Original Article | Published:

Lipids and cardiovascular disease

Impact of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring neurodevelopment: 5-year follow-up of a randomized controlled trial

European Journal of Clinical Nutrition volume 71, pages 11141120 (2017) | Download Citation

Abstract

Background/Objectives:

Evidence regarding the effect of n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy on offspring’s neurodevelopment is not conclusive.

Subjects/Methods:

In this analysis, the effect of a reduced n-6:n-3 LCPUFA ratio in the diet of pregnant/lactating women (1.2 g n-3 LCPUFA together with an arachidonic acid (AA)-balanced diet between 15th wk of gestation-4 months postpartum vs control diet) on child neurodevelopment at 4 and 5 years of age was assessed. A child development inventory (CDI) questionnaire and a hand movement test measuring mirror movements (MMs) were applied and the association with cord blood LCPUFA concentrations examined.

Results:

CDI questionnaire data, which categorizes children as ‘normal’, ‘borderline’ or ‘delayed’ in different areas of development, showed no significant evidence between study groups at 4 (n=119) and 5 years (n=130) except for the area ‘letters’ at 5 years of age (P=0.043). Similarly, the results did not strongly support the hypothesis that the intervention has a beneficial effect on MMs (for example, at 5 years: dominant hand, fast: adjusted mean difference, −0.08 (−0.43, 0.26); P=0.631). Children exposed to higher cord blood concentrations of docosahexaenoic acid, eicosapentaenoic acid and AA, as well as a lower ratio of n-6:n-3 fatty acids appeared to show beneficial effects on MMs, but these results were largely not statistically significant.

Conclusions:

Our results do not show clear benefits or harms of a change in the n-6:n-3 LCPUFA ratio during pregnancy on offspring’s neurodevelopment at preschool age. Findings on cord blood LCPUFAs point to a potential influence on offspring development.

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References

  1. 1.

    . Pregnancy: a window of opportunity for improving current and future health. Int J Gynaecol Obstet 2011; 115 (Suppl 1), S50–S51.

  2. 2.

    , , , . The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res 2001; 40: 1–94.

  3. 3.

    . Dietary (n-3) fatty acids and brain development. J Nutr 2007; 137: 855–859.

  4. 4.

    , , . DHA supplementation: current implications in pregnancy and childhood. Pharmacol Res 2013; 70: 13–19.

  5. 5.

    , . Maternal fatty acid status during pregnancy and lactation and relation to newborn and infant status. Matern Child Nutr 2011; 7 (Suppl 2), 41–58.

  6. 6.

    , , , , , et al. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J Perinat Med 2008; 36: 5–14.

  7. 7.

    , , , , , et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet 2007; 369: 578–585.

  8. 8.

    , , , , , et al. Maternal fish intake during pregnancy, blood mercury levels, and child cognition at age 3 years in a US cohort. Am J Epidemiol 2008; 167: 1171–1181.

  9. 9.

    , , , , , . Maternal fish and other seafood intakes during pregnancy and child neurodevelopment at age 4 years. Public Health Nutr 2009; 12: 1702–1710.

  10. 10.

    , , , , . Maternal fatty acids in pregnancy, FADS polymorphisms, and child intelligence quotient at 8 y of age. Am J Clin Nutr 2013; 98: 1575–1582.

  11. 11.

    , , , , . Higher maternal plasma docosahexaenoic acid during pregnancy is associated with more mature neonatal sleep-state patterning. Am J Clin Nutr 2002; 76: 608–613.

  12. 12.

    , , , . Relationship between DHA status at birth and child problem behaviour at 7 years of age. Prostaglandins Leukot Essent Fatty Acids 2007; 76: 29–34.

  13. 13.

    , , , . Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age. Eur J Clin Nutr 2009; 63: 499–504.

  14. 14.

    , , , , , . Beneficial effects of a polyunsaturated fatty acid on infant development: evidence from the inuit of arctic Quebec. J Pediatr 2008; 152: 356–364.

  15. 15.

    , , , , . Maternal fish oil supplementation in pregnancy: a 12 year follow-up of a randomised controlled trial. Nutrients 2015; 7: 2061–2067.

  16. 16.

    , , , , . Omega 3 fatty acids on child growth, visual acuity and neurodevelopment. Br J Nutr 2012; 107 (Suppl 2), S85–106.

  17. 17.

    , , . Effects of n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on neurodevelopment and visual function in children: a systematic review of randomized controlled trials. J Am Coll Nutr 2010; 29: 443–454.

  18. 18.

    . Prenatal and early postnatal supplementation with long-chain polyunsaturated fatty acids: neurodevelopmental considerations. Am J Clin Nutr 2011; 94 (6 Suppl), 1874s–1879s.

  19. 19.

    , , . The effect of maternal omega-3 (n-3) LCPUFA supplementation during pregnancy on early childhood cognitive and visual development: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr 2013; 97: 531–544.

  20. 20.

    , , , , , . The impact of nutritional fatty acids during pregnancy and lactation on early human adipose tissue development. Rationale and design of the INFAT study. Ann Nutr Metab 2009; 54: 97–103.

  21. 21.

    , , , , , et al. Effect of reducing the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on infant adipose tissue growth within the first year of life: an open-label randomized controlled trial. Am J Clin Nutr 2012; 95: 383–394.

  22. 22.

    , , , , , et al. Effect of dietary intervention to reduce the n-6/n-3 fatty acid ratio on maternal and fetal fatty acid profile and its relation to offspring growth and body composition at 1 year of age. Eur J Clin Nutr 2013; 67: 282–288.

  23. 23.

    , , , , , et al. Breast milk fatty acid profile in relation to infant growth and body composition: results from the INFAT study. Pediatr Res 2013; 74: 230–237.

  24. 24.

    , , , , , et al. Reduction of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring body composition: follow-up results from a randomized controlled trial up to 5 y of age. Am J Clin Nutr 2016; 103: 1472–1481.

  25. 25.

    Child Development Inventory Manual. Behavior Science Systems, Inc: Minneapolis, MN, USA, 1992, 1–39.

  26. 26.

    , , , , , . Elternfragebogen zur Entwicklung im Kleinkindalter (EFkE) - ein Screeninginstrument: I. Normierung. Kinderarztl Prax 2002; 5: 338–344.

  27. 27.

    , , Elternfragebogen zur kindlichen Entwicklung (EFkE)Manual, 1st edn. Verlag Alexander Möckl: Augsburg, Germany, 2003..

  28. 28.

    , , . Evaluation of precision grip using pneumatically controlled loads. J Neurosci Methods 1992; 45: 117–126.

  29. 29.

    , , , . Quantitative evaluation of mirror movements in adults with focal brain lesions. Eur J Neurol 2005; 12: 964–975.

  30. 30.

    , , , , , et al. Mirror movements and the role of handedness: isometric grip forces changes. Motor Control 2007; 11: 16–28.

  31. 31.

    , , , , . The child development inventory: a developmental outcome measure for follow-up of the high-risk infant. J Pediatr 1999; 135: 358–362.

  32. 32.

    . Manualeinlage - Ergänzung zum Kapitel 3.3. Reliabilität und Validität, 2005. In: Brandstetter G, Bode H, Ireton HR. Elternfragebogen zur kindlichen Entwicklung (EFkE), Manual, 1st edn. Verlag Alexander Möckl: Augsburg, Germany, 2003.

  33. 33.

    , , , , . Achieving definitive results in long-chain polyunsaturated fatty acid supplementation trials of term infants: factors for consideration. Nutr Rev 2011; 69: 205–214.

  34. 34.

    , , , . Overflow movements and white matter abnormalities in ADHD. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 441–445.

  35. 35.

    , , , , , et al. White matter development during childhood and adolescence: a cross-sectional diffusion tensor imaging study. Cereb Cortex 2005; 15: 1848–1854.

  36. 36.

    , , , . The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: a review. Nutrients 2013; 5: 2777–2810.

  37. 37.

    , , , , , et al. Mirror movements in healthy humans across the lifespan: effects of development and ageing. Dev Med Child Neurol 2010; 52: 1106–1112.

  38. 38.

    , . Long-chain polyunsaturated fatty acids (LCPUFA) from genesis to senescence: the influence of LCPUFA on neural development, aging, and neurodegeneration. Prog Lipid Res 2014; 53: 1–17.

  39. 39.

    , , , , . Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children's IQ at 4 years of age. Pediatrics 2003; 111: e39–e44.

  40. 40.

    , , , , , . Effect of supplementing pregnant and lactating mothers with n-3 very-long-chain fatty acids on children's IQ and body mass index at 7 years of age. Pediatrics 2008; 122: e472–e479.

  41. 41.

    , , , , , et al. Prenatal DHA status and neurological outcome in children at age 5.5 years are positively associated. J Nutr 2011; 141: 1216–1223.

  42. 42.

    , , , , , et al. Effects of prenatal fish-oil and 5-methyltetrahydrofolate supplementation on cognitive development of children at 6.5 y of age. Am J Clin Nutr 2011; 94 (6 Suppl), 1880S–1888S.

  43. 43.

    , , , , , et al. Four-year follow-up of children born to women in a randomized trial of prenatal DHA supplementation. JAMA 2014; 311: 1802–1804.

  44. 44.

    , , , , , et al. Prenatal supplementation with DHA improves attention at 5 y of age: a randomized controlled trial. JAMA 2017; 317: 1173–1175.

  45. 45.

    , , , , , et al. Prenatal supplementation with DHA improves attention at 5 y of age: a randomized controlled trial. Am J Clin Nutr 2016; 104: 1075–1082.

  46. 46.

    , , , . Cognitive assessment of children at age 2(1/2) years after maternal fish oil supplementation in pregnancy: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2008; 93: F45–F50.

  47. 47.

    , , , . Red blood cell and plasma phospholipid arachidonic and docosahexaenoic acid levels at birth and cognitive development at 4 years of age. Early Hum Dev 2002; 69: 83–90.

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Acknowledgements

We kindly thank Karina Pusch for her support in data collection and trial management. We also thank all families and their children for participating in the study. The study was supported by grants from the Else Kröner-Fresenius Foundation, Bad Homburg; the European Union-funded Early Nutrition Programming Project (EARNEST) consortium (FOOD-CT-2005-007036); and the German Ministry of Education and Research via the Competence Network Obesity (Kompetenznetz Adipositas, 01GI0842). HH has received grants from Riemser and Weight Watchers for clinical trials and payment for lectures from Novartis, Roche Germany and Sanofi-Aventis.

Disclaimer

The analysis of fatty acids was performed by the Laboratory of Lipid Research, Danone Research—Center for Specialised Nutrition using coded samples. There was no intervention from any sponsor with any of the research aspects of the study, including study design, intervention, data collection, data analysis and interpretation, as well as writing of the manuscript.

Author contributions

HH designed the research; RE and FH were involved in the methodological design and gave scientific advice; CB and SB were responsible for the data collection and trial management; PDW and JH developed the algorithm for the mirror movement analysis, provided scientific advice regarding the analysis and edited previous versions of the manuscript; CB analyzed the data; CB and LS were responsible for statistical analysis; CB wrote the manuscript; and all authors contributed to the critical revision of the manuscript.

Author information

Affiliations

  1. Else Kröner-Fresenius Center for Nutritional Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

    • C Brei
    • , L Stecher
    • , S Brunner
    •  & H Hauner
  2. Department of General Pediatrics, Neonatology and Pediatric Cardiology, Experimental Pediatrics and Metabolism, University Children’s Hospital, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

    • R Ensenauer
  3. Research Center, Dr von Hauner Children’s Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

    • R Ensenauer
  4. Department of Pediatric Neurology and Developmental Medicine, Dr von Hauner Children’s Hospital, Ludwig-Maximilians-Universität München, Munich, Germany

    • F Heinen
  5. Department of Sport and Health Sciences, Institute of Human Movement Science, Technische Universität München, Munich, Germany

    • P D Wagner
    •  & J Hermsdörfer
  6. ZIEL – Institute for Food and Health, Nutritional Medicine Unit, Technische Universität München, Freising, Germany

    • H Hauner

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to H Hauner.

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DOI

https://doi.org/10.1038/ejcn.2017.79

Supplementary Information accompanies this paper on European Journal of Clinical Nutrition website (http://www.nature.com/ejcn)

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