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Effects of oral iodine supplementation in very low birth weight preterm infants for the prevention of thyroid function alterations during the neonatal period: results of a randomised assessor-blinded pilot trial and neurodevelopmental outcomes at 24 months

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Abstract

The trace element iodine (I) is essential for the synthesis of thyroid hormones. Parenteral nutrition solutions, formula milk, and human breast milk contain insufficient iodine to meet recommended intake for preterm infants. Iodine deficiency may affect thyroid function and may be associated with morbidity or neurological outcomes. The primary objective is to assess the evidence that dietary supplementation with iodine affects thyroid function during the neonatal period. The design was a randomised controlled pilot trial. Infants who met the inclusion criteria were enrolled through consecutive sampling and assigned to two different groups. The setting was a Spanish university hospital. Ninety-four patients with very low birth weight (under 1500 g) were included. Intervention group: 30 µg I/kg/day of iodine in oral drops given to 47 infants from their first day of life until hospital discharge. Control group: 47 infants without supplements. Formula and maternal milk samples for the determination of iodine content were collected at 1, 7, 15, 21, 30 days, and at discharge. Blood samples were collected for thyroid hormones. Neurological development was assessed at 2 years of age (Bayley III Test). Infants in the supplemented group reached the recommended levels from the first days of life. The researchers detected the effects of iodine balance on the plasma levels of thyroid hormones measured during the first 12 weeks of age. The trial assessed the impact of the intervention on neurodevelopmental morbidity.

Conclusion: Thyroid function is related to iodine intake in preterm infants. Therefore, supplements should be added if iodine intake is found to be inadequate. The analyses found no effects of iodine supplementation on the composite scores for Bayley-III assessments in all major domains. The study results indicate potentially important effects on language development related to low iodine excretion during the first 4 weeks of life

What is Known:

• Thyroid function is related to iodine intake in preterm infants.

• Preterm babies on formula preparations and with exclusive parenteral nutrition are at high risk of iodine deficiency.

What is New:

• Iodine intake should be monitored during the neonatal period.

• Iodine supplements should be added if iodine intake is found to be inadequate.

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All data are detailed in the manuscript.

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Abbreviations

ICCIDD:

International Council for Control of Iodine Deficiency Disorders

TSH:

Thyroxine

T4:

Thyroxine

T3:

3,5,3′-Triiodothyronine

Tg:

Thyroglobulin

TBG:

Thyroid binding globulin

GA:

Gestational age in weeks

BW:

Body weight

ELBW:

Extremely low birth weight babies

SD:

Standard deviation

SE:

Standard error

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Funding

This study was supported by grants from the Spanish National Healthcare Research Fund (Grant PI06/ 1310 to S.A. and PI03/1417 to G.M.E.) and the Instituto de Salud Carlos III, RCMN (03/08).

Author information

Authors and Affiliations

  1. Neonatology Unit, University Hospital LA PAZ, Paseo de la Castellana 261, 28046, Madrid, Spain

    S. Ares & F. Omeñaca

  2. Facultad de Educacion, Universidad Complutense, Madrid, Spain

    B. Saenz-Rico

  3. Neonatology Unit, Hospital Universitario de Burgos, Burgos, Spain

    J. Arnaez

  4. Biostatistics Department, University Hospital LA PAZ, Paseo de la Castellana 261, 28046, Madrid, Spain

    J. Diez-Sebastian

  5. Instituto de Investigaciones Biomédicas, Universidad Autónoma de Madrid, Arturo Duperier 4, Madrid, Spain

    J. Bernal

  6. Center for Research On Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain

    J. Bernal

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  1. S. Ares
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  2. B. Saenz-Rico
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  3. J. Arnaez
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  4. J. Diez-Sebastian
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  5. F. Omeñaca
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  6. J. Bernal
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Contributions

Susana Ares and Juan Arnaez: both doctors have conceptualized and designed the study, collected the samples, recruited the subjects, collected the data and drafted the initial manuscript and approved the final manuscript as submitted. Belen Saenz-Rico applied the neurodevelopmental tests and recorded all the scores. Jesus Diez carried out the initial and final statistical analyses. Felix Omeñaca and Juan Bernal conceptualized and designed the study, prepared the documents for the ethics committee, parents information sheet and critically reviewed and revised the manuscript.

Corresponding author

Correspondence to S. Ares.

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Ethics approval

The study was approved by the Ethics Committee and by the Institutional Review Boards of the enrolment centre (University Hospital LA PAZ, Madrid, Spain).

Consent to participate

All the parents signed the informed consent for their infant participation in the trial. We confirm that all the authors are responsible for the reported research. All the authors have participated in the concept and design; analysis and interpretation of data; drafting or revising of the manuscript, and that they have approved the manuscript as submitted.

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All the authors have approved the manuscript and agree with its submission.

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The authors declare no competing interests.

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Communicated by Daniele De Luca

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Ares, S., Saenz-Rico, B., Arnaez, J. et al. Effects of oral iodine supplementation in very low birth weight preterm infants for the prevention of thyroid function alterations during the neonatal period: results of a randomised assessor-blinded pilot trial and neurodevelopmental outcomes at 24 months. Eur J Pediatr 181, 959–972 (2022). https://doi.org/10.1007/s00431-021-04288-5

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