John Lazarus, Rosalind S. Brown, Chantal Daumerie, Alicja Hubalewska-Dydejczyk, Roberto Negro, Bijay Vaidya Eur Thyroid J 2014; 3:76–94

Abstract: This guideline has been produced as the official statement of the European Thyroid Association guideline committee. Subclinical hypothyroidism (SCH) in pregnancy is defined as a thyroid-stimulating hormone (TSH) level above the preg- nancy-related reference range with a normal serum thyrox- ine concentration. Isolated hypothyroxinaemia (defined as a thyroxine level below the 2.5th centile of the pregnancy-re- lated reference range with a normal TSH level) is also recog- nized in pregnancy. In the majority of SCH the cause is auto- immune thyroiditis but may also be due to iodine deficiency. The cause of isolated hypothyroxinaemia is usually not ap- parent, but iodine deficiency may be a factor. SCH and iso- lated hypothyroxinaemia are both associated with adverse obstetric outcomes. Levothyroxine therapy may ameliorate some of these with SCH but not in isolated hypothyroxin- aemia. SCH and isolated hypothyroxinaemia are both associ- ated with neuro-intellectual impairment of the child, but there is no evidence that maternal levothyroxine therapy im- proves this outcome. Targeted antenatal screening for thyroid function will miss a substantial percentage of women with thyroid dysfunction. In children SCH (serum TSH con- centration >5.5–10 mU/l) normalizes in >70% and persists in the majority of the remaining patients over the subsequent 5 years, but rarely worsens. There is a lack of studies examin- ing the impact of SCH on the neuropsychological develop- ment of children under the age of 3 years. In older children, the evidence for an association between SCH and impaired neuropsychological development is inconsistent. Good qual- ity studies examining the effect of treatment of SCH in children are lacking.

Introduction: Subclinical hypothyroidism (SCH) in pregnancy is de- fined by a serum thyroid-stimulating hormone (TSH) concentration higher than the upper limit of the pregnan- cy-related reference range associated with a normal serum thyroxine [T4; either total (TT4) or free (FT4)] concentration. The serum tri-iodothyronine (T3) level is nor- mal. It occurs in approximately 2–2.5% of pregnant women [1], although in China the incidence has been re- ported to be 4.0% [2], in Belgium 6.8% [3] and in North- ern Spain as high as 13.7% [4]. This is in contrast to overt hypothyroidism (defined as FT4 below normal in con- junction with elevated TSH or TSH higher than 10 mU/l irrespective of FT4 levels) which has a prevalence of around 0.2–0.5% in pregnancy and which will not be con- sidered further in this guideline. In children the preva- lence of SCH is less than 2% [5]. When considering SCH, it was agreed that the so-called isolated hypothyroxin- aemia as a separate entity should also be included in the discussion. This is normally defined as a serum T4 con- centration (TT4 or FT4) as being in the lower 2.5% of the reference range [6]. This definition implies that hypothy- roxinaemia is associated with a normal TSH concentration.

During the last 2 decades advances in our understand- ing of thyroid physiology in pregnancy have led to the appreciation of the adverse effects of SCH on both the mother and child. Furthermore, considerable variation in the management of SCH in pregnancy was observed in a recent European Thyroid Association survey [7]. Hence the European Thyroid Association commissioned a task force to prepare the current guidelines. In addition, there have never been any published guidelines on SCH in chil- dren. The present guideline may usefully be read in con- junction with guidelines on the management of SCH in non-pregnant persons recently published by Pearce et al. [8] in addition to published guidelines of the American Thyroid Association [6] and the American Endocrine So- ciety [9] both addressing the subject of thyroid and preg- nancy.

Methods: The executive committee of the European Thyroid Association and the guideline board nominated a task force for the develop- ment of guidelines on the management of SCH in pregnancy and children. The task force had no commercial support, and the mem- bers declared no conflict of interest. A list of all relevant topics re- lated to SCH in pregnancy and children was created, and the mem- bers then performed a comprehensive literature review, carrying out a systematic Pubmed and Medline search for original and re-view articles published from 1970 to December 2013. The search terms used were TSH, levothyroxine, pregnancy, SCH, adverse ef- fects, abortion, miscarriage, iodine, thyroid antibodies, children and Hashimoto’s disease. The guidelines were constructed based on the best scientific evidence and the skills of the task force. Where available, data derived from randomized clinical trials (RCT) rather than observational studies has been selected for rec- ommendations. The GRADE system is employed which has been used in other guidelines. The quality of the literature concerning each aspect of the statement was graded as high (RCT evidence – level 1), moderate (intervention short of RCT or large observa- tional studies – level 2) or low quality (case series, case reports, expert opinion – level 3) using modified GRADE criteria [10, 11]. The strength of each statement was classified as strong (S, a recom- mendation) or weak (W, a suggestion; see Recommendations be- low), depending upon the clinical significance and weight of opinion favouring the statement. Strong recommendations are clini- cally important best practice and should be applied to most patients in most circumstances. In contrast, weak statements should be considered by the clinician and will be applicable best practice only to certain patients or under certain circumstances.

Download PDF