Archives of Gynecology and Obstetrics

, Volume 300, Issue 3, pp 601–613 | Cite as

Application of the INTERGROWTH-21st chart compared to customized growth charts in fetuses with left heart obstruction: late trimester biometry, cerebroplacental hemodynamics and perinatal outcome

  • Oliver GraupnerEmail author
  • Franziska Helfrich
  • Eva Ostermayer
  • Silvia M. Lobmaier
  • Javier U. Ortiz
  • Peter Ewert
  • Annette Wacker-Gussmann
  • Bernhard Haller
  • Roland Axt-Fliedner
  • Christian Enzensberger
  • Kathrin Abel
  • Anne Karge
  • Renate Oberhoffer
  • Bettina Kuschel
Maternal-Fetal Medicine



Birth weight (BW) is crucial for surgical outcome in children with left heart obstruction (LHO). Head circumference (HC) is believed to correlate with the neurocognitive outcome in LHO. Our aim was to investigate the application of international standardized growth charts from the INTERGROWTH-21st project in comparison to customized growth charts in fetal LHO.


This is a retrospective cohort study consisting of 60 singleton pregnancies complicated by fetal LHO. For the z score calculation of estimated fetal weight (EFW) and biometric parameters, the INTERGROWTH-21st calculator was used as well as algorithms of customized growth charts. Antenatal measurements were compared to newborn biometry and the association with fetal Doppler results (MCA PI: middle cerebral artery pulsatility index and CPR: cerebroplacental ratio) was examined. Furthermore, the ability of each antenatal chart to predict adverse perinatal outcome was evaluated.


At a mean gestational age of 37 weeks, all assessment charts showed significantly smaller mean values for antenatal head circumference (HC) z scores. Highest detection rate for restricted HC growth antenatally was achieved with Hadlock charts. MCA PI and CPR were not associated with neonatal HC. A significant association was observed between EFW and 1-year survival, independent of the considered growth chart.


Growth chart independently, antenatal HC did tend to be smaller in LHO fetuses. A significant association was observed between EFW and 1-year survival rate. Prospective investigations in CHD fetuses should be carried out with internationally standardized growth charts to better examine their prognostic value in this high-risk population.


Congenital heart disease Left heart obstruction Growth charts Fetal biometry Fetal hemodynamics 


Author contributions

OG: project development, data collection, data analysis and manuscript writing. FH: project development, data collection, data analysis, and manuscript writing. EO: data collection and manuscript editing. SML: data collection and manuscript editing. JUO: data collection and manuscript editing. PE: data collection and manuscript editing. AWG: data collection and manuscript editing. BH: data analysis and manuscript editing. RAF: project development and manuscript editing. CE: manuscript editing. KA: manuscript editing. AK: manuscript editing. RO: project development, data collection, data analysis and manuscript editing. BK: project development, data collection, data analysis and manuscript editing.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

404_2019_5198_MOESM1_ESM.docx (18 kb)
Supplementary file1 (DOCX 18 kb)
404_2019_5198_MOESM2_ESM.docx (15 kb)
Supplementary file2 (DOCX 15 kb)


  1. 1.
    Petrossian RA, Kuehl KS, Loffredo CA (2015) Relationship of birth weight with congenital cardiovascular malformations in a population-based study. Cardiol Young 25(6):1086–1092CrossRefGoogle Scholar
  2. 2.
    Matthiesen NB, Henriksen TB, Gaynor JW, Agergaard P, Bach CC, Hjortdal VE, Ostergaard JR (2016) Congenital heart defects and indices of fetal cerebral growth in a nationwide cohort of 924 422 liveborn infants. Circulation 133(6):566–575Google Scholar
  3. 3.
    Mebius MJ, Kooi EMW, Bilardo CM, Bos AF (2017) Brain injury and neurodevelopmental outcome in congenital heart disease: a systematic review. Pediatrics 140(1):e20164055CrossRefGoogle Scholar
  4. 4.
    Cnota JF, Hangge PT, Wang Y, Woo JG, Hinton AC, Divanovic AA, Michelfelder EC, Hinton RB (2013) Somatic growth trajectory in the fetus with hypoplastic left heart syndrome. Pediatr Res 74(3):284–289CrossRefGoogle Scholar
  5. 5.
    Williams RV, Ravishankar C, Zak V, Evans F, Atz AM, Border WL, Levine J, Li JS, Mahony L, Mital S, Pearson GD, Prakash A, Hsu DT, Pediatric Heart Network I (2010) Birth weight and prematurity in infants with single ventricle physiology: pediatric heart network infant single ventricle trial screened population. Congenit Heart Dis 5(2):96–103Google Scholar
  6. 6.
    Alsoufi B, Manlhiot C, Mahle WT, Kogon B, Border WL, Cuadrado A, Vincent R, McCrindle BW, Kanter K (2014) Low-weight infants are at increased mortality risk after palliative or corrective cardiac surgery. J Thorac Cardiovasc Surg 148(6):2508–2514 (e1) Google Scholar
  7. 7.
    Tabbutt S, Ghanayem N, Ravishankar C, Sleeper LA, Cooper DS, Frank DU, Lu M, Pizarro C, Frommelt P, Goldberg CS, Graham EM, Krawczeski CD, Lai WW, Lewis A, Kirsh JA, Mahony L, Ohye RG, Simsic J, Lodge AJ, Spurrier E, Stylianou M, Laussen P, Pediatric Heart Network I (2012) Risk factors for hospital morbidity and mortality after the Norwood procedure: a report from the Pediatric Heart Network Single Ventricle Reconstruction trial. J Thorac Cardiovasc Surg 144(4):882–895Google Scholar
  8. 8.
    Majnemer A, Limperopoulos C, Shevell M, Rosenblatt B, Rohlicek C, Tchervenkov C (2006) Long-term neuromotor outcome at school entry of infants with congenital heart defects requiring open-heart surgery. J Pediatr 148:72–77CrossRefGoogle Scholar
  9. 9.
    Limperopoulos C, Majnemer A, Shevell M, Rosenblatt B, Rohlicek C, Tchervenkov C (2000) Neurodevelopmental status of newborns and infants with congenital heart defects before and after open heart surgery. J Pediatr 137:638–645CrossRefGoogle Scholar
  10. 10.
    Marino BS, Lipkin PH, Newburger JW, Peacock G, Gerdes M, Gaynor JW, Mussatto KA, Uzark K, Goldberg CS, Johnson WH Jr, Li J, Smith SE, Bellinger DC, Mahle WT, American Heart Association Congenital Heart Defects Committee, Council on Cardiovascular Disease in the Young, Council on Cardiovascular Nursing, and Stroke Council (2012) Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation 126(9):1143–1172Google Scholar
  11. 11.
    Hangge PT, Cnota JF, Woo JG, Hinton AC, Divanovic AA, Manning PB, Ittenbach RF, Hinton RB (2013) Microcephaly is associated with early adverse neurologic outcomes in hypoplastic left heart syndrome. Pediatr Res 74(1):61–67CrossRefGoogle Scholar
  12. 12.
    Masoller N, Martínez JM, Gómez O, Bennasar M, Crispi F, Sanz-Cortés M, Egaña- Ugrinovic G, Bartrons J, Puerto B, Gratacós E (2014) Evidence of second-trimester changes in head biometry and brain perfusion in fetuses with congenital heart disease. Ultrasound Obstet Gynecol 44(2):182–187CrossRefGoogle Scholar
  13. 13.
    Masoller N, Sanz-Cortés M, Crispi F, Gómez O, Bennasar M, Egaña-Ugrinovic G, Bargalló N, Martínez JM, Gratacós E (2016) Severity of fetal brain abnormalities in congenital heart disease in relation to the main expected pattern of in utero brain blood supply. Fetal Diagn Ther 39:269–278CrossRefGoogle Scholar
  14. 14.
    Ruiz A, Cruz-Lemini M, Masoller N, Sanz-Cortés M, Ferrer Q, Ribera I, Martínez JM, Crispi F, Arévalo S, Gómez O, Pérez-Hoyos S, Carreras E, Gratacós E, Llurba E (2017) Longitudinal changes in fetal biometries and cerebroplacental haemodynamics in fetuses with congenital heart disease. Ultrasound Obstet Gynecol 49(3):379–386CrossRefGoogle Scholar
  15. 15.
    Hahn E, Szwast A, Cnota J II, Levine JC, Fifer CG, Jaeggi E, Andrews H, Williams IA (2016) Association between fetal growth, cerebral blood flow and neurodevelopmental outcome in univentricular fetuses. Ultrasound Obstet Gynecol 47(4):460–465CrossRefGoogle Scholar
  16. 16.
    Yamamoto Y, Khoo NS, Brooks PA, Savard W, Hirose A, Hornberger LK (2013) Severe left heart obstruction with retrograde arch flow importantly influences fetal cerebral and placental blood flow. Ultrasound Obstet Gynecol 42:294–299CrossRefGoogle Scholar
  17. 17.
    Arduini M, Rosati P, Caforio L, Guariglia L, Clerici G, Di Renzo GC, Scambia G (2011) Cerebral blood flow autoregulation and congenital heart disease: possible causes of abnormal prenatal neurologic development. J Matern Fetal Neonatal Med 24(10):1208–1211CrossRefGoogle Scholar
  18. 18.
    Jansen FA, van Zwet EW, Rijlaarsdam ME, Pajkrt E, van Velzen CL, Zuurveen HR, Kragt A, Bax CL, Clur SA, van Lith JM, Blom NA, Haak MC (2016) Head growth in fetuses with isolated congenital heart defects: lack of influence of aortic arch flow and ascending aorta oxygen saturation. Ultrasound Obstet Gynecol 48(3):357–364CrossRefGoogle Scholar
  19. 19.
    Haveman I, Fleurke-Rozema JH, Mulder EJH, Benders M, du Marchie Sarvaas G, Ter Heide H, de Heus RH, Bilardo CM (2018) Growth patterns in fetuses with isolated cardiac defects. Prenat Diagn 38(5):328–336CrossRefGoogle Scholar
  20. 20.
    Mebius MJ, Clur SAB, Vink AS, Pajkrt E, Kalteren WS, Kooi EMW, Bos AF, du Marchie Sarvaas GJ, Bilardo CM (2018) Growth patterns and cerebro-placental hemodynamics in fetuses with congenital heart disease. Ultrasound Obstet Gynecol. Google Scholar
  21. 21.
    Graupner O, Koch J, Enzensberger C, Götte M, Wolter A, Müller V, Kawecki A, Herrmann J, Axt-Fliedner R (2018) Head biometry in fetuses with isolated congenital heart disease. Ultraschall Med. Google Scholar
  22. 22.
    Graupner O, Koch J, Enzensberger C, Götte M, Wolter A, Müller V, Kawecki A, Herrmann J, Axt-Fliedner R (2019) Cerebroplacental and uterine doppler indices in pregnancies complicated by congenital heart disease of the fetus. Ultraschall Med. Google Scholar
  23. 23.
    Papageorghiou AT, Ohuma EO, Altman DG, Todros T, Cheikh Ismail L, Lambert A, Jaffer YA, Bertino E, Gravett MG, Purwar M, Noble JA, Pang R, Victora CG, Barros FC, Carvalho M, Salomon LJ, Bhutta ZA, Kennedy SH, Villar J (2014) International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. Lancet 384:869–879CrossRefGoogle Scholar
  24. 24.
    Villar J, Cheikh Ismail L, Victora CG, Ohuma EO, Bertino E, Altman DG, Lambert A, Papageorghiou AT, Carvalho M, Jaffer YA, Gravett MG, Purwar M, Frederick IO, Noble AJ, Pang R, Barros FC, Chumlea C, Bhutta ZA, Kennedy SH (2014) International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet 384:857–868CrossRefGoogle Scholar
  25. 25.
    van Velzen C, Clur SA, Rijlaarsdam ME, Pajkrt E, Bax CJ, Hruda J, de Groot CJ, Blom NA, Haak MC (2016) Prenatal diagnosis of congenital heart defects: accuracy and discrepancies in a multicenter cohort. Ultrasound Obstet Gynecol 47(5):616–622CrossRefGoogle Scholar
  26. 26.
    Hadlock FP, Harrist RB, Sharman RS, Deter RL, Park SK (1985) Estimation of fetal weight with the use of head, body, and femur measurements–a prospective study. Am J Obstet Gynecol 151(3):333–337CrossRefGoogle Scholar
  27. 27.
    International Society of Ultrasound in Obstetrics and Gynecology, Carvalho JS, Allan LD, Chaoui R, Copel JA, DeVore GR, Hecher K, Lee W, Munoz H, Paladini D, Tutschek B, Yagel S (2013) ISUOG Practice Guidelines (updated): sonographic screening examination of the fetal heart. Ultrasound Obstet Gynecol 41(3):348–359Google Scholar
  28. 28.
    Graupner O, Ortiz JU, Haller B, Wacker-Gussmann A, Oberhoffer R, Kuschel B, Weyrich J, Lees CC, Lobmaier SM (2018) Performance of computerized cardiotocography based short-term variation in late-onset small for gestational age fetuses and reference ranges for the late third trimester. Arch Gynecol Obstet.
  29. 29.
    Arduini D, Rizzo G (1990) Normal values of Pulsatility Index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. J Perinat Med 18(3):165–172CrossRefGoogle Scholar
  30. 30.
    Baschat AA, Gembruch U (2003) The cerebroplacental Doppler ratio revisited. Ultrasound Obstet Gynecol 21(2):124–127CrossRefGoogle Scholar
  31. 31.
    Snijders RJ, Nicolaides KH (1994) Fetal biometry at 14–40 weeks' gestation. Ultrasound Obstet Gynecol 4(1):34–48CrossRefGoogle Scholar
  32. 32.
    Hadlock FP, Harrist RB, Martinez-Poyer J (1992) Fetal body ratios in second trimester: a useful tool for identifying chromosomal abnormalities? J Ultrasound Med 11(2):81–85CrossRefGoogle Scholar
  33. 33.
    Marsal K, Persson PH, Larsen T, Lilja H, Selbing A, Sultan B (1996) Intrauterine growth curves based on ultrasonically estimated foetal weights. Acta Paediatr 85:843–848CrossRefGoogle Scholar
  34. 34.
    Voigt M, Rochow N, Schneider KT, Hagenah HP, Scholz R, Hesse V, Wittwer-Backofen U, Straube S, Olbertz D (2014) New percentile values for the anthropometric dimensions of singleton neonates: analysis of perinatal survey data of 2007–2011 from all 16 states of Germany. Z Geburtshilfe Neonatol 218(5):210–217CrossRefGoogle Scholar
  35. 35.
    Nicolaides KH, Wright D, Syngelaki A, Wright A, Akolekar R (2018) Fetal medicine foundation fetal and neonatal population weight charts. Ultrasound Obstet Gynecol 52(1):44–51CrossRefGoogle Scholar
  36. 36.
    Berg C, Gembruch O, Gembruch U, Geipel A (2009) Doppler indices of the middle cerebral artery in fetuses with cardiac defects theoretically associated with impaired cerebral oxygen delivery in utero: is there a brain-sparing effect? Ultrasound Obstet Gynecol 34:666–672CrossRefGoogle Scholar
  37. 37.
    Barbu D, Mert I, Kruger M, Bahado-Singh RO (2009) Evidence of fetal central nervous system injury in isolated congenital heart defects: microcephaly at birth. Am J Obstet Gynecol 201(1):43.e1–7CrossRefGoogle Scholar
  38. 38.
    Manzar S, Nair AK, Pai MG, Al-Khusaiby SM (2005) Head size at birth in neonates with transposition of great arteries and hypoplastic left heart syndrome. Saudi Med J 26(3):453–456Google Scholar
  39. 39.
    Matthiesen NB, Henriksen TB, Agergaard P, Gaynor JW, Bach CC, Hjortdal VE, Østergaard JR (2016) congenital heart defects and indices of placental and fetal growth in a nationwide study of 924 422 liveborn infants. Circulation 134(20):1546–1556CrossRefGoogle Scholar
  40. 40.
    Paladini D, Alfirevic Z, Carvalho JS, Khalil A, Malinger G, Martinez JM, Rychik J (2016) Prenatal counselling for neurodevelopmental delay in congenital heart disease. The results of a worldwide survey of experts' attitudes advise caution. Ultrasound Obstet Gynecol 47(6):667–671Google Scholar
  41. 41.
    Limperopoulos C, Majnemer A, Shevell MI, Rohlicek C, Rosenblatt B, Tchervenkov C, Darwish HZ (2002) Predictors of developmental disabilities after open heart surgery in young children with congenital heart defects. J Pediatr 141:51–58CrossRefGoogle Scholar
  42. 42.
    Leibovitz Z, Daniel-Spiegel E, Malinger G, Haratz K, Tamarkin M, Gindes L, Schreiber L, Ben-Sira L, Lev D, Shapiro I, Bakry H, Weizman B, Zreik A, Egenburg S, Arad A, Tepper R, Kidron D, Lerman-Sagie T (2016) Prediction of microcephaly at birth using three reference ranges for fetal head circumference: can we improve prenatal diagnosis? Ultrasound Obstet Gynecol 47(5):586–592CrossRefGoogle Scholar
  43. 43.
    Poljak B, Agarwal U, Jackson R, Alfirevic Z, Sharp A (2017) Diagnostic accuracy of individual antenatal tools for prediction of small-for-gestational age at birth. Ultrasound Obstet Gynecol 49(4):493–499CrossRefGoogle Scholar
  44. 44.
    Cao JY, Lee SY, Phan K, Ayer J, Celermajer DS, Winlaw DS (2018) Early outcomes of hypoplastic left heart syndrome infants: meta-analysis of studies comparing the hybrid and norwood procedures. World J Pediatr Congenital Heart Surg 9(2):224–233CrossRefGoogle Scholar
  45. 45.
    Rychik J, Rome JJ, Collins MH, DeCampli WM, Spray TL (1999) The hypoplastic left heart syndrome with intact atrial septum: atrial morphology, pulmonary vascular histopathology and outcome. J Am Coll Cardiol 34:554–560CrossRefGoogle Scholar
  46. 46.
    Vlahos AP (2004) Hypoplastic left heart syndrome with intact or highly restrictive atrial septum: outcome after neonatal transcatheter atrial septostomy. Circulation 109:2326–2330CrossRefGoogle Scholar
  47. 47.
    Hirsch JC, Copeland G, Donohue JE, Kirby RS, Grigorescu V, Gurney JG (2011) Population-based analysis of survival for hypoplastic left heart syndrome. J Pediatr 159:57–63CrossRefGoogle Scholar
  48. 48.
    Curzon CL, Milford-Beland S, Li JS et al (2008) Cardiac surgery in infants with low birth weight is associated with increased mortality: analysis of the Society of Thoracic Surgeons Congenital Heart Database. J Thorac Cardiovasc Surg 135:546–551CrossRefGoogle Scholar
  49. 49.
    D'Ambrosio V, Vena F, Marchetti C, Di Mascio D, Perrone S, Boccherini C, Pizzuti A, Benedetti Panici P, Giancotti A (2018) Midtrimester isolated short femur and perinatal outcomes: a systematic review and meta-analysis. Acta Obstet Gynecol Scand.
  50. 50.
    Özlü T, Ozcan T (2013) Fetal isolated short femur in the second trimester and adverse pregnancy outcomes. Prenat Diagn 33:1063–1069CrossRefGoogle Scholar
  51. 51.
    Aviram A, Bardin R, Wiznitzer A, Yogev Y, Hadar E (2015) Midtrimester isolated short femur length as a predictor of adverse pregnancy outcome. Fetal Diagn Ther 38(3):205–211CrossRefGoogle Scholar
  52. 52.
    Mailath-Pokorny M, Polterauer S, Worda K, Springer S, Bettelheim D (2015) Isolated short fetal femur length in the second trimester and the association with adverse perinatal outcome: experiences from a tertiary referral center. PLoS ONE 10(6):e0128820CrossRefGoogle Scholar
  53. 53.
    Goetzinger KR, Cahill AG, Macones GA, Odibo AO (2012) Isolated short femur length on second-trimester sonography. J Ultrasound Med 31:1935–1941CrossRefGoogle Scholar
  54. 54.
    Hadlock FP, Deter RL, Harrist RB, Park SK (1984) Estimating fetal age: computer-assisted analysis of multiple fetal growth parameters. Radiology 152(2):497–501CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Oliver Graupner
    • 1
    Email author
  • Franziska Helfrich
    • 1
  • Eva Ostermayer
    • 1
  • Silvia M. Lobmaier
    • 1
  • Javier U. Ortiz
    • 1
  • Peter Ewert
    • 2
  • Annette Wacker-Gussmann
    • 2
    • 3
  • Bernhard Haller
    • 4
  • Roland Axt-Fliedner
    • 5
  • Christian Enzensberger
    • 5
  • Kathrin Abel
    • 1
  • Anne Karge
    • 1
  • Renate Oberhoffer
    • 2
    • 3
  • Bettina Kuschel
    • 1
  1. 1.Department of Obstetrics and Gynecology, University Hospital rechts der IsarTechnical University of MunichMunichGermany
  2. 2.Department of Pediatric Cardiology and Congenital Heart DefectsGerman Heart Centre MunichMunichGermany
  3. 3.Department of Sport and Health SciencesTechnical University of MunichMünchenGermany
  4. 4.Institute for Medical Informatics, Statistics and Epidemiology (IMedIS), University Hospital rechts der IsarTechnical University of MunichMunichGermany
  5. 5.Division of Prenatal Medicine, Department of Obstetrics and Gynecology, University Hospital UKGMJustus-Liebig UniversityGiessenGermany

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