FAs are carboxylic acids with a carboxyl group at one (alpha end) and a methyl group (omega end) at the opposite end. Almost all naturally occurring FAs hold the double bonds in the cis configuration, where the hydrogen atoms on the double bond are on the same side of the molecule, causing a bend in the chain, while in trans isomers the hydrogen atoms are on opposite sides of the molecule. This results in a more stable and rigid chain, making it comparable to saturated fatty acids (Figure 1) (3, 26).

TFAs can be formed through industrial processes or naturally. iTFAs are created during food preparation at high temperatures or through partial hydrogenation of vegetable oils, which involves high temperatures, high pressures, and a catalyst. In this process, polyunsaturated fatty acids (PUFAs) undergo partial saturation of their double bonds to decrease melting point. Additionally, some double bonds in cis configuration are converted to a trans configuration. Several different mono-and polyunsaturated trans isomers can be formed as a result, with the double bond positioned at delta-6 or higher. However, the most prominent ones are the monounsaturated trans isomers of C18. Elaidic acid (EA, C18:1n-9 t), which is the geometrical isomer of oleic acid (C18:1n-9), has the highest prevalence in iTFAs. The most prevalent polyunsaturated TFA is linoelaidic acid (C18:2n-6tt), which is the trans isomer of the essential n-6 linoleic acid (LA, C18:2n-6) and the trans double bonds are in the delta-9 and delta-12 positions (3, 27).

In contrast, rTFAs are formed in the rumen of ruminants through microbial fermentation and biohydrogenation. Although the trans double bonds in rTFAs may be in a similar position to those in iTFAs, the probability of formation and frequency of occurrence differ. The most prominent rTFA is trans vaccenic acid (VA, C18:1n-7), which has a double bond in the delta-11 position. Moreover, ruminants also produce a group of conjugated linoleic acid (CLA), in which the double bonds are conjugated. This means that there is only one single bond between the two double bonds. The most prevalent CLA is rumenic acid (RA, C18:2n-9c7t) (28). Not only the position of the trans double bond can differ between the iTFAs and rTFAs, but also their concentration in foods. The concentration of iTFAs in products can reach up to 50% of the total fatty acids, whereas rTFAs in ruminant milk are typically found in much lower concentrations, usually around 4–6% of the total fatty acids. The most common TFA isomers are listed in Table 1 with their names and origin.

Dietary TFAs can be absorbed from the small bowel, incorporated into serum triacylglycerols (TGs) and structural lipids, and stored in adipose tissue (29, 30). However, TFAs are preferentially incorporated into TGs and phospholipids (PLs), and to a lesser extent into cholesterol esters (31). There may also be differences in tissue incorporation, for example, delta-9 and delta-11 C18:1 t TFAs are incorporated into tissues to a greater extent than other positional trans isomers (32). However, this incorporation is not irreversible, but rather dynamic, so that when dietary intake of TFAs decreases, they are released from membranes. The trans double bond is recognized by enzymes in a similar way to the saturated bond, so EA can be incorporated into phospholipids at the expense of saturated fatty acids (e.g., stearic acid), or cis-9, cis-12, trans-15 C18:3 can be incorporated into cardiolipins instead of LA (33). The effect of TFAs in membranes is similar to that of saturated FAs, because they both have a more rigid structure than cis unsaturated fatty acids, so they both decrease membrane fluidity and therefore the affinity of molecules for receptors.

TFAs have been associated with a number of adult diseases and consequent death cases, such as atherosclerosis, cardiovascular disease and mortality (34, 35), and cancer (36). Animal studies have indicated that TFAs may inhibit the activity of the Δ-6 desaturase enzyme, disrupting the production of omega-3 and omega-6 LCPUFAs (Figure 2) (37). This interference may have significant effects on newborns as the activity of these enzymes is required for the synthesis of LCPUFAs (38, 39). As a matter of fact, the presence of TFAs in milk may cause an insufficient supply of essential fatty acids (EFAs) in both HM (38, 40) and infant blood (39). Some TFAs can also be metabolized in the body, for example, the human body can synthesize RA from VA in healthy adults (41), and also in lactating women (42).

The de novo synthesis of LCPUFAs is rather limited and therefore, infant levels of these FAs depend primarily on maternal dietary intake (43). In contrast, TFAs cannot be synthesized within the body and are entirely dependent on maternal diet. Therefore, a high concentration of TFAs could potentially have a negative impact on the supply of LCPUFAs due to direct competition with metabolic enzymes. It is important to note that there is a positive correlation between the concentrations of most FAs, including TFAs, EFAs, and LCPUFAs, in HM, and their corresponding levels in the infant’s plasma, highlighting the significance of HM in the dietary intake of these FAs (9). On the other hand, the significant inverse relationship between the concentrations of TFAs and EFAs (LA and α-linolenic acid [C18:3n-3, ALA]) in both preterm (44) and term HM (9, 45) suggests a restrictive effect of TFAs on the EFA supply. These results support the need to ensure adequate EFA supply to infants by increasing EFA intake in the maternal diet on the one hand and by limiting TFA consumption on the other.

HM is the best option for infants in the first months of life (46) and therefore exclusive breastfeeding is recommended until the 6th month of life (15). Fat in HM is the primary source of energy (47), while selected FAs, as well as crucial fat-soluble vitamins are essential for the development of infants (48, 49). The FAs of HM are either synthesized in the mammary gland (MG) or derived from plasma FAs that originate from lipid reserves, non-mammary tissues, or diet (47). Depending on the mother’s intake, the concentration of FAs in HM is influenced by the type of diet prevalent in the area where the mother lives (11, 50–53). Therefore, a well-balanced diet is beneficial to both the mother and the breastfed child throughout the period of breastfeeding (54).

Maternal reserve capacity and the metabolic utilization of FAs (transport, synthesis, and oxidation) are directly related to FA levels during lactation (55). It has been estimated that between 60 and 70% of the fat in HM is derived from tissue synthesis and maternal fat deposits, while approximately 30% is derived from the diet of the mother (40, 50). This suggests that maternal diet, as well as the metabolism of FAs during lactation appear to be the most important factors that influence DHA concentration in HM (56). Additionally, the composition of fats in HM undergoes continuous change due to the rapid transport of dietary fats from chylomicrons. This process results in a peak occurring within 6 to 12 h after dietary DHA intake (55). Isotopic studies show, that about 30% of dietary LA intake is directly transferred to HM, but only a maximum 3% is converted and transferred as AA (57, 58). Although approximately 65% of HM ALA is derived from maternal dietary ALA intake, the low efficiency of conversion to its longer-chain metabolites and transfer to HM means that dietary ALA plays a negligible role in the eicosapentaenoic acid (C20:5n-3, EPA) and DHA content of HM (59).

TFAs cannot be synthesized de novo by the human body (60), so their exclusive sources are dietary intake. Ruminant animals naturally produce rTFAs through a process known as biohydrogenation in the rumen. Therefore, meat, milk and dairy products from ruminant animals (cattle, sheep, and goats) are the primary sources of rTFAs in the human diet. Conversely, iTFAs are primarily formed during the hydrogenation of vegetable oils during industrial processes of hardening and deodorization, so iTFAs are primarily consumed through PHOs and food products that contain them, including confectionery and food concentrates, but a small amount of iTFAs are also produced during the thermal processing of food, such as baking or frying (61, 62). The main iTFA present in the food supply is EA (27), which has been detected in larger proportions in HM (38, 40, 63, 64), but other iTFAs, like linoelaidic acid, have also been reported (40, 50, 63, 64). The most prevalent rTFA, found in milk, butter, and beef fat, is VA (26, 27), which has also been detected in HM by several research groups (40).

Based on reported data worldwide, rTFA intake from ruminant products, including meat, milk, and butter, constitutes a small, but constant portion of total TFAs, while the percentage of iTFAs derived from processed foods, bakeries, snacks, and fast food is continuously declining in most countries (65, 66). Bakery products, confectionery, and snack foods accounted for the majority of TFAs in the diets of breastfeeding women on a typical Western diet (11, 67) as well as on a Mediterranean diet (38). Moreover, maternal diet influences the HM TFA concentration with a significantly lower value (0.44%) in vegan compared to vegetarian (0.66%) and omnivorous (1.09%) lactating women (52). Previous studies have analyzed the fatty acid composition of various food categories containing TFAs. In general, older studies reported higher iTFA values, resulting in higher total TFA content in these foods. In a study conducted in Sweden (68), the total TFA content in certain foods was as high as 3.83 w/w% (digestive biscuits) during the period of 1995–1997. In contrast, Germany had even higher total TFA values in 2007–2009 (27): the highest levels were found in certain chocolate products (0.05–40.46 w/w%), doughnuts (0.14–35.11 w/w%), French fries and chips (0.12–16.30 w/w%), and biscuits (0.04–10.66 w/w%).

Considering the detrimental impact of iTFAs on human health, the European Food Safety Authority (EFSA) advises that TFA intake should be restricted to the lowest achievable level in a nutritionally balanced diet (69, 70). Accordingly, the World Health Organization (WHO) recommends limiting consumption of iTFA to less than 1% of daily energy intake to prevent chronic diseases, due to scientific evidence demonstrating its harmful effects (71, 72). Several studies have also examined the impact of regulatory or voluntary restrictions on the total TFA content in various food groups. In Spain, certain products, such as chocolate-stuffed Swiss rolls (1.47–11.85 w/w%), doughnuts (8.47–10.89 w/w%), and chocolate-filled sponge cake (0.6–9.12 w/w%), had high TFA content due to their high iTFA content in 1999 (73). However, the values greatly decreased after regulation by 2010 and further decreased by 2015 (74), e.g., in confectionary and pastry products (2010: 0.657 w/w%; 2015: 0.034 w/w%), chocolate products (2010: 0.721 w/w%; 2015: 0.14 w/w%), and biscuits (2010: 0.311 w/w%; 2015: 0.008 w/w%). By contrast, the TFA content of mainly rTFA-containing products, such as dairy products, remained quite stable. For example, butter had a TFA content of 2.356 w/w% in 2010 and 2.452 w/w% in 2015, while spreadable cheese contained 2.646 w/w% and 2.524 w/w% TFA, respectively. Similar trends were observed in Sweden with the highest total TFA values in 1995–1997 and really low values in 2007 (68) as well as in Argentina (75) and Korea (76). Table 2 summarizes the total TFA values of various food groups based on recent measurements in Thailand (77), Egypt (78), Argentina (75), Spain (74), Jamaica (79) and Malaysia (80). Previous research has shown that both voluntary and regulatory measures to reduce iTFA content in foods have resulted in substantial reductions in global intakes of TFAs over the past two decades (61, 81, 82), including Canada (83) and the European Union (EU) countries (84). The estimated intake of TFAs in 2010 varied widely from 0.2 E% (Barbados) to 6.5 E% (Egypt) (82), while seven years later, intake was lower, ranging from 0.3 E% (China) to 4.2 E% (Iran). In addition, the average intake was below the maximum recommended intake of 1 E% in 22 out of the 29 countries (61). According to the most recent study, TFA intake was below 0.8 E% in most regions across the world, with the highest reported intake in North-, Central-, and Latin America, with levels ranging from 0.8 E% to 1.2 E% (85).

Maternal diet-derived TFAs can be transferred directly to HM (86). Based on the dietary sources and intake of TFAs, HM contains varying levels of TFAs across different populations and regions of the world (87). This systematic literature review found the highest TFA values in North America (6.99 [5.01–8.98]; mean [95% confidence interval for mean]), followed by South America (2.36 [1.14–3.58]), Europe (1.82 [1.61–2.03]) and Oceania (1.21 [1.19–1.23]), and the lowest values in Asia (0.71 [0.65–0.78]) and Africa (0.61 [0.55–0.67]). However, it is also important to consider that the TFA of HM is also dependent on the time of analysis. Higher values were reported in the literature prior to the implementation of the iTFA regulation. For instance, a Canadian study (83) investigated the effect of regulation on the TFA content of HM samples and found that the high values reported before regulation (7.2 ± 0.3% in 1992) were significantly reduced (1.9 ± 0.5% in 2011).

In the literature we can find a wide variety of TFA levels in HM among different populations (Supplementary Tables S1, S2), which range from the highest level in Iranian (88), Canadian (45, 89), and American (90) to the lowest level in Greek (91), Chinese (92) and Latvian lactating mothers (93). However, when dividing the literature into two groups based on the time of the study, it becomes apparent that the studies reporting very high levels of total TFAs are older, probably prior to the TFA regulation (Figure 3A). Total TFA values of 3% or more are exclusively found in studies published in 2010 or before (86, 88–90, 94–96), while very low TFA values of less than 0.5% are found in articles published both before (92, 97) and after 2010 (52, 91, 93, 97). However, this 2010 cut-off date is somewhat arbitrary, as the TFA legislation was adopted at different times around the world. It is worth noting that prior to 2010, neither Iran nor Kuwait had regulations on the TFA content of food, although Kuwait (98) had significantly lower levels of TFA in HM compared to Iran (88). According to WHO, only seven countries had best-practice TFA policy before 2017, including Denmark (since 2004), Austria (since 2009), Chile, Iceland, South Africa (all three since 2011), Hungary and Norway (both since 2014). In 2018 this best-practice TFA policy was implemented in Canada, Latvia, Slovenia, and USA, in 2019 in Lithuania and Thailand, and 2020 in Saudi Arabia also (99). Considering the increasing number of countries applying the regulation, it is expected that the amount of TFAs in HM will decrease further. However, the intake of rTFA remains constant, resulting in no change in the VA content of HM between before and after 2010 (Figure 3B).

The FA composition of HM, including the TFA content, can be influenced by several factors. One of these may be ethnicity, which probably leads to differences in HM TFA content due to distinct dietary habits. For example, in a Czech study, Roma women had significantly higher mean C18:1 t levels in their HM than the average Czech population (2.73 ± 1.88 vs. 2.09 ± 1.24; w/w%, mean ± SD). The difference was explained by the higher consumption of foods with higher TFA content among Roma women, including buns, biscuits, butter, hamburgers, potato chips, and other fried food (96). This was also corroborated in an Asian study, where Chinese women on a Western-style diet had significantly higher TFA levels in their HM compared to lactating women on a traditional Chinese diet (92, 100). Similarly, different C18:1n-9 t values were found in an African country, Nigeria, when comparing the HM of urban and nomadic people (0.08 ± 0.07 vs. 0.03 ± 0.02, w/w%, mean ± SD), although no significant difference was found for most of the measured TFA values (97). However, if there is no difference in dietary habits, then ethnicity alone has no detectable effect on the amount of TFA in HM (63, 101). A Polish study found that EA values in HM was not significantly influenced by body fat, maternal BMI, health problems or n-3 LCPUFA supplementation (102).

When examining groups with differing ethnicities and geographic locations, even larger differences can occur. In HM samples from German mothers on a Western-style diet, significantly higher TFA levels were found in almost all measured TFA isomers compared to Nigerian mothers still on a traditional diet [C14:1 t 0.19 vs. 0.04, p = 0.0009; C16:1 t: 0.46 vs. 0.27, p = 0.001; C18:1 t 3.12 vs. 0.86, p = 0.0017; sum of TFAs: 4.40 vs. 1.20, p = 0.0012; w/w%, median (103)]. Similarly, large differences were measured in the TFA content of HM between US women on a Western-style diet (high in iTFAs) and Bolivian forager-horticulturalists (iTFA-free, but containing rTFAs); C18:1 t was about six times higher than in Bolivia [1.23 ± 1.05 vs. 0.21 ± 0.30; w/w%, mean ± SD (104)]. Although TFA regulation in recent years has resulted in much lower TFA intakes worldwide, it seems that Western-style diets still result in higher TFA intakes compared to traditional diets (sum of TFAs: Australia: 1.21 vs. Cambodia: 0.30; w/w%, median, p < 0.001) (105). Moreover, the different dietary intakes of mothers living in different countries can significantly affect not only relative but also absolute TFA concentrations in HM, as demonstrated in an Asian study (C18:1 t: China: 84.0 ± 468.3, South Korea: 5.9 ± 21.6; Pakistan: 433.6 ± 438.5, Vietnam: 31.4 ± 44.0; mg/l, mean ± SD) (106).

The exclusive source of TFAs in HM is the dietary TFA intake, as discussed previously, therefore, dietary intake of both rTFAs and iTFAs can affect the total TFA content of HM. Mothers who follow a vegan diet, excluding meat, eggs, and dairy products (including milk) have significantly lower levels of TFAs in their HM samples compared to those who follow a vegetarian diet (including dairy products and eggs) or an omnivorous diet (52). There was a positive correlation between higher consumption of eggs or meat and higher levels of TFAs in HM (93). In contrast, diets high in grains, cereals, vegetables, legumes, nuts, and seeds resulted in a low TFA intake, and therefore, in lower TFA values in HM. Not only VA but EA and total TFA were directly associated with maternal milk and dairy intake (107). In Croatian mothers, the consumption of bakery, confectioners, fried foods, dairy products, margarine, and sausages was significantly directly related to the TFA content of HM (38). In Polish mothers, only a high intake of bakery products and snacks (rich in iTFAs, as EA) increased HM total TFA content significantly (67). High dairy fat intake (rich in rTFAs, as VA), on the other hand, can lead to a significant increase in VA content in HM (86). However, in Malaysian mothers with low TFA intakes (1.27 g/day), neither a healthy dietary pattern rich in vegetables and fruits nor frequent consumption of unhealthy deep-fried foods or eating out affected the EA and total TFA content of HM (108). In Brazilian adolescents with somewhat higher daily TFA intake (3.07 g/day), also no correlation was found between dietary intake and HM TFA contents (40). In an experimental study, a high-TFA diet given to lactating women significantly increased C18:1 t in HM samples collected as early as day two compared to the control group, demonstrating that dietary TFA is excreted into HM very rapidly, within 24 h of consumption (109).

It is a well-known fact that fat content, and the concentration of FAs in HM varies over time, depending on the lactation stage and several factors can influence its values, like gestational age at delivery, maternal diet and time of sampling (46, 110). Not only the physiologically important PUFAs, but TFAs can also change depending on the lactation stage (Table 3). The total TFA values in the literature range from 0.19 [mean w/w% (92)] to 3.81 [mean w/w% (95)] in C, with the lowest value in mothers with a traditional Chinese diet and highest value in German mothers with Western-type diet. Previous studies have reported varying results regarding the levels of TFAs in HM during lactation. Some studies have shown a significant decrease in TFA levels over time, with the highest values observed in the C (40, 111, 112, 114, 115), while others have reported a similar trend, but without statistical significance (44, 91). In contrast, some research groups have found opposite results, with the lowest TFA values measured in C increasing over time (67, 92, 116), or showing an initial decrease followed by a non-significant increase (113). Interestingly, in a Spanish study, the highest C18:1 t values were only found in very-preterm and preterm HM that was significantly decreasing over lactation, but they failed to show this trend in the term group (117). A decrease in TFA content may also be associated with the duration of lactation, as the maternal diet becomes more balanced and diverse throughout breastfeeding (107). Since there is no clear change among TFA levels in C, TM, and MM, this raises the possibility of other factors that could also influence TFA levels in HM (47, 89).

Due to the different nutritional needs and metabolic capacities of preterm and term infants, the TFA content in HM may differ. It is essential that preterm infants receive higher amounts of some LCPUFAs, specifically DHA, in order to grow and develop at their optimal level (118). Consequently, preterm HM contains a higher concentration of DHA and other n-3 fatty acids compared to term HM (119–121) although other studies show no difference (43, 122, 123). However, preterm HM, may also contain higher levels of TFAs than term HM, which could potentially interfere with the metabolism and absorption of n-3 fatty acid (46). Although there have been few studies investigating the differences between TFA levels in preterm and term milk, the results are inconclusive. Some papers report no difference between the two groups (122, 124), while others have found higher levels in C in preterm infants (119), or even lower values during the first month of lactation (117) or only in MM (123). A systematic review summarizing EA values in preterm and term milk during lactation found lower values in the preterm group (preterm – C: 0.39 ± 0.02, TM: 0.26 ± 0.03; MM: 0.35 ± 0.04 vs. term – C: 1.95 ± 0.02, TM: 1.13 ± 0.02, MM: 1.16 ± 0.27; weighted least squares mean ± SEM), however, it should be noted that preterm data were based on a much smaller group of studies and included participants, so further studies are needed to demonstrate whether there is a difference between these two groups (125).

LA and ALA cannot be synthesized in the human body, and therefore, they are called EFAs. They can be further metabolized into their longer-chain metabolites, where AA is formed from LA, while EPA, and DHA are formed from ALA (Figure 2) (126). This metabolic process takes place within the hepatic endoplasmic reticulum through the action of desaturase and elongase enzymes, with LA and ALA competing for these enzymes (127). Although humans can convert ALA to its longer-chain metabolites (including EPA and DHA), this conversion efficiency is rather limited, being highest in the perinatal period and decreasing to about 1% by adulthood (128). Due to this fact, DHA in the maternal diet provides a much more efficient source of DHA for the developing fetal and neonatal neural tissue than equivalent amounts of ALA (129).

Animal studies have shown that TFAs can inhibit the activity of the Δ-6 desaturase enzyme, which is involved in the metabolism of PUFAs, and thus TFAs may affect the availability of longer-chain n-3 and n-6 metabolites. As n-3 and n-6 LCPUFAs play an important role in perinatal life, including the maturation of the nervous system and the development of visual acuity, TFAs may negatively affect this process. An indirect sign of this disturbed metabolism can be the relationship between TFA and LCPUFA values. Previous studies found inverse associations between TFAs and the most important n-3 and n-6 LCPUFAs in blood lipids of pregnant women during pregnancy (130) and in term newborns at delivery (130–132). This suggests that there may also be a correlation between TFAs and PUFAs in HM. Although only a relatively small number of studies have examined this relationship, most of them have found inverse associations between these FAs.

EA values correlated inversely to LA in C (r = −0.670, p < 0.001), and to AA in MM (r = −0.364, p < 0.05), while there was a strong positive correlation with ALA values in C (r = +0.844, p < 0.001) and TM samples (r = +0.844, p < 0.001), but not in MM. In contrast, DHA values were significantly inversely correlated to EA in C (r = −0.422, p < 0.05), but directly in TM (r = +0.615, p < 0.001) samples, while in MM no significant correlation was found (111). An early study found an inverse association between C18:1 t values and both LA (r = −0.29, p < 0.0001) and ALA values (r = −0.25, p < 0.001), but not with their longer chain metabolites, AA, EPA, or DHA in Canadian mothers (89). In contrast, a decade later, no association was found between C18:1 t and EFAs (LA, ALA) in American HM (90). However, studies investigating European lactating women found significant negative correlations between C18:1 t and LA, AA, ALA, and EPA values at the 6th week (63), 3rd month (38) and 6th month of lactation (133), but DHA values were only inversely correlated to C18:1 t values at the 6th week (63), 3rd month of lactation (38).

Some studies also investigated the relationship between the total TFA content of HM samples and the PUFA values. In C, significant negative correlation was found between total TFA content on the one hand and essential n-6 LA values on the other hand (44, 111), while no clear relationship was found with the other n-3 and n-6 PUFA values (Table 4). One study found no significant correlations with AA, ALA, EPA, and DHA values (44), while the other study found significant positive correlations were found with AA, ALA, n-6 LCPUFA and n-3 PUFA values and negative correlations with DHA (111). In contrast, only one study investigated the relationship in TM (111) and found a significantly positive relationship between on the one hand TFA and on the other hand ALA, and DHA values. MM showed the clearest correlations: total TFA was significantly negatively correlated with LA in all studies (9, 38, 44, 63, 111, 133), while AA (38, 63, 111, 133), ALA (9, 38, 63, 133), EPA (38, 63), and DHA (38, 63) were significantly negatively correlated with TFA values in most studies, and only one study found a significant positive correlation with ALA, EPA, and DHA (111). In contrast, in American mothers no correlations were found between total or individual TFA values and the LA, ALA, n-3, and n-6 PUFA values (90).

Thus, the results so far suggest that TFAs may interfere with the metabolism of n-3 and n-6 PUFAs in HM during lactation, but the paucity of studies and conflicting results for some FAs suggest that further large-scale studies are needed to establish the actual relationship.

Ethical considerations have played a decisive role in the preference for animal studies over human studies when investigating the effects of TFAs in milk on infant health. The use of animal models, such as rats, mice or pigs allows researchers to investigate the effects of TFAs on infant health without exposing human infants to potential risks.

Animal models can also be used to study the effects of dietary TFA intake during pregnancy or lactation and its incorporation into maternal tissues such as the MG. In a rat experiment, high TFA intake during the early stages of pregnancy (until day 12), resulted in TFAs accumulating in maternal adipose tissue and MG and mobilizing from these stores despite a subsequent (after day 12) TFA-free diet and appearing in maternal, fetal and neonatal plasma samples. Moreover, these previously stored TFAs were distributed to the MG, making them available to the suckling offspring (145).

Dietary TFA intake during lactation is mainly accumulated in maternal liver tissues and MG and is also excreted in milk, where it limits the availability of EFAs to suckling offspring. Maternal TFA supply mainly increased MG lipoprotein lipase activity in a dose-dependent manner, with a less pronounced effect in the liver and no effect on adipose tissue suggesting that these two factors (TFA storage and increased lipoprotein lipase activity in the MG due to TFA) may underlie the higher TFA content in milk samples (146). A study conducted on animals reported that a diet rich in TFAs during lactation and after weaning had an impact on the FA supply of newborn piglets. At 3 days of age, their plasma levels of AA and docosapentaenoic acid (C22:5n-3, DPA) were significantly lower. Furthermore, the consumption of a TFA diet affected the composition of aortic PL FAs. At 3 days of age, it increased LA values and at 48 days of age, it increased C18:1 t and LA values, but decreased AA, EPA, and DHA values (39). Therefore, high maternal TFA intake during lactation can not only influence the plasma fatty acid concentration of their newborns, but also incorporate TFAs into their cells, potentially disrupting the metabolism of EFAs into their longer chain metabolites, AA, EPA, and DHA.

Due to ethical considerations, human studies, contrary to animal studies, are not supplementation studies, but rather determine maternal TFA intake and/or HM TFA content and investigate their effects in early or late childhood. However, compared to animal studies, far fewer studies have examined these effects. As discussed above, the total TFA content of HM has been studied in several countries over lactation, in different ethnic groups, and in HM of preterm and term newborns. As previously stated, the largest portion of HM’s total TFA content is attributed to EA. Therefore, the adverse effects of HM’s total TFA content on infant development are primarily due to its iTFA content. Any potential beneficial effects of rTFA are discussed separately in the text.

Several studies have examined the relationship between maternal plasma TFA levels during pregnancy or at delivery and key pregnancy outcomes, including gestational age at birth, birth weight, and fetal head circumference. Higher maternal TFA levels in plasma may be associated with a shorter gestation period (138, 141), reduced birth weight, and small for gestational age at birth (159). A systematic review and meta-analysis (160) found three studies about the inverse correlation between maternal TFAs during pregnancy and birth weight, while one study did not find any association. Moreover, the cord erythrocyte C18:1 t value, which is a better indicator of the newborn’s supply, may also be inversely associated with birth weight (142). Higher maternal TFA levels during pregnancy may be related to lower fetal head circumference, but prenatal TFA exposure did not seem to affect global brain volume or nonverbal IQ in children (144). By contrast, neither cord plasma TFA (138) nor cord erythrocyte membrane C18:1 t (142) influenced head circumference at birth. From these studies, we can conclude that there might be a disturbing effect of maternal and neonatal TFA supply during pregnancy or at delivery on the infant development, but the effect of TFA intake through HM is a less researched topic and only a few studies can be found about short-and longer-term effects.

Maternal consumption of TFAs greater than 4.5 g/day during lactation appears to increase the odds ratio of higher percent body fat in both mothers (odds ratio: 5.81) and their 3-month-old infants (odds ratio: 2.13) for body fat percentages of 30% or greater in mothers and 24% or greater in infants (161). This study suggests that consuming TFAs during lactation may affect the body composition both mother and infant in the early postpartum period, potentially contributing to childhood and later obesity. However, no such relationship was found in Nigerian mothers regarding HM TFAs and maternal anthropometric values (97).

In a large birth cohort study (n = 1,369) maternal TFA intake during the second trimester was associated with higher fetal growth (162). In contrast, in a Norwegian birth cohort study (n = 789) no association was found between TFA content of HM samples and infant growth or rapid infant growth (163).

Although there were some correlations between maternal TFA supply during pregnancy and neonatal birth dimensions as discussed above, no relationship was found between TFAs in HM and head circumference, gestational age, and birth weight in term (40) as well as weight and height of preterm infants (44).

Animal studies, as discussed above, suggested an increased low-grade inflammation in those offspring that had higher TFA exposure during weaning (mainly iTFA, like EA), which might lead to an increased risk of developing allergies in infancy or childhood. However, rTFAs, like RA, and VA might be preventive. Increased concentration of both RA and VA in HM was correlated with a lower risk of eczema, atopic dermatitis, and allergic sensitization at one year of age, which was largely independent of HM n-3 LCPUFA values (164). Increased maternal VA-levels during pregnancy decreased the risk of atopic eczema in one-year-old children, but no other associations were found with other TFA values (165). Similarly, in children of mothers with allergy HM TFA content was associated with a significantly decreased odds ratio (OR: 0.57 95%CI: 0.33–1.00) of eczema at the age of four years, although no information is available, on whether these TFAs were iTFAs of rTFAs (C18:1 t, C16:1n-7 t, C18:2n-6 t) (166). By contrast, no relationship between maternal TFA intake during pregnancy and cow’s milk allergy in their three-years-old children was found (167).