title: Interventions for clinical and subclinical hypothyroidism pre-pregnancy and during pregnancy.
abstract: BACKGROUND
  Over the last decade there has been enhanced awareness of the appreciable morbidity of thyroid dysfunction, particularly thyroid deficiency. Since treating clinical and subclinical hypothyroidism may reduce adverse obstetric outcomes, it is crucial to identify which interventions are safe and effective.
  
  
  OBJECTIVE
  To identify interventions used in the management of hypothyroidism and subclinical hypothyroidism pre-pregnancy or during pregnancy and to ascertain the impact of these interventions on important maternal, fetal, neonatal and childhood outcomes.
  
  
  METHODS
  We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 March 2013).
  
  
  METHODS
  Randomised controlled trials (RCTs) and quasi-randomised controlled trials that compared a pharmacological intervention for hypothyroidism and subclinical hypothyroidism pre-pregnancy or during pregnancy with another intervention or placebo.
  
  
  METHODS
  Two review authors assessed trial eligibility and quality and extracted the data.
  
  
  RESULTS
  We included four RCTs of moderate risk of bias involving 362 women. In one trial of 115 women, levothyroxine therapy to treat pregnant euthyroid (normal thyroid function) women with thyroid peroxidase antibodies was not shown to reduce pre-eclampsia significantly (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.11 to 3.48) but did significantly reduce preterm birth by 72% (RR 0.28; 95% CI 0.10 to 0.80). Two trials of 30 and 48 hypothyroid women respectively compared levothyroxine doses, but both trials reported only biochemical outcomes. A trial of 169 women compared the trace element selenomethionine (selenium) with placebo and no significant differences were seen for either pre-eclampsia (RR 1.44; 95% CI 0.25 to 8.38) or preterm birth (RR 0.96; 95% CI 0.20 to 4.61). None of the four trials reported on childhood neurodevelopmental delay.There was a non-significant trend towards fewer miscarriages with levothyroxine, and selenium showed some favourable impact on postpartum thyroid function and a decreased incidence of moderate to advanced postpartum thyroiditis.
  
  
  CONCLUSIONS
  This review found no difference between levothyroxine therapy and a control for treating pregnant euthyroid women with thyroid peroxidase antibodies for the outcome of pre-eclampsia, however a reduction in preterm birth and a trend towards reduced miscarriage with levothyroxine was shown. This review also showed no difference for pre-eclampsia or preterm birth when selenium was compared with placebo, however a promising reduction in postpartum thyroiditis was shown. Childhood neurodevelopmental delay was not assessed by any trial included in the review.Given that this review is based on four trials of moderate risk of bias, with only two trials contributing data (n = 284), there is insufficient evidence to recommend the use of one intervention for clinical or subclinical hypothyroidism pre-pregnancy or during pregnancy over another, for improving maternal, fetal, neonatal and childhood outcomes.
authors.affiliation: ARCH: Australian Research Centre for Health of Women and Babies, The Robinson Institute, Discipline of Obstetrics and Gynaecology,The University of Adelaide, Adelaide, Australia. sally.reid@adelaide.edu.au.
authors.forename: Sally M
authors.initials: SM
authors.lastname: Reid
authors.forename: Philippa
authors.initials: P
authors.lastname: Middleton
authors.forename: Mary C
authors.initials: MC
authors.lastname: Cossich
authors.forename: Caroline A
authors.initials: CA
authors.lastname: Crowther
authors.forename: Emily
authors.initials: E
authors.lastname: Bain
mesh_terms: D000022:Abortion, Spontaneous / Q000517:prevention & control; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy*; D011225:Pre-Eclampsia / Q000517:prevention & control; D016742:Preconception Care / Q000379:methods; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D012645:Selenomethionine / Q000627:therapeutic use*; D013961:Thyroid Gland / Q000276:immunology; D013967:Thyroiditis, Autoimmune / Q000188:drug therapy; D013974:Thyroxine / Q000627:therapeutic use*
chemical_list: D012645:Selenomethionine; D013974:Thyroxine