title: The association of maternal thyroid function with placental hemodynamics.
abstract: What is the clinical association of maternal thyroid function with placental hemodynamic function?
  
  
  
  A higher free thyroxine (FT4) concentration in early pregnancy is associated with higher placental vascular resistance.
  
  
  
  Suboptimal placental function is associated with preeclampsia (which, in turn, further deteriorates placental hemodynamics and impairs the fetal blood supply), fetal growth restriction and premature delivery. Studies have suggested that thyroid hormone (TH) has a role in placental development through effects on trophoblast proliferation and invasion.
  
  
  
  This study was embedded in The Generation R cohort, a population-based prospective study from early fetal life onwards in Rotterdam, the Netherlands. In total, 7069 mothers with expected delivery date between April 2002 and January 2006 were enrolled during early pregnancy.
  
  
  
  Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) concentrations were measured during early pregnancy (median 13.4 weeks, 95% range 9.7-17.6 weeks). Placental function was assessed by Doppler ultrasound via measurement of arterial vascular resistance, i.e. umbilical artery pulsatility index (PI) and uterine artery resistance index (RI) (both measured twice, between 18-25th and after 25th gestational weeks) and the presence of uterine artery notching (once after the 25th gestational week) in 5184 pregnant women.
  
  
  
  FT4 was positively linearly associated with umbilical artery PI in the second and third trimesters as well as with uterine artery RI in the second trimester and the risk of uterine artery notching in the third trimester (P < 0.05 for all). The association of thyroid function with preeclampsia and birth weight was partially mediated through changes in placental function, with the percentages of mediated effects being 10.4% and 12.5%, respectively.
  
  
  
  A potential limitation is the availability of only a single time point for TH measurements and different numbers of missing placental ultrasound measurements for the adverse outcomes.
  
  
  
  A higher FT4 concentration in early pregnancy is associated with higher vascular resistance in the second and third trimesters in both the maternal and fetal placental compartment. These effects on placental function might explain the association of FT4 with adverse pregnancy outcomes, including preeclampsia and fetal growth restriction.
  
  
  
  This work was supported by a fellowship from ERAWEB, a project funded by the European Commission (to M.B.) and by clinical fellowship from The Netherlands Organization for Health Research and Development (ZonMw), Project 90700412 (to R.P.P.). The authors have no conflict of interest.
  
  
  
  N/A.
authors.affiliation: The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Dr Molewaterplein 50, Room Ee 502a, 3015 GE, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Barjaktarovic
authors.affiliation: The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Internal Medicine, Erasmus Medical Center, Dr Molewaterplein 50, Room Ee 502a, 3015 GE, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: T I M
authors.initials: TI
authors.lastname: Korevaar
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Dr Molewaterplein 50, Room Ee 502a, 3015 GE, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Chaker
authors.affiliation: The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: V W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Dr Molewaterplein 50, Room Ee 502a, 3015 GE, Rotterdam, The Netherlands.|Department of Clinical Chemistry, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: Y B
authors.initials: YB
authors.lastname: de Rijke
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Dr Molewaterplein 50, Room Ee 502a, 3015 GE, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: T J
authors.initials: TJ
authors.lastname: Visser
authors.affiliation: Department of Obstetrics and Gynecology, Erasmus Medical Center-Sophia Children's Hospital, Rotterdam, The Netherlands.
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Dr Molewaterplein 50, Room Ee 502a, 3015 GE, Rotterdam, The Netherlands.|Rotterdam Thyroid Center, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: R P
authors.initials: RP
authors.lastname: Peeters
mesh_terms: D000328:Adult; D005260:Female; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D010920:Placenta / Q000098:blood supply* / Q000000981:diagnostic imaging; D011247:Pregnancy; D013961:Thyroid Gland / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D018608:Ultrasonography, Doppler; D014469:Umbilical Arteries / Q000000981:diagnostic imaging / Q000502:physiology; D055988:Uterine Artery / Q000000981:diagnostic imaging / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology*; D055815:Young Adult
chemical_list: D013972:Thyrotropin; D013974:Thyroxine
keywords: placenta; placental hemodynamics; pregnancy; thyroid function