Importance of omega-3s in pregnancy and early life

Assistant Professor,

Saw Swee Hock School of Public Health, National University of Singapore

Principal Investigator, CNRC, SICS, A*STAR

MARY CHONG

Importance of omega-3s in pregnancy and early life

Fish is brain food

Scientific truth or old wives’ tale ?

Importance of dietary fat

Infant Adult

Dense source of energy Meet high energy demands

for rapid growth in childhood Essential fatty acids

Energy source Membrane function Hormone production Carry fat-soluble vitamins A,D,E,K Essential fatty acids

Not all fats are equal !

Dietary fat

Quality

What are essential fatty acids ?

Linoleic Acid (LA)Alpha- linolenic

Acid (ALA)

Omega – 6 Family Omega – 3 Family

EicosapentanonicAcid (EPA)

DocosahexaeonicAcids (DHA)

Gamma-linolenic Acid (GLA)

Arachidonic Acid (AA)

converts to

converts to

converts to

converts to

Anti-inflammatory productsPro-inflammatory products

desaturasesand

elongase

Omega-3 fats are essential for healthy brain and visual development

• Large proportion of the brain (60%) is made up of omega-3 fats

• DHA (docosahexanoic acid) is the main type of omega-3 fats in the brain and eyes

• 75% of brain cells are formed before birth and the other 25% are in place by age of

1 year

Linoleic Acid (LA)Alpha- linolenic

Acid (ALA)

Omega – 6 Family Omega – 3 Family

EicosapentanonicAcid (EPA)

DocosahexaeonicAcids (DHA)

Gamma-linolenic Acid (GLA)

Arachidonic Acid (AA)

converts to

converts to

converts to

converts to

Fatty acid desaturaseFADS

Humans are poor DHA synthesizers

Conversion rates are low ( from 0.1 to 10% )

Those with less common genotypes have very

low ability to form EPA and DHA

Conversion rates in infants insufficient to allow for biochemical and functional normality

1

2

3

Linoleic Acid (LA)Alpha- linolenic

Acid (ALA)

Omega – 6 Family Omega – 3 Family

EicosapentanonicAcid (EPA)

DocosahexaeonicAcids (DHA)

Gamma-linolenic Acid (GLA)

Arachidonic Acid (AA)

converts to

converts to

converts to

converts to

Anti-inflammatory productsPro-inflammatory products

desaturasesand

elongase

Important to directly consume pre-formedEPA and DHA

Flaxseed, chia seed, walnuts, canola oil, dark

green vegetables

Fish oil, salmon, tuna, fatty fish, mackerel

Fish oil, salmon, tuna, fatty fish, algae oil

Soya bean, corn, canola oil

Evening primrose oil

Meat

Problem with relying only on food sources

Image Source: http://mediconweb.com

Mercury - neurotoxin

- Avoid swordfish, king mackerel, shark, tilefish

Eat 2 servings of oily fish per week e.g. salmon, mackerel, tuna

- However, oily fish not as common as white fish in Southeast Asia.

Look carefully at fortified products

• Fortified food products with plant-based omega-3s i.e. ALA

Supplementation the way forward for persons of higher requirements

Benefits of EPA & DHA supplementation in mothers & infantsKoletzko B et al Systematic Review and Practice Recommendations from an Early Nutrition Academy Workshop Ann Nutr Metab 2014:65:49-80

Supplementing pregnant and lactating women – Pregnancy Outcomes

• 4 meta-analyses and 2 large RCT consistently show protective effect of omega-3 supplementation during pregnancy with reduction in the incidence of early pre-term births

• Early preterm birth (before 34 weeks gestation) increases short and long term morbidity and mortality

• Effect sizes range from 26% - 87.5%, with greater protective effects at higher intake levels (600 -800 mg DHA/day)

• Most marked and significant reduction in high risk- pregnancies

• No adverse effects reported with higher dosages

Koletzko B et al Systematic Review and Practice Recommendations from an Early Nutrition Academy Workshop Ann Nutr Metab 2014:65:49-80

Supplementing pregnant and lactating women –Infant cognitive and visual development• Recent RCTs (from 2008) are mixed in methods of assessment

-> no conclusive evidence of benefits of omega-3 supplementation

In 5,934 children born in the UK 1990s and IQ measured at 8 yrs,• Breast-fed children had >> IQ points than non-

breast-fed • Breastfed children performed similarly

irrespective of child genotype• Formula fed GG children performed worse than

other children on formula milk (Steer et al, 2010)

• Benefits of enhanced maternal pre and postnatal omega-3 status

“ Poor converters” “Good converters”

Supplementing pregnant and lactating women –Infant immune response and allergies• Strong evidence of supplementation or 2 portions of oily fish/week

resulting in improved neonatal and maternal immune responses.

Skin prick outcomes

Asthma outcomes

Klemens CM et al, 2011, BJOG

Long term effects• Lower rates of allergic asthma at 19 years of

age (Olsen SF, 2008)

Similar effects for high fish consumption• Lower allergic sensitization of children

(Italy; Calvani M et al, 2006)

• Less doctor-diagnosed eczema (Netherlands; Willers SM et al, 2006)

• Less atopic wheezing (Mexico; Romieu I et al), 2007

Supplementing infants born at full term

Allergies and the Immune Response

• Protective effects of omega-3 supplementation were seen if infants received from 1-9 days of life until 12 months (Birch EE, 2010)

• Protective effects of fish intake if fish introduced prior to 9 months of age ( Alm B, 2009).

• Strongest evidence in children with FADS genotype with low omega-3 synthesis.

Koletzko B et al Systematic Review and Practice Recommendations from an Early Nutrition Academy Workshop Ann Nutr Metab 2014:65:49-80

Supplementing infants born at full term

Cognitive Development• Results are mixed - limited by large degree of difference in dosages,

selected outcomes and methods of outcome assessment, no adjustment for genetic variation in PUFA metabolism.

• Trend towards greater likelihood benefit with higher dosages (DHA≥0.32% and AA ≥ 0.66%) and longer duration of higher postnatal omega-3 supplementation (up to 1 year of age).

• Supplementation in early life may be better detectable at later

age in more specific tasks.

Koletzko B et al Systematic Review and Practice Recommendations from an Early NutritionAcademy Workshop Ann Nutr Metab 2014:65:49-80

Supplementing preterm infants• Considerable mixed results but consistent indication that omega-3

supplementation have benefits for visual and cognitive outcomeswith DHA dose dependency

Supplementing older infants• Very few positive effects of omega-3 supplementation in older infants

(>3 months) and young children reported

• To date, studies do not provide evidence that omega-3supplementation (pregnancy or infancy) would changeinfant or later childhood growth or obesity risk

Koletzko B et al Systematic Review and Practice Recommendations from an Early Nutrition Academy Workshop Ann Nutr Metab 2014:65:49-80

Pre-pregnancy

Pregnancy Lactation Infant Childhood

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Summary of evidence

** ** *? **

• Lower pre –term risk• Better cognition and visual

development• Improved immune responses and

allergies

• Improved immune responses and allergies

Recommended levelsPregnant women• Additional supply ≥200 mg DHA, to achieve ≥ 300 mg DHA/day.

• Higher intakes (600 -800 mg) may provide greater protection against pre-term birth

Breast-feeding women

• Obtain ≥200 mg DHA/day to achieve human milk DHA content of 0.3% fatty acids

Infant formula for term infants• To provide 100 mg DHA/day and 140 mg AA/day.

• 2nd 6-months of life: continued supply of 100 mg DHA/day.

Very-low-birth weight infants• 18-60 mg/kg/day DHA and 18-45 mg/kg/day AA.

Koletzko B et al Systematic Review and Practice Recommendations from an Early Nutrition Academy Workshop Ann Nutr Metab 2014:65:49-80

Intakes of essential fatty acids in Indonesia

Undernutrition

• When total energy in low,essential fatty acids arepreferentially used for energyexpenditure.

• Micronutrient deficiencies ofFe and Zn limit conversionrate of essential fatty acids.

Deficiency in EPA & DHA

Neufingerl N et al ( 2016) Intake of essential fatty acids in Indonesian children: a secondary analysis of data from a nationallyrepresentative survey, BJN

Dietary fat qualityConcerns• Median intake of 30 mg/day

when recommended levels for

EPA+DHA are 150-250 mg

• > 80% below recommended

PUFA, ALA and EPA+DHA intakes

• >70% exceed recommended SFA intakes

• > 40% below recommended total fat intake

• Reflection of dietary intakes of adults ?

Major dietary sources of total fat, SFA and PUFA were oils and fats, with vegetable dishes contributing to ALA and fish for EPA+DHA.

A life course approach leads to greater impact

IN UTERO BIRTHINFANCY & CHILDHOOD

• 1200 mothers• 3 major ethnic groups• Deep phenotyping

3 yr 4 yr 5 yr 6 yr 7 yr 8 yr 9 yr

26th – 28th

gestation Birth 3 mth 6 mth 9 mth 12 mth 24 mth

24

Smoking Alcohol

Physical Activities SES

Nutrient Biomarkers Diet Myopia

MRI - Brain/Body Composition

Neurocognitive Test Sleep Quality

Diet Development

Anthropometrics Allergy

Environmental

Oral Health Gut Microbiota

INFANT HEALTH OUTCOMES

PREGNANCY OUTCOMES

GDM Pre-Eclampsia

IUGR Pre-Term

BIRTH OUTCOMES

Anthropometrics BIA/PEAPOD

MRI - Brain/Body Composition

Cord Blood

Neurocognitive Test

MATERNAL HEALTH & PRACTICES

Mental HealthBreastfeeding

Practices

Diet & Feeding Practices and Behaviour

Genes Family Medical History

Existing Health Conditions

Mental Health

Anthropometrics OGTT

Vascular Function Retinal Health

Acknowledgements to Toh Jia Ying for help with slides Epigenes/genes

MaternalNutrition

InfantNutrition

28

Key messages

• Omega-3 fatty acids are important for infant health outcomes (pre-term, neurodevelopment and allergy risk).

• Pre-formed EPA and, in particular DHA are recommended due to low conversion rates and genetic variation.

• Regular supply prior to pregnancy is beneficial as it contributes to accumulation of body stores

• Recommend to consume 2 servings of oily fish as they also contain other nutrients

• Supplementation needed to meet higher requirements during pregnancy and if oily fish intake is inadequate.

Fish :More than just brain food !