Abstract
Background:
A vitamin B1-deficient soy-based infant formula was marketed in Israel in 2003, exposing infants to clinical or subclinical B1 deficiency. We investigated whether subclinical B1 deficiency in early infancy had medical, neurodevelopmental, or cognitive effects at 3–5 y of age.
Methods:
A historical prospective cohort study was conducted consisting of four groups: “exposed,” consuming a B1-deficient soy-based formula exclusively for four consecutive weeks or longer; “control,” consuming no soy-based formula; “mixed,” consuming the formula nonexclusively or exclusively for less than four consecutive weeks; and “other,” consuming soy-based formulas other than Remedia. Participants were evaluated by medical examination, Stanford–Binet (SB) intelligence test, sensory profile evaluation, and Conners scales (attention deficit disorder/attention deficit and hyperactivity disorder (ADD/ADHD)).
Results:
Following adjustment for gender, age, and maternal education, there were no significant differences among the four groups on the mean SB scores, on the verbal and nonverbal scores, or in the proportion of children in each group with scores <90. A significantly higher proportion of exposed children as compared with control children had an impaired sensory profile and scores on the Conners scales (ADD/ADHD), but these proportions were also high in the “other” and “mixed” groups.
Conclusion:
The results do not support an association between subclinical B1 deficiency in infancy and long-term development.
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References
Davis RE, Icke GC . Clinical chemistry of thiamine. Adv Clin Chem 1983;232:93–140.
Food and Nutrition Board, Institute of Medicine. Thiamine. Dietary Reference Intakes: Thiamine, Riboflavin, Niacin, Vitamin B-6, Vitamin B-12, Pantothenic Acid, Biotin, and Choline. Washington DC: National Academy Press, 1998: 58–86.
WHO Publication WHO/NHD/99.13. Thiamine deficiency and its prevention and control in major emergencies, 1999. (http://www.who.int/nut/documents/thiamine_in_emergencies_eng.pdf).
Todd K, Butterworth RF . Mechanisms of selective neuronal cell death due to thiamine deficiency. Ann N Y Acad Sci 1999;893:404–11.
Kliegman RM, Behrman RE, Jenson HB, Stanton BF . Nelson Textbook of Pediatrics, 18th edn. Philadelphia, PA: Saunders Elsevier, 2007: 246–7.
Cook CC, Hallwood PM, Thomson AD . B Vitamin deficiency and neuropsychiatric syndromes in alcohol misuse. Alcohol Alcohol 1998;33:317–36.
Bender DA . Optimum nutrition: thiamin, biotin and pantothenate. Proc Nutr Soc 1999;58:427–33.
Tanphaichitr V . Thiamine. In: Shils M, ed. Nutrition in Health and Disease. 9th edn. Baltimore: Williams & Wilkins, 1999: 381–9.
Müri RM, Von Overbeck J, Furrer J, Ballmer PE . Thiamin deficiency in HIV-positive patients: evaluation by erythrocyte transketolase activity and thiamin pyrophosphate effect. Clin Nutr 1999;18:375–8.
Zuccoli G, Gallucci M, Capellades J, et al. Wernicke encephalopathy: MR findings at clinical presentation in twenty-six alcoholic and nonalcoholic patients. AJNR Am J Neuroradiol 2007;28:1328–31.
Sebrell WH Jr . IV. Clinical nutrition in the United States. Am J Public Health Nations Health 1968;58:2035–42.
Ivanovic DM, Leiva BP, Pérez HT, et al. Head size and intelligence, learning, nutritional status and brain development. Head, IQ, learning, nutrition and brain. Neuropsychologia 2004;42:1118–31.
Ornoy A, Michailevskaya V, Lukashov I, Bar-Hamburger R, Harel S . The developmental outcome of children born to heroin-dependent mothers, raised at home or adopted. Child Abuse Negl 1996;20:385–96.
Ornoy A, Segal J, Bar-Hamburger R, Greenbaum C . Developmental outcome of school-age children born to mothers with heroin dependency: importance of environmental factors. Dev Med Child Neurol 2001;43:668–75.
Ornoy A . The effects of alcohol and illicit drugs on the human embryo and fetus. Isr J Psychiatry Relat Sci 2002;39:120–32.
Ornoy A . The impact of intrauterine exposure versus postnatal environment in neurodevelopmental toxicity: long-term neurobehavioral studies in children at risk for developmental disorders. Toxicol Lett 2003;140-141:171–81.
Ivanovic DM, Olivares MG, Castro CG, Ivanovic RM . Nutrition and learning in Chilean school age children: Chile’s Metropolitan Region Survey 1986-1987. Nutrition 1996;12:321–8.
Ivanovic DM, Leiva BP, Perez HT, et al. Long-term effects of severe undernutrition during the first year of life on brain development and learning in Chilean high-school graduates. Nutrition 2000;16:1056–63.
Grantham-McGregor SM, Fernald LC . Nutritional deficiencies and subsequent effects on mental and behavioral development in children. Southeast Asian J Trop Med Public Health 1997;28: Suppl 2:50–68.
Bryan J, Osendarp S, Hughes D, Calvaresi E, Baghurst K, van Klinken JW . Nutrients for cognitive development in school-aged children. Nutr Rev 2004;62:295–306.
Vikhanski L . Fatal flaw in baby formula sparks reform in Israeli ministry. Nat Med 2004;10:7.
Fattal-Valevski A, Kesler A, Sela BA, et al. Outbreak of life-threatening thiamine deficiency in infants in Israel caused by a defective soy-based formula. Pediatrics 2005;115:e233–8.
Fattal-Valevski A, Bloch-Mimouni A, Kivity S, et al. Epilepsy in children with infantile thiamine deficiency. Neurology 2009;73:828–33.
Fattal-Valevski A, Azouri-Fattal I, Greenstein YJ, Guindy M, Blau A, Zelnik N . Delayed language development due to infantile thiamine deficiency. Dev Med Child Neurol 2009;51:629–34.
Fattal I, Friedmann N, Fattal-Valevski A . The crucial role of thiamine in the development of syntax and lexical retrieval: a study of infantile thiamine deficiency. Brain 2011;134(Pt 6):1720–39.
Yochman A, Parush S, Ornoy A . Responses of preschool children with and without ADHD to sensory events in daily life. Am J Occup Ther 2004;58:294–302.
Hemmi MH, Wolke D, Schneider S . Associations between problems with crying, sleeping and/or feeding in infancy and long-term behavioural outcomes in childhood: a meta-analysis. Arch Dis Child 2011;96:622–9.
Jhala SS, Hazell AS . Modeling neurodegenerative disease pathophysiology in thiamine deficiency: consequences of impaired oxidative metabolism. Neurochem Int 2011;58:248–60.
Shehory-Rubin Z, Shvartz S. “Hadassah for the health of the people”. The Health-Education Work of “Hadassah” in Eretz Israel during the British Mandate. Jerusalem, Israel: The Zionist Library 2004 (Hebrew).
Roid, GH . Stanford-Binet Intelligence Scales, 5th edn. Itasca, IL: Riverside Publishing, 2003.
Dunn W . Performance of typical children on the Sensory Profile: an item analysis. Am J Occup Ther 1994;48:967–74.
Dunn W . The sensations of everyday life: empirical, theoretical, and pragmatic considerations. Am J Occup Ther 2001;55:608–20.
Charach A, Chen S, Hogg-Johnson S, Schachar RJ . Using the Conners’ Teacher Rating Scale-Revised in school children referred for assessment. Can J Psychiatry 2009;54:232–41.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. (DSM IV). Washington, DC: American Psychiatric Association, 1994.
Dunn W . The Sensory Profile Manual. San Antonio, TX: The Psychological Corporation, 1999.
Acknowledgements
The authors thank Yona Amitai and Dorit Nitzan-Kaluski for their help in preparing the study proposal and Boaz Lev for assisting throughout the implementation, as well as the participating children and parents for their contribution.
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Ornoy, A., Tekuzener, E., Braun, T. et al. Lack of severe long-term outcomes of acute, subclinical B1 deficiency in 216 children in Israel exposed in early infancy. Pediatr Res 73, 111–119 (2013). https://doi.org/10.1038/pr.2012.140
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DOI: https://doi.org/10.1038/pr.2012.140
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