Evidence on docosahexaenoic acid and arachidonic acid supplementation for preterm infants.

PURPOSE OF REVIEW: For many decades, docosahexaenoic acid (DHA) supplementation was tested in premature infants to achieve an intake equivalent to the average level in breast milk, but this approach has led to conflicting results in terms of development and health outcomes. Higher doses of DHA closer to fetal accumulation may be needed. RECENT FINDINGS: The efficacy of DHA supplementation for preterm infants at a dose equivalent to the estimated fetal accumulation rate is still under investigation, but this may be a promising approach, especially in conjunction with arachidonic acid supplementation. Current data suggest benefit for some outcomes, such as brain maturation, long-term cognitive function, and the prevention of retinopathy of prematurity. The possibility that supplementation with highly unsaturated oils increases the risk of neonatal morbidities should not be ruled out, but current meta-analyzes do not support a significant risk. SUMMARY: The published literature supports a DHA intake in preterm infants that is closer to the fetal accumulation rate than the average breast milk content. Supplementation with DHA at this level in combination with arachidonic acid is currently being investigated and appears promising.

Arachidonic and docosahexaenoic acid supplementation and brain maturation in preterm infants; a double blind RCT.

BACKGROUND: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important structural components of neural cellular membranes and possess anti-inflammatory properties. Very preterm infants are deprived of the enhanced placental supply of these fatty acids, but the benefit of postnatal supplementation on brain development is uncertain. The aim of this study was to test the hypothesis that early enteral supplementation with ARA and DHA in preterm infants improves white matter (WM) microstructure assessed by diffusion-weighted MRI at term equivalent age. METHODS: In this double-blind, randomized controlled trial, infants born before 29 weeks gestational age were allocated to either 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) or medium chain triglycerides (control). Supplements were started on the second day of life and provided until 36 weeks postmenstrual age. The primary outcome was brain maturation assessed by diffusion tensor imaging (DTI) using Tract-Based Spatial Statistics (TBSS) analysis. RESULTS: We included 120 infants (60 per group) in the trial; mean (range) gestational age was 26+3 (22+6 - 28+6) weeks and postmenstrual age at scan was 41+3 (39+1 - 47+0) weeks. Ninety-two infants underwent MRI imaging, and of these, 90 had successful T1/T2 weighted MR images and 74 had DTI data of acceptable quality. TBSS did not show significant differences in mean or axial diffusivity between the groups, but demonstrated significantly higher fractional anisotropy in several large WM tracts in the ARA:DHA group, including corpus callosum, the anterior and posterior limb of the internal capsula, inferior occipitofrontal fasciculus, uncinate fasciculus, and the inferior longitudinal fasciculus. Radial diffusivity was also significantly lower in several of the same WM tracts in the ARA:DHA group. CONCLUSION: This study suggests that supplementation with ARA and DHA at doses matching estimated fetal accretion rates improves WM maturation compared to control treatment, but further studies are needed to ascertain any functional benefit. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov; ID:NCT03555019.

Breastfeeding Success and Newborn Health before and during the COVID-19 Pandemic:A Single-Centre Comparative Study.

INTRODUCTION: Due to the SARS-CoV-2 pandemic, adjustments in patient and visitor traffic were made in hospitals to limit viral exposure. The primary objective of our study was to compare the breastfeeding success of healthy newborns in a maternity ward during the 2020 lockdown period compared with the same period in the previous year. MATERIAL AND METHODS: Single-center comparative study based on prospectively collected data. All neonates born alive, from a single pregnancy, and with a gestational age greater than 36 weeks were considered for this study. RESULTS: 309 infants born in 2020 and 330 born in 2019 were included. Among women who desired to exclusively breastfeed, the rate of exclusive breastfeeding at discharge from the maternity ward was higher in 2020 than in 2019 (85 vs. 79%; p = 0.078). After logistic regression analysis adjusted for potential confounders (i.e., maternal BMI, parity, mode of delivery, gestational age, and size at birth), study period remained significantly and independently associated with exclusive breastfeeding at discharge (OR [95% CI] = 1.645 [1.005; 2.694]; p = 0.046). Newborns born in 2020 were less likely to have weight loss ≥10% than those born in 2019 (OR [95% CI] = 2.596 [1.148; 5.872]; p = 0.017) but had similar need for phototherapy (p = 0.41). CONCLUSION: The success of exclusive breastfeeding during the 2020 lockdown period was increased compared with the same period in 2019.

Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts.

OBJECTIVES: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g. METHODS: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-to-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached. RESULTS: In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier. CONCLUSIONS: We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants.

Nutri-Score: Its Benefits and Limitations in Children's Feeding.

Reducing the burden of noncommunicable diseases (NCDs) is one of the top priorities of public health policies worldwide. One of the recognized means of achieving this objective is to improve the diet quality. The Nutri-Score (N-S) is a [five-color-A, B, C, D, E letters] front-of-pack labeling logo intended to help consumers quickly identify the healthier prepackaged foods within a food category. Available studies have shown that the N-S is an efficient tool to achieve this aim in terms of consumers' awareness, perception, understanding, and purchasing and that its use may help to reduce the prevalence of NCDs. The N-S is currently implemented on a voluntary basis in 7 European countries and a discussion is underway within the European Commission to achieve a harmonized mandatory label. However, no study on the putative impact of the N-S on children's dietary patterns and health is available. The N-S is not applicable to infants' and young children's formulas and to specific baby foods, the compositions of which are already laid down in European Union regulations. The N-S does not replace age-appropriate dietary guidelines. As children consume an increasing number of adult type and processed foods, the relevance of the N-S for children should be evaluated considering the children's high specific requirements, especially in younger children. This is especially necessary for fitting fat and iron requirements, whereas protein-rich foods should be better framed. Moreover, efforts should be made to inform on how to use the N-S and in education on healthy diets.

Association Between Early Amino Acid Intake and Full-Scale IQ at Age 5 Years Among Infants Born at Less Than 30 Weeks' Gestation.

Importance: An international expert committee recently revised its recommendations on amino acid intake for very preterm infants, suggesting that more than 3.50 g/kg/d should be administered only to preterm infants in clinical trials. However, the optimal amino acid intake during the first week after birth in these infants is unknown. Objective: To evaluate the association between early amino acid intake and cognitive outcomes at age 5 years. Design, Setting, and Participants: Using the EPIPAGE-2 (Epidemiologic Study on Small-for-Gestational-Age Children-Follow-up at Five and a Half Years) cohort, a nationwide prospective population-based cohort study conducted at 63 neonatal intensive care units in France, a propensity score-matched analysis was performed comparing infants born at less than 30 weeks' gestation who had high amino acid intake (3.51-4.50 g/kg/d) at 7 days after birth with infants who did not. Participants were recruited between April 1 and December 31, 2011, and followed up from September 1, 2016, to December 31, 2017. Full-scale IQ (FSIQ) was assessed at age 5 years. A confirmatory analysis used neonatal intensive care unit preference for high early amino acid intake as an instrumental variable to account for unmeasured confounding. Statistical analysis was performed from January 15 to May 15, 2021. Exposures: Amino acid intake at 7 days after birth. Main Outcomes and Measures: The primary outcome was an FSIQ score greater than -1 SD (ie, ≥93 points) at age 5 years. A complementary analysis was performed to explore the association between amino acid intake at day 7 as a continuous variable and FSIQ score at age 5 years. Data from cerebral magnetic resonance imaging at term were available for a subgroup of preterm infants who participated in the EPIRMEX (Cerebral Abnormalities Detected by MRI, Realized at the Age of Term and the Emergence of Executive Functions) ancillary study. Results: Among 1789 preterm infants (929 boys [51.9%]; mean [SD] gestational age, 27.17 [1.50] weeks) with data available to determine exposure to amino acid intake of 3.51 to 4.50 g/kg/d at 7 days after birth, 938 infants were exposed, and 851 infants were not; 717 infants from each group could be paired. The primary outcome was known in 396 of 646 exposed infants and 379 of 644 nonexposed infants who were alive at age 5 years and was observed more frequently among exposed vs nonexposed infants (243 infants [61.4%] vs 206 infants [54.4%], respectively; odds ratio [OR], 1.33 [95% CI, 1.00-1.71]; absolute risk increase in events [ie, the likelihood of having an FSIQ score >-1 SD at age 5 years] per 100 infants, 7.01 [95% CI, 0.06-13.87]; P = .048). In the matched cohort, correlation was found between amino acid intake per 1.00 g/kg/d at day 7 and FSIQ score at age 5 years (n = 775; ß = 2.43 per 1-point increase in FSIQ; 95% CI, 0.27-4.59; P = .03), white matter area (n = 134; ß = 144 per mm2; 95% CI, 3-285 per mm2; P = .045), anisotropy of the corpus callosum (n = 50; ß = 0.018; 95% CI, 0.016-0.021; P < .001), left superior longitudinal fasciculus (n = 42; ß = 0.018; 95% CI, 0.010-0.025; P < .001), and right superior longitudinal fasciculus (n = 42; ß = 0.014 [95% CI, 0.005-0.024; P = .003) based on magnetic resonance imaging at term. Confirmatory and sensitivity analyses confirmed these results. For example, the adjusted OR for the association between the exposure and the primary outcome was 1.30 (95% CI, 1.16-1.46) using the instrumental variable approach among 978 participants in the overall cohort, and the adjusted OR was 1.35 (95% CI, 1.05-1.75) using multiple imputations among 1290 participants in the matched cohort. Conclusions and Relevance: In this cohort study, high amino acid intake at 7 days after birth was associated with an increased likelihood of an FSIQ score greater than -1 SD at age 5 years. Well-designed randomized studies with long-term follow-up are needed to confirm the benefit of this nutritional approach.

Religious dietary rules and their potential nutritional and health consequences.

BACKGROUND: The vast majority of the world population declares affiliation to a religion, predominantly Christianity and Islam. Many religions have special dietary rules, which may be more or less strictly adhered to. METHODS: Religious food rules were collected from holy books and religious websites as well as their translation into dietary practices. The literature was searched for potential associations between these rules and potential nutritional consequences. RESULTS: Jewish, Islamic and Indian religions support prolonged breastfeeding. Religious avoidance of alcohol is probably beneficial to health. When strictly applied, a few rules may lead to nutritional inadequacies, mainly in populations living in unfavourable socio-economic or environmental conditions. In Jewish and Muslim observants, animal slaughtering procedures may increase the risk of iron deficiency. Jews may be at risk of excess sodium intake related to home-prepared foods. A vegan diet, as observed by some believers, often by drifting from original precepts, or by some Hindus or Buddhists, may result in vitamin B12, calcium, iron, zinc, selenium and n-3 fatty acids deficiencies. CONCLUSION: When implemented in accordance with the rules, most religious food precepts are not detrimental to health, as suggested by the fact that they have more or less been followed for millennia. Nevertheless, some practices may lead to nutritional inadequacies, such as iron, calcium, vitamin D and vitamin B12 deficiencies. Patients with low socio-economic status, children and women of childbearing age are of particular risk of such deficiencies. Being aware of them should help health professionals to take an individualized approach to decide whether to supplement or not.

Palm Oil and Beta-palmitate in Infant Formula: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition.

BACKGROUND: Palm oil (PO) is used in infant formulas in order to achieve palmitic acid (PA) levels similar to those in human milk. PA in PO is esterified predominantly at the SN-1,3 position of triacylglycerol (TAG), and infant formulas are now available in which a greater proportion of PA is in the SN-2 position (typical configuration in human milk). As there are some concerns about the use of PO, we aimed to review literature on health effects of PO and SN-2-palmitate in infant formulas. METHODS: PubMed and Cochrane Database of Systematic Reviews were systematically searched for relevant studies on possible beneficial effects or harms of either PO or SN-2-palmitate in infant formula on various health outcomes. RESULTS: We identified 12 relevant studies using PO and 21 studies using SN-2-palmitate. Published studies have variable methodology, subject characteristics, and some are underpowered for the key outcomes. PO is associated with harder stools and SN-2-palmitate use may lead to softer stool consistency. Bone effects seem to be short-lasting. For some outcomes (infant colic, faecal microbiota, lipid metabolism), the number of studies is very limited and summary evidence inconclusive. Growth of infants is not influenced. There are no studies published on the effect on markers of later diseases. CONCLUSIONS: There is insufficient evidence to suggest that PO should be avoided as a source of fat in infant formulas for health reasons. Inclusion of high SN-2-palmitate fat blend in infant formulas may have short-term effects on stool consistency but cannot be considered essential.

Young Child Formula: A Position Paper by the ESPGHAN Committee on Nutrition.

Young child formulae (YCF) are milk-based drinks or plant protein-based formulae intended to partially satisfy the nutritional requirements of young children ages 1 to 3 years. Although widely available on the market, their composition is, however, not strictly regulated and health effects have not been systematically studied. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on Nutrition (CoN) performed a systematic review of the literature to review the composition of YCF and consider their role in the diet of young children. The review revealed limited data but identified that YCF have a highly variable composition, which is in some cases inappropriate with very high protein and carbohydrate content and even high amounts of added sugars. Based on the evidence, ESPGHAN CoN suggests that the nutrient composition of YCF should be similar to that of follow-on formulae with regards to energy and nutrients that may be deficient in the diets of European young children such as iron, vitamin D, and polyunsaturated fatty acids (n-3 PUFAs), whereas the protein content should aim toward the lower end of the permitted range of follow-on formulae if animal protein is used. There are data to show that YCF increase intakes of vitamin D, iron, and n-3 PUFAs. However, these nutrients can also be provided via regular and/or fortified foods or supplements. Therefore, ESPGHAN CoN suggests that based on available evidence there is no necessity for the routine use of YCF in children from 1 to 3 years of life, but they can be used as part of a strategy to increase the intake of iron, vitamin D, and n-3 PUFA and decrease the intake of protein compared with unfortified cow's milk. Follow-on formulae can be used for the same purpose. Other strategies for optimizing nutritional intake include promotion of a healthy varied diet, use of fortified foods, and use of supplements.

Effects of a lipid emulsion containing fish oil on polyunsaturated fatty acid profiles, growth and morbidities in extremely premature infants: A randomized controlled trial.

BACKGROUND & AIMS: The purpose of the study was to compare the effects of the parenteral emulsion SMOFlipid®, with 15% fish oil, with Clinoleic® on retinopathy of prematurity (ROP) and other morbidities and growth, and to compare their impact on longitudinal serum levels of fatty acids. Retinopathy of prematurity, other morbidity and growth were correlated with each parenteral lipid supplement. METHODS: Ninety infants born at gestational age <28 weeks were randomized to treatment with SMOFlipid® or Clinoleic®. Two thirds (66%) of the infants received parenteral nutrition for up to 14 days birth (median 8, range 2-14 days), and additional 25% of the infants received for up to 28 days after birth (median 21, range 15-28 days). Cord blood samples and then venous blood samples were obtained at ages 1, 7, 14, and 28 days and at postmenstrual age (PMA) 32, 36, and 40 weeks. Breastmilk was collected at postnatal day 7, and at PMA 32 and 40 weeks. Serum phospholipid and breastmilk total fatty acids were analyzed by gas chromatography-mass spectrometry. Treatment groups were compared with regard to ROP, bronchopulmonary dysplasia, necrotizing enterocolitis, patent ductus arteriosus sepsis and growth between birth and 36 weeks. RESULTS: Infants on SMOFlipid® had higher fractions of omega-3 LCPUFA eicosapentaenoic acid (EPA) and slightly higher omega-3 LCPUFA docosahexaenoic acid (DHA) fraction and a decreased arachidonic acid (AA) to DHA ratio from one week after birth up to 32 postmenstrual weeks compared to infants on Clinoleic®. Treatment groups did not differ in morbidities or growth. CONCLUSION: Supplementation with SMOFlipid® containing 15% fish oil during parenteral nutrition increased EPA substantially, DHA marginally, reduced AA and decreased AA to DHA ratio. It did not reduce morbidity or affect growth. Since extremely preterm infants accumulate a large deficit of DHA and AA, studies on more prolonged or different levels of DHA and AA supplementation are warranted.

Complementary Feeding: A Position Paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition.

This position paper considers different aspects of complementary feeding (CF), focussing on healthy term infants in Europe. After reviewing current knowledge and practices, we have formulated these recommendations: Timing: Exclusive or full breast-feeding should be promoted for at least 4 months (17 weeks, beginning of the 5th month of life) and exclusive or predominant breast-feeding for approximately 6 months (26 weeks, beginning of the 7th month) is a desirable goal. Complementary foods (solids and liquids other than breast milk or infant formula) should not be introduced before 4 months but should not be delayed beyond 6 months. CONTENT: Infants should be offered foods with a variety of flavours and textures including bitter tasting green vegetables. Continued breast-feeding is recommended alongside CF. Whole cows' milk should not be used as the main drink before 12 months of age. Allergenic foods may be introduced when CF is commenced any time after 4 months. Infants at high risk of peanut allergy (those with severe eczema, egg allergy, or both) should have peanut introduced between 4 and 11 months, following evaluation by an appropriately trained specialist. Gluten may be introduced between 4 and 12 months, but consumption of large quantities should be avoided during the first weeks after gluten introduction and later during infancy. All infants should receive iron-rich CF including meat products and/or iron-fortified foods. No sugar or salt should be added to CF and fruit juices or sugar-sweetened beverages should be avoided. Vegan diets should only be used under appropriate medical or dietetic supervision and parents should understand the serious consequences of failing to follow advice regarding supplementation of the diet. METHOD: Parents should be encouraged to respond to their infant's hunger and satiety queues and to avoid feeding to comfort or as a reward.

Long-Chain Polyunsaturated Fatty Acids and Clinical Outcomes of Preterm Infants.

Long-chain polyunsaturated fatty acids (LCPUFAs) play specific roles during the perinatal period and are very important nutrients to consider. The possible effects of LCPUFAs, particularly docosahexaenoic acid (DHA), on various clinical outcomes of preterm infants are discussed in this paper. Since DHA accumulates in the central nervous system during development, a lot of attention has focused on the effects of DHA on neurodevelopment. Experimental studies as well as recent clinical trials show that providing larger amounts of DHA than currently and routinely provided is associated with better neurological outcomes at 18 months to 2 years. This early advantage, however, does not seem to translate into detectable change in visual and neurodevelopmental outcomes or behavior when assessed in childhood. There is growing evidence that, in addition to effects on development, omega-3 LCPUFAs may reduce the incidence or severity of neonatal morbidities by affecting different steps of the immune and anti-inflammatory response. Studies in preterm infants suggest that the omega-3 LCPUFAs may play a significant role by reducing the risk of bronchopulmonary dysplasia, necrotizing enterocolitis and possibly retinopathy of prematurity and sepsis. Overall, evidence is increasing to support the benefits of high-dose DHA for various health outcomes of preterm infants. These findings are of major clinical relevance mainly because infants born preterm are at particularly high risk for a nutritional deficit in omega-3 fatty acids, predisposing to adverse neonatal outcomes. Further studies are warranted to address these issues as well as to more precisely determine the LCPUFA requirement in order to favor the best possible outcomes of preterm infants.

Recombinant Bile Salt-Stimulated Lipase in Preterm Infant Feeding: A Randomized Phase 3 Study.

INTRODUCTION: Feeding strategies are critical for healthy growth in preterm infants. Bile salt-stimulated lipase (BSSL), present in human milk, is important for fat digestion and absorption but is inactivated during pasteurization and absent in formula. This study evaluated if recombinant human BSSL (rhBSSL) improves growth in preterm infants when added to formula or pasteurized breast milk. PATIENTS AND METHODS: LAIF (Lipase Added to Infant Feeding) was a randomized, double-blind, placebo-controlled phase 3 study in infants born before 32 weeks of gestation. The primary efficacy variable was growth velocity (g/kg/day) during 4 weeks intervention. Follow-up visits were at 3 and 12 months. The study was performed at 54 centers in 10 European countries. RESULTS: In total 415 patients were randomized (rhBSSL n = 207, placebo n = 208), 410 patients were analyzed (rhBSSL n = 206, placebo n = 204) and 365 patients were followed until 12 months. Overall, there was no significantly improved growth velocity during rhBSSL treatment compared to placebo (16.77 vs. 16.56 g/kg/day, estimated difference 0.21 g/kg/day, 95% CI [-0.40; 0.83]), nor were secondary endpoints met. However, in a predefined subgroup, small for gestational age infants, there was a significant effect on growth in favor of rhBSSL during treatment. The incidence of adverse events was higher in the rhBSSL group during treatment. CONCLUSIONS: Although this study did not meet its primary endpoint, except in a subgroup of infants small for gestational age, and there was an imbalance in short-term safety, these data provide insights in nutrition, growth and development in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT01413581.

Prevention of Vitamin K Deficiency Bleeding in Newborn Infants: A Position Paper by the ESPGHAN Committee on Nutrition.

Vitamin K deficiency bleeding (VKDB) due to physiologically low vitamin K plasma concentrations is a serious risk for newborn and young infants and can be largely prevented by adequate vitamin K supplementation. The aim of this position paper is to define the condition, describe the prevalence, discuss current prophylaxis practices and outcomes, and to provide recommendations for the prevention of VKDB in healthy term newborns and infants. All newborn infants should receive vitamin K prophylaxis and the date, dose, and mode of administration should be documented. Parental refusal of vitamin K prophylaxis after adequate information is provided should be recorded especially because of the risk of late VKDB. Healthy newborn infants should either receive 1 mg of vitamin K1 by intramuscular injection at birth; or 3 × 2 mg vitamin K1 orally at birth, at 4 to 6 days and at 4 to 6 weeks; or 2 mg vitamin K1 orally at birth, and a weekly dose of 1 mg orally for 3 months. Intramuscular application is the preferred route for efficiency and reliability of administration. The success of an oral policy depends on compliance with the protocol and this may vary between populations and healthcare settings. If the infant vomits or regurgitates the formulation within 1 hour of administration, repeating the oral dose may be appropriate. The oral route is not appropriate for preterm infants and for newborns who have cholestasis or impaired intestinal absorption or are too unwell to take oral vitamin K1, or those whose mothers have taken medications that interfere with vitamin K metabolism. Parents who receive prenatal education about the importance of vitamin K prophylaxis may be more likely to comply with local procedures.

Lipid Quality in Infant Nutrition: Current Knowledge and Future Opportunities.

Dietary lipids are key for infants to not only meet their high energy needs but also fulfill numerous metabolic and physiological functions critical to their growth, development, and health. The lipid composition of breast milk varies during lactation and according to the mother's diet, whereas the lipid composition of infant formulae varies according to the blend of different fat sources. This report compares the compositions of lipids in breast milk and infant formulae, and highlights the roles of dietary lipids in term and preterm infants and their potential biological and health effects. The major differences between breast milk and formulae lie in a variety of saturated fatty acids (such as palmitic acid, including its structural position) and unsaturated fatty acids (including arachidonic acid and docosahexaenoic acid), cholesterol, and complex lipids. The functional outcomes of these differences during infancy and for later child and adult life are still largely unknown, and some of them are discussed, but there is consensus that opportunities exist for improvements in the qualitative lipid supply to infants through the mother's diet or infant formulae. Furthermore, research is required in several areas, including the needs of term and preterm infants for long-chain polyunsaturated fatty acids, the sites of action and clinical effects of lipid mediators on immunity and inflammation, the role of lipids on metabolic, neurological, and immunological outcomes, and the mechanisms by which lipids act on short- and long-term health.

Enteral and parenteral lipid requirements of preterm infants.

Lipids provide infants with most of their energy needs. The major portion of the fat in human milk is found in the form of triglycerides, the phospholipids and cholesterol contributing for only a small proportion of the total fat. Long-chain polyunsaturated fatty acids (LC-PUFAs) are crucial for normal development of the central nervous system and have potential for long-lasting effects that extend beyond the period of dietary insufficiency. Given the limited and highly variable formation of docosahexaenoic acid (DHA) from α-linolenic acid, and because DHA is critical for normal retinal and brain development in the human, DHA should be considered to be conditionally essential during early development. In early enteral studies, the amount of LC-PUFAs administered in formula was chosen to produce the same concentration of arachidonic acid and DHA as in term breast milk. Recent studies report outcome data in preterm infants fed formula with DHA content 2-3 times higher than the current concentration. Overall, these studies show that providing larger amounts of DHA supplements is associated with better neurological outcomes and may provide other health benefits. One study further suggests that the smallest babies are the most vulnerable to DHA deficiency and likely to reap the greatest benefit from high-dose DHA supplementation. Current nutritional management may not provide sufficient amounts of preformed DHA during the parenteral and enteral nutrition periods and in very preterm/very low birth weight infants until due date and higher amounts than those routinely used are likely to be necessary to compensate for intestinal malabsorption, DHA oxidation, and early deficit. Recommendations for the healthcare provider are made in order to prevent lipid and more specifically LC-PUFA deficit. Research should be continued to fill the gaps in knowledge and to further refine the adequate intake for each group of preterm infants.

Respective effects of phlebotomy losses and erythropoietin treatment on the need for blood transfusion in very premature infants.

BACKGROUND: The benefit to risk ratio of the treatment with erythropoietin (EPO) as a means of limiting the number of transfusions in very preterm infants during hospitalization, seems to be modest since the adoption of restrictive transfusion criteria and of policy limiting phlebotomy losses. We therefore aim to evaluate the factors associated with the number of late blood transfusion in very preterm infants in a unit where the routine use of EPO has been discontinued. METHODS: A comparative "before-after" study was carried out in premature infants born before 32 weeks postmenstrual age (PMA), over a period of one year before (EPO group) and one year after (non-EPO group) the discontinuation of EPO therapy. RESULTS: A total of 48 infants were included in the study (EPO = 21; non-EPO = 27). The number of infants transfused after the 15 day of life (D15) and the number of transfusions per infant after D15 were not significantly different between the two groups. In a multivariate analysis, the gestational age and the volume of blood drawn off during the first month of life significantly influenced the need for transfusions after the 15th day of life, independently of the treatment with EPO. The hemoglobin levels measured at different times of hospitalization (median postnatal age: 16, 33 and 67 days) were not significantly different between the two groups. CONCLUSIONS: Our study shows that the discontinuation of EPO did not change the number of late transfusions. Even when a policy limiting phlebotomy losses is used, blood loss is an important and independent risk factor for late transfusion of very preterm infants.

Lipid needs of preterm infants: updated recommendations.

Long-chain polyunsaturated fatty acids (LCPUFAs) are of nutritional interest because they are crucial for normal development of the central nervous system and have potential long-lasting effects that extend beyond the period of dietary insufficiency. Here we review the recent literature and current recommendations regarding LCPUFAs as they pertain to preterm infant nutrition. In particular, findings that relate to fetal accretion, LCPUFA absorption and metabolism, effects on development, and current practices and recommendations have been used to update recommendations for health care providers. The amounts of long-chain polyunsaturated fatty acids (LCPUFAs) used in early studies were chosen to produce the same concentrations as in term breast milk. This might not be a wise approach for preterm infants, however, particularly for very and extremely preterm infants, whose requirements for LCPUFAs and other nutrients exceed what is normally provided in the small volumes that they are able to tolerate. Recent studies have reported outcome data in preterm infants fed milk with a docosahexaenoic acid (DHA) content 2-3 times higher than the current concentration in infant formulas. Overall, these studies show that providing larger amounts of DHA supplements, especially to the smallest infants, is associated with better neurologic outcomes in early life. We emphasize that current nutritional management might not provide sufficient amounts of preformed DHA during the parenteral and enteral nutrition periods and in very preterm/very low birth weight infants until their due date, and that greater amounts than used routinely likely will be needed to compensate for intestinal malabsorption, DHA oxidation, and early deficit. Research should continue to address the gaps in knowledge and further refine adequate intake for each group of preterm infants.