Promoção das competências alimentares do recém-nascido: intervenções centradas no neurodesenvolvimento / Promoting newborn feeding skills: interventions focused on neurodevelopment

A evolução científica e tecnológica na área de enfermagem, tem ganho um destaque no cuidado ao recém-nascido, sendo que nas unidades de cuidados intensivos neonatais se tem assistido a uma mudança de cultura na promoção de cuidados holísticos e de intervenções neuroprotetoras. Apesar dos avanços científicos e tecnológicos os recém-nascidos pré-termo mantêm-se vulneráveis às consequências da prematuridade, nomeadamente no que diz respeito à otimização da nutrição. Um dos desafios dos enfermeiros é potenciar o desenvolvimento de competências do RN na transição para a alimentação oral, de forma segura e eficaz, promovendo a autonomia alimentar. O presente Relatório de Estágio pretende evidenciar o desenvolvimento e aquisição das competências de Enfermeiro Especialista em Enfermagem de Saúde Infantil e Pediátrica durante o percurso de formação, sob a temática escolhida: promoção das competências alimentares no recém-nascido. O processo formativo foi suportado numa metodologia crítica e reflexiva, baseada na evidência científica e no Modelo de Sistemas de Betty Neuman, enquanto referencial teórico de enfermagem, nos Cuidados Centrados na Família e nos Cuidados Não Traumáticos enquanto pilares de enfermagem pediátrica e ainda no modelo dos Cuidados para o Desenvolvimento, baseados na Teoria Sinativa de Desenvolvimento de Als. Das atividades desenvolvidas destacam-se a realização de duas sessões de formação sobre as competências alimentares do recém-nascido e a apresentação a escala de avaliação das competências oromotoras através da escala Early Feeding Skills Versão Modificada.

The scientific and technological development in nursing has gained prominence in newborn care and neonatal intensive care units have witnessed a change of culture in the promotion of holistic care and neuroprotective interventions. Despite scientific and technological advances, preterm newborns remain vulnerable to the consequences of prematurity, particularly regarding the optimisation of nutrition. One of the main challenges nurses face is to promote the development of the newborn's skills in the transition to oral feeding, by safely and effectively promoting feeding autonomy. This Report aims to highlight the development and acquisition of skills as Specialist Nurse in Child Health and Paediatric Nursing, during the reflective practice, under the main problematic: promotion of feeding skills in newborns. This learning process is based on a critical and reflective methodology, supported by scientific evidence and Betty Neuman's Systems Model, as a nursing theoretical framework. It is also sustained by Family Centred Care and Non-Trauma Care, as pillars of paediatric nursing, and backed by Developmental Care Model, based on Als´s Synactive Theory of development. Among the activities developed, two training sessions stand out regarding the feeding skills of the newborn and the presentation of oromotor skills, using the Early Feeding Skills Modified Version asessment scale.

Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years.

BACKGROUND: Docosahexaenoic acid (DHA) is a component of neural tissue. Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks' gestation do not receive the normal supply of DHA. The effect of this deficiency on subsequent cognitive development is not well understood. METHODS: We assessed general intelligence at 5 years in children who had been enrolled in a trial of neonatal DHA supplementation to prevent bronchopulmonary dysplasia. In the previous trial, infants born before 29 weeks' gestation had been randomly assigned in a 1:1 ratio to receive an enteral emulsion that provided 60 mg of DHA per kilogram of body weight per day or a control emulsion from the first 3 days of enteral feeds until 36 weeks of postmenstrual age or discharge home, whichever occurred first. Children from 5 of the 13 centers in the original trial were invited to undergo assessment with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 5 years of corrected age. The primary outcome was the full-scale intelligence quotient (FSIQ) score. Secondary outcomes included the components of WPPSI. RESULTS: A total of 1273 infants underwent randomization in the original trial; of the 656 surviving children who had undergone randomization at the centers included in this follow-up study, 480 (73%) had an FSIQ score available - 241 in the DHA group and 239 in the control group. After imputation of missing data, the mean (±SD) FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group (adjusted difference, 3.45; 95% confidence interval, 0.38 to 6.53; P = 0.03). The results for secondary outcomes generally did not support that obtained for the primary outcome. Adverse events were similar in the two groups. CONCLUSIONS: In infants born before 29 weeks' gestation who had been enrolled in a trial to assess the effect of DHA supplementation on bronchopulmonary dysplasia, the use of an enteral DHA emulsion until 36 weeks of postmenstrual age was associated with modestly higher FSIQ scores at 5 years of age than control feeding. (Funded by the Australian National Health and Medical Research Council and Nu-Mega Ingredients; N3RO Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.).

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth.

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) -0.11[95% CI -0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

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.

Antioxidant Effect of Melatonin in Preterm Newborns.

INTRODUCTION: Preterm infants are at risk of free radical-mediated diseases from oxidative stress (OS) injury. Increased free radical generation has been demonstrated in preterm infants during the first seven days of life. Melatonin (MEL) is a powerful antioxidant and scavenger of free radicals. In preterm neonates, melatonin deficiency has been reported. Exogenous melatonin administration appears a promising strategy in the treatment of neonatal morbidities in which OS has a leading role. OBJECTIVE: The aim was to evaluate plasma MEL concentrations and OS biomarkers in preterm newborns after early administration of melatonin. METHODS: A prospective, randomized double-blind placebo-controlled pilot study was conducted from January 2019 to September 2020. Thirty-six preterm newborns were enrolled. Starting from the first day of life, 21 received a single dose of oral melatonin 0.5 mg/kg once a day, in the morning (MEL group); 15 newborns received an equivalent dose of placebo (placebo group). Samples of 0.2 mL of plasma were collected at 24 and 48 hours after MEL administration. Plasma concentrations of melatonin, non-protein-bound iron (NPBI), advanced oxidation protein products (AOPP), and F2-isoprostanes (F2-Isopr) were measured. Babies were clinically followed until discharge. RESULTS: At 24 and 48 hours after MEL administration, the MEL concentrations were significantly higher in the MEL group than in the placebo group (52759.30 ± 63529.09 vs. 28.57 ± 46.24 pg/mL and 279397.6 ± 516344.2 vs. 38.50 ± 44.01 pg/mL, respectively). NPBI and AOPP did not show any statistically significant differences between the groups both at 24 and 48 hours. At 48 hours, the mean blood concentrations of F2-Isopr were significantly lower in the MEL group than in the placebo group (36.48 ± 33.85 pg/mL vs.89.97 ± 52.01 pg/mL). CONCLUSIONS: Early melatonin administration in preterm newborns reduces lipid peroxidation in the first days of life showing a potential role to protect high-risk newborns. Trial Registration. This trial is registered with NCT04785183, Early Supplementation of Melatonin in Preterm Newborns: the Effects on Oxidative Stress.

Length of Nutritional Transition Associates Negatively with Postnatal Growth in Very Low Birthweight Infants.

Very low birthweight (VLBW, <1500 g) infants may be predisposed to undernutrition during the nutritional transition phase from parenteral to enteral nutrition. We studied the associations among the length of the transition phase, postnatal macronutrient intake, and growth from birth to term equivalent age in VLBW infants. This retrospective cohort study included 248 VLBW infants born before 32 weeks of gestation and admitted to the Children's Hospital, Helsinki, Finland during 2005-2013. Daily nutrient intakes were obtained from computerized medication administration records. The length of the transition phase correlated negatively with cumulative energy, protein, fat, and carbohydrate intake at 28 days of age. It also associated negatively with weight and head circumference growth from birth to term equivalent age. For infants with a long transition phase (over 12 d), the estimates (95% CI) for weight and head circumference z-score change from birth to term equivalent age were -0.3 (-0.56, -0.04) and -0.44 (-0.81, -0.07), respectively, in comparison to those with a short transition phase (ad 7 d). For VLBW infants, rapid transition to full enteral feeding might be beneficial. However, if enteral nutrition cannot be advanced, well-planned parenteral nutrition during the transition phase is necessary to promote adequate growth.

Early Enteral Feeding in Preterm Infants: A Narrative Review of the Nutritional, Metabolic, and Developmental Benefits.

Enteral feeding is the preferred method of nutrient provision for preterm infants. Though parenteral nutrition remains an alternative to provide critical nutrition after preterm delivery, the literature suggests that enteral feeding still confers significant nutritional and non-nutritional benefits. Therefore, the purpose of this narrative review is to summarize health and clinical benefits of early enteral feeding within the first month of life in preterm infants. Likewise, this review also proposes methods to improve enteral delivery in clinical care, including a proposal for decision-making of initiation and advancement of enteral feeding. An extensive literature review assessed enteral studies in preterm infants with subsequent outcomes. The findings support the early initiation and advancement of enteral feeding impact preterm infant health by enhancing micronutrient delivery, promoting intestinal development and maturation, stimulating microbiome development, reducing inflammation, and enhancing brain growth and neurodevelopment. Clinicians must consider these short- and long-term implications when caring for preterm infants.

Questioning the adequacy of standardized vitamin D supplementation protocol in very low birth weight infants: a prospective cohort study.

OBJECTIVES: Preterm infants are at increased risk for vitamin D deficiency (VDD). We aimed to assess the adequacy of standardized vitamin D supplementation protocol in very low birth weight (VLBW) infants. Additionally, vitamin D status of mother/infant couples and the associations between vitamin D status at birth and morbidities of the infants were investigated. METHODS: In this single-center, prospective cohort study blood samples were collected from 55 mothers just before delivery and from their infants at birth and on the 30th day of life (DOL) for 25 hydroxy vitamin D (25OHD) measurements. Vitamin D was initiated in dose of 160 IU/kg by parenteral nutrition on the first DOL and oral vitamin D supplementation (400 IU/day) was administered when enteral feedings reached 50% of total intake or on the 15th DOL. RESULTS: The median 25OHD levels of the infants were 16.12 (9.14-20.50) in cord blood and 36.32 (31.10-44.44) in venous blood on the 30th DOL (p<0.01). In 98% of the VLBW infants 25OHD reached sufficient levels on the 30th DOL. None of the mothers had sufficient vitamin D levels (25OHD >30 ng/mL). Maternal 25OHD levels were correlated with the 25OHD levels of the infants in cord blood (r=0.665, p<0.001). There was a significant difference in mean cord 25OHD levels between winter (13.65 ± 5.69 ng/mL) and summer seasons (19.58 ± 11.67 ng/mL) (p=0.021). No association was found between neonatal morbidity and vitamin D status. CONCLUSIONS: The results clearly show that by utilizing the current supplementation protocol, the majority of VLBW infants with deficient/insufficient serum 25OHD levels reached sufficient levels on the 30th DOL. Furthermore, vitamin D levels in mother/infant couples were found to be highly correlated.

Efficacy of medium-chain triglyceride oil massage on growth in preterm infants: a randomized controlled trial: A CONSORT-compliant article.

BACKGROUND: Medium-chain triglyceride (MCT) oil consists of 8-12 carbons with higher absorption and provides better calories than long-chain triglyceride oil. This study was to explore the effect of MCT oil massage on growth in preterm infants. METHODS: A prospective, single-blind, randomized (two treatments and one control) study was conducted. Preterm infants weighing between 1500 and 2000 g were recruited and randomly assigned to three groups: the MCT oil massage, massage alone and no massage groups. The standardized massage intervention consisted of two 5-min phases, including tactile and kinesthetic stimulation, which were given three times a day for 7 consecutive days. Premature infants in the oil massage group received massage with 10 mL/kg/day of MCT oil divided equally into three applications. Weight, length and head circumference were measured in the three groups at birth and on study days 1 to 7. RESULTS: Forty-eight neonates were evaluated with 16 in each of three groups. The linear mixed effect model was adjusted for other factors, and results showed that weight gain on the 4th day in the oil massage group was greater than that in the no massage group (P < .05). From the 5th to 7th day, weight gain in the oil massage group was greater than that in the other two groups (P < .05). Regarding head circumference and height, this study found that the MCT oil massage group did not have better results than the other two groups. No adverse events were noted in the massage groups. CONCLUSION: The results indicate that preterm infant daily massage with MCT oil is an effective intervention for weight gain that should be recognized as part of low-birth-weight infant developmental care. TRIAL REGISTRATION: clinicaltrials.gov identifier NCT04281563, Registered on 24 February 2020.

Effects of Total Enteral Nutrition on Early Growth, Immunity, and Neuronal Development of Preterm Infants.

The feeding of colostrum and mother's transitional milk improves immune protection and neurodevelopmental outcomes. It also helps with gut maturation and decreases the risks of infection. The supply of nutrients from human milk (HM) is not adequate for preterm infants, even though preterm mother's milk contains higher concentrations of protein, sodium, zinc, and calcium than mature HM. The human milk fortifiers, particularly those with protein, calcium, and phosphate, should be used to supplement HM to meet the necessities of preterm infants. The management of fluid and electrolytes is a challenging aspect of neonatal care of preterm infants. Trace minerals such as iron, zinc, copper, iodine, manganese, molybdenum, selenium, chromium, and fluoride are considered essential for preterm infants. Vitamins such as A, D, E, and K play an important role in the prevention of morbidities, such as bronchopulmonary dysplasia, retinopathy of prematurity, and intraventricular hemorrhage. Therefore, supplementation of HM with required nutrients is recommended for all preterm infants.

Safety and Efficacy of Early High Parenteral Lipid Supplementation in Preterm Infants: A Systematic Review and Meta-Analysis.

The objective of this systematic review and meta-analysis was to summarize the effects of early initiation and achievement of a high dose of parenteral lipids (≥1.5 g/kg/day reached within the first 24 h of birth) on growth and adverse outcomes in preterm infants. PubMed, EMBASE, and Cochrane databases were utilized to search for publications for this meta-analysis. Randomized controlled trials were eligible if data on growth or clinical outcome was available. The search returned nine studies. The mean proportion of postnatal weight loss (%) was lower (mean difference [MD]: -2.73; 95% confidence interval [CI]: -3.69, -1.78), and the mean head circumference near the term equivalent age (cm) was higher in the early high lipid treatment group (MD: 0.67; 95% CI: 0.25, 1.09). There was a favorable association of early high lipid administration with the incidence of extrauterine growth restriction (relative risk [RR]: 0.27; 95% CI: 0.15, 0.48). Generally, there were no differences in morbidities or adverse outcomes with early high lipid administration. Early initiation of parenteral lipids and high dose achieved within the first 24 h of life appear to be safe and endurable and offer benefits in terms of growth.

Fortification of Breast Milk With Preterm Formula Powder vs Human Milk Fortifier in Preterm Neonates: A Randomized Noninferiority Trial.

Importance: Fortification of expressed breast milk (EBM) using commercially available human milk fortifiers (HMF) increases short-term weight and length in preterm very low-birth-weight (VLBW) neonates. However, the high cost and increased risk of feed intolerance limit their widespread use. Preterm formula powder fortification (PTF) might be a better alternative in resource-limited settings. Objective: To demonstrate that fortification of EBM by preterm formula powder is noninferior to fortification by HMF, in terms of short-term weight gain, in VLBW neonates. Design, Setting, and Participants: Open-label, noninferiority, randomized trial conducted from December 2017 to June 2019 at a level 3 neonatal unit in India. The trial enrolled preterm (born at or before 34 weeks of gestation) VLBW neonates receiving at least 100 mL/kg/d of feeds and consuming 75% of milk or more as EBM. Interventions: Neonates were randomly assigned to receive fortification by either PTF or HMF. Calcium, phosphorus, iron, vitamin D, and multivitamins were supplemented in PTF and only vitamin D in the HMF group to meet the recommended dietary allowances. Main Outcomes and Measures: The primary outcome was the weight gain until discharge from the hospital or 40 weeks' postmenstrual age, whichever was earlier; the prespecified noninferiority margin was 2 g/kg/d. Secondary outcomes included morbidities such as necrotizing enterocolitis, feed intolerance, and extrauterine growth restriction (<10th percentile on the Fenton chart at 40 weeks' postmenstrual age). Results: Of the 123 neonates enrolled, 60 and 63 were randomized to the PTF and HMF groups, respectively. The mean gestation (30.5 vs 29.9 weeks) and birth weight (1161 vs 1119 g) were comparable between the groups. There was no difference in the mean (SD) weight gain between the PTF and HMF groups (15.7 [3.9] vs 16.3 [4.0] g/kg/d; mean difference, -0.5 g/kg/d; 95% CI, -1.9 to 0.7). The lower bound of 95% CI did not cross the noninferiority margin. The incidence of feed intolerance was lower in the PTF group (1.4 vs 6.8 per 1000 patient-days; incidence rate ratio 0.19; 95% CI, 0.04 to 0.95), and fewer neonates required withholding of fortification for 24 hours or more (5% vs 22%; risk ratio, 0.22; 95% CI, 0.07 to 0.75). The incidence of necrotizing enterocolitis stage II or more (0 vs 5%) and extrauterine growth restriction (73% vs 81%) was comparable between the groups. Conclusions and Relevance: Fortification with preterm formula powder is not inferior to fortification with human milk fortifiers in preterm neonates. Given the possible reduction in feed intolerance and lower costs, preterm formula might be a better option for fortification, especially in resource-restricted settings. Trial Registration: Clinical Trial Registry, India Identifier: CTRI/2017/11/010593.

Longitudinal Study Depicting Differences in Complementary Feeding and Anthropometric Parameters in Late Preterm Infants up to 2 Years of Age.

Ensuring the nutritional demands of preterm (PT) infants during complementary feeding could contribute significantly to the infants' long-term health and development. However, the dietary guidelines for complementary feeding in PT are scarce. Thus, describing dietary intake and identifying nutritional targets for these infants could be of great interest. The aim of this study is to assess the food intake and anthropometric parameters in a Mediterranean infant cohort from 6 to 24 months and to identify nutritional targets especially focused on late preterm infants. This is a longitudinal prospective study analyzing information from administered questionnaires about general characteristics and food frequency consumption in 115 infants (20 PT (32 to 36 gestational weeks), 95 full-term (FT)) at 6, 12 and 24 months of age. Results show that the differences in the prevalence of underweight observed in PT infants vs. FT infants are maintained for up to 6 months of age but disappear at 12 and 24 months. The age of inclusion of new foods and the average intake of the main food groups was not different from that of FTs. Although protein intake at 6 months was directly correlated with weight gain and growth in FT, these associations were not observed in PT. At the nutritional level, the low intake of vitamin D in preterm infants is noteworthy. These findings may be useful when designing new intervention strategies for this population group.

Exosomal circRNAs contribute to intestinal development via the VEGF signalling pathway in human term and preterm colostrum.

Human breast milk (HBM) provides essential nutrients for newborn growth and development, and contains a variety of biologically active ingredients that can affect gastrointestinal tract and immune system development in breastfed infants. HBM also contains mRNAs, microRNAs and lncRNAs, most of which are encapsulated in milk-derived exosomes and exhibit various important infant development related biological functions. While previous studies have shown that exosomal circRNAs are involved in the intestinal epithelial cells' proliferation and repair. However, the effect of HBM exosomal circRNAs on intestinal development is not clear. In this study, we identified 6756 circRNAs both in preterm colostrum (PC) and term colostrum (TC), of which 66 were upregulated, and 42 were downregulated (|fold change>2|, p < 0.05) in PC. Pathway analysis showed that the VEGF signalling pathway was involved, and network analysis revealed that the differentially expressed circRNAs bound various miRNAs. Further analyses showed that has_circRNA_405708 and has_circRNA_104707 were involved in the VEGF signalling pathway, and that they all bound various mirRNAs. Exosomes found in preterm colostrum (PC) and term colostrum (TC) promoted VEGF protein expression and induced the proliferation and migration of small intestinal epithelial cells (FHCs). Exosomal circRNAs found in human colostrum (HC) binding to related miRNAs may regulate VEGF signalling, and intestinal development.

Enteral zinc supplementation for prevention of morbidity and mortality in preterm neonates.

BACKGROUND: Preterm and low birth weight infants are born with low stores in zinc, which is a vital trace element for growth, cell differentiation and immune function. Preterm infants are at risk of zinc deficiency during the postnatal period of rapid growth. Systematic reviews in the older paediatric population have previously shown that zinc supplementation potentially improves growth and positively influences the course of infectious diseases. In paediatric reviews, the effect of zinc supplementation was most pronounced in those with low nutritional status, which is why the intervention could also benefit preterm infants typically born with low zinc stores and decreased immunity. OBJECTIVES: To determine whether enteral zinc supplementation, compared with placebo or no supplementation, affects important outcomes in preterm infants, including death, neurodevelopment, common morbidities and growth. SEARCH METHODS: Our searches are up-to-date to 20 February 2020. For the first search, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 8), MEDLINE via PubMed (1966 to 29 September 2017), Embase (1980 to 29 September 2017), and CINAHL (1982 to 29 September 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. We ran an updated search from 1 January 2017 to 20 February 2020 in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost. SELECTION CRITERIA: We included RCTs and quasi-RCTs that compared enteral zinc supplementation versus placebo or no supplementation in preterm infants (gestational age < 37 weeks), and low birth weight babies (birth weight < 2500 grams), at any time during their hospital admission after birth. We included zinc supplementation in any formulation, regimen, or dose administered via the enteral route. We excluded infants who underwent gastrointestinal (GI) surgery during their initial hospital stay, or had a GI malformation or another condition accompanied by abnormal losses of GI juices, which contain high levels of zinc (including, but not limited to, stomas, fistulas, and malabsorptive diarrhoea). DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. Two review authors separately screened abstracts, evaluated trial quality and extracted data. We synthesised effect estimates using risk ratios (RR), risk differences (RD), and standardised mean differences (SMD). Our primary outcomes of interest were all-cause mortality and neurodevelopmental disability. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included five trials with a total of 482 preterm infants; there was one ongoing trial. The five included trials were generally small, but of good methodological quality. Enteral zinc supplementation compared to no zinc supplementation Enteral zinc supplementation started in hospitalised preterm infants may decrease all-cause mortality (between start of intervention and end of follow-up period) (RR 0.55, 95% CI 0.31 to 0.97; 3 studies, 345 infants; low-certainty evidence). No data were available on long-term neurodevelopmental outcomes at 18 to 24 months of (post-term) age. Enteral zinc supplementation may have little or no effect on common morbidities such as bronchopulmonary dysplasia (RR 0.66, 95% CI 0.31 to 1.40, 1 study, 193 infants; low-certainty evidence), retinopathy of prematurity (RR 0.14, 95% CI 0.01 to 2.70, 1 study, 193 infants; low-certainty evidence), bacterial sepsis (RR 1.11, 95% CI 0.60 to 2.04, 2 studies, 293 infants; moderate-certainty evidence), or necrotising enterocolitis (RR 0.08, 95% CI 0.00 to 1.33, 1 study, 193 infants; low-certainty evidence). The intervention probably improves weight gain (SMD 0.46, 95% CI 0.28 to 0.64; 5 studies, 481 infants; moderate-certainty evidence); and may slightly improve linear growth (SMD 0.75, 95% CI 0.36 to 1.14, 3 studies, 289 infants; low-certainty evidence), but may have little or no effect on head growth (SMD 0.21, 95% CI -0.02 to 0.44, 3 studies, 289 infants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Enteral supplementation of zinc in preterm infants compared to no supplementation or placebo may moderately decrease mortality and probably improve short-term weight gain and linear growth, but may have little or no effect on common morbidities of prematurity. There are no data to assess the effect of zinc supplementation on long-term neurodevelopment.

High versus low medium chain triglyceride content of formula for promoting short-term growth of preterm infants.

BACKGROUND: In-hospital growth of preterm infants remains a challenge in clinical practice. The high nutrient demands of preterm infants often lead to growth faltering. For preterm infants who cannot be fed maternal or donor breast milk or may require supplementation, preterm formulas with fat in the form of medium chain triglycerides (MCTs) or long chain triglycerides (LCTs) may be chosen to support nutrient utilization and to improve growth. MCTs are easily accessible to the preterm infant with an immature digestive system, and LCTs are beneficial for central nervous system development and visual function. Both have been incorporated into preterm formulas in varying amounts, but their effects on the preterm infant's short-term growth remain unclear. This is an update of a review originally published in 2002, then in 2007. OBJECTIVES: To determine the effects of formula containing high as opposed to low MCTs on early growth in preterm infants fed a diet consisting primarily of formula.  SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 8), in the Cochrane Library; Ovid MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily, and Ovid MEDLINE(R); MEDLINE via PubMed for the previous year; and Cumulative Index to Nursing and Allied Health Literature (CINAHL), on 16 September 2020. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included all randomized and quasi-randomized trials comparing the effects of feeding high versus low MCT formula (for a minimum of five days) on the short-term growth of preterm (< 37 weeks' gestation) infants. We defined high MCT formula as 30% or more by weight, and low MCT formula as less than 30% by weight. The infants must be on full enteral diets, and the allocated formula must be the predominant source of nutrition. DATA COLLECTION AND ANALYSIS: The review authors assessed each study's quality and extracted data on growth parameters as well as adverse effects from included studies. All data used in analysis were continuous; therefore, mean differences with 95% confidence intervals were reported. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We identified 10 eligible trials (253 infants) and extracted relevant growth data from 7 of these trials (136 infants). These studies were found to provide evidence of very low to low certainty. Risk of bias was noted, as few studies described specific methods for random sequence generation, allocation concealment, or blinding. We found no evidence of differences in short-term growth parameters when high and low MCT formulas were compared. As compared to low MCT formula, preterm infants fed high MCT formula showed little to no difference in weight gain velocity (g/kg/d) during the intervention, with a typical mean difference (MD) of -0.21 g/kg/d (95% confidence interval (CI) -1.24 to 0.83; 6 studies, 118 infants; low-certainty evidence). The analysis for weight gain (g/d) did not show evidence of differences, with an MD of 0.00 g/d (95% CI -5.93 to 5.93; 1 study, 18 infants; very low-certainty evidence), finding an average weight gain of 20 ± 5.9 versus 20 ± 6.9 g/d for high and low MCT groups, respectively. We found that length gain showed no difference between low and high MCT formulas, with a typical MD of 0.10 cm/week (95% CI -0.09 to 0.29; 3 studies, 61 infants; very low-certainty evidence). Head circumference gain also showed little to no difference during the intervention period, with an MD of -0.04 cm/week (95% CI -0.17 to 0.09; 3 studies, 61 infants; low-certainty evidence). Two studies reported skinfold thickness with different measurement definitions, and evidence was insufficient to determine if there was a difference (2 studies, 32 infants; very low-certainty evidence). There are conflicting data (5 studies) as to formula tolerance, with 4 studies reporting narrative results of no observed clinical difference and 1 study reporting higher incidence of signs of gastrointestinal intolerance in high MCT formula groups. There is no evidence of effect on the incidence of necrotizing enterocolitis (NEC), based on small numbers in two trials. Review authors found no studies addressing long-term growth parameters or neurodevelopmental outcomes. AUTHORS' CONCLUSIONS: We found evidence of very low to low certainty suggesting no differences among short-term growth data for infants fed low versus high MCT formulas. Due to lack of evidence and uncertainty, neither formula type could be concluded to improve short-term growth outcomes or have fewer adverse effects. Further studies are necessary because the results from included studies are imprecise due to small numbers and do not address important long-term outcomes. Additional research should aim to clarify effects on formula tolerance and on long-term growth and neurodevelopmental outcomes, and should include larger study populations to better evaluate effect on NEC incidence.

Human Milk Hormone Intake in the First Month of Life and Physical Growth Outcomes in Preterm Infants.

CONTEXT: Human milk contains hormones that regulate metabolism. Extrauterine growth restriction remains common among preterm infants, but the effect of ingesting milk hormones on preterm infant growth is poorly understood. OBJECTIVE: To quantify associations of longitudinal exposure to leptin, adiponectin, and insulin in milk with physical growth of preterm infants. DESIGN/METHODS: In 50 preterm neonates (median gestational age 29.4 weeks), we sampled maternal milk on day-of-life 7, 14, 21, and 28 and measured hormone levels in whole milk by ELISA. Milk leptin levels were available for a subset of 18 infants. We calculated milk hormone doses by multiplying the hormone level by the milk volume ingested on each day and estimated the area under the curve (AUC) to reflect longitudinal exposure. We analyzed associations of milk hormone exposure with growth outcomes in generalized estimated equations. MAIN OUTCOME MEASURES: Weight gain velocity and z-scores in weight, length, head circumference, and body mass index at 36 weeks' postmenstrual age (PMA). RESULTS: Higher leptin intake was associated with greater weight gain (2.17g/kg/day [95% CI, 1.31, 3.02]) and weight z-score at 36 weeks' PMA (0.30 [0.08, 0.53] higher z-score per tertile). Higher adiponectin intake was associated with greater length z-score (0.41 [0.13, 0.69]), however, this association was nullified after adjustment of protein and calorie intake. Higher adiponectin was associated with smaller head circumference z-score (-0.36 [-0.64, -0.07]). Insulin was not associated with growth outcomes. CONCLUSIONS: Milk leptin and adiponectin exposures may affect growth of preterm infants. The long-term effects of milk hormones warrant further investigation.

Early protein intake predicts functional connectivity and neurocognition in preterm born children.

Nutritional intake can promote early neonatal brain development in very preterm born neonates (< 32 weeks' gestation). In a group of 7-year-old very preterm born children followed since birth, we examined whether early nutrient intake in the first weeks of life would be associated with long-term brain function and neurocognitive skills at school age. Children underwent resting-state functional MRI (fMRI), intelligence testing (Wechsler Intelligence Scale for Children, 5th Ed) and visual-motor processing (Beery-Buktenica, 5th Ed) at 7 years. Relationships were assessed between neonatal macronutrient intakes, functional connectivity strength between thalamic and default mode networks (DMN), and neuro-cognitive function using multivariable regression. Greater functional connectivity strength between thalamic networks and DMN was associated with greater intake of protein in the first week (ß = 0.17; 95% CI 0.11, 0.23, p < 0.001) but lower intakes of fat (ß = - 0.06; 95% CI - 0.09, - 0.02, p = 0.001) and carbohydrates (ß = - 0.03; 95% CI - 0.04, - 0.01, p = 0.003). Connectivity strength was also associated with protein intake during the first month (ß = 0.22; 95% CI 0.06, 0.37, p = 0.006). Importantly, greater thalamic-DMN connectivity strength was associated with higher processing speed indices (ß = 26.9; 95% CI 4.21, 49.49, p = 0.02) and visual processing scores (ß = 9.03; 95% CI 2.27, 15.79, p = 0.009). Optimizing early protein intake may contribute to promoting long-term brain health in preterm-born children.

Effect of Enteral Protein Amount on Growth and Health Outcomes in Very-Low-Birth-Weight Preterm Infants: Phase II of the Pre-B Project and an Evidence Analysis Center Systematic Review.

Adequate protein intake by very-low-birth-weight preterm infants (≤1,500 g at birth) is essential to optimize growth and development. The estimated needs for this population are the highest of all humans, however, the recommended intake has varied greatly over the past several years. A literature search was conducted in PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases to identify randomized controlled trials evaluating the effect of prescribed protein intake and identified outcomes. Articles were screened by 2 reviewers, risk of bias was assessed, data were synthesized quantitatively and narratively, and each outcome was separately graded for certainty of evidence. The literature search retrieved 25,384 articles and 2 trials were included in final analysis. No trials were identified that evaluated effect of protein amount on morbidities or mortality. Moderate certainty evidence found a significant difference in weight gain when protein intake of greater than 3.5 g/kg/day from preterm infant formula was compared with lower intakes. Low-certainty evidence found no evidence of effect of protein intake of 2.6 vs 3.1 vs 3.8 g/kg/day on length, head circumference, skinfold measurements, or mid-arm circumference. Low-certainty evidence found some improvement in development measures when higher protein intake of 3.8 vs 3.1 vs 2.6 g/kg/day were compared. Low-certainty evidence found no significant difference in bone mineral content when these protein intakes were compared. No studies were identified that compared protein intake greater than 4.0 g/kg/day. This systematic review found that protein intake between 3.5 and 4.0 g/kg/day promotes weight gain and improved development.