Individualized versus standard diet fortification for growth and development in preterm infants receiving human milk.

BACKGROUND: Human milk as compared to formula reduces morbidity in preterm infants but requires fortification to meet their nutritional needs and to reduce the risk of extrauterine growth failure. Standard fortification methods are not individualized to the infant and assume that breast milk is uniform in nutritional content. Strategies for individualizing fortification are available; however it is not known whether these are safe, or if they improve outcomes in preterm infants. OBJECTIVES: To determine whether individualizing fortification of breast milk feeds in response to infant blood urea nitrogen (adjustable fortification) or to breast milk macronutrient content as measured with a milk analyzer (targeted fortification) reduces mortality and morbidity and promotes growth and development compared to standard, non-individualized fortification for preterm infants receiving human milk at < 37 weeks' gestation or at birth weight < 2500 grams. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), on September 20, 2019. We also searched clinical trials databases and the reference lists of retrieved articles for pertinent randomized controlled trials (RCTs) and quasi-randomized trials. SELECTION CRITERIA: We considered randomized, quasi-randomized, and cluster-randomized controlled trials of preterm infants fed exclusively breast milk that compared a standard non-individualized fortification strategy to individualized fortification using a targeted or adjustable strategy. We considered studies that examined any use of fortification in eligible infants for a minimum duration of two weeks, initiated at any time during enteral feeding, and providing any regimen of human milk feeding. DATA COLLECTION AND ANALYSIS: Data were collected using the standard methods of Cochrane Neonatal. Two review authors evaluated the quality of the studies and extracted data. We reported analyses of continuous data using mean differences (MDs), and dichotomous data using risk ratios (RRs). We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Data were extracted from seven RCTs, resulting in eight publications (521 total participants were enrolled among these studies), with duration of study interventions ranging from two to seven weeks. As compared to standard non-individualized fortification, individualized (targeted or adjustable) fortification of enteral feeds probably increased weight gain during the intervention (typical mean difference [MD] 1.88 g/kg/d, 95% confidence interval [CI] 1.26 to 2.50; 6 studies, 345 participants), may have increased length gain during the intervention (typical MD 0.43 mm/d, 95% CI 0.32 to 0.53; 5 studies, 242 participants), and may have increased head circumference gain during the intervention (typical MD 0.14 mm/d, 95% CI 0.06 to 0.23; 5 studies, 242 participants). Compared to standard non-individualized fortification, targeted fortification probably increased weight gain during the intervention (typical MD 1.87 g/kg/d, 95% CI 1.15 to 2.58; 4 studies, 269 participants) and may have increased length gain during the intervention (typical MD 0.45 mm/d, 95% CI 0.32 to 0.57; 3 studies, 166 participants). Adjustable fortification probably increased weight gain during the intervention (typical MD 2.86 g/kg/d, 95% CI 1.69 to 4.03; 3 studies, 96 participants), probably increased gain in length during the intervention (typical MD 0.54 mm/d, 95% CI 0.38 to 0.7; 3 studies, 96 participants), and increased gain in head circumference during the intervention (typical MD 0.36 mm/d, 95% CI 0.21 to 0.5; 3 studies, 96 participants). We are uncertain whether there are differences between individualized versus standard fortification strategies in the incidence of in-hospital mortality, bronchopulmonary dysplasia, necrotizing enterocolitis, culture-proven late-onset bacterial sepsis, retinopathy of prematurity, osteopenia, length of hospital stay, or post-hospital discharge growth. No study reported severe neurodevelopmental disability as an outcome. One study that was published after our literature search was completed is awaiting classification. AUTHORS' CONCLUSIONS: We found moderate- to low-certainty evidence suggesting that individualized (either targeted or adjustable) fortification of enteral feeds in very low birth weight infants increases growth velocity of weight, length, and head circumference during the intervention compared with standard non-individualized fortification. Evidence showing important in-hospital and post-discharge clinical outcomes was sparse and of very low certainty, precluding inferences regarding safety or clinical benefits beyond short-term growth.

Dose-response Relationship Between Donor Human Milk, Mother's Own Milk, Preterm Formula, and Neonatal Growth Outcomes.

BACKGROUND: A dose-response relationship between proportions of donor human milk (DHM) intake and in-neonatal intensive care unit (in-NICU) growth rates, if any, remains poorly defined. Objective was to evaluate interrelationships between percentages of DHM, mother's own milk (MOM), and preterm formula (PF) intake and neonatal growth parameters at 36 weeks postmenstrual age or NICU discharge. METHODS: Infants eligible for this single-center retrospective study were inborn at ≤32 weeks gestation or ≤1800 g, stayed in the NICU for ≥7 days, and received enteral nutrition consisting of human milk fortified with Enfamil human milk fortifier acidified liquid. Study exposures were defined as 10% increments in the total volumetric proportions of infant diet provided as MOM, DHM, or PF. Outcomes were growth parameters at 36 weeks postmenstrual age or NICU discharge. Multivariable linear regression modeled the adjusted additive effect of infant diet on individual growth parameters. RESULTS: A total of 314 infants records were eligible for analysis. Using MOM as reference, the adjusted mean growth velocity for weight significantly decreased by 0.17 g ·â€Škg ·â€Šday for every 10% increase in DHM intake, but did not vary with PF intake. The adjusted mean change in weight z score significantly decreased with increasing proportion of DHM intake but significantly improved with increasing PF intake. The adjusted mean head circumference velocity was significantly decreased by 0.01 cm/wk for every 10% increase in DHM intake, in reference to MOM, but did not vary with PF intake. Neither proportion of DHM nor PF intake was associated with length velocity. CONCLUSIONS: When DHM and MOM are fortified interchangeably, preterm infants receiving incremental amounts of DHM are at increased risk of postnatal growth restriction. The dose-response relationship between DHM, MOM, and PF and long-term growth and neurodevelopmental outcomes warrants further research.

Avoidant/Restrictive Food Intake Disorder Characteristics and Prevalence in Adult Celiac Disease Patients.

Background and Aims: The objective of this study was to identify the prevalence of avoidant/restrictive food intake disorder (ARFID) in patients with celiac disease (CD) and assess metabolic complications, disease control, diet adherence, and correlation with symptom and quality-of-life metrics. Methods: This was a retrospective study of 137 adult patients with CD who completed an ARFID survey in the CD clinic between 2018 and 2020. Demographics, clinical results, standardized diet assessment, and results of Celiac Disease Symptom Diary and Impact of a Gluten-free Diet Questionnaire were reviewed. The primary outcome measured was the rate of suspected ARFID based on patient-reported survey responses. Results: Seventy-eight patients (57%) met suspected ARFID criteria. There were no differences in age, gender, body mass index, micronutrient deficiencies, or bone disease in those with or without ARFID. Patients with ARFID did not have a difference in biopsy activity or better adherence to a gluten-free diet compared with non-ARFID patients. Food and social burden on Impact of a Gluten-free Diet Questionnaire was most predictive of ARFID. Conclusion: ARFID is common and has a high impact in patients with CD. Although some eating behavior is certainly due to their CD, there was no distinct difference in disease control between those with or without suspected ARFID, suggesting these maladaptive behaviors are not necessary for disease control. We did not find increased metabolic complications, but this was a 2-year snapshot. We need to further understand the social and food impacts on patients who score high on this survey to prevent further deficiencies and impaired, long-term detrimental eating behaviors.

Macronutrient analysis of donor human milk labelled as 24 kcal/oz.

OBJECTIVE: To measure the macronutrient content (MNC) of donor human milk labelled as 24 kcal/oz ("high-calorie DHM," hcDHM), compare to bank-labelled MNC, and examine variability of hcDHM MNC among milk banks. STUDY DESIGN: MNC was measured with near-infrared spectroscopy for 75 convenience samples from five milk banks collected during September 2016-July 2017. Concordance of measured MNC with labelled values was evaluated using three different thresholds: within ±20%, similar to FDA labelling standards for class II nutrients in foods; ±10%; and ±5%. RESULTS: Protein and caloric content differed significantly between measured and labelled values and varied significantly among milk banks. Measured caloric content ranged from 16.50 to 30.27 kcal/oz, with 89.3% of hcDHM samples within ±20%, 58.7% within ±10%, and 18.7% within ±5% of labelled content. CONCLUSIONS: MNC of hcDHM used in clinical practice shows variation that may result in differences from desired diet. The clinical implications of such differences are unexplored.

Five-Year Secular Trends and Predictors of Nonconsent to Receive Donor Milk in the Neonatal Intensive Care Unit.

OBJECTIVE: To identify independent maternal and infant factors associated with donor milk nonconsent and to examine secular trends in nonconsent rates. MATERIALS AND METHODS: Mothers of infants eligible to receive donor milk (≤32 weeks of gestation or ≤1,800 g) born between August 2010 and 2015 were included. Multivariable logistic regression modeled odds of nonconsent. RESULTS: Of the 486 mother/infant dyads from the first 5 years of the donor milk program, nonwhite race (adjusted odds ratio [aOR] 1.69; 95% confidence interval [CI] 1.04-2.76) and increasing gestational age (aOR 1.11; 95% CI 1.03-1.21) independently predicted nonconsent. Each year the program existed, there was a 48% reduction in odds of nonconsent (aOR 0.52; 95% CI 0.43-0.62). The most common reason given for nonconsent was "it's someone else's milk." CONCLUSION: Program duration was associated with reduced nonconsent rates and may reflect increased exposure to information and acceptance of donor milk use among neonatal intensive care unit staff and parents. Despite overall improvements in consent rates, race-specific disparities in rates of nonconsent for donor milk persisted after 5 years of this donor milk program. Further research is warranted to clarify the basis for race-based disparities in donor milk nonconsent rates, with the goal of designing interventions to reduce donor milk refusal among minority mothers.

Patterns and predictors of donor human milk non-consent in the neonatal ICU.

BACKGROUND: Previous research has not evaluated predictors of donor human milk (DHM) non-consent status in a neonatal intensive care unit (ICU) setting within the United States. The purpose of this study is to identify and describe maternal and infant factors associated with DHM consent status in a Level IV inner-city neonatal ICU. MATERIALS AND METHODS: Demographics and additional maternal/infant data were stratified by DHM consent and compared with the appropriate parametric/nonparametric hypothesis testing statistic. A predictive multivariable logistic regression model was constructed, adjusted for independent predictors identified in the bivariate analysis (p≤0.2) using a backwards selection process (retention threshold p≤0.1). The adjusted odds ratios generated from the multivariable model identified predictors independently associated with DHM non-consent. RESULTS: Data were analyzed for 113 mother-infant dyads from the first 18 months of a DHM program, with 65 mothers consenting to DHM and 48 not consenting. Race, ethnicity, marital status, education, delivery mode, and presence of a breastfeeding duration goal qualified for inclusion into the multivariable model. Only race and marital status were retained in the final model. In this sample, black race, other race, and being married are all independent predictors for DHM non-consent. CONCLUSIONS: Black race, other race, and marital status statistically predicted DHM non-consent in a Level IV inner-city neonatal ICU. These results are relevant to all neonatal ICUs who use DHM and to those who are developing DHM programs.