Red blood cell and plasma phospholipid arachidonic and docosahexaenoic acid levels at birth and cognitive development at 4 years of age

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Abstract

Objective: The long-chain polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA) and arachidonic acid (AA) have biophysical properties that may mediate behavioral outcome, especially cognitive development. This study examined the relationship between the LCPUFA-status at birth and cognitive development at 4 years of age. Methods: Cognitive development of 128 full-term neonates, whose umbilical venous plasma and/or red blood cell phospholipid DHA and AA levels were known, was assessed at 4 years of age. Pearson correlation coefficients were calculated between cognitive development and DHA, AA, maternal intelligence, birth weight, duration of breast-feeding and paternal educational attainment. Multiple linear regressions were employed with cognitive development as the dependent variable and whereby the above-mentioned covariables were entered in step one while each of the four LCPUFAs was entered in step two. Results: In bivariate analysis, maternal intelligence, birth weight, maternal smoking habits during pregnancy, paternal education and duration of breast-feeding showed significant correlations with cognitive development (p<0.01). The association of cognitive development with DHA and AA measured zero in bivariate analysis (plasma levels: r=0.03 and r=−0.03, respectively; erythrocyte levels: r=0.01 and r=0.05) and in multiple regression analysis (plasma DHA r=0.01, p=0.88; plasma AA r=0.02, p=0.80; erythrocyte DHA r=−0.01, p=0.95) except for erythrocyte AA (r=0.15, p=0.09). Conclusion: No evidence was found for an association of the DHA or AA-status at birth with cognitive development at 4 years of age.

Introduction

The nutritionally essential polyunsaturated fatty acids (LCPUFAs) docosahexaenoic acid (DHA; 22:6n-3) and arachidonic acid (AA; 20:4n-6) may be of importance to human cognitive development. DHA and AA represent over 30% of all fatty acids in the gray matter of the human brain [1]. Their highest concentrations are found in the synapses of the neurons [2], where they have an important role in signal transduction [3]. AA may also influence neurotransmission through its effect on the eicosanoid metabolism, as it is a precursor of, e.g. prostaglandins [4].

Whether these biological properties mediate alterations at the behavioral level remains a contentious issue. Indirect evidence comes from several sources. Rats display different learning rates in response to the manipulations of the LCPUFAs in their diet (for a review see Wainwright [5]). Human milk-fed infants show a long-lasting better cognitive development (for a meta-analysis on low birth-weight and normal birth-weight samples, see Anderson et al. [6]) putatively due to the fact that mother's milk unlike standard formulas contains DHA and AA. In several studies, neonates fed with LCPUFA-enriched formulas versus standard formula were found to have better results on cognitive developmental scales—both in preterm [7], [8] and in term samples [9]—and on problem solving tasks by term infants [10]. Other studies with term neonates failed to show this association [11], [12], [13] or showed an association that disappeared with age [14], [15]. Scott et al. [16] reported a negative association with language development at 14 months of age. O'Connor et al. found no association with the Bayley Mental Development Index in preterm infants. The positive association they found with the Fagan Test of novelty preference at 6 months disappeared at 9 months [17].

These studies deal with differences in LCPUFA levels acquired through postnatal nutrition. Yet, newborns show different LCPUFA levels at birth as well [18]. These interindividual differences occur in the midst of the brain growth support in which DHA accretion in the brain is very high [19]. So, they as well may be associated with differences in cognitive development. Therefore, the aim of the present study is to examine the association between the AA and DHA status at birth and later cognitive development. A direct study on the relationship of cognitive functioning with the AA and DHA status of the brain is not possible. This study used the LCPUFA status in the umbilical venous red blood cell and plasma phospholipids as a proxy. It took into account the associations of cognitive development with birth weight, breast-feeding, maternal IQ, maternal and paternal educational attainment and maternal smoking during pregnancy.

Note that the AA and DHA measures represent the levels at birth.

Section snippets

Subjects

This study is one part of the follow-up of a research line on essential fatty acids, pregnancy and pregnancy outcome. During the period 1990–1995, blood samples were collected in 998 neonates of healthy Caucasian mothers. The neonates born between January 1990 and December 1993 were examined at 7 years of age (results to be presented elsewhere). The present study reports on the neonates born between January 1994 and September 1995. Their cognitive assessment took place at 4 years of age. Of 246

Results

At the time of the assessment, the mean age of the 128 subjects was 47 months (SD=1.3 months). Plasma and red blood cell LCPUFA levels were known in 124 and 112 neonates, respectively. Eighty-four percent of the neonates were first born. Fifty-five and a half percent were boys. At the time of the assessment, none of the participating children had suffered any neurologically damaging disorder or event. All mothers were present in the household while 4% of the fathers had left the home. Five

Discussion

Until now, almost all studies investigating the potential importance of brain LCPUFA for cognitive development were based on LCPUFA differences in postnatal diet or feeding type. Although studies with preterm infants demonstrate a functional benefit of adding LCPUFA to infant formulas [7], [8], results for term infants have been inconclusive [11], [12], [14], [15], [16]. The present study approached this relationship from another angle. It investigated the association between the perinatal DHA

References (49)

  • R. Matorras et al.

    Intake of long chain w3 polyunsaturated fatty acids during pregnancy and the influence of levels in the mother on new-born levels

    Eur. J. Obstet. Gynecol. Reprod. Biol.

    (1999)
  • S.M. Innis

    Plasma and red blood cell fatty acid values as indexes of essential fatty acids in the developing organs of infants fed with milk or formulas

    J. Pediatr.

    (1992)
  • M. Makrides et al.

    Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants

    Am. J. Clin. Nutr.

    (1994)
  • R.A. Gibson

    Long-chain polyunsaturated fatty acids and infant development (commentary)

    Lancet

    (1999)
  • C.R. Jones et al.

    Evidence for the involvement of docosahexaenoic acid in cholinergic stimulated signal transduction at the synapse

    Neurochem. Res.

    (1997)
  • I.P.M. Wauben et al.

    The influence of neonatal nutrition on behavioral development: a critical appraisal

    Nutr. Rev.

    (1999)
  • K.S. Bjerve et al.

    Clinical studies with a-linolenic acid and long-chain n-3 fatty acids

    Nutrition

    (1992)
  • S.E. Carlson et al.

    Long-chain fatty acids and early visual and cognitive development of preterm infants

    Eur. J. Clin. Nutr.

    (1994)
  • C. Agostoni et al.

    Neurodevelopmental quotient of healthy term infants at 4 months and feeding practice: the role of long-chain polyunsaturated fatty acids

    Pediatr. Res.

    (1995)
  • M. Makrides et al.

    A critical appraisal of the role of dietary long-chain polyunsaturated fatty acids on neural indices in term infants: a randomized, controlled trial

    Pediatrics

    (2000)
  • N. Auestad et al.

    Growth and development in term infants fed long-chain polyunsaturated fatty acids: a double-masked, randomized, parallel, prospective, multivariate study

    Pediatrics

    (2001)
  • C. Agostoni et al.

    Developmental quotient at 24 months and fatty acid composition of diet in early infancy: a follow up study

    Arch. Dis. Child.

    (1997)
  • R.A. Gibson et al.

    Effect of increasing breast milk docosahexaenoic acid on plasma and erythrocyte phospholipid fatty acids and neural indices of exclusively breast fed infants

    Eur. J. Clin. Nutr.

    (1997)
  • D.T. Scott et al.

    Formula supplementation with long-chain polyunsaturated fatty acids: are there developmental benefits?

    Pediatrics

    (1998)
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      The maternal plasma levels were used as a proxy for the foetal exposure, as a number of studies have shown that maternal LCPUFA plasma levels correlate highly with the LCPUFA levels of foetuses [6–8]. In earlier studies the association between fish intake (primary source of DHA and EPA) [9–15], LCPUFAs intake calculated based on answers to questions regarding fish consumption [10,12,15] and/or LCPUFA concentrations in blood [12,14–19] and cognition has been studied, but the results of these studies do not show consistent patterns. Similarly, results from randomized controlled trials are mixed.

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    Guarantor: A. Ghys; contributors: Esther Bakker contributed to the study design, assisted with the data analyses and the interpretation of the results and reviewed the paper. Gerard Hornstra and Marcel van den Hout supervised the project, contributed to the study design, assisted with the analyses of data and the interpretation of the results and reviewed the paper. Alex Ghys wrote the protocol, carried out the data analyses and wrote the paper.

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