“Early Nutrition Programming of Long-Term Health”

Mini-Symposium
“Early Nutrition Programming
of Long-Term Health”
December 1st 2014, Warsaw
PROJECT EARLYNUTRITION
6TH BIANNUAL MEETING MINI-SYMPOSIUM:
“EARLY NUTRITION PROGRAMMING OF LONG-TERM HEALTH”
14.30-14.40
Welcome / Introduction H. Szajewska / B. Koletzko
Chairperson: P. Socha
14.40-15.10
Early nutrition programming: introduction to the concept B. Koletzko
15.10-15.40
Nutrition early in life and later outcomes in preterm infants
H. van Goudoever
15.40-16.10
Early programming of obesity
D. Gruszfeld
16.10-16.40
Early gluten exposure and celiac disease risk
L. Mearin
16.40-17.00
Coffee Break
Chairperson: H. van Goudoever
17.00-17.30
LCPUFA, genes, mental performance
P. Socha
17.30-18.00
Maternal obesity: Human intervention studies
in EarlyNutrition Consortium
L. Poston
18.00-18.30
Microbiota modification in early life
H. Szajewska
18.30-19.00
Connecting evidence to clinical practice
(Using systematic reviews in guideline development)
J. Brożek
Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Berthold V. Koletzko
Dr. med., Dr. med. habil., Dr. h.c.,
University-Professor, Professor h.c.
• Professor of Paediatrics (C3, Extraordinarius),
Ludwig-Maximilians-University of Munich, Germany
• Head, Div. Metabolic & Nutritional Medicine,
Dr. von Hauner Children’s Hospital, Univ. of Munich
Scientiﬁc publications:
• 751 journal articles (13 506 times cited, H-index 59), 193 book chapters, 31 books/monographies
Leadership roles:
• Co-ordinator, EU FP7 EarlyNutrition Project (project-earlynutrition.eu)
• Co-ordinator, ESPEN Network Project on Disease Associated Malnutrition in Children
• President, European Society Paediatric Gastroenterology, Hepatology & Nutrition
(www.espghan.org)
• Managing Director, Early Nutrition Academy (www.early-nutrition.org)
• Chair, Committee on Nutrition, German Society Paediatrics (www.dgkj.de)
• Chair, Child Health Foundation German (www.kindergesundheit.de/)
• Member, Central Grant Review Board Medicine, German Research Council (www.dfg.de)
• Chair, Scientiﬁc Committee, National Network Young Families (www.gesund-ins-leben.de)
• Board Member, German Platform Nutrition and Physical Activity (www.pebonline.de)
• Board Member, International Society f. t. Study of Fatty Acids and Lipids (www.issfal.org)
• Member, Center of Advanced StudiesLMU, University of Munich
• Member, Munich Center of Health Sciences
Research funding:
• European Commission DG Research and Innovation
• European Research Council
• German Research Council (DFG)
• Bundesministerium f. Bildung u. Forschung / Federal Ministry of Education and Research
Scientiﬁc journal editor:
• Editor in Chief, Annals Nutrition & Metabolism
• Editor in Chief, World Review of Nutrition and Dietetics
• Associate Editor, Current Opinion Clin Nutrition Metabolic Care
• Associate Editor, Monatsschrift Kinderheilkunde
Advisor to governmental bodies:
• Member and Rapporteur, European Commission Scientiﬁc Committee on Food
• Scientiﬁc Advisor, European Parliament Committee on Consumer Protection
• Scientiﬁc Advisor, Innovation Initiative of the Chancellor of the Federal Republic of Germany
• Scientiﬁc Advisor, Forum Early Childhood Education, German Federal Minister of Family, Seniors, Women and Youth
• Scientiﬁc Advisor, New Zealand Ministry of Business, Innovation and Employment
• Scientiﬁc Advisor, New Zealand Ministry of Primary Industries
• Scientiﬁc Advisor, BPOM Food Safety Authority, Government of Indonesia
• Scientiﬁc Advisor, Food Safety and Quality Division, Ministry of Health, Government of Malaysia
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Selected honours:
• 1989 Hans-Adolf-Krebs-Award, German Society for Nutrition
• 1991 Kraft Research Award
• 1995 John Harries Prize, European Society for Paediatric Gastroenterology, Hepatology and Nutrition
• 1999 Research Award of the German Society for Nutritional Medicine
• 2000 Corresponding Member, Swiss Society for Paediatrics
• 2001 Konstantin-Horemis-Award, Panhellenic Society for Paediatrics
• 2002 Honorary Member, Polish Society for Paediatric Gastroenterology and Nutrition
• 2004 Jean Rey Award, European Society for Paediatric Gastroenterology, Hepatology and Nutrition
• 2004 Dr. Sreemanta Banjerjee Memorial Lecture, Bengal Obstetric & Gynecological Society
• 2006 Freedom to Discover Award, Bristol-Myers Squibb Foundation New York
• 2006 Dr. Werner Fekl Award
• 2006 Honorary Medal, Children’s Memorial Institute Warsaw
• 2006 Infant and Toddler Nutrition Research Award, European Society for Paediatric Gastroenterology,
Hepatology and Nutrition (ESPGHAN)
• 2009 ESPEN Network Grant
• 2009 Comprix Gold Award for Innovative Health Communication
• 2012 Rank Lecture Award, The Nutrition Society
• 2012 Arved Wretlind Lecture Award, European Society Clinical Nutrition Metabolism
• 2012-2014 Guest Professor, Poznan Univ. of Med. Sciences, Poznan, Poland
• 2013-2018 European Research Council Advanced Grant Award 2013-2018
• 2013 Fit4Future Award, Cleven Foundation
• 2014 Doctor and Professor honoris causa, University of Pecs, Hungary
The concept
of early nutrition programming
Berthold Koletzko, for the EarlyNutrition Research Project.
Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University of Munich, München, Germany
Many characteristics of an individual persist to some extent from early childhood to old age, which is usually
explained by genetic determination of phenotypic characteristics. However, we have come to appreciate that
environmental influences during sensitive time periods of early development modify the effects of the genome
on phenotype (1). An important influencing factor is early nutrition during the first about 1000 days of life,
from conception to early childhood, which can modulate cytogenesis, organogenesis, metabolic and endocrine
responses, pre- and postnatal growth trajectories, epigenetic regulation of gene expression, and hence induce
programming effects on long-term health and disease risks until old age (www.project-earlynutrition.eu)
(2, 3). One of several mechanisms by which the early environment can modify phenotype is epigenetic modification of an individual’s genome. Epigenetics refers to heritable changes in gene expression not caused by
changes in the DNA sequence, but by biochemical modifications of DNA which can determine whether or
not genes are expressed. Most available evidence on epigenetic effects of nutrition in animal models, but increasingly human studies emerge indicating an alteration of DNA methylation in relationship to long-term
outcomes such as obesity. Nutritional effects on DNA methylation so far have been mostly studied in animal
models and only in a few human studies. These and other mechanisms might explain the observed major
impact of pre- and postnatal nutrition on long-term health, performance and later disease risk up to old age.
For example, meta-analyses of large cohort studies reveal that breast feeding reduces obesity at school age by
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
about 20% compared to conventional bottle feeds, adjusted for biological and socio-demographic variables.
Currently, we follow three key hypothesis in early nutrition programming research: the “fuel mediated ‘in
utero’ hypothesis” proposing that intrauterine exposure to an excess of fuels such as glucose and fatty acids,
causes permanent changes of the fetus that lead to obesity in postnatal life; the “accelerated postnatal growth
hypothesis” which proposes an association between rapid weight gain in infancy and early childhood and an
increased risk of later obesity and other adverse outcomes; and the “mismatch hypothesis” which suggests
that experiencing a developmental ‘mismatch’ between pre-and postnatal metabolic conditions and growth
trajectories, with a sub-optimal perinatal environment followed by an obesogenic childhood environment
which is related to a particular predisposition to obesity and corresponding co-morbidities.
The “Accelerated Postnatal Growth Hypothesis” is supported by numerous studies documenting that rapid early weight gain from birth to about 2 years is a key predictor of later adiposity, obesity and associated disease outcomes such as diabetes, heart disease and other non-communicable diseases (NCD) (4-6). Numerous
observational studies found an association of rapid early weight gain from birth to ≈2 years to a higher likelihood of obesity. Breastfeeding is associated with less rapid weight gain in infancy than feeding conventional
infant formula (IF) and protects against later obesity (7). Meta-analyses of numerous observational studies
show breastfeeding associated with ≈15-20 % less obesity later (5, 8). Conventional IF provide 150 to 200% of
the protein supply with breastfeeding. We followed the hypothesis that the greater weight gain in formula-fed
infants, relative to breastfed infants, is at least in part caused by the different intakes of metabolizable protein
(9). Protein supply is usually 55-80% higher in formula-fed babies, as compared to breastfed infants, which
could enhance both early weight gain and later obesity risk (the “Early Protein Hypothesis”) (10). A high protein intake in excess of metabolic requirements may enhance the secretion of insulin and IGF-1. Epidemiological studies found high protein intakes in infancy and the second year, but not of energy, fat or carbohydrates,
predictive of an early occurrence of the adiposity rebound and a high BMI in childhood (11-15). We tested the
“Early Protein Hypothesis” in a randomized clinical trial, the European Childhood Obesity Project (16). This
multicentre RCT was set up in study centres in five European countries (Belgium, Germany, Italy, Poland,
Spain). Apparently healthy, term infants born from uncomplicated, singleton pregnancies were eligible for
study enrolment. Breastfed children had to be exclusively breastfed for the first 3 months. Formula-fed infants
had to be exclusively formula-fed at the end of the 8th week of life and were randomized to infant formulae
which were replaced by follow-on formulae from the 5th month of age onwards with lower protein (LP) and
higher protein (HP) content. The two types of formulae had an identical energy density achieved by adaptation of the fat content, whereas the protein contents were 1.8 vs. 2.9 g protein/100 kcal in the infant formulae
and 2.2 vs. 4.4. g protein/100 kcal in the follow-on formulae. The relative contents of amino acids did not differ. A total of 1678 infants were enrolled. The median age at the baseline visit was 16 days. The protein intake
was significantly different between the two formula groups at all time points up to 12 months of age but not
thereafter. The difference ranged between 5.5 g per day (95% CI 5.1–5.9) in the first month to 8.5 g (7.8–9.3) at
six months. Energy intake in the lower and higher protein formula group was identical at 3, 12, and 24 months
but was slightly higher (24 kcal [95% CI 6–43]) at 6 months of age in the lower protein formula group.
Differences in weight and weight-for-length between the formula groups emerged at six months of age and
remained relatively stable thereafter with a decreasing tendency towards the end of the study. At 24 months
of age, length was not different between the intervention groups. The mean weight attained at 24 months was
12.42 kg and 12.60 kg for the lower and higher protein groups, respectively. HP led to a significantly higher
BMI than LP during the intervention period from 6 months onwards as well as after the end of the intervention. Of interest, the BMI in the LP group was identical to the breastfed group at 2 years of age. The effect of
the intervention was not different among the countries for any of the analysed anthropometric measures. In
addition to total body growth, also a significant effect on kidney growth was found (17). Follow up at 6 years
shows that children fed lower protein formula in the first year of life had the same low BMI at early school
age as previously breastfed children, whereas children previously fed a high protein formula had a markedly
higher BMI at school age (18). Obesity prevalence at early school age was markedly reduced by infant feeding with low protein formula (adj. relative risk 2.87, 95%CI 1.22, 6.75, P=0.016). Studies exploring mechanisms
provided indications that the effects of protein intake on weight gain velocity is mediated through marked
dietary effects on IGF-I (19, 20), and that high protein intakes increases branched chain amino acids to concentrations where their catabolism is saturated (21).
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Conclusions: Infant feeding has powerful long-term programming effects, with very large effect sizes on
later obesity and associated disease risk. Our results indicate that breastfeeding protects causally against later
obesity and thus should be actively promoted, protected and supported. Infants who are not fully breastfed
should get state of the art infant formulae with reduced protein contents but high protein quality. Unmodified
cows’ milk contains three times as much protein as human breast milk, hence the feeding of cow’s milk (and
other unmodified animal milks) markedly increases infant protein intake and long-term disease risk. Therefore, drinking cow’s milk should be avoided during the 1st year of life whenever feasible and affordable. 
Acknowledgments: The work of the authors is financially supported in part by the Commission of the European Communities (FP7/2007-13, EarlyNutrition Project, www.project-earlynutrition.eu) and the European Research Council (Advanced Grant
n° 3226059). This abstract does not necessarily reflect the views of the Commission and in no way anticipates the future policy
in this area. Further support has been provided by the German Federal Ministry of Education and Research and the German
Research Council.
Author’s address:
Berthold Koletzko, Dr. med Dr. med habil (MD PhD), Professor of Paediatrics
Dr. von Hauner Children’s Hospital, Ludwig-Maximilians-University of Munich, Lindwurmstr. 4,
D-80337 München, Germany. [email protected]
References:
1. Koletzko B, Brands B, Chourdakis M, Cramer S, Grote V, Hellmuth C, et al. The Power of Programming and The Early Nutrition Project: opportunities for health promotion by nutrition during the first thousand days of life and beyond. Ann Nutr Metab
2014;64:141–50.
2. Symonds ME, Mendez MA, Meltzer HM, Koletzko B, Godfrey K, Forsyth S, et al. Early life nutritional programming of obesity:
mother-child cohort studies. Ann Nutr Metab. 2013;62(2):137-45.
3. Koletzko B, Brands B, Poston L, Godfrey K, Demmelmair H, Early Nutrition P. Early nutrition programming of long-term health.
Proc Nutr Soc. 2012 Aug;71(3):371-8.
4. Brands B, Demmelmair H, Koletzko B, The EarlyNutrition P. How growth due to infant nutrition influences obesity and later disease
risk. Acta Paediatr. 2014 Feb 12.
5. Koletzko B, Chourdakis M, Grote V, Hellmuth C, Prell C, Rzehak P, et al. Regulation of early human growth: impact on long-term
health. Ann Nutr Metab. 2014:in press.
6. Ward LC, Poston L, Godfrey KM, Koletzko B. Assessing early growth and adiposity: report from an EarlyNutrition Academy workshop. Ann Nutr Metab. 2013;63(1-2):120-30.
7. Oddy WH, Mori TA, Huang RC, Marsh J, Pennell C, Jacoby P, et al. Early infant feeding and adiposity risk: from infancy to adulthood. Ann Nutr Metab. 2014;64:215–23.
8. Arenz S, Ruckerl R, Koletzko B, von Kries R. Breast-feeding and childhood obesity – a systematic review. Int J Obes Relat Metab
Disord. 2004 Oct;28(10):1247-56.
9. Koletzko B, von Kries R, Monasterolo RC, Subias JE, Scaglioni S, Giovannini M, et al. Infant feeding and later obesity risk. Adv
Exp Med Biol. 2009;646:15-29.
10. Koletzko B, Broekaert I, Demmelmair H, Franke J, Hannibal I, Oberle D, et al. Protein intake in the first year of life: a risk factor
for later obesity? The E.U. childhood obesity project. Adv Exp Med Biol. 2005;569:69-79.
11. Baird J, Poole J, Robinson S, Marriott L, Godfrey K, Cooper C, et al. Milk feeding and dietary patterns predict weight and fat gains
in infancy. Paediatr Perinat Epidemiol. 2008 Nov;22(6):575-86.
12. Parizkova J, Rolland-Cachera MF. High proteins early in life as a predisposition for later obesity and further health risks. Nutrition.
1997 Sep;13(9):818-9.
13. Gunther AL, Remer T, Kroke A, Buyken AE. Early protein intake and later obesity risk: which protein sources at which time points
throughout infancy and childhood are important for body mass index and body fat percentage at 7 y of age? Am J Clin Nutr. 2007
Dec;86(6):1765-72.
14. Gunther AL, Buyken AE, Kroke A. Protein intake during the period of complementary feeding and early childhood and the association
with body mass index and percentage body fat at 7 y of age. Am J Clin Nutr. 2007 Jun;85(6):1626-33.
15. Gunther AL, Buyken AE, Kroke A. The influence of habitual protein intake in early childhood on BMI and age at adiposity rebound:
results from the DONALD Study. Int J Obes (Lond). 2006 Jul;30(7):1072-9.
16. Koletzko B, von Kries R, Closa R, Escribano J, Scaglioni S, Giovannini M, et al. Lower protein in infant formula is associated with
lower weight up to age 2 y: a randomized clinical trial. Am J Clin Nutr. 2009 Jun;89(6):1836-45.
17. Escribano J, Luque V, Ferre N, Zaragoza-Jordana M, Grote V, Koletzko B, et al. Increased protein intake augments kidney volume
and function in healthy infants. Kidney Int. 2011 Apr;79(7):783-90.
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
18. Weber M, Grote V, Closa-Monasterolo R, Escribano J, Langhendries JP, Dain E, et al. Lower protein content in infant formula
reduces BMI and obesity risk at school age: follow-up of a randomized trial. Am J Clin Nutr. 2014 May;99(5):1041-51.
19. Socha P, Grote V, Gruszfeld D, Janas R, Demmelmair H, Closa-Monasterolo R, et al. Milk protein intake, the metabolic-endocrine
response, and growth in infancy: data from a randomized clinical trial. Am J Clin Nutr. 2011 Dec;94(6 Suppl):1776S-84S.
20. Rzehak P, Thijs C, Standl M, Mommers M, Glaser C, Jansen E, et al. Variants of the FADS1 FADS2 gene cluster, blood levels of
polyunsaturated fatty acids and eczema in children within the first 2 years of life. PLoS One. 2010;5(10):e13261.
21. Kirchberg FF, Harder U, Weber M, Grote V, Demmelmair H, Peissner W, et al. Dietary protein intake affects amino acid and
acylcarnitine metabolism in infants aged 6 months. J Clin Endocrinol Metab. 2014 Nov 4:jc20143157.
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Prof. dr. J.B. (Hans) van Goudoever
Emma Children’s Hospital AMC – VU University
Medical Center Department of Paediatrics
Hans van Goudoever is Professor of paediatrics at the University of Amsterdam and at the VU University in Amsterdam. He is
director of the Emma Children’s Hospital AMC and chairman of the Department of Paediatrics at VU University Medical Center
in Amsterdam, The Netherlands.
He received his medical education and paediatric training at the Erasmus University. He performed his PhD thesis on ‘Nitrogen
metabolism of the preterm infant’. From 1998 until 2000 he held a post-doctorate position at the laboratory of the late Peter
Reeds, Baylor College of Medicine, Children’s Nutrition Research Center, Houston, Texas. He is a board member of the International Paediatric Research Foundation, a council member of the ESPGHAN and was chair of the ESPGHAN Committee on Nutrition. He is a member of the Dutch National Breast Feeding Council since 2011 and the Dutch Health Council since 2013. He was
scientiﬁc chairman of the 2009 ESPR meeting in Hamburg and many other national and international congresses and symposia.
He has a particular interest in neonatal nutrition, gastroenterology and metabolism. He published over 225 peer reviewed papers
and received many grants, both national and international (including FP-7 EU funding).
He serves as a reviewer for the Lancet, BMJ, AJCN, Pediatrics, J Pediatrics and many more international journals. He is on
the editorial board of the Journal of Nutrition and Metabolism, the Journal of Pediatric Gastroenterology and Nutrition and the
Chinese Medical Journal and the Medical Journal of the People’s Liberation Army.
Nutrition in early life and later
outcomes in preterm infants
Hans van Goudoever
Amsterdam, The Netherlands
The goal of paediatricians involved in the nutritional management of preterm infants is to mimick intra uterine growth but also to obtain a functional outcome comparable to infants born at term, as stated by the Committee on Nutrition from the European Paediatric Society of Gastroenterology, Hepatology and Nutrition1.
In utero, the fetal amino acid uptake exceeds the amount that is necessary for net protein accretion, which indicates that the human fetus oxidizes amino acids to generate energy2-4. After preterm birth survival, growth,
and development are dependent on nutritional supply of amino acids, fat and carbohydrates. A decade ago
many VLBW infants received only glucose, or small amounts of amino acids during the first few days of life,
resulting in large protein and energy deficits, subsequently accompanied by weight loss. Retrospective data
indicate that initial suboptimal management might have large implications for future neurocognitive development5. Administration of glucose and amino acids within a few hours after birth prevents infants from
a catabolic state. Nowadays it has become clear that preterm infants, with their small nutritional reserves,
need administration of total parenteral nutrition soon after birth. Several studies have demonstrated that
administration of 1-2.5 g amino acids/(kg.d) starting within a few hours after birth can reverse a negative
nitrogen balance into a positive balance, thus leading to anabolism6-11. Very recently, we have shown that early
amino acid administration associates with improved outcome at two years of life in preterm infants12. More
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
recent studies demonstrated that the nitrogen balance can be improved further by administration of amino
acids up to 3.6 g/(kg‧d)13-16 when provided with additional energy. So providing appropriate intakes in the first
period following life are pivotal for short and long term outcomes.
Not only quantity maters, also quality is important for both parenteral and enteral support. In term infants,
the benefits of breastfeeding are described in numerous articles and meta-analyses. Breast-feeding is also
associated with a demonstrable impact on infant morbidity in industrialised countries, for example, a reduction of gastrointestinal infection and acute otitis media17. Breast-feeding is associated with an enhanced
neurodevelopment, but causal relation is difficult to establish because of many confounding factors. A metaanalysis of showed an increment in cognitive function of 3.2 points after adjustment for maternal intelligence
in breast-fed infants compared with formula-fed infants18. Better cognitive development was present as early
as 6 months of age and was sustained throughout childhood and adolescence. The most important residual
confounding factor is the influence of maternal socioeconomic status on the child’s cognitive development.
However, a study from the Philippines evaluated the relation between breast-feeding and cognitive development in a population in which socioeconomic advantage was inversely correlated with rate of breast-feeding,
the opposite of industrialised countries19. Scores at 8.5 and 11.5 years were higher for infants breast-fed longer.
The large cluster randomisation study from Belarus showed that breast-feeding promotion resulted in a significant increase in verbal IQ (7.5 points; 95% CI 0.8–14.3)20.
The benefits of breast milk may be related to its content of docosahexaenoic acid (DHA, 22: 6[omega]3), that
plays an important role in brain and retina development21,22. It has been recently shown that the association between breast-feeding and better cognitive development was moderated by a genetic variant in FADS2,
a gene encoding the delta-6 desaturase that is the rate-limiting step on the metabolic pathway leading to
arachidonic and DHA production23. In preterm infants, benefits of human milk on cognitive development are
clearly shown in a randomized trial24. In addition blood lipid profile seems to be more beneficial in adolescents who received human milk when born preterm as compared to infants fed formula milk 25.
In conclusion, both the quantity and the quality of the nutritional support are key factors that influence
short and long term outcomes in preterm infants. As these infants depend almost entirely on how health care
professionals are addressing their needs, we are obliged to provide them with nutritional management which
is in line with the newest guidelines. 
1.
Agostoni C, Buonocore G, Carnielli VP, De Curtis M, Darmaun D, Decsi T, et al. Enteral nutrient supply for preterm infants:
commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. Journal of
pediatric gastroenterology and nutrition 2010;50(1):85-91.
2. Chien PF, Smith K, Watt PW, Scrimgeour CM, Taylor DJ, Rennie MJ. Protein turnover in the human fetus studied at term using
stable isotope tracer amino acids. Am J Physiol 1993;265(1 Pt 1):E31-5.
3. van den Akker CH, Schierbeek H, Dorst KY, Schoonderwaldt EM, Vermes A, Duvekot JJ, et al. Human fetal amino acid metabolism at term gestation. The American journal of clinical nutrition 2009;89(1):153-60.
4. van den Akker CH, Schierbeek H, Minderman G, Vermes A, Schoonderwaldt EM, Duvekot JJ, et al. Amino acid metabolism in
the human fetus at term: leucine, valine, and methionine kinetics. Pediatr Res 2011;70(6):566-71.
5. Stephens BE, Walden RV, Gargus RA, Tucker R, McKinley L, Mance M, et al. First-week protein and energy intakes are associated
with 18-month developmental outcomes in extremely low birth weight infants. Pediatrics 2009;123(5):1337-43.
6. Anderson TL, Muttart CR, Bieber MA, Nicholson JF, Heird WC. A controlled trial of glucose versus glucose and amino acids in
premature infants. J Pediatr 1979;94(6):947-51.
7. Rivera A, Jr., Bell EF, Bier DM. Effect of intravenous amino acids on protein metabolism of preterm infants during the first three days
of life. Pediatr Res 1993;33(2):106-11.
8. Saini J, MacMahon P, Morgan JB, Kovar IZ. Early parenteral feeding of amino acids. Arch Dis Child 1989;64(10 Spec No):1362-6.
9. Van Goudoever JB, Colen T, Wattimena JL, Huijmans JG, Carnielli VP, Sauer PJ. Immediate commencement of amino acid supplementation in preterm infants: effect on serum amino acid concentrations and protein kinetics on the first day of life. The Journal of
pediatrics 1995;127(3):458-65.
10. van Lingen RA, van Goudoever JB, Luijendijk IH, Wattimena JL, Sauer PJ. Effects of early amino acid administration during total
parenteral nutrition on protein metabolism in pre-term infants. Clin Sci (Lond) 1992;82(2):199-203.
11. Thureen PJ, Anderson AH, Baron KA, Melara DL, Hay WW, Jr., Fennessey PV. Protein balance in the first week of life in ventilated
neonates receiving parenteral nutrition. Am J Clin Nutr 1998;68(5):1128-35.
12. van den Akker CH, Te Braake FW, Weisglas-Kuperus N, van Goudoever JB. Observational outcome results following a randomized controlled trial of early amino Acid administration in preterm infants. Journal of pediatric gastroenterology and nutrition
2014;59(6):714-9.
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
13. Ibrahim HM, Jeroudi MA, Baier RJ, Dhanireddy R, Krouskop RW. Aggressive early total parental nutrition in low-birth-weight
infants. Journal of perinatology: official journal of the California Perinatal Association 2004;24(8):482-6.
14. te Braake FW, van den Akker CH, Wattimena DJ, Huijmans JG, van Goudoever JB. Amino acid administration to premature
infants directly after birth. The Journal of pediatrics 2005;147(4):457-61.
15. Thureen PJ, Melara D, Fennessey PV, Hay WW, Jr. Effect of low versus high intravenous amino acid intake on very low birth weight
infants in the early neonatal period. Pediatr Res 2003;53(1):24-32.
16. Vlaardingerbroek H, Roelants JA, Rook D, Dorst K, Schierbeek H, Vermes A, et al. Adaptive regulation of amino acid metabolism
on early parenteral lipid and high-dose amino acid administration in VLBW infants – A randomized, controlled trial. Clin Nutr 2014.
17. Agostoni C, Braegger C, Decsi T, Kolacek S, Koletzko B, Michaelsen KF, et al. Breast-feeding: A commentary by the ESPGHAN
Committee on Nutrition. Journal of pediatric gastroenterology and nutrition 2009;49(1):112-25.
18. Anderson JW, Johnstone BM, Remley DT. Breast-feeding and cognitive development: a meta-analysis. The American journal of
clinical nutrition 1999;70(4):525-35.
19. Daniels MC, Adair LS. Breast-feeding influences cognitive development in Filipino children. The Journal of nutrition 2005;135(11):
2589-95.
20. Kramer MS, Aboud F, Mironova E, Vanilovich I, Platt RW, Matush L, et al. Breastfeeding and child cognitive development: new
evidence from a large randomized trial. Archives of general psychiatry 2008;65(5):578-84.
21. Makrides M, Neumann MA, Byard RW, Simmer K, Gibson RA. Fatty acid composition of brain, retina, and erythrocytes in breastand formula-fed infants. The American journal of clinical nutrition 1994;60(2):189-94.
22. Jensen CL, Voigt RG, Prager TC, Zou YL, Fraley JK, Rozelle JC, et al. Effects of maternal docosahexaenoic acid intake on visual function and neurodevelopment in breastfed term infants. The American journal of clinical nutrition 2005;82(1):125-32.
23. Caspi A, Williams B, Kim-Cohen J, Craig IW, Milne BJ, Poulton R, et al. Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism. Proceedings of the National Academy of Sciences of the United States of America
2007;104(47):18860-5.
24. Lucas A, Morley R, Cole TJ. Randomised trial of early diet in preterm babies and later intelligence quotient. BMJ 1998;317(7171):1481-7.
25. Singhal A, Cole TJ, Fewtrell M, Lucas A. Breastmilk feeding and lipoprotein profile in adolescents born preterm: follow-up of a prospective randomised study. Lancet 2004;363(9421):1571-8.
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Dariusz Gruszfeld M.D., Ph.D.
Children’s Memorial Health Institute in Warsaw
Pediatrician, specialist in neonatology. Deputy Head of Neonatal Department in Children’s
Memorial Health Institute in Warsaw, Head of Neonatal Intensive Care Unit. Co-author and
author of several papers in the ﬁeld of neonatology and nutritional programming – in particular the ‘early protein hypothesis’. Participates in the EU Childhood Obesity Project (CHOP)
from the very beginning. As a coordinator of the Polish team collaborates in EarlyNutrition
Project with the group of Prof. Bert Koletzko from Germany.
Early programming of obesity
Dariusz Gruszfeld
Children’s Memorial Health Institute, Neonatal Department
The prevalence of obesity increases all over the world, including developed as well as developing countries.
Of particular concern is the rising prevalence of obesity in children.
The origins of obesity and mechanisms responsible for such a rapid increase in obesity rates is an exciting,
strategic area of current research.
It is commonly accepted that the current environment, including diet and lifestyle can affect the health of
an individual. However, in recent decades it has become evident that the early life environment and in particular early nutrition, may have long-lasting effects on the susceptibility of an individual to develop a wide
spectrum of conditions including obesity, type 2 diabetes and cardiovascular disease.
When a stimulus or insult occurs during a critical period of early development it may cause a permanent
alterations in metabolic pathways of organs and tissues, leading to irreversible changes in the structure and
function of the body.
Epidemiological studies on obesity focus on the effects of intrauterine malnutrition and low birth weight
on subsequent increased risk of obesity. The risk is additionally increased when there is a conflict between
undernutrition in utero and adequate early postnatal nutrition.
Recently, some randomized clinical studies demonstrated a causal relationship between early postnatal
nutrition and obesity risk in children. In the EU Childhood Obesity Project (CHOP) infants were randomized
either to conventional formula feeding with a relatively higher protein supply during the 1st year of life or to
a protein reduced intervention formula. Feeding conventional formula in infancy induced faster weight gain
and BMI up to 2 years of life.
Animal studies not only confirm the results of epidemiological studies in humans but they also elucidate
potential mechanisms responsible for metabolic “programming”.
Several factors and pathways may be involved in pathogenesis of childhood obesity, including IGF-1, insulin, leptin, glucocorticoids and branched-chain amino acids. They all seem to play a role in a complex interaction of peripheral and central mechanisms controlling energy balance and fat tissue accumulation.
Finally, there is growing evidence, that epigenetic modifications due to environmental exposures during
early life, such as DNA methylation can induce persistent alterations in the epigenome, which may lead to an
increased risk of obesity later in life.
The new results may help to predict an individual’s obesity risk at a young age and to introduce targeted
prevention strategies. Several epigenetic marks are modifiable, by changing the exposure in utero and by
lifestyle changes. 
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
M. Luisa Mearin Manrique, M.D., Ph.D.
Pediatric Gastroenterologist, Associate Professor
Leiden University Medical Center (LUMC), Department of Pediatrics
Luisa Mearin (MD, PhD) is paediatric gastroenterologist and Associate Professor of Paediatrics at the University of Leiden, the Netherlands and leads the Unit of Paediatric Gastroenterology of the Leiden University Medical Center (LUMC). She is a member of the Dutch
Society of Pediatrics (NVK) and of the Gastroenterology Committee and of the Council of
the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).
She is scientiﬁc ofﬁcer (Coeliac Disease Expertise Centrum) of the Dutch Coeliac Disease Consortium (CDC). She maintains
national and international collaborations, with both clinical and basic researchers. She is involved in many international project
collaborations with researchers in Europe and from countries outside of Europe. In addition, she has experience in the coordination of EU funded projects: Biomed 2 Programme 1996; CDEUSSA (Food – CT – 2005–) and PreventCD Inﬂuence of the dietary
history in the prevention of coeliac disease: possibilities of induction of tolerance for gluten in genetic predisposed children
(Food – CT – 2006). She has a long experience in the diagnosis and treatment of children with gastrointestinal diseases and their
families. She is actively involved in research on gastrointestinal diseases in childhood, including the epidemiology, immunology,
genetics, treatment, prevention, (complications and quality of life). Her ambition is to improve the health and quality of life of
sick children, especially of those with gastrointestinal diseases, particularly coeliac disease.
Early gluten exposure
and celiac disease risk
M. Luisa Mearin
Dept. of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands
Several studies have suggested a protective role of breast feeding and/or the timing and quantity of gluten
introduction in the subsequent development of coeliac disease (CD) and the existence of a ”window of opportunity” between 4-6 months of age in which gluten can be introduced in small amounts has been suggested.
Therefore, the European Society for Pediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) recommends avoiding gluten introduction before the age of 4 months and after the age of 7 months and that gluten
should be preferably introduced during on-going breast feeding. However, the influence of breast feeding in
the development of CD is not clear, since some studies report prevention and others not. In addition, most of
the studies on this topic had been observational and retrospective. For these reasons prospective studies are
needed to understand the relationship between early nutrition in particular and for environmental factors in
general concerning the development and possible prevention of CD. One example is the European multicenter
PreventCD project (www.preventcd.com) a multicenter, randomized, double-blind, placebo-controlled dietary
intervention study involving 944 children who were positive for HLA-DQ2 or HLADQ8 and had at least one
first-degree relative with celiac disease. From 16 to 24 weeks of age, 475 participants received 100 mg of immunologically active gluten daily, and 469 received placebo. Anti-transglutaminase type 2 and antigliadin antibodies
were periodically measured. The primary outcome was the frequency of biopsy-confirmed CD at 3 years of age.
CD was confirmed in 80 children; median age, 2.8 years; 59% girls. The cumulative incidence of CD was 5.2%
(95% confidence interval [CI], 3.6 to 6.8), with similar rates in the gluten group and the placebo group (5.9% [95%
CI, 3.7 to 8.1] and 4.5% [95% CI,2.5 to 6.5], respectively (NEJM 2014;371:1304-15). Breast-feeding, regardless of
whether it was exclusive or whether it was ongoing during gluten introduction, did not significantly influence
the development of CD or the effect of the intervention. These results do not provide evidence to support any
specific feeding recommendation with respect to the timing of gluten introduction for infants at risk for CD. 
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Prof. Piotr Socha, M.D., Ph.D.
Piotr Socha is a Head of the Gastroenterology, Hepatology and Nutrition Disorders Ward in
The Children’s Memorial Health Institute in Warsaw.
His research and clinical work were devided into two streams – nutrition and liver. He described nutritional problems in cholestatic liver disease-eg. He developed the concept of
TPGS (water soluble vitamin) therapy, indicated the risks and causes of LCPUFA deﬁciency.
His research concentrated also on non-alcoholic fatty liver disease with critical approach
to therapy. His clinical experience with rare diseases brought to scientiﬁc contribution in
research on Wilson disease and newly described PGM-1 as a defect of glycosylation. Most of the recent research work was
devoted to obesity prevention and therapy and feeding disorders became one of the major clinical interests.
Piotr Socha was the chair of the Hepatology Committee of ESPGHAN (2010-2013). He was awarded with John Harries Prize
by ESPGHAN in 1995. Piotr Socha contributs/contributed to 7 EU projects (CHOP, EUROWILSON, EARNEST, PERFECT, NUTRIMENTHE, TOYBOX, EARLY NUTRITION). He is the president of the Polish Society for Pediatric Gastroenterology, Hepatology and
Nutrition. He published over 250 peer reviewed papers and contributed to 26 books. He is the Associated Editor of the Journal
of Pediatric Gastroenterology, Hepatology and Nutrition.
The major research interests at present are childhood obesity and its complications (mainly non-alcoholic fatty liver disease),
feeding disorders, immune deﬁciencies causing severe inﬂammatory bowel disease, Wilson’s disease, congenital defects of
glycosylation and gene modiﬁers in those frequent and rare diseases.
LCPUFA, genes, mental performance
Piotr Socha
Children’s Memorial Health Institute
Long-chan polyunstaurated fatty acid supplementation (LCPUFA) were studies in different populations to
investigate various outcomes – including cardiovascular risk, infections, risk of premature birth and mental
performance. Mental performance seems to be one of the major interest in respect of LCPUFA supplementation or mainly docosahexaenoic acid (DHA) was investigated in infancy and during pregnancy, but its
supplementation seems to be promissing also in adults. The recent metaanalysis by Jiao J et al., addressed
the question of LCPUFA supplementation on cognitive function through the life span. The authors finally
included 34 randomized controlled studies of a total of 12,999 participants and showed that n-3PUFA supplements significantly improved cognitive development in infants, including the Mental Development Index, the
Psychomotor Development Index and language, motor, and cognitive abilities. However, n-3 PUFAs did not
promote cognitive function in children, adults, or the elderly, except for the attention domain. n-3 PUFA supplements were not associated with improvements in cognitive decline or with any effects on Alzheimer disease in elderly people.
The effects of DHA supplementation in pregnancy and infancy were also recognized by EFSA. The claim
on maintenence of normal brain function and normal vision were accepted. The major consideration was the
dose of DHA that is required in infancy for improvement of mental performance as the effects could not be
clearly seen with low doses. It seems that min 100 mg per day for healthy infants is required that corresponds
with the DHA content exceeding 0,3% of total fatty acids in an infant formula. Pregnant women are adviced
to be supplemented with minimum 200 mg of DHA per day.
However, it is not only dietary factors which are responsible for tissue LCPUFA levels as it is also mediated by endogenous synthesis via the successive elongation and desaturation of dietary fatty acid precursors.
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Delta-5 desaturase (D5D) and delta-6 desaturase (D6D) are two key enzymes required for the synthesis of
LCPUFA in mammals – they are respectively encoded by the FADS1 and FADS2 genes. Many studies reported
associations between genetic variants in the FADS1 – FADS2 gene cluster and LCPUFA levels. Based on the
HELENA study Bokor S et al. showed that rare alleles of several SNPs in the FADS gene cluster are associated with higher D6D activity and lower D5D activity in European adolescents. Koletzko B et al. investigated
the role of genetic variants for LCPUFA status in preganant women and conlcuded that FADS genotypes
influence DHA amounts in maternal RBC phospholipids and might affect the child’s DHA supply during
pregnancy. The same group investigated the influence of maternal arachidonic acid and DHA on fetal neural
development and child child IQ by 8 years of age and found that the endogenous synthesis of these fatty acids
by FADS genes, especially FADS2, may be important.
In conclusion, it seems that requirements for DHA may vary in the population. Future studies should address FADS genotypes in evaluation of clinical outcomes of LCPUFA supplementation. 
Reading
• Jiao J, Li Q, Chu J, Zeng W, Yang M, Zhu S. Effect of n-3 PUFA supplementation on cognitive function throughout the life span from
infancy to old age: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2014 Dec;100(6):1422-36.
• Szilvia Bokor, Julie Dumont, Andre Spinneker, Marcela Gonzalez-Gross, Esther Nova, Kurt Widhalm, George Moschonis, Peter Stehle, Philippe Amouyel, Stefaan De Henauw, Dènes Molnàr, Luis A. Moreno, Aline Meirhaeghe, and Jean Dallongeville,
1, on behalf ofthe HELENA Study Group. Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and
delta-6 desaturase activities estimated by serum fatty acid ratios J. Lipid Res . 2010. 51: 2325–2333.
• Berthold Koletzko, Eva Lattka, Sonja Zeilinger, Thomas Illig, and Colin Steer. Genetic variants of the fatty acid desaturase gene
cluster predict amounts of red blood cell docosahexaenoic and other polyunsaturated fatty acids in pregnant women: findings from the Avon
Longitudinal Study of Parents and Children. Am J Clin Nutr 2011;93:211–9.
• Steer CD1, Lattka E, Koletzko B, Golding J, Hibbeln JR. Maternal fatty acids in pregnancy, FADS polymorphisms, and child intelligence quotient at 8 y of age. Am J Clin Nutr. 2013 Dec;98(6):1575-82.
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Professor Lucilla Poston
Professor Lucilla Poston is Head of the Division of Women’s Health and Director of Research
of the Women’s Health Academic Centre at Kings College London and Kings’ Health Partners.
She holds the Tommy’s Charity Chair of Maternal and Fetal Health. A graduate in Physiology
(University College London) with a PhD in the ﬁeld of medicine, she directs a multidisciplinary
team of health professionals which she established in 1995, based at St. Thomas’ Hospital. Her
research team aims to improve the health of women and their children by better understanding of the processes which lead to complications in pregnancy, particularly premature birth,
obesity, gestational diabetes and pre-eclampsia. Professor Poston is an honorary Fellow of the
Royal College of Obstetricians and Gynaecologists (RCOG), a National Institute of Health Research (NIHR), Senior Investigator and
a Fellow of the UK Academy of Medical Sciences. Professor Poston has published more than 250 original research papers.
Maternal obesity:
human intervention studies
in the EarlyNutrition Consortium
Lucilla Poston, Fionnuala McAuliffe, Jodie Dodd, Ricardo Rueda
Maternal obesity is associated with poor outcomes in pregnancy, including a high incidence of gestational
diabetes and delivery of large for gestational age infants. Increasing evidence suggests that children of obese
women are more at risk of obesity and cardiometabolic disorders than children of lean women, and that this
may be a consequence of intrauterine exposure to excess nutrients and a sub-optimal hormonal environment
during early development. The majority of studies addressing associations between maternal obesity and
offspring health have been undertaken in observational mother – child cohorts, which are subject to residual
confounding. Intervention studies are needed to better define this relationship.
In EarlyNutrition we are addressing the influence of maternal obesity and excess fetal nutrition in utero in
four intervention studies with closely aligned objectives. The UPBEAT study (UK), which has recently completed
recruitment of 1556 obese pregnant women, whilst primarily designed to prevent gestational diabetes through
a lifestyle intervention (low glycemic diet and increased physical activity), provides an ideal opportunity to address whether the intervention also reduces the incidence of childhood obesity. Children are being studied at
6 months and 3 years of age. With very detailed information on body composition, diet, physical activity and
metabolic markers in mother and child, UPBEAT will be able to determine accurately the influence of maternal
obesity and metabolic variables on offspring body composition. The ROLO study, an investigation from Ireland
of 800 women who had previously delivered a large for gestational age infant, has shown that dietary advice in
pregnancy can improve maternal glycemic control. ROLO, which also has very detailed maternal and child data
has already reported associations between maternal inflammatory mediators and offspring adiposity, and an influence of the maternal LGI diet and neonatal anthropometry. In EarlyNutrition the ROLO team are determining
whether the intervention has influenced childhood body composition at the age of five years. When childhood
follow up is complete in these two studies we shall undertake a metanalysis of data from ROLO and UPBEAT
children, and from three year old children in the LIMIT study from Australia. LIMIT has already reported that
a lifestyle intervention in 2212 overweight and obese pregnant women led to a reduction in the number of macrosomic infants. Finally, EarlyNutrition partners are undertaking a new trial, NiGoHealth, a study of low glycemic
dietary supplement given to 324 obese pregnant women, to determine whether this dietary regime is effective in
improving maternal glycemia, and thereby may reduce the risk of macrosomia and obesity in later life. 
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Prof. Hania Szajewska, M.D.
The Medical University of Warsaw, Department of Paediatrics
e-mail: [email protected]
Hania Szajewska is Professor and Chair of Department of Paediatrics at the Medical University of Warsaw.
She has broad interests in paediatric nutrition but her research focuses on probiotics and
prebiotics, the effects of early dietary interventions on later outcomes, acute and chronic
diarrheal diseases, and coeliac disease. She is or has been actively involved in several European Union-funded projects (e.g., PREVENTCD, NUTRIMENTHE, EarlyNutrition). She is an enthusiastic advocate for the practice
of evidence-based medicine.
She served as a member of the Council of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition
(ESPGHAN), and more recently as the General Secretary of ESPGHAN. She also served as a member and then as the Secretary
of the ESPGHAN Committee on Nutrition. Currently, she serves as the co-chairperson of the ESPGHAN Working Group on Probiotics and Prebiotics, and the chairperson of the ESPGHAN Working Group on Outcomes in Nutrition Trials.
Since 1 March 2014, she serves as the Editor-in-Chief (Europe) of the Journal of Pediatric Gastroenterology and Nutrition.
She has published over 170 publications and 20 book chapters. Citations 4884; Hirsh index 41 (Web of Science, October 2014).
Microbiota modiﬁcation in early life
Prof. Hania SZAJEWSKA
The Medical University of Warsaw, Department of Paediatrics
Humans have ten times more microbial cells than human cells, with the highest concentration of microorganisms located within the digestive tract. Up to 1000 different species have been identified with current microbiological techniques. These microbiota mediate many key functions, including metabolic, trophic, and protective (barrier) functions. Although causality remains to be confirmed, current evidence supports the view
that the gut microbiota play role in human health and disease. If so, it is logical to assume that manipulation
of the gut microbiota, such as through the administration of probiotics (and/or prebiotics) could potentially
be a preventive and/or therapeutic measure in the evolution of disease states. Here, some examples of current
research related to the use of probiotics in early life are described.
Necrotizing enterocolitis (NEC). The possible consequences of abnormal patterns of gut colonization in
preterm infants to health are not known. However, it has been speculated that they may contribute to increased susceptibility to infections and the pathogenesis of NEC. Certain probiotics prevent NEC. Controversy exists whether current evidence is sufficient to change practice and start the routine use of probiotics
in preterm infants to prevent NEC. In settings in which the incidence of NEC is high, one may consider the
use of probiotics – single or in combination. However, care should be given to choose those that are the best
studied, with the highest effect size, and the best safety profile.
Allergic diseases. It has been speculated that altered microbial exposure in the gastrointestinal tract may
be partly responsible for the increased prevalence of allergic diseases. The immunological basis for these
diseases, including the role of three subgroups of regulatory T cells that has revolutionized the so-called
hygiene hypothesis, has been elaborated. Alterations in gut microbiota preceding the development of allergic
disorders have been identified. There are studies that show a protective effect, no effect, or even a predisposing effect of using probiotics for preventing the allergic condition. Confirmatory studies are needed before
any recommendations can be made.
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Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Functional gastrointestinal disorders. Exclusively or predominantly breastfed infants with infantile colic
benefit from the administration of L. reuteri DSM 17938 compared with placebo. Preliminary data suggest that
L. reuteri may be effective in the prevention of some functional gastrointestinal disorders, such as colic and
regurgitation. This innovative approach needs further evaluation by an independent research team.
Overweight & obesity. The link between gut microbiota and obesity via increasing the energy harvest from
food ingredients is more and more recognized. Differences are apparent within the first week of life, although
currently it is impossible to describe obesogenic gut microbiota. Preliminary studies both in animals and humans indicate that the administration of specific probiotics might be associated with weight modification.
In summary, it is clear that the composition of microbial communities plays a significant role in the development of a number of conditions. However, there are still more questions than answers. The field is rising,
with a huge potential and some first clinical applications. It is definitely worth observing closely, if not being
the subject of active research. 
17
Project EarlyNutrition – 6 th biannual meeting mini-symposium: „Early nutrition programming of long-term health”
Jan Brożek, M.D, Ph.D.
McMaster University in Hamilton, Ontario, Canada
Dr Jan Brożek is a general internist with special interest in allergy and immunology. He is an
assistant professor in the Department of Clinical Epidemiology & Biostatistics and the Department of Medicine at McMaster University in Hamilton, Ontario, Canada – the birthplace
of problem based learning and a leading institution in the development of evidence-based
medicine. He is an active member of the GRADE working group the aim of which is to create a sensible, systematic, and transparent approach to the development of clinical practice
guidelines. He is a member of the Cochrane Collaboration’s Applicability and Recommendations Methods Group. Dr Brożek is
a methodologist for the American Thoracic Society where he has been involved in the development of multiple clinical practice
guidelines. He has also developed guidelines with World Allergy Organization, European Respiratory Society, Infectious Diseases Society of America and has collaborated with guideline panels of various organizations including WHO. His academic
interests focus on systematic reviews of therapeutic and diagnostic interventions particularly in allergy, improving presentation
of research evidence to patients, clinicians and health care decision makers, and the development and adaptation of clinical
practice guidelines.
Using systematic reviews
in guideline development
Jan Brożek
McMaster University in Hamilton, Ontario, Canada
Health care guideline recommendations need to be based on research evidence, consideration of costs, and
values and preferences of those for whom recommendations are made. A summary of all relevant research
evidence is essential when developing a recommendation and should be based on a systematic review. It is
sometimes more practical and efficient to use existing systematic reviews for guideline development and only
occasionally perform systematic reviews de novo. 
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