Chapter 1: Fat Requirements in Pregnancy and Infancy

Pregnancy is a critical phase in life when several metabolic adaptations take place to support fetal growth and development. When the metabolic balance is disturbed due to inadequate dietary intake or inappropriate maternal nutritional status, such as obesity, the health of both mother and child may be disturbed. Obesity increases the risk of gestational diabetes (GDM), a condition affecting one in six live births worldwide, posing serious health risks for both mother and child.¹  The risks during pregnancy and in the years to come include an increased risk for pre-eclampsia and type two diabetes in the mother and macrosomia and obesity in the child. Importantly fetal and early infancy events may permanently change the child's bodily structure, function, and metabolism i.e. a kind of re-programming of the body's metabolic pathways, conferring a life-long risk of developing serious diseases.² 

Fats play a key role in the growth and development of the fetus and infant. They also contribute to the health of both mother and child due to their many metabolic and structural roles in the human body. Fat stores are needed as an energy source in maternal and infant bodies during pregnancy but in addition, they have other functions acting as precursors for bioactive signaling compounds and immune regulation. The dietary quality of the fat is of major significance not only as a supply of long-chain polyunsaturated fatty acids (LC-PUFA), including the essential fatty acids linoleic acid (LA; 18:2 n-6) and alpha-linolenic acid (ALNA; 18:3 n-3) needed from dietary sources, but also their longer chain derivatives, arachidonic acid (AA; 20:4 n-6), eicosapentaenoic acid (EPA; 20:5 n-3), and docosahexaenoic acid (DHA; 20:6 n-3). These fatty acids may be considered as being conditionally essential during pregnancy, as the fetus obtains his/her supply from the mother.³ Both AA and DHA are present at high concentrations in the structural lipids of the central nervous system; in the developing fetus, placental function is critically important for delivery of these fatty acids during the rapid phases of development, particularly during the last trimester of pregnancy. After birth, these fatty acids should be present in the newborn's diet.⁴  These fatty acids are present in breast milk and nowadays are included in most milk formulas utilized for infant feeding when breast milk is not available in sufficient amounts due to some compelling reason (e.g. maternal illness).

While breastfeeding is the natural mode of feeding an infant, it also supports the recovery of the mother from pregnancy and aids in bonding between the mother and child. Breastfeeding has also been linked with many health benefits for both mother and child.⁵  In the switch from breastfeeding to complementary feeding, the dietary intake of fat decreases as typically also does the supply of LC-PUFA. All these aspects of infant feeding may influence the growth and development and health initially of the fetus and later of the child. Energy and nutrient requirements during pregnancy, breastfeeding, and infancy are driven by the elevated metabolic requirements due to the growth and development of the fetus and infant as well as maternal tissue deposition (Figure 1.1). These needs are supplied by maternal and infant diet but also by maternal nutrient stores laid down before pregnancy and during the anabolic phases of the pregnancy.

All in all, pregnancy is an important phase in human life defining the health of both mother and fetus both in the short- and long-term with sequelae taking place during breastfeeding and/or infant complementary feeding. In this chapter, these issues are reviewed in more detail, emphasizing the importance of overall maternal–fetal–infant metabolic communication. Another focus is on the factors influencing the dietary intake and supply of LC-PUFAs.

Energy is required during pregnancy to meet the maternal demands of basal metabolism, placental and fetal tissue growth and function, as well as physical activity.⁶  A pregnant woman's energy requirements increase because of the need to accumulate maternal body mass and the demands of fetal growth, as well as due to pregnancy-associated physiological changes including a higher cardiac output. Overall pregnancy is an anabolic state when energy is stored but on a closer look, while the first and second trimesters are anabolic, the third trimester is catabolic.⁷  The energy needed during pregnancy is obtained from the diet but also from maternal stores, thus maternal dietary intake and nutritional status before as well as during pregnancy, are of crucial importance (Figure 1.1). Energy requirements vary over the course of pregnancy, ranging from very little additional demands in early pregnancy to substantial needs in late pregnancy when the growth of the fetus is at its greatest. The estimated total cost of pregnancy in terms of energy is 375 kJ per day in the first trimester, 1200 kJ per day in the second, and 1959 kJ per day in the third trimester.⁸  The energy needed for physical activity is variable between women but commonly there are reductions in the amounts of physical activity toward the last phases of pregnancy. The guidelines for weight gain during pregnancy are set based on the categories of the pre-pregnancy BMI. This is due to the fact that the risks for complications during pregnancy rise with an increase in BMI, and maintaining the weight gain within the limits set based on pre-pregnancy BMI secures fetal health and avoids either macrosomia or birth small-for-gestational age (SGA).⁹  Normal weight women (BMI 18.15–24.9 kg m⁻²) should gain 11.5–16 kg over the course of pregnancy, overweight women (25.0–29.9 kg m⁻²) 7–11.5 kg, women with obesity (≥30.0 kg m⁻²) 5–9 kg and underweight women (<18.5 kg m⁻²) 12.5–18 kg.

Along with the maternal energy requirements, the fetal growth is fastest in the third trimester of pregnancy. There is only marginal accumulation of lipids for the first 25 weeks of pregnancy but it increases thereafter with gestational age^3,10  ranging from 1.6–3.4 g per day in the last weeks of gestation.¹¹  In a human fetus, precursors of fat lobules are found in the 14th week of gestation.¹²  Both white and brown adipose cells are recognized by 28 weeks. The process of fetal adipogenesis and the prevailing regulatory factors have been explained in detail by Desoy and Herrera.¹²  The fetal fat accretion is achieved by two mechanisms; (1) by fatty acids that cross the placenta, and (2) by fetal lipogenesis.³  In the latter case, the fetus has the capacity to use glycerol and fatty acids derived from glycolysis. Glucose is obtained from the maternal supply as the fetus does not synthesize glucose. Fetal lipogenesis for the deposition of triglycerides takes place in the liver and adipocytes. An increase in the fetal lipogenesis is seen from 10 weeks of gestation onwards, the main precursors being glucose, lactate, and ketone bodies.¹² 

It is estimated that at birth about 14% of the body weight is fat with baby girls having a slightly higher proportion of body fat than boys.¹³  Due to differences in subcutaneous lipid mass, a large interindividual variation is observed in a newborn's body fat mass.¹⁴  The largest constituent of white adipose tissue (WAT) fat at 40 weeks gestation is SFA (298 mg g⁻¹ WAT) followed by MUFA (226 mg g⁻¹) and PUFA (23.2 mg g⁻¹).¹⁴  N-6 PUFA (21.3 g g⁻¹ WAT) dominated over n-3 PUFA (1.8 mg g⁻¹ WAT) in this infant sample of stillborn infants from Curacao. These amounted to 262 g saturated fatty acids (SFA), 194 g monounsaturated fatty acids (MUFA), and 20.4 g PUFA (including 1.46 g DHA and 3.15 g AA) in a 3500 g term infant.¹⁴  Fetal fat accretion is at its highest in the last five weeks of gestation when accretion rates of 342 mg per day for LA, 95 mg per day for AA and 42 mg per day for DHA were determined.¹⁵  At term, about half of the total DHA is located in adipose tissue, 23% in brain and 21% in skeletal muscle. In fact, a newborn infant accumulates a total of about 3 g DHA during gestation.¹⁵  Fetal fat has many roles (as reviewed in ref. 12); it provides insulation against the temperature changes after birth, acts as an energy store to sustain cerebral function (glycerol or ketone bodies), and furthermore may contribute to molecular signaling and the infant's immune functions.

When the fat mass at birth of 183 infants was modeled, the strongest predictors were found to be parity, gestational age, pregravid weight, maternal weight gain, and neonatal sex.¹³  Of interest here is that also maternal pre-pregnancy obesity has been demonstrated to associate with increased neonatal fat mass; infants of mothers who are overweight and obese have a higher body fat proportion and more fat mass at birth compared to infants of normal weight mothers.¹⁶  In addition, maternal GDM has been related to increased fetal adiposity.¹⁷  A higher adiposity of a newborn baby per se has been linked with childhood obesity.^18,19  On the other hand, the higher adiposity of a human newborn may be important for supporting brain development.²⁰  The maternal diet during pregnancy may influence fetal adiposity as demonstrated in studies in which the newborn body composition has been measured with sophisticated equipment, air displacement plethysmography, within a few days after birth.^21–25  A positive association has been found between maternal intake of polyunsaturated fats and neonatal fat mass index (calculated with a body composition measurement using air displacement plethysmography).²³  In another study, increases in the intake of total fat, SFA, unsaturated fat, and total carbohydrates were associated with elevated neonatal fat mass.²¹  Investigations evaluating maternal diet patterns and indices have also revealed associations with newborn fat mass. Starling and colleagues identified a diet pattern characterized by an intake of eggs, starchy vegetables, and non-whole grains, which was associated with greater newborn adiposity.²⁵  In a similar manner, lower healthy eating index (HEI-2010) scores were associated with a higher proportion of newborn fat mass²⁴  and the proinflammatory potential of the maternal diet, which was measured several times during pregnancy, was related to an increase in fat mass and the proportion of body fat mass in the newborn infants.²²  A study in obese women revealed an association between higher maternal carbohydrate intake (the highest quartile, median 238 g per day, compared to the lowest quartile, 188 g per day) in late pregnancy, but not in early pregnancy, with a higher proportion of body fat in the newborn as measured by dual-energy X-ray absorptiometry.²⁶ 

There have been very few intervention studies conducted; in one, the impact of a behavioral lifestyle intervention involving goals for both diet intake (glycemic load and SFA intake) and physical activity in obese women during pregnancy on infant adiposity assessed by subscapular and triceps skinfold thicknesses was evaluated in the UK Pregnancies Better Eating and Activity Trial (UPBEAT).²⁷  No benefit of the intervention was seen in the triceps skinfold thickness, but the subscapular skinfold thickness z-score was lowered on average by 0.26 sd in the intervention group indicating that maternal behavioral intervention during pregnancy could contribute to a reduction in infant adiposity. Bernard and colleagues suggested that the maternal plasma PUFA status during 26 to 28 weeks of gestation was related to newborn adiposity.²⁸  They demonstrated that maternal LA levels were positively associated with neonatal abdominal adipose tissue volume, as measured by magnetic resonance imaging (MRI), but no association was detected with other measured fatty acids, AA, ALNA, EPA, or DHA. In another study, plasma n-3 PUFA concentrations were measured at a median of 20.5 weeks of gestation and infants’ body compositions somewhat later, at the age of 1.5 months by skin fold thicknesses.²⁹  With respect to the central-to-total subcutaneous fat ratio in the infants, maternal total n-3 PUFA, and EPA, docosapentaenoic acid (DPA) and DHA levels were associated with higher ratios whereas the n-6 to n-3 ratio was associated with a lower central-to-total subcutaneous fat ratio. The authors speculated that the maternal n-3 PUFA status may stimulate central subcutaneous fat mass development in early infancy, but as no associations were found later at the age of two years, this is likely a transient effect which does not persist.²⁹  As a potential mechanism, they proposed that there could be increased activation of peroxisome proliferator-activated receptor (PPAR)-c with a subsequently increased deposition of subcutaneous fat mass.

Many metabolic adaptations take place during pregnancy. These adaptations are driven by the increased energy requirements of pregnancy to support fetal growth and development as well as preparing for the additional energy demands of lactation, i.e. deposition of maternal fat. The key metabolic adaptations take place in maternal glucose and lipid metabolism with an anabolic state present in early pregnancy and a subsequent catabolic state in late pregnancy. The main metabolic adaptations in pregnancy are summarized in Figure 1.2.

During pregnancy, overall about 3.5 kg of fat is deposited in maternal tissues, both subcutaneously and viscerally.³⁰  The fat is utilized as an energy source but also contributes to insulin resistance.³¹  From the point of view of lipid metabolism, there is net lipogenesis in early pregnancy and net lipolysis in late pregnancy as reviewed previously.^7,10,32–34  Briefly, lipid deposition is due to maternal hyperphagia but also due to the higher insulin concentrations and increased insulin sensitivity observed in early pregnancy. It is known that there is an enhanced de novo lipogenesis taking place in early pregnancy. The increase in lipoprotein lipase (LPL) activity results in an uptake of fatty acids from the circulation into adipose tissue. In the catabolic state of the last trimester of the pregnancy, the lipolytic activity of adipose tissue is enhanced due to an increase in the activity of hormone sensitive lipase (HSL) and the lowered activity of LPL. The released glycerol is taken up for hepatic triglyceride synthesis and subsequently released into the circulation in very low-density lipoprotein (VLDL) and an increase in the concentration of non-esterified fatty acids (NEFA). In the fasting state, glycerol may be also used for glucose synthesis thus securing the fetal requirements regardless of the mother's fasting state. As the metabolic requirements during late pregnancy are high, NEFA may be used for energy production with the synthesis of ketone bodies which are utilized as a glucose substitute by both mother and fetus during fasting states in the mother. Thus the transfer of ketone bodies across the placenta is considered to be of particular importance for securing embryonic development e.g. for brain lipid synthesis. Nonetheless, their presence may also be harmful as long periods of maternal hyperketonemia may be associated with fetal malformation, impaired neurophysiological development, and stillbirth as reviewed in ref. 34.

Overall, due to the prevailing catabolic state, late pregnancy is manifested by hyperlipidemia with an increased concentration not only of triglycerides (VLDL) but also of phospholipids, cholesterols and glycerol. Cholesterol is important for fetal development, it is an essential component of cell membranes, a precursor for bile acids and steroid hormones and has many other functional roles including cell communication. Thus, its supply to the fetus is secured by transplacental transfer from the maternal circulation and by fetal de novo synthesis as reviewed in Zeng et al. 2017.³⁴  They also provided evidence that low maternal serum cholesterol levels during pregnancy would associate with reduced birth weights and an elevated incidence of microcephaly; in contrast hypercholesterolemia in term promoted atherogenicity. Adipose tissue may also play a role in maternal gestational complications³⁵  and fetal growth with potential long-term health consequences,^36,37  since it is a source of inflammatory mediators, i.e. adipocytokines. The cytokines are also expressed in placenta.

Many hormones drive and regulate the metabolic adaptations in pregnancy.^10,32,34,38  The anabolic state in early pregnancy, including maternal lipogenesis and fat deposition, is driven by hyperinsulinemia and also the insulin sensitivity of the tissues is elevated. Insulin increases the activity of LPL in adipose tissue and consequently fatty acids are taken up from circulating triglycerides into adipose tissue. Towards the third trimester of pregnancy, insulin resistance develops in a progressive manner and consequently LPL activity is lowered. Furthermore, in pregnant women, adipose tissue derived cytokines and tumor necrosis factor (TNF)-alpha secreted by the placenta mediate the state of insulin resistance. Insulin resistance, and an increase in the amounts of free fatty acids and glycerol, drives lipolysis in adipose tissue and hepatic gluconeogenesis and ketogenesis. The concentration of estrogen increases throughout the pregnancy and contributes to the catabolic state, and thus to the hyperlipidemia encountered in pregnant women. Hyperlipidemia is also induced by progesterone, cortisol, prolactin, and leptin; these hormones are involved in decreasing the body's responsiveness to insulin. Two other hormones deserve a mention; human placental lactogen stimulates insulin secretion whereas human placental growth hormone evokes insulin resistance.

Hyperlipidemia in pregnancy is a normal physiological situation that ensures the supply of nutrients to the fetus, but excessively elevated levels may be harmful. Two meta-analyses have explored this issue; in the first, based on an evaluation of case-control studies, higher serum levels of triglycerides were shown to associate with pre-eclampsia.³⁹  They also found evidence from cohort studies that hypertriglyceridemia preceded the onset of pre-eclampsia. In the second meta-analysis, other lipid fractions were also evaluated and pre-eclampsia was found to associate with higher levels of total cholesterol, non-high-density lipoprotein (HDL) cholesterol and triglycerides in all trimesters and with lower levels of HDL cholesterol in the third trimester.⁴⁰  Based on yet another meta-analysis, women with GDM were also shown to display elevated triglyceride levels in all trimesters of pregnancy.⁴¹  In the same analysis, the third trimester HDL cholesterol levels were found to be lower in women with GDM, whilst no differences in total cholesterol or low-density lipoprotein (LDL) cholesterol levels were seen between women with or without GDM.⁴¹  Hyperlipidemia may be harmful as it contributes to the risk of acute myocardial infarction of the mother in pregnancy, labor and delivery, and also postpartum,⁴²  and to acute pancreatitis during pregnancy;⁴³  although both conditions are rare, they are potentially lethal for both mother and child.

From the point of view of the fetus, metabolic adaptations in pregnant woman are necessary to support fetal growth and development. Fatty acids are obtained from the maternal circulation to supply energy, essential fatty acids, and LC-PUFAs for growth and development including tissue development, primarily adipose tissue.^33,34  The fetus also gains fat stores during pregnancy, as discussed in the previous paragraph. While the maternal hyperlipidemic state supports these metabolic needs of the fetus, it may contribute to an excessive growth of the fetus. In an Asian study population, highly elevated maternal fasting triglyceride levels (above 3.6 mmol l⁻¹) were associated with large-for-gestational-age (LGA) status independently of pre-pregnancy BMI, GDM, and insulin resistance.⁴⁴  Similar findings were found in another study; triglyceride levels in the mothers of LGA infants increased faster than those of the control group and the infants of mothers with the highest triglyceride levels (above 1.19 mmol l⁻¹) were larger than those with lower triglyceride levels.⁴⁵  The authors of a Chinese population-based study (17 610 singleton pregnancies with lipid data from early and middle pregnancy) also reported that serum lipids are increased from early to middle pregnancy with the rise being related to adverse pregnancy outcomes including a risk of gestational diabetes and LGA.⁴⁶  Maternal hyperlipidemia may also influence uterine blood flow as measured by blood flow velocity waveforms in women with GDM, potentially indicating the presence of vascular damage.⁴⁷  Thus, excessive hypertriglyceridemia is clearly not desirable. Wang and co-workers calculated reference values for serum lipids that would lower the risk of adverse pregnancy outcomes, namely total cholesterol <5.64 mmol L⁻¹, triglycerides <1.95 mmol L⁻¹, HDL cholesterol >1.23 mmol L⁻¹ and LDL cholesterol <3.27 mmol L⁻¹ in early pregnancy and total cholesterol <7.50 mmol L⁻¹, triglycerides <3.56 mmol L⁻¹, HDL cholesterol >1.41 mmol L⁻¹, and LDL cholesterol <4.83 mmol L⁻¹ in middle pregnancy.

The latest research has applied metabolomics to investigate lipid metabolism in maternal or cord blood. The cord blood lipidomics profile, and also the profiles of other metabolites like amino acids, have been linked with birth weight⁴⁸  and adiposity,^49,50  as measured by skinfold thicknesses, and furthermore the lipidomics profile in pregnancy has been linked with birth weight;⁵¹  these may potentially represent new biomarkers for child health outcomes in the future. One example is a study in which the ratio of particular metabolites in maternal serum during pregnancy was shown to predict fetal growth restriction.⁵² 

Placenta has an important role in ensuring the success of the pregnancy; it influences the rate of fetal growth through the transport of nutrients from the mother to the fetus and the placenta also has a capacity to synthetize hormones.³²  Many placental hormones including growth hormone, prolactin, placental lactogens, and steroid hormones, mediate the maternal adaptations to pregnancy as reviewed in detail in ref. 53. In cases of placental insufficiency fetal development is endangered and manifested as conditions like intrauterine growth restriction. To secure the fetal demands, the structure and function of the placenta change over the course of pregnancy. Placental structure allows a maximal surface area for the exchange of membrane-permeable molecules as well as those molecules that require transporters for crossing the cellular membranes.⁵⁴  Placenta has the capacity to affect nutrient availability to the fetus by the transfer of nutrients from the mother and storage of nutrients for delivery to the fetus as needed. In addition, new substrates may be metabolized in the placenta for fetal needs. LC-PUFAs do not seem to be synthetized in the placenta, instead the fetus relies on the maternal supply and synthesis through chain elongation and desaturation processes.³  Fetal growth is mainly attributable to glucose but in addition to carbohydrates, lipids and amino acids are needed for fetal growth. Considering lipid metabolism, a fetus can synthetize some saturated and monounsaturated fatty acids from glucose but must obtain essential fatty acids from the mother through the placenta. LC-PUFAs are particularly important for fetal neurodevelopment and further fatty acids and their derivatives, e.g. eicosanoids have important signaling roles including those necessary for the initiation and progression of labor.

Placental fatty acid transfer has been recently reviewed in detail.^54,55  Briefly, the placenta takes up fatty acids from the maternal circulation either as free fatty acids or from triglycerides by the action of lipases expressed in the placenta. The majority of the fatty acids are esterified in the placenta, and again oxidized or released by esterases. Placental fatty acid binding protein (FABS) and fatty acid transport protein facilitate the transport of fatty acids down a concentration gradient to the fetus. Fatty acids are also converted to acylcarnitines, which are particularly important for the selectivity of LC-PUFA transfer across the placenta.

It is noteworthy that not all the fatty acids are unidirectionally transferred to the fetus; fatty acids are also released into the maternal circulation. Some fatty acids may be selectively transferred to the fetus as demonstrated in ¹³C-labeled fatty acid studies.^56,57  Pregnant women received ¹³C-labeled palmitic acid, oleic acid, LA, or DHA 12 hours before cesarean section, and cord blood and placenta were analyzed. Higher concentrations of the labeled DHA were found in cord plasma than maternal plasma and furthermore, DHA was detected at higher concentrations than the other fatty acids in the placenta. This may be due to the need to sustain high fetal needs for brain and retinal development. In addition to placental function, also the maternal supply, i.e. the dietary intake but also fat stores are important for satisfying the fatty acids needs of the fetus, particularly for essential fatty acids and LC-PUFAs including DHA. DHA can also be formed by fetal endogenous synthesis. Interestingly, maternal metabolic conditions may influence the placental transfer of DHA to the fetus. A lower placental uptake and reduced transfer of DHA to the fetus were observed in women with GDM in comparison to controls.⁵⁸  Furthermore, an altered expression of genes involved in placental lipid metabolism has been demonstrated in women with obesity and GDM indicating that the transport and storage of lipids are modified under these conditions.^59,60 

The fetus requires fatty acids for energy, to maintain the fluidity, structure, and permeability of membranes and for precursors of a range of bioactive compounds including eicosanoids. The LC-PUFAs are needed for structural and metabolic functions. Thus, although LC-PUFAs – AA, EPA and DHA – are not essential fatty acids, they may be viewed as conditionally essential during pregnancy as the fetus benefits from the supply from the mother³ . Fatty acids are required already in very early stages of development for cell division and cell growth and differentiation by the embryo and oocytes. Thereafter, the need for fats increases exponentially throughout the course of the pregnancy. The requirements for DHA are particularly high close to term, being around 300 mg per day whilst the requirement at 25 weeks of gestation is 100 mg per day.³  The fetus efficiently stores DHA which is of particular importance after birth when the maternal supply through the placenta has ceased. A rise in newborn plasma triglycerides and free fatty acids is seen within a few hours of birth, as reviewed by Haggarty.³  Interestingly, a higher conversion of ALNA to its long-chain derivatives has been detected in women compared to men, one mechanism ensuring a sufficient supply of these important fatty acids for fetal growth and development.⁶¹ 

The European Food Safety Authority has set dietary reference values for the European Union.⁶²  Firstly, pregnant women should increase their energy intake by 0.29 MJ per day in the first trimester, by 1.1 MJ per day in the second trimester and by 2.1 MJ per day in the third trimester of pregnancy. The reference intake range for total fat is set at 20–35% of energy intake and SFA intake and trans-fatty acid intakes should be as low as possible. Adequate intakes for LA and ALNA have been set to 4 and 0.5 percent of energy intake respectively and the DHA intake should be 100 to 200 mg higher than in non-pregnant women. The fatty acid requirements have also been evaluated in expert reports which have concluded that “dietary fat intake in pregnancy and lactation (energy%) should be as recommended for the general population; pregnant and lactating women should aim to achieve an average dietary intake of at least 200 mg DHA per d”.⁶³  They also concluded that intakes of up to 1 g per day of DHA or 2.7 g per day n-3 LC-PUFA are safe, as no significant adverse effects have been noted in randomized clinical trials. A recommendation for fish intake was given; one to two portions of sea fish per week, including oily fish, for women of childbearing age. In another expert report, 300 mg per day of DHA was recommended for pregnant and lactating women.⁶⁴ 

The dietary intake varies across countries and obviously between individuals. Overall total fat intakes are higher and intakes of PUFAs are commonly lower than recommended.^65,66  Forsyth and colleagues estimated the dietary intake of DHA and arachidonic acid in 175 countries around the world. The DHA was below 200 mg per day in 64% of the countries, with the lowest intakes in Sub-Saharan Africa, and Central and Southern Asian populations.⁶⁷  The mean intake of DHA in the European Union was 198 mg per day; other values were as follows – Australia and New Zealand 184 mg per day, USA and Canada 221 mg per day, China 298 mg per day and Japan 473 mg per day, whilst the intake in low-income countries was 96 mg per day. It was reported that only 27% of Canadian pregnant women met the recommended intake of DHA, but women who consumed food supplements improved the likelihood that they would fulfill the recommendation.⁶⁸ 

A higher dietary intake of n-3 LC-PUFAs is reflected in the proportion of these fatty acids in maternal plasma during pregnancy, with the greatest changes being observed in the phospholipid fraction.⁶⁹  In a systematic review, in addition to higher fish consumption and a higher PUFA intake, a higher maternal n-3 status was explained by a higher education level and older maternal age.⁷⁰  Similarly changes in cord blood fatty acids have been observed.⁷¹  In supplement studies, a daily dose of 500 to 1000 mg of n-3 LC-PUFA, but not a smaller dose, effectively increased fetal n-3 fatty acid status as measured from cord blood.⁷² 

Maternal higher dietary intake of n-3 LC-PUFAs, particularly EPA and DHA, as fish or fish oil supplements have been often claimed to improve health and development outcomes of the child. In a population-based European study, fish consumption of at least once per week during pregnancy was related to a lower risk of preterm birth and to a higher birth weight compared to the situation in women who ate fish less commonly.⁷³  A Cochrane systematic review of randomized controlled trials with n-3 LC-PUFA either as food or supplements during pregnancy concluded that there was a lower risk for preterm birth and increased the risk for prolonged gestation beyond 42 weeks in women who consumed n-3 LC-PUFA supplements.⁷⁴  Furthermore, a reduced risk of low birthweight was seen. No benefits of the n-3 LC-PUFAs in terms of child cognition, IQ, vision, or other neurodevelopment and growth outcomes or language and behavior were seen although the authors called for further follow-up of the completed trials to assess longer-term health outcomes of the supplementation.⁷⁴  A review of observational studies concluded that there were some benefits of fish intake during pregnancy for child neurodevelopment.⁷⁵  A study with a modern method for assessing neurodevelopment, pattern-reversal visual evoked potentials (pVEP), demonstrated that the maternal consumption of fish at least three times per week during the last trimester of pregnancy was associated with better neurodevelopment of the child's visual system when he/she was 2 years old.⁷⁶  The limited evidence from systematic reviews and meta-analyses indicates that n-3 LC-PUFA supplementation or fish consumption during pregnancy can lower the risk of allergy in the child.^77,78  In pooled estimates of data from nine clinical trials, a lowered risk of sensitization to egg and peanut allergy was demonstrated due to n-3 LCPUFA supplementation during pregnancy.⁷⁸  In addition to the reduction in the incidence of atopic eczema, any positive skin prick test, sensitization to egg and sensitization to any food in the first year of life were detected after increased consumption of n-3 LC-PUFA or fish during pregnancy.⁷⁷  Instead, in another meta-analysis, no benefit was evident of fish intake during pregnancy for child allergy outcomes, but consumption of fish during the first year of life reduced the risk of eczema and allergic rhinitis.⁷⁹  It is of importance to acknowledge that dietary fat intake will influence the intake of fat-soluble vitamins, which are also of importance for brain development.⁸⁰  Evidently, the mother's overall diet quality is likely to be of significance with respect to her child's cognitive and behavioral outcomes.⁸¹ 

Infancy, the first year of life, is a period of rapid growth and development and thus the needs for energy and nutrients are high. The nutritional requirements vary but growth patterns are closely linked to nutrition.⁸²  The needs of a newborn in terms of energy are high, 450 to 480 kJ kg⁻¹ per day, being higher in boys due to their higher weight and thereby decline to about 400 kJ kg⁻¹ per day by three months of life and to about 340 kJ kg⁻¹ per day by six months of life.⁸³  EFSA, in its scientific opinion on dietary reference values, estimated that the energy requirement of an infant at six months of age would be 2.3 MJ per day, increasing up to 2.8 MJ per day by 11 months of age.⁶²  The basal metabolic rate accounts for 60 to 70% of the energy requirements during the first year of life. The thermic effect of feeding amounts to 10% of the energy requirements. The energy needed for thermoregulation, i.e. for maintenance of normal body temperature and the energy needed for physical activity are variable; energy is needed more at lower than at higher temperatures and the energy expended on physical activity increases as the infant grows and develops.⁸³  The last element of total energy expenditure is the cost of growth, which is an indicator for the balance between energy supply and demand.

Dietary fats are required for many purposes by the infants.⁸⁴  Fats are the main energy source in the infant diet, they slow gastric emptying and intestinal motility and thus affect satiety, they also facilitate the absorption of fat-soluble vitamins and provide essential fatty acids. Lipids are structural components of tissues and membranes, they are particularly rich in brain, retina, and other neural tissues, and act as precursors for eicosanoids as well as other autocrine and paracrine mediators that play a role in many physiological functions including immune responses. An essential fatty acid deficiency develops soon within 7 to 10 days in infants if adequate amounts are not supplied.⁸²  In addition to the essential fatty acids, LA and ALNA, AA and DHA may also be considered as essential for infants. The blood and tissue concentrations of AA and DHA decrease after birth if they are not supplied via the diet.^85,86  Thus, dietary sources of LC-PUFAs are needed, as the endogenous synthesis from essential fatty acids is not sufficient to compensate for the lack of long-chain fatty acid derivatives from the diet.⁸⁷  In addition, the DHA concentration in an infant's red blood cells is related to that in breast milk but a plateau is reached at breast milk DHA amounts above 0.8% of total fatty acids.⁸⁸  On the other hand, infants have the capacity to convert ALNA to DHA and a rapid phase of DHA accumulation is seen from the last trimester of pregnancy to 6 to 10 months of life.⁸⁹  Regarding many health effects, the focus has been on n-3 LC-PUFAs, but n-6 LC-PUFAs, particularly AA, are also of importance for growth.^90,91  The European Food Safety Authority has set levels for an adequate intake of fats for infants aged 7 to 11 months: ALNA 0.5% of energy intake, DHA 100 mg per day, and LA 4% of energy intake. Furthermore, the total fat intake should be 40% of the energy intake and the intakes of SFA and trans-fatty acids should be as low as possible,⁶²  although the reference values vary between different bodies.⁹² 

Breastfeeding is the natural mode of feeding an infant; it provides not only nutrients but also bioactive molecules that support the maturation of the infant's gastrointestinal tract. Breast milk has many important roles in growth and development, but it also acts as a determinant of current and later health. Breastfeeding has been shown to confer protection from infections and to increase intelligence, and potentially lower the risk of overweightness and diabetes, although the benefit with regard to asthma or blood pressure or cholesterol levels was not demonstrated in a meta-analysis.⁵  Infants, whether born term or preterm, and also those at risk for allergic diseases, do benefit from breastfeeding.⁹³  However, another review of supplementation studies with n-3 LC-PUFAs in doses ranging from 200 mg to 1183 mg during pregnancy and/or lactation was not able to provide solid evidence for benefits with regard to obesity.⁹⁴  Yet another review on randomized controlled trials with n-3 LC-PUFA supplementation, conducted over the past 10 years, did not detect any consistent benefits of supplementation during pregnancy and/or lactation on childhood cognitive and visual development.⁹⁵  Similarly it was concluded in a Cochrane systematic review that supplementation of LC-PUFA during breastfeeding (some studies also included during pregnancy) did not improve the neurodevelopment, visual acuity, or growth of the child.⁹⁶  These investigators found a benefit from only one study with respect to child attention. In contrast, another systematic review and meta-analysis did conclude that n-3 PUFA supplementation for mothers or infants improved childhood psychomotor and visual development.⁹⁷  There are several reasons for the variable results e.g. why some trials have failed to detect positive effects, one being the follow-up time, as the benefits of consuming LC-PUFAs may not be evident in infancy, but may emerge later at 3 to 6 years of age.⁹⁸  It is nevertheless well known that the brain accumulates DHA during both the fetal and early postnatal periods up to two years of life and indeed an adequate supply of LC-PUFAs for the child is important for growth and development.⁹⁹  A recent study using multimodal MRI indicated that infants consuming formula with added DHA displayed improvements in brain structure, signaling, and function at the age of nine years.¹⁰⁰  A Cochrane systematic review of randomized controlled trials evaluated the effects on visual function, neurodevelopment, and physical growth of consuming LC-PUFA supplemented infant formulas, but found no benefits as compared to non-supplemented infant formula.¹⁰¹ 

The majority of the fat in breast milk is present in milk fat globules that contain a triglyceride-rich core and a tri-layer membrane, the milk fat globule membrane.¹⁰²  There is recent evidence indicating that milk fat globules, including the membrane-associated glycerophospholipids, sphingolipids, cholesterol, and proteins, have many biological properties that contribute to the maturation of the newborn's gut and subsequent infant growth as reviewed by Lee and co-workers.¹⁰²  The fat content of the breast milk varies pending on the feeding period, i.e. colostrum, transitional and mature milk, and on each feeding time as well.¹⁰³  The fat content of the colostrum (18 to 24 g L⁻¹) is lower than that of transitional or mature milk (31 to 44 g L⁻¹). The mother's diet also influences the fatty acid composition of her breast milk.^104,105  For example, its fat content as well as the n-3 and n-6 LC-PUFA concentrations are influenced by maternal dietary intakes of foods and supplements. Some evidence also exists that there is a higher concentration of SFA and an elevated n-6/n-3 fatty acid ratio in breast milk if the mother has a higher BMI value.¹⁰⁵ 

Palmitic acid (16:0), oleic acid (18:1 n-9), and LA are the most abundant fatty acids in breast milk.¹⁰⁶  The DHA concentration of breast milk, 0.32%, is less than that of AA, 0.47%, as indicated by data from 65 studies of 2474 women.¹⁰⁷  The concentration of AA appears to be at a relatively fixed level⁹¹  but the concentration seems to vary across countries and regions, with diet being an important source for the differences.¹⁰⁸  In the review of Hadley and co-workers, it was suggested that AA would be critical for infant growth, brain development, and health, and that a balanced intake of AA and DHA is important, as DHA may suppress the benefits provided by AA.⁹¹  Infant formulas and follow-on formulas (from 6 months onwards) aim to mimic breast milk; typically, they also have added AA and DHA to secure optimal fetal development and growth.¹⁰⁹  The supplemented infant formula, as compared to non-supplemented formulas, indeed yield higher concentrations of plasma DHA and AA, but the concentrations of LC-PUFAs are nevertheless higher in breast-fed infants as compared to formula-fed infants.¹¹⁰  Similarly, fish consumption at least three times per week by breastfeeding mothers increased their serum DHA and total n-3 LC-PUFA as compared to non-consumers measured at one month after delivery.¹¹¹  Furthermore, the maternal dietary intakes along with higher serum levels of n-3 LC-PUFAs were related to serum fatty acid levels in one-month-old infants.

Optimally the duration of exclusive breastfeeding lasts for at least four months and preferably the infant is fed predominantly breast milk for more than the first six months of her/his life, with breastfeeding continuing until 12 months of age. Complementary foods should be introduced after four months of age and at six months of age at the latest.¹¹² 

When the infant switches from breastfeeding (or formula feeding) to complementary feeding, the proportion of fats in the diet becomes reduced.¹¹³  Fat intake is still important as a supply of energy during the rapid growth in infancy. The consumption of energy dense complementary foods resulting in a high fat intake may induce excessive weight gain in infancy and this has been associated with later obesity, although this proposal has not been universally accepted, as concluded in a position paper.¹¹²  One recent longitudinal study indicated that a rapid increase of fat mass, as measured by air displacement plethysmograph, during the first six months of life was associated with higher adiposity at the age of two years.¹¹⁴ 

The intakes of LC-PUFAs, including DHA and AA⁹¹  decrease with the onset of complementary feeding and generally the intakes are lower than recommended.¹¹⁵  The dietary supply can increase the circulating LC-PUFA levels as indicated in a trial in which the infants in the intervention consumed a good source of DHA (salmon) compared to a control group (LA-rich corn oil), when the complementary feeding was started. The children in the intervention group exhibited increased erythrocyte and plasma EPA, DHA and total n-3 LC-PUFA levels.¹¹⁶  The fat composition of the infant diet also influenced serum lipoprotein cholesterol concentrations, the higher PUFA and lower SFA intakes may reduce total cholesterol and LDL cholesterol levels, rather than the dietary cholesterol, which may be of importance considering the programming leading to the later cardiovascular disease risk.^113,117 

An adequate supply of energy and all nutrients during pregnancy and lactation and by infants when transferring to the complementary feeding are important to secure the optimal growth and development of the fetus and not to increase the susceptibility from a lifestyle-related disease in both the mother and her child. In particular, the intakes of LC-PUFAs, essential fatty acids LA and ALNA, but also those of AA and DHA during the vulnerable periods of life, are of importance, especially for fetal and infant brain development. Even though the clinical benefit of consuming the LC-PUFAs for many health outcomes is inconclusive, there is convincing evidence for the presence of mechanisms that would lead to beneficial health outcomes. Many dietary intake studies suggest that dietary intakes of LC-PUFAs, particularly n-3 fatty acids, are lower than optimal. The importance of an overall healthy maternal diet^118,119  must be emphasized for providing an optimal environment for fetal and infant growth and development, and for programming towards health² . Equally, it is important to ensure a sufficient supply of LC-PUFAs in the infant's diet when switching from breast milk to complementary feeding.

New research topics in the area include the role that the gut microbiota plays for infant health and nutrition, as the host–microbiota interaction is known to be of major significance for human physiology and health.¹²⁰  It has been claimed that the maternal microbiota already during pregnancy may influence the development of fetal microbiota with consequential effects on his/her health.^121,122  It should be remembered that breast milk contains a pool of microbes¹²³  and, there is an interaction between dietary fats and the gut microbiota,¹²⁴  an interesting topic for further research.