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Metabolic bone disease of prematurity: causes, recognition, prevention, treatment and long-term consequences.
Chinoy, A, Mughal, MZ, Padidela, R
Archives of disease in childhood. Fetal and neonatal edition. 2019;(5):F560-F566
Abstract
Metabolic bone disease of prematurity (MBDP) is characterised by skeletal demineralisation, and in severe cases it can result in fragility fractures of long bones and ribs during routine handling. MBDP arises from prenatal and postnatal factors. Infants who are born preterm are deprived of fetal mineral accumulation, 80% of which occurs in the third trimester. Postnatally, it is difficult to maintain a comparable intake of minerals, and medications, such as corticosteroids and diuretic therapy, lead to bone resorption. With improvements in neonatal care and nutrition, the incidence of MBDP in preterm infants appears to have decreased, although the recent practice of administering phosphate supplements alone will result in secondary hyperparathyroidism and associated bone loss, worsening MBDP. Postnatal immobilisation and loss of placental supply of oestrogen also contribute to skeletal demineralisation. There is no single diagnostic or screening test for MBDP, with pitfalls existing for most radiological and biochemical investigations. By reviewing the pathophysiology of calcium and phosphate homeostasis, one can establish that plasma parathyroid hormone is important in determining the aetiology of MBDP - primarily calcipaenia or phosphopaenia. This will then direct treatment with the appropriate supplements while considering optimal physiological calcium to phosphate ratios.
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Human milk protein vs. formula protein and their use in preterm infants.
Gianni, ML, Roggero, P, Mosca, F
Current opinion in clinical nutrition and metabolic care. 2019;(1):76-81
Abstract
PURPOSE OF REVIEW We review the current available evidence on the metabolic fate of human milk proteins and their potential clinical implications for growth and body composition development vs. those of formula proteins in preterm infants. RECENT FINDINGS The decreased content of human milk protein in preterm mothers throughout lactation might contribute to the reduced growth reported in exclusively human milk-fed infants compared with that of formula-fed infants. Recent studies have demonstrated that preterm infants are capable of degrading human milk proteins regardless of their degree of prematurity or postnatal age, with limited contribution from milk proteases to protein digestion. The nitrogen balance of fortified human milk-fed preterm infants is higher than that of formula-fed preterm infants. Moreover, the growth of human milk-fed preterm infants appears to be accompanied by fat-free mass deposition. SUMMARY Provided that adequate protein and energy intakes are delivered, human milk enhances protein use rather than oxidation as well as promotes tissue growth, leading to preferential fat-free mass deposition and contributing to the recovery of the body composition in preterm infants. Human milk feeding should be supported and promoted for all preterm mother-infant pairs.
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Choline and choline-related nutrients in regular and preterm infant growth.
Bernhard, W, Poets, CF, Franz, AR
European journal of nutrition. 2019;(3):931-945
Abstract
BACKGROUND Choline is an essential nutrient, with increased requirements during development. It forms the headgroup of phosphatidylcholine and sphingomyelin in all membranes and many secretions. Phosphatidylcholine is linked to cell signaling as a phosphocholine donor to synthesize sphingomyelin from ceramide, a trigger of apoptosis, and is the major carrier of arachidonic and docosahexaenoic acid in plasma. Acetylcholine is important for neurodevelopment and the placental storage form for fetal choline supply. Betaine, a choline metabolite, functions as osmolyte and methyl donor. Their concentrations are all tightly regulated in tissues. CLINCAL IMPACT During the fetal growth spurt at 24-34-week postmenstrual age, plasma choline is higher than beyond 34 weeks, and threefold higher than in pregnant women [45 (36-60) µmol/L vs. 14 (10-17) µmol/L]. The rapid decrease in plasma choline after premature birth suggests an untimely reduction in choline supply, as cellular uptake is proportional to plasma concentration. Supply via breast milk, with phosphocholine and α-glycerophosphocholine as its major choline components, does not prevent such postnatal decrease. Moreover, high amounts of liver PC are secreted via bile, causing rapid hepatic choline turnover via the enterohepatic cycle, and deficiency in case of pancreatic phospholipase A2 deficiency or intestinal resection. Choline deficiency causes hepatic damage and choline accretion at the expense of the lungs and other tissues. CONCLUSION Choline deficiency may contribute to the impaired lean body mass growth and pulmonary and neurocognitive development of preterm infants despite adequate macronutrient supply and weight gain. In this context, a reconsideration of current recommendations for choline supply to preterm infants is required.
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A Review of Bioactive Factors in Human Breastmilk: A Focus on Prematurity.
Gila-Diaz, A, Arribas, SM, Algara, A, Martín-Cabrejas, MA, López de Pablo, ÁL, Sáenz de Pipaón, M, Ramiro-Cortijo, D
Nutrients. 2019;(6)
Abstract
Preterm birth is an increasing worldwide problem. Prematurity is the second most common cause of death in children under 5 years of age. It is associated with a higher risk of several pathologies in the perinatal period and adulthood. Maternal milk, a complex fluid with several bioactive factors, is the best option for the newborn. Its dynamic composition is influenced by diverse factors such as maternal age, lactation period, and health status. The aim of the present review is to summarize the current knowledge regarding some bioactive factors present in breastmilk, namely antioxidants, growth factors, adipokines, and cytokines, paying specific attention to prematurity. The revised literature reveals that the highest levels of these bioactive factors are found in the colostrum and they decrease along the lactation period; bioactive factors are found in higher levels in preterm as compared to full-term milk, they are lacking in formula milk, and decreased in donated milk. However, there are still some gaps and inconclusive data, and further research in this field is needed. Given the fact that many preterm mothers are unable to complete breastfeeding, new information could be important to develop infant supplements that best match preterm human milk.
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What Is New about Transfusions for Preterm Infants? An Update.
Kirpalani, H, Whyte, RK
Neonatology. 2019;(4):406-410
Abstract
Currently the question of whether to maintain a higher hemoglobin level by transfusing more liberally, as opposed to a more restrictive strategy with lower hemoglobin maintenance levels, has not been answered. We review summarized conclusions of a Cochrane systematic review and meta-analysis of 614 infants in 4 randomized controlled trials (RCT) pooling data. This suggests potential benefits of higher hemoglobin levels, i.e., a possible improved cognition of infants at 18-21 months' corrected age and a reduction of apnea. However, the data on cognition is hypothesis generating as it derives from a post hoc analysis from a single trial in 451 infants. Moreover, the data on apnea need confirmation in larger trials. The effect of adding data of cognitive 2-year outcomes of 1,744 infants from 2 RCT, which will be reported soon, should expand our understanding. This new data will need to be integrated with the older generation of RCTs but also with emerging suggestions from observational data on potential risks of blood transfusions. We discuss some of these warnings from observational studies. Finally, we ask whether we are ready to individualize blood transfusion to physiological measures made in individual infants, and we point to some current difficulties hindering this step.
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Review shows that donor milk does not promote the growth and development of preterm infants as well as maternal milk.
Hård, AL, Nilsson, AK, Lund, AM, Hansen-Pupp, I, Smith, LEH, Hellström, A
Acta paediatrica (Oslo, Norway : 1992). 2019;(6):998-1007
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Abstract
AIM: This nonsystematic review examined differences in the composition of raw maternal breastmilk and pasteurised donor milk and possible health effects on preterm infants. METHODS We searched PubMed up to July 2018 for studies published in English that focused on four comparisons as follows: raw maternal milk versus donor milk, human milk before and after Holder pasteurisation, milk from mothers who delivered preterm and at term and milk collected during early and late lactation. We also searched for possible effects of the milk components, as well as the effects of maternal and donor milk on preterm infants' health. RESULTS Raw maternal milk contained factors involved in antioxidant and anti-inflammatory defence, gut microbiome establishment and the maturation of immune defences, food tolerability and metabolism. Many of these factors were reduced or abolished in processed donor milk. Both maternal milk and donor milk have been associated with a reduced incidence of necrotising enterocolitis. High-dose feeding with maternal milk during the neonatal period reportedly reduced the risk of other morbidities and promoted growth and neurodevelopment. CONCLUSION Many of the components in raw maternal breastmilk were lacking in pasteurised donor milk, which was inferior in promoting the growth and development of very preterm infants.
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Protein intakes to optimize outcomes for preterm infants.
Embleton, ND, van den Akker, CHP
Seminars in perinatology. 2019;(7):151154
Abstract
Proteins are key structural components of all human cells and are also involved in key physiologic processes through their roles as enzymes, hormones and transport proteins. Protein requirements are substantially higher in preterm infants than those born at term, yet inadequate protein intakes are a common problem on many neonatal units. Very preterm infants (VPT, <32 weeks) commonly receive parenteral amino acid solutions which are typically commenced on admission, and increased over the next few days. Several recent studies have explored differing parenteral amino acid intakes in the first few days, and recommendations have recently been updated. Parenteral nutrition intakes are decreased as enteral feeds are tolerated, but human milk alone will not meet protein needs in most VPT and supplementation or fortification will be required. This review paper considers basic protein and amino acid physiology in the newborn period, and the evidence base for current recommendations.
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Effect of different doses of vitamin D supplementation on preterm infants - an updated meta-analysis.
Yang, Y, Li, Z, Yan, G, Jie, Q, Rui, C
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2018;(22):3065-3074
Abstract
OBJECTIVE Vitamin D deficiency (VDD) is common among infants, especially in preterm babies. There are some controversies over its use on body development, immune function and incidence of bronchopulmonary dysplasia (BPD). METHODS We systematically reviewed PubMed, Embase, and Cochrane databases for studies in English, and in Wanfang, VIP, and Cnki databases for Chinese studies (databases were last launched on 1 August 2016). RESULTS Twelve original random controlled studies (seven in English and five in Chinese) were included (1). There are no differences between high-dose (800-1000 IU/d) and low-dose (400 IU/d) groups on calcium, phosphorus, and 25(OH)D concentrations (p > .05). However, length gain and head circumference gain are significantly increased in the high-dose group (p < .05) (2). IL-2, Ig-A, and Ig-G levels are significant increased in the vitamin D supplementation group compared with the control group (p < .05) (3). With respect to BPD, there is no significant difference between the vitamin D supplementation group and the control group (p > .05). CONCLUSIONS In preterm infants, daily supplementation of vitamin D in doses of 800-1000 IU compared with 400 IU appears to be better not only in development but also in immune function. But clinical trials with a larger sample size are still needed.
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Fat supplementation of human milk for promoting growth in preterm infants.
Amissah, EA, Brown, J, Harding, JE
The Cochrane database of systematic reviews. 2018;(6):CD000341
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Abstract
BACKGROUND As preterm infants do not experience the nutrient accretion and rapid growth phase of the third trimester of pregnancy, they are vulnerable to postnatal nutritional deficits, including of fat. Consequently, they require higher fat intakes compared to their full term counterparts to achieve adequate growth and development. Human milk fat provides the major energy needs of the preterm infant and also contributes to several metabolic and physiological functions. Although human milk has many benefits for this population, its fat content is highly variable and may be inadequate for their optimum growth and development. This is a 2018 update of a Cochrane Review last published in 2000. OBJECTIVES To determine whether supplementation of human milk with fat compared with unsupplemented human milk fed to preterm infants improves growth, body composition, cardio-metabolic, and neurodevelopmental outcomes without significant adverse effects. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 1), MEDLINE via PubMed (1966 to 08 February 2018), Embase (1980 to 08 February 2018), and CINAHL (1982 to 08 February 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA Published and unpublished randomised controlled trials were eligible if they used random or quasi-random methods to allocate preterm infants fed human milk in hospital to supplementation or no supplementation with additional fat. DATA COLLECTION AND ANALYSIS No new randomised controlled trials matching the selection criteria were found but we extracted data from the previously included trial due to changes in review outcomes from when the protocol was first published. Two reviewers independently abstracted data, assessed trial quality, and the quality of evidence at the outcome level using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. We planned to perform meta-analyses using risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with their respective 95% confidence intervals (CIs). We planned to use a fixed-effect model and to explore potential causes of heterogeneity via sensitivity analyses. MAIN RESULTS One randomised trial involving 14 preterm infants was included. There was no evidence of a clear difference between the fat-supplemented and unsupplemented groups in in-hospital rates of growth in weight (MD 0.6 g/kg/day, 95% CI -2.4 to 3.6; 1 RCT, n = 14 infants, very low-quality evidence), length (MD 0.1 cm/week, 95% CI -0.08 to 0.3; 1 RCT, n = 14 infants, very low-quality evidence) and head circumference (MD 0.2 cm/week, 95% CI -0.07 to 0.4; 1 RCT n = 14 infants, very low-quality evidence). There was no clear evidence that fat supplementation increased the risk of feeding intolerance (RR 3.0, 95% CI 0.1 to 64.3; 1 RCT, n = 16 infants, very low-quality evidence). No data were available regarding the effects of fat supplementation on long-term growth, body mass index, body composition, neurodevelopmental, or cardio-metabolic outcomes. AUTHORS' CONCLUSIONS The one included trial suggests no evidence of an effect of fat supplementation of human milk on short-term growth and feeding intolerance in preterm infants. However, the very low-quality evidence, small sample size, few events, and low precision diminishes our confidence that these results reflect the true effect of fat supplementation of human milk in preterm infants, and no long-term outcomes were reported. Further high-quality research should evaluate the effect on short and long-term growth, neurodevelopmental and cardio-metabolic outcomes in the context of the development of multicomponent fortifiers. Optimal dosage, adverse effects, and delivery practices should also be evaluated.
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Early postnatal growth and neurodevelopment in children born moderately preterm or small for gestational age at term: A systematic review.
Taine, M, Charles, MA, Beltrand, J, Rozé, JC, Léger, J, Botton, J, Heude, B
Paediatric and perinatal epidemiology. 2018;(3):268-280
Abstract
BACKGROUND Clinicians' interest in the long-term effects of early postnatal growth (EPG) is growing. There is compelling evidence linking rapid EPG with later cardiovascular risk, but its neurodevelopmental benefits still remain hypothetical in individuals born moderately preterm (MP) or small for gestational at term (SGAT). METHODS The objective was to perform a systematic review of the relationship between EPG before age 3 years and neurodevelopmental outcome for individuals born MP (32-36 weeks' gestational age) or SGAT. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, 3 independent investigators searched for articles published on this topic in the Web of Science, EMBASE and PubMed from database inception to July 1, 2017. A detailed quality scale was used to evaluate articles. RESULTS We selected 19 articles relying on 12 distinct study populations; 7 articles from 3 study populations were considered at moderate or high quality. The lack of standardisation of growth analysis methods prevented performing a meta-analysis. Overall, EPG was positively associated with neurodevelopmental outcome, especially Intelligence Quotient (IQ) when available. In this relationship, the first 6 months of life might be a critical period. Analysis of the few articles investigating the shape of the relationships revealed a non-linear association, with a plateau for IQ with higher weight gain, which suggests a possible ceiling effect. CONCLUSIONS A positive association was generally found between EPG and neurodevelopmental outcome for individuals born MP or SGAT. Strategies for future epidemiological studies are suggested to improve the characterisation of this relationship.