Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Maternal and pediatric nutrition

Polyunsaturated fatty acid status at birth, childhood growth, and cardiometabolic risk: a pooled analysis of the MEFAB and RHEA cohorts

European Journal of Clinical Nutrition volume 73, pages 566–576 (2019)Cite this article

Subjects

Abstract

Background/objectives

Polyunsaturated fatty acid (PUFA) status during pregnancy has been suggested to influence offspring obesity and cardiometabolic health. We assessed whether prenatal PUFA exposure is associated with rapid infant growth, childhood BMI, and cardiometabolic profile.

Subjects/methods

In the Dutch MEFAB (n = 266) and Greek RHEA (n = 263) cohorts, we measured n-3 and n-6 PUFA concentrations in cord blood phospholipids, which reflect fetal exposure in late pregnancy. We defined rapid infant growth from birth to 6 months of age as an increase in weight z-score >0.67. We analyzed body mass index (BMI) as continuous and in categories of overweight/obesity at 4 and 6 years. We computed a cardiometabolic risk score at 6–7 years as the sum of waist circumference, non-high-density lipoprotein cholesterol and blood pressure z-scores. Associations of PUFAs with child health outcomes were assessed using generalized linear models for binary outcomes and linear regression models for continuous ones after adjusting for important covariates, and for the pooled estimates, a cohort indicator.

Results

In pooled analyses, we found no association of PUFA levels with rapid infant growth, childhood BMI (β per SD increase in the total n-3:n-6 PUFA ratio = −0.04 SD; 99% CI: −0.15, 0.06; P = 0.65 at 4 years, and −0.05 SD; 99% CI: −0.18, 0.08; P = 0.78 at 6 years), and overweight/obesity. We also found no associations for clustered cardiometabolic risk and its individual components. The results were similar across cohorts.

Conclusions

Our findings suggest that PUFA concentrations at birth are not associated with later obesity development and cardiometabolic risk in childhood.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. NCD Risk Factor Collaboration. Worldwide trends in body-mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet. 2017. https://doi.org/10.1016/S0140-6736(17)32129-3.

    Article  Google Scholar 

  2. Raitakari OT, Juonala M, Kahonen M, Taittonen L, Laitinen T, Maki-Torkko N, et al. Cardiovascular risk factors in childhood and carotid artery intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA. 2003;290:2277–83.

    Article  CAS  Google Scholar 

  3. Symonds ME, Sebert SP, Hyatt MA, Budge H. Nutritional programming of the metabolic syndrome. Nat Rev Endocrinol. 2009;5:604–10.

    Article  CAS  Google Scholar 

  4. Ailhaud G, Guesnet P, Cunnane SC. An emerging risk factor for obesity: does disequilibrium of polyunsaturated fatty acid metabolism contribute to excessive adipose tissue development? Br J Nutr. 2008;100:461–70.

    Article  CAS  Google Scholar 

  5. Kalupahana NS, Claycombe KJ, Moustaid-Moussa N. (n-3) Fatty acids alleviate adipose tissue inflammation and insulin resistance: mechanistic insights. Adv Nutr. 2011;2:304–16.

    Article  CAS  Google Scholar 

  6. Stratakis N, Gielen M, Chatzi L, Zeegers MP. Effect of maternal n-3 long-chain polyunsaturated fatty acid supplementation during pregnancy and/or lactation on adiposity in childhood: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2014;68:1277–87.

    Article  CAS  Google Scholar 

  7. Donahue SM, Rifas-Shiman SL, Gold DR, Jouni ZE, Gillman MW, Oken E. Prenatal fatty acid status and child adiposity at age 3 y: results from a US pregnancy cohort. Am J Clin Nutr. 2011;93:780–8.

    Article  CAS  Google Scholar 

  8. Standl M, Thiering E, Demmelmair H, Koletzko B, Heinrich J. Age-dependent effects of cord blood long-chain PUFA composition on BMI during the first 10 years of life. Br J Nutr. 2014;111:2024–31.

    Article  CAS  Google Scholar 

  9. Vidakovic AJ, Gishti O, Voortman T, Felix JF, Williams MA, Hofman A, et al. Maternal plasma PUFA concentrations during pregnancy and childhood adiposity: the Generation R Study. Am J Clin Nutr. 2016;103:1017–25.

    Article  CAS  Google Scholar 

  10. Rytter D, Bech BH, Halldorsson T, Christensen JH, Schmidt EB, Danielsen I, et al. No association between the intake of marine n-3 PUFA during the second trimester of pregnancy and factors associated with cardiometabolic risk in the 20-year-old offspring. Br J Nutr. 2013;110:2037–46.

    Article  CAS  Google Scholar 

  11. de Vries PS, Gielen M, Rizopoulos D, Rump P, Godschalk R, Hornstra G, et al. Association between polyunsaturated fatty acid concentrations in maternal plasma phospholipids during pregnancy and offspring adiposity at age 7: the MEFAB cohort. Prostaglandins Leukot Essent Fat Acids. 2014;91:81–5.

    Article  Google Scholar 

  12. Moon RJ, Harvey NC, Robinson SM, Ntani G, Davies JH, Inskip HM, et al. Maternal plasma polyunsaturated fatty acid status in late pregnancy is associated with offspring body composition in childhood. J Clin Endocr Metab. 2013;98:299–307.

    Article  CAS  Google Scholar 

  13. Voortman T, van den Hooven EH, Braun KV, van den Broek M, Bramer WM, Chowdhurry R, et al. Effects of polyunsaturated fatty acid intake and status during pregnancy, lactation, and early childhood on cardiometabolic health: a systematic review. Prog Lipid Res. 2015;59:67–87.

    Article  CAS  Google Scholar 

  14. Ahrens W, Moreno LA, Marild S, Molnar D, Siani A, De Henauw S, et al. Metabolic syndrome in young children: definitions and results of the IDEFICS study. Int J Obes. 2014;38(Suppl 2):S4–14.

    Article  Google Scholar 

  15. Berenson GS. Childhood risk factors predict adult risk associated with subclinical cardiovascular disease. The Bogalusa Heart Study. Am J Cardiol. 2002;90:3L–7L.

    Article  Google Scholar 

  16. WHO Multicentre Growth Reference Study Group. WHO Child Growth Standards: Length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: Methods and development. Geneva: World Health Organization; 2006.

    Google Scholar 

  17. de Onis M, Onyango AW, Borghi E, Siyam A, Nishida C, Siekmann J. Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ. 2007;85:660–7.

    Article  Google Scholar 

  18. Monteiro PO, Victora CG. Rapid growth in infancy and childhood and obesity in later life--a systematic review. Obes Rev. 2005;6:143–54.

    Article  CAS  Google Scholar 

  19. Cole TJ, Lobstein T. Extended international (IOTF) body mass index cut-offs for thinness, overweight and obesity. Pediatr Obes. 2012;7:284–94.

    Article  CAS  Google Scholar 

  20. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents; National Heart Lung and Blood Institute. Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011;128(Suppl 5):S213–S56.

    PubMed Central  Google Scholar 

  21. Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med. 2003;157:821–7.

    Article  Google Scholar 

  22. Zou G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159:702–6.

    Article  Google Scholar 

  23. Ben J. NLCHECK: Stata module to check linearity assumption after model estimation. Statistical Software Components S456968. Boston College Department of Economics 2008.

  24. Netherlands Institute for Public Health and the Environment. (RIVM). Indeling opleidingsniveau. 2008.

  25. Vafeiadi M, Roumeliotaki T, Myridakis A, Chalkiadaki G, Fthenou E, Dermitzaki E, et al. Association of early life exposure to bisphenol A with obesity and cardiometabolic traits in childhood. Environ Res. 2016;146:379–87.

    Article  CAS  Google Scholar 

  26. Vidakovic AJ, Jaddoe VW, Gishti O, Felix JF, Williams MA, Hofman A, et al. Body mass index, gestational weight gain and fatty acid concentrations during pregnancy: the Generation R Study. Eur J Epidemiol. 2015;30:1175–85.

    Article  CAS  Google Scholar 

  27. Institute of Medicine (US) and National Research Council (US). Committee to Reexamine IOM Pregnancy Weight Guidelines. Weight Gain During Pregnancy: Reexamining the Guidelines. Washington: National Academies Press; 2009.

  28. Karachaliou M, Georgiou V, Roumeliotaki T, Chalkiadaki G, Daraki V, Koinaki S, et al. Association of trimester-specific gestational weight gain with fetal growth, offspring obesity, and cardiometabolic traits in early childhood. Am J Obstet Gynecol. 2015;212:502 e1–14.

    Article  Google Scholar 

  29. Koletzko B. Fatty acids and early human growth. Am J Clin Nutr. 2001;73:671–2.

    Article  CAS  Google Scholar 

  30. Grootendorst-van Mil NH, Tiemeier H, Steenweg-de Graaff J, Koletzko B, Demmelmair H, Jaddoe VWV, et al. Maternal plasma n-3 and n-6 polyunsaturated fatty acids during pregnancy and features of fetal health: Fetal growth velocity, birth weight and duration of pregnancy. Clin Nutr. 2017 Jun 10. pii: S0261-5614(17)30221-2. https://doi.org/10.1016/j.clnu.2017.06.010. [Epub ahead of print].

    Article  CAS  Google Scholar 

  31. McMillen IC, Robinson JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev. 2005;85:571–633.

    Article  CAS  Google Scholar 

  32. Chatzi L, Rifas-Shiman SL, Georgiou V, Joung KE, Koinaki S, Chalkiadaki G, et al. Adherence to the Mediterranean diet during pregnancy and offspring adiposity and cardiometabolic traits in childhood. 2017; https://doi.org/10.1111/ijpo.12191.

    Article  Google Scholar 

  33. Wijndaele K, Beunen G, Duvigneaud N, Matton L, Duquet W, Thomis M, et al. A continuous metabolic syndrome risk score: utility for epidemiological analyses. Diabetes Care. 2006;29:2329.

    Article  Google Scholar 

  34. Bland JM, Altman DG. Multiple significance tests: the Bonferroni method. BMJ. 1995;310:170.

    Article  CAS  Google Scholar 

  35. Faul F, Erdfelder E, Buchner A, Lang AG. Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods. 2009;41:1149–60.

    Article  Google Scholar 

  36. Stark KD, Van Elswyk ME, Higgins MR, Weatherford CA, Salem N Jr.. Global survey of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid in the blood stream of healthy adults. Prog Lipid Res. 2016;63:132–52.

    Article  CAS  Google Scholar 

  37. Hodson L, Skeaff CM, Fielding BA. Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res. 2008;47:348–80.

    Article  CAS  Google Scholar 

  38. Hornstra G. Essential fatty acids in mothers and their neonates. Am J Clin Nutr. 2000;71:1262S–9S.

    Article  CAS  Google Scholar 

  39. Haggarty P. Fatty acid supply to the human fetus. Annu Rev Nutr. 2010;30:237–55.

    Article  CAS  Google Scholar 

  40. Gillman MW. The first months of life: a critical period for development of obesity. Am J Clin Nutr. 2008;87:1587–9.

    Article  CAS  Google Scholar 

  41. Jelena Vidakovic A, Santos S, Williams MA, Duijts L, Hofman A, Demmelmair H, et al. Maternal plasma n-3 and n-6 polyunsaturated fatty acid concentrations during pregnancy and subcutaneous fat mass in infancy. Obesity. 2016;24:1759–66.

    Article  CAS  Google Scholar 

  42. Much D, Brunner S, Vollhardt C, Schmid D, Sedlmeier EM, Bruderl M, 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;67:282–8.

    Article  CAS  Google Scholar 

  43. Muhlhausler BS, Yelland LN, McDermott R, Tapsell L, McPhee A, Gibson RA, et al. DHA supplementation during pregnancy does not reduce BMI or body fat mass in children: follow-up of the DHA to Optimize Mother Infant Outcome randomized controlled trial. Am J Clin Nutr. 2016;103:1489–96.

    Article  CAS  Google Scholar 

  44. Wood K, Mantzioris E, Lingwood B, Couper J, Makrides M, Gibson RA, et al. The effect of maternal DHA supplementation on body fat mass in children at 7 years: follow-up of the DOMInO randomized controlled trial. Prostaglandins Leukot Essent Fatty Acids. 2017. pii: S0952-3278(17)30147-3. https://doi.org/10.1016/j.plefa.2017.09.013. [Epub ahead of print].

    Article  CAS  Google Scholar 

  45. Brei C, Stecher L, Much D, Karla MT, Amann-Gassner U, Shen J, 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;103:1472–81.

    Article  CAS  Google Scholar 

  46. Gutierrez-Gomez Y, Stein AD, Ramakrishnan U, Barraza-Villarreal A, Moreno-Macias H, Aguilar-Salinas C, et al. Prenatal docosahexaenoic acid supplementation does not affect nonfasting serum lipid and glucose concentrations of offspring at 4 y of age in a follow-up of a randomized controlled clinical trial in Mexico. J Nutr. 2017;147:242–7.

    Article  CAS  Google Scholar 

  47. Rytter D, Schmidt EB, Bech BH, Christensen JH, Henriksen TB, Olsen SF. Fish oil supplementation during late pregnancy does not influence plasma lipids or lipoprotein levels in young adult offspring. Lipids. 2011;46:1091–9.

    Article  CAS  Google Scholar 

  48. Rytter D, Christensen JH, Bech BH, Schmidt EB, Henriksen TB, Olsen SF. The effect of maternal fish oil supplementation during the last trimester of pregnancy on blood pressure, heart rate and heart rate variability in the 19-year-old offspring. Br J Nutr. 2012;108:1475–83.

    Article  CAS  Google Scholar 

  49. Vidakovic AJ, Jaddoe VW, Voortman T, Demmelmair H, Koletzko B, Gaillard R. Maternal plasma polyunsaturated fatty acid levels during pregnancy and childhood lipid and insulin levels. Nutr Metab Cardiovasc Dis. 2017;27:78–85.

    Article  CAS  Google Scholar 

  50. Vidakovic AJ, Gishti O, Steenweg-de Graaff J, Williams MA, Duijts L, Felix JF, et al. Higher maternal plasma n-3 PUFA and lower n-6 PUFA concentrations in pregnancy are associated with lower childhood systolic blood pressure. J Nutr. 2015;145:2362–8.

    Article  CAS  Google Scholar 

  51. Boeke CE, Oken E, Kleinman KP, Rifas-Shiman SL, Taveras EM, Gillman MW. Correlations among adiposity measures in school-aged children. BMC Pediatr. 2013;13:99.

    Article  Google Scholar 

Download references

Acknowledgements

We would like to thank Professor Emeritus Gerard Hornstra, who made the MEFAB study possible. We are also extremely grateful to the MEFAB and RHEA study participants for their time and commitment.

Funding

The MEFAB cohort was financially supported by the University Hospital of Maastricht (Profilerings Fonds), and the Dutch Organization for Scientific Research (NWO, Grant number 904 62 186). The RHEA Mother Child Cohort in Crete project was financially supported by European projects [EU FP6-003-Food-3-NewGeneris-contract no. 16320, EU FP6 STREP Hiwate-contract no. 36224, EU FP7 ENV.2007.1.2.2.2. Project No. 211250 Escape, EU FP7-2008-ENV-1.2.1.4 Envirogenomarkers contract no. 226756, EU FP7-HEALTH-2009-single stage CHICOS contract no. 241604, EU FP7 ENV.2008.1.2.1.6. proposal no. 226285 ENRIECO, EU-FP7, proposal no. 264357 MeDALL, EU- FP7- HEALTH-2012 proposal no. 308333 HELIX], and the Greek Ministry of Health (Program of Prevention of obesity and neurodevelopmental disorders in preschool children, in Heraklion district, Crete, Greece: 2011-2014; “Rhea Plus”: Prevention Program of Environmental Risk Factors for Reproductive Health, and Child Health: 2012-2015).

Author contributions

The authors’ responsibilities were as follows: NS, MG, LC, and MPZ designed the research; MA and EGS carried out the fatty acid analysis for the RHEA cohort; all authors contributed to the acquisition of data; NS and KM analyzed the data and performed statistical analysis; NS, MG, and LC wrote the paper; MG, LC, RHMdG, and MPZ contributed to study supervision. All authors read and approved the final manuscript.

Author information

Author notes

    Authors and Affiliations

    1. Section of Complex Genetics and Epidemiology, Departments of Genetics and Cell Biology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands

      Nikos Stratakis, Marij Gielen, Renate H. M. de Groot, Maurice P. Zeegers & Leda Chatzi

    2. Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece

      Nikos Stratakis, Katerina Margetaki, Georgia Chalkiadaki, Marina Vafeiadi, Vasiliki Leventakou, Marianna Karachaliou & Leda Chatzi

    3. Welten Institute-Research Centre for Learning, Teaching and Technology, Open University of the Netherlands, Heerlen, The Netherlands

      Renate H. M. de Groot

    4. Environmental Chemical Processes Laboratory (ECPL), Department of Chemistry, University of Crete, Heraklion, Greece

      Maria Apostolaki & Euripides G. Stephanou

    5. Department of Pharmacology and Toxicology, School for Nutrition and Translational Research in Metabolism (NUTRIM), Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, The Netherlands

      Roger W. Godschalk

    6. ISGlobal, Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain

      Manolis Kogevinas

    7. IMIM Hospital del Mar Medicine Research Institute, Barcelona, Spain

      Manolis Kogevinas

    8. Spanish Consortium for Research in epidemiology and Public Health (CIBERESP), Madrid, Spain

      Manolis Kogevinas

    9. The Cyprus Institute, Nicosia, Cyprus

      Euripides G. Stephanou

    10. School CAPHRI: Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands

      Maurice P. Zeegers

    11. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, USA

      Leda Chatzi

    Authors
    1. Nikos Stratakis
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Marij Gielen
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Katerina Margetaki
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Renate H. M. de Groot
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Maria Apostolaki
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Georgia Chalkiadaki
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Marina Vafeiadi
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Vasiliki Leventakou
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Marianna Karachaliou
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Roger W. Godschalk
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Manolis Kogevinas
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Euripides G. Stephanou
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Maurice P. Zeegers
      View author publications

      You can also search for this author in PubMed Google Scholar

    14. Leda Chatzi
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Nikos Stratakis.

    Ethics declarations

    Conflict of interest

    The authors declare that they have no conflict of interest.

    Additional information

    These authors contributed equally: Maurice P. Zeegers, Leda Chatzi.

    Electronic supplementary material

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Stratakis, N., Gielen, M., Margetaki, K. et al. Polyunsaturated fatty acid status at birth, childhood growth, and cardiometabolic risk: a pooled analysis of the MEFAB and RHEA cohorts. Eur J Clin Nutr 73, 566–576 (2019). https://doi.org/10.1038/s41430-018-0175-1

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1038/s41430-018-0175-1

    Search

    Advanced search

    Quick links