Human milk feeding improves long-term neurocognitive development 39 — 41 and cardiovascular health outcomes Studies comparing solely donor human milk vs.
That is why HM is the recommended feeding for all neonates including premature infants. When mother's milk is not available, pasteurized donor human milk DHM should be used. Infants born early in the third trimester miss the placental transfer of nutrients which would create stores for use in the postnatal period. The main challenge is to meet the high and variable nutrient requirements of these preterm infants during the whole hospitalization period.
Insufficient nutrient intakes place the infant at risk of impaired neurodevelopment. To prevent EUGR, which is associated with poor neurocognitive outcome, and to avoid specific nutrient deficiencies, nutrient fortification of HM is necessary 19 , 29 , 42 — The consequences of intakes falling short of requirements vary from nutrient to nutrient. Evidence suggests that inadequate intake of protein is important for slow growth and it is particularly responsible for decreased fat-free mass FFM gains which are directly related to poor neurocognitive outcomes 14 , Intake of energy is also clearly important.
In a single blinded randomized clinical trial, Bellagamba et al. Insufficient intake of some nutrients leads to specific deficiency states, such as osteopenia due to insufficient intake of calcium and phosphorus and to various micronutrient deficiencies, such as zinc deficiency. It is important that VLBW infants receive adequate amounts of iron, zinc, copper, selenium, and iodine.
The need of fortification is less clear with regard to manganese, chromium, and molybdenum For the great majority of other nutrients, small shortfalls may have less serious effects, especially when they are temporary.
With protein however, any shortfall is prone to affect growth and carries the risk of neurocognitive impairment. Thus, protein supply needs special attention in early life and meeting the requirements should be the goal 43 , Nutrient requirements of preterm infants are defined as intakes that enable the infant to grow at the same rate as a fetus Requirements for most nutrients have been derived from accretion rates of protein, fat and minerals obtained by the analysis of fetal body composition at various stages of gestation 44 , 50 , Additionally, empirical methods have been employed to define requirements including those for nutrients such as vitamins 44 , 51 Tables 1 , 2.
Therefore, HM fortification needs to be adapted to the specific needs of each infant at each time. Table 1. Requirements for protein and energy; best estimates by factorial and empirical methods Table 2. Requirements for major minerals and electrolytes determined by factorial method, listed by body weight This table comprises the recommendations of the experts and expert panels 50 , 52 , Table 3.
Recommended enteral protein and energy intakes for clinically stable very low birthweight infants 50 , 52 , There are a number of products available for fortifying human milk for preterm babies which differ by the origin of milk used bovine, human or donkey , and by nutrient composition multi-nutrient fortifiers or supplements of protein, lipids, carbohydrates. Bovine-based multi-nutrient fortifiers contain varying amounts of protein, energy, minerals, trace-elements, vitamins, and electrolytes Table 4.
The addition of lipids to multi-nutrient fortifiers with a concomitant reduction in carbohydrate content has allowed a reduction in osmolality of these products In addition, lipids provide a source of essential fatty acids EFA which has been shown to improve EFA status in preterm infants As indicated, standard fortification using previously available products was unable to support a satisfactory postnatal growth See Current Fortification Practices in Neonatal Intensive Care Units: Terminology-Definitions.
New fortifiers with higher protein content have been shown to improve short term weight gain Most multi-nutrient fortifiers contain bovine milk protein.
Donkey milk was more recently proposed as its composition is very close to human milk During the past 15 years, some for-profit companies have been set up to collect and buy HM, to manufacture and to sell HM-based products. Vat differs from Holder pasteurization which is the commonly used method in non-profit HM banks.
Meredith-Dennis et al. Human milk-based fortifier is obtained by concentrating heat-treated donor HM and then adding vitamins and minerals. Various caloric densities of this fortifier allow for individual adjustment based on growth or blood urea nitrogen BUN. More recently, a novel HM derived cream supplement has been produced by the same company 59 , Although some studies suggested a benefit in terms of morbidity and mortality when babies are fed an exclusively human milk based diet including HM-based fortifier, leading to a reduction of costs 33 , 61 , much of the work is observational 62 — 64 , and there are still concerns about the efficacy of these products For example, Sullivan et al.
Sullivan et al. However, the HM-based fortifier was never directly compared with the bovine based fortifier and many of the babies who developed NEC on the bovine fortifier were also on the bovine formula.
In , most facilities in US fortified human milk, and approximately one out of five used a HM-based fortifier In summary, HM-based products have been adopted in neonatal care despite being costly and supported by limited efficacy data.
Some aspects have not been fully investigated yet, such as metabolic effects and body composition, which are needed before considering these products to be totally safe and effective. It is essential to evaluate the benefit-risk ratio, particularly as these products are very expensive and use large amounts of donated milk to make the fortifier which could be used more directly to feed preterm babies. At the present time these products are available mainly in North America. According to regulations in some European countries, only HM banks in each country are authorized to collect, treat and distribute HM or HM-based products 68 , Finally, there could be some ethical concerns.
According to available information ethical concerns seem to be well-controlled by present manufacturers but, if the evidence confirms a benefit, the need for these products could increase sharply and ethical questions related to the origin of HM could become a major concern. In some fortifiers, manufacturers used a hydrolyzed protein source Table 4. There is no evidence supporting the use of such a protein source. It has been shown that preterm infants fed a formula with partially hydrolyzed protein have a shorter transit time, but also a reduced intestinal absorption The rationale cannot be related to the hypothetical prevention of allergy.
Indeed, no increased risk of allergy was detected with preterm infants fed on formulas based on cow's milk even those with a high protein content. It has even been suggested that preterm birth reduces the chances of the subsequent development of severe atopic disease Nevertheless, the use of a hydrolyzed protein source is a response to clinicians' preferences, as a lot of professionals are reluctant to add whole bovine protein to HM.
This current opinion of professionals comes from a study suggesting that, in a subgroup of preterm infants with a family history of atopy, early exposure to cow's milk increased the risk of allergic reaction However, more recent studies showed that, compared to exclusively breastfed, preterm infants supplemented with HMF or fed exclusively a preterm formula for 4 months after discharge did not have an increased risk of developing allergic diseases during the first year of life Furthermore, it was previously shown that protein supplementation using whole-protein is efficient 43 , 74 , In summary, there is no strong evidence to support the use of hydrolyzed protein source in fortifiers, but it is current practice.
Other products containing only protein, lipids, or carbohydrates are also available. They are useful when individualizing fortification 74 — Usually, carbohydrate supplements are composed of dextrin maltose, and lipids are composed of medium chain triglycerides. More recently, a novel HM-derived cream supplement has been produced to enhance the energy density of feeds.
Infants were supplemented with the 2. When compared to the control group these infants had improved weight and length growth rates and were discharged slightly earlier.
This reduction in length of stay was greater in the subgroup of preterm infants with bronchopulmonary dysplasia 59 , However, this finding needs to be replicated in other settings to ensure that this can be done without compromising protein to energy ratio.
Protein supplements have been available for years in some countries, but are not specifically designed for neonates 74 — One of them contained extensively hydrolyzed protein source Recently a new protein supplement—including partially hydrolyzed protein source—specifically designed for preterm infants, became available in most European countries 54 Product G, Table 4.
There is no consensus about how to use these products as studies are scarce. That being said, protein supplements are essential to enable individualized fortification, particularly for Adjustable ADJ fortification which has been shown to be associated with clinical benefits 74 see Individualized Fortification. Following the first introduction of the commercial HM fortifiers in the s, HM fortification has become part of the standard nutritional care for preterm infants in most NICUs.
The quality of the fortifiers and the methods of HM fortification have improved over time but nutrient fortification remains suboptimal. Individualized HM fortification:. Targeted HM fortification 76 , 79 — Table 5. Current human milk fortification methods 43 , 74 , 76 — This is the most widely used fortification method.
The standard practice is to add a fixed amount of multinutrient fortifier per ml of HM to achieve the recommended nutrient intakes. This fixed amount has been calculated and determined by the manufacturer assuming a fixed protein content for all milk samples without considering intra-, inter-individual and temporal variations. The systematic review evaluated 1, infants in 14 trials. The trials were generally small and weak methodologically.
Meta-analyses provided low-quality evidence that STD multi-nutrient fortification of HM, in comparison to the unfortified HM, improved in-hospital weight gain, linear growth, and head circumference growth.
Only very little data were available for growth and developmental outcomes beyond infancy and these did not show long-term advantage. However, when comparisons are made between fortified HM in STD fashion and preterm formula PF 83 — 85 the findings indicate that despite fortification, HM fed preterm infants continue to grow more slowly than PF fed infants.
Henriksen et al. Maas et al. The trend toward poorer weight gain with higher proportions of HM intake persisted also at the time of discharge. Of course these findings cannot be a reason to favor preterm formula vs. Considering all the clinical benefits deriving from the use of HM as already stated in the previous Sections, fortified HM should be the first feeding option for these infants.
However, HM fortification should be optimized. Undernutrition, particularly protein undernutrition: STD fortification does not take into account the variability of HM macronutrient content and variability of the infants' requirements. Protein is essential for tissue and organ development, and is a rate limiting factor for growth. A rate of postnatal growth similar to the intrauterine growth can be reached only with adequate protein and energy intakes 3. Standard fortification usually provides the recommended energy intakes, but cannot provide the adequate protein intakes for many VLBW infants actual protein intake 2.
Arslanoglu et al. Actual protein intakes were consistently and significantly lower than assumed when fortification was performed in STD fashion range of discrepancy between 0. On the other hand, the differences in energy intake were small and not consistently significant. This observation was important, because it provided a rational basis for simply adding more protein to milk in those infants whose enteral diet came from milk, especially over long periods after birth Similar findings have been reported in the following years by other researchers 75 , 90 , Picaud et al.
In the recent systematic review and meta-analysis regarding the macronutrient and energy composition of preterm human milk, Mimouni et al. During the same time frame; fat, lactose and energy content showed a significant linear increase.
The main reason for ongoing protein undernutrition despite HM fortification is that the STD regimen is based on assumptions about the protein content of the milk. Usually the assumed protein concentration by the manufacturers is 1. Thus, the protein intake would be inadequate most of the time throughout the fortification period 43 , 44 , Optimization of HM fortification is being widely studied.
Improvement of the quality and source of the fortifiers, increasing the protein content of the products, early initiation of fortification are all efforts to improve STD fortification. An attempt at earlier initiation of fortification has resulted in better in-hospital head growth and weight gain in a very recent pre-, post- implementation study However, a systematic review and meta-analysis aiming to ascertain whether randomized controlled trials determined the efficacy of early vs.
In this review Mimouni et al. Individualization of fortification is believed to be a solution to the problem of protein undernutrition with STD fortification and is currently the recommended method by scientific authorities and expert panels 29 , 42 , The two methods of individualized fortification Table 5 ; Adjustable and Targeted methods are discussed in the following Sections separately.
ADJ method was designed specifically to avoid both protein undernutition and overnutrition. With this method, protein intake is adjusted on the basis of each infant's metabolic response. Human milk fortification is initiated with a multi-nutrient fortifier in a STD fashion and as soon as full strength fortification is tolerated, it is guided by blood urea nitrogen BUN levels as a surrogate for assessing protein adequacy.
Table 6. The products required and the threshold values of the metabolic marker used for the Adjustable ADJ fortification method Table 7. The scheme for adjustable fortification updated in This model was evaluated in a randomized controlled trial RCT by Arslanoglu et al. In this study the mean actual measured protein intakes reached 3. During the 3 weeks intervention period the infants in ADJ group had better weight and head circumference gains compared to STD group 17 vs.
ADJ fortification; i. Adjusting the protein intake according to these values 74 , the investigators observed that there was the need to increase the level of fortification during most of the fortification period; and the protein intakes could not reach the recommended intakes at the first week of the fortification.
There was need to refine the protocol, and to be cautious only a small increase has been suggested. Tables 6 , 7 show the details of the current ADJ fortification regimen.
Protein adequacy is evaluated by twice weekly BUN determinations. Extra-protein is added in the form of protein supplement according to the protocol in 3 levels up to 1. In , Alan et al. The study replicated similar results in terms of higher protein intake and better in-hospital growth including linear growth with ADJ fortification.
According to the practice in their NICU they used weekly measured urea levels and growth together to determine the need for extra protein. They confirmed the findings of Arslanoglu et al. In two observational studies, slightly modified forms of ADJ fortification were associated with both better growth and better neurodevelopmental outcomes. Ergenekon et al. This improvement in growth was associated with significant improvement of Bayley scores at 18 months corrected age. Also, in the observational study of Biasini et al.
At 24 months, small for gestational age SGA preterm infants having higher protein intake had higher scores. Very recently, Mathes et al. That is what he said when he was last in Wisconsin, to speak. These authors simply compared the 2 methods of fortification. In their background they discussed the need to fortify breastmilk for VLBW and very premature infants. You, I, and many others, know that much more work is needed to identify who really needs this fortification.
Formula fed infants grow faster than breastmilk fed infants, right? And I would ask how much milk did mom have stored up in the freezer prior to discharge, which would impact how long her milk lasted; so many variables.
Just thoughts. Your email address will not be published. Notify me via e-mail if anyone answers my comment. About Contact Donate Login. Among NICU graduates, fortification by adding formula powder to expressed breastmilk is associated with continued breastmilk feedings at 4 months as compared to supplementation with bottles of formula. What is the difference between fortifying breastmilk with formula powder versus supplementing with a few bottles of formula a day for premature infants upon hospital discharge?
If baby is not growing according to your pediatrician , baby needs supplementation. This most often occurs in premature babies when they experience rapid growth spurts. Fortifying breast milk is the first-line treatment for increasing calories in babies under six months of age.
This allows the baby to still receive all the benefits of breast milk plus additional nutrients, as opposed to the exclusive use of formula first. Commercially prepared human breast milk fortifiers are available in liquid and powder form. Breast milk can also be fortified by adding powdered formula to it and giving the combination in a bottle.
If baby does need some additional nutrients, encourage moms not to give up on breastfeeding! If fortification is needed, determine the best method for both mom and baby before switching to formula.
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