Polyunsaturated fatty acids in the newborn

Just after birth, intensive building of cellular structures is very sensitive to the amount and nature of fatty acid intake (INNIS, 1991), especially for the brain, whose growth begins during the three last months of fetal life and continues up to the age of 12. The most important model for PUFAs requirements is human milk. Though partially controlled by secretory cells of the mammary gland, the fatty acid composition of milk lipids also depends on diet composition: the “nor-mal” composition for these fatty acids is linked to a well-balanced diet of the mother (INSULL and AHRENS, 1959; HARZER et al., 1983; FERRIS and JANSEN, 1984; HARRIS et al., 1984). Mother’s milk remains the reference on which the definition of newborn requirements is based; this milk contains approximately 3.5% lipids, representing about 50% of total energy intake. Average fatty acid composition is shown in table 17 (TOMARELLI, 1988; GUESNETet al., 1993).

In the newborn, only a limited number of blood components or of physiologi-cal tests (vision, hearing, few cognitive, mental or psychomotor tests) can be used to link dietary intakes to physiological functions. Therefore, the determina-tion of optimal criteria only relies on animal models. However, some authors obtained data from suddenly dead newborns (FARQUHARSON et al., 1995;

MAKRIDESet al., 1994).

Table 17

PUFAs in mother’s milk (%)

According to Tomarelli (1988) According to Guesnet et al., 1993 (France)

Fatty acids Mean Extremes Mean Extremes

18:2 n-6 10.2 7.0-16.0 13,0 6.1-24.1

20:4 n-6 0.5 0.3-0.8 0.45 0.3-0.8

Total LC-PUFAs n-6 1.1 0.7-2.0 1.1 0.8-1.8

18:3 n-3 1.0 0.4-1.5 0.6 0.4-1.2

22:6 n-3 0.3 tr-0.6 0.4 0.1-0.6

Total LC-PUFAs n-3 0.6 tr-1.4 0.5 0.2-0.9

18:2 n-6/18:3 n-3 10.9 9.0-21.0 20.9 7.2-47.3

20:4 n-6/22:6 n-3 1.7 — 1.2 0.6-4.0

LC-PUFAs: = long chain polyunsaturated fatty acids (>18 carbons); tr = traces

3.1.5.1 Linoleic acid

In Western countries, linoleic acid represents about 12-13% of total fatty acids of mother’s milk. This mean corresponds approximately to 400 mg/100 mL milk, or 5.5% of total energy content. It is noteworthy that lino-leic acid content has increased markedly during the past ten years and that individual content is highly variable, strongly influenced by dietary habits and ranging from 7 to 22% of total fatty acids.

Linoleic acid requirements, and thus artificial milk contents, were evaluated from these data (table 18). Practically, the European Society for Pediatric

Gas-troenterology and Nutrition (ESPGAN, 1994) recommends that at least 4.5% of total energy be provided by linoleic acid in milk replacers, or around 9% of total fatty acids. This represents a supply of 2.6 g for 100 g dry matter (AGGETTet al., 1991). Though the effects of an excess in linoleic acid have not been specifically studied — and observing that newborns fed a mother’s milk whose 18:2 n-6 content is the highest observable in human milk (22% of total fatty acids) do not present any pathological symptoms — it is recommended that the linoleic acid content not exceed 11% of total energy (or 22% of total fatty acids).

Table 18

Recommended or regulated intakes for polyunsaturated fatty acids in newborns

mg/100 kcal* % total % milk total mg/100 g milk calories fatty acids dry matter*

Linoleic acid (18:2 n-6)

Minimum 300 2.7 5.4 1,560

(French legislation)

Recommended minimum** 500 4.5 9 2,600

(ESPGAN)***

Recommended maximum 1,200 11 22 6,200

(ESPGAN)

α-linolenic acid (18:3 n-3)

Minimum 50 0.45 0.9 260

(EU legislation)

Recommended minimum** 55 0.5 1 290

(ESPGAN)***

Recommended maximum 165 1.5 3 870

(ESPGAN)

n-6 long chain PUFAs

Recommended minimum** 55 0.5 1 290

including 20:4 n-6 22 0.2 0.4 116

(ESPGAN)

Recommended maximum 110 1 2 580

including 20:4 n-6 55 0.5 1 290

(EU legislation)

n-3 long chain PUFAs

Recommended minimum** 27.5 0.25 0.5 145

including 22:6 n-3 16.5 0.15 0.3 90

(ESPGAN)

Maximum 55 0.5 1 290

with 22:6 n-3/20:5 n-3 >1

NB1: The ratio 18:2 n-6/18:3 n-3 must not be below 5 and should not exceed 15 (European Directive, 16 February 1996). However, a value below 10 is preferable.

NB2: It is recommended that the ratio 20:4 n-6/22:6 n-3 be comprised between 1 and 5.

* for artificial milk containing 13% dry matter, or 67.5 kcal (280 kJ) for 100 mL.

** recommended on the basis of the average composition of human milk fatty acids.

*** ESPGAN = European society of pediatric gastroenterology and nutrition.

3.1.5.2 α-linolenic acid

In most Western countries, α-linolenic acid represents between 1 and 1.5%

of total fatty acid of mother’s milk (only 0.6% in France) (GUESNETet al., 1993), or 0.5 to 0.75% of total energy content. From various published data, ESPGAN recommends an 18:3 n-3 content in milk replacers for newborns ranging from 1 to 3% of total fatty acids (AGGETTet al., 1991) (table 18). The ratio 18:2 n-6/18:3 n-3 is 9 for the minimal supplies and 7.3 for the maximal supplies; however, a ratio ranging from 5 to 15 is admitted by ESPGAN. This is made mandatory by the European directive (Directive, 1996). Some authors (VAN AERDEand CLANDI -NIN, 1993; INNIS, 1993; BILLEAUDet al., 1997) argue for a ratio below 10, as also proposed by others for rats (BOURRE et al., 1990). In addition, a recent study (JENSENet al., 1997) has shown that the growth of newborns fed a formula with a ratio less than 5 was lower than normal. It thus seems that a ratio 18:2 n-6/18:3 n-3 comprised between 5 and 10, at least not exceeding 10, could be recommended.

3.1.5.3 Long chain polyunsaturated fatty acids (LC-PUFAs):

arachidonic acid (20:4 n-6) and docosahexaenoic acid (22:6 n-3)

In addition to precursor fatty acids (linoleic and linolenic acids), mother’s milk contains various long chain derivatives, the most important being DHA and arachidonic acid (KOLETZKOet al., 1992), which respectively represent 0.3-0.4%

and 0.4-0.5% of total fatty acids of mother’s milks in industrialized countries (TOMARELLI, 1988; GUESNET et al., 1993). The average value recommended by ESPGAN for the ratio 20:4 n-6/22:6 n-3 is 1.3.

Yet, milk replacers are generally only made with precursor PUFAs. Nume-rous studies have shown that, in newborns fed milk replacers, contents in 20:4 n-6 and 22:6 n-3 of plasma or red cell phospholipids are always lower than those observed in breast-fed babies (GUESNET and ALESSANDRI, 1995). These differences are observed as well in premature newborns as in those born at term. They appear as early as 15 days after birth (KOHNet al., 1994) and persist until one year of age (AUESTAD et al., 1997), although children receive a mixed diet after 4 months. The deficiency is generally more pronounced for DHA than for arachidonic acid (FARQUHARSONet al., 1995; MAKRIDESet al., 1994), even if α-linolenic acid level is increased to 2.5% of total energy content of the diet.

This suggests that, if the newborn is able to elongate and desaturate precursor PUFAs, as recently shown by studies using precursors labeled with stable iso-topes (DEMMELMAIR et al., 1995; CARNIELLI et al., 1996; SALEM et al., 1996;

SAUERWALD et al., 1996), this capacity remains insufficient as compared to requirements, as it was previously suspected (PUTNAMet al., 1982). From stu-dies in rats (GUESNET et al., 1995) and newborns (MAKRIDES et al., 1996), the optimal amount of DHA ranges from 0.7 to 1% of total milk fatty acids.

Though there are still controversies about physiological consequences of the absence of supplemental LC-PUFAs in milk replacers, ESPGAN recommends that infant milks be supplemented with these fatty acids, in proportion similar to those determined in Western mother’s milks (AGGETTet al., 1991). Since 1996, the European Directive 94/4/CE (Directive, 1996) allows their addition in foods for babies, with a maximum of 2% for total LC-PUFAs, including 1% for arachi-donic acid and 1% for total n-3 LC-PUFAs, the content in 22:6 n-3 being higher than or at least equal to that of 20:5 n-3 (table 18).