Expressed Breast Milk Analysis: Role of Individualized Protein Fortification to Avoid Protein Deficit After Preterm Birth and Improve Infant Outcomes

Background: Expressed breast milk (EBM) protein content is highly variable between mothers and often below published values that are still used for EBM protein fortification strategies. This approach may result in significant protein deficit and suboptimal protein energy (P/E) ratio. The study aim was to determine whether individualized EBM protein analysis and fortification will reduce preterm infant protein deficits and improve growth and neurodevelopmental outcome.Study Methods: In a single-center randomized, blinded study of infants born at 24 0/7–29 6/7 weeks, mother-specific protein values measured by a milk analyzer were used to individualize infant-specific protein intake (interventional group, IG), and compared this to a standardized protein fortification scheme based on published values of EBM protein content of 1.4 g/dL (control group, CG). For IG, milk analyzer protein values of mother's EBM were used to adjust protein content of the EBM. The CG EBM protein content was adjusted using the standard published value of 1.4 g/dL and not based on milk analyzer values. EBM protein content, protein intake, protein/energy (P/E) ratio, weight (WT), head circumference (HC), length (L), growth velocity (GV) from 2 to 6 weeks of age, WT, HC and L Z-Scores at 32- and 35-weeks PMA, and lean body mass (35 weeks PMA skin fold thickness) were measured. Neurodevelopment was assessed by Bayley III at average 24 months corrected gestational age (CGA).Results: EBM protein content before fortification was significantly below published values of 1.4 g/dL at all time points in both CG and IG. CG protein deficit was significantly decreased and progressively worsened throughout the study. Individualized protein fortification in IG avoided protein deficit and optimized P/E ratio. Although no significant change in short-term GV (at 6 weeks of age) was seen between groups, IG infants born at <27 weeks had significant improvements in WT and L z-scores, and leaner body mass at 32 and 35 weeks PMA. IG exhibited significantly improved cognitive scores at 24 months CGA.Conclusions: Infant-specific protein supplementation of mother's EBM optimized P/E ratio by eliminating protein deficit and improved growth z scores at 32- and 35-weeks PMA and neurocognitive testing at 24 months.

Using Nature to Nurture: Breast Milk Analysis and Fortification to Improve Growth and Neurodevelopmental Outcomes in Preterm Infants

Premature infants are born prior to a critical window of rapid placental nutrient transfer and fetal growth—particularly brain development—that occurs during the third trimester of pregnancy. Subsequently, a large proportion of preterm neonates experience extrauterine growth failure and associated neurodevelopmental impairments. Human milk (maternal or donor breast milk) is the recommended source of enteral nutrition for preterm infants, but requires additional fortification of macronutrient, micronutrient, and energy content to meet the nutritional demands of the preterm infant in attempts at replicating in utero nutrient accretion and growth rates. Traditional standardized fortification practices that add a fixed amount of multicomponent fortifier based on assumed breast milk composition do not take into account the considerable variations in breast milk content or individual neonatal metabolism. Emerging methods of individualized fortification—including targeted and adjusted fortification—show promise in improving postnatal growth and neurodevelopmental outcomes in preterm infants.

Individualized Target Fortification of Breast Milk: Optimizing Macronutrient Content Using Different Fortifiers and Approaches

Background: Native breast milk composition displays significant inter- and intra-individual variation which persists after standard fortification with fixed doses and challenges target fortification. This study aims to analyze the macronutrient composition of different commercially available fortifiers and the effect of different fortification strategies on nutritional intake of preterm infants.Methods: In 103 preterm infants, native breast milk samples were collected from 24-h feeding batches (n = 3,338) and fat, protein and carbohydrate contents were analyzed. Nutrient content was compared for breast milk that had undergone either (i) standard fortification, (ii) targeted fortification, (iii) selective batching according to breast milk composition, or (iv) partial lyophilization. For (i) eight commercially available standard fortifiers were tested. Targeted fortification (ii) involved the addition of single component modulars of either protein, fat or carbohydrates to standard fortified breast milk. Using a mathematical growth model, the combined effect of protein, fat and carbohydrate intake on growth was assessed. The best composition of standard fortifiers as the initial step for target fortification was explored assuming three clinical scenarios for milk analysis.Results: Macronutrient content was highly variable between native breast milk samples, and this variation was still present after standard fortification, however at elevated macronutrient levels. Standard fortification, breast milk batching, as well as partial lyophilization of human milk resulted in deficient and imbalanced enteral intakes in a significant proportion of infants. Target fortification reduced this variation in a, respectively, higher percentage of samples. The effect size was dependent on the number of measurements per week. The optimum composition of standard fortifiers was dependent on the clinical scenario (measurement frequency) for target fortification.Conclusions: To provide precise and accurate intakes of macronutrients, breast milk should be target fortified. Standard fortified breast milk can result in excess above recommended intakes of some macronutrients which limits the efficiency of target fortification. Standard fortifiers with improved composition are needed for target fortification.

Exploring Innovations in Human Milk Analysis in the Neonatal Intensive Care Unit: A Survey of the United States

Introduction: Human milk (HM) is the ideal enteral feeding for nearly all infants and offers unique benefits to the very low birthweight (VLBW) infant population. It is a challenge to meet the high nutrient requirements of VLBW infants due to the known variability of HM composition. Human milk analysis (HMA) assesses the composition of HM and allows for individualized fortification. Due to recent U.S. Food and Drug Administration (FDA) approval, it has relatively recent availability for clinical use in the US.Aim: To identify current practices of HMA and individualized fortification in neonatal intensive care units (NICUs) across the United States (US) and to inform future translational research efforts implementing this nutrition management method.Methods: An institutional review board (IRB) approved survey was created and collected data on the following subjects such as NICU demographics, feeding practices, HM usage, HM fortification practices, and HMA practices. It was distributed from 10/30–12/21/2020 via online pediatric nutrition groups and listservs selected to reach the intended audience of NICU dietitians and other clinical staff. Each response was assessed prior to inclusion, and descriptive analysis was performed.Results: About 225 survey responses were recorded during the survey period with 119 entries included in the analysis. This represented 36 states and Washington D.C., primarily from level III and IV NICUs. HMA was reported in 11.8% of responding NICUs. The most commonly owned technology for HMA is the Creamatocrit Plus TM (EKF Diagnostics), followed by the HM Analyzer by Miris (Uppsala, Sweden). In NICUs practicing HMA, 84.6% are doing so clinically.Discussion: Feeding guidelines and fortification of HM remain standard of care, and interest in HMA was common in this survey. Despite the interest, very few NICUs are performing HMA and individualized fortification. Barriers identified include determining who should receive individualized fortification and how often, collecting a representative sample, and the cost and personnel required.Conclusions: Human milk analysis and individualized fortification are emerging practices within NICUs in the US. Few are using it in the clinical setting with large variation in execution among respondents and many logistical concerns regarding implementation. Future research may be beneficial to evaluate how practices change as HMA and individualized fortification gain popularity and become more commonly used in the clinical setting.

Raw Cow Milk Protein Stability under Natural and Technological Conditions of Environment by Analysis of Variance

Heat stability (HS) is substantial technology property of raw milk. Analysis of sources of HS variation and its regular monitoring can contribute to creating higher added value in the dairy industry. The goal of this analysis was to assess the practice sources of raw cow milk HS variability on the results of an extensive data set of bulk tank milk samples. There was implemented neither a compositional technology modification nor acidity adjustment of milk, just original raw milk was used for the analysis. A total 2634 HS analyses were performed, including other milk indicators, during three years of an experimental period. The log HS mean and standard deviation were 1.273654 ± 0.144189, equal to the HS geometric mean of 18.8 min. Explanation of the HS variability through the linear model used was 41.1% (p < 0.0001). According to the results of the variance analysis, the milk HS was influenced (p = 0.0033 and mostly <0.0001) by all the farm factors such as year; season; calendar month; altitude; total annual rainfall; herd size by the number of cows; milk yield; cow breed; type of milking; litter type in the stable; summer grazing application; farm effect. During the calendar months (p < 0.0001), milk HS values suggest similar seasonal dynamics with the somatic cell count, total count of mesophilic microorganisms, coli bacteria count and urea and lactose concentration and opposite configuration pattern to fat, crude protein, solids-not-fat and total solids content and milk freezing point depression. Here performed quantification of these effects by analyzing the variance may allow efficient raw milk selection to be processed into specific dairy products.

Advances in Atypical FT-IR Milk Screening: Combining Untargeted Spectra Screening and Cluster Algorithms

Fourier-transform mid-infrared spectrometry is an attractive technology for screening adulterated liquid milk products. So far, studies on how infrared spectroscopy can be used to screen spectra for atypical milk composition have either used targeted methods to test for specific adulterants, or have used untargeted screening methods that do not reveal in what way the spectra are atypical. In this study, we evaluate the potential of combining untargeted screening methods with cluster algorithms to indicate in what way a spectrum is atypical and, if possible, why. We found that a combination of untargeted screening methods and cluster algorithms can reveal meaningful and generalizable categories of atypical milk spectra. We demonstrate that spectral information (e.g., the compositional milk profile) and meta-data associated with their acquisition (e.g., at what date and which instrument) can be used to understand in what way the milk is atypical and how it can be used to form hypotheses about the underlying causes. Thereby, it was indicated that atypical milk screening can serve as a valuable complementary quality assurance tool in routine FTIR milk analysis.