title: Thyroid Autoimmunity Impairs the Thyroidal Response to Human Chorionic Gonadotropin: Two Population-Based Prospective Cohort Studies.
abstract: Thyroperoxidase antibody (TPOAb) positivity is the main risk factor for thyroid dysfunction during pregnancy and is consistently associated with premature delivery. However, the underlying mechanism is currently unknown. We hypothesized that TPOAb positivity may interfere with gestational thyroid stimulation induced by the pregnancy hormone human chorionic gonadotropin (hCG).
  
  
  
  Thyrotropin (TSH), free thyroxine (FT4), TPOAbs, and/or hCG concentrations were measured in early and late pregnancy of 7587 pregnant women from 2 Dutch population-based prospective cohorts (n = 5924, Generation R study; n = 1663, Holistic Approach to Pregnancy and the First Postpartum Year study).
  
  
  
  None.
  
  
  
  Thyroidal response to hCG stimulation, premature delivery.
  
  
  
  In TPOAb-negative women, hCG was positively associated with FT4 and negatively with TSH in both cohorts (P < 0.0001). In contrast, in TPOAb-positive women, hCG was not associated with FT4 or TSH in either cohort (all P > 0.40; P for interaction TPOAb positive vs negative ≤ 0.05). Overall, TPOAb positivity was associated with a 1.7-fold higher risk of premature delivery. TPOAb-positive women with an adequate response of FT4 to hCG (high FT4 concentration with high hCG concentration) did not have a higher risk of premature delivery. In contrast, TPOAb-positive women with an inadequate FT4 response to hCG (low FT4 concentration with high hCG concentration) had a 2.2- to 2.8-fold higher risk of premature delivery.
  
  
  
  TPOAb-positive women display an impaired thyroidal response to hCG and this may explain the higher risk of premature delivery in these women. This abnormal response in TPOAb-positive women might suggest that these women require a different treatment approach than TPOAb-negative women.
authors.affiliation: The Generation R Study Group, and Departments of.|Internal Medicine.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Tim I M
authors.initials: TI
authors.lastname: Korevaar
authors.affiliation: Obstetrics and Gynecology.
authors.forename: Eric A P
authors.initials: EA
authors.lastname: Steegers
authors.affiliation: Department of Medical and Clinical Psychology, Tilburg University, Warandelaan 2, Tilburg 5000 LE, The Netherlands; and.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Pop
authors.affiliation: Laboratory of Clinical Chemistry and Hematology, Máxima Medical Centre, Veldhoven, De Run, 4600, The Netherlands.
authors.forename: Maarten A
authors.initials: MA
authors.lastname: Broeren
authors.affiliation: Internal Medicine.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Layal
authors.initials: L
authors.lastname: Chaker
authors.affiliation: Clinical Chemistry.
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.affiliation: The Generation R Study Group, and Departments of.|Pediatrics.|Epidemiology, and.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: The Generation R Study Group, and Departments of.|Internal Medicine.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Medici
authors.affiliation: Internal Medicine.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.affiliation: Epidemiology, and.|Child and Adolescent Psychiatry, Erasmus Medical Center and/or Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: Internal Medicine.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000097:blood*; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007453:Iodide Peroxidase / Q000097:blood*; D033862:Iron-Binding Proteins / Q000097:blood*; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D047928:Premature Birth / Q000453:epidemiology* / Q000276:immunology; D011379:Prognosis; D011446:Prospective Studies; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology*; D013972:Thyrotropin / Q000097:blood*; D013974:Thyroxine / Q000097:blood*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D006063:Chorionic Gonadotropin; D033862:Iron-Binding Proteins; D013972:Thyrotropin; C056658:TPO protein, human; D007453:Iodide Peroxidase; D013974:Thyroxine