title: 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 4 large clinical trials.
abstract: OBJECTIVE
  To find out whether supplementation of formula milk by long-chain polyunsaturated fatty acids (LCPUFA) affects neurodevelopment at 18 months of age in term or preterm infants by an individual patient data (IPD) meta-analysis.
  
  
  METHODS
  Data of 870 children from 4 large randomised clinical trials for formula milk with and without LCPUFAs allowed for assessing the effect of LCPUFA with adjustment for potential confounders and extensive subgroup analysis on prematurity, LCPUFA source, and dosage. Any additional clinical trials examining the effect of LCPUFA supplementation on Bayley Scales of Infant Development at 18 months were regarded as relevant. Two relevant studies were identified by MEDLINE, but were not available to us. An IPD meta-analysis was performed with subgroup analyses by preterm delivery, very low birth weight (<1500 g), trials with higher amounts of docosahexaenoic acid (DHA) and arachidonic acid (AA), and specific sources of LCPUFA. The sample size of 870 children was sufficient to detect clinically relevant differences in Bayley Scales even in subgroups.
  
  
  RESULTS
  There were no significant differences in mental or psychomotor developmental indexes between LCPUFA-supplemented and control groups for all children or in subgroups. This was confirmed with adjustment for the possible confounders: sex, gestational age, birth weight, maternal age, and maternal smoking. The adjusted mean differences in mental developmental index and psychomotor developmental index for all of the children were -0.8 (95% confidence interval -2.8 to 1.2) and -1.0 (-2.7 to 0.7), respectively.
  
  
  CONCLUSIONS
  These data based on considerable sample size provide substantial evidence that LCPUFA supplementation of infant formula does not have a clinically meaningful effect on the neurodevelopment as assessed by Bayley scores at 18 months. Inclusion of all relevant data should not have led to differing conclusions except, possibly, for very-low-birth-weight infants.
authors.affiliation: Division of Epidemiology, Institute of Social Paediatrics and Adolescent Medicine, Ludwig-Maximilians University of Munich, Munich, Germany. andreas.beyerlein@med.uni-muenchen.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Beyerlein
authors.forename: Mijna
authors.initials: M
authors.lastname: Hadders-Algra
authors.forename: Katherine
authors.initials: K
authors.lastname: Kennedy
authors.forename: Mary
authors.initials: M
authors.lastname: Fewtrell
authors.forename: Atul
authors.initials: A
authors.lastname: Singhal
authors.forename: Eva
authors.initials: E
authors.lastname: Rosenfeld
authors.forename: Alan
authors.initials: A
authors.lastname: Lucas
authors.forename: Hylco
authors.initials: H
authors.lastname: Bouwstra
authors.forename: Berthold
authors.initials: B
authors.lastname: Koletzko
authors.forename: Rüdiger
authors.initials: R
authors.lastname: von Kries
mesh_terms: D002657:Child Development / Q000187:drug effects*; D003071:Cognition / Q000187:drug effects; D004041:Dietary Fats / Q000008:administration & dosage / Q000494:pharmacology*; D019587:Dietary Supplements; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D041943:Infant Formula; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007234:Infant, Premature / Q000254:growth & development / Q000523:psychology; D019102:Infant, Very Low Birth Weight / Q000254:growth & development / Q000523:psychology; D011597:Psychomotor Performance / Q000187:drug effects
chemical_list: D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated