Elsevier

Clinical Biochemistry

Volume 74, December 2019, Pages 19-23
Clinical Biochemistry

Establishment of reference intervals for thyroid hormones in premature infants beyond the first week of life using Beckman Coulter Unicel DxI 800

https://doi.org/10.1016/j.clinbiochem.2019.09.003Get rights and content

Highlights

  • Thyroid hormone reference intervals were established for preterm infants.

  • Free triiodothyronine and thyroxine levels were correlated with gestational age.

  • Thyrotropin levels were slightly inversely correlated with gestational age.

  • Establishing instrument-specific reference intervals for preterm infants is vital.

Abstract

Background

This 4-year retrospective cohort study aimed to establish reference intervals for free triiodothyronine (FT3), free thyroxine (FT4), and thyrotropin (TSH) in premature infants using the Beckman Coulter Unicel DxI 800 automated immunoassay system.

Methods

Study subjects included 605 preterm infants with a gestational age of 26–36 weeks (corrected: 29–38 weeks). Pearson correlation was used to evaluate the association between hormone levels and gestational and corrected gestational ages. A nonparametric method was used to establish reference intervals based on corrected gestational age.

Results

FT3 and FT4 levels were positively correlated with gestational and corrected gestational ages, respectively. TSH levels were slightly negatively correlated with gestational and corrected gestational ages. FT3 significantly differed according to corrected gestational age (29–33 weeks vs 34–38 weeks); however, the difference was smaller than the reference change value (RCV) for the FT3 test. Thus, we combined the FT3 reference intervals into a single reference interval: 2.65–4.93 pmol/L (29–38 weeks). The reference intervals of FT4 and TSH were 11.20–24.97 pmol/L (29–38 weeks) and 1.01–10.14 mIU/L (29–38 weeks), respectively.

Conclusions

Unlike those of full-term infants or adults, the reference intervals established in this study are applicable in premature infants. These results highlight the importance and complexity of establishing instrument-specific thyroid hormone reference intervals for preterm infants.

Introduction

Thyroid dysfunction is among the most common preventable causes of neonatal neurodevelopmental delay. Because of their immature hypothalamic-pituitary-thyroid axis, immature thyroid hormone synthesis and metabolism, systemic diseases, and physiological and non-physiological factors such as immature thyroid enrichment and iodine synthesis, premature infants likely have a wider thyroid hormone reference compared to full-term infants [1]. The use of established reference intervals for full-term infants or even those provided in the reagent instructions (typically established for adults) results in frequent and unnecessary retesting and intervention [2]. Mixing of reference intervals established by different detection systems is also well-known to be inappropriate. Therefore, it is essential to determine instrument-specific reference intervals for vulnerable populations such as premature infants. Chinese guidelines for the diagnosis and treatment of thyroid disease during pregnancy and postpartum [3] stipulate that early thyroid hormone screening should be carried out in newborns in China. Blood samples should be obtained from full-term neonates from 72 h up to 7 days post-birth, and the guidelines recommend delaying sampling until 7 days post-birth for premature neonates. However, few studies have examined the reference intervals of thyroid hormones in preterm infants after the first week of life. It is difficult to obtain a large number of blood samples from healthy preterm infants. Thus, in this study, we used the hospital database to obtain preterm infant inpatient medical records using appropriate screening methods and referred to the EP28-A3c file [4] revised by the Clinical and Laboratory Standards Institute (CLSI) of America and International Federation of Clinical Chemistry to establish thyroid hormone reference intervals in our region using the Beckman DxI 800 automated immunoassay system. All hospitalized premature infants were subjected to venous blood sampling for thyroid hormone testing 7 days after birth.

Section snippets

Study subjects

Preterm infants born between 2015 and 2018 in the neonatal department of Women and Children's Hospital, Xiamen city, Fujian Province of China, were selected. We carefully reviewed the infants' medical records, which included the basic condition and detailed disease information, mode of departure from the hospital (e.g., infant death), and the mother's health condition (e.g., diagnosed endocrine disease), with a special focus on the discharge summary. The infants had a gestational age of

Demographic results of the study cohort

We extracted 2235 neonatal thyroid data from 2015 to 2018. After carefully reviewing the medical records according to the inclusion and exclusion criteria, 605 “normal” preterm infants (361 males and 244 females) were included in the study. The mean (SD) gestational age of this cohort was 32.7 weeks (2.1). The mean (SD) corrected gestational age was 34.6 weeks (2.0) at the time of testing. The median age at the time of testing was 11 days (IQR = 9–15). Other demographic characteristics are

Discussion

According to the recommendations of CLSI, healthy subjects should be selected and a direct reference method should be used to establish a reference interval; however, this would be costly. Moreover, samples must be collected from a vulnerable group of premature infants, which is difficult to achieve. Because of ethical and practical considerations, we retrospectively reviewed medical records provided by the hospital database to identify newborns who were “healthy except for prematurity.” We

Acknowledgments

This study was supported by Foundation of Fujian Provincial Health System for Outstanding Young Doctor (No.2015-WZQ- ZD-32) and the Xiamen Youth Innovation Talents Project (No.2015-A-03).

Declarations of Competing Interest

None.

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      Sun et al. [18] reported that the reference intervals of TSH and FT4 for preterm neonates with very low birth weight were 1.14~11.04 mIU/L and 10.9~21.4 pmol/L, respectively, but these were not stratified by GA. The reference intervals of FT3 and TSH were 2.65~4.93 pmol/L and 1.01~10.14 mIU/L [9] in preterm neonates beyond the first week of life, which align with the results in our study during the first week of life. The limitations of the previous study were the lack of reference intervals of 26–28 weeks, which were included in our study.

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    1Ye Wang and Xingdong Wu equally contributed to this study.

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