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Factors Associated With in Utero Demise of Fetuses That Have Underlying Cardiac Pathologies

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Abstract

Factors associated with in utero fetal demise (IUFD) of fetuses that have underlying cardiac pathologies are largely unknown. This case–control study aimed to define the prevalence of IUFD in fetuses with a diagnosis of cardiac pathologies and to identify prenatal predictors of IUFD. Between January 2004 and December 2010, 74 IUFD cases [4.6 %; 95 % confidence interval (CI) 3.7–5.8 %] were identified from 1,584 cases with a diagnosis of structural or functional cardiac lesions in the Hospital for Sick Children database. The cases were divided into right-sided (N = 28), left-sided (N = 23), great artery (N = 8), and miscellaneous (N = 15) groups. The control subjects (1:1 ratio) were fetuses that had cardiac pathology diagnosed within 48 h of the IUFD case. Multivariable regression models were used to determine echocardiographic predictors of IUFD. The prevalence of IUFD was greatest in hypertrophic cardiomyopathy (8/16, 50 %) and Ebstein’s anomaly/tricuspid dysplasia (4/15, 27 %) and lowest in transposition of the great arteries (2/85, 1 %). The findings showed IUFD to be associated with hydrops in 17 (23 %) of the 74 cases and arrhythmia in 11 (15 %) of the 74 cases. The factors identified by univariable logistic regression analyses were right ventricular dysfunction [odds ratio (OR) 2.7; p = 0.001], left ventricular dysfunction (OR 1.8; p = 0.007), umbilical vein pulsations (OR 10.9; p = 0.002), and abnormal ductus venosus flow (OR 3.3; p = 0.01). The factors associated with IUFD in multivariable logistic regression models were cardiomegaly (OR 5.6; p = 0.01), hydrops (OR 29.5; p = 0.001), pericardial effusion (OR 4.1; p = 0.06), and extracardiac abnormalities (OR 7.2; p < 0.001). The prevalence of IUFD is greatest in conditions affecting the ventricular myocardium. The onset of IUFD appears to be related initially to right ventricular dysfunction. Closer surveillance is recommended for lesions at risk of IUFD.

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Abbreviations

CHD:

Congenital heart disease

TTTS:

Twin–twin transfusion syndrome

RV:

Right ventricle

LV:

Left ventricle

TV:

Tricuspid valve

IUFD:

In utero fetal demise

References

  1. Ahmad N, Kantor PF, Grosse-Wortmann L, Seller N, Jaeggi ET, Friedberg MK, Mertens L (2012) Influence of RV restrictive physiology on LV diastolic function in children after tetralogy of Fallot repair. J Am Soc Echocardiogr 25:866–873

    Article  PubMed  Google Scholar 

  2. Anderson PA, Manring A, Glick KL, Crenshaw CC Jr (1982) Biophysics of the developing heart: III. A comparison of the left ventricular dynamics of the fetal and neonatal lamb heart. Am J Obstet Gynecol 143:195–203

    CAS  PubMed  Google Scholar 

  3. Apitz C, Webb GD, Redington AN (2009) Tetralogy of fallot. Lancet 374:1462–1471

    Article  CAS  PubMed  Google Scholar 

  4. Bulkley BH, Weisfeldt ML, Hutchins GM (1977) Asymmetric septal hypertrophy and myocardial fiber disarray: features of normal, developing, and malformed hearts. Circulation 56:292–298

    Article  CAS  PubMed  Google Scholar 

  5. Bulkley BH, D’Amico B, Taylor AL (1983) Extensive myocardial fiber disarray in aortic and pulmonary atresia: relevance to hypertrophic cardiomyopathy. Circulation 67:191–198

    Article  CAS  PubMed  Google Scholar 

  6. Eronen M (1997) Outcome of fetuses with heart disease diagnosed in utero. Arch Dis Child Fetal Neonatal Ed 77:F41–F46

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Fesslova V, Villa L, Nava S, Boschetto C, Redaelli C, Mannarino S (2002) Spectrum and outcome of atrioventricular septal defect in fetal life. Cardiol Young 12:18–26

    Article  PubMed  Google Scholar 

  8. Fogel MA, Weinberg PM, Gupta KB, Rychik J, Hubbard A, Hoffman EA, Haselgrove J (1998) Mechanics of the single left ventricle: a study in ventricular–ventricular interaction II. Circulation 98:330–338

    Article  CAS  PubMed  Google Scholar 

  9. Gardiner HM, Pasquini L, Wolfenden J, Barlow A, Li W, Kulinskaya E, Henein M (2006) Myocardial tissue Doppler and long-axis function in the fetal heart. Int J Cardiol 113:39–47

    Article  PubMed  Google Scholar 

  10. Ghai A, Silversides C, Harris L, Webb GD, Siu SC, Therrien J (2002) Left ventricular dysfunction is a risk factor for sudden cardiac death in adults late after repair of tetralogy of Fallot. J Am Coll Cardiol 40:1675–1680

    Article  PubMed  Google Scholar 

  11. Hirji A, Bernasconi A, McCrindle BW, Dunn E, Gurofsky R, Manlhiot C, Miner SE, Kingdom JC, Jaeggi ET, Van Arsdell G, Nield LE (2010) Outcomes of prenatally diagnosed tetralogy of Fallot: implications for valve-sparing repair versus transannular patch. Can J Cardiol 26:e1–e6

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Huggon IC, Cook AC, Smeeton NC, Magee AG, Sharland GK (2000) Atrioventricular septal defects diagnosed in fetal life: associated cardiac and extracardiac abnormalities and outcome. J Am Coll Cardiol 36:593–601

    Article  CAS  PubMed  Google Scholar 

  13. Ilercil A, Barack J, Malone MA, Barold SS, Herweg B (2006) Association of noncompaction of left ventricular myocardium with Ebstein’s anomaly. Echocardiography 23:432–433

    Article  PubMed  Google Scholar 

  14. Ishii T, McElhinney DB, Harrild DM, Marcus EN, Sahn DJ, Truong U, Tworetzky W (2012) Circumferential and longitudinal ventricular strain in the normal human fetus. J Am Soc Echocardiogr 25:105–111

    Article  PubMed  Google Scholar 

  15. Jaeggi ET, Hamilton RM, Silverman ED, Zamora SA, Hornberger LK (2002) Outcome of children with fetal, neonatal, or childhood diagnosis of isolated congenital atrioventricular block: a single institution’s experience of 30 years. J Am Coll Cardiol 39:130–137

    Article  PubMed  Google Scholar 

  16. Jouk PS, Usson Y, Michalowicz G, Grossi L (2000) Three-dimensional cartography of the pattern of the myofibres in the second trimester fetal human heart. Anat Embryol 202:103–118

    Article  CAS  PubMed  Google Scholar 

  17. Lacour-Gayet F, Maruszewski B, Mavroudis C, Jacobs JP, Elliott MJ (2000) Presentation of the International Nomenclature for Congenital Heart Surgery: the long way from nomenclature to collection of validated data at the EACTS. Eur J Cardiothorac Surg 18:128–135

    Article  CAS  PubMed  Google Scholar 

  18. Lagopoulos ME, Manlhiot C, McCrindle BW, Jaeggi ET, Friedberg MK, Nield LE (2010) Impact of prenatal diagnosis and anatomical subtype on outcome in double-outlet right ventricle. Am Heart J 160:692–700

    Article  PubMed  Google Scholar 

  19. Lim JS, McCrindle BW, Smallhorn JF, Golding F, Caldarone CA, Taketazu M, Jaeggi ET (2005) Clinical features, management, and outcome of children with fetal and postnatal diagnoses of isomerism syndromes. Circulation 112:2454–2461

    Article  PubMed  Google Scholar 

  20. Lougheed J, Sinclair BG, Fung Kee Fung K, Bigras JL, Ryan G, Smallhorn JF, Hornberger LK (2001) Acquired right ventricular outflow tract obstruction in the recipient twin in twin–twin transfusion syndrome. J Am Coll Cardiol 38:1533–1538

    Article  CAS  PubMed  Google Scholar 

  21. Makikallio K, McElhinney DB, Levine JC, Marx GR, Colan SD, Marshall AC, Lock JE, Marcus EN, Tworetzky W (2006) Fetal aortic valve stenosis and the evolution of hypoplastic left heart syndrome: patient selection for fetal intervention. Circulation 113:1401–1405

    Article  PubMed  Google Scholar 

  22. Makikallio K, Rasanen J, Makikallio T, Vuolteenaho O, Huhta JC (2008) Human fetal cardiovascular profile score and neonatal outcome in intrauterine growth restriction. Ultrasound Obstet Gynecol 31:48–54

    Article  CAS  PubMed  Google Scholar 

  23. Maron BJ, Sato N, Roberts WC, Edwards JE, Chandra RS (1979) Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum: comparison of fetuses and infants with and without congenital heart disease and patients with hypertrophic cardiomyopathy. Circulation 60:685–696

    Article  CAS  PubMed  Google Scholar 

  24. Matsumori M, Ito T, Toyono M, Harada K, Takada G (1997) Influence of right ventricular volume and pressure overloads on assessment of left ventricular volume using two-dimensional echocardiography in infants and children with congenital heart diseases. Am J Cardiol 80:965–968

    Article  CAS  PubMed  Google Scholar 

  25. Messing B, Porat S, Imbar T, Valsky DV, Anteby EY, Yagel S (2005) Mild tricuspid regurgitation: a benign fetal finding at various stages of pregnancy. Ultrasound Obstet Gynecol 26:606–609 discussion 610

    Article  CAS  PubMed  Google Scholar 

  26. Messing B, Cohen SM, Valsky DV, Shen O, Rosenak D, Lipschuetz M, Yagel S (2011) Fetal heart ventricular mass obtained by STIC acquisition combined with inversion mode and VOCAL. Ultrasound Obstet Gynecol 38:191–197

    Article  CAS  PubMed  Google Scholar 

  27. Moss AJ, Allen HD (2008) Moss and Adams’ heart disease in infants, children, and adolescents: including the fetus and young adult, 7th edn. Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  28. Paladini D, Chita SK, Allan LD (1990) Prenatal measurement of cardiothoracic ratio in evaluation of heart disease. Arch Dis Child 65:20–23

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Papanna R, Mann LK, Molina S, Johnson A, Moise KJ (2011) Changes in the recipient fetal Tei index in the perioperative period after laser photocoagulation of placental anastomoses for twin–twin transfusion syndrome. Prenat Diagn 31:176–180

    Article  PubMed  Google Scholar 

  30. Pedra SR, Smallhorn JF, Ryan G, Chitayat D, Taylor GP, Khan R, Abdolell M, Hornberger LK (2002) Fetal cardiomyopathies: pathogenic mechanisms, hemodynamic findings, and clinical outcome. Circulation 106:585–591

    Article  PubMed  Google Scholar 

  31. Roman KS, Fouron JC, Nii M, Smallhorn JF, Chaturvedi R, Jaeggi ET (2007) Determinants of outcome in fetal pulmonary valve stenosis or atresia with intact ventricular septum. Am J Cardiol 99:699–703

    Article  PubMed  Google Scholar 

  32. Rudolph AM (1985) Distribution and regulation of blood flow in the fetal and neonatal lamb. Circ Res 57:811–821

    Article  CAS  PubMed  Google Scholar 

  33. Rudolph AM, Heymann MA (1970) Circulatory changes during growth in the fetal lamb. Circ Res 26:289–299

    Article  CAS  PubMed  Google Scholar 

  34. Rychik J, Tian Z, Bebbington M, Xu F, McCann M, Mann S, Wilson RD, Johnson MP (2007) The twin–twin transfusion syndrome: spectrum of cardiovascular abnormality and development of a cardiovascular score to assess severity of disease. Am J Obstet Gynecol 197:392 e391–e398

  35. Schneider C, McCrindle BW, Carvalho JS, Hornberger LK, McCarthy KP, Daubeney PE (2005) Development of z-scores for fetal cardiac dimensions from echocardiography. Ultrasound Obstet Gynecol 26:599–605

    Article  CAS  PubMed  Google Scholar 

  36. Sedmera D, Pexieder T, Vuillemin M, Thompson RP, Anderson RH (2000) Developmental patterning of the myocardium. Anat Rec 258:319–337

    Article  CAS  PubMed  Google Scholar 

  37. Smolich JJ, Walker AM, Campbell GR, Adamson TM (1989) Left and right ventricular myocardial morphometry in fetal, neonatal, and adult sheep. Am J Physiol 257:H1–H9

    CAS  PubMed  Google Scholar 

  38. Smolich JJ, Berger PJ, Walker AM (1996) Interrelation between ventricular function, myocardial blood flow, and O2 consumption changes at birth in lambs. Am J Physiol 270:H741–H749

    CAS  PubMed  Google Scholar 

  39. Stirnemann JJ, Mougeot M, Proulx F, Nasr B, Essaoui M, Fouron JC, Ville Y (2010) Profiling fetal cardiac function in twin–twin transfusion syndrome. Ultrasound Obstet Gynecol 35:19–27

    Article  CAS  PubMed  Google Scholar 

  40. Stollberger C, Kopsa W, Finsterer J (2006) Noncompaction of the right atrium and left ventricle in Ebstein’s malformation. J Heart Valve Dis 15:719–720

    PubMed  Google Scholar 

  41. van der Hulst AE, Delgado V, Holman ER, Kroft LJ, de Roos A, Hazekamp MG, Blom NA, Bax JJ, Roest AA (2010) Relation of left ventricular twist and global strain with right ventricular dysfunction in patients after operative “correction” of tetralogy of Fallot. Am J Cardiol 106:723–729

    Article  PubMed  Google Scholar 

  42. Wald RM, Tham EB, McCrindle BW, Goff DA, McAuliffe FM, Golding F, Jaeggi ET, Hornberger LK, Tworetzky W, Nield LE (2007) Outcome after prenatal diagnosis of tricuspid atresia: a multicenter experience. Am Heart J 153:772–778

    Article  PubMed  Google Scholar 

  43. Willruth AM, Geipel AK, Berg CT, Fimmers R, Gembruch UG (2011) Comparison of global and regional right and left ventricular longitudinal peak systolic strain, strain rate, and velocity in healthy fetuses using a novel feature tracking technique. J Perinat Med 39:549–556

    Article  PubMed  Google Scholar 

  44. Yinon Y, Yagel S, Hegesh J, Weisz B, Mazaki-Tovi S, Lipitz S, Achiron R (2007) Fetal cardiomyopathy: in utero evaluation and clinical significance. Prenat Diagn 27:23–28

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Fetal Cardiac Program, Labatt Family Heart Centre, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Christine E. MacColl, Cedric Manlhiot, Christiana Page, Brian W. McCrindle, Edgar T. Jaeggi & Lynne E. Nield

  2. University of Toronto, Toronto, ON, Canada

    Steven E. S. Miner

Authors
  1. Christine E. MacColl
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  2. Cedric Manlhiot
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  3. Christiana Page
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  4. Brian W. McCrindle
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  5. Steven E. S. Miner
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  6. Edgar T. Jaeggi
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  7. Lynne E. Nield
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Correspondence to Christine E. MacColl.

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MacColl, C.E., Manlhiot, C., Page, C. et al. Factors Associated With in Utero Demise of Fetuses That Have Underlying Cardiac Pathologies. Pediatr Cardiol 35, 1403–1414 (2014). https://doi.org/10.1007/s00246-014-0943-1

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  • DOI: https://doi.org/10.1007/s00246-014-0943-1

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