Effect van vroege postnatale LCPUFA toevoeging aan flessenmelk  op de ontwikkeling van gezonde ŕ terme geboren zuigelingen

De vraag of pre- en/of postnatale toevoeging van lange keten meervoudig onverzadigde vetzuren (long-chain polyunsaturated fatty acids, LCPUFA) aan voeding de ontwikkeling van op tijd geboren baby’s al of niet beďnvloedt is volop in discussie. Momenteel onderzoekt onze groep door middel van twee RCTs het effect van prenatale en vroeg postnatale toevoeging van LCPUFA op de ontwikkeling van het kind.

Momenteel loopt een prospectief dubbel-blind RCT onderzoek. Drie groepen kinderen worden gevolgd: een groep die controle flessenvoeding kreeg (zonder LCPUFA; CF; n=169), een groep die flessenvoeding met extra LCPUFA kreeg; LF; n=146), en een borstgevoede groep (BF; n=159).  De kinderen werden neurologisch onderzocht in de neonatale periode en op de leeftijden van 3 en 18 maanden. We vonden dat LCPUFAs een gunstig effect hadden op de neurologische conditie op de leeftijd van 3 maanden, maar niet op die van 18 maanden. De neurologische conditie op 3 maanden van de borstgevoede kinderen was beter dan die van beide groepen kinderen die flessenvoeding kregen.

In een groot deel van de onderzoekspopulatie konden we ook de vetzuurstatus van de bloedvaten in de navelstreng bepalen. De neonatale vetzuurstatus, die in feite de prenatale vetzuur conditie weerspiegelt, bleek gerelateerd te zijn aan de neurologische conditie kort na de geboorte en op de leeftijd van 3 en 18 maanden.

EarnestRecent onderzochten we de kinderen weer op de leeftijd van 9 jaar. Het na-onderzoek omvatte een evaluatie van de neurologische conditie, het cognitieve functioneren en de aanwezigheid van leer- en gedragsproblemen. Het na-onderzoek maakte deel uit van EARNEST, dat op zijn beurt hoort bij het 6e RTD framework programma van de EU. We vonden inmiddels dat de neurologische conditie op 9 jaar niet beďnvloed werd door de aanwezigheid van LCPUFA in flesvoeding. Dit maal konden we wel een effect van borstvoeding aantonen. Met name de handvaardigheid van borstgevoede kinderen was wat beter dan die van flesgevoede kinderen. Binnenkort hopen we meer resultaten uit dit onderzoek bekend te kunnen maken.

Onderzoekers:

Dr. Günther Boehm - Numico Research, Friedrichsdorf, Duitsland
Dr. Tamás Decsi - Dept Paediatrics, Univ Pécs, Hongarije
Prof. Dr. Mijna Hadders-Algra - Ontwikkelingsneurologie
Drs. Corina de Jong - Ontwikkelingsneurologie   
Hedwig Kikkert, MSc - Ontwikkelingsneurologie

Recente publicaties:

  1. Dijck-Brouwer DAJ, Hadders-Algra M, Bouwstra H, Decsi T, Boehm G, Martini IA, Boersma ER, Muskiet FAJ. Lower fetal status of docosahexaenoic acid, arachidonic acid and essential fatty acids is associated with is less favourable neonatal neurological condition. Prostaglandins Leukot Essent Fatty Acids 2005; 72: 21-8.
  2. Bouwstra H, Dijck-Brouwer DAJ, Boehm G, Boersma ER, Muskiet FAJ, Hadders-Algra M. Long-chain polyunsaturated fatty acids and neurological developmental outcome at 18 months in healthy term infants. Acta Paediatr 2005; 94: 26-32.
  3. Dijck-Brouwer DAJ, Hadders-Algra M, Bouwstra H, Decsi T, Boehm G, Martini IA, Boersma ER, Muskiet FAJ. Impaired maternal glucose homeostasis during pregnancy is associated with low status of long chain polyunsaturated fatty acids (LCP) and essentially fatty acids (EFA) in the fetus. Prostaglandins Leukot Essent Fatty Acids 2005; 73: 85-7.
  4. Hadders-Algra M. The role of long-chain polyunsaturated fatty acids (LCPUFA) in growth and development. Adv Exp Med Biol. 2005; 569: 80-94.
  5. Hadders-Algra M. Effect of prenatal and early postnatal nutritional supplementation with long-chain polyunsaturated fatty acids (LCPUFA) on neurodevelopmental outcome in term infants. Current Nutrition & Food Science 2005; 1: 259-64.
  6. Bouwstra H, Dijck-Brouwer DAJ, Decsi T, Boehm G, Boersma ER, Muskiet FAJ, Hadders-Algra M. Relationship between umbilical cord essential fatty acid content and the quality of general movements of healthy term infants at 3 months. Pediatr Res 2006; 59: 717-22.
  7. Bouwstra H, Dijck-Brouwer DAJ, Decsi T, Boehm G, Boersma ER, Muskiet FAJ, Hadders-Algra M. Neurological condition at 18 months: positive association with venous umbilical DHA-status and negative association with umbilical trans-fatty acids. Pediatr Res, 2006; 60: 1-7
  8. Muskiet FAJ, Van Goor SA, Kuipers RS, Velzing-Aarts FV, Smit EN, Bouwstra H, Dijck-Brouwer DAJ, Boersma ER, Hadders-Algra M. Long-chain polyunsaturated fatty acids in maternal and infant nutrition. Prostaglandins Leukot Essent Fatty Acids 2006, 75: 135-44.
  9. Hadders-Algra M, Bouwstra H, Van Goor SA, Dijck-Brouwer DAJ, Muskiet FAJ.  Prenatal fatty and early postnatal fatty acid status and neurodevelopmental outcome. J. Perinat Med 2007, 35: S28-34.
  10. Hadders-Algra M. Prenatal long-chain polyunsaturated fatty acid status: the importance of a balanced intake of docosahexaenoic acid and arachidonic acid. J Perinat Med 2008; 36: 101-9.
  11. Hadders-Algra M Prenatal docosahexaenoic acid (DHA) and arachidonic acid (AA) supplementation better for neurodevelopment than supplementation with DHA only? J Perinat Med 2008; 36: 268-9,
  12. Fewtrell M, Kennedy K, Singhal A, Martin RM, Ness A, Hadders-Algra M, Koletzko B, Lucas A. How much loss to follow-up is acceptable in long-term rendomised trials and prospective studies. Arch Dis Child 2008; 93: 458-61.
  13. Oken E, Řsterdal ML, Gillman MW, Kundsen VK, Halldorsson TI, Strřm M, Bellinger DC, Hadders-Algra M, Michaelsen KF, Olsen SF. Associations of maternal fish intake during pregnancy and breastfeeding duration with attained developmental milestones in early childhood: a study from the Danish National Birth Cohort. Am J Clin Nutr 2008; 88:789-96. 
  14. Rosenfeld E, Beyerlein A, Hadders-Algra M, Kennedy K, Singhal A, Koletzko B, Von Kries R. IPD meta-analysis shows no effect of LC-PUFA supplementation on infant growth at 18 months. Acta Paediatr 2009; 98: 91-7.
  15. Van Goor SA, Dijck-Brouwer DAJ, Hadders-Algra M, Doornbos B, Erwich JJHM, Schaafsma A, Muskiet FAJ. Human milk arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation during pregnancy and lactation. Prostaglandins Leukot Essent Fatty Acids 2008, accepted for publication.
  16. Van Goor SA, Dijck-Brouwer DAJ, Doornbos J, Erwich JJHM, Schaafsma A,  Muskiet FAJ, Hadders-Algra M. Supplementation of DHA but not DHA with arachidonic acid during pregnancy and lactation influences general movement quality in twelve week old term infants. Brit J Nutr 2010; 103: 235-42.
  17. Beyerlein A, Hadders-Algra M, Kennedy K, Fewtrell M, Singhal A, Rosenfeld E, Lucas A, Bouwstra H, Koletzko B, Von Kries R. Infant formula supplementation with long-chain polyunsaturated fatty acids has no effect on Bayley developmental scores at 18 months of age – IPD meta-analysis of four large clinical trials. J Pediatr Gastroenterol Nutr,2010;50:79-84.
  18. Hadders-Algra M. Effect of long-chain polyunsaturated fatty acid supplementation on neurodevelopmental outcome in term infants. Nutrients 2010; 2: 790-804.
  19. De Jong C, Kikkert HK, Fidler V, Hadders-Algra M. The Groningen LCPUFA-study: effect of postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years. Br J Nutr 2010; 104: 566-72.
  20. Beyerlein A, Ness AR, Streuling I, Hadders-Algra M, Von Kries R. Early rapid growth.  No associations with later cognitive functions in children born not small-for-gestational age. Am J Clin Nutr 2010; 92:585-93.
  21. Hadders-Algra M. Prenatal and early postnatal supplementation with long-chain polyunsaturated fatty acids – neurodevelopmental considerations. Am J Clin Nutr, accepted for publication.
  22. Escolano-Margarit MV, Ramos R, Beyer J, Csábi Gy, Parrilla-Roure M, Cruz F, Pérez-García M, Hadders-Algra M, Gil A, Decsi T, Koletzko B, Campoy C. Fish oil supplementation to pregnant women and neurological outcome of their children at 4 and 5˝ years of age. J Nutr, accepted for publication.

Financiële ondersteuning:

Numico BV, Junior Scientific Master Class, en de Europese Unie
.

Effect of early postnatal LCPUFA supplementation of infant formula on neurodevelopmental outcome of healthy term infants

It is debated whether pre- or postnatal supplementation of nutrition with long-chain polyunsaturated fatty acids (LCPUFA) has an effect on neurodevelopmental outcome of term infants. Currently we study by means of two RCT the effect of prenatal and early postnatal supplementation with LCPUFA.

A prospective double-blind randomised control study was conducted. Three groups were formed: a control (CF; n=169), a LCPUFA-supplemented (LF; n=146), and a breastfed (BF; n=159) group. Information on potential confounders was collected at enrolment. Children were studied neurologically in the neonatal period, at 3 and 18 months. We found that LCPUFA supplementation had a beneficial effect on neurological condition measured by means of the quality of general movement at 3 months. Children who had received breast feeding performed best at 3 months, in particular when breastfeeding had been continued for at least 6 weeks. At 18 months the three feeding groups did not differ any more in neurological condition.

In part of the population studied fatty acid status could be determined in umbilical vessels. Neonatal fatty acid status was related to neonatal neurological condition and to neurological condition at 3 and 18 months. At present, we investigate whether neonatal fatty acid status also has an impact on neurological condition at 3 and 18 months.

EarnestRecently Currently, the children are have been re-assessed at the age of 9 years.  Re-assessment consisted of neurological, neuropsychological, behavioural and anthropometric evaluation. The follow-up forms part of EARNEST, which belongs to EU’s 6th RTD framework programme [Earnest Logo]. The first results showed that neurological condition at 9 years was not affected by the presence of LCPUFA in formula. But neurological condition, in particular fine manipulative ability, of breastfed children was slightly better than that of formula fed children. We hope to publish in the near future more results of the study.

Main investigators:

Günther Boehm, MD, PhD - Numico Research, Friedrichsdorf, Germany
Tamás Decsi, MD, PhD - Dept Paediatrics, Univ Pécs, Hungary
Mijna Hadders-Algra, MD, PhD - Developmental Neurology, UMCG
Corina de Jong, MSc - Developmental Neurology   
Hedwig Kikkert, MSc - Developmental Neurology

Recent publications:

  1. Dijck-Brouwer DAJ, Hadders-Algra M, Bouwstra H, Decsi T, Boehm G, Martini IA, Boersma ER, Muskiet FAJ. Lower fetal status of docosahexaenoic acid, arachidonic acid and essential fatty acids is associated with is less favourable neonatal neurological condition. Prostaglandins Leukot Essent Fatty Acids 2005; 72: 21-8.
  2. Bouwstra H, Dijck-Brouwer DAJ, Boehm G, Boersma ER, Muskiet FAJ, Hadders-Algra M. Long-chain polyunsaturated fatty acids and neurological developmental outcome at 18 months in healthy term infants. Acta Paediatr 2005; 94: 26-32.
  3. Dijck-Brouwer DAJ, Hadders-Algra M, Bouwstra H, Decsi T, Boehm G, Martini IA, Boersma ER, Muskiet FAJ. Impaired maternal glucose homeostasis during pregnancy is associated with low status of long chain polyunsaturated fatty acids (LCP) and essentially fatty acids (EFA) in the fetus. Prostaglandins Leukot Essent Fatty Acids 2005; 73: 85-7.
  4. Hadders-Algra M. The role of long-chain polyunsaturated fatty acids (LCPUFA) in growth and development. Adv Exp Med Biol. 2005; 569: 80-94.
  5. Hadders-Algra M. Effect of prenatal and early postnatal nutritional supplementation with long-chain polyunsaturated fatty acids (LCPUFA) on neurodevelopmental outcome in term infants. Current Nutrition & Food Science 2005; 1: 259-64.
  6. Bouwstra H, Dijck-Brouwer DAJ, Decsi T, Boehm G, Boersma ER, Muskiet FAJ, Hadders-Algra M. Relationship between umbilical cord essential fatty acid content and the quality of general movements of healthy term infants at 3 months. Pediatr Res 2006; 59: 717-22.
  7. Bouwstra H, Dijck-Brouwer DAJ, Decsi T, Boehm G, Boersma ER, Muskiet FAJ, Hadders-Algra M. Neurological condition at 18 months: positive association with venous umbilical DHA-status and negative association with umbilical trans-fatty acids. Pediatr Res, 2006; 60: 1-7
  8. Muskiet FAJ, Van Goor SA, Kuipers RS, Velzing-Aarts FV, Smit EN, Bouwstra H, Dijck-Brouwer DAJ, Boersma ER, Hadders-Algra M. Long-chain polyunsaturated fatty acids in maternal and infant nutrition. Prostaglandins Leukot Essent Fatty Acids 2006, 75: 135-44.
  9. Hadders-Algra M, Bouwstra H, Van Goor SA, Dijck-Brouwer DAJ, Muskiet FAJ.  Prenatal fatty and early postnatal fatty acid status and neurodevelopmental outcome. J. Perinat Med 2007, 35: S28-34.
  10. Hadders-Algra M. Prenatal long-chain polyunsaturated fatty acid status: the importance of a balanced intake of docosahexaenoic acid and arachidonic acid. J Perinat Med 2008; 36: 101-9.
  11. Hadders-Algra M Prenatal docosahexaenoic acid (DHA) and arachidonic acid (AA) supplementation better for neurodevelopment than supplementation with DHA only? J Perinat Med 2008; 36: 268-9,
  12. Fewtrell M, Kennedy K, Singhal A, Martin RM, Ness A, Hadders-Algra M, Koletzko B, Lucas A. How much loss to follow-up is acceptable in long-term rendomised trials and prospective studies. Arch Dis Child 2008; 93: 458-61.
  13. Oken E, Řsterdal ML, Gillman MW, Kundsen VK, Halldorsson TI, Strřm M, Bellinger DC, Hadders-Algra M, Michaelsen KF, Olsen SF. Associations of maternal fish intake during pregnancy and breastfeeding duration with attained developmental milestones in early childhood: a study from the Danish National Birth Cohort. Am J Clin Nutr 2008; 88:789-96. 
  14. Rosenfeld E, Beyerlein A, Hadders-Algra M, Kennedy K, Singhal A, Koletzko B, Von Kries R. IPD meta-analysis shows no effect of LC-PUFA supplementation on infant growth at 18 months. Acta Paediatr 2009; 98: 91-7.
  15. Van Goor SA, Dijck-Brouwer DAJ, Hadders-Algra M, Doornbos B, Erwich JJHM, Schaafsma A, Muskiet FAJ. Human milk arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation during pregnancy and lactation. Prostaglandins Leukot Essent Fatty Acids 2008, accepted for publication.
  16. Van Goor SA, Dijck-Brouwer DAJ, Doornbos J, Erwich JJHM, Schaafsma A,  Muskiet FAJ, Hadders-Algra M. Supplementation of DHA but not DHA with arachidonic acid during pregnancy and lactation influences general movement quality in twelve week old term infants. Brit J Nutr 2010; 103: 235-42.
  17. Beyerlein A, Hadders-Algra M, Kennedy K, Fewtrell M, Singhal A, Rosenfeld E, Lucas A, Bouwstra H, Koletzko B, Von Kries R. Infant formula supplementation with long-chain polyunsaturated fatty acids has no effect on Bayley developmental scores at 18 months of age – IPD meta-analysis of four large clinical trials. J Pediatr Gastroenterol Nutr,2010;50:79-84.
  18. Hadders-Algra M. Effect of long-chain polyunsaturated fatty acid supplementation on neurodevelopmental outcome in term infants. Nutrients 2010; 2: 790-804.
  19. De Jong C, Kikkert HK, Fidler V, Hadders-Algra M. The Groningen LCPUFA-study: effect of postnatal long-chain polyunsaturated fatty acids in healthy term infants on neurological condition at 9 years. Br J Nutr 2010; 104: 566-72.
  20. Beyerlein A, Ness AR, Streuling I, Hadders-Algra M, Von Kries R. Early rapid growth.  No associations with later cognitive functions in children born not small-for-gestational age. Am J Clin Nutr 2010; 92:585-93.
  21. Hadders-Algra M. Prenatal and early postnatal supplementation with long-chain polyunsaturated fatty acids – neurodevelopmental considerations. Am J Clin Nutr, accepted for publication.
  22. Escolano-Margarit MV, Ramos R, Beyer J, Csábi Gy, Parrilla-Roure M, Cruz F, Pérez-García M, Hadders-Algra M, Gil A, Decsi T, Koletzko B, Campoy C. Fish oil supplementation to pregnant women and neurological outcome of their children at 4 and 5˝ years of age. J Nutr, accepted for publication.

Financial support:

Numico BV, Junior Scientific Master Class, and European Union