In primary prevention, screening is defined as testing for a disease when there are no signs or symptoms, with the aim of improving health outcomes by early diagnosis followed by treatment (when required) or monitoring. Because I have been directly involved, already back in 1998, by proposing two algorithms for systematic screening for thyroid disorders associated with pregnancy, and also because I was a member of the recent international ad hoc committee involved in the establishment of clinical practice guidelines for thyroid diseases and pregnancy, I will present in this section my own views on this rather ‘touchy’ and difficult question [1, 194].

In order to justify systematic screening in primary prevention in medicine in general, a number of prerequisites has, ideally, to be met:

When trying to assess whether such prerequisites have been met (completely or partially) for thyroid disorders associated with pregnancy, what can we conclude?

Concerning the prevalence of thyroid disorders, studies have shown that 5-15% of pregnant women have thyroid autoantibodies, 2-3% of them have undiagnosed hypothyroidism, and 0.3-0.5% undiagnosed hyperthyroidism [407]. Based on our own pregnancy studies in Belgium, Figure 14-20 presents a synopsis of the different thyroid conditions that were observed in two successive prospective cohort studies (involving altogether ~2.400 women). The data indicate clearly that the overall prevalence of thyroid disorders associated with pregnancy is sufficiently high to – at least strongly consider – and probably warrant screening.

With regard to the laboratory techniques (reliability & safety), no real problem exists. The two main candidates for screening are serum TSH and detection of TPO-Ab. More complete testing would also include measurement of serum free T4, although the clinical significance of isolated hypothyroxinemia remains unclear. Preliminary results from an going prospective study in Wales, (the controlled antenatal thyroid screening study ‘CATS’), utilizing both serum TSH and free T4 measurements to diagnose thyroid function abnormalities, indicate that the abnormalities tend to cluster around two main pregnant subpopulations [408]. In about half the women with abnormalities, an isolated low serum free T4 level was found (defined as in the lowest 2.5th centile of normals) and an equal number of women having an isolated high serum TSH (defined as above the 97.5th centile of normals), with very few having both a low T4 and a high TSH.

Concerning the financial burden of thyroid testing, the latest calculations I made for my country (Belgium) indicate that measuring TSH, free T4 and TPO-Ab amounts to a total cost of 38.40 € (i.e. ~50 $). Patients who are covered by the national social security system (i.e. almost 100% of the population) would have to contribute 8.70 €, and the state would reimburse the difference to the laboratory (i.e. 29.70 €). When considering the average medical ‘cost’ of an uncomplicated pregnancy in our country (~2.500 €), the inclusion of thyroid screening would add 1.5% to the overall cost.

Concerning screening procedures themselves, several schemes can be proposed, although all encompass advantages and disadvantages that need to be carefully considered. The optimal timing of screening has not been determined, although there are good arguments to favor early screening during gestation. Immune suppression of autoantibody production points to the necessity to check the presence of TPO-Ab as early as possible during gestation. On the other hand, the normal physiologic (transient) blunting in serum TSH near the end of first trimester makes the delineation of an optimal timing for screening by TSH more complex. Therefore, nomograms or trimester-specific references for normality have been proposed by some authors to facilitate the interpretation of TSH changes during pregnancy. Measurements of serum free T4 can also be altered artefactually during pregnancy and this needs to be considered as well, and might perhaps be minimized by using laboratory-specific or assay-specific or trimester-specific serum free T4 reference norms, that need to be locally established.

Concerning benefits of treatment with regard to obstetrical outcomes and fetal development, there is good evidence that they outweigh largely the risks associated with absence of treatment for overt hypothyroidism & hyperthyroidism (related mainly to Graves’ disease) (see Table 14-15). Concerning subclinical hypothyroidism and thyroid autoimmunity features in women who have normal thyroid function in early pregnancy, studies have now convincingly shown the advantages of early treatment with restoration and/or maintenance of euthyroidism throughout gestation [190, 223]. Concerning subclinical hyperthyroidism (related mainly to gestational hCG-induced hyperthyroidism), advantages of treatment have not been demonstrated so far, except in the severe cases with hyperemesis gravidarum. After screening, and notwithstanding the decision to treat a thyroid condition or monitor thyroid function, it is important to note that diagnosing chronic autoimmune thyroiditis also allows for delineating a group of women who are obviously at risk of developing thyroid dysfunction during the postpartum period and/or hypothyroidism later in life [193].

Besides the issues of cost, practicality, or feasibility of systematic screening in pregnancy, potential disadvantages must also be considered. For instance, the results of screening might induce unnecessary anxiety. Also, finding a low serum TSH (without hyperthyroidism) might be followed by the administration of antithyroid drugs, even when treatment is not justified. Finally, there are also legal considerations in this matter: if universal screening is to become mandatory, then any deviation from the accepted guidelines might be a cause for legal suits.

Policy considerations concerning routine thyroid screening before or during pregnancy remain controversial and the subject of hot debate, especially in the United States. Between 2000 & 2004, the American College of Obstetricians and Gynecologists (ACOG), the American Thyroid Association (ATA), and a consensus panel involving the American Association of Clinical Endocrinologists (AACE), the ATA, and the Endocrine Society (ES) have either found insufficient evidence to recommend routine screening in pregnancy (or in women desiring pregnancy) or have not endorsed it [409-411]. Subsequently, the leadership of AACE, ATA, and ES has invited a second group to determine whether there were areas of legitimate and significant disagreement with the conclusions of the consensus panel and this group concluded in ‘favor of routine screening for subclinical thyroid dysfunction in adults, including pregnant women and those contemplating pregnancy’ [412].

In 2005, an international ad hoc committee was established under the auspices of the American Endocrine Society to review the best evidence for thyroid disorders associated with pregnancy and develop evidence-based guidelines for clinical practice. Members of the ten-person task force (chaired by Leslie De Groot) included representatives of the ES, ATA, ETA, LATS, AOTA, AACE and ACOG. The issue of “universal screening” was hotly debated in the task force. Our main consideration was that negative outcomes have clearly been linked to abnormalities in thyroid function associated with pregnancy and we therefore felt that renewed attention should be focused on screening for thyroid dysfunction in the peri-partum period. Specifically, the association of infertility with thyroid autoimmunity and/or dysfunction, the association of an increased risk of miscarriage with thyroid abnormalities, the association of a poorer obstetrical outcome with thyroid dysfunction, the association of a decreased IQ in the offspring with subtle degrees of maternal thyroid dysfunction, and finally the association of postpartum thyroid disorders with thyroid autoimmunity, all contributed to the apparent merit of universal screening. However after reviewing the available evidence, force was for us to admit that the overall lack of carefully conducted studies evaluating the impact of medical intervention on the negative outcomes associated with thyroid abnormalities during pregnancy and postpartum precluded a recommendation for universal screening. As already alluded to above, individual members of our committee considered that they had good arguments to believe that the evidence (albeit incomplete or indirect) was probably sufficient to justify screening before/during pregnancy. In fact, this practice has been adopted in many university hospital centers, for instance (but not only) in Europe. A recent survey by Haddow et al. indicated that many practitioners in Maine have also instituted routine TSH testing in pregnancy, in spite of a lack of consensus among professional organizations [413].

Finally our committee came to the conclusion that although it was presently not possible to recommend universal screening, an acceptable compromise was to propose aggressive case finding, namely routine screening in selected high-risk women (see Table 14-8). We strongly believe that the benefits of treatment outweigh largely the minor risk of potential adverse outcomes related to medical intervention. Thus, targeted case finding in high risk populations may provide (temporarily?) an appropriate balance between inaction and screening entire populations (the details can be found in the section on “primary hypothyroidism”). On a personal note, it is regrettable that the ACOG, eventually, did not endorse the recommendations of our committee, for reasons that presently remain largely unclear to this writer. It could indeed be argued that the high frequency of thyroid hormone and TSH determinations that are out of the ‘normal’ range, but normal for pregnancy, constitute an adverse effect of systematic screening by health care providers other than endocrinologists [414]. These values could wrongly be misinterpreted by non-endocrine providers and result in unnecessary anxiety, referral, and even undue treatments for the pregnant woman. Alternatively, and as already elaborated earlier, there are good arguments to advise that routine screening for thyroid disorders is warranted in the general population, and especially in pregnant women [412].

Is an aggressive case-finding approach sufficient? Vaidya et al. have recently evaluated the results of screening only pregnant women who were classified as ‘high-risk’ [415]. In this study, the authors showed that the use of high-risk criteria detected only 70% of women with hypothyroidism, and that these criteria were no better than the low-risk criteria for the identification of women with a fully suppressed serum TSH. It is therefore reasonable to conclude that such study highlights the benefits and shortcomings of targeted screening and help reminding us that this strategy remains a partial solution [407, 416].