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ωω--3 fatty acids:3 fatty acids:

The Effects during Pregnancy and The Effects during Pregnancy and

Breast feedingBreast feeding

Antonis ZampelasAntonis 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

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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-3Thromboxane Α2 (pro-aggregatory) Prostacycline (anti-aggrega tory)

Leukotriene Β4 (promotes aggregation Thromboxane Α3 (less active)of leukocytes) Leukotriene Β5 (< 5-10% active compared to Β4)

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1

1,5

2

Mixed oilCorn Oil

Postprandial plasma TG and LPL responses following ac ute test meals of different fatty acid composition

Plasma TG (mmol/L)

150

200

250

LPL (nmol oleate released/min/ml plasma )

0

0,5

Fish oil

Time postprandially (min)

Zampelas A et al Eur J Clin Nutr 1994, 48: 842-848

0

50

100

5 15

Mixed oil Corn oil Fish oil

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Fish consumption

No < 150 g/w 150–300 g/w > 300 g/w P ⊥

N

(%) 319 (11%)

1719

(56%)

745

(24%)

259

(9%)

-

CRP (mg/L) 2.7±1.2 2.0±1.1** 2.0±2.1** 1.8±1.1** 0.004

Inflammatory markers and fish consumption: Inflammatory markers and fish consumption:

the ATTICA Study the ATTICA Study

CRP (mg/L) 2.7±1.2 2.0±1.1 2.0±2.1 1.8±1.1 0.004

IL – 6 (ng/ml) 1.5 ±0.5 1.3±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** < 0.001

Amyloid A (mg/dl) 6.4 ±4 5.9±4 5.1±4* 4.6±3** 0.004

No gender differences were observed.* P < 0.05 and ** P < 0.01 (Bonferroni corrected) for the differences between fish consumption groups vs. noconsumption. 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).

Zampelas A et al J Am Coll Cardiol 2005;46:120-4

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

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• The brain weight in the newborn corresponds to approximately

10% of the total body weight

• Following adipose tissue, brain is the 2nd richer organ in fat

• 50-60% of the dry weight is fat

The brain

The fatty acids AA and DHA are main constituents

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�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 �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.

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� Photoreceptor outer segments

have the highest DHA segment

of any cell

� Prolonged dietary deprivation

required to reduce DHA

contentcontent

- only then functional

impairment occur

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

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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 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

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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 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

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� 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.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.: CD007901

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�Maternal plasma and erythrocyte arachidonic acid and total �Maternal plasma and erythrocyte arachidonic acid 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): e0147359

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• 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])

Effect of nEffect of n--3 Long3 Long--chain Polyunsaturated Fatty chain Polyunsaturated Fatty Acid Intake during Pregnancy on Maternal, Acid Intake during Pregnancy on Maternal,

Infant, and Child Health Outcomes: A Systematic Infant, and Child Health Outcomes: A Systematic ReviewReview

• 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): 91–107

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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 Epidemiol 2012;26 (Suppl 1):91–107

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Palmer DJ et al BMJ 2012;344:e184

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Palmer DJ et al BMJ 2012;344:e184

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� 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 dermatitis (eczema), allergic rhinitis (hay fever) and asthma/wheeze) in their

children.

� Selection criteria: Randomised controlled 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.: CD010085.

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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;129:1141–1149

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Qawasmi A et al Pediatrics 2012;129:1141–1149

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Qawasmi A et al

Pediatrics 2012;Pediatrics 2012;

129:1141–1149

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� 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 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

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� 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 200 – 500 mg/d.

� When breastfeeding is not - infant formulae should contain DHA 0.2 � 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

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Common Variables mg of n-3 Fatty Acids EPA and DHA

Per 4 Ounces of Cooked Fish

Micrograms of Mercury

Per 4 Ounces of Cooked

Fish

Salmon

Anchovies, Herring

Mackerel

Tuna

1200-2400

2300-2400

1350-2100

1700

2

5-10

8-13

54-58Tuna

Sardines

Trout

Shark

Swordfish

Mackerel, King

1700

1100=1700

1000-1100

1250

1000

450

54-58

2

11

151

147

110

FDA, 2014

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Paediatric Perinatal Epidemiol 2012;

26 (Suppl. 1):91–107

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Imhoff-Kunsch B et al Paediatric Perinatal Epidemiol 2012;226 (Suppl. 1):91–107

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Imhoff-Kunsch B et al Paediatric Perinatal Epidemiol 2012;226 (Suppl. 1):91–107

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Imhoff-Kunsch B et al Paediatric Perinatal Epidemiol 2012;226 (Suppl. 1):91–107

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Imhoff-Kunsch B et al Paediatric Perinatal Epidemiol 2012;226 (Suppl. 1):91–107