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.

Infant milk-feeding practices and diabetes 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) feeding a lower versus higher intensity of human milk to mixed-fed infants with type 1 and type 2 diabetes 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 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 4 systematic reviews included 21, 37, 18, and 1 articles, respectively. Observational evidence suggests that never versus ever feeding human milk (limited evidence) and shorter versus longer durations of any (moderate evidence) and exclusive (limited evidence) human milk feeding are associated with higher type 1 diabetes risk. Insufficient evidence examined type 2 diabetes. Limited evidence suggests that the durations of any and exclusive human milk feeding are not associated with intermediate outcomes (e.g., fasting glucose, insulin resistance) during childhood. CONCLUSIONS: Limited to moderate evidence suggests that feeding less or no human milk is associated with higher risk of type 1 diabetes in offspring. Limited evidence suggests no associations between the durations of any and exclusive human milk feeding and intermediate diabetes outcomes in children. Additional research is needed on infant milk-feeding practices and type 2 diabetes and intermediate outcomes in US populations, which may have distinct metabolic risk.

Calcium and Vitamin D Supplementation in Boys with Risperidone-Induced Hyperprolactinemia: A Randomized, Placebo-Controlled Pilot Study.

BACKGROUND: The chronic use of antipsychotics has been associated with impaired bone mineralization, partially mediated by hyperprolactinemia. We examined if calcium and vitamin D supplementation promote bone mineral accrual in boys with risperidone-induced hyperprolactinemia. METHODS: Between February 2009 and November 2013, medically healthy, 5- to 17-year-old boys were enrolled in a 36-week double-blind, placebo-controlled study, examining the skeletal effects of supplementation with 1250 mg calcium carbonate and 400 IU of vitamin D3 in risperidone-induced hyperprolactinemia. Anthropometric, dietary, physical activity, and psychiatric assessments were conducted at baseline and week 18 and 36. Plasma prolactin and vitamin D concentrations were measured at baseline and week 36. Total body less head bone mineral content (BMC) and radius trabecular bone mineral density (BMD) were measured at baseline, week 18, and week 36, using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography, respectively. Linear mixed-effects regression analysis examined the longitudinal effect of treatment on skeletal outcomes. RESULTS: Forty-seven boys (mean age: 11.0 ± 2.6 years) were randomized and 38 completed the study. At study entry, the average dietary calcium intake was below the recommended limit, but the average vitamin D concentration was normal. Calcium and vitamin D supplementation failed to significantly increase BMC or trabecular BMD. It also failed to affect several other skeletal and anthropometric outcomes, including plasma vitamin D concentration. CONCLUSIONS: In this 9-month long pilot study, supplementation with a modest dose of calcium and vitamin D did not increase bone mass accrual in risperidone-treated boys with hyperprolactinemia. Alternative approaches should be investigated to optimize bone health in this population to prevent future morbidity and premature mortality. ClinicalTrials.gov Identifier: NCT00799383.

Preterm Infant Growth Velocity Calculations: A Systematic Review.

CONTEXT: Clinicians assess the growth of preterm infants and compare growth velocity using a variety of methods. OBJECTIVE: We determined the numerical methods used to describe weight, length, and head circumference growth velocity in preterm infants; these methods include grams/kilogram/day (g/kg/d), grams/day (g/d), centimeters/week (cm/week), and change in z scores. DATA SOURCES: A search was conducted in April 2015 of the Medline database by using PubMed for studies that measured growth as a main outcome in preterm neonates between birth and hospital discharge and/or 40 weeks' postmenstrual age. English, French, German, and Spanish articles were included. The systematic review was conducted by using Preferred Reporting Items for Systematic Reviews and Meta-analyses methods. STUDY SELECTION: Of 1543 located studies, 373 (24%) calculated growth velocity. DATA EXTRACTION: We conducted detailed extraction of the 151 studies that reported g/kg/d weight gain velocity. RESULTS: A variety of methods were used. The most frequently used method to calculate weight gain velocity reported in the 1543 studies was g/kg/d (40%), followed by g/d (32%); 29% reported change in z score relative to an intrauterine or growth chart. In the g/kg/d studies, 39% began g/kg/d calculations at birth/admission, 20% at the start of the study, 10% at full feedings, and 7% after birth weight regained. The kilogram denominator was not reported for 62%. Of the studies that did report the denominators, the majority used an average of the start and end weights as the denominator (36%) followed by exponential methods (23%); less frequently used denominators included birth weight (10%) and an early weight that was not birth weight (16%). Nineteen percent (67 of 355 studies) made conclusions regarding extrauterine growth restriction or postnatal growth failure. Temporal trends in head circumference growth and length gain changed from predominantly cm/wk to predominantly z scores. LIMITATIONS AND CONCLUSIONS: The lack of standardization of methods used to calculate preterm infant growth velocity makes comparisons between studies difficult and presents an obstacle to using research results to guide clinical practice.

The Use of Multinutrient Human Milk Fortifiers in Preterm Infants: A Systematic Review of Unanswered Questions.

There is evidence that multinutrient fortification of human milk increases in-hospital growth of preterm infants, but fortification has not been shown to improve long-term growth and neurodevelopmental outcome. We aimed to ascertain whether randomized controlled trials have determined the effect of early versus late introduction of fortifiers on growth and/or other outcomes, and have compared the efficacy/adverse effects of human milk-based versus cow milk-based fortifiers. We conclude that there is little evidence that early introduction of human milk fortification affects important outcomes, and limited evidence that a bovine fortifier places the infant at a higher risk of NEC.

Lack of Effect of Graded Doses of Vitamin D on Bone Metabolism of Breastfed Infants.

OBJECTIVE: A range of doses of supplemental vitamin D has been shown to be effective in preventing rickets in breastfed infants, but the effect of different doses of vitamin D on bone metabolism and mineral content has not been delineated. METHODS: In a randomized trial, breastfed infants received from 2 to 9 months daily supplements of vitamin D in doses of 200 IU/d, 400 IU/d, 600 IU/d or 800 IU/d. Measures of bone metabolism (plasma) were determined periodically and bone mineral content (DXA) was determined at study entry and at the end of winter when infants were 5.5 to 9 months old. The main findings have been reported; here we report findings related to bone metabolism. RESULTS: There were no consistent meaningful effects of vitamin D dose on markers of bone metabolism. Some markers showed changes with age. Bone mineral content increased with age but showed no effect of vitamin D dose. CONCLUSION: Vitamin D in daily doses from 200 IU/d to 800 IU/d had no measurable effect on bone mineral content or bone metabolism of breastfed infants.

Protein Needs of Preterm Infants: Why Are They So Difficult to Meet?

Because of their exceedingly high rate of growth, premature infants have very high needs for all nutrients. Requirements have been estimated by the factorial method based on the body composition of the fetus. Failure to meet the high requirements for protein impairs growth and places the infant at risk of neurodevelopmental impairments. Human milk, the preferred feeding for premature infants because of its protective effects, does not provide adequate amounts of nutrients and must be fortified. On the basis of studies performed several decades ago using very high protein intakes, in the past it has been believed that protein intakes that met the high needs of premature babies are dangerous for premature babies. To prevent protein intakes from being too high, the protein content of fortifiers in the past has been kept low. Today, this fear of protein is still the reason why protein intakes tend to be kept low, with the result that protein intakes are often too low.

Serum Ferritin, Weight Gain, Disruptive Behavior, and Extrapyramidal Symptoms in Risperidone-Treated Youth.

BACKGROUND: Iron deficiency disrupts dopaminergic signaling in rodents, resulting in cognitive deficits that may be reversed with psychostimulants. In humans, iron deficiency with or without anemia has similarly been found to cause neuropsychological and behavioral impairments. However, the clinical effects of low body iron stores in antipsychotic-treated children have not been examined. METHODS: Medically healthy, 5- to 17-year-old boys treated with risperidone for at least 1 year were enrolled between February 2009 and November 2013 in a multiphase study, examining the skeletal effects of calcium and vitamin D supplementation in risperidone-induced hyperprolactinemia. Anthropometric measures were collected and medical and pharmacy records were reviewed to obtain treatment history. Psychiatric diagnoses were based on clinical interviews, structured interviews, rating scales, and a review of their medical records. Extrapyramidal symptoms were assessed, and a food frequency questionnaire was completed in a subsample. Laboratory tests, including ferritin concentration (a marker of body iron status), were obtained upon study entry. RESULTS: A total of 114 participants (mean age: 11.0 ± 2.6 years) were included, the vast majority (>90%) having attention-deficit/hyperactivity disorder and/or disruptive behavior disorder. They had taken risperidone for an average 3.1 ± 2.0 years. Their serum ferritin concentration was 37.3 ± 25.6 µg/L with 21% of the sample having a level <20 µg/L, despite appropriate daily dietary iron intake. Ferritin concentration was inversely associated with weight gain following risperidone treatment onset but was not significantly associated with prolactin. After adjusting for the weight-adjusted dose of psychostimulants and risperidone and the daily dose of selective serotonin reuptake inhibitors, ferritin was inversely associated with the severity of disruptive behavior and positively associated (albeit marginally) with prosocial behavior. No association was found between ferritin concentration and extrapyramidal symptoms. CONCLUSIONS: Body iron stores are inversely related to risperidone-induced weight gain, even after extended treatment and despite adequate iron intake. Low iron stores are associated with poorer treatment response. Future research should examine iron absorption during antipsychotic treatment and whether repleting iron stores would facilitate clinical response.

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.

Iron homeostasis during risperidone treatment in children and adolescents.

OBJECTIVE: Previous cross-sectional evidence has linked antipsychotic-related weight gain to reduced body iron concentration. Using longitudinal data, we examined the association between changes in weight following risperidone initiation or discontinuation and ferritin concentration. METHOD: Study 1: Between April 2004 and September 2007, participants were enrolled from outpatient settings in a prospective randomized clinical trial comparing the efficacy of risperidone monotherapy to the combination of risperidone and behavior therapy in targeting disruptive behavior in 4- to 13-year-old children with DSM-IV-TR-based autism spectrum disorder. Study 2: Medically healthy 7- to 17-year-old participants in long-term open-label risperidone treatment at study entry returned for follow-up 1.5 years later, between July 2007 and July 2011. Available blood samples were used to measure ferritin. Linear multivariable regression analysis tested the association between ferritin concentration and change in age-sex-specific body mass index (BMI) z score between study entry and endpoint, adjusting for relevant confounders. RESULTS: Study 1 sample consisted of 73 participants (85% males, mean age: 7.7 ± 2.4 years). After 18.0 ± 2.0 weeks on risperidone, their BMI z score increased by 0.93 ± 0.70 points and ferritin concentration declined by 6.8 ± 13.3 µg/L. After adjusting for age and sex, change in BMI z score was inversely correlated with percent change in ferritin concentration (ß = -18.3, P < .003). Study 2 participants had all been receiving risperidone at study entry. At follow-up, 1.5 ± 0.3 years later, risperidone was discontinued in 26 of the 96 who were included in the analysis. Neither change in BMI z score nor in ferritin concentration was different between those who continued versus discontinued risperidone. However, a reduction in BMI z score between study entry and follow-up was associated with higher ferritin concentration at follow-up in participants who discontinued risperidone compared to those who continued it (P = .01). CONCLUSIONS: Risperidone-related weight gain is associated with a reduction in body iron reserves, which appears to improve with weight loss following risperidone discontinuation. Preliminary evidence suggests that risperidone may also directly inhibit iron absorption. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00080145.

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.

Nutrient Needs for Catch-Up Growth in Low-Birthweight Infants.

Growth restriction among low-birthweight (LBW) infants occurs prenatally as well as postnatally. Regardless of when and how the growth restriction occurs, growth-restricted infants have the potential for catch-up growth. Catch-up growth has decidedly beneficial effects on later cognition. It also may have adverse effects on cardiovascular and metabolic health. Although the benefits for later cognition are well documented in a number of studies, growth-restricted LBW infants often do not experience catch-up growth and therefore do not enjoy its benefits. One reason is that for catch-up growth to occur, extraordinarily high protein intakes are required. Nutrient intakes have been estimated with the use of the factorial method based on the assumption that catch-up growth comprises essentially a restoration of lean body mass, with restoration of fat mass optional. The basic (no catch-up) nutritional needs of growth-restricted LBW infants are altered to a modest degree, with energy needs increased and protein needs decreased. With catch-up, however, protein needs are increased sharply. Since energy needs are only modestly increased, the protein/energy ratio of requirements is appreciably increased. The high protein needs are difficult to meet with the usual feedings for LBW infants unless special measures are taken to increase protein intakes and to increase the protein/energy ratio. Without the necessary protein intake, catch-up growth is not possible or will be delayed, which may compromise the realization of the long-term benefits on cognition.