A Pilot Randomized Controlled Trial of a New Supplementary Food Designed to Enhance Cognitive Performance during Prevention and Treatment of Malnutrition in Childhood

Susan B Roberts, Maria Angela Franceschini, Amy Krauss, Pei-Yi Lin, Augusto Braima de Sa, Raimundo Có, Salima Taylor, Carrie Brown, Oliver Chen, Elizabeth J Johnson, William Pruzensky, Nina Schlossman, Carlito Balé, Kuan-Cheng Tony Wu, Katherine Hagan, Edward Saltzman, Paul Muentener, Susan B Roberts, Maria Angela Franceschini, Amy Krauss, Pei-Yi Lin, Augusto Braima de Sa, Raimundo Có, Salima Taylor, Carrie Brown, Oliver Chen, Elizabeth J Johnson, William Pruzensky, Nina Schlossman, Carlito Balé, Kuan-Cheng Tony Wu, Katherine Hagan, Edward Saltzman, Paul Muentener

Abstract

Background: Cognitive impairment associated with childhood malnutrition and stunting is generally considered irreversible.

Objective: The aim was to test a new nutritional supplement for the prevention and treatment of moderate-acute malnutrition (MAM) focused on enhancing cognitive performance.

Methods: An 11-wk, village-randomized, controlled pilot trial was conducted in 78 children aged 1-3 or 5-7 y living in villages in Guinea-Bissau. The supplement contained 291 kcal/d for young children and 350 kcal/d for older children and included 5 nutrients and 2 flavan-3-ol-rich ingredients not present in current food-based recommendations for MAM. Local bakers prepared the supplement from a combination of locally sourced items and an imported mix of ingredients, and it was administered by community health workers 5 d/wk. The primary outcome was executive function abilities at 11 wk. Secondary outcomes included additional cognitive measures and changes in z scores for weight (weight-for-age) and height (height-for-age) and hemoglobin concentrations at 11 wk. An index of cerebral blood flow (CBF) was also measured at 11 wk to explore the use of this measurement as a biological index of cognitive impairment.

Results: There were no significant differences in any outcome between groups at baseline. There was a beneficial effect of random assignment to the supplement group on working memory at 11 wk in children aged 1-3 y (P < 0.05). This difference contrasted with no effect in older children and was not associated with faster growth rate. In addition, CBF correlated with task-switching performance (P < 0.05).

Conclusions: These preliminary data suggest that cognitive impairment can be monitored with measurement of CBF. In addition, the findings provide preliminary data that suggest that it may be possible to improve poor cognitive performance in young children through changes in the nutritional formulation of supplementary foods used to prevent and treat MAM. Powered studies of the new supplement formulation are needed. This trial was registered at clinicaltrials.gov as NCT03017209.

Keywords: Guinea-Bissau; blended fortified foods; cerebral blood flow; cognition; height-for-age z score; moderate-acute malnutrition (MAM); near-infrared spectroscopy; ready-to-use supplementary food; stunting; weight-for-age z score.

Conflict of interest statement

Author disclosures: SBR, AK, P-YL, ABdS, RC, ST, C Brown, OC, EJJ, WP, NS, C Balé, K-CW, KH, ES, and PM, no conflicts of interest. MAF has patents on the near-infrared spectroscopy–diffuse correlation spectroscopy (NIRS-DCS) technologies used for these measurements. Tufts University has submitted a provisional patent based on the results described in this report.

Figures

FIGURE 1
FIGURE 1
Relation between brain blood flow and number of sorting tasks performed correctly and illustration of measurements being conducted in a rural village in Guinea-Bissau. R2 represents the line of best fit. CBFi, cerebral blood flow index.

References

    1. World Bank Investing in early childhood development [Internet]. Washington (DC): The World Bank; 2006. [cited 2015 Dec 15]. Available from: .
    1. Kar BR, Rao SL, Chandramouli BA.. Cognitive development in children with chronic protein energy malnutrition. Behav Brain Funct 2008;4:31.
    1. Crookston BT, Schott W, Cueto S, Dearden KA, Engle P, Georgiadis A, Lundeen EA, Penny ME, Stein AD, Behrman JR.. Postinfancy growth, schooling, and cognitive achievement: young lives. Am J Clin Nutr 2013;98:1555–63.
    1. Waber DP, Eaglesfield D, Fitzmaurice GM, Bryce C, Harrison RH, Galler JR.. Cognitive impairment as a mediator in the developmental pathway from infant malnutrition to adolescent depressive symptoms in Barbadian youth. J Dev Behav Pediatr 2011;32:225–32.
    1. Alamy M, Bengelloun WA.. Malnutrition and brain development: an analysis of the effects of inadequate diet during different stages of life in rat. Neurosci Biobehav Rev 2012;36:1463–80.
    1. Pollitt E, Saco-Pollitt C, Jahari A, Husaini MA, Huang J.. Effects of an energy and micronutrient supplement on mental development and behavior under natural conditions in undernourished children in Indonesia. Eur J Clin Nutr 2000;54(Suppl 2):S80–90.
    1. Grantham-McGregor SM, Powell CA, Walker SP, Himes JH.. Nutritional supplementation, psychosocial stimulation, and mental development of stunted children: the Jamaican study. Lancet 1991;338:1–5.
    1. Walker SP, Chang SM, Powell CA, Grantham-McGregor SM.. Effects of early childhood psychosocial stimulation and nutritional supplementation on cognition and education in growth-stunted Jamaican children: prospective cohort study. Lancet 2005;366:1804–7.
    1. Prado EL, Maleta K, Ashorn P, Ashorn U, Vosti SA, Sadalaki J, Dewey KG.. Effects of maternal and child lipid-based nutrient supplements on infant development: a randomized trial in Malawi. Am J Clin Nutr 2016;103:784–93.
    1. WHO The Healthy Growth Project. Geneva (Switzerland): WHO; 2016.
    1. Zeisel SH, da Costa KA.. Choline: an essential nutrient for public health. Nutr Rev 2009;67):615–23.
    1. Mudd AT, Getty CM, Sutton BP, Dilger RN.. Perinatal choline deficiency delays brain development and alters metabolite concentrations in the young pig. Nutr Neurosci 2016;19:425–33.
    1. Walker SP, Wachs TD, Meeks Gardner J, Lozoff B, Wasserman GA, Pollitt E, Carter JA.. Child development: risk factors for adverse outcomes in developing countries. Lancet 2007;369:145–57.
    1. Semba RD, Zhang P, Gonzalez-Freire M, Moaddel R, Trehan I, Maleta KM, Ordiz MI, Ferrucci L, Manary MJ.. The association of serum choline with linear growth failure in young children from rural Malawi. Am J Clin Nutr 2016;104:191–7.
    1. Daiello LA, Gongvatana A, Dunsiger S, Cohen RA, Ott BR; Alzheimer's Disease Neuroimaging Initiative . Association of fish oil supplement use with preservation of brain volume and cognitive function. Alzheimers Dement 2015;11:226–35.
    1. Sitaram N, Weingartner H, Gillin J.. Human serial learning: enhancement with arecholine and choline impairment with scopolamine. Science 1978;201:274–6.
    1. Brickman AM, Khan UA, Provenzano FA, Yeung L-K, Suzuki W, Schroeter H, Wall M, Sloan RP, Small SA.. Enhancing dentate gyrus function with dietary flavanols improves cognition in older adults. Nat Neurosci 2014;17:1798–803.
    1. Simmer K, Patole SK, Rao SC.. Long-chain polyunsaturated fatty acid supplementation in infants born at term. Cochrane Database Syst Rev 2011;12:CD000376.
    1. Dyall SC.. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci 2015;7:52.
    1. Kuratko CN, Barrett EC, Nelson EB, Norman S.. The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: a review. Nutrients 2013;5:2777–810.
    1. Sheppard KW, Cheatham CL.. Executive functions and the omega-6-to-omega-3 fatty acid ratio: a cross-sectional study. Am J Clin Nutr 2017;105:32–41.
    1. Wightman EL, Haskell CF, Forster JS, Veasey RC, Kennedy DO.. Epigallocatechin gallate, cerebral blood flow parameters, cognitive performance and mood in healthy humans: a double-blind, placebo-controlled, crossover investigation. Hum Psychopharmacol 2012;27:177–86.
    1. Boespflug EL, Eliassen JC, Dudley JA, Shidler MD, Kalt W, Summer SS, Stein AL, Stover AN, Krikorian R.. Enhanced neural activation with blueberry supplementation in mild cognitive impairment. Nutr Neurosci 2017;21:1–9.
    1. Lamport DJ, Pal D, Moutsiana C, Field DT, Williams CM, Spencer JP, Butler LT.. The effect of flavanol-rich cocoa on cerebral perfusion in healthy older adults during conscious resting state: a placebo controlled, crossover, acute trial. Psychopharmacology (Berl) 2015;232:3227–34.
    1. Krikorian R, Boespflug EL, Fleck DE, Stein AL, Wightman JD, Shidler MD, Sadat-Hossieny S.. Concord grape juice supplementation and neurocognitive function in human aging. J Agric Food Chem 2012;60:5736–42.
    1. Nehlig A... The neuroprotective effects of cocoa flavanol and its influence on cognitive performance. Br J Clin Pharmacol 2013;75:716–27.
    1. Hsu DP, French AJ, Madson SL, Palmer JM, Gidvani-Diaz V.. Evaluation of a noninvasive hemoglobin measurement device to screen for anemia in infancy. Matern Child Health J 2016;20:827–32.
    1. Batra P, Schlossman N, Balan I, Pruzensky W, Balan A, Brown C, Gamache MG, Schleicher MM, de Sa AB, Saltzman E, et al. . A randomized controlled trial offering higher- compared with lower-dairy second meals daily in preschools in Guinea-Bissau demonstrates an attendance-dependent increase in weight gain for both meal types and an increase in mid-upper arm circumference for the higher-dairy meal. J Nutr 2016;146:124–32.
    1. Schlossman N, Brown C, Batra P, Braima de Sa A, Balan I, Balan A, Gamache MG, Wood L, Pruzensky W, Saltzman E, et al. . A randomized controlled trial of two ready-to-use supplementary foods demonstrates benefit of the higher dairy supplement for reduced wasting in mothers, and differential impact in infants and children associated with maternal supplement response. Food Nutr Bull 2017;38:275–90.
    1. Buckley EM, Parthasarathy AB, Grant PE, Yodh AG, Franceschini MA.. Diffuse correlation spectroscopy for measurement of cerebral blood flow: future prospects. Neurophotonics 2014;1:1–7.
    1. Kennedy C, Sokoloff L.. An adaptation of the nitrous oxide method to the study of the cerebral circulation in children: normal values for cerebral blood flow and cerebral metabolic rate in childhood. J Clin Invest 1957;36:1130–7.
    1. Chugani HT, Phelps ME, Mazziotta JC.. Positron emission tomography study of human brain functional development. Ann Neurol 1987;22:487–97.
    1. Chugani HT.. A critical period of brain development: studies of cerebral glucose utilization with PET. Prev Med 1998;27:184–8.
    1. Roche-Labarbe N, Fenoglio A, Aggarwal A, Dehaes M, Carp SA, Franceschini MA, Grant PE.. Near-infrared spectroscopy assessment of cerebral oxygen metabolism in the developing premature brain. J Cereb Blood Flow Metab 2012;32:481–8.
    1. Lin PY, Roche-Labarbe N, Dehaes M, Fenoglio A, Grant PE, Franceschini MA.. Regional and hemispheric asymmetries of cerebral hemodynamic and oxygen metabolism in newborns. Cereb Cortex 2013;23:339–48.
    1. Franceschini MA, Thaker S, Themelis G, Krishnamoorthy KK, Bortfeld H, Diamond SG, Boas DA, Arvin K, Grant PE.. Assessment of infant brain development with frequency-domain near-infrared spectroscopy. Pediatr Res 2007;61(5 Pt 1):546–51.
    1. Chugani HT, Phelps ME.. Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography. Science 1986;231:840–3.
    1. McGovern-Dole The global effort to reduce child hunger and increase school attendance. Report to the United States Congress, fiscal years 2012#x20132014. USDA/Foreign Agricultural Service; 2016. [cited 2016 Aug 20] Available from: .
    1. World Food Programme Specialized nutritious foods. Rome (Italy): World Food Programme; 2016..
    1. Institute of Medicine DRI: the essential guide to nutrient requirements. Washington (DC): Institute of Medicine; 2006.
    1. Ferland G... Vitamin K and the nervous system: an overview of its actions. Adv Nutr 2012;3:204–12.
    1. Abbaspour N, Hurrell R, Kelishadi R.. Review on iron and its importance for human health. J Res Med Sci 2014;19:164–74.
    1. Hughes C, Ensor R.. Executive function and theory of mind in 2 year olds: a family affair? Dev Neuropsychol 2005;28:645–68.
    1. Hostinar CE, Stellern SA, Schaefer C, Carlson SM, Gunnar MR.. Associations between early life adversity and executive function in children adopted internationally from orphanages. Proc Natl Acad Sci USA 2012;109(Suppl 2):17208–12.
    1. Carlson SM, Mandell DJ, Williams L.. Executive function and theory of mind: stability and prediction from ages 2 to 3. Dev Psychol 2004;40:1105–22.
    1. Onyango AW, de Onis M.. WHO child growth standards: training course on child growth assessment. Geneva (Switzerland): WHO; 2008.
    1. Hata TR, Scholz TA, Ermakov IV, McClane RW, Khachik F, Gellermann W, Pershing LK.. Non-invasive raman spectroscopic detection of carotenoids in human skin. J Invest Dermatol 2000;115:441–8.
    1. Ermakov IV, Ermakova MR, Gellermann W, Lademann J.. Noninvasive selective detection of lycopene and β-carotene in human skin using Raman spectroscopy. J Biomed Opt 2004;9:332–8.
    1. Boas DA, Yodh AG.. Spatially varying dynamical properties of turbid media probed with diffusing temporal light correlation. J Opt Soc Am A Opt Image Sci Vis 1997;14:192–215.
    1. Cheung C, Culver JP, Takahashi K, Greenberg JH, Yodh AG.. In vivo cerebrovascular measurement combining diffuse near-infrared absorption and correlation spectroscopies. Phys Med Biol 2001;46:2053–65.
    1. Durduran T, Yodh AG.. Diffuse correlation spectroscopy for non-invasive, micro-vascular cerebral blood flow measurement. Neuroimage 2014;85(Pt 1):51–63.
    1. Mesquita RC, Durduran T, Yu G, Buckley EM, Kim MN, Zhou C, Choe R, Sunar U, Yodh AG.. Direct measurement of tissue blood flow and metabolism with diffuse optics. Philos Trans A Math Phys Eng Sci 2011;369:4390–406.
    1. Boas DA, Franceschini MA.. Haemoglobin oxygen saturation as a biomarker: the problem and a solution. Philos Trans A Math Phys Eng Sci 2011;369:4407–24.
    1. Yoxall CW, Weindling AM.. Measurement of cerebral oxygen consumption in the human neonate using near infrared spectroscopy: cerebral oxygen consumption increases with advancing gestational age. Pediatr Res 1998;44:283–90.
    1. Dehaes M, Aggarwal A, Lin PY, Rosa Fortuno C, Fenoglio A, Roche-Labarbe N, Soul JS, Franceschini MA, Grant PE.. Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia. J Cereb Blood Flow Metab 2014;34:87–94.
    1. Matcher SJ, Kirkpatrick PJ, Nahid K, Cope M, Delpy DT.. Absolute quantification methods in tissue near-infrared spectroscopy. SPIE 1995;2389:486–95.
    1. Roche-Labarbe N, Carp SA, Surova A, Patel M, Boas DA, Grant PE, Franceschini MA.. Noninvasive optical measures of CBV, StO(2), CBF index, and rCMRO(2) in human premature neonates' brains in the first six weeks of life. Hum Brain Mapp 2010;31:341–52.
    1. Selb J, Boas DA, Chan ST, Evans KC, Buckley EM, Carp SA.. Sensitivity of near-infrared spectroscopy and diffuse correlation spectroscopy to brain hemodynamics: simulations and experimental findings during hypercapnia. Neurophotonics 2014;1:1–15.
    1. Trans Cranial Technologies, Ltd 10/20 System positioning manual. Hong Kong; 2012. Available from: .
    1. WHO WHO global database on child growth and malnutrition. Guinea-Bissau: WHO; 2014.
    1. Calder PC.. Omega-3 fatty acids and inflammatory processes. Nutrients 2010;2:355–74.
    1. Kuratko CN, Barrett EC, Nelson EB, Salem N Jr.. The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: a review. Nutrients 2013;5:2777–810.
    1. Nehlig A, Daval JL, Debry G.. Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev 1992;17:139–70.
    1. Mueni E, Opiyo N, English M.. Caffeine for the management of apnea in preterm infants. Int Health 2009;1:190–5.
    1. Alloway TP, Alloway RG.. Investigating the predictive roles of working memory and IQ in academic attainment. J Exp Child Psychol 2010;106:20–9.
    1. Mulder H, Pitchford NJ, Marlow N.. Processing speed and working memory underlie academic attainment in very preterm children. Arch Dis Child Fetal Neonatal Ed 2010;95:F267–72.
    1. Lloyd-Fox S, Papademetriou M, Darboe MK, Everdell NL, Wegmuller R, Prentice AM, Moore SE, Elwell CE.. Functional near infrared spectroscopy (fNIRS) to assess cognitive function in infants in rural Africa. Sci Rep 2014;4:4740.
    1. Carp SA, Farzam P, Redes N, Hueber DM, Franceschini MA.. Combined multi-distance frequency domain and diffuse correlation spectroscopy system with simultaneous data acquisition and real-time analysis. Biomed Opt Express 2017;8:3993–4006.
    1. Bhutta ZA, Ahmed T, Black RE, Cousens S, Dewey K, Giugliani E, Haider BA, Kirkwood B, Morris SS, Sachdev HP, et al. . What works? Interventions for maternal and child undernutrition and survival. Lancet 2008;371:417–40.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner