Congenital heart diseases (CHDs) are reported in 0.8% of newborns. Numerous factors influence cardiovascular development and CHD prevalence, and possibly also development of cardiovascular disease later in life. However, known factors explain the probable etiology in only a fraction of patients. Past large-scale population-based studies have made invaluable contributions to the understanding of cardiac disease, but none recruited participants prenatally and focused on the neonatal period. The Copenhagen Baby Heart Study (CBHS) is a population-based study of the prevalence, spectrum, and prognosis of structural and functional cardiac abnormalities. The CBHS will also establish normal values for neonatal cardiac parameters and biomarkers, and study prenatal and early childhood factors potentially affecting later cardiovascular disease risk. The CBHS is an ongoing multicenter, prospective study recruiting from second trimester pregnancy (gestational weeks 18–20) (expected n = 25,000). Information on parents, pregnancy, and delivery are collected. After birth, umbilical cord blood is collected for biochemical analysis, DNA purification, and biobank storage. An echocardiographic examination, electrocardiography, and post-ductal pulse oximetry are performed shortly after birth. Infants diagnosed with significant CHD are referred to a specialist or admitted to hospital, depending on CHD severity. CBHS participants will be followed prospectively as part of specific research projects or regular clinical follow-up for CHD. CBHS design and methodology are described. The CBHS aims to identify new mechanisms underlying cardiovascular disease development and new targets for prevention, early detection, and management of CHD and other cardiac diseases presenting at birth or developing later in life.
Congenital heart disease Cardiovascular development Cardiovascular disease Risk factors Epidemiology Reference material
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The CBHS receives financial support from the Danish Heart Association, the Danish Children’s Heart Foundation, Candy’s Foundation, the Toyota Foundation, the Herlev-Gentofte Hospital Research Foundation, and the Gangsted Foundation. The funders have no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of manuscripts; or in decisions to publish results.
AS wrote the manuscript and participated in the study design and acquisition of data. All authors participated in the study design and acquisition of data. KI and HB had the original idea for the study and wrote the protocol. All authors critically revised the manuscript and approved the final version. AS is the guarantor of the paper.
Compliance with ethical standards
Conflict of interest
The Copenhagen Baby Heart Study receives financial support from the Danish Heart Association, the Danish Children’s Heart Foundation, Candy’s Foundation, the Toyota Foundation, the Herlev-Gentofte Hospital Research Foundation, and the Gangsted Foundation. The funders have no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of manuscripts; or in decisions to publish results. All authors have no other conflicts of interests to declare.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained for all individual participants included in the study.
Bernier P-L, Stefanescu A, Samoukovic G, Tchervenkov CI. The challenge of congenital heart disease worldwide: epidemiologic and demographic facts. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2010;13(1):26–34.CrossRefPubMedCentralGoogle Scholar
Dolk H, Loane M, Garne E, European Surveillance of Congenital Anomalies (EUROCAT) Working Group. Congenital heart defects in Europe: prevalence and perinatal mortality, 2000–2005. Circulation. 2011;123(8):841–9.CrossRefPubMedCentralGoogle Scholar
Gilboa SM, Salemi JL, Nembhard WN, Fixler DE, Correa A. Mortality resulting from congenital heart disease among children and adults in the United States, 1999–2006. Circulation. 2010;122(22):2254–63.CrossRefPubMedCentralGoogle Scholar
da Rocha LA, Araujo Júnior E, Nardozza LMM, Moron AF. Screening of fetal congenital heart disease: the challenge continues. Rev Bras Cir Cardiovasc Orgao Of Soc Bras Cir Cardiovasc. 2013;28(3):V–VII.CrossRefGoogle Scholar
Salomon LJ, Alfirevic Z, Berghella V, Bilardo C, Hernandez-Andrade E, Johnsen SL, et al. Practice guidelines for performance of the routine mid-trimester fetal ultrasound scan. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2011;37(1):116–26.CrossRefGoogle Scholar
Bishop KC, Kuller JA, Boyd BK, Rhee EH, Miller S, Barker P. Ultrasound examination of the fetal heart. Obstet Gynecol Surv. 2017;72(1):54–61.CrossRefPubMedCentralGoogle Scholar
International Society of Ultrasound in Obstetrics and Gynecology null, Carvalho JS, Allan LD, Chaoui R, Copel JA, DeVore GR, et al. ISUOG Practice Guidelines (updated): sonographic screening examination of the fetal heart. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2013;41(3):348–59.CrossRefGoogle Scholar
Jørgensen DES, Vejlstrup N, Jørgensen C, Maroun LL, Steensberg J, Hessellund A, et al. Prenatal detection of congenital heart disease in a low risk population undergoing first and second trimester screening. Prenat Diagn. 2015;35(4):325–30.CrossRefPubMedCentralGoogle Scholar
Jenkins KJ. Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation. 2007;115(23):2995–3014.CrossRefPubMedCentralGoogle Scholar
Tararbit K, Houyel L, Bonnet D, De Vigan C, Lelong N, Goffinet F, et al. Risk of congenital heart defects associated with assisted reproductive technologies: a population-based evaluation. Eur Heart J. 2011;32(4):500–8.CrossRefPubMedCentralGoogle Scholar
Zhao Q-M, Ma X-J, Jia B, Huang G-Y. Prevalence of congenital heart disease at live birth: an accurate assessment by echocardiographic screening. Acta Paediatr Oslo Nor 1992. 2013;102(4):397–402.Google Scholar
Ishikawa T, Iwashima S, Ohishi A, Nakagawa Y, Ohzeki T. Prevalence of congenital heart disease assessed by echocardiography in 2067 consecutive newborns. Acta Paediatr Oslo Nor 1992. 2001;100(8):e55–60.Google Scholar
Cantinotti M, Kutty S, Franchi E, Paterni M, Scalese M, Iervasi G, et al. Pediatric echocardiographic nomograms: what has been done and what still needs to be done. Trends Cardiovasc Med. 2017;27(5):336–49.CrossRefPubMedCentralGoogle Scholar
Schwartz PJ, Garson A, Paul T, Stramba-Badiale M, Vetter VL, Wren C, et al. Guidelines for the interpretation of the neonatal electrocardiogram: a task force of the European Society of Cardiology. Eur Heart J. 2002;23(17):1329–44.CrossRefPubMedCentralGoogle Scholar
Lancellotti P, Badano LP, Lang RM, Akhaladze N, Athanassopoulos GD, Barone D, et al. Normal Reference Ranges for Echocardiography: rationale, study design, and methodology (NORRE Study). Eur Heart J Cardiovasc Imaging. 2013;14(4):303–8.CrossRefPubMedCentralGoogle Scholar
Lai WW, Geva T, Shirali GS, Frommelt PC, Humes RA, Brook MM, et al. Guidelines and standards for performance of a pediatric echocardiogram: a report from the Task Force of the Pediatric Council of the American Society of Echocardiography. J Am Soc Echocardiogr Off Publ Am Soc Echocardiogr. 2006;19(12):1413–30.CrossRefGoogle Scholar
Pettersen MD, Du W, Skeens ME, Humes RA. Regression equations for calculation of z scores of cardiac structures in a large cohort of healthy infants, children, and adolescents: an echocardiographic study. J Am Soc Echocardiogr Off Publ Am Soc Echocardiogr. 2008;21(8):922–34.CrossRefGoogle Scholar
Sluysmans T, Colan SD. Structural measurements and adjustment for growth. In: Lai WW, Mertens LL, Cohen MS, editors. Echocardiography in congenital and pediatric heart disease. Oxford: Wiley-Blackwell; 2009. p. 53–62.Google Scholar
Dawber TR, Meadors GF, Moore FE. Epidemiological approaches to heart disease: the Framingham study. Am J Public Health Nations Health. 1951;41(3):279–81.CrossRefPubMedCentralGoogle Scholar
Schnohr P, Jensen G, Nyboe J, Eybjaerg Hansen A. The Copenhagen City Heart Study. A prospective cardiovascular population study of 20,000 men and women. Ugeskr Laeger. 1977;139(32):1921–3.PubMedPubMedCentralGoogle Scholar
Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298(3):299–308.CrossRefPubMedCentralGoogle Scholar
Frikke-Schmidt R, Nordestgaard BG, Stene MCA, Sethi AA, Remaley AT, Schnohr P, et al. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. JAMA. 2008;299(21):2524–32.CrossRefPubMedCentralGoogle Scholar
Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301(22):2331–9.CrossRefGoogle Scholar
Sempos CT, Bild DE, Manolio TA. Overview of the Jackson Heart Study: a study of cardiovascular diseases in African American men and women. Am J Med Sci. 1999;317(3):142–6.CrossRefPubMedCentralGoogle Scholar
Wong N. Epidemiological studies of CHD and the evolution of preventive cardiology. Nat Rev Cardiol. 2014;25:11.Google Scholar
Fyler DC, Buckley LP, Hellenbrand WE, Cohn HE, Nadas AS. 104 new england regional infant cardiac program (NERICP) Effects on Care Delivery. Pediatr Res. 1978;12(S4):381.CrossRefGoogle Scholar
Talner CN. Report of the New England Regional Infant Cardiac Program, by Donald C. Fyler, MD, Pediatrics, 1980;65(suppl):375–461. Pediatrics. 1998;102(1 Pt 2):258–9.Google Scholar
Ferencz C, Rubin JD, Loffredo CA, Magee CM. Epidemiology of congenital heart disease, the Baltimore–Washington Infant Study (1981–1989). Perspectives in Pediatric Cardiology. Vol 4. MountKisco, NY: Futura Publishing Co.Inc; 1993.Google Scholar
Hinton RB. Genetic and environmental factors contributing to cardiovascular malformation: a unified approach to risk. J Am Heart Assoc Cardiovasc Cerebrovasc Dis [Internet]. 2013 Jun 21 [cited 2018 Mar 27];2(3). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3698798/. Accessed 27 Mar 2018.
Cantinotti M, Scalese M, Molinaro S, Murzi B, Passino C. Limitations of current echocardiographic nomograms for left ventricular, valvular, and arterial dimensions in children: a critical review. J Am Soc Echocardiogr Off Publ Am Soc Echocardiogr. 2012;25(2):142–52.CrossRefGoogle Scholar
Schwartz PJ, Stramba-Badiale M, Segantini A, Austoni P, Bosi G, Giorgetti R, et al. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med. 1998;338(24):1709–14.CrossRefPubMedCentralGoogle Scholar
Schwartz PJ, Stramba-Badiale M, Crotti L, Pedrazzini M, Besana A, Bosi G, et al. Prevalence of the congenital long-QT syndrome. Circulation. 2009;120(18):1761–7.CrossRefPubMedCentralGoogle Scholar
Yoshinaga M, Ushinohama H, Sato S, Tauchi N, Horigome H, Takahashi H, et al. Electrocardiographic screening of 1-month-old infants for identifying prolonged QT intervals. Circ Arrhythm Electrophysiol. 2013;6(5):932–8.CrossRefPubMedCentralGoogle Scholar
Glasser L, Sutton N, Schmeling M, Machan JT. A comprehensive study of umbilical cord blood cell developmental changes and reference ranges by gestation, gender and mode of delivery. J Perinatol Off J Calif Perinat Assoc. 2015;35(7):469–75.CrossRefGoogle Scholar
Kotaska K, Urinovska R, Klapkova E, Prusa R, Rob L, Binder T. Re-evaluation of cord blood arterial and venous reference ranges for pH, pO(2), pCO(2), according to spontaneous or cesarean delivery. J Clin Lab Anal. 2010;24(5):300–4.CrossRefPubMedCentralGoogle Scholar
Perkins SL, Livesey JF, Belcher J. Reference intervals for 21 clinical chemistry analytes in arterial and venous umbilical cord blood. Clin Chem. 1993;39(6):1041–4.PubMedPubMedCentralGoogle Scholar
Qaiser DH, Sandila MP, Omair A, Ghori GM. Correlation of routine haematological parameters between normal maternal blood and the cord blood of healthy newborns in selected hospitals of Karachi. J Coll Physicians Surg-Pak JCPSP. 2013;23(2):128–31.PubMedPubMedCentralGoogle Scholar
Zhang R, Dong S, Ma W-W, Cai X-P, Le Z-Y, Xiao R, et al. Modulation of cholesterol transport by maternal hypercholesterolemia in human full-term placenta. PLoS ONE. 2017;12(2):e0171934.CrossRefPubMedCentralGoogle Scholar
Erichsen R, Lash TL, Hamilton-Dutoit SJ, Bjerregaard B, Vyberg M, Pedersen L. Existing data sources for clinical epidemiology: the Danish national pathology registry and data bank. Clin Epidemiol. 2010;9(2):51–6.CrossRefGoogle Scholar
Storm HH, Michelsen EV, Clemmensen IH, Pihl J. The Danish cancer registry—history, content, quality and use. Dan Med Bull. 1997;44(5):535–9.PubMedPubMedCentralGoogle Scholar