Here’s to You, Baby! A Step Forward in Support of Universal Screening of Thyroid Function during Pregnancy

Thyroid hormone abnormalities (particularly hypothyroidism) are common in women of childbearing age (1, 2) and are easily detected with a simple assessment of serum TSH. When identified, a safe, inexpensive supplement of levothyroxine adequately treats this condition. Yet, when untreated, several investigations demonstrate harmful effects on the pregnancy and/or the fetus (3, 4). The paradigm above sets the stage for a simple yet hotly debated question impacting over 4 million women in the United States annually: Should women seeking pregnancy (or those newly pregnant) be screened for thyroid illness? Making the answer to this question more difficult is the variability and heterogeneity of clinical scenarios impacted by this answer. Who should be assessed? When and how often should they be tested? And, are the presumed benefits equally applicable to all permutations of the answers to these questions? The latter question is easier to answer than the former—and the answer is an emphatic “No.” But while all of the these answers are sorted out, the potential harm induced by maternal hypothyroidism cannot be ignored. Although much attention has been recently paid to the potential adverse effects of mild to moderate maternal hypothyroidism on fetal cognitive development (and the fetal brain), it is increasingly apparent that the mother herself may be most susceptible to the risk imparted by even the mildest case of hypothyroidism. This was first suggested by a large-scale, retrospective analysis of subclinical hypothyroidism in more than 17,000 women (5). In comparison to euthyroid controls, women with subclinical hypothyroidism (an elevated TSH and normal free T4 concentration) experienced a 3-fold increase in placental abruption and a 2-fold increase in preterm birth. Now, the publication by Negro et al. (6) in this month’s issue of JCEM provides another supportive step forward in this regard, although deciphering the data is complex. Few can fault conclusions drawn from a randomized, prospective investigation of 4562 women. But the conclusions are confusing and can be misinterpreted, even to the point of assuming that there is no benefit in universal screening. How can such a dichotomy exist? The answers lie in the study design and fine detailing of what really is the primary objective of the investigation itself. Negro et al. (6) conclude that universal screening did not impact the rate of adverse events in comparison to targeted high-risk case-finding, implying a negative outcome. In keeping with the highest of ethical standards, this was indeed the predefined primary objective stated a priori and registered at www.clinicaltrials.gov. However, reading of this manuscript clarifies that the ultimate rationale for doing the study was to assess the potential reduction in adverse pregnancy events after levothyroxine replacement in hypothyroid women compared with patients not receiving levothyroxine. This blinded intervention occurred only among the 3600 patients defined as “low-risk” but nonetheless demonstrated a highly impressive result. Rates of pregnancy-related adverse events were reduced by nearly 40% after detection and treatment. This effect was large enough that approximately 40 low-risk women would require screening (and intervention) to prevent a single adverse pregnancyoutcome.Suchstatistics compare favorably to those of other intervention trials for common illnesses such as hypertension or hypercholesterolemia (7, 8). Why then should analysis of the entire study cohort (an additional 1000 women) demonstrate an opposing con-