in extremely low gestational age newborns during the first postnatal week.
        Pediatrics. 2007; 119 (PubMed PMID: 17272616; PMCID: PMC2803046): 273-280https://doi.org/10.1542/peds.2006-1138
        • Clyman R.I.
        • Mauray F.
        • Heymann M.A.
        • Roman C.
        Cardiovascular effects of patent ductus arteriosus in preterm lambs with respiratory distress.
        J Pediatr. 1987; 111 (Epub 1987/10/01, PubMed PMID: 3655990): 579-587https://doi.org/10.1016/s0022-3476(87)80126-9
        • Liebowitz M.
        • Clyman R.I.
        Prophylactic indomethacin compared with delayed conservative management of the patent ductus arteriosus in extremely preterm infants: effects on neonatal outcomes.
        J Pediatr. 2017; 187 (e1. Epub 2017/04/12, PubMed PMID: 28396025; PMCID: PMC5533630): 119-126https://doi.org/10.1016/j.jpeds.2017.03.021
        • Kluckow M.
        • Evans N.
        Low systemic blood flow in the preterm infant.
        Semin Neonatol. 2001; 6 (Epub 2001/02/13, PubMed PMID: 11162287): 75-84https://doi.org/10.1053/siny.2000.0035
        • Evans N.
        • Iyer P.
        Change in blood pressure after treatment of patent ductus arteriosus with indomethacin.
        Arch Dis Child. 1993; 68 (Epub 1993/05/01, PubMed PMID: 8323360; PMCID: PMC1029308): 584-587https://doi.org/10.1136/adc.68.5_spec_no.584
        • Noori S.
        • McCoy M.
        • Anderson M.P.
        • Ramji F.
        • Seri I.
        Changes in cardiac function and cerebral blood flow in relation to peri/intraventricular hemorrhage in extremely preterm infants.
        J Pediatr. 2014; 164 (e1-3. Epub 2013/11/05, PubMed PMID: 24183212): 264-270https://doi.org/10.1016/j.jpeds.2013.09.045
        • Evans N.
        • Kluckow M.
        Early ductal shunting and intraventricular haemorrhage in ventilated preterm infants.
        Arch Dis Child Fetal Neonatal Ed. 1996; 75 (Epub 1996/11/01, PubMed PMID: 8976684; PMCID: PMC1061197): F183-F186https://doi.org/10.1136/fn.75.3.f183
        • Kluckow M.
        • Evans N.
        Low superior vena cava flow and intraventricular haemorrhage in preterm infants.
        Arch Dis Child Fetal Neonatal Ed. 2000; 82 (Epub 2000/05/05. PubMed PMID: 10794784; PMCID: PMC1721081): F188-F194
        • Noori S.
        • Seri I.
        Hemodynamic antecedents of peri/intraventricular hemorrhage in very preterm neonates.
        Semin Fetal Neonatal Med. 2015; 20 (Epub 2015/03/31, PubMed PMID: 25818879): 232-237https://doi.org/10.1016/j.siny.2015.02.004
        • Patel J.
        • Roberts I.
        • Azzopardi D.
        • Hamilton P.
        • Edwards A.D.
        Randomized double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus.
        Pediatr Res. 2000; 47 (Epub 2000/01/07. PubMed PMID: 10625080): 36-42
        • Romagnoli C.
        • De Carolis M.P.
        • Papacci P.
        • Polimeni V.
        • Luciano R.
        • Piersigilli F.
        • Delogu A.B.
        • Tortorolo G.
        Effects of prophylactic ibuprofen on cerebral and renal hemodynamics in very preterm neonates.
        Clin Pharmacol Ther. 2000; 67 (Epub 2000/06/29, PubMed PMID: 10872650): 676-683https://doi.org/10.1067/mcp.2000.107048
        • Schmidt B.
        • Davis P.
        • Moddemann D.
        • Ohlsson A.
        • Roberts R.S.
        • Saigal S.
        • Solimano A.
        • Vincer M.
        • Wright L.L.
        Trial of Indomethacin Prophylaxis in Preterms I. Long-term effects of indomethacin prophylaxis in extremely-low-birth-weight infants.
        N Engl J Med. 2001; 344 (Epub 2001/06/30, PubMed PMID: 11430325): 1966-1972https://doi.org/10.1056/NEJM200106283442602
        • Schena F.
        • Francescato G.
        • Cappelleri A.
        • Picciolli I.
        • Mayer A.
        • Mosca F.
        • Fumagalli M.
        Association between hemodynamically significant patent ductus arteriosus and bronchopulmonary dysplasia.
        J Pediatr. 2015; 166 (Epub 2015/04/18, PubMed PMID: 25882876): 1488-1492https://doi.org/10.1016/j.jpeds.2015.03.012
        • Lemmers P.M.
        • Benders M.J.
        • D'Ascenzo R.
        • Zethof J.
        • Alderliesten T.
        • Kersbergen K.J.
        • Isgum I.
        • de Vries L.S.
        • Groenendaal F.
        • van Bel F.
        Patent ductus arteriosus and brain volume.
        Pediatrics. 2016; 137 (PubMed PMID: 27030421)https://doi.org/10.1542/peds.2015-3090
        • Lemmers P.M.
        • Toet M.C.
        • van Bel F.
        Impact of patent ductus arteriosus and subsequent therapy with indomethacin on cerebral oxygenation in preterm infants.
        Pediatrics. 2008; 121 (Epub 2008/01/02, PubMed PMID: 18166568): 142-147https://doi.org/10.1542/peds.2007-0925
        • Kluckow M.
        • Lemmers P.
        Hemodynamic assessment of the patent ductus arteriosus: beyond ultrasound.
        Semin Fetal Neonatal Med. 2018; 23 (PubMed PMID: 29730050): 239-244https://doi.org/10.1016/j.siny.2018.04.002
        • Clyman R.I.
        • Liebowitz M.
        • Kaempf J.
        • Erdeve O.
        • Bulbul A.
        • Hakansson S.
        • Lindqvist J.
        • Farooqi A.
        • Katheria A.
        • Sauberan J.
        • Singh J.
        • Nelson K.
        • Wickremasinghe A.
        • Dong L.
        • Hassinger D.C.
        • Aucott S.W.
        • Hayashi M.
        • Heuchan A.M.
        • Carey W.A.
        • Derrick M.
        • Fernandez E.
        • Sankar M.
        • Leone T.
        • Perez J.
        • Serize A.
        • Investigators P.-T.T.
        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 (Epub 2018/10/21, PubMed PMID: 30340932; PMCID: PMC6502709): 41-48 e6https://doi.org/10.1016/j.jpeds.2018.09.012
        • Neu J.
        • Walker W.A.
        Necrotizing enterocolitis.
        N Engl J Med. 2011; 364 (Epub 2011/01/21, PubMed PMID: 21247316; PMCID: PMC3628622): 255-264https://doi.org/10.1056/NEJMra1005408
        • Wong S.N.
        • Lo R.N.
        • Hui P.W.
        Abnormal renal and splanchnic arterial Doppler pattern in premature babies with symptomatic patent ductus arteriosus.
        J Ultrasound Med. 1990; 9 (PubMed PMID: 2407859): 125-130https://doi.org/10.7863/jum.1990.9.3.125
        • Dollberg S.
        • Lusky A.
        • Reichman B.
        Patent ductus arteriosus, indomethacin and necrotizing enterocolitis in very low birth weight infants: a population-based study.
        J Pediatr Gastroenterol Nutr. 2005; 40 (Epub 2005/02/09. PubMed PMID: 15699694): 184-188
        • McCurnin D.
        • Clyman R.I.
        Effects of a patent ductus arteriosus on postprandial mesenteric perfusion in premature baboons.
        Pediatrics. 2008; 122 (Epub 2008/11/13, PubMed PMID: 19001037; PMCID: PMC2597012): e1262-e1267https://doi.org/10.1542/peds.2008-2045
        • Meyers R.L.
        • Alpan G.
        • Lin E.
        • Clyman R.I.
        Patent ductus arteriosus, indomethacin, and intestinal distension: effects on intestinal blood flow and oxygen consumption.
        Pediatr Res. 1991; 29 (Epub 1991/06/01. PubMed PMID: 1866213): 569-574
        • Coombs R.C.
        • Morgan M.E.
        • Durbin G.M.
        • Booth I.W.
        • McNeish A.S.
        Gut blood flow velocities in the newborn: effects of patent ductus arteriosus and parenteral indomethacin.
        Arch Dis Child. 1990; 65 (PubMed PMID: 2241229; PMCID: PMC1590251): 1067-1071https://doi.org/10.1136/adc.65.10_spec_no.1067
        • Gordon P.
        • Christensen R.
        • Weitkamp J.H.
        • Maheshwari A.
        Mapping the new world of necrotizing enterocolitis (NEC): review and opinion.
        EJ Neonatol Res. 2012; 2 (PubMed PMID: 23730536; PMCID: PMC3666872): 145-172
        • Cassady G.
        • Crouse D.T.
        • Kirklin J.W.
        • Strange M.J.
        • Joiner C.H.
        • Godoy G.
        • Odrezin G.T.
        • Cutter G.R.
        • Kirklin J.K.
        • Pacifico A.D.
        • et al.
        A randomized, controlled trial of very early prophylactic ligation of the ductus arteriosus in babies who weighed 1000 g or less at birth.
        N Engl J Med. 1989; 320 (Epub 1989/06/08, PubMed PMID: 2498657): 1511-1516https://doi.org/10.1056/nejm198906083202302
        • Kabra N.S.
        • Schmidt B.
        • Roberts R.S.
        • Doyle L.W.
        • Papile L.
        • Fanaroff A.
        Trial of Indomethacin Prophylaxis in Preterms I. 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 Pediatr. 2007; 150 (34 e1. Epub 2007/02/20, PubMed PMID: 17307535): 229-234https://doi.org/10.1016/j.jpeds.2006.11.039
        • Mirea L.
        • Sankaran K.
        • Seshia M.
        • Ohlsson A.
        • Allen A.C.
        • Aziz K.
        • Lee S.K.
        • Shah P.S.
        • Canadian Neonatal N.
        Treatment of patent ductus arteriosus and neonatal mortality/morbidities: adjustment for treatment selection bias.
        J Pediatr. 2012; 161 (PubMed PMID: 22703954): 689-694https://doi.org/10.1016/j.jpeds.2012.05.007
        • Jegatheesan P.
        • Ianus V.
        • Buchh B.
        • Yoon G.
        • Chorne N.
        • Ewig A.
        • Lin E.
        • Fields S.
        • Moon-Grady A.
        • Tacy T.
        • Milstein J.
        • Schreiber M.
        • Padbury J.
        • Clyman R.
        Increased indomethacin dosing for persistent patent ductus arteriosus in preterm infants: a multicenter, randomized, controlled trial.
        J Pediatr. 2008; 153 (Epub 2008/06/07, PubMed PMID: 18534218): 183-189https://doi.org/10.1016/j.jpeds.2008.01.031
        • de Freitas Martins F.
        • Ibarra Rios D.
        • MHFR
        • Javed H.
        • Weisz D.
        • Jain A.
        • de Andrade Lopes J.M.
        • McNamara P.J.
        Relationship of patent ductus arteriosus size to echocardiographic markers of shunt volume.
        J Pediatr. 2018; 202 (e3. Epub 2018/08/18, PubMed PMID: 30115452): 50-55https://doi.org/10.1016/j.jpeds.2018.06.045
        • Schwarz C.E.
        • Preusche A.
        • Wolf M.
        • Poets C.F.
        • Franz A.R.
        Prospective observational study on assessing the hemodynamic relevance of patent ductus arteriosus with frequency domain near-infrared spectroscopy.
        BMC Pediatr. 2018; 18 (Epub 2018/02/18, PubMed PMID: 29452581; PMCID: PMC5816508): 66https://doi.org/10.1186/s12887-018-1054-6
        • Broadhouse K.M.
        • Price A.N.
        • Durighel G.
        • Cox D.J.
        • Finnemore A.E.
        • Edwards A.D.
        • Hajnal J.V.
        • Groves A.M.
        Assessment of PDA shunt and systemic blood flow in newborns using cardiac MRI.
        NMR Biomed. 2013; 26 (Epub 2013/02/16, PubMed PMID: 23412748): 1135-1141https://doi.org/10.1002/nbm.2927
        • Chock V.Y.
        • Rose L.A.
        • Mante J.V.
        • Punn R.
        Near-infrared spectroscopy for detection of a significant patent ductus arteriosus.
        Pediatr Res. 2016; 80 (Epub 2016/11/02, PubMed PMID: 27603562): 675-680https://doi.org/10.1038/pr.2016.148
        • Alderliesten T.
        • Dix L.
        • Baerts W.
        • Caicedo A.
        • van Huffel S.
        • Naulaers G.
        • Groenendaal F.
        • van Bel F.
        • Lemmers P.
        Reference values of regional cerebral oxygen saturation during the first 3 days of life in preterm neonates.
        Pediatr Res. 2016; 79 (PubMed PMID: 26389823): 55-64https://doi.org/10.1038/pr.2015.186
        • Dix L.
        • Molenschot M.
        • Breur J.
        • de Vries W.
        • Vijlbrief D.
        • Groenendaal F.
        • van Bel F.
        • Lemmers P.
        Cerebral oxygenation and echocardiographic parameters in preterm neonates with a patent ductus arteriosus: an observational study.
        Arch Dis Child Fetal Neonatal Ed. 2016; 101 (PubMed PMID: 27034323): F520-F526https://doi.org/10.1136/archdischild-2015-309192
        • Mileder L.P.
        • Muller T.
        • Baik-Schneditz N.
        • Pansy J.
        • Schwaberger B.
        • Binder-Heschl C.
        • Urlesberger B.
        • Pichler G.
        Influence of ductus arteriosus on peripheral muscle oxygenation and perfusion in neonates.
        Physiol Meas. 2017; 39 (Epub 2017/11/22, PubMed PMID: 29161235)015003https://doi.org/10.1088/1361-6579/aa9c3b
        • Weisz D.E.
        • McNamara P.J.
        • El-Khuffash A.
        Cardiac biomarkers and haemodynamically significant patent ductus arteriosus in preterm infants.
        Early Hum Dev. 2017; 105 (PubMed PMID: 27998626): 41-47https://doi.org/10.1016/j.earlhumdev.2016.12.007
        • El-Khuffash A.F.
        • Slevin M.
        • McNamara P.J.
        • Molloy E.J.
        • Troponin T.
        N-terminal pro natriuretic peptide and a patent ductus arteriosus scoring system predict death before discharge or neurodevelopmental outcome at 2 years in preterm infants.
        Arch Dis Child Fetal Neonatal Ed. 2011; 96 (PubMed PMID: 21071684): F133-F137https://doi.org/10.1136/adc.2010.185967
        • Torigoe T.
        • Sato S.
        • Nagayama Y.
        • Sato T.
        • Yamazaki H.
        Influence of patent ductus arteriosus and ventilators on electrical velocimetry for measuring cardiac output in very-low/low birth weight infants.
        J Perinatol. 2015; 35 (Epub 2015/01/31, PubMed PMID: 25634518): 485-489https://doi.org/10.1038/jp.2014.245
        • Choi B.M.
        • Lee K.H.
        • Eun B.L.
        • Yoo K.H.
        • Hong Y.S.
        • Son C.S.
        • Lee J.W.
        Utility of rapid B-type natriuretic peptide assay for diagnosis of symptomatic patent ductus arteriosus in preterm infants.
        Pediatrics. 2005; 115 (PubMed PMID: 15687418): e255-e261https://doi.org/10.1542/peds.2004-1837
        • El-Khuffash A.F.
        • Amoruso M.
        • Culliton M.
        • Molloy E.J.
        N-terminal pro-B-type natriuretic peptide as a marker of ductal haemodynamic significance in preterm infants: a prospective observational study.
        Arch Dis Child Fetal Neonatal Ed. 2007; 92 (PubMed PMID: 17712194; PMCID: PMC2675377): F421-F422https://doi.org/10.1136/adc.2007.119701
        • El-Khuffash A.F.
        • Molloy E.J.
        Influence of a patent ductus arteriosus on cardiac troponin T levels in preterm infants.
        J Pediatr. 2008; 153 (Epub 2008/06/07, PubMed PMID: 18534211): 350-353https://doi.org/10.1016/j.jpeds.2008.04.014
        • Hsu K.H.
        • Nguyen J.
        • Dekom S.
        • Ramanathan R.
        • Noori S.
        Effects of patent ductus arteriosus on organ blood flow in infants born very preterm: a prospective study with serial echocardiography.
        J Pediatr. 2019; (Epub 2019/10/16, PubMed PMID: 31610928)https://doi.org/10.1016/j.jpeds.2019.08.057
        • Majed B.
        • Bateman D.A.
        • Uy N.
        • Lin F.
        Patent ductus arteriosus is associated with acute kidney injury in the preterm infant.
        Pediatr Nephrol. 2019; 34 (Epub 2019/02/02, PubMed PMID: 30706125): 1129-1139https://doi.org/10.1007/s00467-019-4194-5
        • Sellmer A.
        • Bech B.H.
        • Bjerre J.V.
        • Schmidt M.R.
        • Hjortdal V.E.
        • Esberg G.
        • Rittig S.
        • Henriksen T.B.
        Urinary Neutrophil gelatinase-associated Lipocalin in the evaluation of patent ductus arteriosus and AKI in very preterm neonates: a cohort study.
        BMC Pediatr. 2017; 17 (Epub 2017/01/11, PubMed PMID: 28068947; PMCID: PMC5223413): 7https://doi.org/10.1186/s12887-016-0761-0
        • West C.R.
        • Groves A.M.
        • Williams C.E.
        • Harding J.E.
        • Skinner J.R.
        • Kuschel C.A.
        • Battin M.R.
        Early low cardiac output is associated with compromised electroencephalographic activity in very preterm infants.
        Pediatr Res. 2006; 59 (Epub 2006/03/22, ad. PubMed PMID: 16549539): 610-615https://doi.org/10.1203/01.pdr.0000203095.06442
        • Pereira J.
        • Sburlea A.I.
        • Muller-Putz G.R.
        EEG patterns of self-paced movement imaginations towards externally-cued and internally-selected targets.
        Sci Rep. 2018; 8 (Epub 2018/09/08, PubMed PMID: 30190543; PMCID: PMC6127278): 13394https://doi.org/10.1038/s41598-018-31673-2
        • Kaempf J.W.
        • Wu Y.X.
        • Kaempf A.J.
        • Kaempf A.M.
        • Wang L.
        • Grunkemeier G.
        What happens when the patent ductus arteriosus is treated less aggressively in very low birth weight infants?.
        J Perinatol. 2012; 32 (Epub 2011/08/06, PubMed PMID: 21818064): 344-348https://doi.org/10.1038/jp.2011.102