title: Fetal Environment Is a Major Determinant of the Neonatal Blood Thyroxine Level: Results of a Large Dutch Twin Study.
abstract: BACKGROUND
  The interindividual variability in thyroid hormone function parameters is much larger than the intraindividual variability, suggesting an individual set point for these parameters. There is evidence to suggest that environmental factors are more important than genetic factors in the determination of this individual set point.
  
  
  OBJECTIVE
  This study aimed to quantify the effect of genetic factors and (fetal) environment on the early postnatal blood T4 concentration.
  
  
  METHODS
  This was a classical twin study comparing the resemblance of neonatal screening blood T4 concentrations in 1264 mono- and 2566 dizygotic twin pairs retrieved from the population-based Netherlands Twin Register. Maximum-likelihood estimates of variance explained by genetic and environmental influences were obtained by structural equation modeling in data from full-term and preterm twin pairs.
  
  
  RESULTS
  In full-term infants, genetic factors explained 40%/31% of the variance in standardized T4 scores in boys/girls, and shared environment, 27%/22%. The remaining variance of 33%/47% was due to environmental factors not shared by twins. For preterm infants, genetic factors explained 34%/0% of the variance in boys/girls, shared environment 31%/57%, and unique environment 35%/43%. In very preterm twins, no significant contribution of genetic factors was observed.
  
  
  CONCLUSIONS
  Environment explains a large proportion of the resemblance of the postnatal blood T4 concentration in twin pairs. Because we analyzed neonatal screening results, the fetal environment is the most likely candidate for these environmental influences. Genetic influences on the T4 set point diminished with declining gestational age, especially in girls. This may be due to major environmental influences such as immaturity and nonthyroidal illness in very preterm infants.
authors.affiliation: Department of Pediatric Endocrinology (N.Z.-S., E.T.M., B.W., A.S.P.v.T.), Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Netherlands Twin Register, Department of Biological Psychology (C.E.M.v.B., D.I.B.), VU University Amsterdam, 1081 BT Amsterdam, The Netherlands; National Institute for Public Health and the Environment (P.O.), 3720 BA Bilthoven, The Netherlands; and Department of Pediatric Endocrinology (M.J.J.F.), VU University Medical Center, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Nitash
authors.initials: N
authors.lastname: Zwaveling-Soonawala
authors.affiliation: Department of Pediatric Endocrinology (N.Z.-S., E.T.M., B.W., A.S.P.v.T.), Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Netherlands Twin Register, Department of Biological Psychology (C.E.M.v.B., D.I.B.), VU University Amsterdam, 1081 BT Amsterdam, The Netherlands; National Institute for Public Health and the Environment (P.O.), 3720 BA Bilthoven, The Netherlands; and Department of Pediatric Endocrinology (M.J.J.F.), VU University Medical Center, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Catharina E M
authors.initials: CE
authors.lastname: van Beijsterveldt
authors.affiliation: Department of Pediatric Endocrinology (N.Z.-S., E.T.M., B.W., A.S.P.v.T.), Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Netherlands Twin Register, Department of Biological Psychology (C.E.M.v.B., D.I.B.), VU University Amsterdam, 1081 BT Amsterdam, The Netherlands; National Institute for Public Health and the Environment (P.O.), 3720 BA Bilthoven, The Netherlands; and Department of Pediatric Endocrinology (M.J.J.F.), VU University Medical Center, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Ertirea T
authors.initials: ET
authors.lastname: Mesfum
authors.affiliation: Department of Pediatric Endocrinology (N.Z.-S., E.T.M., B.W., A.S.P.v.T.), Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Netherlands Twin Register, Department of Biological Psychology (C.E.M.v.B., D.I.B.), VU University Amsterdam, 1081 BT Amsterdam, The Netherlands; National Institute for Public Health and the Environment (P.O.), 3720 BA Bilthoven, The Netherlands; and Department of Pediatric Endocrinology (M.J.J.F.), VU University Medical Center, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Brenda
authors.initials: B
authors.lastname: Wiedijk
authors.affiliation: Department of Pediatric Endocrinology (N.Z.-S., E.T.M., B.W., A.S.P.v.T.), Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Netherlands Twin Register, Department of Biological Psychology (C.E.M.v.B., D.I.B.), VU University Amsterdam, 1081 BT Amsterdam, The Netherlands; National Institute for Public Health and the Environment (P.O.), 3720 BA Bilthoven, The Netherlands; and Department of Pediatric Endocrinology (M.J.J.F.), VU University Medical Center, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Oomen
authors.affiliation: Department of Pediatric Endocrinology (N.Z.-S., E.T.M., B.W., A.S.P.v.T.), Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Netherlands Twin Register, Department of Biological Psychology (C.E.M.v.B., D.I.B.), VU University Amsterdam, 1081 BT Amsterdam, The Netherlands; National Institute for Public Health and the Environment (P.O.), 3720 BA Bilthoven, The Netherlands; and Department of Pediatric Endocrinology (M.J.J.F.), VU University Medical Center, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Martijn J J
authors.initials: MJ
authors.lastname: Finken
authors.affiliation: Department of Pediatric Endocrinology (N.Z.-S., E.T.M., B.W., A.S.P.v.T.), Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Netherlands Twin Register, Department of Biological Psychology (C.E.M.v.B., D.I.B.), VU University Amsterdam, 1081 BT Amsterdam, The Netherlands; National Institute for Public Health and the Environment (P.O.), 3720 BA Bilthoven, The Netherlands; and Department of Pediatric Endocrinology (M.J.J.F.), VU University Medical Center, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.affiliation: Department of Pediatric Endocrinology (N.Z.-S., E.T.M., B.W., A.S.P.v.T.), Emma Children's Hospital, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Netherlands Twin Register, Department of Biological Psychology (C.E.M.v.B., D.I.B.), VU University Amsterdam, 1081 BT Amsterdam, The Netherlands; National Institute for Public Health and the Environment (P.O.), 3720 BA Bilthoven, The Netherlands; and Department of Pediatric Endocrinology (M.J.J.F.), VU University Medical Center, 1081 HZ Amsterdam, The Netherlands.
authors.forename: A S Paul
authors.initials: AS
authors.lastname: van Trotsenburg
mesh_terms: D004200:Diseases in Twins / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology; D004777:Environment; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D012042:Registries; D013959:Thyroid Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D013974:Thyroxine / Q000097:blood*; D014427:Twins
chemical_list: D013974:Thyroxine