Professor, of Human Nutrition

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1 ω-3 fatty acids: The Effects during Pregnancy and Breast feeding Antonis Zampelas Professor, of Human Nutrition Director, Laboratory of Food Chemistry and Human Nutrition, Department of Food Science and Human Nutrition, Agricultural University of Athens Visiting Professor, Department of Life Sciences, University of Nicosia 1

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3 γ-linolenic acid (18:3 ω-6) eicosapentaenoic acid (20:5 ω-3) ( fish oils) arachidonic acid (20:4 ω-6) docosahexaenoic acid (22:6 ω-3) (meat) (fish oils) Eicosanoids from ω-6 Eicosanoids from ω-3 ThromboxaneΑ 2 (pro-aggregatory) Prostacycline (anti-aggregatory) LeukotrieneΒ 4 (promotes aggregation ThromboxaneΑ 3 (less active) of leukocytes) LeukotrieneΒ 5 (< 5-10% active compared toβ 4 ) 3

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5 Postprandial plasma TG and LPL responses following acute test meals of different fatty acid composition 2 1,5 Plasma TG (mmol/l) LPL (nmol oleate released/min/ml plasma) ,5 Mixed oil Corn Oil Fish oil Time postprandially (min) Mixed oil Corn oil Fish oil Zampelas A et al Eur J Clin Nutr 1994, 48:

6 Inflammatory markers and fish consumption: the ATTICA Study Fish consumption No < 150 g/w g/w > 300 g/w P N (%) 319 (11%) (56%) (24%) (9%) CRP (mg/l) 2.7± ±1.1 ** 2.0±2.1 ** 1.8±1.1 ** IL 6 (ng/ml) 1.5± ±0.6 * 1.2±1.1 ** 1.0±0.3 ** 0.03 TNF α (mg/dl) 5.3±3 5.1±2 4.7±3 ** 4.2±2 ** < Amyloid A (mg/dl) 6.4±4 5.9±4 5.1±4 * 4.6±3 ** No gender differences were observed. * P < 0.05 and ** P < 0.01 (Bonferroni corrected) for the differences between fish consumption groups vs. no consumption. Probability values derived from the ANOVA test. P values derived from ANOVA test that evaluated the associations between inflammatory markers (dependent) and fish intake (independent factor). ZampelasA et al J Am CollCardiol 2005;46:

7 Calder PC, Ann Nutr Metab 2016;69(suppl 1):8 21 7

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9 The brain The brain weight in the newborn corresponds to approximately 10% of the total body weight Following adipose tissue, brain is the 2 nd richer organ in fat 50-60% of the dry weight is fat The fatty acids AA and DHA are main constituents 9

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11 The human brain growth spurt occurs from approximately the beginning of the third trimester of pregnancy to 18 months after birth. The amount of DHA in the brain increases dramatically during the brain growth spurt. In humans, brain weight increases from about 100 g at 30 weeks of gestation to about 1,100 g at 18 months of age Over this period, the DHA content of the brain increases from 900 μg/g (90 mg in total) to 3,000 μg/g (3,300 mg total). This represents a 35-fold increase in total brain DHA. 11

12 Photoreceptor outer segments have the highest DHA segment of any cell Prolonged dietary deprivation required to reduce DHA content -only then functional impairment occur 12

13 Calder PC, Ann Nutr Metab 2016;69(suppl 1):

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15 METHODS:RCTs assessing the efficacy of LCPUFA supplementation of infant formulas on infant visual acuity. RCTs assessing the effects of LCPUFA supplementation on visual acuity in the first year of life were included in this meta-analysis RESULTS: Nineteen studies involving 1949 infants were included Qawasmi A et al Pediatrics 2013;131:e262 e272 15

16 A,Difference in visual acuity as assessed by Visual Evoked Potential (VEP) at the age of 2 months between infants fed formula supplemented with LCPUFAs and nonsupplemented formula B, Difference in visual acuity as assessed by VEP at the age of 4 months between infants fed formula supplemented with LCPUFAs and nonsupplemented formula C,Difference in visual acuity as assessed by VEP at the age of 12 months between infants fed formula supplemented with LCPUFAs and nonsupplemented formula Qawasmi A et al Pediatrics 2013;131:e262 e272 16

17 Objectives:To assess the effectiveness and safety of supplementation with LCPUFA in breastfeeding mothers in the cognitive and physical development of their infants as well as safety for the mother and infant. Selection Criteria: Randomised controlled trials or cluster-randomised controlled trials evaluating the effects of LCPUFA supplementation on breastfeeding mothers (including the pregnancy period) and their infants. Conclusion: Based on the available evidence, LCPUFA supplementation did not appear to improve children s neurodevelopment, visual acuity or growth. In child attention at five years of age, weak evidence was found (one study) favouring the supplementation. Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No.: CD

18 Maternal plasma and erythrocyte arachidonicacid and total erythrocyte omega-6 fatty acid levels at T2 were higher (p<0.05 for both) in the LBW group. Total erythrocyte omega-3 fatty acid levels were lower (p<0.05) while total erythrocyte omega-6 fatty acid levels were higher(p<0.05) in the LBW group at delivery. PLoS ONE 11(1): e

19 Effect of n-3 Long-chain Polyunsaturated Fatty Acid Intake during Pregnancy on Maternal, Infant, and Child Health Outcomes: A Systematic Review 15 RCTs eligible for inclusion in the meta-analysis, and 14 observational studies were included in the general review. n-3 LCPUFA supplementation during pregnancy resulted in a modest increase in birthweight (mean difference = 42.2 g; [95% CI 14.8, 69.7]) Women receiving n-3 LCPUFA had a 26% lower risk of early preterm delivery (<34 weeks) (RR = 0.74; [95% CI 0.58, 0.94]) and there was a suggestion of decreased risk of preterm delivery (RR = 0.91; [95% CI 0.82, 1.01]) and low birthweight (RR = 0.92; [95% CI 0.83, 1.02]). n-3 LCPUFA in pregnancy did not influence the occurrence of pre-eclampsia, high blood pressure, infant death, or stillbirth. Imhoff-Kunsch B et al Paediatric and Perinatal Epidemiol 2012;26 (Suppl 1):

20 Effect of n-3 LCPUFA supplementation during pregnancy on risk of early pre-term birth. Effect of n-3 LCPUFA supplementation during pregnancy on birthweight. Imhoff-Kunsch B et al Paediatric and Perinatal Epidemiol2012;26 (Suppl 1):

21 Palmer DJ et al BMJ 2012;344:e184 21

22 Palmer DJ et al BMJ 2012;344:e184 22

23 Objectives: To assess the effect of n-3 LCPUFA supplementation in pregnant and/or breastfeeding women on allergy outcomes (food allergy, atopic dermatitis (eczema), allergic rhinitis (hay fever) and asthma/wheeze) in their children. Selection criteria: Randomisedcontrolled trials (RCTs) evaluating the effect of n-3 LCPUFA supplementation of pregnant and/or lactating women (compared with placebo or no treatment) on allergy outcomes of the infants or children. Conclusion: Overall, there is limited evidence to support maternal n-3 LCPUFA supplementation during pregnancy and/or lactation for reducing allergic disease in children. Cochrane Database of Systematic Reviews 2015, Issue 7. Art. No.: CD

24 METHODS: Randomized controlled clinical trials assessing the efficacy of LCPUFA supplementation of infant formulas on cognition. Analysis was restricted to randomized controlled clinical trials that examined the effect of LCPUFA supplementation on infant cognition using Bayley Scales of Infant Development. Primary outcome was the weighted mean difference in Bayley Scales of Infant Development score between infants fed formula supplemented with LCPUFA compared with unsupplemented formula. RESULTS: Twelve trials involving 1802 infants met inclusion criteria. Qawasmi A et al Pediatrics 2012;129:

25 Qawasmi A et al Pediatrics 2012;129:

26 Qawasmi A et al Pediatrics 2012; 129:

27 Despite the positive findings from some observational studies, many randomized controlled intervention trials have failed to demonstrate a conclusive benefit of maternal DHA supplementation on infant neurodevelopment. Few trials have evaluated supplementation during the lactation period. In contrast, many trials have been conducted on LCPUFA supplementation of infant formula. Regardless of the time period of the intervention, there is a large degree of heterogeneity between the studies with respect to the DHA dose, the intervention period and outcomes assessed 27

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30 Fat intake during pregnancy and lactation does not differ from the recommended for the general population During pregnancy and lactation women should aim at an intake of DHA at least mg/d. When breastfeeding is not - infant formulae should contain DHA 0.2 up to 0.5% of total fatty acids Caution to fish that may contain methyl-mercury, such as shark and sword fish 30

31 Common Variables Salmon Anchovies, Herring Mackerel Tuna Sardines Trout mg of n-3fatty Acids EPA and DHA Per 4 Ounces of Cooked Fish = Micrograms of Mercury Per 4 Ounces of Cooked Fish Shark Swordfish Mackerel, King FDA,

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38 Paediatric Perinatal Epidemiol 2012; 26 (Suppl. 1):

39 Imhoff-Kunsch B et al Paediatric Perinatal Epidemiol 2012;226 (Suppl. 1):

40 Imhoff-Kunsch B et al Paediatric Perinatal Epidemiol 2012;226 (Suppl. 1):

41 Imhoff-Kunsch B et al Paediatric Perinatal Epidemiol 2012;226 (Suppl. 1):

42 Imhoff-Kunsch B et al Paediatric Perinatal Epidemiol 2012;226 (Suppl. 1):

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