Lyophilized (freeze-dried) human milk for preterm infants: a scoping review.

Freeze-drying (FD), or lyophilization, is commonly used to preserve foods. FD offers potential to create a human milk-derived human milk fortifier, and an alternative to freeze-storing human milk. However, processing human milk is known to affect its components. This scoping review explores the effect of FD on the; macronutrient, micronutrient, vitamin, bioactive components, microbes and anti-microbial factors in human milk, and studies where lyophilized human milk has been given to newborn infants. 48 articles were identified after full text review. FD human milk reduces the fat globule size and as well as the quantity of enzymes, vitamin C and immunoglobulin. Common serum electrolyte disturbances have been reported when preterm infants' are fed FD human milk however it appears a promising method to avoid exposure of preterm infants' to cows' milk. Due to limited data, further studies exploring the safety and efficacy of FD human milk in preterm infants are needed.

A Quality Improvement Initiative to Reduce Necrotizing Enterocolitis in Very Preterm Infants.

OBJECTIVE: To reduce the incidence of necrotizing enterocolitis (NEC) among very preterm infants in the Calgary Health Region to ≤2% within 2 years. METHODS: A multidisciplinary team developed key drivers for NEC. Targeted interventions included strategies to increase mothers' own milk (MOM), improve compliance with feeding regimens, standardize management of feeding intolerance, prevent intestinal microbial aberrations, and feed conservatively during blood transfusion and the treatment of patent ductus arteriosus. The outcome measure was NEC (≥ stage 2). Changes in NEC rates were examined among racial and ethnic groups. Process measures included MOM feeding at discharge, the difference between actual and expected time to reach full feeds, lowest hemoglobin, and the duration of empirical antibiotics. Growth, the rate of blood transfusion, and the duration of parenteral nutrition were balancing measures. The preintervention, intervention, and sustainment periods were January 2013 to June 2016, July 2016 to December 2018, and December 2018 to December 2021, respectively. RESULTS: We included 2787 infants born at ≤326/7 weeks' gestation (1105 preintervention, 763 during intervention, and 919 in sustainment). NEC decreased from 5.6% to 1.9%. Process measures indicated increased MOM feeding at discharge, improved compliance with feeding regimens, increased lowest hemoglobin levels, and shorter durations of empirical antibiotics. Balancing measures revealed improved weight Z-scores, shorter durations on parenteral nutrition, and increased rates of blood transfusion. CONCLUSIONS: Quality improvement initiatives to increase MOM, improve compliance with feeding regimens, feed conservatively during blood transfusion and treatment of patent ductus arteriosus, and prevent intestinal microbial aberrations were associated with reduced NEC.

Enteral long-chain polyunsaturated fatty acids and necrotizing enterocolitis: A systematic review and meta-analysis.

BACKGROUND: Preterm infants are at risk of long-chain polyunsaturated fatty acid (LCPUFA) deficiency. Recent studies on high-dose DHA; n-3 LCPUFA in preterm infants suggested potential positive effects on cognitive outcomes but raised concerns about some increased neonatal morbidities. These studies and recent recommendations for DHA supplementation generated controversy owing to the lack of balance between DHA and arachidonic acid (ARA; n-6 LCPUFA). OBJECTIVES: To identify the effect of enteral supplementation of DHA, with and without ARA, on necrotizing enterocolitis (NEC) in very preterm infants. METHODS: A systematic review of randomized and controlled trials compared enteral LCPUFAs with placebo or no supplementation in very preterm infants. We searched PubMed, Ovid-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and CINHAL databases from inception to July 2022. Data were extracted in duplicate using a structured proforma. A meta-analysis and metaregression with random-effects models were used. The interventions evaluated were DHA alone vs. that combined with ARA, source of DHA, dose, and supplement delivery methods. Methodological qualities and risk of bias were assessed using the Cochrane risk-of-bias tool. RESULTS: Fifteen randomized clinical trials (RCTs) included 3963 very preterm infants with 217 cases of NEC. Supplementation with DHA alone increased NEC (2620 infants; RR: 1.56; 95% CI: 1.02, 2.39) with no evidence of heterogeneity (I2 = 0.0%, P = 0.46). Multiple metaregression revealed significant reduction in NEC when ARA was supplemented with DHA (aRR 0.42; 95% CI: 0.21, 0.88). The source of DHA, dose, and feeding type revealed no associations with NEC. Two RCTs supplemented high-dose DHA to lactating mothers. There was a significant increase in risk of NEC with this approach (1148 infants; RR: 1.92; 95% CI: 1.02, 3.61) with no evidence of heterogeneity (I2 = 0.0, P = 0.81). CONCLUSIONS: Supplementation with DHA alone may increase risk of NEC. Concurrent supplementation with ARA needs to be considered when adding DHA to preterm infants' diet.

Hindmilk as a Rescue Therapy in Very Preterm Infants with Suboptimal Growth Velocity.

Despite advances in neonatal nutrition, very preterm infants remain at increased risk of extrauterine growth faltering. This prospective study aimed to examine the effect of hindmilk, the milk at the end of a breast expression session, on growth and plasma fatty acids (FAs) of infants born <30 weeks' gestation who had been on full enteral feeds for ≥2 weeks and had a weight gain of <15 g/kg/day despite optimizing energy and protein intakes. Weight and plasma FAs were assessed before and two weeks after feeding hindmilk. Growth anthropometrics were assessed weekly for four weeks. Paired t-tests and multiple linear regression were used for statistical analyses of data from 34 infants and their 29 mothers. There was a significant increase in weight gain in the two weeks after feeding hindmilk (MD 3.9, 95%CI 1.2-6.5 g/kg/day). Weight Z-scores were larger at two weeks (MD 0.61, 95%CI 0.02-1.20) and onwards. Head circumference Z-scores were larger at three weeks (MD 0.83, 95%CI 0.20-1.47) and onwards. Plasma linoleic acid (LA) and α-linolenic acid (ALA) increased after feeding hindmilk. In conclusion, hindmilk may improve weight and head growth and increase LA and ALA in very preterm infants with suboptimal growth. A large randomized controlled trial is required to examine and validate the potential benefits of hindmilk.

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.

The Role of Dietary Fats in the Development and Prevention of Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a significant cause of mortality and morbidity in preterm infants. The pathogenesis of NEC is not completely understood; however, intestinal immaturity and excessive immunoreactivity of intestinal mucosa to intraluminal microbes and nutrients appear to have critical roles. Dietary fats are not only the main source of energy for preterm infants, but also exert potent effects on intestinal development, intestinal microbial colonization, immune function, and inflammatory response. Preterm infants have a relatively low capacity to digest and absorb triglyceride fat. Fat may thereby accumulate in the ileum and contribute to the development of NEC by inducing oxidative stress and inflammation. Some fat components, such as long-chain polyunsaturated fatty acids (LC-PUFAs), also exert immunomodulatory roles during the early postnatal period when the immune system is rapidly developing. LC-PUFAs may have the ability to modulate the inflammatory process of NEC, particularly when the balance between n3 and n6 LC-PUFAs derivatives is maintained. Supplementation with n3 LC-PUFAs alone may have limited effect on NEC prevention. In this review, we describe how various fatty acids play different roles in the pathogenesis of NEC in preterm infants.

Effect of Oral Lipid Matrix Supplement on Fat Absorption in Cystic Fibrosis: A Randomized Placebo-Controlled Trial.

Pancreatic enzyme therapy does not normalize dietary fat absorption in patients with cystic fibrosis and pancreatic insufficiency. Efficacy of LYM-X-SORB (LXS), an easily absorbable lipid matrix that enhances fat absorption, was evaluated in a 12-month randomized, double-blinded, placebo-controlled trial with plasma fatty acids (FA) and coefficient of fat absorption (CFA) outcomes. A total of 110 subjects (age 10.4 ±â€Š3.0 years) were randomized. Total FA increased with LXS at 3 and 12 months (+1.58, +1.14 mmol/L) and not with placebo (P = 0.046). With LXS, linoleic acid (LA) increased at 3 and 12 months (+298, +175 nmol/mL, P ≤ 0.046), with a 6% increase in CFA (P < 0.01). LA increase was significant in LXS versus placebo (445 vs 42 nmol/mL, P = 0.038). Increased FA and LA predicted increased body mass index Z scores. In summary, the LXS treatment improved dietary fat absorption compared with placebo as indicated by plasma FA and LA and was associated with better growth status.