Human Milk-fed Preterm Infants Research Articles

Enteral Multiple Micronutrient Supplementation in Preterm and Low Birth Weight Infants: A Systematic Review and Meta-analysis.

To assess effects of supplementation with 3 or more micronutrients (multiple micronutrients; MMN) compared to no MMN in human milk-fed preterm and low birth weight (LBW) infants. Data on a subgroup of 414 preterm or LBW infants from 2 randomized controlled trials (4 reports) were included. The certainty of evidence ranged from low to very low. For growth outcomes in the MMN compared to the non-MMN group, there was a small increase in weight-for-age (2 trials, 383 participants) and height-for-age z-scores (2 trials, 372 participants); a small decrease in wasting (2 trials, 398 participants); small increases in stunting (2 trials, 399 participants); and an increase in underweight (2 trials, 396 participants). For neurodevelopment outcomes at 78 weeks, we found small increases in Bayley Scales of Infant Development, Version III (BISD-III), scores (cognition, receptive language, expressive language, fine motor, gross motor) in the MMN compared to the non-MMN group (1 trial, 27 participants). There were no studies examining dose or timing of supplementation. Evidence is insufficient to determine whether enteral MMN supplementation to preterm or LBW infants who are fed mother's own milk is associated with benefit or harm. More trials are needed to generate evidence on mortality, morbidity, growth, and neurodevelopment.

Enteral Calcium or Phosphorus Supplementation in Preterm or Low Birth Weight Infants: a Systematic Review and Meta-analysis.

To assess effects of calcium or phosphorous supplementation compared with no supplementation in human milk-fed preterm or low birth weight infants. Data sources include Cochrane Central Register of Controlled Trials, Medline and Embase. We included Randomized controlled trials (RCTs) and non-randomized trials (quasi-randomized). Three studies (4 reports; 162 infants) were included. At latest follow-up (38 weeks), there was reduction in osteopenia (3 studies, 159 participants, relative risk 0.68, 95% confidence interval [CI] 0.46-0.99). At latest follow-up (6 weeks), there was no effect on weight (1 study, 40 participants, mean difference [MD] 138.50 g, 95% CI -82.16 to 359.16); length (1 study, 40 participants, MD 0.77 cm, 95% CI -0.93 to 2.47); and head circumference (1 study, 40 participants, MD 0.33 cm, 95% CI -0.30 to 0.96). At latest follow-up, there was no effect on alkaline phosphatase (55 weeks) (2 studies, 122 participants, MD -126.11 IU/L, 95% CI -298.5 to 46.27, I2 = 73.4%); serum calcium (6 weeks) (1 study, 40 participants, MD 0.54 mg/dL, 95% CI -0.19 to 1.27); and serum phosphorus (6 weeks) (1 study, 40 participants, MD 0.07 mg/dL, 95% CI -0.22 to 0.36). The certainty of evidence ranged from very low to low. No studies reported on mortality and neurodevelopment outcomes. The evidence is insufficient to determine whether enteral supplementation with calcium or phosphorus for preterm or low birth weight infants who are fed mother's own milk or donor human milk is associated with benefit or harm.

Enteral Iron Supplementation in Preterm or Low Birth Weight Infants: A Systematic Review and Meta-analysis

Iron is needed for growth and development of infants globally, but preterm and low birth weight (LBW) infants are at risk for severe iron deficiencies. To assess the effect of enteral iron supplementation on mortality, morbidity, growth, and neurodevelopment outcomes in preterm or LBW infants fed human milk. Secondary objectives were to assess the effect on biomarkers and dose and timing. Data sources include PubMed, Embase and Cochrane Library databases to March 16, 2021. Study Selection includes controlled or quasi experimental study designs. Two reviewers independently extracted data. Eight trials (eleven reports; 1093 participants, 7 countries) were included. No trials reported mortality. At latest follow-up, there was little effect on infection (very low certainty evidence, 4 studies, 401 participants, relative risk [RR] 0.98, 95% confidence interval [95% CI] 0.56 to 1.73, I2 = 0.00%) and necrotising enterocolitis (3 studies, 375 participants, RR 1.47, 95% CI 0.68 to 3.20, I2 = 0.00%). There was an increase in linear growth (length) (moderate certainty evidence, 3 studies, 384 participants, mean difference 0.69 cm, 95% CI 0.01 to 1.37, I2 = 0%) but little effect on weight, head circumference, or cognitive development. There was an improvement in anemia (moderate certainty evidence, 2 studies, 381 participants, RR 0.25, 95% CI 0.10 to 0.62, I2 = 0.00%) but no effect on serum ferritin. Limitations include heterogeneity in the included studies. There are important benefits for human milk-fed preterm and LBW infants from enteral iron supplementation. However, more randomized control trials are required to improve the certainty of evidence.

Enteral Low-Dose Vitamin A Supplementation in Preterm or Low Birth Weight Infants to Prevent Morbidity and Mortality: a Systematic Review and Meta-analysis.

To assess effects of enteral "low" dose (daily doses of ≤10 000 international unit) vitamin A supplementation compared with no vitamin A supplementation in human milk-fed preterm and low birth weight (LBW) infants. Cochrane Central Register of Controlled Trials; Medline, Embase, Scopus, Web of Science, CINAHL from inception to 16 March 2021. Randomized trials were screened. Primary outcomes were mortality, morbidity, growth, neurodevelopment. Secondary outcomes were feed intolerance and duration of hospitalization. We also assessed the dose and timing of vitamin A supplementation. Data were extracted and pooled with fixed and random-effects models. Four trials including 800 very LBW <1.5 kg or <32 weeks' gestation infants were found. At latest follow-up, we found little or no effect on: mortality, sepsis, bronchopulmonary dysplasia, retinopathy of prematurity, duration of hospitalisation. However, we found a increased level of serum retinol mean difference of 4.7 μg/ml (95% CI 1.2 to 8.2, I2 =0.00%, one trial, 36 participants,). Evidence ranged from very low to moderate certainty. There were no outcomes reported for length, head circumference or neurodevelopment. Heterogeneity and small sample size in the included studies. Low-dose vitamin A increased serum retinol concentration among very LBW and very preterm infants but had no effect on other outcomes. More trials are needed to assess effects on clinical outcomes and to assess effects in infants 1.5 to 2.4 kg or 32 to 26 weeks' gestation.

Preterm Infant Fecal Microbiota and Metabolite Profiles Are Modulated in a Probiotic Specific Manner.

To compare the impact of two probiotic supplements on fecal microbiota and metabolites, as well as on gut inflammation in human milk-fed preterm infants. In this single-center observational cohort study, we assessed the effects of Bifidobacterium longum subsp. infantis or Lactobacillus reuteri supplementation on the infant gut microbiota by 16S rRNA gene sequencing and fecal metabolome by 1 H nuclear magnetic resonance spectroscopy. Fecal calprotectin was measured as a marker of enteric inflammation. Aliquots of human or donor milk provided to each infant were also assessed to determine human milk oligosaccharide (HMO) content. As expected, each probiotic treatment was associated with increased proportions of the respective bacterial taxon. Fecal HMOs were significantly higher in L. reuteri fed babies despite similar HMO content in the milk consumed. Fecal metabolites associated with bifidobacteria fermentation products were significantly increased in B. infantis supplemented infants. Fecal calprotectin was lower in infants receiving B. infantis relative to L. reuteri ( P &lt; 0.01, Wilcoxon rank-sum test) and was negatively associated with the microbial metabolite indole-3-lactate (ILA). This study demonstrates that supplementing an HMO-catabolizing Bifidobacterium probiotic results in increased microbial metabolism of milk oligosaccharides and reduced intestinal inflammation relative to a noncatabolizing Lactobacillus probiotic in human milk-fed preterm infants. In this context, Bifidobacterium may provide greater benefit in human milk-fed infants via activation of the microbiota-metabolite-immune axis.

Iron Homeostasis Disruption and Oxidative Stress in Preterm Newborns.

Iron is an essential micronutrient for early development, being involved in several cellular processes and playing a significant role in neurodevelopment. Prematurity may impact on iron homeostasis in different ways. On the one hand, more than half of preterm infants develop iron deficiency (ID)/ID anemia (IDA), due to the shorter duration of pregnancy, early postnatal growth, insufficient erythropoiesis, and phlebotomy losses. On the other hand, the sickest patients are exposed to erythrocytes transfusions, increasing the risk of iron overload under conditions of impaired antioxidant capacity. Prevention of iron shortage through placental transfusion, blood-sparing practices for laboratory assessments, and iron supplementation is the first frontier in the management of anemia in preterm infants. The American Academy of Pediatrics recommends the administration of 2 mg/kg/day of oral elemental iron to human milk-fed preterm infants from one month of age to prevent ID. To date, there is no consensus on the type of iron preparations, dosages, or starting time of administration to meet optimal cost-efficacy and safety measures. We will identify the main determinants of iron homeostasis in premature infants, elaborate on iron-mediated redox unbalance, and highlight areas for further research to tailor the management of iron metabolism.

Effect of 100% human milk-derived fortifier on growth of premature infants with birth weight of 1000–1500 g

Background: Preterm birth has the highest risk of perinatal morbidity and mortality. Nutrition plays a key role in the growth and development of a preterm infant. Fortification of expressed breast milk is followed to provide an optimal nutrition and a faster catch up growth. The new 100% human milk-derived fortifier (HMDF) can help in providing a safe nutritional option for a premature infant. Objective: The objective of the study was to assess the feed tolerance and impact of a new 100% HMDF on growth outcomes of preterm infants. Materials and Methods: In a single-center study, exclusively human milk-fed preterm infants (1000–1500 g birth weight) were chosen to receive human milk fortified with a new 100% HMDF. The fortifier was initiated when the enteral feed volume reached 100 ml/kg/day and was administered until discharge. The primary outcome of the study was to assess feed tolerance and the secondary endpoints included growth parameters. Results: The cohort study comprised 13 infants with a mean gestational age of 31.64±2.2 weeks and birth weight of 1314.62±110.1 g. During the study period, feed interruptions were nil and none of the infants showed any adverse events of clinical significance. Growth outcomes recorded at the end of the study period showed a mean weight gain of 25.97±7.7 g/day, mean length gain of 0.32±0.23 cm/week, and mean head circumference gain of 0.39±0.20 cm/week. The mean weight growth velocity of the infants was 18.37±5.1 g/kg/day. Conclusion: Preterm infants who received a new 100% HMDF demonstrated feed tolerance and weight gain without any clinically significant record of adverse events. The findings indicate that the new HMDF is a safe option for providing an exclusive human milk-based diet. However, a study with a larger study population may be required to reinforce the findings of this study.

Optimizing the Use of Human Milk Cream Supplement in Very Preterm Infants: Growth and Cost Outcomes

An exclusive human milk-based diet has been shown to decrease necrotizing enterocolitis and improve outcomes for infants ≤1250 g birth weight. Studies have shown that infants who received an exclusive human milk diet with a donor-human milk-derived cream supplement (cream) had improved weight and length velocity when the cream was added to mother's own milk or donor-human milk when energy was <20 kcal/oz using a human milk analyzer. Our objective was to compare growth and cost outcomes of infants ≤1250 g birth weight fed with an exclusive human milk diet, with and without human milk cream, without the use of a human milk analyzer. Two cohorts of human milk-fed premature infants were compared from birth to 34 weeks postmenstrual age. Group 1 (2010-2011) received a donor-human milk fortifier, whereas Group 2 (2015-2016) received donor-human milk fortifier plus the commercial cream supplement, if weight gain was <15 g/kg/d. There was no difference in growth between the 2 groups for weight (P = 0.32) or head circumference (P = 0.90). Length velocity was greater for Group 1 (P = 0.03). The mean dose of donor-human milk fortifier was lower in Group 2 (P < 0.001). Group 2 saved an average of $2318 per patient on the cost of human milk products (P < 0.01). Infants receiving a human milk diet with cream supplementation for growth faltering achieve appropriate growth in a cost-effective feeding strategy.

Human milk protein vs. formula protein and their use in preterm infants.

We review the current available evidence on the metabolic fate of human milk proteins and their potential clinical implications for growth and body composition development vs. those of formula proteins in preterm infants. The decreased content of human milk protein in preterm mothers throughout lactation might contribute to the reduced growth reported in exclusively human milk-fed infants compared with that of formula-fed infants. Recent studies have demonstrated that preterm infants are capable of degrading human milk proteins regardless of their degree of prematurity or postnatal age, with limited contribution from milk proteases to protein digestion. The nitrogen balance of fortified human milk-fed preterm infants is higher than that of formula-fed preterm infants. Moreover, the growth of human milk-fed preterm infants appears to be accompanied by fat-free mass deposition. Provided that adequate protein and energy intakes are delivered, human milk enhances protein use rather than oxidation as well as promotes tissue growth, leading to preferential fat-free mass deposition and contributing to the recovery of the body composition in preterm infants. Human milk feeding should be supported and promoted for all preterm mother-infant pairs.

Pragmatism vs idealism in preterm human milk fortification

In this volume of The Journal, Schanler et al report the results of a randomized trial of an acidified human milk fortifier, compared with a non-acidified human milk fortifier, in premature infants weighing 700-1500 grams at birth. The authors hypothesized that infants fed the acidified human milk fortifier would have more acidosis and consequently, poorer growth than infants fed a non-acidified fortifier. To address this, the primary outcome of the study was the rate of weight gain. Other outcomes of interest were feeding tolerance and basic biochemical assessments including electrolytes and bicarbonate levels. Although the study showed significant differences in feeding tolerance and biochemical assessments between the groups, there were no differences in the primary outcome of weight gain for study days 1-29. Although the same nutrition protocol was described for all sites, some aspects of the trial were pragmatic and clinical teams were able to individualize nutritional management. As is typical in clinical practice, some infants received mostly donor milk, and some received non-study fortifiers, formula, or protein supplements that may have been prescribed to help with feeding tolerance and weight gain. This heterogeneity prompted the authors to perform extensive secondary and post-hoc analyses. From these analyses, we see that only about one-half of the infants received the ideal combination of >50% mother's own milk and the study fortifier, but this subgroup showed better weight gain with the non-acidified liquid fortifier. Although the investigators were not able to show a difference in the primary study outcome, the results of this study should be helpful to neonatologists as the trial reflected the “real world” use of human milk fortifiers and reaffirmed that in clinical practice, optimizing weight gain in preterm infants may be more complicated than the choice of a human milk fortifier. Article page 31 ▶ Improved Outcomes in Preterm Infants Fed a Nonacidified Liquid Human Milk Fortifier: A Prospective Randomized Clinical TrialThe Journal of PediatricsVol. 202PreviewTo compare growth, feeding tolerance, and clinical and biochemical evaluations in human milk-fed preterm infants randomized to receive either an acidified or a nonacidified liquid human milk fortifier. Full-Text PDF

Improved Outcomes in Preterm Infants Fed a Nonacidified Liquid Human Milk Fortifier: A Prospective Randomized Clinical Trial

To compare growth, feeding tolerance, and clinical and biochemical evaluations in human milk-fed preterm infants randomized to receive either an acidified or a nonacidified liquid human milk fortifier. This prospective, controlled, parallel, multicenter growth and tolerance study included 164 preterm infants (≤32 weeks of gestation, birth weight 700-1500 g) who were randomized to acidified or nonacidified liquid human milk fortifier from study day 1, the first day of fortification, through study day 29 or until hospital discharge. There was no difference in the primary outcome of weight gain from study days 1 to 29 (acidified liquid human milk fortifier, 16.4 ± 0.4 g/kg/day; nonacidified liquid human milk fortifier, 16.9 ± 0.4 g/kg/day). However, in both the intention-to-treat and the protocol evaluable analyses, infants fed nonacidified liquid human milk fortifier had significantly greater weight gain from study days 1 to 15 (17.9 g/kg/day vs 15.2 g/kg/day; P = .001). Infants fed with acidified liquid human milk fortifier received more protein (4.26 vs g/kg/day 4.11 g/kg/day, P = .0099) yet had lower blood urea nitrogen values (P = .010). The group fed acidified liquid human milk fortifier had more vomiting (10.3% vs 2.4%; P = .018), gastric residuals (12.8% vs 3.7%; P = .022), and metabolic acidosis (27% vs 5%; P < .001) in the intention-to-treat analysis and more abdominal distension (14.0% vs 1.7%; P = .015) in the protocol evaluable analysis. Infants fed an acidified liquid human milk fortifier had higher rates of metabolic acidosis and poor feeding tolerance compared with infants fed a nonacidified liquid human milk fortifier. Initial weight gain was poorer with the acidified liquid human milk fortifier. ClinicalTrials.gov: NCT02307760.

Associations of Measured Protein and Energy Intakes with Growth and Adiposity in Human Milk-Fed Preterm Infants at Term Postmenstrual Age: A Cohort Study.

To determine the associations of measured protein, energy, and protein-to-energy (PER) intakes with body composition in human milk (HM)-fed preterm infants. Neonates born at < 33 gestational weeks were eligible. Standard fortification method with modular supplements was used and the HM composition was measured. The weight gain velocity was calculated, and body composition was assessed by air displacement plethysmography at 40 weeks' postmenstrual age (PMA). The fat mass percentage and fat mass index were used as indicators of adiposity, with convenience cut-offs ≤ -1 and ≥ + 1 z-scores for low and high adiposity, respectively. Thirty-three infants were included (median [interquartile range] gestational age: 30 [28-31] weeks; birth weight: 1.175 [1.010-1.408] g); 36.4 and 84.8% did not receive the minimum recommended protein and energy intakes, respectively. Weight gain velocity showed positive weak-to-moderate correlations with nutrient intakes. Overall, no correlations between nutrient intakes and body composition were found. Infants with lower adiposity received lower energy, protein, and PER intakes, while those with higher adiposity received lower energy intake but higher PER intake. Overall, no correlations of nutrient intakes with body composition were found; however, differences in nutrient intakes were found between infants with lower and higher adiposity at term PMA.

Growth monitoring and follow-up in preterm infants

Preterm infants are often significantly growth retarded at the time of hospital discharge.They often in the nutritional crisis after hospital discharge, and should be carefully follow up evaluated.Preterm formula and fortified breast milk may improve the growth of preterm infants and is a reasonable option for preterm infants.Preterm formula and fortified breast milk are recommended for preterm infants with weights below the 10th percentile for age at the time of hospital discharge and those birth weights below 1 500 g. After hospital discharge, exclusively human milk-fed preterm infants are at increased risk for suboptimal growth compared to formula-fed infants.Infants with BPD are at increased risk of growth retardation after hospital discharge.Protein and mineral enriched formula may provide short-term growth catch-up. Key words: Infant, premature; Growth; Human milk; Fortified human milk; Preterm formula

Considerations in meeting protein needs of the human milk-fed preterm infant.

Preterm infants provided with sufficient nutrition to achieve intrauterine growth rates have the greatest potential for optimal neurodevelopment. Although human milk is the preferred feeding for preterm infants, unfortified human milk provides insufficient nutrition for the very low-birth-weight infant. Even after fortification with human milk fortifier, human milk often fails to meet the high protein needs of the smallest preterm infants, and additional protein supplementation must be provided. Although substantial evidence exists to support quantitative protein goals for human milk-fed preterm infants, the optimal type of protein for use in human milk fortification remains uncertain. This question was addressed through a PubMed literature search of prospective clinical trials conducted since 1990 in preterm or low-birth-weight infant populations. The following 3 different aspects of protein quality were evaluated: whey-to-casein ratio, hydrolyzed versus intact protein, and bovine milk protein versus human milk protein. Because of a scarcity of current studies conducted with fortified human milk, studies examining protein quality using preterm infant formulas were included to address certain components of the clinical question. Twenty-six studies were included in the review study. No definite advantage was found for any specific whey-to-casein ratio. Protein hydrolyzate products with appropriate formulations can support adequate growth and biochemical indicators of nutrition status and may reduce gastrointestinal transit time, gastroesophageal reflux events, and later incidence of atopic dermatitis in some infants. Plasma amino acid levels similar to those of infants fed exclusive human milk-based diets can be achieved with products composed of a mixture of bovine proteins, peptides, and amino acids formulated to replicate the amino acid composition of human milk. Growth and biochemical indicators of nutrition status are similar for infants fed human milk fortified with human milk protein and bovine milk protein.

Iron deficiency and anemia in iron-fortified formula and human milk-fed preterm infants until 6 months post-term

An iron intake of >2 mg/kg/d is recommended for preterm infants. We hypothesized that human milk (HM)-fed preterm infants require iron supplementation after discharge, whereas iron-fortified formulae (IFF; 0.8-1.0 mg iron/100 ml) may provide sufficient dietary iron until 6 months post-term. At term age, 3 and 6 months post-term, ferritin (μg/l) was measured in 92 IFF-fed infants (gestational age (median (interquartile range)) 30.7 (1.4) weeks, birth weight 1,375 (338) gram) and 46 HM-fed infants (gestational age 30.0 (1.7) weeks, birth weight 1,400 (571) gram). Iron intake (mg/kg/d) between term age and 6 months post-term was calculated. Iron was supplemented to 71.7% of HM-fed and 83.7% of IFF-fed infants between term age and 3 months post-term and to 13% of HM-fed and 0% of IFF-fed infants between 3 and 6 months post-term. IFF-fed infants had an iron intake from supplements and formula of 2.66 (1.22) mg/kg/d between term age and 3 months post-term and 1.19 (0.32) mg/kg/d between 3 and 6 months post-term. At 3 and 6 months post-term, the incidence of ferritin <12 μg/l was higher in HM-fed compared to IFF-fed infants (23.8 vs. 7.8% and 26.3 vs. 9.5%, P < 0.02). This observational study demonstrates that ferritin <12 μg/l is more prevalent in HM-fed infants until 6 months post-term. This may be due to early cessation of additional iron supplementation. We speculate that additional iron supplementation is not necessary in preterm infants fed IFF (0.8-1.0 mg iron/100 ml), as they achieve ferritin ≥12 μg/l without additional iron supplements between 3 and 6 months post-term.

A Comparison of Two Probiotic Strains of Bifidobacteria in Premature Infants

To determine the impact of 2 probiotic bifidobacteria on the fecal microbiota of premature infants fed either human milk or formula. In the first of two phase 1 clinical trials, 12 premature infants receiving formula feedings were assigned randomly to receive either Bifidobacterium longum ssp infantis or Bifidobacterium animalis ssp lactis in increasing doses during a 5-week period. In the second, 9 premature infants receiving their mother's milk received each of the two bifidobacteria for 2 weeks separated by a 1-week washout period. Serial stool specimens from each infant were analyzed by terminal restriction fragment-length polymorphism and quantitative polymerase chain reaction for bacterial composition. Among the formula-fed infants, there was a greater increase in fecal bifidobacteria among infants receiving B infantis (Binf) than those receiving B lactis (Blac). This difference was most marked at a dose of 1.4× 10(9) colony-forming units twice daily (P < .05). Bacterial diversity improved over dose/time in those infants receiving Binf. Among the human milk-fed infants, greater increases in fecal bifidobacteria and decreases in γ-Proteobacteria followed the administration of Binf than Blac. The B longum group (which includes Binf but not Blac) was the dominant bifidobacteria among the human milk-fed infants, regardless of the probiotic administered. Binf was more effective at colonizing the fecal microbiota than Blac in both formula-fed and human milk-fed premature infants. The combination of human milk plus Binf resulted in the greatest fecal levels of bifidobacteria.

Resonance Raman Spectroscopy and the Preterm Infant Carotenoid Status

The aim of the study was to validate the noninvasive resonance Raman spectroscopy (RRS) method in infants in comparison with the high-performance liquid chromatography (HPLC) method, and to evaluate the carotenoid status in preterm infants fed with mother's milk or formula. In the first phase of the study, resonance Raman measurements were made on male term infants' skin and correlated with tissue harvested at the time of circumcision. Each baby's foreskin was weighed, enzymatically digested, and the total carotenoids were extracted and quantitated by the HPLC. Next, to evaluate the carotenoid status of preterm infants (BW <1500 g), the skin and serum carotenoids in infants fed with either human milk or preterm formula were studied from the start of feedings and every 2 weeks until hospital discharge. Skin carotenoids were measured by RRS and the serum total carotenoids by HPLC. Foreskin carotenoid levels measured by RRS correlated with HPLC measurements of total serum carotenoids (R = 0.52, P < 0.01, n = 16). Forty preterm infants were studied for their carotenoid status. Thirty-two infants were fed mother's milk, whereas 8 were fed a preterm infant formula that was not enriched with carotenoids. The gestation and birth weight of the 2 feeding groups were similar. The infants fed human milk had a higher serum total carotenoid concentration and skin Raman counts than formula-fed infants. The skin Raman counts and total serum carotenoid correlated (R = 0.44, P = 0.01). The human milk-fed infants' serum total carotenoid concentrations and Raman values did not change during the study period; however, the formula-fed group's total serum and skin carotenoid decreased significantly during the study. RRS of infant's skin reliably assesses total carotenoid status noninvasively. Human milk-fed preterm infants have higher serum and skin carotenoids than formula-fed infants suggesting that formula-fed infants may benefit from carotenoid supplementation.

Effect of increasing protein content of human milk fortifier on growth in preterm infants born at

Preterm human milk-fed infants often experience suboptimal growth despite the use of human milk fortifier (HMF). The extra protein supplied in fortifiers may be inadequate to meet dietary protein requirements for preterm infants. We assessed the effect of human milk fortified with a higher-protein HMF on growth in preterm infants. This is a randomized controlled trial in 92 preterm infants born at <31 wk gestation who received maternal breast milk that was fortified with HMF containing 1.4 g protein/100 mL (higher-protein group) or 1.0 g protein/100 mL (current practice) until discharge or estimated due date, whichever came first. The HMFs used were isocaloric and differed only in the amount of protein or carbohydrate. Length, weight, and head-circumference gains were assessed over the study duration. Length gains did not differ between the higher- and standard-protein groups (mean difference: 0.06 cm/wk; 95% CI: -0.01, 0.12 cm/wk; P = 0.08). Infants in the higher-protein group achieved a greater weight at study end (mean difference: 220 g; 95% CI: 23, 419 g; P = 0.03). Secondary analyses showed a significant reduction in the proportion of infants who were less than the 10th percentile for length at the study end in the higher-protein group (risk difference: 0.186; 95% CI: 0.370, 0.003; P = 0.047). A higher protein intake results in less growth faltering in human milk-fed preterm infants. It is possible that a higher-protein fortifier than used in this study is needed. This trial was registered with the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au/) as ACTRN12606000525583.

Human Milk and Kangaroo Mother Care

Significant benefits on infant host defense, sensory-neural development, gastrointestinal maturation, and some aspects of nutritional status are observed when preterm infants are fed with their mothers' own milk. A reduction in infection-related morbidity in human milk-fed preterm infants has been reported. Studies on neuro-developmental outcomes have reported significantly positive effects for human milk intake on mental and motor development. Human milk-fed infants also have decreased rates of rehospitalization following discharge. Hospital-based practices may contribute to increased rates of breast milk feeding for preterm infants for longer periods of time. There is quite a lot of information available on using KMC to promote maternal breastfeeding with the aim of increasing its frequency and duration in preterm infants. The positive effects of Kangaroo skin-to-skin contact on breastfeeding can be stated with some confidence. The provision of personal breastfeeding education and support by a skilled nurse as an integral part of the interventions is likely to increase the success of the intervention both in terms of breastfeeding outcomes and the acceptability of KMC. We should not therefore pass up the opportunity to introduce a low cost intervention such as KMC with consistently beneficial effects demonstrated. Keywords: Kangaroo Mother Care, breastfeeding, very low birth weight, human milk, preterm infants, skin-to-skin contact, gastrointestinal maturation, necrotizing enterocolitis, infant host defense

Improved Cognitive Development Among Preterm Infants Attributable to Early Supplementation of Human Milk With Docosahexaenoic Acid and Arachidonic Acid

The objective of our study was to evaluate the effect of supplementation with docosahexaenoic acid and arachidonic acid for human milk-fed preterm infants. The primary end point was cognitive development at 6 months of age. The study was a randomized, double-blind, placebo-controlled study among 141 infants with birth weights of <1500 g. The intervention with 32 mg of docosahexaenoic acid and 31 mg of arachidonic acid per 100 mL of human milk started 1 week after birth and lasted until discharge from the hospital (on average, 9 weeks). Cognitive development was evaluated at 6 months of age by using the Ages and Stages Questionnaire and event-related potentials, a measure of brain correlates related to recognition memory. There was no difference in adverse events or growth between the 2 groups. At the 6-month follow-up evaluation, the intervention group performed better on the problem-solving subscore, compared with the control group (53.4 vs 49.5 points). There was also a nonsignificant higher total score (221 vs 215 points). The event-related potential data revealed that infants in the intervention group had significantly lower responses after the standard image, compared with the control group (8.6 vs 13.2). There was no difference in responses to novel images. Supplementation with docosahexaenoic acid and arachidonic acid for very preterm infants fed human milk in the early neonatal period was associated with better recognition memory and higher problem-solving scores at 6 months.