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Importance: Maternal milk feeding may have unique long-term neurodevelopmental benefits in very preterm infants., Objective: To examine the extent to which maternal milk feeding after very preterm birth is associated with cognitive, academic, and behavioral outcomes at school age., Design, Setting, and Participants: This prospective cohort study assessed 586 infants born at less than 33 weeks' gestation at 5 Australian perinatal centers and enrolled in the Docosahexaenoic Acid for Improvement of Neurodevelopmental Outcomes study (January 1, 2001, to December 31, 2005) who were evaluated at a corrected age of 7 years. The statistical analysis was completed on January 19, 2022., Exposures: Maternal milk intake, including mean volume (milliliters per kilogram per day) during neonatal hospitalization and total duration (in months)., Main Outcomes and Measures: Neurodevelopmental outcomes at 7 years of age were (1) IQ (Wechsler Abbreviated Scale of Intelligence), (2) academic achievement (Wide Range Achievement Test, Fourth Edition), (3) symptoms of attention-deficit/hyperactivity disorder (ADHD) (Conners Third Edition ADHD Index, parent reported), (4) executive function (Behavior Rating Inventory of Executive Functioning, parent reported), and (5) behavior (Strengths and Difficulties Questionnaire, parent reported)., Results: A total of 586 infants (mean [SD] gestational age at birth, 29.6 [2.3] weeks; 314 male [53.6%]) born to 486 mothers (mean [SD] age, 30.6 [5.5] years; 447 [92.0%] White) were included. Mean (SD) maternal milk intake in the neonatal intensive care unit was 99 (48) mL/kg daily, and mean (SD) maternal milk duration was 5.1 (5.4) months. Mean (SD) full-scale IQ was 98.5 (13.3) points. After covariate adjustment, higher maternal milk intake during the neonatal hospitalization was associated with higher performance IQ (0.67 points per additional 25 mL/kg daily; 95% CI, 0.10-1.23 points), reading scores (1.14 points per 25 mL/kg daily; 95% CI, 0.39-1.89 points), and math scores (0.76 points per 25 mL/kg daily; 95% CI, 0.14-1.37 points) and fewer ADHD symptoms (-1.08 points per 25 mL/kg daily; 95% CI, -1.96 to -0.20 points). Longer duration of maternal milk intake was associated with higher reading (0.33 points per additional month; 95% CI, 0.03-0.63 points), spelling (0.31 points per month; 95% CI, 0.01-0.62 points), and math (0.30 points per month; 95% CI, 0.03-0.58 points) scores. Maternal milk was not associated with improved full-scale IQ, verbal IQ, executive function, or behavior. Most associations were stronger among infants born at lower gestational ages, particularly less than 30 weeks (interaction P values <.01)., Conclusions and Relevance: In this cohort study of preterm infants, maternal milk feeding during the neonatal hospitalization and after discharge were associated with better school-age performance IQ and academic achievement and with a reduction in ADHD symptoms, particularly among infants born at less than 30 weeks' gestation.

Aim: To determine the impact of the pumping regimes of women with preterm infants on the daily milk production, and on the short-term rate of milk synthesis during early lactation to support evidence-based recommendations for optimising milk production., Methods: Mothers of preterm infants (n=25) recorded start time, finish time and expression volumes from every breast expression on days 10, 15-20 postpartum., Results: Expressing more often than five times per day did not result in a significant increase in daily milk production. Milk volume per expression per breast increased for intervals between expressions of between 2and6 hours then reached a plateau when the interval between expression was 7 hours or longer. The short-term rate of milk synthesis decreased as the interval between expressions increased until about 7.5 hours at which point it begun to increase (p value associated with interval between expressions^2<0.001)., Conclusion: The strong inverse association between the short-term rate of milk synthesis and the interval between expressions for intervals up to 7 hours suggest that the maximum interval between expressions should be 7 hours. Data suggest that, on average, the mothers should express at least five times a day to maximise daily milk production. Considering inter-individual variation, determination of an individual mother's maximum interval between expressions that does not compromise the short-term rate of milk synthesis will help to optimise daily milk production while minimising the demands on the mother's time., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Supplementation with probiotics in preterm infants reduces necrotizing enterocolitis and sepsis. Bovine lactoferrin is a promising supplement that may further reduce disease burden, but its effects on probiotic bacteria in human breast milk has not been evaluated. We aimed to characterise the antimicrobial activity of bovine and human lactoferrin in human breast milk against probiotics and typical neonatal sepsis pathogens. Lactoferrin levels were determined by enzyme linked immunosorbent assay in fresh and pasteurised human breast milk. The neonatal pathogens Staphylococcus epidermidis and Escherichia coli, and the probiotic Bifidobacterium breve strain M-16V were cultured in human breast milk or infant formula in the presence or absence of clinically relevant doses of bovine or human lactoferrin. Standard microbiological methods were used to determine the effects of lactoferrin on bacterial growth. Unpasteurised human breast milk contained significantly higher lactoferrin levels and resulted in superior inhibition of pathogenic bacterial growth compared to infant formula and pasteurised human breast milk. Human lactoferrin was significantly more effective at inhibiting bacterial growth, when compared to bovine lactoferrin. Supplementation with human lactoferrin or high dose bovine lactoferrin inhibited growth of the probiotic strain B. breve M-16V in pasteurised human breast milk. Although unpasteurised human breast milk and human lactoferrin had the greatest antimicrobial activity against all bacterial species tested, higher doses of bovine lactoferrin also showed activity against B. breve and. S. epidermidis. This study suggests that simultaneous administration of lactoferrins and probiotics may affect colonisation with probiotic bacteria, warranting further investigations., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of this study was to measure consumption and absorption of human milk oligosaccharides (HMOs) in a cohort of premature infants treated with probiotic Bifidobacterium breve., Methods: Twenty-nine premature infants (median gestational age 28 weeks, range 23-32 weeks) cared for in the neonatal intensive care unit of the King Edward and Princess Margaret Hospital in Perth, Australia, were treated with B breve at a dose of 1.66 billion organisms per day. Samples of feces, urine, and milk were obtained at initiation of the probiotic and again 3 weeks later. 16S ribosomal RNA from the feces was analyzed by next-generation sequencing. Quantitation of HMO content of the milk, urine, and feces was performed using nano-high-performance liquid chromatography-chip/time-of-flight mass spectrometry., Results: There was heterogeneity in colonization with bifidobacteria. "Responders" received milk with higher percentages of fucosylated HMOs and had higher percentages of bifidobacteria and lower percentages of Enterobacteriaceae in their feces than "nonresponders." Several individual HMOs in the milk were associated with changes in fecal bifidobacteria over time. Changes over time in milk, fecal, and urine HMOs suggested heterogeneity among HMO structures in consumption by microbes in the gut lumen and absorption from the intestine., Conclusions: Colonization of the premature infant intestinal tract with probiotic B breve is influenced by prebiotic HMOs. B breve is a selective consumer of HMOs in the premature infant.

Background: The effect of human milk intake on neurodevelopment in preterm infants is uncertain., Methods: We analyzed data from 611 participants in the DHA for Improvement of Neurodevelopmental Outcomes study, enrolled at ≤33 wk gestation from five Australian perinatal centers. The main exposures were (i) average daily human milk intake during the neonatal hospitalization and (ii) total duration of human milk intake before and after discharge. Outcomes were Bayley Scales of Infant Development, 2nd Edition Mental (MDI), and Psychomotor (PDI) Development Indexes., Results: Adjusting for confounders in linear regression, human milk intake was not associated with higher MDI (0.2 points per 25 ml/kg/d; 95% confidence interval (CI): -0.6, 1.0) or PDI (-0.3 points; 95% CI: -1.1, 0.4). Longer duration of human milk intake was also not associated with MDI (0.1 points per month; 95% CI: -0.2, 0.3) or PDI (-0.2 points per month; 95% CI: -0.5, 0.01) scores, except in infants born 29-33 wk gestation (n = 364, MDI 0.3 points higher per additional month, 95% CI: 0.1, 0.6)., Conclusions: We found no associations of human milk intake during the neonatal hospitalization with neurodevelopment at 18 mo corrected age.

There are wide variations in the macronutrient values adopted by neonatal intensive care units and industry to fortify milk in efforts to achieve recommended intakes for preterm infants. Contributing to this is the variation in macronutrient composition of preterm milk between and within mothers and the variable quality of milk analyses used to determine the macronutrient content of milk. We conducted a systematic review of the literature using articles published in English between 1959 and 2013 that reported the concentrations of one or more macronutrients or energy content in human preterm milk, sampled over a representative 24-h period. Searched medical databases included Ovid Medline, Scopus, CINAHL and the Cochrane Library. Results are presented as mean values and ranges for each macronutrient during weeks 1-8 of lactation, and preferred mean values (g/100 ml) for colostrum (week 1) and mature milk (weeks 2-8; protein: 1·27, fat: 3·46, lactose: 6·15 and carbohydrate: 7·34), using data from studies employing the highest-quality analyses. Industry-directed fortification practices using these mean values fail to meet protein targets for infants weighing <1000 g when the fortified milk is fed <170-190 ml/kg per d, and the protein:energy ratio of the fortified milk is inadequate. This study aimed to provide additional information to industry in order to guide their future formulation of breast milk fortifiers. Quality macronutrient analyses of adequately sampled preterm breast milk would improve our understanding of the level of fortification needed to meet recommended protein and energy intakes and growth targets, as well as support standardised reporting of nutritional outcomes.

Pasteurized donor human milk is provided by milk banks to very preterm babies where their maternal supply is insufficient or unavailable. Donor milk is currently processed by Holder pasteurization, producing a microbiologically safe product but significantly reducing immunoprotective components. Ultraviolet-C (UV-C) irradiation at 254 nm is being investigated as an alternative treatment method and has been shown to preserve components such as lactoferrin, lysozyme and secretory IgA considerably better than Holder pasteurization. We describe the inactivation of cytomegalovirus, a virus commonly excreted into breast milk, using UV-C irradiation. Full replication was ablated by various treatment doses. However, evidence of viral immediate early proteins within the cells was never completely eliminated indicating that some viral gene transcription was still occurring. In conclusion, UV-C may be a safe alternative to pasteurisation for the treatment of human donor milk that preserves the bioactivity. However, our data suggests that CMV inactivation will have to be carefully evaluated for each device designed to treat breast milk using UV-C irradiation.

There is a paucity of data on the effect of preterm birth on the immunological composition of breast milk throughout the different stages of lactation. We aimed to characterise the effects of preterm birth on the levels of immune factors in milk during the 1st month postpartum, to determine whether preterm milk is deficient in antimicrobial factors. Colostrum (days 2-5 postpartum), transitional milk (days 8-12) and mature milk (days 26-30) were collected from mothers of extremely preterm (<28 weeks of gestation, n 15), very preterm (28-<32 weeks of gestation, n 15), moderately preterm (32-<37 weeks of gestation, n 15) and term infants (37-41 weeks of gestation, n 15). Total protein, lactoferrin, secretory IgA, soluble CD14 receptor (sCD14), transforming growth factor-β2 (TGF-β2), α defensin 5 (HD5), β defensins 1 (HBD1) and 2, IL-6, IL-10, IL-13, interferon-γ, TNF-α and lysozyme (LZ) were quantified in milk. We examined the effects of lactation stage, gestational age, volume of milk expressed, mode of delivery, parity and maternal infection on milk immune factor concentrations using repeated-measures regression analysis. The concentrations of all factors except LZ and HD5 decreased over the 1st month postpartum. Extremely preterm mothers had significantly higher concentrations of HBD1 and TGF-β2 in colostrum than term mothers did. After controlling for other variables in regression analyses, preterm birth was associated with higher concentrations of HBD1, LZ and sCD14 in milk samples. In conclusion, preterm breast milk contains significantly higher concentrations of some immune proteins than term breast milk.

The variable content of human breast milk suggests that its routine fortification may result in sub-optimal nutritional intakes and growth. In a pragmatic trial, we randomised infants born below 30 weeks of gestation to either the intervention (Igp) of fortifying milk on measured composition according to birth weight criteria and postmenstrual age (PMA) or our routine practice (RPgp) of fortifying on assumed milk composition to target 3·8-4·4 g protein/kg per d and 545-629 kJ/kg per d. Milk composition was measured using the MIRIS® Human Milk Analyser. Percentage fat mass (%FM) was measured using PEA POD (COSMED). The effects of macronutrient intakes and clinical variables on growth were assessed using mixed model analysis. Mean measured protein content (1·6 g/100 ml) was higher than the assumed value (1·4 g/100 ml), often leading to lower amounts of fortifier added to the milk of intervention infants. At discharge (Igp v. RPgp), total protein (3·2 (SD 0·3) v. 3·4 (SD 0·4) g; P=0·067) and energy (456 (SD 39) v. 481 (SD 48) kJ; P=0·079) intakes from all nutrition sources, weight gain velocity (11·4 (SD 1·4) v. 12·1 (SD 1·6) g/kg per d; P=0·135) and %FM (13·7 (SD 3·6) v.13·6 (SD 3·5) %; P=0·984) did not significantly differ between groups. A protein intake >3·4 g/kg per d reduced %FM by 2%. Nutrition and growth was not improved by targeting milk fortification according to birth weight criteria and PMA using measured milk composition, compared with routine practice. Targeting fortification on measured composition is labour intensive, requiring frequent milk sampling and precision measuring equipment, perhaps reasons for its limited practice. Guidance around safe upper levels of milk fortification is needed.

Aim: Preterm nutrition guidelines target nutrient accretion and growth at intrauterine rates, yet at term equivalent age, the phenotype of the preterm infant differs from that of term infants. Monitoring early changes in preterm body composition (BC) in response to macronutrient intakes may facilitate our understanding of how best to meet preterm nutrition and growth targets., Method: Macronutrient intakes based on milk analysis were calculated from birth for infants born <33 weeks gestation. BC was measured in the PEA POD when infants were thermodynamically stable, free of intravenous lines and independent of respiratory support. Subsequent BC measurements were taken at least fortnightly until term age. Regression analysis was used to assess macronutrient influences on changes in BC., Results: Median (range) gestation and birthweight of preterm infants (n = 27) were 29 (25-32) weeks and 1395 (560-2148) g, respectively. The youngest corrected gestational and postnatal ages that infants qualified for a PEA POD measurement were 31.86 and 1.43 weeks, respectively. Fat and total energy intakes were positively associated with increasing fat mass. Protein (with carbohydrate) intake was positively associated with increasing fat-free mass., Conclusion: Preterm infants can be measured in the PEA POD as early as 31 weeks corrected gestational age and the method appears sufficiently sensitive to detect influences of macronutrient intake on changes in BC., (© 2015 The Authors. Journal of Paediatrics and Child Health © 2015 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Background: Extremely preterm infants are highly susceptible to bacterial infections but breast milk provides some protection. It is unknown if leukocyte numbers and subsets in milk differ between term and preterm breast milk. This study serially characterised leukocyte populations in breast milk of mothers of preterm and term infants using multicolour flow cytometry methods for extended differential leukocyte counts in blood., Methods: Sixty mothers of extremely preterm (<28 weeks gestational age), very preterm (28-31 wk), and moderately preterm (32-36 wk), as well as term (37-41 wk) infants were recruited. Colostrum (d2-5), transitional (d8-12) and mature milk (d26-30) samples were collected, cells isolated, and leukocyte subsets analysed using flow cytometry., Results: The major CD45+ leukocyte populations circulating in blood were also detectable in breast milk but at different frequencies. Progression of lactation was associated with decreasing CD45+ leukocyte concentration, as well as increases in the relative frequencies of neutrophils and immature granulocytes, and decreases in the relative frequencies of eosinophils, myeloid and B cell precursors, and CD16- monocytes. No differences were observed between preterm and term breast milk in leukocyte concentration, though minor differences between preterm groups in some leukocyte frequencies were observed., Conclusions: Flow cytometry is a useful tool to identify and quantify leukocyte subsets in breast milk. The stage of lactation is associated with major changes in milk leukocyte composition in this population. Fresh preterm breast milk is not deficient in leukocytes, but shorter gestation may be associated with minor differences in leukocyte subset frequencies in preterm compared to term breast milk.

Objective: We investigated the levels and antimicrobial activity of antimicrobial proteins and peptides (AMPs) in breast milk consumed by preterm infants, and whether deficiencies of these factors were associated with late-onset neonatal sepsis (LOS), a bacterial infection that frequently occurs in preterm infants in the neonatal period., Study Design: Breast milk from mothers of preterm infants (≤ 32 weeks gestation) was collected on days 7 (n = 88) and 21 (n = 77) postpartum. Concentrations of lactoferrin, LL-37, beta-defensins 1 and 2, and alpha-defensin 5 were measured by enzyme-linked immunosorbent assay. The antimicrobial activity of breast milk samples against Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Streptococcus agalactiae was compared to the activity of infant formula, alone or supplemented with physiological levels of AMPs. Samples of breast milk fed to infants with and without subsequent LOS were compared for levels of AMPs and inhibition of bacterial growth., Results: Levels of most AMPs and antibacterial activity in preterm breast milk were higher at day 7 than at day 21. Lactoferrin was the only AMP that limited pathogen growth >50% when added to formula at a concentration equivalent to that present in breast milk. Levels of AMPs were similar in the breast milk fed to infants with and without LOS, however, infants who developed LOS consumed significantly less breast milk and lower doses of milk AMPs than those who were free from LOS., Conclusions: The concentrations of lactoferrin and defensins in preterm breast milk have antimicrobial activity against common neonatal pathogens.

Human milk is the feed of choice for preterm infants. However, human milk does not provide enough nutrition, especially protein, for preterm infants to achieve target growth rates similar to those in utero (15-20 g/kg per day). Fortifiers for human milk, manufactured from bovine milk, are commercially available and routinely used for patients born <32 weeks' gestation prior to discharge home. Recent recommended dietary intakes (RDI) have been revised. Up to 4.2 g of protein and 135 kcal/kg per day is recommended for infants born very preterm. Additional supplements are needed to current commercial fortifiers to achieve these RDI and reduce the incidence of ex-uterine growth failure. A human milk fortifier that is manufactured from donor human milk is available in some developed countries and may confer some clinical benefits, including a reduction in necrotizing enterocolitis. Fortification can be added in a standardized protocol as per manufacturers' instructions. Human milk composition can be analyzed and fortification individualized to take into account the large variation from mother to mother. Alternatively, fortification can be increased in a stepwise manner based on assumed composition while monitoring blood urea levels for safety. The current aim is to prevent preterm infants dropping percentiles and falling below the 10th percentile at 36 weeks' corrected gestational age or discharge home. More data are required on how best to fortify human milk for preterm infants to achieve optimal growth, development and health outcomes in the long term. There is an urgent need for well-designed and informed randomized clinical trials in this vulnerable preterm population., (© 2015 Nestec Ltd., Vevey/S. Karger AG, Basel.)

Aim: Preterm nutritional audits have previously been conducted using assumed milk composition. We audited protein and energy intakes in the first 28 days of preterm life using both assumed milk composition and milk analysis to assess their effect on weight gain and to determine if the recommended reasonable range of intakes were met., Methods: Parenteral and enteral intakes and weight gain were recorded daily for infants (n = 63) born <33 weeks gestation, using assumed milk composition. Macronutrient composition was determined by milk analysis for a subset of infants (n = 36). Linear mixed models analysis was used to assess the influence of energy and protein intakes on weight gain., Results: (Data median (range)): Infants (n = 63) gestation and birth weight were 30 (24-32) weeks and 1400 (540-2580) g, respectively. Macronutrient milk composition was variable: protein 16.6 (13.4-27.6) g/L, fat 46.1 (35.0-62.4) g/L, lactose 68.0 (50.9-74.8) g/L, energy 3074 (2631-3761) kJ/L. Intakes based on measured composition differed from assumed. Protein intake was significantly associated with weight gain. Compared to infants with longer gestations, those born <28 weeks gestation were fed lower volumes, were more reliant on parenteral nutrition, took an additional seven days to transition to fortified feeds and median weight gain velocity took a fortnight longer to reach targets., Conclusion: Preterm milk composition is variable and routine fortification using assumed composition may result in inappropriate nutrition. Fortification regimens stratified by birth gestation may be necessary to achieve preterm nutrition and growth targets. Milk analysis is required for accurate nutritional audit., (© 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).)

Introduction: Although omega (n)-3 long-chain polyunsaturated fatty acids (LCPUFA), particularly docosahexaenoic acid (DHA), intakes are important during infancy, the optimal method of increasing infant status remains unclear. We hypothesized that high-dose infant fish oil supplementation would have greater relative effects upon n-3 LCPUFA status at six months of age than breast milk fatty acids., Patients and Methods: Infants (n=420) were supplemented daily from birth to six months with fish oil or placebo. In a subset of infants, LCPUFA levels were measured in cord blood, breast milk and in infant blood at 6 months., Results: DHA levels increased in the fish oil group relative to placebo (p<05). Breast milk DHA was the strongest predictor of infant erythrocyte DHA levels (p=<001). This remained significant after adjustment for cord blood DHA, supplementation group and adherence., Conclusion: In this cohort, breast milk DHA was a greater determinant of infant erythrocyte n-3 LCPUFA status, than direct supplementation with fish oil., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Aim: Breastfeeding mothers expressed their breasts hourly for periods up to 7 hours, without exogenous oxytocin, to determine the consistency of milk removal and the relationship between the volume of milk removed and the mother's 24-hour milk production., Methods: Mothers (n = 20) measured their 24-hour milk production from each breast by test-weighing their babies at home. Mothers came to the research laboratory for a day visit and expressed milk from either both or one breast (left or right) for 10-15 minutes, every hour for 2-7 hours. Mothers were not instructed to restrict breastfeeding prior to the first (0-hour) expression., Results: It was found that the milk volume at 1 hour (59.7 +/- 36.5 and 46.5 +/- 25.6 mL/hour for the right and left breast, respectively) was significantly (p < 0.05) higher than the milk volume from subsequent hourly intervals. The average hourly volumes obtained from the 2nd to 7th hour (18.0 +/- 3.1 and 14.0 +/- 4.8 mL/hour for the right and left breast, respectively) were not significantly different from the average hourly rates calculated for the 24-hour milk production (18.4 +/- 6.3 and 15.5 +/- 5.1 mL/hour for the right and left breast, respectively). Furthermore, local inhibition was not observed during hourly expressions of up to 7 hours., Conclusion: The average hourly volumes of milk from the 2nd to 7th hour expressions could provide an estimate of the rate of milk secretion. Further study is required to fully validate these findings.

The combination of ultrasound and heat (thermoultrasound) is an emerging food preservation technique that retains higher quantities of bioactive components compared with current thermal pasteurization practice, but has not yet been assessed for pasteurizing human milk. Artificially contaminated human milk samples were treated with ultrasound (20 kHz, 150 watts) with and without heating. The retention of four human milk proteins was quantified by biochemical assay and laser scattering particle sizing was used to determine the extent of homogenization. While ultrasonic treatment was effective at inactivating Escherichia coli (D4 degrees C=5.94 min), Staphylococcus epidermidis exhibited resistance (D4 degrees C=16.01 min). Thermoultrasonic treatment was considerably more effective (Esch. coli D45 degrees C=1.74 min, D50 degrees C=0.89 min; Staph. epidermidis D45 degrees C=2.08 min, D50 degrees C=0.94 minutes) with a predicted retention (2.8 min treatment, 50 degrees C) of secretory IgA lysozyme, lactoferrin and bile salt stimulated lipase of 91, 80, 77, and 45%, respectively. Homogenization of the milk samples occurred after 5 min and 2 min of ultrasonic and thermoultrasonic treatment, respectively. Thermoultrasonic treatment is an effective method for pasteurizing donor human milk and retaining a greater proportion of bioactive components compared with current practices. However, further studies are required to assess the practicality of applying this technique routinely to donor human milk.

Background: It is necessary to fortify human milk to promote optimal growth of the very preterm infant. However, the addition of non-human milk components to human milk is not ideal because of the risk of feeding intolerance and necrotizing enterocolitis. Human milk products (HMP) are an alternative to commercially available fortifiers, but their preparation is likely to result in modifications to the qualities of human milk., Methods: Ten batches of HMP were prepared with the aim of meeting a desired protein:energy ratio of 3.0 g of protein/100 kcal. Ultrafiltration was used to produce a skim milk concentrate, to which cream was then added to produce the final HMP. Characterization of HMP and human milk fortified with commercial human milk fortifiers (Nutriprem [Cow & Gate, Limerick, Ireland] and S-26 SMA human milk fortifier [Wyeth Nutrition, Baulkham Hills, NSW, Australia]) included quantifying macronutrient content, osmolality, microbial content, and particle distribution., Results: Average protein:energy ratio of the final batch was 2.93 +/- 0.10 g of protein/100 kcal, equating to an inaccuracy of 2.5% relative to the desired ratio of 3.0 g of protein/100 kcal. Significantly greater fat (P < 0.01), lower lactose (P < 0.001), and lower osmolality (P < 0.001) were characteristic of the HMP compared to human milk fortified with either commercial fortifier. Microbial growth occurred during preparation of HMP but did not exceed 10(5) colony-forming units/mL, and pasteurization of human milk prevented contamination in 80% of batches., Conclusions: HMP can be designed to accurately target the protein and energy requirements of the preterm infant, but modifications of the macronutrient, biochemical, structural, and microbial characteristics of human milk may affect the quality of the final product.

Pasteurizing donor human milk inactivates bacteria that may be of concern to the preterm infant. However, current practice for Holder Pasteurization (62.5 degrees C for 30 min) is detrimental to the bioactivity of human milk. An experimental pasteurizer was used to determine the maximum temperature at which 90% of secretory IgA, lysozyme, and lactoferrin were retained and whether this temperature was capable of inactivating five common bacterial contaminants. The retention of these proteins was also compared using a commercially available bottle immersion or holding chamber system. After pasteurization at 62.5 degrees C for 30 min, the retention across all three systems was 72.3 +/- 3.6%, 21.8 +/- 3.3%, and 39.4 +/- 11.5% for sIgA, lactoferrin, and lysozyme, respectively (n = 22). The retention of all three proteins was at least 90% when human milk was pasteurized at 57 degrees C for 30 min, and this temperature was also effective at removing 99.9% of all inoculated bacterial species. In addition, human milk that was pasteurized in the experimental system had a significantly higher proportion of lysozyme compared with samples pasteurized in the bottle immersion system. These findings suggest that optimizing pasteurization temperature and improving pasteurizer design enhances the quality of pasteurized donor human milk.

Aims: To investigate the possibility of a dose-response relationship for the use of domperidone in treating insufficient milk supply in mothers of preterm infants, and to quantify the exposure of the breastfed infant to domperidone., Methods: Six preterm mothers received domperidone (30 mg daily or 60 mg daily) in a double-blind, randomized, crossover trial. Milk production and serum prolactin were measured before and during the trial, and domperidone concentration in milk was measured during drug treatment., Results: For milk production, two of the mothers were 'nonresponders', whereas the other four were 'responders' and showed a significant increase in milk production from 8.7 +/- 3.1 g h(-1) in the run-in phase (mean +/- SEM), 23.6 +/- 3.9 g h(-1) for the 30-mg dose (P = 0.0217) and 29.4 +/- 6.6 g h(-1) for the 60-mg dose (P = 0.0047). In all participants, serum prolactin was significantly increased for both doses, but the response was not dose dependent. Median (interquartile range) domperidone concentrations in milk over a dose interval at steady-state were 0.28 microg l(-1) (0.24-0.43) and 0.49 microg l(-1) (0.33-0.72) for the 30-mg and 60-mg doses, respectively. The mean relative infant dose was 0.012% at 30 mg daily and 0.009% at 60 mg daily., Conclusion: In one-third of mothers, domperidone did not increase milk production. In the remainder, milk production increased at both domperidone doses, and there was a trend for a dose-response relationship. The amount of domperidone that transfers into milk was extremely low, and infant exposure via breastfeeding was not considered to be significant.

Background: The optimal form and dose of selenium supplementation required to achieve indicators of selenium status equivalent to those in breastfed infants are unclear., Objective: The objective was to evaluate the effect of fortifying infant formula (6 microg Se/L) with 2 concentrations of selenate (7 and 15 microg/L) on biochemical indicators of selenium status and growth at 16 wk in term infants., Design: A randomized dose-response trial was conducted in 3 groups of term infants fed formula with different selenium concentrations [6 microg/L, F+0 (control); 13 microg/L, F+7; and 21 microg/L, F+15] and in a parallel breastfed reference group (BF; 11 +/- 2 microg Se/L)., Results: One hundred sixty-one (47% males) infants completed the 16-wk study. Baseline plasma selenium was 0.3 +/- 0.1 micromol/L. At 16 wk, plasma selenium had increased in all groups (P < 0.001) and was greater (P < 0.01) in the F+7 and F+15 groups and lower (P < 0.05) in the F+0 group than in the BF group. Plasma glutathione peroxidase increased in the F+15 group, decreased in the F+0 group, and, at 16 wk, was lower in the F+0 group than in the other groups (all P < 0.05). Erythrocyte selenium and glutathione peroxidase decreased in all groups (P < 0.05), but the magnitude of the change was greater in the F+0 than in the F+15 group (P < 0.05). There was no effect of selenium supplementation on growth., Conclusions: Selenate fortification of formula resulted in an increase in plasma indicators of selenium status relative to indicators observed in infants fed low-selenium-containing formula. Although the erythrocyte indicators decreased in all groups, the 21-microg/L dose (F+15 group) resulted in a smaller decrease and in higher erythrocyte selenium than did the standard formula. Supplementation of low-selenium formula to provide a net selenium concentration close to that found in the breast milk of US women (18 microg/L) may be justified.

Objective: The onset of copious milk secretion after birth is known as lactogenesis II. The objective of this study was to investigate the effect of preterm birth and antenatal corticosteroids on the timing of lactogenesis II after birth., Methods: Women who had received antenatal betamethasone treatment and were expressing for a preterm infant whose gestational age was <34 weeks (N = 50) were included. On days 1 to 10 postpartum, participants measured the volume of milk expressed in 24-hour periods and collected milk samples. Lactose and citrate levels were analyzed in the milk., Results: The gestational age at delivery was 31 weeks (range: 24.2-33.7). Milk volume was recorded by 46 women on 320 expression days and was positively associated with gestational age. Gestational age modified the effect of interval between betamethasone administration and delivery on milk volume. At gestational age 28 to 34 weeks, women who delivered 0 to 2 days after betamethasone treatment obtained significantly greater volumes than women who delivered 3 to 9 days after treatment. Milk samples (N = 324) were collected by 42 mothers. Mean +/- SD lactose and citrate levels were 156.800 +/- 36.217 and 3.458 +/- 1.442 mM, respectively. There was a significant positive effect of gestational age on milk lactose levels but not citrate levels. Betamethasone treatment did not alter lactose or citrate levels in milk., Conclusions: Delivery at extremely preterm gestational ages caused a significant delay in the onset of lactogenesis II. The volume of milk was reduced further when antenatal corticosteroids were administered between 28 and 34 weeks' gestation and delivery occurred 3 to 9 days later. In view of the advantages of mothers' own milk, additional support with lactation is recommended for mothers of preterm infants, particularly those who have been treated with corticosteroids before the delivery.

This study evaluated the longitudinal effect of fish oil in pregnancy on breast milk fatty acid composition and infant outcomes. In a randomized, controlled trial, 98 women received 2.2 g docosahexaenoic acid (DHA) and 1.1 g eicosapentaenoic acid (EPA) or olive oil from 20 wk of gestation until delivery. Fatty acid composition in breast milk (at 3 d, 6 wk, and 6 mo) and infant erythrocyte membranes (at 1 y) were determined by gas liquid chromatography. Breast milk fatty acids were examined in relationship to growth and development. Compared with control group, breast milk from women who received fish oil had proportionally higher DHA and EPA levels at 3 d and 6 wk after delivery, but this difference was no longer apparent by 6 mo. Infant DHA status at 1 y of age was directly related to DHA levels at 3 d, 6 wk, and 6 mo postpartum (but not to antenatal supplementation). Both EPA and DHA in breast milk were positively correlated with Griffith's developmental scores including hand and eye coordination. Thus, supplementation in pregnancy was associated with increased n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in breast milk, particularly in early lactation, and this was positively associated with infant DHA status at 1 y.

Until the establishment of the PREM Bank (Perron Rotary Express Milk Bank) donor human milk banking had not occurred in Australia for the past 20 years. In re-establishing donor human milk banking in Australia, the focus of the PREM Bank has been to develop a formal and consistent approach to safety and quality in processing during the operation of the human milk bank. There is currently no existing legislation in Australia that specifically regulates the operation of donor human milk banks. For this reason the PREM Bank has utilised existing and internationally recognised management practices for managing hazards during food production. These tools (specifically HACCP) have been used to guide the development of Standard Operating Procedures and Good Manufacturing Practice for the screening of donors and processing of donor human milk. Donor screening procedures are consistent with those recommended by other human milk banks operating internationally, and also consistent with the requirements for blood and tissue donation in Australia. Controlled documentation and record keep requirements have also been developed that allow complete traceability from individual donation to individual feed dispensed to recipient and maintain a record of all processing and storage conditions. These operational requirements have been developed to reduce any risk associated with feeding pasteurised donor human milk to hospitalised preterm or ill infants to acceptable levels.

Background: Breast milk contains many immunomodulatory factors (soluble CD14 (sCD14), IgA and cytokines) with the potential to influence infant immune development., Objective: To determine if changes in breast milk omega-3 polyunsaturated fatty acid (n-3 PUFA) composition as a result of maternal dietary fish oil supplementation during pregnancy can modify levels of these immunological parameters in breast milk., Method: In a randomized controlled trial, 83 atopic women received either 4 g fish oil capsules (containing 3.7 g n-3 PUFA) (n = 40) or 4 g olive oil capsules (n = 43) from 20 weeks gestation until delivery. Breast milk was collected 3 days post-partum and fatty acids were analysed by gas liquid chromatography and IgA, sCD14 and cytokines (IL-5, IL-6, IL-10, TNF-alpha and IFN-gamma) were quantitated by ELISA or time resolved fluorescence (TRF)., Results: Omega-3 docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) levels were significantly higher (P < 0.001) in breast milk from women supplemented with fish oil (n = 33, DHA mean 1.15%, SD 0.47% and EPA mean 0.16%, SD 0.07%) than in samples from the control group (n = 40, DHA mean 0.50%, SD 0.17% and EPA mean 0.05%, SD 0.02%). Breast milk arachidonic acid (AA; 20:4n-6) levels were significantly lower (P = 0.045) in the fish oil group (mean 0.55%, SD 0.12%) compared with the control group (mean 0.61%, SD 0.14%). Breast milk IgA was positively correlated with DHA (P = 0.046) and 22:5n-3 (P = 0.003), but inversely correlated with linoleic acid (LA; 18:2n-6) (P=0.034). Levels of sCD14 were also positively correlated with 22:5n-3 (P=0.009). Cytokines involved in IgA synthesis (IL-10 and IL-6) were also significantly correlated with both IgA and n-3 PUFA levels, although there were no differences in the levels of breast milk IgA, sCD14 or cytokines between study groups., Conclusion: Supplementation with fish oil during pregnancy significantly alters early post-partum breast milk fatty acid composition. omega-3 PUFA levels were positively associated with IgA and sCD14 levels, suggesting a relationship between fatty acid status and mucosal immune function.

Metabolic bone disease (MBD) in the newborn predominantly affects preterm infants. The risk of MBD is inversely proportional to gestational age and birthweight, and directly related to postnatal complications. Poor bone mineralization has been shown in 55% of infants born at less than 1000 g. Optimal nutrition for very preterm infants is thought to be mother's own milk but supplementation is required to meet dietary requirements. However, there is insufficient evidence to determine that supplementation of human milk with commercial fortifiers has an effect on bone mineral content. We report a case of severe MBD with fractures in an extremely preterm infant who was fed with fortified mother's milk.

Human milk (HM) is considered to be the optimal feed of choice for neonates, however, for preterm infants, HM fortifiers are often added to increase growth. If HM is unavailable, preterm formula is the next best option for preterm infants. Choosing which fortifier, if any, to use or which formula can be confusing. In this paper, the composition of milk feeds available in Australia and New Zealand is reviewed with the aim of assisting paediatricians to decide which feed is most appropriate for their patients.

Objective: A nutritional audit was performed to determine whether current feeding regimes were achieving nutritional goals and to evaluate the use of breastmilk (BM) in a neonatal unit (NNU)., Methods: All fluid consumed or infused daily was documented with daily weight and weekly length and head circumference measurements in 90 preterm infants (gestational age 30.1 +/- 2.6 weeks) while in the NNU for 60 +/- 27 days. Daily protein and energy intakes were calculated using values for South Australian preterm BM., Results: Parenteral nutrition provided 85% of the daily energy in week 1 falling to 11% by week 6. Ninety per cent of infants received some of their mother's BM and 62% were discharged at least partially breastfed. Protein and energy intakes were 1.03 +/- 0.35 g and 55 +/- 10 kcal/kg/day in week 1, increasing to 2.52 +/- 0.60 g and 109 +/- 15 kcal/kg per day by week 4. Protein intake correlated with weight gain (r2 = 0.39). Weight gain was 14.0 +/- 2.0 g/kg per day and z-scores for weight declined from -0.25 on admission to -1.22 on discharge, P < 0.0001. When infants were divided into two groups comprising those who received BM or formula as their predominant enteral feed, growth and protein intake (but not energy intake) were lower in the BM-fed infants. However, enteral feeds were tolerated earlier and more quickly in those infants receiving predominantly BM., Conclusion: Energy requirements were readily met using current feeding regimes for preterm infants but protein intakes were marginal. Mothers of preterm infants had similar breastfeeding rates to mothers of term infants in South Australia. The long-term effects of the lower growth rates of preterm infants fed predominantly BM compared with those fed predominantly formula are unknown and need be balanced against the benefits of BM.

The purpose of our study was to assess whether a supplement of fish oil (FO) and evening primrose oil (EPO) for formula-fed infants was capable of avoiding reductions in erythrocyte docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) associated with standard formula feeding. Healthy, term infants, whose mothers chose to formula feed, were randomized to either a placebo or supplemented formula for their first 30 wk of life. A reference group of beast-fed infants also was enrolled. Erythrocyte fatty acids were measured by capillary gas chromatography on day 5 and in weeks 6, 16, and 30. Supplementation of formula with 0.36% of total fatty acids as DHA resulted in erythrocyte DHA being maintained at or above breast-fed levels for the entire 30-wk study period, and breast feeding (0.21% DHA) resulted in a modest fall in erythrocyte DHA relative to baseline (day 5) values. The level of erythrocyte DHA in placebo formula-fed infants was halved by week 16. AA levels decreased in all infants in the first six weeks, but the levels in breast- and placebo formula-fed infants increased with age and returned to approximate baseline (day 5) values by 16 and 30 wk of age, respectively. Erythrocyte AA in FO+EPO-supplemented infants remained low and below breast- and placebo formula-fed levels. Our data suggest that dietary supplementation with DHA at 0.36% total fatty acids results in erythrocyte DHA levels above those found in breast-fed infants. EPO supplementation was not effective at maintaining erythrocyte AA when given with FO.

We investigated whether the disparity in neural maturation between breastfed and formula-fed term infants could be corrected by the addition of fish oil, a source of docosahexaenoic acid (DHA, 22:6 omega 3), to infant formula. Healthy, term infants were randomised at birth to receive either a supplemented or placebo formula if their mothers had chosen to bottle feed. Breastfed term infants were enrolled as a reference group. Infant erythrocyte fatty acids and anthropometry were assessed on day 5 and at 6, 16, and 30 weeks of age. Visual evoked potential (VEP) acuity was determined at 16 and 30 weeks. VEP acuities of breastfed and supplemented-formula-fed infants were better than those of placebo-formula-fed infants at both 16 and 30 weeks of age (p < 0.001 and p < 0.01). Erythrocyte DHA in breastfed and supplemented-formula-fed infants was maintained near birth levels throughout the 30-week study period but fell in placebo-formula-fed infants (p < 0.001). Erythrocyte DHA was the only fatty acid that consistently correlated with VEP acuity in all infants at both ages tested. A continuous supply of DHA may be required to achieve optimum VEP acuity since infants breastfed for short periods (< 16 weeks) had slower development of VEP than infants receiving a continuous supply of DHA from either breastmilk or supplemented formula. Erythrocyte arachidonic acid (20:4 omega 6) in supplemented-formula-fed infants was reduced below that of infants fed breastmilk or placebo formula at 16 and 30 weeks (p < 0.001), although no adverse effects were noted, with growth of all infants being similar. DHA seems to be an essential nutrient for the optimum neural maturation of term infants as assessed by VEP acuity. Whether supplementation of formula-fed infants with DHA has long-term benefits remains to be elucidated.

The fatty acid composition of breast milk from 23 breast-feeding women was serially assessed by capillary gas chromatography from the 6th to the 30th wk of lactation. The proportions of total n-3 and n-6 fatty acids were unchanged with time, although some significant differences were noted for individual polyunsaturated fatty acids (PUFAs). Of the n-3 PUFAs, only docosahexaenoic acid (DHA, 22:6n-3) concentrations changed, decreasing between 6 and 16 wk from 0.26 +/- 0.13% to 0.21 +/- 0.13% of total fatty acids but remaining at this proportion until 30 wk. Of the n-6 PUFAs, 18:3, 20:3, 20:4, and 22:5 all showed reductions with time. Compared with concentrations observed in a 1981 study, linoleic acid was higher (14% compared with 11% of total fatty acids), whereas the concentration of DHA was lower (0.21% compared with 0.32% of total fatty acids), possibly reflecting a general change in the diets of Australian women.

Commercial infant formulas with a ratio of linoleic acid (LA) to alpha-linolenic acid (ALA) of 10:1 or higher are nutritionally inadequate; the tissue levels of docosahexaenoic acid (DHA) are lower and the visual function indices are reduced in infants who are fed these formulas. All the evidence points to using LA:ALA ratios of less than 8:1, but there has been only one study in infants that used formulas with reduced LA:ALA ratios, and only biochemical indices were monitored. There is a need for both short-term studies to establish the ratios of LA to ALA that will make possible the accumulation of DHA to levels close to those in breast-fed infants and long-term trials to determine the effects of such fat blends on growth and development.

A preliminary investigation was made into the effectiveness of two breastmilk fortifiers on the Australian market (FM-85 [Nestlé, Vevey, Switzerland] and Enfamil Human Milk Fortifier [EHMF; Mead Johnson, Evansville, IN, USA]). Infants < 1800 g and < 34 weeks gestation at birth, who were receiving breast milk, were randomized to receive either of the fortifiers (n = 14 for FM-85, n = 10 for EHMF), until a weight of 2 kg was reached. Infants not receiving breast milk (n = 9) were fed a preterm formula (Prenan, Nestlé). The two fortifier groups were similar in most parameters examined: (i) weight gain (17.9 +/- 3.0 vs 17.4 +/- 3.5 g/kg per day); (ii) head circumference growth (1.02 +/- 0.28 vs 1.03 +/- 0.25 cm/week); (iii) arm muscle area growth (32.6 +/- 20.0 vs 33.5 +/- 13.7 mm2/week); (iv) arm fat area growth (14.0 +/- 8.7 mm2/week); (v) plasma calcium (2.52 +/- 0.08 vs 2.58 +/- 0.15 mmol/L); (vi) plasma phosphate (2.02 +/- 0.21 vs 2.13 +/- 0.32 mmol/L); (vii) plasma copper (5.28 +/- 2.83 vs 5.66 +/- 3.07 mumol/L); and (vii) plasma zinc (13.3 +/- 5.5 vs 15.8 +/- 9.2 mumol/L). The FM-85 group had a higher alkaline phosphatase level (355 +/- 110 vs 231 +/- 70 iu/L) than the EHMF group; however, no values were outside the normal range. The Prenan group had a higher rate of weight gain (23.6 +/- 3.3 g/kg per day) and higher arm fat area growth rate (25.2 +/- 7.6 mm2/week) than the fortifier groups while all other parameters were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast-fed infants in Bangladeshi villages were weighed at 1, 2, 6, 9 and 12 months. The concentrations of zinc and copper in the breast milk were measured and the daily intake of these elements calculated. Breast milk Zn concentration decreased over the year but was comparable with that found in developed countries. The calculated daily intake decreased from 17.7 to 8.0 mumol (10-30% of recommended dietary allowances (RDA); National Academy of Sciences, 1980). Breast milk Cu concentration also fell over the year and was lower than that reported from developed countries. Calculated daily Cu intake was 1.95-2.63 mumol (RDA 7.81-15.63 mumol). Deficiencies of trace elements may therefore be a problem in poorly nourished communities where breast feeding is continued for several years with only small amounts of additional food. Breast milk may not be adequate as the only source of infant nutrition after the first few months of life in Bangladesh.