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Prospective study of thyroid function in the first year of life in infants with Down syndrome

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Abstract

Current American Academy of Pediatrics (AAP) Guidelines recommend monitoring thyroid function in infants with Down syndrome (DS) at birth, 6 and 12 months, and annually thereafter. This study aimed to determine whether these guidelines are optimal for early diagnosis and treatment of (subclinical) hypothyroidism. Enrolled infants with DS less than age 7 months, born at ≥ 30 weeks gestation to monitor thyroid function test (TFT). A filter paper (FP) blood sample was analyzed for TSH and total T4 at ages 2 and 4 weeks and monthly thereafter until 12 months. Subjects with abnormal FP sample and confirmatory serum TFT for hypothyroidism promptly started treatment. Subjects with thyroid dysfunction identified had thyroid antibodies measured at diagnosis and 12 months. Descriptive statistics determined average time to diagnosis of abnormal TFT. Sixteen (30%) of 54 subjects were diagnosed with a thyroid disorder, the majority with subclinical hypothyroidism (SH) and 1 with hyperthyroidism. Diagnosis occurred in 6 (11%), 9 (17%), and 12 (22.2%) infants in the first 30, 60, and 90 days of life (DOL), respectively. Eight infants had an abnormal NBS and half were diagnosed with a thyroid disorder by DOL 8 and the remainder prior to 4 months. Among subjects with a normal NBS, four were diagnosed at a mean of 104 days and three at a mean of 101 days prior to the 6-month and 12-month routine screens, respectively.

  Conclusion: Based on current AAP guidelines, thyroid disorder diagnosis would have been delayed in nearly 20% of the subjects. An additional TFT screen at 1 and 3 months can lead to earlier diagnosis and treatment.

What is Known:

• Current American Academy of Pediatrics (AAP) Guidelines recommend thyroid function tests (TFT) in infants with Down syndrome (DS) at birth and 6 and 12 months.

• Peer- reviewed retrospective studies report an increased incidence of hypothyroidism in infants with DS undetected by the newborn screen (NBS) and prior to 6 months.

What is New:

• This prospective study monitored TFT in infants with DS at age 2 weeks and monthly throughout the first year of life.

• The findings in this study support additional TFT screens at 1 and 3 months in infants with DS.

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Data availability

The data that support the findings of this study are available and can be provided by the corresponding author, based upon reasonable request.

Abbreviations

AAP:

American Academy of Pediatrics

BW:

Birthweight

CH:

Congenital hypothyroidism

CHD:

Congenital heart disease

DOL:

Day of life

DX:

Diagnosis

DS:

Down syndrome

FT4:

Free T4

FP:

Filter paper

GA:

Gestational age

NBS:

Newborn screen

SH:

Subclinical hypothyroidism

TFT:

Thyroid function tests

TG:

Thyroglobulin antibody

TPO:

Thyroid peroxidase antibody

TSHR:

TSH receptor antibody

T4:

Thyroxine

TSH:

Thyrotropin

USG:

Ultrasound

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Acknowledgements

We appreciate Karen Cullen, BSN, RN, CDCES, Dr. Beverly Hay, Dr. Pamela High, Dr. Madelena Martin, Dr. Brian Skotko, Gwen Sokoloff, RN, BSN, M.P.H., CHES, Massachusetts Down Syndrome Congress, UMASS Memorial Children’s Medical Center NICU staff, Dr. Kishor Vellody, and Angela Wolf for assistance with referring infants with DS to participate in this study. We are grateful to Dr. Neil Aronin and Danielle Abate for reviewing the manuscript, Dr. Michael Fahey for classifying the cardiac defects, and Dodi Feldman for formatting the tables in the manuscript.

Funding

This work was supported by The Gerber Foundation [National Research Grant #3210].

Author information

Authors and Affiliations

  1. UMass Chan Medical School, Department of Pediatrics, Worcester, MA, USA

    Penny M. Feldman, Nicolas Rodriguez & Mary M. Lee

  2. UMASS Chan Medical School, Population and Quantitative Health Sciences, Worcester, MA, USA

    Emily Morrison & Bruce Barton

  3. Nemours Children Health, Wilmington, DE, USA

    Mary M. Lee

  4. Sidney Kimmel Medical College, Jefferson University, Philadelphia, PA, USA

    Mary M. Lee

Authors
  1. Penny M. Feldman
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Contributions

Penny Feldman, M.D., Mary Lee, M.D., and Bruce Barton, Ph.D., contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Penny Feldman, M.D., Nicolas Rodriguez, Bruce Barton, Ph.D., and Emily Morrison. The first draft of the manuscript was written by Penny Feldman, M.D., and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Penny M. Feldman.

Ethics declarations

Ethics approval

This study was approved by the IRB at the UMASS Chan Medical School in Worcester, MA 01655 (approval 2/10/2013, number: H00000722).

Consent to participate

Written informed consent was obtained from the parents/guardians.

Competing interests

The authors declare no competing interests.

Additional information

Communicated by Peter de Winter.

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Feldman, P.M., Rodriguez, N., Morrison, E. et al. Prospective study of thyroid function in the first year of life in infants with Down syndrome. Eur J Pediatr 182, 2903–2911 (2023). https://doi.org/10.1007/s00431-023-04954-w

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