Focus Module - LC-PUFAs in Pregnancy, Lactation and Infancy

Although fat is the most energy dense macronutrient, the human body requires dietary fats not only as an important energy source, but for many other body functions. In this context, the quality of fat is of great value throughout the life cycle, especially in pregnant and lactating women, as well as in the developing and growing child. While saturated fatty acids are mostly attributed negative health outcomes, the awareness of the positive effects of the unsaturated types, especially long-chain polyunsaturated fatty acids (LC-PUFAs), is increasing. They play a critical role in cell membrane structure, the functioning of the brain and nervous system and are most abundantly found in the brain, retina and the central nervous system.

Being essential fatty acids, a sufficient intake and possible supplementation of LC-PUFAs is crucial to positively influence body functions and health outcomes. Early life, pregnancy and lactation are considered life stages that go along with special needs for LC-PUFAs because of their role in growth, development, vision, neurological and immune function.

In this module, the perinatal importance of LC-PUFAs from pregnancy until late infancy is going to be discussed in detail, with an overview of chemistry, metabolism and physiological action, health outcomes for mothers and their offspring, as well as recommended intakes in the different life stages.

This module has received accreditation by the German Medical Association with 11 CME credits.

This module has received accreditation by the European Accreditation Council for Continuing Medical Education (EACCME) with 8 CME credits.



Module overview

Dietary fats can be classified according to their degree of unsaturation. Polyunsaturated fatty acids (PUFAs) of the omega-3 and omega-6 series and their long-chain metabolites (long-chain polyunsaturated fatty acids or LC-PUFA's), have received special attention in recent years because of their reported effects on human health throughout life.

The PUFAs linoleic acid (LA) and α-linolenic acid (ALA) are essential substrates that must be regularly supplied with our diet, as they cannot be synthesized in the human body. Once taken up into cells they can undergo metabolic conversion into LC-PUFAs, which exert various physiological functions. These include incorporation into tissues and cell membranes, especially in the brain, retina and platelets, interaction with transcription factors and involvement in signal transduction pathways. LC-PUFA's can be further metabolized into highly potent, short-lived lipids, so called eicosanoids, docosanoids and resolvins, which in turn influence a variety of body systems and clinical outcomes. Their effects on human health depend on the type of eicosanoid produced and are not only beneficial, but can also have some negative consequences; the development of the human diet towards an excessively increased ratio of n-6/n-3 fatty acids is hypothesized to promote inflammation and inflammatory related diseases through the production of n-6-derived pro-inflammatory eicosanoids.

An adequate intake of LC-PUFA's is vital throughout the lifespan with special emphasis in pregnant and lactating women as well as infants. Rapid accumulation of LC-PUFA's in the brain and retina takes place during the last trimester and to a lesser extent during the first two years of life, implying their importance for optimal development and function of these tissues.

To understand the dimension of the meaning of LC-PUFA's for human development and health, it is important to first look at the chemistry and metabolism of PUFA's and LC-PUFA's, in order to interpret their role in physiology and pathophysiology and to give appropriate recommendations of intake throughout the life span.

The unborn child depends almost entirely on LC-PUFA supply from the maternal bloodstream, as desaturase activity in fetal tissues and in the placenta is very low. Therefore, LC-PUFA intake and status of the mother have a direct impact on the LC-PUFA status of the newborn. LC-PUFA's are preferentially transported across the placenta compared to other fatty acids, and increased amounts are transferred to the fetus during the third trimester when DHA rapidly accumulates in the central nervous system. In pregnancies complicated by gestational diabetes mellitus or intrauterine growth restriction, placental function is impaired, leading to alterations in nutrient transfer. Both inadequate maternal intakes during pregnancy and complications affecting placental function can therefore have negative health outcomes for mother and child.

Triggered by observational studies and biological plausibility, short- and long-term health outcomes in both mothers and children after n-3 LC-PUFA supplementation during pregnancy were investigated intensively. While an effect on pregnancy duration and risk of early preterm birth has been well established, the role on other maternal health outcomes such as perinatal depression needs further research. Short- or long-term effects on a child's health remain controversial. Available observational and intervention studies differ greatly in methodology (start and duration of intervention, dose and administration form of LC-PUFA's and measured outcomes), making the studies difficult to compare and complicated to draw conclusions. Therefore, more long-term, well-designed randomized controlled trials are required to be able to draw any definite conclusions on the effects of LC-PUFA supply and status during pregnancy on health outcomes of mothers and their offspring.

Based on the demonstrated risk reduction for early preterm birth and in consideration of the potential benefits, authoritative bodies recommend a higher supply of n-3 LC-PUFA's during pregnancy, which can be achieved by regular consumption of ocean fish, in particular oily fish.

After the rapid accretion of LC-PUFA's in utero, the newborn remains dependent on external DHA and ARA supply as endogenous conversion rates are too low to meet the high requirements of the rapidly developing central nervous system (CNS). LC-PUFA basal levels are always contained in breastmilk and are mainly derived from maternal stores. Both short-term dietary intake and endogenous synthesis contribute to total LC-PUFA content of breastmilk and with higher LC-PUFA intakes, basal levels increase considerably.

The average concentrations of ARA and DHA measured in breastmilk serve as a reference for the development of infant formula. Nowadays, most of the marketed products are enriched with DHA and ARA. Yet, the evidence on beneficial health outcomes of enriched formulae is still inconclusive and requires further investigation using uniform protocols.

In infants born preterm, current data point towards beneficial effects on cognitive development and visual acuity and most experts acknowledge the importance of LC-PUFA's for preterm infants. Further research is needed to determine the best formulation of parenteral and enteral feeds, as well as the optimal dosage of DHA and ARA for the preterm infant.

The health impact for older infants has not been studied as extensively as for other age groups. Dietary requirements are supposed to remain high as the CNS is still developing rapidly, but the supply from complementary foods is low in most regions of the world. Despite theoretical and biologically plausible high requirements, there is not enough scientific evidence to set dietary reference intake values for older infants, but adequate intake values are provided by international authoritative bodies.

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