Human Milk Fortifiers for Preterm Infants: Do We Offer the Best Amino Acid Mix?

For preterm and small-for-gestational age infants on enteral nutrition, the best solution is to add human milk fortifier (HMF) to human milk (HM) which is provided by the mother or a milk bank. HMF provides a means to add additional protein, energy, and micronutrients, while maintaining HM as the main source of nutrition. Because of their rapid increase of lean body mass, preterm infants have much higher protein requirements than term infants. Recommendations on protein requirements of preterm infants are available, but protein quality - i.e. the amino acid (AA) profile in HMFs has not been systematically assessed. Present guidelines for enteral nutrition recommend protein intakes around 4 g/kg body weight (BW) for preterm infants <1,500 g, an intake that is not achievable with unfortified HM intakes <200 mL/kg BW/day. It is generally assumed that the AA profile of HM is the best reference for the AA profile of HMF. We calculated advisable intakes of AAs for preterm infants between 400-2,500 g which are based on AA increments of the fetus. Corrections for absorption, inevitable losses, oxidation, and variation of AAs in HM were introduced. Our calculations indicate that extremely low birth weight (ELBW <1,000 g) and very low birth weight (VLBW <1,500 g) infants have substantially higher AA requirements than low birth weight (LBW) infants growing from 1,900 to 2,400 g. In ELBW infants, daily intakes of the different indispensable AAs (IAA) with 4 g of (term) HM protein/kg BW range between 59 and 125% of the respective advisable intakes. Intakes of 7 IAAs and 3 conditionally indispensable AAs (CIAA) are below advisable intakes. On the other hand, with 4 g HM protein per kg BW/day, the IAAs isoleucine and leucine and some dispensable AAs are already supplied in abundance. In VLBW infants, daily intakes of the IAA methionine and 3 CIAAs are still below the advisable intakes. In LBW infants (<2,000 g) receiving 3.5 g HM protein per kg BW daily intakes of 1 IAA and 3 CIAAs would be too low. Preterm infants should receive HMFs which provide adequate amounts of AAs which are needed for their rapid growth and development while avoiding excessive intakes. In particular, very high AA requirements of ELBW infants are a challenge. AA composition of present HMFs for preterm infants should be reconsidered: spiking HMF protein with the AAs which are presently undersupplied or providing targeted AA-based HMF are options to further improve the AA profile in fortifiers.

Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota: A Randomized Clinical Trial.

BACKGROUND: Post-natal gut maturation in infants interrelates maturation of the morphology, digestive, and immunological functions and gut microbiota development. Here, we explored both microbiota development and markers of gut barrier and maturation in healthy term infants during their early life to assess the interconnection of gut functions during different infant formulae regimes. METHODS: A total of 203 infants were enrolled in this randomized double-blind controlled trial including a breastfed reference group. Infants were fed starter formulae for the first four weeks of life, supplemented with different combination of nutrients (lactoferrin, probiotics (Bifidobacterium animal subsp. Lactis) and prebiotics (Bovine Milk-derived Oligosaccharides-BMOS)) and subsequently fed the control formula up to eight weeks of life. Stool microbiota profiles and biomarkers of early gut maturation, calprotectin (primary outcome), elastase, α-1 antitrypsin (AAT) and neopterin were measured in feces at one, two, four, and eight weeks. RESULTS: Infants fed formula containing BMOS had lower mean calprotectin levels over the first two to four weeks compared to the other formula groups. Elastase and AAT levels were closer to levels observed in breastfed infants. No differences were observed for neopterin. Global differences between the bacterial communities of all groups were assessed by constrained multivariate analysis with hypothesis testing. The canonical correspondence analysis (CCA) at genus level showed overlap between microbiota profiles at one and four weeks of age in the BMOS supplemented formula group with the breastfed reference, dominated by bifidobacteria. Microbiota profiles of all groups at four weeks were significantly associated with the calprotectin levels at 4 (CCA, p = 0.018) and eight weeks of age (CCA, p = 0.026). CONCLUSION: A meaningful correlation was observed between changes in microbiota composition and gut maturation marker calprotectin. The supplementation with BMOS seems to favor gut maturation closer to that of breastfed infants.

Iron bioavailability from bouillon fortified with a novel ferric phytate compound: a stable iron isotope study in healthy women (part II).

Bouillon cubes are widely consumed and when fortified with iron could contribute in preventing iron deficiency. We report the development (part I) and evaluation (current part II) of a novel ferric phytate compound to be used as iron fortificant in condiments such as bouillon. Ferric pyrophosphate (FePP), is the compound of choice due to its high stability in foods, but has a modest absorption in humans. Our objective was to assess iron bioavailability from a novel iron fortificant consisting of ferric iron complexed with phytic acid and hydrolyzed corn protein (Fe-PA-HCP), used in bouillon with and without an inhibitory food matrix. In a randomised single blind, cross-over study, we measured iron absorption in healthy adult women (n = 22). In vitro iron bioaccessibility was assessed using a Caco-2 cell model. Iron absorption from Fe-PA-HCP was 1.5% and 4.1% in bouillon with and without inhibitory matrix, respectively. Relative iron bioavailability to FeSO4 was 2.4 times higher than from FePP in bouillon (17% vs 7%) and 5.2 times higher when consumed with the inhibitory meal (41% vs 8%). Similar results were found in vitro. Fe-PA-HCP has a higher relative bioavailability versus FePP, especially when bouillon is served with an inhibitory food matrix.

Micronutrient-fortified infant cereal improves Hb status and reduces iron-deficiency anaemia in Indian infants: an effectiveness study.

Anaemia affects approximately 69 % of Indian children aged 6-12 months, with Fe deficiency (ID) being a common cause. The effectiveness of micronutrient-fortified infant cereal in improving Fe status and neurodevelopment was evaluated in non-anaemic and mildly anaemic Indian infants. An intervention group (IC) enrolled at age 6 months consumed 50 g/d of rice-based cereal providing 3·75 mg Fe/d as ferrous fumarate for 6 months (n 80) and was compared with a matched static cross-sectional control group (CG) without intervention enrolled at age 12 months (n 80). Mean Hb was higher in IC (118·1 (sd 10·2) g/l) v. CG (109·5 (sd 16·4) g/l) at age 12 months (adjusted mean difference: 9·7 g/l; 95 % CI 5·1, 14·3; P < 0·001), while geometric mean serum ferritin tended to be higher (27·0 (-1 sd 13·4, +1 sd 54·4) v. 20·3 (-1 sd 7·5, +1 sd 55·0) ng/ml); P = 0·085) and soluble transferrin receptor was lower (1·70 (-1 sd 1·19, +1 sd 2·43) v. 2·07 (-1 sd 1·29, +1 sd 3·33) mg/l; P = 0·014). Anaemia (23 v. 45 %; P = 0·007) and ID (17 v. 40 %; P = 0·003) were lower in IC v. CG. Bayley Scales of Infant and Toddler Development Third Edition scores for language (P = 0·003), motor development (P = 0·018), social-emotional (P = 0·004) and adaptive behaviour (P < 0·001), but not cognitive development (P = 0·980), were higher in IC v. CG. No significant difference in anthropometric Z-scores was observed between the groups. Consuming a micronutrient-fortified infant cereal daily for 6 months during complementary feeding promoted better Fe status while reducing the risk for anaemia and ID and was associated with superior neurodevelopmental scores.

The bioavailability of iron picolinate is comparable to iron sulfate when fortified into a complementary fruit yogurt: a stable iron isotope study in young women.

PURPOSE: A technological gap exists for the iron (Fe) fortification of difficult-to-fortify products, such as wet and acid food products containing polyphenols, with stable and bioavailable Fe. Fe picolinate, a novel food ingredient, was found to be stable over time in this type of matrix. The objective of this study was to measure the Fe bioavailability of Fe picolinate in a complementary fruit yogurt. METHODS: The bioavailability of Fe picolinate was determined using stable iron isotopes in a double blind, randomized cross-over design in non-anemic Swiss women (n = 19; 25.1 ± 4.6 years). Fractional Fe absorption was measured from Fe picolinate (2.5 mg 57Fe per serving in two servings given morning and afternoon) and from Fe sulfate (2.5 mg 54Fe per serving in two servings given morning and afternoon) in a fortified dairy complementary food (i.e. yogurt containing fruits). Fe absorption was determined based on erythrocyte incorporation of isotopic labels 14 days after consumption of the last test meal. RESULTS: Geometric mean (95% CI) fractional iron absorption from Fe picolinate and Fe sulfate were not significantly different: 5.2% (3.8-7.2%) and 5.3% (3.8-7.3%) (N.S.), respectively. Relative bioavailability of Fe picolinate versus Fe sulfate was 0.99 (0.85-1.15). CONCLUSION: Therefore, Fe picolinate is a promising compound for the fortification of difficult-to-fortify foods, to help meet Fe requirements of infants, young children and women of childbearing age.

Ferrous ammonium phosphate (FeNH4PO4) as a new food fortificant: iron bioavailability compared to ferrous sulfate and ferric pyrophosphate from an instant milk drink.

PURPOSE: The main purpose of this study was to establish bioavailability data in humans for the new (Fe) fortification compound ferrous ammonium phosphate (FAP), which was specially developed for fortification of difficult-to-fortify foods where soluble Fe compounds cannot be used due to their negative impact on product stability. METHODS: A double-blind, randomized clinical trial with cross-over design was conducted to obtain bioavailability data for FAP in humans. In this trial, Fe absorption from FAP-fortified full-cream milk powder was compared to that from ferric pyrophosphate (FPP) and ferrous sulfate. Fe absorption was determined in 38 young women using the erythrocyte incorporation dual stable isotope technique (57Fe, 58Fe). RESULTS: Geometric mean Fe absorption from ferrous sulfate, FAP and FPP was 10.4, 7.4 and 3.3 %, respectively. Fe from FAP was significantly better absorbed from milk than Fe from FPP (p < 0.0001). Fe absorption from FAP was significantly lower than Fe absorption from ferrous sulfate, which was used as water-soluble reference compound (p = 0.0002). Absorption ratios of FAP and FPP relative to ferrous sulfate as a measure of relative bioavailability were 0.71 and 0.32, respectively. CONCLUSIONS: The results of the present studies show that replacing FPP with FAP in full-cream milk could significantly improve iron bioavailability.

Instant coffee with high chlorogenic acid levels protects humans against oxidative damage of macromolecules.

SCOPE: Coffee is among the most frequently consumed beverages. Its consumption is inversely associated to the incidence of diseases related to reactive oxygen species; the phenomenon may be due to its antioxidant properties. Our primary objective was to investigate the impact of consumption of a coffee containing high levels of chlorogenic acids on the oxidation of proteins, DNA and membrane lipids; additionally, other redox biomarkers were monitored in an intervention trial. METHODS AND RESULTS: The treatment group (n=36) consumed instant coffee co-extracted from green and roasted beans, whereas the control consumed water (800 mL/P/day, 5 days). A global statistical analysis of four main biomarkers selected as primary outcomes showed that the overall changes are significant. 8-Isoprostaglandin F2α in urine declined by 15.3%, 3-nitrotyrosine was decreased by 16.1%, DNA migration due to oxidized purines and pyrimidines was (not significantly) reduced in lymphocytes by 12.5 and 14.1%. Other markers such as the total antioxidant capacity were moderately increased; e.g. LDL and malondialdehyde were shifted towards a non-significant reduction. CONCLUSION: The oxidation of DNA, lipids and proteins associated with the incidence of various diseases and the protection against their oxidative damage may be indicative for beneficial health effects of coffee.

Supplementation with 200 mg/day docosahexaenoic acid from mid-pregnancy through lactation improves the docosahexaenoic acid status of mothers with a habitually low fish intake and of their infants.

BACKGROUND/AIMS: The supply of docosahexaenoic acid (DHA, 22:6omega-3), important for fetal/infant neurodevelopment, depends on the maternal fatty acid (FA) status, which may be marginal in central Europe. Therefore, we investigated the effect of a daily vitamin/mineral supplement with and without 200 mg DHA from mid-pregnancy through lactation on the DHA concentrations in maternal and infant red blood cell phospholipids (RBC%), and in breast milk FA (%). METHODS: At 21 weeks' gestation, 144 women were enrolled into a randomised, double-blind clinical trial receiving daily: (1) a basic vitamin-mineral supplement (Vit/Min group), (2) Vit/Min plus 4.5 g fructo-oligosaccharide (FOS group), or (3) Vit/Min plus 4.5 g FOS plus 200 mg fish oil-derived DHA (DHA-FOS group). FAs were determined by capillary gas-liquid chromatography. RESULTS: While maternal RBC-DHA% at enrolment was not different, at 37 weeks gestation, and 3 months after delivery RBC-DHA% were significantly higher in the DHA-FOS group. The breast milk DHA% was twice as high in the DHA-FOS group (0.50%) than in the two others (0.25 %) (p < 0.001), and the ratio ARA/DHA in the DHA-FOS group was 1.0 +/- 0.43, in the others 2.1 +/- 0.43 (p < 0.001). The RBC-DHA% of the infants in the DHA-FOS group was also significantly higher, and correlated significantly with maternal RBC-DHA% before and 3 months after delivery. CONCLUSIONS: In central Europe, a dose of 200 mg/day DHA from mid-pregnancy through lactation seems appropriate to improve the DHA status of mothers and infants.