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Cited by 754Retinoids in leukemia and cellular processesPregnancy and Medication ImpactPharmacological Effects and Toxicity Studies

Teratogenicity of high vitamin A intake

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Rothman, Kenneth J., Moore, Lynn L., Singer, Martha R., Nguyen, Uyen-Sa D.T., Mannino, Salvatore, Milunsky, Aubrey·1995·New England Journal of Medicine
DOI 10.1056/nejm199511233332101
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Abstract

BACKGROUND: Studies in animals indicate that natural forms of vitamin A are teratogenic. Synthetic retinoids chemically similar to vitamin A cause birth defects in humans; as in animals, the defects appear to affect tissues derived from the cranial neural crest. METHODS: Between October 1984 and June 1987, we identified 22,748 pregnant women when they underwent screening either by measurement of maternal serum alpha-fetoprotein or by amniocentesis. Nurse interviewers obtained information on the women's diet, medications, and illnesses during the first trimester of pregnancy, as well as information on their family and medical history and exposure to environmental agents. We obtained information on the outcomes of pregnancy from the obstetricians who delivered the babies or from the women themselves. Of the 22,748 women, 339 had babies with birth defects; 121 of these babies had defects occurring in sites that originated in the cranial neural crest. RESULTS: For defects associated with cranial-neural-crest tissue, the ratio of the prevalence among the babies born to women who consumed more than 15,000 IU of preformed vitamin A per day from food and supplements to the prevalence among the babies whose mothers consumed 5000 IU or less per day was 3.5 (95 percent confidence interval, 1.7 to 7.3). For vitamin A from supplements alone, the ratio of the prevalence among the babies born to women who consumed more than 10,000 IU per day to that among the babies whose mothers consumed 5000 IU or less per day was 4.8 (95 percent confidence interval, 2.2 to 10.5). Using a smoothed regression curve, we found an apparent threshold near 10,000 IU per day of supplemental vitamin A. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the seventh week of gestation. CONCLUSIONS: High dietary intake of preformed vitamin A appears to be teratogenic. Among the babies born to women who took more than 10,000 IU of preformed vitamin A per day in the form of supplements, we estimate that about 1 infant in 57 had a malformation attributable to the supplement.

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  • High vitamin A intake by the mother can lead to teratogenic effects in the developing fetus.

    “Although the placenta has been believed to protect the fetus against high-vitamin A intake from pregnant women being over-supplemented with vitamin A, several studies have reported that high vitamin A intake by the mother can lead to teratogenic effects in the developing fetus [117,118,119].”

    From Vitamin A Update: Forms, Sources, Kinetics, Detection, Function, Deficiency, Therapeutic Use and Toxicity (2021) · cites this paper as [118]

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Research works printed but not linked: 2

  1. [3]3. National Research Council. Recommended dietary allowances. 10th ed. Washington, D.C.: National Academy Press, 1989:84.
  2. [10]10. Use of supplements containing high-dose vitamin A -New York State, 1983-1984. MMWR Morb Mortal Wkly Rep 1987;36:80-2.

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Authors
Rothman, K. J., Moore, L. L., Singer, M. R., Nguyen, U.-S. D. T., Mannino, S., & Milunsky, A.
Affiliations
  • Boston University (US)
  • University of Chieti-Pescara (IT)
ORCID
Venue
New England Journal of Medicine
Publisher
Massachusetts Medical Society
Published
1995-11-23
Volume
333
Issue
21
Pages
1369-1373
ISSN
  • 0028-4793 (ISSN-L)
  • 1533-4406
DOI
10.1056/nejm199511233332101
OpenAlex
W2334286404
Cited by
754
References
21
Citations by year
2026: 26 · 2025: 16 · 2024: 24 · 2023: 21 · 2022: 20 · 2021: 22 · 2020: 22 · 2019: 30 · 2018: 15 · 2017: 24 · 2016: 16 · 2015: 24 · 2014: 29 · 2013: 20 · 2012: 37
FWCI
10.99
Type
journal article
Language
en
Open access
Locations
  • New England Journal of Medicine (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ns019561-05)
  • National Institute of Neurological Disorders and Stroke (NS 19561)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
Keywords
vitamin A, teratogenicity, congenital malformations, cranial neural crest, vitamin A intake, first trimester, maternal serum alpha-fetoprotein, amniocentesis, birth defect prevalence, threshold dose
MeSH terms
Abnormalities, Drug-Induced, Dose-Response Relationship, Drug, Facial Bones, Female, Heart Defects, Congenital, Humans, Infant, Newborn, Neural Tube Defects, Pregnancy, Prospective Studies, Skull, Vitamin A, Prevalence

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