What is “Normal” Thyroid Functioning in Preterm Infants?

What is “Normal” Thyroid Functioning in Preterm Infants? 1024 683 Mary Bates, PhD
Baby in NICU

Study provides one of the largest samples of thyroid values in preterm infants to establish reference intervals.

Preterm infants are born with an immature hypothalamic-pituitary-thyroid axis, putting them at risk for hypothyroidism from a delayed rise in thyroid-stimulating hormone (TSH). Currently in the United States, the thyroid function of all infants is evaluated within the first few days of life as a component of the state-mandated metabolic newborn screen. However, there is little data establishing reference interval values for preterm infants at various gestational ages. In preterm infants, the specific free thyroxine (FT4) serum levels needed for optimal brain maturation remain unclear, and there is variability in TSH cutoff values.

In a new study from Nationwide Children’s Hospital, researchers worked to establish reference intervals for TSH and FT4 in preterm infants at specific postmenstrual ages (PMAs, gestational age at birth plus postnatal chronological age).

“The term people use now is reference intervals, but historically it has been normal ranges,” says Dustin Bunch, PhD, DABCC, the assistant director of Clinical Chemistry and Laboratory Informatics at Nationwide Children’s and one of the study’s authors.

“But there is no preterm ‘normal.’ We wanted to create a sample that could be as representative of a ‘normal’ extremely preterm infant population currently in an intensive care unit as possible in order to create reference levels.”

Dr. Bunch and his colleagues gathered data from the electronic medical records of preterm infants admitted to the Nationwide Children’s NICU between 2011 and 2018. As per protocol, these infants’ TSH and FT4 values were measured right after birth and again at about 30 days of age. To ensure the sample was as “normal” as possible, the researchers excluded infants with a diagnosis suggesting their thyroid axis would be permanently altered and those being treated with a thyroid medication.

“We found that in preterm infants <31 weeks postmenstrual age, the FT4 values were a little bit lower than what has previously been reported, while the TSH values were slightly higher,” says George Ziegler, MD, a neonatology fellow at Nationwide Children’s and one of the study’s authors.

“The reference intervals we identified are reflective of a maturing hypothalamic-pituitary-thyroid axis and represent an appropriate profile for what ‘normal’ thyroid function should be in these preterm infants.”

Currently, there are limited TSH and FT4 data in preterm infants to help guide clinicians in interpreting these thyroid test results across varied PMAs. The researchers hope that these new reference intervals, which vary by PMA, will aid the evaluation of preterm infants who are at risk of a delayed hypothyroidism diagnosis that can be missed on the initial newborn screen.

“This study is a great first step,” says Jonathan Slaughter, MD, MPH, a neonatologist and principal investigator in the Center for Perinatal Research within The Abigail Wexner Research Institute at Nationwide Children’s, and one of the study’s authors.

“It’s the largest study of these values in preterm infants that has ever been published. These reference intervals are important for neonatologists and endocrinologists taking care of these babies.”



Ziegler GM, Slaughter JL, Chaudhari M, Singh H, Sánchez PJ, Bunch DR. Preterm to term infant postmenstrual age reference intervals for thyroid-stimulating hormone and free thyroxine. Pediatric Research. 2021 Nov 13. doi: 10.1038/s41390-021-01838-3. Epub ahead of print.

About the author

Mary a freelance science writer and blogger based in Boston. Her favorite topics include biology, psychology, neuroscience, ecology, and animal behavior. She has a BA in Biology-Psychology with a minor in English from Skidmore College in Saratoga Springs, NY, and a PhD from Brown University, where she researched bat echolocation and bullfrog chorusing.