Human Milk Banking.

Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula.

Adequacy of Infant Formula With Protein Content of 1.6 g/100 kcal for Infants Between 3 and 12 Months.

OBJECTIVES: Infant formulas provide more protein than breast milk. High protein intakes may place infants at risk of later obesity. The present study tested whether a formula with protein content below the regulatory level supports normal growth from age 3 months. METHODS: Randomized double-blind trial enrolled healthy infants less than age 3 months. At 3 months, formula-fed infants were assigned to experimental (EXPL, 1.61 g protein/100 kcal; modified bovine whey proteins with caseinoglycomacropeptide removed) or control (CTRL 2.15 g protein/100 kcal; unmodified bovine milk protein with a whey/casein ratio of 60/40) formula; breast-fed (BF) infants were enrolled in a reference group. Complementary foods were allowed in small amounts from 4 to 6 months and unrestricted after 6 months. RESULTS: Weight gain (g/day) from 3 to 6 months was similar in the EXPL and CTRL groups (EXPL-CTRL -0.84 g/day; 95% confidence interval -2.25 to 0.57) and faster in the EXPL and CTRL groups than in the BF group. Weight analyzed longitudinally from 4 to 12 months was lower in the EXPL group than in the CTRL group (P = 0.031) but higher than in the BF group (P < 0.0001). Longitudinal analysis of odds ratios from 4 to 12 months indicated fewer infants with weight >85th percentile in the EXPL group than in the CTRL group (P = 0.015). Length z scores were lower than, and body mass index z scores were similar to, World Health Organization Standards in all of the groups. Serum biochemical parameters in the EXPL group reflected lower protein intake and were closer to parameters in the BF infants than in the CTRL group. CONCLUSIONS: A formula with 1.61 g of protein/100 kcal supports normal growth of infants after age 3 months. This protein content is adequate if provided from a high-quality source.

Vitamin D supplementation of breastfed infants: a randomized dose-response trial.

BACKGROUND: Breastfed infants require supplementation with vitamin D (vD), but little is known about the necessary dose. This double blind trial evaluated four different doses of vD. METHODS: Exclusively breastfed infants (N = 213) were randomized at 1 mo to one of four doses, which they received through 9 mo while receiving no formula. The supplements provided daily 200 IU, 400 IU, 600 IU, or 800 IU of vD. The primary endpoint was plasma 25(OH)D level, and secondary outcomes were plasma parathyroid hormone and calcium, and illness incidence. The study was conducted during winter at 41° N. RESULTS: Most infants had low (<50 nmol/l) 25(OH)D levels at 1 mo, but with supplementation levels rose. Overall, levels of 25(OH)D differed significantly in proportion to vD dose. There were no effects of vD on illness incidence or growth. Low levels were common, with 7.8% of levels being <50 nmol/l and 15 infants having 2 to 4 low levels. CONCLUSION: The four doses of vD produced different plasma levels of 25(OH)D. The higher doses were somewhat more efficacious in maintaining vD sufficiency in breastfed infants. The findings support the recommended dose of 400 IU/d, and stress the need to start supplementation at birth.

Low-protein formula slows weight gain in infants of overweight mothers.

OBJECTIVES: Infant formulas provide more protein than breast milk. High protein intakes, as well as maternal obesity, are risk factors for later obesity. The present study tested whether a formula with lower protein content slows weight gain of infants of overweight mothers (body mass index [BMI] >25 kg/m). METHODS: In a randomized double-blind study infants of overweight mothers received from 3 months an experimental (EXPL) formula with 1.65 g of protein/100 kcal (62.8 kcal/100 mL) and containing probiotics, or a control (CTRL) formula with 2.7 g of protein/100 kcal (65.6 kcal/100 mL). Breast-fed infants were studied concurrently. Primary assessment was between 3 and 6 months, although formulas were fed until 12 months. Biomarkers of protein metabolism (blood urea nitrogen, insulin growth factor-1, insulinogenic amino acids) were measured. RESULTS: Infants fed the low-protein EXPL formula gained less weight between 3 and 6 months (-1.77 g/day, P=0.024) than infants fed the CTRL formula. In the subgroup of infants of mothers with BMI>30 kg/m the difference was -4.21 g/day (P=0.017). Weight (P=0.011) and BMI (P=0.027) of EXPL infants remained lower than that of CTRL infants until 2 years but were similar to that of breast-fed infants. Blood urea nitrogen, insulin growth factor-1, and insulinogenic amino acids at 6 months were significantly lower in EXPL compared with CTRL. CONCLUSIONS: A low-protein formula with probiotics slowed weight gain between 3 and 6 months in infants of overweight mothers. Weight gain and biomarkers were more like those of breast-fed infants.

Fast growth of infants of overweight mothers: can it be slowed down?

Data from 3 recently completed studies were pooled and analyzed to answer the question whether breastfed infants of overweight/obese mothers show accelerated growth. It was shown that these infants gain weight faster than indicated by the WHO standards and that they grow significantly faster than infants of lean mothers. The question whether fast infant growth can be slowed down by lowering the protein content of formulas was examined. It was shown that formulas with a protein content that is just moderately above that of human milk support normal growth while significantly slowing down fast growth.

The WHO growth standards: strengths and limitations.

PURPOSE OF REVIEW: To describe the creation of the World Health Organization Child Growth Standards (WHO standards) released in 2006, to show their main features and to compare them with existing charts. RECENT FINDINGS: The WHO standards are the first globally representative growth standards. They describe the growth of children worldwide who are living in favorable circumstances. The WHO standards are well suited for intercountry comparisons. SUMMARY: Comparison with other charts reveals important differences with implications for child health monitoring. Recent studies comparing the use of the WHO standards to use country-specific growth references suggest that the latter may describe the growth of children more faithfully than the WHO standards. Use of the WHO standards in public health surveys must await the development of specific cutoffs.

Dry cereals fortified with electrolytic iron or ferrous fumarate are equally effective in breast-fed infants.

Precooked, instant (dry) infant cereals in the US are fortified with electrolytic iron, a source of low reactivity and suspected low bioavailability. Iron from ferrous fumarate is presumed to be more available. In this study, we compared a dry infant rice cereal (Cereal L) fortified with electrolytic iron (54.5 mg iron/100 g cereal) to a similar cereal (Cereal M) fortified with ferrous fumarate (52.2 mg Fe/100 g) for efficacy in maintaining iron status and preventing iron deficiency (ID) in breast-fed infants. Ascorbic acid was included in both cereals. In this prospective, randomized double-blind trial, exclusively breast-fed infants were enrolled at 1 mo and iron status was determined periodically. At 4 mo, 3 infants had ID anemia and were excluded. Ninety-five infants were randomized at 4 mo, and 69 (36 Cereal L, 33 Cereal M) completed the intervention at 9 mo. From 4 to 9 mo, they consumed daily one of the study cereals. With each cereal, 2 infants had mild ID, a prevalence of 4.2%, but no infant developed ID anemia. There were no differences in iron status between study groups. Iron intake from the study cereals was (mean ± SD) 1.21 ± 0.31 mg⋅kg(-1)⋅d(-1) from Cereal L and 1.07 ± 0.40 mg⋅kg(-1)⋅d(-1) from Cereal M. Eleven infants had low birth iron endowment (plasma ferritin < 55 µg/L at 2 mo) and 54% of these infants had ID with or without anemia by 4 mo. We conclude that electrolytic iron and ferrous fumarate were equally efficacious as fortificants of this infant cereal.

Meeting the nutritional needs of the low-birth-weight infant.

Delivering adequate amounts of nutrients to premature infants at all times is challenging because the infant's immature gastrointestinal tract is initially unable to accept feedings, necessitating the use of parenteral nutrition. In the past, inadequate amounts of nutrients have commonly been given to premature infants because the administration of nutrients was thought to be hazardous. Inadequate nutrient intakes have resulted in widespread postnatal growth restriction. Now that it is known that postnatal growth restriction is associated with poor neurocognitive development, efforts are made to increase nutrient intakes. In this review, nutrient requirements of premature infants that have been determined by the factorial and empirical methods are reviewed. Current good practices regarding parenteral nutrition are discussed, as are guidelines for the introduction and advancement of enteral feedings. Because of its trophic effects on the gastrointestinal tract and its anti-infectious effects, human milk is strongly preferred as the early feeding of choice for premature infants. Human milk also protects infants against necrotizing enterocolitis. Once full feeding is achieved, the challenge is to provide nutrients in amounts that support the infant's growth like that of the fetus. In the case of the infant fed his/her mother's milk or banked donor milk, nutrient fortification is necessary and is generally practiced. However, adequate intakes of protein are seldom achieved with routine fortification and methods of providing additional fortification are discussed.

Donor human milk in preterm infant feeding: evidence and recommendations.

In preterm infants, feeding with human milk (HM) is a very effective intervention for the prevention of infections and necrotizing enterocolitis (NEC), and for potentially improved neurocognitive and cardiovascular outcomes in the long-term. Hospitals and physicians are advised to recommend HM for preterm and other high-risk infants either by direct breastfeeding and/or using the mother's own expressed milk. Donor HM is the preferred feeding when the mother's own milk is not available in sufficient quantity. While in some countries donor HM has been considered an effective tool in the delivery of health care to infants, skepticism regarding its nutritional and immunological quality has limited its distribution in other countries. The purpose of this paper is to summarize the clinical benefits of donor HM in preterm infants, and to discuss common concerns limiting its distribution as standard care. Clinically, the use of donor HM has been shown to prevent NEC, reduce feeding intolerance and improve long-term outcomes in premature infants. Common concerns, such as slow growth and loss of important biological components of donor HM due to storage and pasteurization, should not be a reason for denial of donor milk. Optimization of banking procedures and of HM fortification is available and should be applied. Banked donor milk should be promoted as standard component of health care for premature infants.

Optimization of human milk fortification for preterm infants: new concepts and recommendations.

Preterm infants fed fortified human milk (HM) in standard (STD) fashion grow slower than preterm formula fed infants. Recently, low protein intake has been proven to be the primary limiting factor responsible for this growth failure. The main reason of protein undernutrition despite fortification is that STD fortification is based on the customary assumptions about the composition of HM. However, the protein concentration of preterm HM is variable and decreases with the duration of lactation. Also, the protein concentration of banked donor milk, which is most often provided by mothers of term infants, is likely to be lower. Hence, most of the HM fed to preterm infants during the fortification period is likely to have an inadequately low protein concentration. This hypothesis has been confirmed very recently by comparing the assumed and actual protein intakes in preterm infants fed fortified HM. Novel fortification models have been devised to deal with the problem of ongoing protein undernutrition. Individualized fortification is the recommended method to optimize HM fortification. There are two models of individualization: "adjustable fortification" and "targeted fortification". Both ways are feasible and effective in improving protein intakes and growth. Adjustable fortification has the advantage of being practical and avoids excessive protein intakes.

Potential roles and clinical utility of prebiotics in newborns, infants, and children: proceedings from a global prebiotic summit meeting, New York City, June 27-28, 2008.

Initial bacterial colonization, including colonization with health-positive bacteria, such as bifidobacteria and lactobacilli, is necessary for the normal development of intestinal innate and adaptive immune defenses. The predominance of beneficial bacteria in the gut microflora of breast-fed infants is thought to be, at least in part, supported by the metabolism of the complex mixture of oligosaccharides present in human breast milk, and a more adult-type intestinal microbiota is found in formula-fed infants. Inadequate gut colonization, dysbiosis, may lead to an increased risk of infectious, allergic, and autoimmune disorders later in life. The addition of appropriate amounts of selected prebiotics to infant formulas can enhance the growth of bifidobacteria or lactobacilli in the colonic microbiota and, thereby, might produce beneficial effects. Among the substrates considered as prebiotics are the oligosaccharides inulin, fructo-oligosaccharides, galacto-oligosaccharides, and lactulose. There are some reports that such prebiotics have beneficial effects on various markers of health. For example, primary prevention trials in infants have provided promising data on prevention of infections and atopic dermatitis. Additional well-designed prospective clinical trials and mechanistic studies are needed to advance knowledge further in this promising field.

Tolerance of a standard intact protein formula versus a partially hydrolyzed formula in healthy, term infants.

BACKGROUND: Parents who perceive common infant behaviors as formula intolerance-related often switch formulas without consulting a health professional. Up to one-half of formula-fed infants experience a formula change during the first six months of life. METHODS: The objective of this study was to assess discontinuance due to study physician-assessed formula intolerance in healthy, term infants. Infants (335) were randomized to receive either a standard intact cow milk protein formula (INTACT) or a partially hydrolyzed cow milk protein formula (PH) in a 60 day non-inferiority trial. Discontinuance due to study physician-assessed formula intolerance was the primary outcome. Secondary outcomes included number of infants who discontinued for any reason, including parent-assessed. RESULTS: Formula intolerance between groups (INTACT, 12.3% vs. PH, 13.7%) was similar for infants who completed the study or discontinued due to study physician-assessed formula intolerance. Overall study discontinuance based on parent- vs. study physician-assessed intolerance for all infants (14.4 vs.11.1%) was significantly different (P = 0.001). CONCLUSION: This study demonstrated no difference in infant tolerance of intact vs. partially hydrolyzed cow milk protein formulas for healthy, term infants over a 60-day feeding trial, suggesting nonstandard partially hydrolyzed formulas are not necessary as a first-choice for healthy infants. Parents frequently perceived infant behavior as formula intolerance, paralleling previous reports of unnecessary formula changes. TRIAL REGISTRATION: clinicaltrials.gov: NCT00666120.

Human Milk-A Valuable Tool in the Early Days of Life of Premature Infants.

The objective of early premature infant nutrition is to maintain, during the turbulent early days of life, a flow of nutrients that differs only minimally from that which would have prevailed had the infant remained in utero. Out of necessity, nutrients have at first to be provided mainly via the parenteral route. While that is going on, the feeding of small amounts of human milk (gut priming) is initiated as soon as practical. As mother's own milk is not available in sufficient quantity at this time, donor milk needs to be used temporarily. If not available, formula should be used. Gastric residuals are physiologic at this stage and are monitored to guide the increase of the size of feedings. As the volume of milk is gradually increased, nutrient fortification is initiated when the milk volume reaches around 20 ml/kg/day. There is no need to start with less than full-strength fortification. Fortification should employ one of the liquid fortifiers. Adjustable fortification may be employed but is labor-intensive and is not a necessity as long as full feeding volumes of around 170 ml/kg/day are maintained. As the infant grows beyond 1,500 g the level of fortification can be reduced gradually by omitting fortification first from one, and then from more feedings. After discharge there is still a need for fortification, which requires the mother to express some of her milk so it can be fortified. Nutrient supplementation directly to the infant would obviate the need for milk expression.

Infant milk-feeding practices and childhood leukemia: a systematic review.

BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the US Departments of Agriculture and Health and Human Services initiated a review of evidence on diet and health in these populations. OBJECTIVES: The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding, and 4) feeding a lower versus higher intensity of human milk to mixed-fed infants with acute childhood leukemia, generally, and acute lymphoblastic leukemia, specifically. METHODS: The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January 1980 to March 2016, dual-screened the results using predetermined criteria, extracted data from and assessed risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: We included 24 articles from case-control or retrospective studies. Limited evidence suggests that never feeding human milk versus 1) ever feeding human milk and 2) feeding human milk for durations ≥6 mo are associated with a slightly higher risk of acute childhood leukemia, whereas evidence comparing never feeding human milk with feeding human milk for durations <6 mo is mixed. Limited evidence suggests that, among infants fed human milk, a shorter versus longer duration of human milk feeding is associated with a slightly higher risk of acute childhood leukemia. None of the included articles examined exclusive human milk feeding or the intensity of human milk fed to mixed-fed infants. CONCLUSIONS: Feeding human milk for short durations or not at all may be associated with slightly higher acute childhood leukemia risk. The evidence could be strengthened with access to broadly generalizable prospective samples; therefore, we recommend linking surveillance systems that collect infant feeding and childhood cancer data.

Infant milk-feeding practices and cardiovascular disease outcomes in offspring: a systematic review.

BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the US Departments of Agriculture and Health and Human Services initiated a review of evidence on diet and health in these populations. OBJECTIVES: The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding, and 4) lower versus higher intensities of human milk fed to mixed-fed infants with intermediate and endpoint cardiovascular disease (CVD) outcomes in offspring. METHODS: The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January 1980-March 2016, dual-screened the results using predetermined criteria, extracted data from and assessed the risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: The 4 systematic reviews included 13, 24, 6, and 0 articles, respectively. The evidence was insufficient to draw conclusions about endpoint CVD outcomes across all 4 systematic reviews. Limited evidence suggests that never versus ever being fed human milk is associated with higher blood pressure within a normal range at 6-7 y of age. Moderate evidence suggests there is no association between the duration of any human milk feeding and childhood blood pressure. Limited evidence suggests there is no association between the duration of exclusive human milk feeding and blood pressure or metabolic syndrome in childhood. Additional evidence about intermediate outcomes for the 4 systematic reviews was scant or inconclusive. CONCLUSIONS: There is insufficient evidence to draw conclusions about the relationships between infant milk-feeding practices and endpoint CVD outcomes; however, some evidence suggests that feeding less or no human milk is not associated with childhood hypertension.

Infant milk-feeding practices and food allergies, allergic rhinitis, atopic dermatitis, and asthma throughout the life span: a systematic review.

BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the USDA and Department of Health and Human Services initiated a review of evidence on diet and health in these populations. OBJECTIVES: The aim of these systematic reviews was to examine the relation of 1) never versus ever feeding human milk, 2) shorter versus longer durations of any human milk feeding, 3) shorter versus longer durations of exclusive human milk feeding prior to infant formula introduction, 4) feeding a lower versus higher intensity of human milk to mixed-fed infants, and 5) feeding a higher intensity of human milk by bottle versus breast with food allergies, allergic rhinitis, atopic dermatitis, and asthma. METHODS: The Nutrition Evidence Systematic Review team conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published between January 1980 and March 2016, dual-screened the results according to predetermined criteria, extracted data from and assessed the risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: The systematic reviews numbered 1-5 above included 44, 35, 1, 0, and 0 articles, respectively. Moderate, mostly observational, evidence suggests that 1) never versus ever being fed human milk is associated with higher risk of childhood asthma, and 2) among children and adolescents who were fed human milk as infants, shorter versus longer durations of any human milk feeding are associated with higher risk of asthma. Limited evidence does not suggest associations between 1) never versus ever being fed human milk and atopic dermatitis in childhood or 2) the duration of any human milk feeding and allergic rhinitis and atopic dermatitis in childhood. CONCLUSIONS: Moderate evidence suggests that feeding human milk for short durations or not at all is associated with higher childhood asthma risk. Evidence on food allergies, allergic rhinitis, and atopic dermatitis is limited.

Infant milk-feeding practices and diagnosed celiac disease and inflammatory bowel disease in offspring: a systematic review.

BACKGROUND: During the Pregnancy and Birth to 24 Months Project, the USDA and US Department of Health and Human Services initiated an evidence review on diet and health in these populations. OBJECTIVE: The aim of these systematic reviews was to examine the relationships of never versus ever feeding human milk, shorter versus longer durations of any and exclusive human milk feeding, and feeding a lower versus a higher intensity of human milk to mixed-fed infants with diagnosed celiac disease and inflammatory bowel disease (IBD). METHODS: The Nutrition Evidence Systematic Review team (formerly called the Nutrition Evidence Library) conducted systematic reviews with external experts. We searched CINAHL, Cochrane, Embase, and PubMed for articles published January, 1980 to March, 2016, dual-screened the results using predetermined criteria, extracted data from and assessed risk of bias for each included study, qualitatively synthesized the evidence, developed conclusion statements, and graded the strength of the evidence. RESULTS: We included 9 celiac disease and 17 IBD articles. Limited case-control evidence suggests never versus ever being fed human milk is associated with higher risk of celiac disease, but concerns about reverse causality precluded a conclusion about the relationship of shorter versus longer durations of any human milk feeding with celiac disease. Evidence examining never versus ever feeding human milk and IBD was inconclusive, and limited, but consistent, case-control evidence suggests that, among infants fed human milk, shorter versus longer durations of any human milk feeding are associated with higher risk of IBD. For both outcomes, evidence examining the duration of exclusive human milk feeding was scant and no articles examined the intensity of human milk fed to mixed-fed infants. CONCLUSION: Limited case-control evidence suggests that feeding human milk for short durations or not at all associates with higher risk of diagnosed IBD and celiac disease, respectively. The small number of studies and concern about reverse causality and recall bias prevent stronger conclusions.