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July 2006

N-3 fatty acids and pregnancy outcomes.

PURPOSE OF REVIEW: To discuss new data from the literature on the relationship between the supply of n-3 polyunsaturated fatty acids during pregnancy and pregnancy outcomes, evaluated as the fatty acid composition of blood and breast milk, fetal and infantile development and maternal health. RECENT FINDINGS: Supplementation of alpha-linolenic acid in high doses or docosahexaenoic acid in low doses did not result in a significant enhancement of the blood docosahexaenoic acid status of the offspring. In contrast, supplementation of docosahexaenoic acid in relatively high doses led to significant increases in infantile docosahexaenoic acid values and to a significant enhancement of breast milk docosahexaenoic acid content. Electroretinogram data obtained during the first week of life and pattern-reversal visual evoked potentials investigated at 50 and 66 weeks postconception were significantly associated with the docosahexaenoic acid status of the infant at birth. Children whose mothers received docosahexaenoic acid supplementation during pregnancy and lactation scored better in mental processing tests carried out at 4 years than children whose mothers received placebo. SUMMARY: Beneficial health outcomes are more likely to result from supplementation with docosahexaenoic acid itself, rather than its precursor alpha-linolenic acid. Trials have shown that a higher maternal docosahexaenoic acid intake during pregnancy may be favourable for the visual and cognitive development of the offspring. The significant positive association between maternal docosahexaenoic acid intake during pregnancy and the children’s mental processing scores at 4 years suggest that optimization of the docosahexaenoic acid status of expectant women may offer long-term developmental benefits to their children.

Curr Opin Clin Nutr Metab Care. 2005 Mar;8(2):161-6

The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder.

BACKGROUND: Developmental coordination disorder (DCD) affects approximately 5% of school-aged children. In addition to the core deficits in motor function, this condition is associated commonly with difficulties in learning, behavior, and psychosocial adjustment that persist into adulthood. Mounting evidence suggests that a relative lack of certain polyunsaturated fatty acids may contribute to related neurodevelopmental and psychiatric disorders such as dyslexia and attention-deficit/hyperactivity disorder. Given the current lack of effective, evidence-based treatment options for DCD, the use of fatty acid supplements merits investigation. METHODS: A randomized, controlled trial of dietary supplementation with omega-3 and omega-6 fatty acids, compared with placebo, was conducted with 117 children with DCD (5-12 years of age). Treatment for 3 months in parallel groups was followed by a 1-way crossover from placebo to active treatment for an additional 3 months. RESULTS: No effect of treatment on motor skills was apparent, but significant improvements for active treatment versus placebo were found in reading, spelling, and behavior over 3 months of treatment in parallel groups. After the crossover, similar changes were seen in the placebo-active group, whereas children continuing with active treatment maintained or improved their progress. CONCLUSIONS: Fatty acid supplementation may offer a safe efficacious treatment option for educational and behavioral problems among children with DCD. Additional work is needed to investigate whether our inability to detect any improvement in motor skills reflects the measures used and to assess the durability of treatment effects on behavior and academic progress.

Pediatrics. 2005 May;115(5):1360-6

Directly quantitated dietary (n-3) fatty acid intakes of pregnant Canadian women are lower than current dietary recommendations.

During pregnancy, (n-3) PUFA are incorporated into fetal brain and retinal lipids. Docosahexaenoic acid [DHA, 22:6(n-3)], in particular, is required physiologically for optimal development and function of the central nervous system. Maternal intake of (n-3) PUFA must be sufficient to maintain maternal tissues stores and meet fetal accruement. Recommendations for pregnant women include an Acceptable Macronutrient Distribution Range (AMDR) of 0.6-1.2% of energy for (n-3) PUFA intake in the current Dietary Reference Intakes, and > or =300 mg/d of DHA suggested by the International Society for the Study of Fatty Acids and Lipids working group. The present study directly quantitated the (n-3) PUFA intake, including DHA, of pregnant, Canadian women (n = 20) in their 2nd and 3rd trimester. Fatty acid intakes were quantitated in triplicate by lipid extraction and GLC of 3-d duplicate food collections calibrated with an internal standard before homogenization. Total fat intakes were also estimated using dietary analysis software from simultaneous 3-d food records to corroborate biochemical analyses. The mean (n-3) PUFA intake was 0.57 +/- 0.06% of energy, with 65% of the women below the AMDR. The mean DHA intake was 82 +/- 33 mg/d, with 90% of the women consuming <300 mg/d. Nutritional education of pregnant women to ensure adequate intakes of (n-3) PUFA for optimal health of mother and child and the inclusion of DHA in prenatal vitamins may be pertinent.

J Nutr. 2005 Feb;135(2):206-11

Essential fatty acid transfer and fetal development.

Docosahexaenoic acid (22:6n-3) and arachidonic acid (20:4n-6) are important structural components of the central nervous system. These fatty acids are transferred across the placenta, and are accumulated in the brain and other organs during fetal development. Depletion of 22:6n-3 from the retina and brain results in reduced visual function and learning deficits: these may involve critical roles of 22:6n-3 in membrane-dependent signaling pathways and neurotransmitter metabolism. Transfer of 22:6n-3 across the placenta involves specific binding and transfer proteins that facilitate higher concentrations of 22:6n-3 and 20:4n-6, but lower linoleic acid (18:2n-6) in fetal compared with maternal plasma, or in the breast-fed or formula-fed infant. However, human and animal studies both demonstrate that maternal diet impacts fetal 22:6n-3 and 20:4n-6 accretion. After birth, parenteral lipid, human milk and infant formula feeding all result in a marked decrease in plasma 22:6n-3 and 20:4n-6 and an increase in 18:2n-6. Estimation of fetal tissue fatty acid accretion suggests that current preterm infant feeds are unlikely to meet in utero rates of 22:6n-3 accretion. Consideration needs to be given to whether fetal plasma 22:6n-3 and 20:4n-6 enrichment and the low 18:2n-6 facilitates accretion of 22:6n-3 and 20:4n-6 in developing tissues.

Placenta. 2005 Apr;26 Suppl A:S70-5

Can prenatal N-3 fatty acid deficiency be completely reversed after birth? Effects on retinal and brain biochemistry and visual function in rhesus monkeys.

Our previous studies of rhesus monkeys showed that combined prenatal and postnatal n-3 fatty acid deficiency resulted in reduced visual acuity, abnormal retinal function, and low retina and brain docosahexaenoic acid content. We now report effects of n-3 fatty acid deficiency during intrauterine development only. Rhesus infants, born to mothers fed an n-3 fatty acid deficient diet throughout pregnancy, were repleted with a diet high in alpha-linolenic acid from birth to 3y. Fatty acid composition was determined for plasma and erythrocytes at several time points, for prefrontal cerebral cortex biopsies at 15, 30, 45, and 60 wk, and for cerebral cortex and retina at 3 y. Visual acuity was determined behaviorally at 4, 8, and 12 postnatal weeks, and the electroretinogram was recorded at 3-4 mo. Total n-3 fatty acids were reduced by 70-90% in plasma, erythrocytes, and tissues at birth but recovered to control values within 4 wk in plasma, 8 wk in erythrocytes, and 15 wk in cerebral cortex. At 3 y, fatty acid composition was normal in brain phospholipids, but in the retina DHA recovery was incomplete (84% of controls). Visual acuity thresholds did not differ from those of control infants from mothers fed a high linolenic acid diet. However, the repleted group had lower amplitudes of cone and rod ERG a-waves. These data suggest that restriction of n-3 fatty acid intake during the prenatal period may have long-term effects on retinal fatty acid composition and function.

Pediatr Res. 2005 Nov;58(5):865-72

A quantitative analysis of prenatal intake of n-3 polyunsaturated fatty acids and cognitive development.

Although a rich source of n-3 polyunsaturated fatty acids (PUFAs) that may confer multiple health benefits, some fish also contain methyl mercury (MeHg), which may harm the developing fetus. US government recommendations for women of childbearing age are to modify consumption of high-MeHg fish to reduce MeHg exposure, while recommendations encourage fish consumption among the general population because of the nutritional benefits. The Harvard Center for Risk Analysis convened an expert panel (see acknowledgements) to quantify the net impact of resulting hypothetical changes in fish consumption across the population. This paper estimates the impact of prenatal n-3 intake on cognitive development. Other papers quantify the negative impact of prenatal exposure to MeHg on cognitive development, and the extent to which fish consumption protects against coronary heart disease mortality and stroke in adults. This paper aggregates eight randomized controlled trials (RCTs) comparing cognitive development in controls and in children who had received n-3 PUFA supplementation (seven studies of formula supplementation and one study of maternal dietary supplementation). Our analysis assigns study weights accounting for statistical precision, relevance of three endpoint domains (general intelligence, verbal ability, and motor skills) to prediction of IQ, and age at evaluation. The study estimates that increasing maternal docosahexaenoic acid (DHA) intake by 100 mg/day increases child IQ by 0.13 points. The paper notes that findings were inconsistent across the RCTs evaluated (although our findings were relatively robust to changes in the weighting scheme used). Also, for seven of the eight studies reviewed, effects are extrapolated from formula supplementation to maternal dietary intake.

Am J Prev Med. 2005 Nov;29(4):366-74

Maternal fish oil supplementation in lactation and growth during the first 2.5 years of life.

Fish oil addition to infant formulas has raised concern on whether increased intake of n-3 long-chain polyunsaturated fatty acid (n-3LCPUFA) affects infant growth. The objective of this study was to determine whether maternal fish oil supplementation during 0-4 mo of lactation influences growth in infancy and early childhood. In a randomized, blinded intervention trial, lactating Danish mothers with a fish intake below the population median were randomized to 4.5 g/d fish oil or olive oil. A reference group of 53 mothers with a fish intake in the highest quartile of the population and their infants were included in the study. Head circumference, weight, length, skinfold thickness, and waist circumference of children were measured at 2, 4, and 9 mo and at 2.5 y. One hundred children completed the intervention trial, and 72 were followed up at 2.5 y together with 29 from the reference group. Growth in weight, length, and head circumference did not differ between the randomized groups up to 9 mo, but at 2.5 y, body composition differed significantly. Children in the fish oil group had larger waist circumference body mass index (BMI; 0.6 kg/m(2); p = 0.022), and head circumference compared with those in the olive oil group. Adjusted for sex, ponderal index at birth and current energy intake, BMI at 2.5 y was associated with docosahexaenoic acid in maternal erythrocytes after the intervention. In conclusion, the n-3LCPUFA intake of lactating mothers may be important for growth of young children. The long-term effect on weight and BMI remains to be investigated.

Pediatr Res. 2005 Aug;58(2):235-42

Maternal fish oil supplementation in lactation: effect on developmental outcome in breast-fed infants.

Docosahexaenoic acid (DHA) accumulates in the brain during the 1st and 2nd years of life. The objective of this study was to see if an increased content of DHA in breast-milk via maternal fish oil (FO)-supplementation affects mental development in term infants. one hundred twenty-two Danish mothers with a habitual fish intake below the population median were randomized to 4.5 g.d(-1) of FO or olive oil (OO) for the first four months of lactation. Fifty-three mothers with habitual fish intake in the highest quartile were included as reference group. The effect of the resulting increase in infant DHA-intake and RBC-DHA level was assessed on problem solving ability at nine months and language at one and two years of age. Infants in the three groups performed equally well on the problem test and no association was observed between problem solving and erythrocyte-DHA at four months. Passive vocabulary at one year was lower in the children of the FO- compared with the OO-group (P < 0.05), but no differences were found at two years of age. Word comprehension at one year was inversely associated with erythrocyte-DHA at four months. The trial indicate a small effect of DHA levels in breast-milk on early language development of breast-fed infants.

Reprod Nutr Dev. 2005 Sep-Oct;45(5):535-47

Breastfeeding, very long polyunsaturated fatty acids (PUFA) and IQ at 6 1/2 years of age.

AIM: Breastfeeding seems to be favorable for cognitive development. Could levels of polyunsaturated fatty acids (PUFA) explain this? METHODS: Pregnant mothers were recruited consecutively at maternity care centres. PUFA were analysed in colostrum and breast milk at 1 and 3 mo. The product-precursor ratios of n-6+n-3 PUFA were examined as measures of activity in respective steps in the fatty acid metabolic chain. Also, the quotient between DHA and AA was analysed. The children were tested with the full WISC-III at 6.5 y. RESULTS: First, the influence of length of breastfeeding was analysed by multiple regression together with relevant cofactors (except for PUFA). In the best models, 46% of the variation in total IQ was explained. Length of breastfeeding contributed significantly to total IQ (beta = 0.228, p = 0.021), verbal IQ (beta = 0.204, p = 0.040) and performance IQ (beta = 0.210, p = 0.056). There were no significant single correlations between PUFA and measures of cognitive development. However, in multiple regression analysis of colostrum, significant beta-coefficients were found for steps 4+5 in the fatty acid metabolic chain (beta = 0.559, p = 0.002). If length of breastfeeding and gestation week were added to steps 4+5, this three-factor model could explain 67% of the variation of total IQ. Introducing length of breastfeeding and gestation week together with the quotient DHA/AA (beta = 0.510, p < 0.001) yielded a three-factor model, which explained 76% of the variation in total IQ. CONCLUSION: Our findings could be interpreted as supporting the importance of high levels of PUFA for cognitive development. However, the sample is small and the results must be interpreted with caution.

Acta Paediatr. 2004 Oct;93(10):1280-7