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Using Nature to Nurture: Breast Milk Analysis and Fortification to Improve Growth and Neurodevelopmental Outcomes in Preterm Infants.
Ottolini, KM, Schulz, EV, Limperopoulos, C, Andescavage, N
Nutrients. 2021;(12)
Abstract
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.
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Preventing Brain Injury in the Preterm Infant-Current Controversies and Potential Therapies.
Yates, N, Gunn, AJ, Bennet, L, Dhillon, SK, Davidson, JO
International journal of molecular sciences. 2021;(4)
Abstract
Preterm birth is associated with a high risk of morbidity and mortality including brain damage and cerebral palsy. The development of brain injury in the preterm infant may be influenced by many factors including perinatal asphyxia, infection/inflammation, chronic hypoxia and exposure to treatments such as mechanical ventilation and corticosteroids. There are currently very limited treatment options available. In clinical trials, magnesium sulfate has been associated with a small, significant reduction in the risk of cerebral palsy and gross motor dysfunction in early childhood but no effect on the combined outcome of death or disability, and longer-term follow up to date has not shown improved neurological outcomes in school-age children. Recombinant erythropoietin has shown neuroprotective potential in preclinical studies but two large randomized trials, in extremely preterm infants, of treatment started within 24 or 48 h of birth showed no effect on the risk of severe neurodevelopmental impairment or death at 2 years of age. Preclinical studies have highlighted a number of promising neuroprotective treatments, such as therapeutic hypothermia, melatonin, human amnion epithelial cells, umbilical cord blood and vitamin D supplementation, which may be useful at reducing brain damage in preterm infants. Moreover, refinements of clinical care of preterm infants have the potential to influence later neurological outcomes, including the administration of antenatal and postnatal corticosteroids and more accurate identification and targeted treatment of seizures.
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Sex-specific effects of nutritional supplements in infants born early or small: protocol for an individual participant data meta-analysis (ESSENCE IPD-MA).
Lin, L, Crowther, C, Gamble, G, Bloomfield, F, Harding, JE, ,
BMJ open. 2020;(1):e033438
Abstract
INTRODUCTION Preterm and small for gestational age (SGA) infants are at increased risk of poor growth, disability and delayed development. While growing up they are also at increased risk of obesity, diabetes and later heart disease. The risk of such adverse outcomes may be altered by how preterm and SGA infants are fed after birth. Faltering postnatal growth is common due to failure to achieve recommended high energy and protein intakes, and thus preterm and SGA infants are often provided with supplemental nutrition soon after birth. Enhanced nutrition has been associated with improved early growth and better cognitive development. However, limited evidence suggests that faster growth may increase the risk for later adiposity, metabolic and cardiovascular disease, and that such risks may differ between girls and boys. METHODS AND ANALYSIS We will search Ovid MEDLINE, Embase, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, controlled-trials.com, ClinicalTrials.gov and anzctr.org.au for randomised trials that studied the effects of macronutrient supplements for preterm and SGA infants on (i) developmental and metabolic and (ii) growth outcomes after hospital discharge. The outcomes will be (i) cognitive impairment and metabolic risk (co-primary) and (ii) body mass index. Individual participant data (IPD) from all available trials will be included using an intention-to-treat approach. A one-stage procedure for IPD meta-analysis (MA) will be used, accounting for clustering of participants within studies. Exploratory subgroup analyses will further investigate sources of heterogeneity, including sex and size of infants, different timing, duration and type of supplements. ETHICS AND DISSEMINATION This IPD-MA is approved by the University of Auckland Human Participants Ethics Committee (reference number: 019874). Individual studies have approval from relevant local ethics committees. Results will be disseminated in a peer-reviewed journal and presented at international conferences. PROSPERO REGISTRATION NUMBER CRD42017072683.
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Caffeine for preterm infants: Fixed standard dose, adjustments for age or high dose?
Saroha, V, Patel, RM
Seminars in fetal & neonatal medicine. 2020;(6):101178
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Abstract
Caffeine is an effective treatment for apnea of prematurity and has several important benefits, including decreasing respiratory morbidity and motor impairment. In this article, we focus on the dose of caffeine. We review the evidence regarding the efficacy and safety of standard caffeine dosing and alternative dosing approaches, including the use of high dose caffeine and routine dose adjustments for age. Current evidence suggests high dose caffeine may provide additional benefit in reducing the risk of bronchopulmonary dysplasia and extubation failure, but may also increase the risk of cerebellar hemorrhage and seizures. Increasing the standard caffeine citrate dose every 1-2 weeks to a goal dose of 8 mg per kilogram every 24 h may help maintain therapeutic effect. We conclude by highlighting the need for additional trials before high dose caffeine is routinely used.
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National and international guidelines for neonatal caffeine use: Are they evidenced-based?
Eichenwald, EC
Seminars in fetal & neonatal medicine. 2020;(6):101177
Abstract
The Caffeine for Apnea of Prematurity (CAP) trial showed that caffeine was safe when used with standard dosing and provided both pulmonary and neurological benefits to preterm infants. Since its publication almost 15 years ago, the use of caffeine in extremely premature infants in Newborn Intensive Care Units worldwide has increased, with almost all receiving the drug during their hospital stay. Subsequent observational studies suggested that administration of caffeine before 3 days of age may have greater benefits, leading many neonatologists to start caffeine prophylactically in all very low birth weight infants. Several publicly available national and international guidelines on caffeine advocate prophylactic use, and some recommend higher doses than those used in the CAP trial. This article will review the evidence basis for neonatal caffeine therapy in light of these guidelines.
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6.
Protective effects of different doses of human milk on neonatal necrotizing enterocolitis.
Zhang, B, Xiu, W, Dai, Y, Yang, C
Medicine. 2020;(37):e22166
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Abstract
We aim to summarize the evidence focusing on the effects of various doses of human milk on the risk of neonatal necrotizing enterocolitis (NEC). The eligible articles in the study were those investigating the association between human milk and NEC published before June 26, 2019, in the PubMed, EMBASE, the Cochrane Library, VIP database, CNKI database, and Wangfang database. The included criteria were as follows: premature infants of <37 weeks; randomly controlled trials (RCTs); those fed by mother's own milk or donor human milk; studies focused on the comparison of human milk and formula milk, involving various breast milk doses; and NEC-related studies. Compared with the exclusive formula, the incidence of NEC in the infants fed by exclusive human milk was significantly lower. The incidence of NEC in the infants fed by exclusive human milk was significantly lower than that of partial human milk [risk ratio (RR) = 0.54, 95% confidence interval (95% CI): 0.36-0.79, P < .05]. The incidence of NEC in the infants fed mainly by human milk was significantly lower than that of mainly fed by formula. Incidence of NEC in the infants fed by exclusive human milk was significantly lower than that of any formula (RR = 0.49, 95% CI: 0.34-0.71, P < .05). In summary, this meta-analysis was based on the RCTs involving the prevention of NEC using human milk. Exclusive human milk and partial human milk reduced the incidence of NEC in premature infants, especially in the those fed by high proportion of human milk. In addition, more RCTs are needed to further validate such conclusion.
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New Nutritional and Therapeutical Strategies of NEC.
Teresa, C, Antonella, D, de Ville de Goyet Jean,
Current pediatric reviews. 2019;(2):92-105
Abstract
Necrotizing enterocolitis (NEC) is an acquired severe disease of the digestive system affecting mostly premature babies, possibly fatal and frequently associated to systemic complications. Because of the severity of this condition and the possible long-term consequences on the child's development, many studies have aimed at preventing the occurrence of the primary events at the level of the bowel wall (ischemia and necrosis followed by sepsis) by modifying or manipulating the diet (breast milk versus formula) and/or the feeding pattern (time for initiation after birth, continuous versus bolus feeding, modulation of intake according clinical events). Feeding have been investigated so far in order to prevent NEC. However, currently well-established and shared clinical nutritional practices are not available in preventing NEC. Nutritional and surgical treatments of NEC are instead well defined. In selected cases surgery is a therapeutic option of NEC, requiring sometimes partial intestinal resection responsible for short bowel syndrome. In this paper we will investigate the available options for treating NEC according to the Walsh and Kliegman classification, focusing on feeding practices in managing short bowel syndrome that can complicate NEC. We will also analyze the proposed ways of preventing NEC.
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Neuroprotection of the preterm brain.
Fleiss, B, Gressens, P
Handbook of clinical neurology. 2019;:315-328
Abstract
Despite notable advances in the care and survival of preterm infants, a significant proportion of preterm neonates will have life-long cognitive, behavioral, and motor deficits, and robustly effective neuroprotective strategies are still missing. These therapies must target the pathophysiologic mechanisms observed in contemporaneous infants and rely on modern epidemiology, imaging, and experimental models and assessment techniques. Two drugs, magnesium sulfate and caffeine, are already in use in several units, and although their targets are apnea of prematurity and myometrial contractility (respectively), they do offer improved odds of positive outcomes. Nevertheless, these drugs have limited efficacy, and NICU-to-NICU administration varies greatly. As such, there is an obvious need for additional specific neurotherapeutic strategies to further enhance the outcome of this very fragile population of neonates. The chapter reviews these issues, highlights bottlenecks that need to be solved for meaningful progress in the field, and proposes future innovative avenues for intervention, including delayed interventions.
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Care of the Neonatal Intensive Care Unit Graduate after Discharge.
Goldstein, RF, Malcolm, WF
Pediatric clinics of North America. 2019;(2):489-508
Abstract
Premature and critically ill term infants are often discharged from the neonatal intensive care unit (NICU) with ongoing medical problems, including respiratory problems; growth, nutrition and feeding problems; and neurologic injury. At discharge, they may also be dependent on technology such as supplemental oxygen, tracheostomy, mechanical ventilation, feeding tube, and monitors. Primary care physicians must have special knowledge and understanding of the medical complications of NICU graduates to coordinate post-discharge care. We examine the most common post-discharge medical problems in premature and critically ill term infants and inform the primary care provider about expected outcomes and possible new problems.
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Dysbiosis and Prematurity: Is There a Role for Probiotics?
Baldassarre, ME, Di Mauro, A, Capozza, M, Rizzo, V, Schettini, F, Panza, R, Laforgia, N
Nutrients. 2019;(6)
Abstract
Healthy microbiota is a critical mediator in maintaining health and it is supposed that dysbiosis could have a role in the pathogenesis of a number of diseases. Evidence supports the hypothesis that maternal dysbiosis could act as a trigger for preterm birth; aberrant colonization of preterm infant gut might have a role in feeding intolerance and pathogenesis of necrotizing enterocolitis. Despite several clinical trials and meta-analyses, it is still not clear if modulation of maternal and neonatal microbiota with probiotic supplementation decreases the risk of preterm birth and its complications.