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January 20, 2021
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Thyroid disorders before, during pregnancy raise thyroid cancer risk in children

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Children born to mothers diagnosed with thyroid disorders before or during pregnancy were significantly more likely to develop thyroid cancer, with risk persisting into adulthood, according to an analysis of registry data.

Cari Kitahara

“This was a very large and unique study combining maternal birth and cancer registry data from four Nordic countries,” Cari Kitahara, PhD, investigator in the division of cancer epidemiology and genetics, radiation epidemiology branch, of the NIH’s National Cancer Institute told Healio. “This type of study design allowed us to evaluate whether parental characteristics or exposures occurring around the time of birth might be associated with risk for developing thyroid cancer later in life.”

Children born to mothers diagnosed with thyroid disorders before or during pregnancy have an increased risk for thyroid cancer. The highest risks were in children whose mothers had a goiter or benign thyroid neoplasms.

In a population-based, nested case-control study, Kitahara and colleagues analyzed registry data from four Nordic countries to assess thyroid cancer risk in children in relation to maternal medical history, pregnancy complications and birth characteristics.

Patients with thyroid cancer (cases) were children born and subsequently diagnosed with first primary thyroid cancer from 1973 to 2013 in Denmark, 1987 to 2014 in Finland, 1967 to 2015 in Norway or 1973 to 2014 in Sweden. Researchers matched each case with up to 10 peers without thyroid cancer (controls) based on birth year, sex, country and county of birth. Cases and matched controls with a previous diagnosis of any cancer, other than nonmelanoma skin cancer, at the time of thyroid cancer diagnosis were excluded. Researchers used conditional logistic regression models to calculate ORs for thyroid cancer.

The findings were published in The Lancet Diabetes & Endocrinology.

Of the 2,437 thyroid cancer cases, 1,967 cases, or 81.4%, were papillary carcinomas. Most cases (77.1%) were women, and 1,384, or 56.7%, were diagnosed before age 30 years.

Researchers identified several factors associated with increased risk for thyroid cancer among offspring, including a higher birth weight (OR per kg = 1.14; 95% CI, 1.05-1.23) congenital hypothyroidism (OR = 4.55; 95% CI, 1.58-13.08), maternal diabetes before pregnancy (OR = 1.69; 95% CI, 0.98-2.93) and postpartum hemorrhage (OR = 1.28; 95% CI, 1.06-1.55).

Registry data in Denmark suggested that the strongest indicators of thyroid cancer risk in offspring were maternal hypothyroidism (OR = 18.12; 95% CI, 10.52-31.2), hyperthyroidism (OR = 11.91; 95% CI, 6.77-20.94), goiter (OR = 67.36; 95% CI, 39.89-113.76) and benign thyroid neoplasms (OR = 22.5; 95% CI, 6.93-73.06).

“We found that maternal thyroid disorders diagnosed before or during pregnancy were strongly linked to an increased risk for thyroid cancer in the offspring, and that this risk remained elevated well into adulthood,” Kitahara said.

Kitahara said data pointed to fetal iodine deficiency as a potentially important underlying mechanism in the development of thyroid cancer, adding that the hypothesis should be evaluated in future studies.

“Future studies are needed to better understand the reasons, or causal mechanisms, underlying the very strong associations we observed between maternal thyroid disorders and thyroid cancer risk in the offspring,” Kitahara said. “We could not determine from our data whether the associations observed were due to treatments received for maternal thyroid disorders during pregnancy, thyroid hormone levels or thyroid autoimmunity, fetal iodine deficiency, sex steroid or growth hormone levels, or other factors.”

For more information:

Cari Kitahara, PhD, can be reached at meinholdc@mail.nih.gov; Twitter: @cari_kitahara.