title: Risk factors and a clinical prediction model for low maternal thyroid function during early pregnancy: two population-based prospective cohort studies.
abstract: BACKGROUND
  Low maternal thyroid function during early pregnancy is associated with various adverse outcomes including impaired neurocognitive development of the offspring, premature delivery and abnormal birthweight.
  
  
  OBJECTIVE
  To aid doctors in the risk assessment of thyroid dysfunction during pregnancy, we set out to investigate clinical risk factors and derive a prediction model based on easily obtainable clinical variables.
  
  
  METHODS
  In total, 9767 women during early pregnancy (≤18 week) were selected from two population-based prospective cohorts: the Generation R Study (N = 5985) and the ABCD study (N = 3782). We aimed to investigate the association of easily obtainable clinical subject characteristics such as maternal age, BMI, smoking status, ethnicity, parity and gestational age at blood sampling with the risk of low free thyroxine (FT4) and elevated thyroid stimulating hormone (TSH), determined according to the 2·5th-97·5th reference range in TPOAb negative women.
  
  
  RESULTS
  BMI, nonsmoking and ethnicity were risk factors for elevated TSH levels; however, the discriminative ability was poor (range c-statistic of 0·57-0·60). Sensitivity analysis showed that addition of TPOAbs to the model yielded a c-statistic of 0·73-0·75. Maternal age, BMI, smoking, parity and gestational age at blood sampling were risk factors for low FT4, which taken together provided adequate discrimination (range c-statistic of 0·72-0·76).
  
  
  CONCLUSIONS
  Elevated TSH levels depend predominantly on TPOAb levels, and prediction of elevated TSH levels is not possible with clinical characteristics only. In contrast, the validated clinical prediction model for FT4 had high discriminative value to assess the likelihood of low FT4 levels.
authors.affiliation: The Generation R Study Group, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Tim I M
authors.initials: TI
authors.lastname: Korevaar
authors.affiliation: Department of Public Health, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Daan
authors.initials: D
authors.lastname: Nieboer
authors.affiliation: Department of Endocrinology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Peter H L T
authors.initials: PH
authors.lastname: Bisschop
authors.affiliation: Department of Reproductive Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Mariette
authors.initials: M
authors.lastname: Goddijn
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Marco
authors.initials: M
authors.lastname: Medici
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Layal
authors.initials: L
authors.lastname: Chaker
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.|Department of Clinical Chemistry, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Yolanda B
authors.initials: YB
authors.lastname: de Rijke
authors.affiliation: The Generation R Study Group, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Vincent W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.affiliation: Department of Public Health, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.affiliation: Department of Epidemiology, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.|Department of Child and Adolescent Psychiatry, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: Department of Public Health, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Tanja G
authors.initials: TG
authors.lastname: Vrijkotte
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus University Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Robin P
authors.initials: RP
authors.lastname: Peeters
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D005865:Gestational Age; D006801:Humans; D007037:Hypothyroidism / Q000175:diagnosis*; D007453:Iodide Peroxidase / Q000276:immunology; D033862:Iron-Binding Proteins / Q000276:immunology; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests; D011247:Pregnancy; D011248:Pregnancy Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D033862:Iron-Binding Proteins; D013972:Thyrotropin; C056658:TPO protein, human; D007453:Iodide Peroxidase; D013974:Thyroxine