Antenatal Thyroid Screening and Childhood Cognitive Function

Lazarus, John H.; Bestwick, Jonathan P.; Channon, Sue; Paradice, Ruth; Maina, Aldo; Rees, Rhian; Chiusano, Elisabetta; John, Rhys; Guaraldo, Varvara; George, Lynne M.; Perona, Marco; Dall'Amico, Daniela; Parkes, Arthur B.; Joomun, Mohammed; Wald, Nicholas J.

doi:10.1056/nejmoa1106104

Cited by 635Thyroid Disorders and TreatmentsMaternal Mental Health During Pregnancy and PostpartumThyroid Cancer Diagnosis and Treatment

Antenatal Thyroid Screening and Childhood Cognitive Function

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Lazarus, John H., Bestwick, Jonathan P., Channon, Sue, Paradice, Ruth, Maina, Aldo, Rees, Rhian, Chiusano, Elisabetta, John, Rhys +7 more·2012·New England Journal of Medicine

DOI 10.1056/nejmoa1106104PMC PMC3814060

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Abstract

BACKGROUND: Children born to women with low thyroid hormone levels have been reported to have decreased cognitive function. METHODS: We conducted a randomized trial in which pregnant women at a gestation of 15 weeks 6 days or less provided blood samples for measurement of thyrotropin and free thyroxine (T(4)). Women were assigned to a screening group (in which measurements were obtained immediately) or a control group (in which serum was stored and measurements were obtained shortly after delivery). Thyrotropin levels above the 97.5th percentile, free T(4) levels below the 2.5th percentile, or both were considered a positive screening result. Women with positive findings in the screening group were assigned to 150 μg of levothyroxine per day. The primary outcome was IQ at 3 years of age in children of women with positive results, as measured by psychologists who were unaware of the group assignments. RESULTS: Of 21,846 women who provided blood samples (at a median gestational age of 12 weeks 3 days), 390 women in the screening group and 404 in the control group tested positive. The median gestational age at the start of levothyroxine treatment was 13 weeks 3 days; treatment was adjusted as needed to achieve a target thyrotropin level of 0.1 to 1.0 mIU per liter. Among the children of women with positive results, the mean IQ scores were 99.2 and 100.0 in the screening and control groups, respectively (difference, 0.8; 95% confidence interval [CI], -1.1 to 2.6; P=0.40 by intention-to-treat analysis); the proportions of children with an IQ of less than 85 were 12.1% in the screening group and 14.1% in the control group (difference, 2.1 percentage points; 95% CI, -2.6 to 6.7; P=0.39). An on-treatment analysis showed similar results. CONCLUSIONS: Antenatal screening (at a median gestational age of 12 weeks 3 days) and maternal treatment for hypothyroidism did not result in improved cognitive function in children at 3 years of age. (Funded by the Wellcome Trust UK and Compagnia di San Paulo, Turin; Current Controlled Trials number, ISRCTN46178175.).

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There is no evidence to support a benefit to offspring IQ by levothyroxine treatment of subclinical hypothyroidism or hypothyroxinemia.
“Noteworthy, there is no evidence to support a benefit to offspring IQ by LT4 treatment of subclinical hypothyroidism or hypothyroxinemia [29, 30].”
From Risks of suboptimal and excessive thyroid hormone replacement across ages (2023) · cites this paper as [29]

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Preconception Thyroid Screening and Childhood Neurocognitive Function Assessment at 6 Months Old [314]
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Authors: Lazarus, J. H., Bestwick, J. P., Channon, S., Paradice, R., Maina, A., Rees, R., Chiusano, E., John, R., Guaraldo, V., George, L. M., Perona, M., Dall'Amico, D., Parkes, A. B., Joomun, M., & Wald, N. J.
Affiliations: Cardiff University (GB)
Queen Mary University of London (GB)
Ospedale Regina Margherita (IT)
University Hospital of Wales (GB)
ORCID: Lazarus, John H.
Bestwick, Jonathan P.
Channon, Sue
Joomun, Mohammed
Wald, Nicholas J.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2012-02-09
Volume: 366
Issue: 6
Pages: 493-501
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1106104
PMC: PMC3814060
OpenAlex: W2170972205
Cited by: 635
References: 18
Citations by year: 2026: 12 · 2025: 24 · 2024: 31 · 2023: 32 · 2022: 52 · 2021: 28 · 2020: 46 · 2019: 52 · 2018: 58 · 2017: 43 · 2016: 32 · 2015: 59 · 2014: 62 · 2013: 59 · 2012: 44
FWCI: 57.49
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Funders: Wellcome Trust (065143, 085966)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords: maternal hypothyroidism, levothyroxine, thyroid-stimulating hormone, free thyroxine, child neurodevelopment
MeSH terms: Child, Preschool, Female, Gestational Age, Humans, Hypothyroidism, Intelligence, Intelligence Tests, Male, Intellectual Disability, Pregnancy, Pregnancy Complications, Pregnancy Trimester, Second, Prenatal Diagnosis, Prenatal Exposure Delayed Effects, Thyroid Hormones, Thyrotropin, Thyroxine, Intention to Treat Analysis

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