title: Congenital Heart Defects and Indices of Fetal Cerebral Growth in a Nationwide Cohort of 924 422 Liveborn Infants.
abstract: BACKGROUND
  Neurodevelopmental disorders are the most common and distressful comorbidities associated with congenital heart defects (CHD). Head circumference at birth (HC), a proxy for prenatal cerebral growth, is an established risk factor for neurodevelopmental disorders.
  
  
  RESULTS
  In a nationwide cohort, we included all 924 422 liveborn Danish singletons, 1997 to 2011. CHD was present in 5519. The association between CHD and growth indices was analyzed by multivariable linear regression, adjusted for potential confounders. We report mean differences in gestational age-specific z scores in comparison with the general population. CHD was associated with lower HC z scores, -0.10 (95% confidence interval [CI], -0.13 to -0.08). Several CHD subtypes were associated with smaller HC, eg, hypoplastic left heart syndrome, -0.39 (95% CI, -0.58 to -0.21); common arterial trunk, -0.41 (95% CI, -0.74 to -0.09); and major ventricular septal defects, -0.25 (95% CI, -0.35 to -0.15). Other single-ventricle defects, transposition of the great arteries, tetralogy of Fallot, and anomalous pulmonary venous return, were also associated with smaller HC. Transposition of the great arteries was associated with smaller HC relative to birth weight, -0.26 (95% CI, -0.39 to -0.13). Major ventricular septal defects were associated with larger HC relative to birth weight. The results were consistent under various conditions, eg, when siblings of infants with CHD (n=5311) or infants with other major malformations (n=24 974) were used as the reference.
  
  
  CONCLUSIONS
  Several subtypes of CHD were associated with smaller HC. The associations with major ventricular septal defects, common arterial trunk, and anomalous pulmonary venous return have not previously been described. Only infants with transposition of the great arteries had smaller HC relative to birth weight.
authors.affiliation: From Department of Pediatrics, Aarhus University Hospital, Denmark (N.B.M., T.B.H., P.A., C.C.B., J.R.O.); Centre for Rare Diseases, Aarhus University Hospital, Denmark (N.B.M., J.R.O.); Perinatal Epidemiology Research Unit, Aarhus University Hospital, Denmark (T.B.H., C.C.B., N.B.M.); Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, PA (J.W.G.); and Department of Cardiothoracic Surgery, Aarhus University Hospital, Denmark (V.H.). nielsbm@ki.au.dk.
authors.forename: Niels B
authors.initials: NB
authors.lastname: Matthiesen
authors.affiliation: From Department of Pediatrics, Aarhus University Hospital, Denmark (N.B.M., T.B.H., P.A., C.C.B., J.R.O.); Centre for Rare Diseases, Aarhus University Hospital, Denmark (N.B.M., J.R.O.); Perinatal Epidemiology Research Unit, Aarhus University Hospital, Denmark (T.B.H., C.C.B., N.B.M.); Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, PA (J.W.G.); and Department of Cardiothoracic Surgery, Aarhus University Hospital, Denmark (V.H.).
authors.forename: Tine B
authors.initials: TB
authors.lastname: Henriksen
authors.affiliation: From Department of Pediatrics, Aarhus University Hospital, Denmark (N.B.M., T.B.H., P.A., C.C.B., J.R.O.); Centre for Rare Diseases, Aarhus University Hospital, Denmark (N.B.M., J.R.O.); Perinatal Epidemiology Research Unit, Aarhus University Hospital, Denmark (T.B.H., C.C.B., N.B.M.); Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, PA (J.W.G.); and Department of Cardiothoracic Surgery, Aarhus University Hospital, Denmark (V.H.).
authors.forename: J William
authors.initials: JW
authors.lastname: Gaynor
authors.affiliation: From Department of Pediatrics, Aarhus University Hospital, Denmark (N.B.M., T.B.H., P.A., C.C.B., J.R.O.); Centre for Rare Diseases, Aarhus University Hospital, Denmark (N.B.M., J.R.O.); Perinatal Epidemiology Research Unit, Aarhus University Hospital, Denmark (T.B.H., C.C.B., N.B.M.); Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, PA (J.W.G.); and Department of Cardiothoracic Surgery, Aarhus University Hospital, Denmark (V.H.).
authors.forename: Peter
authors.initials: P
authors.lastname: Agergaard
authors.affiliation: From Department of Pediatrics, Aarhus University Hospital, Denmark (N.B.M., T.B.H., P.A., C.C.B., J.R.O.); Centre for Rare Diseases, Aarhus University Hospital, Denmark (N.B.M., J.R.O.); Perinatal Epidemiology Research Unit, Aarhus University Hospital, Denmark (T.B.H., C.C.B., N.B.M.); Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, PA (J.W.G.); and Department of Cardiothoracic Surgery, Aarhus University Hospital, Denmark (V.H.).
authors.forename: Cathrine C
authors.initials: CC
authors.lastname: Bach
authors.affiliation: From Department of Pediatrics, Aarhus University Hospital, Denmark (N.B.M., T.B.H., P.A., C.C.B., J.R.O.); Centre for Rare Diseases, Aarhus University Hospital, Denmark (N.B.M., J.R.O.); Perinatal Epidemiology Research Unit, Aarhus University Hospital, Denmark (T.B.H., C.C.B., N.B.M.); Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, PA (J.W.G.); and Department of Cardiothoracic Surgery, Aarhus University Hospital, Denmark (V.H.).
authors.forename: Vibeke E
authors.initials: VE
authors.lastname: Hjortdal
authors.affiliation: From Department of Pediatrics, Aarhus University Hospital, Denmark (N.B.M., T.B.H., P.A., C.C.B., J.R.O.); Centre for Rare Diseases, Aarhus University Hospital, Denmark (N.B.M., J.R.O.); Perinatal Epidemiology Research Unit, Aarhus University Hospital, Denmark (T.B.H., C.C.B., N.B.M.); Division of Cardiothoracic Surgery, The Children's Hospital of Philadelphia, PA (J.W.G.); and Department of Cardiothoracic Surgery, Aarhus University Hospital, Denmark (V.H.).
authors.forename: John R
authors.initials: JR
authors.lastname: Østergaard
mesh_terms: D000328:Adult; D001921:Brain / Q000196:embryology* / Q000254:growth & development*; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000453:epidemiology*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011247:Pregnancy
keywords: brain; epidemiology; heart defects, congenital; pediatrics