Vegan/vegetarian diet and human milk donation: An EMBA survey across European milk banks.

The nutritional adequacy of human milk (HM) from vegan/vegetarian mothers has been a matter of debate, and a variety of recommendations regarding the eligibility of these mothers as human milk donors exists. According to the latest evidence, HM from vegans/vegetarians is similar in its composition to that from omnivores, however, some differences may be observed regarding vitamin B12 and omega-3 fatty acids concentrations. Maternal supplementation of these compounds has been proven effective in increasing their HM concentration. With this survey, we aimed to explore the practices currently in use in European human milk banks (HMBs) regarding potential donors following vegan/vegetarian diets. The online survey was distributed to European HMBs between January and July 2022. A total of 188 HMBs were contacted, and 118 replied (response rate 63%). Vegan and vegetarian mothers were recommended supplements of vitamin B12 to be accepted as donors in 27% and 26% of HMBs, respectively. Additional omega-3 fatty acid supplementation was required in 8% HMBs. In the remaining HMBs, these mothers were either systematically excluded or included regardless of supplementation. The dosage of the recommended supplements was extremely variable. Fifty-one percent of HMBs were following recommendations to guide their practice, national or local recommendations mainly. Great variability in European HMBs practices towards potential donors following vegan/vegetarian diets exists. Some of these practices can result in loss of donors and/or in potential nutritional deficiencies. Standardised evidence-based recommendations on this issue and their implementation in daily HMB practice are needed.

Does antenatal corticosteroid therapy improve neonatal outcomes in late preterm birth?

BACKGROUND: Infants who are born at 34°/7 to 366/7 weeks of gestation (late preterm) are at greater risk for respiratory and other neonatal morbidities. The objective of this study was to examine the effects of the administration of antenatal corticosteroids (ACS) to women at risk for late preterm delivery on the incidence of neonatal outcomes. METHOD: This was a prospective cohort study of singleton gestations at risk of imminent delivery between 34°/7 and 366/7 weeks. Neonatal outcomes were compared between mothers who received ACS and those who did not. The primary outcome was the rate of composite respiratory morbidity defined as the need for treatment within 72 h of life (continuous positive airway pressure or high flow nasal cannula for least 2 h or supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least four continuous hours or mechanical ventilation). RESULTS: During the 3-year study period, 595 subjects were included in this study, comprising 234 subjects that received ACS and 361 that did not. Administration of ACS significantly reduced the rates of composite respiratory morbidity (aOR 0.63 95% CI 0.40-0.99), the use of CPAP or HFNC for at least 2 h (aOR 0.57 95% CI 0.35-0.94), and transient tachypnea of the newborn (aOR 0.48 95% CI 0.28-0.82). Neonatal hypoglycemia was more significantly increased in the ACS group compared with controls (aOR 1.64 95% CI 1.04-2.59). We found no significant between-group differences in the rate of respiratory distress syndrome, surfactant use, need for resuscitation, jaundice requiring phototherapy, admission to neonatal intensive care or special care nursery, and duration of hospitalization. CONCLUSION: Administration of ACS during the late preterm period decreased neonatal respiratory complications, however, increased the rate of hypoglycemia.

Does antenatal corticosteroid therapy improve neonatal outcomes in late preterm birth?

BACKGROUND: Infants who are born at 340/7 to 366/7 weeks of gestation (late preterm) are at greater risk for respiratory and other neonatal morbidities. The objective of this study was to examine the effects of administration of antenatal corticosteroids (ACSs) to women at risk for late preterm delivery on the incidence of neonatal outcomes. METHODS: This was a prospective cohort study of singleton gestations at risk of imminent delivery between 340/7 and 366/7 weeks. Neonatal outcomes were compared between mothers who received ACS and those who did not. Primary outcome was the rate of composite respiratory morbidity defined as the need for treatment within 72 h of life (continuous positive airway pressure or high flow nasal cannula for least 2 h or supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least four continuous hours or mechanical ventilation). RESULTS: During the 3-year study period, 595 subjects were included in this study, comprising 234 subjects that received ACS and 361 that did not. Administration of ACS significantly reduced the rates of composite respiratory morbidity (adjusted odds ratio (aOR) 0.63, 95% confidence interval (CI) 0.40-0.99), the use of CPAP or HFNC for at least 2 h (aOR 0.57, 95% CI 0.35-0.94) and transient tachypnea of newborn (aOR 0.48, 95% CI 0.28-0.82). Neonatal hypoglycemia was more significantly increased in the ACS group compared with controls (aOR 1.64, 95% CI 1.04-2.59). We found no significant between-group differences in the rate of respiratory distress syndrome, surfactant use, need for resuscitation, jaundice requiring phototherapy, admission to neonatal intensive care or special care nursery and duration of hospitalization. CONCLUSION: Administration of ACS during the late preterm period decreased neonatal respiratory complications, however, increased the rate of hypoglycemia.

Fortification of Human Milk for Preterm Infants: Update and Recommendations of the European Milk Bank Association (EMBA) Working Group on Human Milk Fortification.

Evidence indicates that human milk (HM) is the best form of nutrition uniquely suited not only to term but also to preterm infants conferring health benefits in both the short and long-term. However, HM does not provide sufficient nutrition for the very low birth weight (VLBW) infant when fed at the usual feeding volumes leading to slow growth with the risk of neurocognitive impairment and other poor health outcomes such as retinopathy and bronchopulmonary dysplasia. HM should be supplemented (fortified) with the nutrients in short supply, particularly with protein, calcium, and phosphate to meet the high requirements of this group of babies. In this paper the European Milk Bank Association (EMBA) Working Group on HM Fortification discusses the existing evidence in this field, gives an overview of different fortification approaches and definitions, outlines the gaps in knowledge and gives recommendations for practice and suggestions for future research. EMBA recognizes that "Standard Fortification," which is currently the most utilized regimen in neonatal intensive care units, still falls short in supplying sufficient protein for some VLBW infants. EMBA encourages the use of "Individualized Fortification" to optimize nutrient intake. "Adjustable Fortification" and "Targeted Fortification" are 2 methods of individualized fortification. The quality and source of human milk fortifiers constitute another important topic. There is work looking at human milk derived fortifiers, but it is still too early to draw precise conclusions about their use. The pros and cons are discussed in this Commentary in addition to the evidence around use of fortifiers post discharge.

Nutritional adequacy of a novel human milk fortifier from donkey milk in feeding preterm infants: study protocol of a randomized controlled clinical trial.

BACKGROUND: Fortification of human milk is a standard practice for feeding very low birth weight infants. However, preterm infants often still experience suboptimal growth and feeding intolerance. New fortification strategies and different commercially available fortifiers have been developed. Commercially available fortifiers are constituted by a blend of ingredients from different sources, including plant oils and bovine milk proteins, thus presenting remarkable differences in the quality of macronutrients with respect to human milk. Based on the consideration that donkey milk has been suggested as a valid alternative for children allergic to cow's milk proteins, due to its biochemical similarity to human milk, we hypothesized that donkey milk could be a suitable ingredient for developing an innovative human milk fortifier. The aim of the study is to evaluate feeding tolerance, growth and clinical short and long-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk, in comparison to an analogous population fed with traditional fortifier and protein supplement containing bovine milk proteins. METHODS: The study has been designed as a randomized, controlled, single-blind clinical trial. Infants born <1500 g and <32 weeks of gestational age were randomized to receive for 21 days either a combination of control bovine milk-based multicomponent fortifier and protein supplement, or a combination of a novel multicomponent fortifier and protein supplement derived from donkey milk. The fortification protocol followed is the same for the two groups, and the two diets were designed to be isoproteic and isocaloric. Weight, length and head circumference are measured; feeding tolerance is assessed by a standardized protocol. The occurrence of sepsis, necrotizing enterocolitis and adverse effects are monitored. DISCUSSION: This is the first clinical study investigating the use of a human milk fortifier derived from donkey milk for the nutrition of preterm infants. If donkey milk derived products will be shown to improve the feeding tolerance or either of the clinical, metabolic, neurological or auxological outcomes of preterm infants, it would be an absolute innovation in the field of feeding practices for preterm infants. TRIAL REGISTRATION: ISRCTN - ISRCTN70022881 .

Effect of unconjugated hyperbilirubinemia on neonatal autonomic functions: evaluation by heart rate variability.

BACKGROUND: Serum bilirubin levels beyond the physiological limits, may lead to alterations in autonomic regulation in a newborn infant. Heart rate variability (HRV), is a noninvasive and quantitative marker of the activity of the autonomic nervous system (ANS). To date, few studies have demonstrated the undesirable effects of severe unconjugated hyperbilirubinemia (UHB) on autonomic functions, and only one study has used HRV as a marker of the autonomic activity. However, the relationship between altered cardiac autonomic functions and UHB by using the HRV derived from 24-hour Holter electrocardiography (ECG) recording has not been investigated previously. OBJECTIVE: We aimed to assess whether a relationship exists between severe UHB and cardiac autonomic dysfunction by evaluating HRV via 24-hour Holter ECG recording. METHODS: This single-center, prospective, case-control study was conducted on 50 full-term newborn infants with severe UHB requiring phototherapy and 50 healthy infants as controls. HRV assessment was performed by using 24-hour Holter ECG recording. RESULTS: There was no significant difference in terms of mean average heart rate, mean maximum heart rate and mean RR duration between the groups. However, mean minimum heart rate was significantly lower in the study group. When 24-hour time and frequency domain parameters were compared, time and frequency domain parameters rMSDD as well as high frequency (HF), which represent parasymphathetic activity, were significantly higher in the study group. Furthermore, low frequency to high frequency (LF/HF) ratio, that serves as an indicator of sympathovagal balance, was significantly lower in the study group. CONCLUSION: Severe UHB may cause cardiac autonomic dysfunction in favor of parasympathetic predominance in jaundiced neonates.

Similar Occurrence of Febrile Episodes Reported in Non-Atopic Children at Three to Five Years of Age after Prebiotics Supplemented Infant Formula.

This is a follow up study of a multicenter randomised placebo-controlled trial in seven centres in five West European countries. The RCT assessed the effect of infant formula supplemented with a mixture of prebiotics (with neutral short-chain and long-chain oligosaccharides and pectin-derived acidic oligosaccharides) during infancy in term-born children (n=1130). In the follow-up study 672 children (60% of the study population) participated: 232 (56%) from the prebiotics group (PG), 243 (58%) from the control group (CG), and 197 (66%) from the non-randomised breast-fed group (BG). The primary outcome was the occurrence of febrile episodes at three to five years of age prospectively documented by the parents: in the PG 1.17 (interquartile range 0.50-2.08) episodes per year versus 1.20 (0.52-2.57) in the CG; and 1.48 (0.65-2.60) in the BG. This specific prebiotics mixture given during infancy in healthy non-atopic subjects does not decrease febrile episodes and therefore seems not to prevent infection between their third and fifth birthday.

Optimization of human milk fortification for preterm infants: new concepts and recommendations.

Preterm infants fed fortified human milk (HM) in standard (STD) fashion grow slower than preterm formula fed infants. Recently, low protein intake has been proven to be the primary limiting factor responsible for this growth failure. The main reason of protein undernutrition despite fortification is that STD fortification is based on the customary assumptions about the composition of HM. However, the protein concentration of preterm HM is variable and decreases with the duration of lactation. Also, the protein concentration of banked donor milk, which is most often provided by mothers of term infants, is likely to be lower. Hence, most of the HM fed to preterm infants during the fortification period is likely to have an inadequately low protein concentration. This hypothesis has been confirmed very recently by comparing the assumed and actual protein intakes in preterm infants fed fortified HM. Novel fortification models have been devised to deal with the problem of ongoing protein undernutrition. Individualized fortification is the recommended method to optimize HM fortification. There are two models of individualization: "adjustable fortification" and "targeted fortification". Both ways are feasible and effective in improving protein intakes and growth. Adjustable fortification has the advantage of being practical and avoids excessive protein intakes.

Early dietary intervention with a mixture of prebiotic oligosaccharides reduces the incidence of allergic manifestations and infections during the first two years of life.

A mixture of neutral short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS) has been shown to reduce the incidence of atopic dermatitis (AD) and infectious episodes during the first 6 mo of life. This dual protection occurred through the intervention period. The present study evaluated if these protective effects were lasting beyond the intervention period. In a prospective, randomized, double-blind, placebo-controlled design, healthy term infants with a parental history of atopy were fed either a prebiotic-supplemented (8 g/L scGOS/lcFOS) or placebo-supplemented (8 g/L maltodextrin) hypoallergenic formula during the first 6 mo of life. Following this intervention period, blind follow-up continued until 2 y of life. Primary endpoints were cumulative incidence of allergic manifestations. Secondary endpoints were number of infectious episodes and growth. Of 152 participants, 134 infants (68 in placebo, 66 in intervention group) completed the follow-up. During this period, infants in the scGOS/lcFOS group had significantly lower incidence of allergic manifestations. Cumulative incidences for AD, recurrent wheezing, and allergic urticaria were higher in the placebo group, (27.9, 20.6, and 10.3%, respectively) than in the intervention group (13.6, 7.6, and 1.5%) (P < 0.05). Infants in the scGOS/lcFOS group had fewer episodes of physician-diagnosed overall and upper respiratory tract infections (P < 0.01), fever episodes (P < 0.00001), and fewer antibiotic prescriptions (P < 0.05). Growth was normal and similar in both groups. Early dietary intervention with oligosaccharide prebiotics has a protective effect against both allergic manifestations and infections. The observed dual protection lasting beyond the intervention period suggests that an immune modulating effect through the intestinal flora modification may be the principal mechanism of action.

Ursodeoxycholic acid treatment in preterm infants: a pilot study for the prevention of cholestasis associated with total parenteral nutrition.

In a prospective, double-blind, placebo-controlled trial, the efficacy and safety of ursodeoxycholic acid (UDCA) was evaluated in preterm infants, in terms of its potential impact on fat absorption, advancement of enteral feeding, development of cholestasis, growth, nutritional status, and metabolic status. Although fecal fat excretion slightly decreased and achievement of full enteral feeding was earlier in the UDCA group, these differences were not significant. Interestingly, whereas serum gamma-glutamyl transferase activity increased during the parenteral nutrition period in the placebo group, we observed a constant and significant decrease in the UDCA group. This observation warrants further investigation to determine the utility of prophylactic UDCA in preventing cholestasis in infants with prolonged parenteral nutrition.

Early supplementation of prebiotic oligosaccharides protects formula-fed infants against infections during the first 6 months of life.

A mixture of neutral short chain galactooligosaccharides and long chain fructo-oligosaccharides (scGOS/lcFOS) has been shown to have prebiotic and immunomodulatory effects comparable to human milk oligosaccharides. This can be translated into clinical practice as a potential to prevent infections and allergy. The hypothesis of this study was that this specific prebiotic mixture could have a preventive effect against infections during the first 6 mo of life. In a prospective, randomized, double-blind, placebo-controlled trial, healthy term infants with a parental history of atopy were fed either prebiotic-supplemented (8 g/L scGOS/lcFOS) or placebo-supplemented (8 g/L maltodextrin) hypoallergenic formula during the first 6 mo of life. The primary outcome measures were infectious episodes, number of infections requiring antibiotics, and incidence of infections. During the study period, infants in the scGOS/lcFOS group had fewer episodes of all types of infections combined (P = 0.01). They also tended to have fewer upper respiratory tract infection episodes (P = 0.07) and fewer infections requiring antibiotic treatment (P = 0.10). Similarly, the cumulative incidence of recurring infections was significantly lower in the scGOS/lcFOS group. The cumulative incidence of any recurring infection and recurring respiratory infections was 3.9 and 2.9% in the scGOS/lcFOS group and 13.5 and 9.6% in the placebo group, respectively (P < 0.05). Oligosaccharide prebiotics reduced the number of infectious episodes and the incidence of recurring, particularly respiratory, infections during the first 6 mo of life. Although the exact mechanism of action is under investigation, it is very likely that the immune modulating effect of this prebiotic mixture through intestinal flora modification is the principal mechanism for the observed infection prevention early in life.

Management of bovine protein allergy: new perspectives and nutritional aspects.

OBJECTIVES: Awareness of the considerable incidence of bovine protein allergy in infancy makes it necessary to eliminate cow's milk antigens from the diet in special cases. The primary objective of this review is to discuss the nutritional aspects and appropriate use of hypoallergenic formulas as a substitute for cow's milk formulas and to present new alternative feeding modalities in this field. DATA SOURCES: Related articles in PubMed (National Library of Medicine) were reviewed. This review is a synthesis of these sources along with the discussions with experts in this field and the expert opinion of the authors. RESULTS: Soy protein-based and hydrolyzed milk protein formulas are the most commonly used alternative protein sources in the case of bovine protein allergy. Despite the adequacy of their nutritional values, there are still some problems to be solved regarding these formulas. In addition, a considerable percentage of the infants with bovine protein allergy may also present allergenic reactions to soy proteins as well as to hydrolyzed milk proteins. Thus, there still exists chaos in the selection of the most appropriate formula for infants sensitized to cow's milk protein. Rice protein-based formulas, probiotics, and prebiotics are expected to be new effective alternatives. CONCLUSIONS: Bovine protein allergy constitutes an important place in childhood food allergies. Soy protein-based and hydrolyzed protein formulas have some disadvantages and risk of allergenic activity that is not to be underestimated. So, substitution of cow's milk protein with an alternative protein source in sensitized infants has become an art rather than a science. Rice protein, prebiotics, and probiotics appear to be valuable alternatives giving hope for the future.

Protective effect of dietary supplementation with L-arginine and L-carnitine on hypoxia/reoxygenation-induced necrotizing enterocolitis in young mice.

Oxygen-derived free radicals are important components of gastrointestinal injury in necrotizing enterocolitis (NEC). In the present investigation, we examined the protective actions of L-arginine, a nitric oxide synthase substrate, and L-carnitine against hypoxia-reoxygenation (H/R) induced NEC in young mice. Young mice were divided into four groups: group 1 mice were subjected to H/R only; group 2 H/R mice were supplemented with L-arginine in the drinking water (2 g/l) for 7 days; group 3 H/R mice were given L-carnitine solution in water (50 mg/kg p.o.) for 7 days, and group 4 mice served as controls. Hypoxia was induced by placing the mice in a 100% CO(2) chamber for 5 min. After hypoxia, the mice were reoxygenated for 10 min with 100% oxygen. We examined the intestinal lesions by light microscopy and measured the intestinal generation of thiobarbituric acid reactive substances (TBARS) and the activities of superoxide dismutase and catalase in the H/R-induced model of NEC. In both L-arginine and L-carnitine groups, the NEC-induced intestinal tissue damage was greatly attenuated, with necrosis limited partially to the mucosa. The tissue TBARS level was significantly higher in group 1 than in any of the other groups (p < 0.001). However, those treated with L-arginine and L-carnitine had TBARS levels similar to those in the control animals. An increased tissue concentration of nitrate, a stable metabolite of nitric oxide, was found in the L-arginine-supplemented group as compared with the control group (p < 0.05). Both superoxide dismutase and catalase activities in the intestine were similar in H/R groups when compared with the intestine of control animals. The present study suggests that oxygen-derived free radicals are involved in the pathogenesis of H/R-induced NEC. This study also shows that dietary supplementation with L-arginine and L-carnitine ameliorates the histological evidence of H/R-induced intestinal injury and significantly decreases lipid peroxidation in H/R-induced bowel injury. Based on these findings, the beneficial effects of L-arginine and L-carnitine in this model may be mediated via mechanisms preventing free radical damage.