title: Maternal and Birth Characteristics Are Determinants of Offspring Thyroid Function.
abstract: BACKGROUND
  Intrauterine adaptation to the outside environment is an important mechanism via which the fetus increases its chance to thrive after birth. Therefore, various maternal-, pregnancy-, and labor-related factors are potential determinants of thyroid function of the offspring. Animal studies suggest that very high maternal thyroid hormone levels during pregnancy can alter the development of the hypothalamic-pituitary-thyroid axis set point of the child. However, to what extent maternal and birth characteristics (including maternal thyroid function, smoking, and birth weight) are associated with thyroid function of the offspring is currently unknown.
  
  
  METHODS
  We selected 4273 mother-child pairs from a large population-based prospective cohort with data available on maternal gestational TSH and free T4 (FT4) levels and newborn TSH and FT4 (n = 3339; at birth) or childhood TSH and FT4 (n = 2523; median age, 6 y). We used multivariable (non)linear regression models to study the association of potential determinants (including maternal TSH, FT4, thyroid peroxidase antibodies, iodine excretion, age, body mass index, smoking status, parity, pre-eclampsia, fetal distress, gestational age at birth, birth weight, mode of delivery, and thyroid function-associated single nucleotide polymorphisms) with newborn and childhood TSH and FT4.
  
  
  RESULTS
  There was a strong association of maternal TSH and FT4 levels during pregnancy with newborn and childhood TSH and FT4 levels, respectively (for both, P < .0001). Maternal FT4 was also associated with newborn TSH levels (P = .0009). Birth weight, fetal distress, gestational age at birth and maternal parity were all associated with newborn TSH and/or FT4 (P < .0001), but these associations did not persist into childhood. Genetic risk scores for TSH and FT4 were strongly associated with newborn and childhood thyroid function (P ≤ .0005). The association between maternal and offspring thyroid function did not change after correction for genetic risk scores.
  
  
  CONCLUSIONS
  In this study, childhood thyroid function was predominantly determined by maternal TSH or FT4 levels and thyroid-specific single nucleotide polymorphisms. Effects of stress-related changes in thyroid function at birth were transient. Other potential factors were not associated with offspring thyroid function.
authors.affiliation: The Generation R Study Group (T.I.M.K., V.W.V.J., M.M.) and Departments of Internal Medicine (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Pediatrics (V.W.V.J.), and Epidemiology (V.W.V.J.), Erasmus Medical Center-Sophia Children's Hospital, 3000 CA, Rotterdam, The Netherlands; and Rotterdam Thyroid Center (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Tim I M
authors.initials: TI
authors.lastname: Korevaar
authors.affiliation: The Generation R Study Group (T.I.M.K., V.W.V.J., M.M.) and Departments of Internal Medicine (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Pediatrics (V.W.V.J.), and Epidemiology (V.W.V.J.), Erasmus Medical Center-Sophia Children's Hospital, 3000 CA, Rotterdam, The Netherlands; and Rotterdam Thyroid Center (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Layal
authors.initials: L
authors.lastname: Chaker
authors.affiliation: The Generation R Study Group (T.I.M.K., V.W.V.J., M.M.) and Departments of Internal Medicine (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Pediatrics (V.W.V.J.), and Epidemiology (V.W.V.J.), Erasmus Medical Center-Sophia Children's Hospital, 3000 CA, Rotterdam, The Netherlands; and Rotterdam Thyroid Center (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: The Generation R Study Group (T.I.M.K., V.W.V.J., M.M.) and Departments of Internal Medicine (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Pediatrics (V.W.V.J.), and Epidemiology (V.W.V.J.), Erasmus Medical Center-Sophia Children's Hospital, 3000 CA, Rotterdam, The Netherlands; and Rotterdam Thyroid Center (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.affiliation: The Generation R Study Group (T.I.M.K., V.W.V.J., M.M.) and Departments of Internal Medicine (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Pediatrics (V.W.V.J.), and Epidemiology (V.W.V.J.), Erasmus Medical Center-Sophia Children's Hospital, 3000 CA, Rotterdam, The Netherlands; and Rotterdam Thyroid Center (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Medici
authors.affiliation: The Generation R Study Group (T.I.M.K., V.W.V.J., M.M.) and Departments of Internal Medicine (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Pediatrics (V.W.V.J.), and Epidemiology (V.W.V.J.), Erasmus Medical Center-Sophia Children's Hospital, 3000 CA, Rotterdam, The Netherlands; and Rotterdam Thyroid Center (T.I.M.K., L.C., T.J.V., M.M., R.P.P.), Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
mesh_terms: D000328:Adult; D001724:Birth Weight; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D014644:Genetic Variation; D006801:Humans; D007231:Infant, Newborn; D009035:Mothers; D036801:Parturition / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood; D011446:Prospective Studies; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood / Q000235:genetics; D013974:Thyroxine / Q000097:blood / Q000235:genetics
chemical_list: D013972:Thyrotropin; D013974:Thyroxine