Debate Continues Over Universal Thyroid Screening in Pregnancy

Kristin Jenkins

November 06, 2018

Although universal thyroid screening in early pregnancy holds promise for improving fetal and maternal outcomes, achieving consensus on its merits is unlikely without more controlled trials to address "areas of uncertainty," experts say.

Results from a literature review on the risks and benefits of universal thyroid screening during pregnancy confirm that there is a lack of high-quality evidence for screening and management of asymptomatic borderline abnormalities that make up the bulk of thyroid dysfunction cases seen in pregnancy.

"A universal screening strategy is likely to predominantly identify women with subclinical thyroid disease for whom the benefits of systematic screening and correction remain controversial," write Peter N. Taylor, MBChB, of the Thyroid Research Group, Systems Immunity Research Institute, Cardiff University School of Medicine, Wales, United Kingdom, and colleagues.

Their findings were published online on October 25 in Frontiers in Endocrinology.

"Whilst all societal guidelines endorse treatment of overt thyroid disease, the uncertainty lies in the management of subclinical hypothyroidism, isolated hypothyroxinemia, and euthyroid autoimmunity," the authors write.

Concern is growing that subclinical hypothyroidism and isolated hypothyroxinemia are associated with fetal loss, prematurity, and impaired cognitive function in offspring, they point out. There is also evidence that maternal thyroid autoimmunity could be a potential risk factor for fetal loss.

The incidence of overt hypothyroidism in pregnancy ranges from approximately 0.2% to 0.6%, whereas subclinical hypothyroidism, with elevated thyroid-stimulating hormone (TSH) and normal free thyroxine (FT4) concentrations, occurs in 2% to 3% of pregnancies. Isolated hypothyroxinemia, defined as a normal TSH and low FT4, occurs in about 2% of pregnancies.

Guidelines for the management of thyroid disease in pregnancy were published online by the American Thyroid Association in January 2017.

To assess the findings from their literature review, the authors used criteria that have informed screening decisions for the past 50 years. They found that the evidence satisfied most of the 10 criteria set out by James Wilson and Gunnar Jungner in their seminal 1968 article, "Principles and practice of screening for disease." These criteria "have stood the test of time as a gold standard tool for screening policies," Taylor and colleagues say.

The exception was criterion 8: "There should be an agreed policy on whom to treat as patients." This was not met by evidence in the literature, the authors note.

"This is understandable given that thyroid dysfunction, like some other conditions with screening programs such as hypertension or dyslipidemia, is a continuum in which the thresholds for intervention are uncertain."

The other nine criteria were easily satisfied because it is well-established that overt hypothyroidism is common in women of childbearing age and, if left untreated during pregnancy, can result in substantial adverse obstetric and child neurodevelopmental outcomes.

The case for universal screening is also bolstered by the fact that both diagnosing and treating thyroid dysfunction is easy and inexpensive. As such, universal screening could be cost effective.

Universal thyroid screening is currently recommended in countries such as Spain, China, and Poland, they point out. In the United States and United Kingdom, a case-finding approach has been adopted to target women at high risk, including those with clinical signs and symptoms, or a history of autoimmune disease or preterm delivery.

However, screening only high-risk patients could miss the majority of cases, the authors note.

"Clinical trials should aspire to recruit women preconception or as early as possible in pregnancy," the authors advise. In the meantime, existing screening programs should be audited regularly to gain insight into practical issues, and centers already offering universal or high-risk screening should integrate thyroid autoimmunity into their decision-making.

As previously reported by Medscape Medical News, results from an earlier study by Taylor and colleagues indicated that giving levothyroxine to more pregnant women with mild hypothyroidism could prevent more stillbirths, low-birth-weight babies, and early cesarean sections.

"If you screen for [thyroid-hormone deficiency] during pregnancy and treat those who are borderline, you do get substantial benefit," Taylor said in an interview.

Forthcoming results from the multicenter UK randomized controlled TABLET trial, which is testing the effect of levothyroxine on pregnancy and neonatal outcomes in women with thyroid antibodies, will be of interest, the study authors say.

Taylor and coauthors have reported no relevant financial relationships.

Front Endocrinol. Published online on October 25, 2018. Full text

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