title: Maternal Thyroid Disease and Preterm Birth: Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Thyroid disease in pregnancy is increasing with rising average maternal ages in developed countries. The evidence for an association between preterm birth and thyroid disease has been confounded by small studies with varying outcomes and methodology.
  
  
  OBJECTIVE
  The aim of this meta-analysis is to review the literature regarding thyroid disease including subclinical and overt hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia and the specific outcome of preterm birth.
  
  
  METHODS
  A search of PubMed and Embase databases was performed in May 2015. A fixed-effects model was used to calculate the overall combined odds ratio (OR) with its corresponding 95% confidence interval (95% CI) to evaluate the relationship between thyroid disease and preterm delivery.
  
  
  METHODS
  Studies were considered eligible if they met the following criteria: prospective cohort study or a case control study; the exposure of interest was maternal thyroid disease, including subclinical hypothyroidism, overt hypothyroidism, hyperthyroidism, or isolated hypothyroxinemia; the outcome of interest was preterm delivery; and data regarding numbers of preterm births in each cohort were reported.
  
  
  METHODS
  Data were recorded in a database evidence table including any incidence data for maternal thyroid disease and preterm birth compared to a reference group.
  
  
  RESULTS
  Fourteen cohort studies and one case control study involving 2 532 704 participants were included. The combined OR of preterm delivery for pregnant women with overt hypothyroidism compared with the reference group was 1.19 (95% CI, 1.12-1.26; P < .00001). There was also a significant risk of preterm birth in women with hyperthyroidism (OR, 1.24 [95%, CI 1.17-1.31]; P < .00001). Subclinical hypothyroidism and isolated hypothyroxinemia showed no significant increase in OR. Sensitivity analysis made no change to these results.
  
  
  CONCLUSIONS
  Both overt hypothyroidism and hyperthyroidism are associated with a small but statistically significant increase in OR for preterm birth not seen in subclinical hypothyroidism or isolated hypothyroxinemia.
authors.affiliation: Department of Obstetrics and Gynaecology (P.M.S., F.D.S.C.), University of Melbourne, Parkville, Victoria, Australia; Royal Women's Hospital (P.M.S., A.N., F.D.S.C.), Melbourne, Victoria, Australia; Department of Obstetrics (E.A.J.), Paulista School of Medicine - Federal University of São Paulo, São Paulo-SP, Brazil; Pregnancy Research Centre (P.M.S., F.D.S.C.), Royal Women's Hospital, Melbourne, Victoria, Australia.
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Sheehan
authors.affiliation: Department of Obstetrics and Gynaecology (P.M.S., F.D.S.C.), University of Melbourne, Parkville, Victoria, Australia; Royal Women's Hospital (P.M.S., A.N., F.D.S.C.), Melbourne, Victoria, Australia; Department of Obstetrics (E.A.J.), Paulista School of Medicine - Federal University of São Paulo, São Paulo-SP, Brazil; Pregnancy Research Centre (P.M.S., F.D.S.C.), Royal Women's Hospital, Melbourne, Victoria, Australia.
authors.forename: Alison
authors.initials: A
authors.lastname: Nankervis
authors.affiliation: Department of Obstetrics and Gynaecology (P.M.S., F.D.S.C.), University of Melbourne, Parkville, Victoria, Australia; Royal Women's Hospital (P.M.S., A.N., F.D.S.C.), Melbourne, Victoria, Australia; Department of Obstetrics (E.A.J.), Paulista School of Medicine - Federal University of São Paulo, São Paulo-SP, Brazil; Pregnancy Research Centre (P.M.S., F.D.S.C.), Royal Women's Hospital, Melbourne, Victoria, Australia.
authors.forename: Edward
authors.initials: E
authors.lastname: Araujo Júnior
authors.affiliation: Department of Obstetrics and Gynaecology (P.M.S., F.D.S.C.), University of Melbourne, Parkville, Victoria, Australia; Royal Women's Hospital (P.M.S., A.N., F.D.S.C.), Melbourne, Victoria, Australia; Department of Obstetrics (E.A.J.), Paulista School of Medicine - Federal University of São Paulo, São Paulo-SP, Brazil; Pregnancy Research Centre (P.M.S., F.D.S.C.), Royal Women's Hospital, Melbourne, Victoria, Australia.
authors.forename: Fabricio
authors.initials: F
authors.lastname: Da Silva Costa
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000453:epidemiology; D007037:Hypothyroidism / Q000453:epidemiology; D007752:Obstetric Labor, Premature / Q000453:epidemiology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D013959:Thyroid Diseases / Q000453:epidemiology*