No. 39 / November 2015 2015, Nestlé Nutrition Institute Printed in M Programming Power of Programming for a Healthy Life by? Mary S. Fewtrell, London (UK) David M. Fleischer, Aurora, CO (USA) Pinkal Patel and Jatinder Bhatia, Augusta, GA (USA)
Programming for a Healthy Life by? Mary S. Fewtrell Childhood Nutrition Research Centre UCL Institute of Child Health London, UK m.fewtrell@ucl.ac.uk Complementary feeding practices could potentially influence later health outcomes by programming effects, but also by lasting effects on food preferences, appetite, and eating behaviour. Delaying the introduction of complementary feeding until the age of 4 months may protect against later obesity and possibly against allergy and the development of coeliac disease, with little evidence that timing is influential beyond this age. A high protein intake during the complementary feeding period may be associated with an increased obesity risk. Complementary feeding (CF) practices could potentially influence later health outcomes by a number of mechanisms including programming effects, but also by lasting effects on food preferences, appetite, and eating behaviour. Traditional weaning practices such as feeding to comfort the infant and forced feeding, as well as our taste and flavour preferences, evolved to be suitable in conditions where food was scarce. They are not appropriate for modern obesogenic environments, and this may result in later problems such as distinguishing hunger from other distress cues, ignoring satiety signals, and preferring unsuitably sweet, energy-dense foods. However, although there is a clear genetic component to aspects of taste, flavour preferences, and appetite, parents and caregivers can modify environmental influences. For example, innate preferences for sweet flavours and dislike of bitter flavours can be modified by exposures during pregnancy and early infancy from breast milk but also from infant formulas; and these preferences can persist with continued exposure to a flavour [1, 2]. Parenting behaviour can also have positive effects on infant feeding practices and growth. A recent systematic review concluded that the most promising interventions for reducing the risk of overweight and obesity in infancy and early childhood are those that focus on diet and responsive feeding, including education on recognising infant hunger and satiety cues and non-food management of infant behaviour [3]. Twin studies suggest that some aspects of infant appetite are highly heritable, including eating speed and satiety [4], whilst appetite is probably causally related to weight gain [5]. This raises the intriguing possibility that it may be possible to identify individuals who are at risk of over-eating in an obesogenic environment and intervene to prevent adverse outcomes. The evidence that nutritional aspects of CF the timing and content of foods influence later health outcomes is limited in quantity and quality but suggests that delaying the introduction of CF until the age of 4 months may protect against later obesity [6] and possibly against allergy and the development of coeliac disease, with little evidence that timing is influential beyond this age [7 9]. Few studies have examined later outcomes in relation to specific nutrients or foods during the CF period, although there is concern that a high protein intake during this period could increase obesity risk [9]. CF practices vary markedly between and within countries. Given the complex interplay between nutrition, feeding behaviour, and psychological factors during this period, a holistic approach is required; a one size fits all approach is not feasible or sensible given the variation between infants, their environments, and their cultural factors. Foto: Clipdealer References 1. Mennella JA: Ontogeny of taste preferences: basic biology and implications for health. Am J Clin Nutr 2014;99:704S 711S. 2. Nehring I, Kostka T, von Kries R, Rehfuess EA: Impacts of in utero and early infant taste experiences on later taste acceptance: a systematic review. J Nutr 2015;145: 1271 1279. 3. Redsell SA, Edmonds B, Swift JA, Siriwardena AN, Weng S, Nathan D, Glazebrook C: Systematic review of randomised controlled trials of interventions that aim to reduce the risk, either directly or indirectly, of overweight and obesity in infancy and early childhood. Matern Child Nutr 2015, DOI: 10.1111/mcn.12184. 4. Llewellyn CH, van Jaarsveld CH, Johnson L, Carnell S, Wardle J: Nature and nurture in infant appetite: analysis of the Gemini twin birth cohort. Am J Clin Nutr 2010;91: 1172 1179. 5. van Jaarsveld CH, Llewellyn CH, Johnson L, Wardle J: Prospective associations between appetitive traits and weight gain in infancy. Am J Clin Nutr 2011;94:1562 1567. 6. Daniels L, Mallan KM, Fildes A, Wilson J: The timing of solid introduction in an obesogenic environment: a narrative review of the evidence and methodological issues. Aust NZ J Public Health 2015;39:366 373. 7. Anagnostou K, Stiefel G, Brough H, du Toit G, Lack G, Fox AT: Active management of food allergy: an emerging concept. Arch Dis Child 2015;100:386 390. 8. Szajewska H, Shamir R, Chmielewska A, Pieścik-Lech M, Auricchio R, Ivarsson A, Kolacek S, Koletzko S, Korponay-Szabo I, Mearin ML, Ribes-Koninckx C, Troncone R; PREVENTCD Study Group: Systematic review with meta-analysis: early infant feeding and coeliac disease update 2015. Aliment Pharmacol Ther 2015;41:1038 1054. 9. Hörnell A, Lagström H, Lande B, Thorsdottir I: Protein intake from 0 to 18 years of age and its relation to health: a systematic literature review for the 5th Nordic Nutrition Recommendations. Food Nutr Res 2013;57:21083. 2 3
David M. Fleischer Department of Pediatrics, University of Colorado Denver School of Medicine, Section of Allergy, Children s Hospital Colorado, Aurora, CO, USA david.fleischer@childrenscolorado.org Data from a randomized controlled trial that studied the timing of peanut introduction and peanut allergy outcomes clearly demonstrate that peanut allergy can be prevented by earlier introduction of peanut into an infant s diet. While more randomized controlled trials are under way, the message that earlier introduction of highly allergenic foods can prevent food allergy needs to be communicated to medical providers around the world who care for infants. The correct age to introduce complementary food that will result in oral tolerance has been debated for decades (fig. 1). Recommendations to delay introduction of allergenic foods such as milk, egg, and peanut were made in 2000 [1] but then retracted in 2008 [2]; both statements were based on sparse firm data. Over the last several years, though, observational studies demonstrated that earlier introduction of highly allergenic foods might prevent the onset of allergies to them [3 5]. Recently, the landmark study Learning Early About Peanut (LEAP) was published [6]. LEAP is the first large randomized controlled trial (RCT) to investigate the timing of peanut introduction. LEAP-ON Enquiring About Tolerance (EAT) Hen s Egg Allergy Prevention (HEAP) Beating Egg Allergy Trial (BEAT) Starting Time for Egg Protein (STEP) Table 1. Other food allergy prevention RCTs being performed LEAP was performed in the UK in a cohort of 640 high-risk infants, defined as having severe eczema and/or egg allergy, who were randomized either to peanut introduction early between the age of 4 11 months versus peanut avoidance until the age of 5 years. At study entry, 542 infants had negative skin prick tests (SPT) to peanut, while 98 infants had SPT wheal diameters between 1 and 4 mm (minimally SPT positive). A total of 76 children were excluded prior to randomization based on a peanut SPT >5 mm and were presumed peanut-allergic. After 5 years of peanut protein consumption of 2 g thrice weekly or avoidance, food challenges were performed. An intention-to-treat analysis showed that 17.2% of the children in the peanut avoidance group compared Effect of 1-year peanut discontinuation on peanut allergy Investigating the effect of early introduction in infants (3 months) of 6 allergenic foods together with breastfeeding versus standard introduction (6 months); followed up to the age of 3 years Infants randomized at 4 6 months to egg introduction or placebo, with effect on egg allergy measured at 12 months Infants randomized to egg introduction versus placebo at 4 6 months, with egg allergy assessment at 8 and 12 months Infants without eczema but atopic mothers randomized to egg introduction versus placebo at 4 6 months to 3.2% of the children in the peanut consumption group developed food challenge-proven peanut allergy, corresponding to a 14% absolute risk reduction and a relative risk reduction of 80%. Based on these LEAP data, allergy, pediatric, and dermatology organizations from around the world formulated a consensus statement that recommended early introduction of peanut (between 4 and 11 months of age) into the diet of high-risk infants in countries where peanut allergy is prevalent in order to prevent peanut allergy [7]. The organizations further recommended that certain high-risk infants, such as those with early-onset severe eczema or IgE-mediated food allergy, might benefit from evaluation to diagnose possible food allergy prior to Pre-2000 s 2000 2008 2012 No formal advice exists on what to avoid or include in an infant s/child s diet to prevent allergy. Fig. 1. Evolution of food allergy prevention. peanut introduction. The National Institutes of Health and an expert panel are developing more formal guidelines for peanut allergy prevention. More RCTs investigating early versus delayed food introduction will be published in the coming years that will shine light on other major food allergens (table 1), as the specific time for introduction may be different for different foods and at-risk patients. A clear paradigm shift, though, has occurred, now backed by data, that earlier complementary food introduction is better for allergy prevention. Mothers should eliminate peanut and tree nuts and consider eliminating egg, cow s milk, fish and perhaps other foods from their diets while breastfeeding. Recommend delayed introduction of the following highly allergenic foods in infants at high risk for allergic disease, to prevent development of future allergy: cow s milk until age 1 year, egg until age 2 years; peanuts, tree nuts, and fish until 3 years. No convincing evidence for delaying the introduction of specific highly allergenic foods, but no specific guidelines on when and how to introduce the highly allergenic foods listed above. References 1. American Academy of Pediatrics. Committee on Nutrition. Hypoallergenic infant formulas. Pediatrics 2000;106:346 349. 2. Greer FR, Sicherer SH, Burks AW; American Academy of Pediatrics Committee on Nutrition, American Academy of Pediatrics Section on Allergy and Immunology: Effects of early nutritional interventions on the development of atopic disease in infants and children: the role of maternal dietary restriction, breastfeeding, timing of introduction of complementary foods, and hydrolyzed formulas. Pediatrics 2008;121: 183 191. 3. Du Toit G, Katz Y, Sasieni P, Mesher D, Maleki SJ, Fisher HR, et al: Early consumption of peanuts in infancy is associated with a low prevalence of peanut allergy. J Allergy Clin Immunol 2008;122:984 991. Emerging data suggest the delayed introduction of complementary foods may increase the risk of food allergy, asthma, or eczema, and the early introduction of allergenic foods may prevent them. 4. Koplin JJ, Osborne NJ, Wake M, Martin PE, Gurrin LC, Robinson MN, et al: Can early introduction of egg prevent egg allergy in infants? A population-based study. J Allergy Clin Immunol 2010;126:807 813. 5. Katz Y, Rajuan N, Goldberg MR, Eisenberg E, Heyman E, Cohen A, et al: Early exposure to cow s milk protein is protective against IgE-mediated cow s milk protein allergy. J Allergy Clin Immunol 2010;126:77.e1 82.e1. 6. Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, et al: Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med 2015;372: 803 813. 7. Fleischer DM, Sicherer S, Greenhawt M, Campbell D, Chan E, Muraro A, et al: Consensus communication on early peanut introduction and the prevention of peanut allergy in high-risk infants. J Allergy Clin Immunol 2015;136:258 261. 4 5
Pinkal Patel Jatinder Bhatia Children s Hospital of Georgia Medical College of Georgia Augusta, GA, USA PIPATEL@gru.edu JATINDEB@gru.edu Potential to improve nutritional status No increased risk of eczema development Premature infants are a diverse population whose nutritional needs, developmental maturity, and long-term outcomes are different from those of term infants. Introduction of complementary feeds is a critical step in the advancement of feeding in preterm infants to avoid growth delay and important nutrient deficiencies. Developmental readiness rather than chronological age should be considered as an important factor to introduce complementary feeds. Premature infants (23 37 weeks) are a special group of the population whose nutritional requirements are different from those of term infants, especially for energy, protein, long-chain polyunsaturated fatty acids, iron, zinc, calcium, and selenium. Optimal nutritional intake is very important in these infants from birth until infancy to provide appropriate growth, especially head growth, which may have an impact on the long-term neurodevelopmental outcome and linear growth. Associated comorbidities such as feeding problems, gastroesophageal reflux, and respiratory compromise may delay the introduction of complementary foods in premature infants. Complementary foods refer to nutrient- and energy-containing solid or semi-solid foods (or liquids) fed to infants in addition to human milk or formula [1]. Introduction of complementary feeds is considered to be a critical step in the infants diet which can affect growth and may have long-term health consequences [2]. The American Academy of Pediatrics (AAP) and the World Health Organization recommend exclusive breastfeeding for the first 6 months of age, with the introduction of complementary foods and continued breastfeeding thereafter, and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends the introduction of complementary foods no earlier than 4 months and no later than 6 months of age [3 5]. There are no specific guidelines for preterm infants. The AAP recommends the introduction of solid foods based on developmental readiness, which is usually achieved at 4 6 months of age [6]. Studies suggest that preterm infants are significantly more likely to be introduced to solid food earlier than term infants [2]. Early introduction of complementary foods has been linked to rapid weight gain, obesity, diabetes mellitus, allergies, and atopic disease. Nevertheless, late introduction of complementary foods may lead to inadequate nutritional status and compromised immune development [7 10]. The selection of complementary foods should be based on the preterm infant s need for balanced energy source from protein, carbohydrate, and fat, especially long-chain polyunsaturated fatty acids, iron, and zinc. The common practice in the United States is to introduce iron-fortified cereals, followed by fruits or vegetables, with later introduction of meat [1]. Signs of developmental readiness for solid foods in infants are a reduced tongue thrust reflex and the ability to hold the head up well, to sit in a stable supported position, to open the mouth, and to lean forward towards the spoon [8]. Parents should choose a first food that provides the required nutrients and also helps meeting energy requirements. Solid foods should not be introduced before 6 months of age as gross motor development of infants, especially head control, is very important to safely introduce solid foods [1]. Parents should introduce one single-ingredient new food at a time and should not introduce other new foods for at least 3 5 days. By 7 8 months of age, infants should be consuming foods from all food groups. Whole cow s milk should not be introduced until 12 months of age, and fruit juice should not be offered before 6 months and its intake after that should be limited. Foods rich in zinc and iron should be included in complementary foods such as red meat, pork, and poultry [1]. The AAP encourages the consumption of meats, vegetables with higher iron content, and iron-fortified cereals for infants and toddlers between 6 and 24 months of age [1]. Parents should prepare homemade complementary foods in a safe and healthy manner. Head control for safe eating 0 1 2 3 4 5 6 Fig. 1. Adapted from Palmer and Makrides [8]. Age (months, corrected) The literature suggests that, given the lack of consensus and insufficient evidence, the decision to introduce preterm infants to solids/complementary foods should be made on an individual basis, considering postmenstrual age, nutritional status and requirement, and developmental readiness, especially motor development [7 11]. References: 1. American Academy of Pediatrics Committee on Nutrition; Kleinman RE, Greer FR (eds): Pediatric Nutrition, ed 7. Elk Grove Village, American Academy of Pediatrics, 2013. 2. Braid S, Harvey EM, Bernstein J, Matoba N: Early introduction of complementary foods in preterm infants. J Pediatr Gastroenterol Nutr 2015;60:811 818. 3. Eidelman AK, Schanler RJ: Breastfeeding and the use of human milk. Pediatrics 2012;129: e817 e841. 4. World Health Organization, UNICEF: Global strategy for infant and young child feeding. http://whqlibdoc.who.int/publications/2003/924562218.pdf. 2003. 5. Agostoni C, Decsi T, Fewtrell M, et al: Complementary feeding: a commentary by the ESPGHAN Committee on Nutrition. J Pediatr Gastroenterol Nutr 2008;46:99 110. 6. LaHood A, Bryant CA: Outpatient care of the premature infant. Am Fam Physician 2007;76:1159 1164. 7. King C: What s new in enterally feeding the preterm infant? Arch Dis Child Fetal Neonatal Ed 2010;95:F304 F308. 8. Palmer DJ, Makrides M: Introducing solid foods to preterm infants in developed countries. Ann Nutr Metab 2012:60:31 38. 9. King C: An evidence based guide to weaning preterm infants. Paediatr Child Health 2009;19:405 414. 10. Weng SF, Redsell SA, Swift JA, et al: Systemic review and meta-analysis of risk factors for childhood overweight identifiable during infancy. Arch Dis Child 2012;97:1019 1026. 11. Farano S, Borsani G, Vigi V: Complementary feeding practices in preterm infants: an observational study in a cohort of Italian infants. J Pediatr Gastroenterol Nutr 2007;45:S210 S214. 6 7
No. 39 / November 2015 2015, Nestlé Nutrition Institute Printed in This booklet is protected by copyright. However, it may be reproduced without the prior written permission of Nestlé Nutrition Institute or S. Karger AG, but is subject to acknowledgement of the original publication. Programming Power of Programming for a Healthy Life by? Mary S. Fewtrell, London (UK) David M. Fleischer, Aurora, CO (USA) Pinkal Patel and Jatinder Bhatia, Augusta, GA (USA) The material contained in this booklet was submitted as previously unpublished material, except in the instances in which credit has been given to the source from which some of the illustrative material was derived. Source of illustrations: Nestlé Nutrition Collection Great care has been taken to maintain the accuracy of the information contained in this booklet. However, neither Nestlé Nutrition Institute nor S. Karger AG can be held responsible for errors or for any consequences arising from the use of the information contained herein. Published by S. Karger AG,, for Nestlé Nutrition Institute Avenue Reller 22 Copyright 2015 by Nestlé Nutrition Institute, ISSN 1270 9743 To learn more about the Nestlé Nutrition Institute and its resources and fellowship opportunities visit: