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1.
Early erythropoiesis-stimulating agents in preterm or low birth weight infants.
Ohlsson, A, Aher, SM
The Cochrane database of systematic reviews. 2020;(2):CD004863
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Abstract
BACKGROUND Preterm infants have low plasma levels of erythropoietin (EPO), providing a rationale for the use of erythropoiesis-stimulating agents (ESAs) to prevent or treat anaemia and to provide neuro protection and protection against necrotising enterocolitis (NEC). Darbepoetin (Darbe) and EPO are currently available ESAs. OBJECTIVES To assess the effectiveness and safety of ESAs (erythropoietin (EPO) and/or Darbe) initiated early (before eight days after birth) compared with placebo or no intervention in reducing red blood cell (RBC) transfusions, adverse neurological outcomes, and feeding intolerance including necrotising enterocolitis (NEC) in preterm and/or low birth weight infants. Primary objective for studies that primarily investigate the effectiveness and safety of ESAs administered early in reducing red blood cell transfusions: To assess the effectiveness and safety of ESAs initiated early in reducing red blood cell transfusions in preterm infants. Secondary objectives: Review authors performed subgroup analyses of low (≤ 500 IU/kg/week) and high (> 500 IU/kg/week) doses of EPO and the amount of iron supplementation provided: none, low (≤ 5 mg/kg/d), and high (> 5 mg/kg/d). Primary objective for studies that primarily investigate the neuro protective effectiveness of ESAs: To assess the effectiveness and safety of ESAs initiated early in reducing adverse neurological outcomes in preterm infants. Primary objective for studies that primarily investigate the effectiveness of EPO or Darbe administered early in reducing feeding intolerance: To assess the effectiveness and safety of ESAs administered early in reducing feeding intolerance (and NEC) in preterm infants. Other secondary objectives: To compare the effectiveness of ESAs in reducing the incidence of adverse events and improving long-term neurodevelopmental outcomes. SEARCH METHODS We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2), MEDLINE via PubMed (1966 to 10 March 2017), Embase (1980 to 10 March 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 10 March 2017). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised and quasi-randomised controlled trials. SELECTION CRITERIA Randomised and quasi-randomised controlled trials of early initiation of EAS treatment versus placebo or no intervention in preterm or low birth weight infants. DATA COLLECTION AND ANALYSIS We used the methods described in the Cochrane Handbook for Systematic Reviews of Interventions and the GRADE approach to assess the quality of evidence. MAIN RESULTS This updated review includes 34 studies enrolling 3643 infants. All analyses compared ESAs versus a control consisting of placebo or no treatment. Early ESAs reduced the risk of 'use of one or more [red blood cell] RBC transfusions' (typical risk ratio (RR) 0.79, 95% confidence interval (CI) 0.74 to 0.85; typical risk difference (RD) -0.14, 95% CI -0.18 to -0.10; I2 = 69% for RR and 62% for RD (moderate heterogeneity); number needed to treat for an additional beneficial outcome (NNTB) 7, 95% CI 6 to 10; 19 studies, 1750 infants). The quality of the evidence was low. Necrotising enterocolitis was significantly reduced in the ESA group compared with the placebo group (typical RR 0.69, 95% CI 0.52 to 0.91; typical RD -0.03, 95% CI -0.05 to -0.01; I2 = 0% for RR and 22% for RD (low heterogeneity); NNTB 33, 95% CI 20 to 100; 15 studies, 2639 infants). The quality of the evidence was moderate. Data show a reduction in 'Any neurodevelopmental impairment at 18 to 22 months' corrected age in the ESA group (typical RR 0.62, 95% CI 0.48 to 0.80; typical RD -0.08, 95% CI -0.12 to -0.04; NNTB 13, 95% CI 8 to 25. I2 = 76% for RR (high heterogeneity) and 66% for RD (moderate); 4 studies, 1130 infants). The quality of the evidence was low. Results reveal increased scores on the Bayley-II Mental Development Index (MDI) at 18 to 24 months in the ESA group (weighted mean difference (WMD) 8.22, 95% CI 6.52 to 9.92; I2 = 97% (high heterogeneity); 3 studies, 981 children). The quality of the evidence was low. The total volume of RBCs transfused per infant was reduced by 7 mL/kg. The number of RBC transfusions per infant was minimally reduced, but the number of donors to whom infants who were transfused were exposed was not significantly reduced. Data show no significant difference in risk of stage ≥ 3 retinopathy of prematurity (ROP) with early EPO (typical RR 1.24, 95% CI 0.81 to 1.90; typical RD 0.01, 95% CI -0.02 to 0.04; I2 = 0% (no heterogeneity) for RR; I2 = 34% (low heterogeneity) for RD; 8 studies, 1283 infants). Mortality was not affected, but results show significant reductions in the incidence of intraventricular haemorrhage (IVH) and periventricular leukomalacia (PVL). AUTHORS' CONCLUSIONS Early administration of ESAs reduces the use of red blood cell (RBC) transfusions, the volume of RBCs transfused, and donor exposure after study entry. Small reductions are likely to be of limited clinical importance. Donor exposure probably is not avoided, given that all but one study included infants who had received RBC transfusions before trial entry. This update found no significant difference in the rate of ROP (stage ≥ 3) for studies that initiated EPO treatment at less than eight days of age, which has been a topic of concern in earlier versions of this review. Early EPO treatment significantly decreased rates of IVH, PVL, and NEC. Neurodevelopmental outcomes at 18 to 22 months and later varied in published studies. Ongoing research should evaluate current clinical practices that will limit donor exposure. Promising but conflicting results related to the neuro protective effect of early EPO require further study. Very different results from the two largest published trials and high heterogeneity in the analyses indicate that we should wait for the results of two ongoing large trials before drawing firm conclusions. Administration of EPO is not currently recommended because limited benefits have been identified to date. Use of darbepoetin requires further study.
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2.
The Course Of IGF-1 Levels and Nutrient Intake in Extremely and Very Preterm Infants During Hospitalisation.
Yumani, DFJ, Calor, AK, van Weissenbruch, MM
Nutrients. 2020;(3)
Abstract
BACKGROUND Insulin-like growth factor 1 (IGF-1) plays an important role in the complex association between nutrition, growth, and maturation in extremely and very preterm infants. Nevertheless, in this population, research on associations between IGF-1 and nutrition is limited. Therefore this study aimed to evaluate the possible associations between the course of IGF-1 levels and nutrient intake between preterm birth and 36 weeks postmenstrual age (PMA). METHODS 87 infants born between 24 and 32 weeks gestational age were followed up to 36 weeks PMA. Actual daily macronutrient intake was calculated, and growth was assessed weekly. IGF-1 was sampled from umbilical cord blood at birth and every other week thereafter. RESULTS There was an inverse relationship between the amount of parenteral nutrition in the second week of life and IGF-1. Total protein, fat, and carbohydrate intake, as well as total energy intake, primarily showed a positive association with IGF-1 levels, particularly between 30 and 33 weeks PMA. Gestational age, bronchopulmonary dysplasia (BPD), and weight were significant confounders in the association between nutrient intake and IGF-1 levels. CONCLUSION Parenteral nutrition was found to be a negative predictor of IGF-1 levels, and there could potentially be a time frame in which macronutrient intake is unable to impact IGF-1 levels. Future research should aim to narrow down this time frame and to gain more insight into factors enhancing or decreasing the response of IGF-1 to nutrition, e.g., age and inflammatory state, to align nutritional interventions accordingly.
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3.
Protein supplementation of human milk for promoting growth in preterm infants.
Amissah, EA, Brown, J, Harding, JE
The Cochrane database of systematic reviews. 2020;(9):CD000433
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Abstract
BACKGROUND Preterm infants require high protein intake to achieve adequate growth and development. Although breast milk feeding has many benefits for this population, the protein content is highly variable, and inadequate to support rapid infant growth. This is a 2020 update of a Cochrane Review first published in 1999. OBJECTIVES To determine whether protein-supplemented human milk 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 Cochrane Central Register of Controlled Trials (CENTRAL 2019, Issue 8) in the Cochrane Library and MEDLINE via PubMed on 23 August 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA Published and unpublished RCTs were eligible if they used random or quasi-random methods to allocate hospitalised preterm infants who were being fed human milk, to additional protein supplementation or no supplementation. DATA COLLECTION AND ANALYSIS Two review authors independently abstracted data, assessed risk of bias and the quality of evidence at the outcome level, using GRADE methodology. We performed meta-analyses, using risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with their respective 95% confidence intervals (CIs). We used a fixed-effect model and had planned to explore potential causes of heterogeneity via subgroup or sensitivity analyses. MAIN RESULTS We included six RCTs, involving 204 preterm infants. The risk of bias for most methodological domains was unclear as there was insufficient detail reported. Low-quality evidence showed that protein supplementation of human milk may increase in-hospital rates of growth in weight (MD 3.82 g/kg/day, 95% CI 2.94 to 4.7; five RCTs, 101 infants; I² = 73%), length (MD 0.12 cm/wk, 95% CI 0.07 to 0.17; four RCTs, 68 infants; I² = 89%), and head circumference (MD 0.06 cm/wk, 95% CI 0.01 to 0.12; four RCTs, 68 infants; I² = 84%). Protein supplementation may lead to longer hospital stays (MD 18.5 days, 95% CI 4.39 to 32.61; one RCT, 20 infants; very low-quality evidence). Very low quality evidence means that the effect of protein supplementation on the risk of feeding intolerance (RR 2.70, 95% CI 0.13 to 58.24; one RCT, 17 infants), or necrotizing enterocolitis (RR 1.11, 95% CI 0.07 to 17.12; one RCT, 76 infants) remains uncertain. No data were available about the effects of protein supplementation on neurodevelopmental outcomes. AUTHORS' CONCLUSIONS Low-quality evidence showed that protein supplementation of human milk, fed to preterm infants, increased short-term growth. However, the small sample sizes, low precision, and very low-quality evidence regarding duration of hospital stay, feeding intolerance, and necrotising enterocolitis precluded any conclusions about these outcomes. There were no data on outcomes after hospital discharge. Our findings may not be generalisable to low-resource settings, as none of the included studies were conducted in these settings. Since protein supplementation of human milk is now usually done as a component of multi-nutrient fortifiers, future studies should compare different amounts of protein in multi-component fortifiers, and be designed to determine the effects on duration of hospital stay and safety, as well as on long-term growth, body composition, cardio-metabolic, and neurodevelopmental outcomes.
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Human milk fortification: the clinician and parent perspectives.
Hair, AB, Ferguson, J, Grogan, C, Kim, JH, Taylor, SN
Pediatric research. 2020;(Suppl 1):25-29
Abstract
This study reports on the human milk fortification session at the 2019 NEC Society Symposium, which included clinicians and parents discussing the evidence comparing fortification options such as efficacy, safety, cost effectiveness, and the need for parents to be informed about fortifier choice. With the current literature available and the varying standard of care practices for human milk fortification, further studies are needed to determine the most complete diet for preterm infants. The optimal diet would not only provide key nutrients and energy for growth and development, but also improve short- and long-term outcomes. Parents, as advocates and providers for their infant, should be informed, educated, and included in the discussion and decisions regarding fortification of human milk for their infant.
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The association of macronutrients in human milk with the growth of preterm infants.
Lin, YH, Hsu, YC, Lin, MC, Chen, CH, Wang, TM
PloS one. 2020;(3):e0230800
Abstract
BACKGROUND Breast milk is the optimal choice for feeding premature babies. However, the prevalence rate of extrauterine growth restriction in preterm infants remains high. OBJECTIVES The purpose of this study was to analyze the macronutrients present in human milk and the correlation with the growth of in-hospital preterm infants. METHODS This prospective study is based on data from 99 in-hospital preterm infants younger than 37 weeks of gestational age on an exclusively human milk diet. Infants who had previously received parenteral nutrition were eligible, but they had to have reached full enteral feeding at the time that the samples were taken. A total of 3282 samples of raw human milk or donor pasteurized milk were collected. The levels of lactose, protein, fat, and energy in the samples were measured using a Miris human milk analyzer. The primary outcome was weight growth velocity (g/kg/day) which was obtained using two-point approach. RESULTS The mean (±standard deviation) macronutrient composition per 100 mL of milk was 7.2 (±0.3) g of lactose, 1.1 (±0.2) g of true protein, 3.5 (±0.9) g of fat, and 66.9 (±6.5) kcal of energy. The protein concentration in human milk had a positive, significant correlation with body weight gain, with a coefficient of 0.41 (p < 0.001). After adjusting for gestational age, postmenstrual age, small-for-gestational age, intraventricular hemorrhage, patent ductus arteriosus or congestive heart failure, duration of total parenteral nutrition support, bottle feeding or use of orogastric tube, and ventilator support, total daily protein intake was associated with body weight growth (p < 0.001). CONCLUSION Both the protein concentration in human milk and the daily total protein intake had a positive correlation with the body weight gain of premature infants. Routine analysis of breast milk and individualized fortification might be indicated to optimize the growth of preterm infants.
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6.
Preterm neonatal immunology at the intestinal interface.
Van Belkum, M, Mendoza Alvarez, L, Neu, J
Cellular and molecular life sciences : CMLS. 2020;(7):1209-1227
Abstract
Fetal and neonatal development represents a critical window for setting a path toward health throughout life. In this review, we focus on intestinal immunity, how it develops, and its implications for subsequent neonatal diseases. We discuss maternal nutritional and environmental exposures that dictate outcomes for the developing fetus. Although still controversial, there is evidence in support of an in utero microbiome. Specific well-intentioned and routine applications of antibiotics, steroids, and surgical interventions implemented before, during, and after birth skew the neonate towards pro-inflammatory dysbiosis. Shortly after birth, a consortium of maternal and environmentally derived bacteria, through cross-talk with the developing host immune system, takes center stage in developing or disrupting immune homeostasis at the intestinal interface. We also examine subsequent immunological cross-talks, which involve neonatal myeloid and lymphoid responses, and their potential impacts on health and disease such as necrotizing enterocolitis and sepsis, especially critical disease entities for the infant born preterm.
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Formula vs. Donor Breast Milk for Preterm or Low-Birth-Weight Infants.
Ireson, D
The American journal of nursing. 2020;(9):67
Abstract
Editor's note: The mission of Cochrane Nursing is to provide an international evidence base for nurses involved in delivering, leading, or researching nursing care. Cochrane Corner provides summaries of recent systematic reviews from the Cochrane Library. For more information, see https://nursing.cochrane.org.
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Early Premature Infant Oral Motor Intervention Improved Oral Feeding and Prognosis by Promoting Neurodevelopment.
Li, XL, Liu, Y, Liu, M, Yang, CY, Yang, QZ
American journal of perinatology. 2020;(6):626-632
Abstract
OBJECTIVE This study aimed to explore the clinical significance of early premature infant oral motor intervention (PIOMI) in the prognosis of premature infants. STUDY DESIGN Infants were randomly divided into an intervention group (n = 78) and a control group (n = 73). PIOMI was given to the intervention group 15 to 30 minutes before feeding once a day for 14 days. The whole procedure lasted 15 minutes, including oral stimulation and nonnutritive sucking. Oral feeding ability and neuromotor development were evaluated using the Preterm Infant Oral Feeding Readiness Assessment (PIOFRA) scale and Infant Neurological International Battery (Infanib) scale. RESULTS The PIOFRA score was higher in the intervention group and increased with time, showing a group-time interaction effect. The intervention group exhibited a higher feeding efficiency, a shorter transition time from assisted oral feeding to independent oral feeding, and lower body weight at achievement of independent oral feeding. The percentages of infants with a normal score on the Infanib scale were higher in the intervention group at 3 and 6 months of age, and an abnormal ratio was lower in the intervention group at 6 months (p < 0.01). CONCLUSION PIOMI promoted neuromotor coordination by improving neurodevelopment, thereby improving the oral feeding ability and prognosis of preterm infants.
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9.
Sound reduction management in the neonatal intensive care unit for preterm or very low birth weight infants.
Almadhoob, A, Ohlsson, A
The Cochrane database of systematic reviews. 2020;(1):CD010333
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Abstract
BACKGROUND Infants in the neonatal intensive care unit (NICU) are subjected to stress, including sound of high intensity. The sound environment in the NICU is louder than most home or office environments and contains disturbing noises of short duration and at irregular intervals. There are competing auditory signals that frequently challenge preterm infants, staff and parents. The sound levels in NICUs often exceed the maximum acceptable level of 45 decibels (dB), recommended by the American Academy of Pediatrics. Hearing impairment is diagnosed in 2% to 10% of preterm infants versus 0.1% of the general paediatric population. Noise may cause apnoea, hypoxaemia, alternation in oxygen saturation, and increased oxygen consumption secondary to elevated heart and respiratory rates and may, therefore, decrease the amount of calories available for growth. Elevated levels of speech are needed to overcome the noisy environment in the NICU, thereby increasing the negative impacts on staff, newborns, and their families. High noise levels are associated with an increased rate of errors and accidents, leading to decreased performance among staff. The aim of interventions included in this review is to reduce sound levels to 45 dB or less. This can be achieved by lowering the sound levels in an entire unit, treating the infant in a section of a NICU, in a 'private' room, or in incubators in which the sound levels are controlled, or reducing the sound levels that reaches the individual infant by using earmuffs or earplugs. By lowering the sound levels that reach the neonate, the resulting stress on the cardiovascular, respiratory, neurological, and endocrine systems can be diminished, thereby promoting growth and reducing adverse neonatal outcomes. OBJECTIVES Primary objective To determine the effects of sound reduction on growth and long-term neurodevelopmental outcomes of neonates. Secondary objectives 1. To evaluate the effects of sound reduction on short-term medical outcomes (bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular leukomalacia, retinopathy of prematurity). 2. To evaluate the effects of sound reduction on sleep patterns at three months of age. 3. To evaluate the effects of sound reduction on staff performance. 4. To evaluate the effects of sound reduction in the neonatal intensive care unit (NICU) on parents' satisfaction with the care. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, abstracts from scientific meetings, clinical trials registries (clinicaltrials.gov; controlled-trials.com; and who.int/ictrp), Pediatric Academic Societies Annual meetings 2000 to 2014 (Abstracts2ViewTM), reference lists of identified trials, and reviews to November 2014. SELECTION CRITERIA Preterm infants (< 32 weeks' postmenstrual age (PMA) or < 1500 g birth weight) cared for in the resuscitation area, during transport, or once admitted to a NICU or a stepdown unit. DATA COLLECTION AND ANALYSIS We performed data collection and analyses according to the Cochrane Neonatal Review Group. MAIN RESULTS One small, high quality study assessing the effects of silicone earplugs versus no earplugs qualified for inclusion. The original inclusion criteria in our protocol stipulated an age of < 48 hours at the time of initiating sound reduction. We made a deviation from our protocol and included this study in which some infants would have been > 48 hours old. There was no significant difference in weight at 34 weeks postmenstrual age (PMA): mean difference (MD) 111 g (95% confidence interval (CI) -151 to 374 g) (n = 23). There was no significant difference in weight at 18 to 22 months corrected age between the groups: MD 0.31 kg, 95% CI -1.53 to 2.16 kg (n = 14). There was a significant difference in Mental Developmental Index (Bayley II) favouring the silicone earplugs group at 18 to 22 months corrected age: MD 14.00, 95% CI 3.13 to 24.87 (n = 12), but not for Psychomotor Development Index (Bayley II) at 18 to 22 months corrected age: MD -2.16, 95% CI -18.44 to 14.12 (n =12). AUTHORS' CONCLUSIONS To date, only 34 infants have been enrolled in a randomised controlled trial (RCT) testing the effectiveness of reducing sound levels that reach the infants' ears in the NICU. Based on the small sample size of this single trial, we cannot make any recommendations for clinical practice. Larger, well designed, conducted and reported trials are needed.
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10.
Updates on Assessment and Monitoring of the Postnatal Growth of Preterm Infants.
Cordova, EG, Belfort, MB
NeoReviews. 2020;(2):e98-e108
Abstract
Assessing and monitoring the physical growth of preterm infants is fundamental to NICU care. The goals of nutritional care are to approximate the growth and body composition of the healthy fetus and to support optimal brain development while minimizing future cardiometabolic risk. Both poor and excessive growth predict adverse long-term health outcomes. Growth curves are clinical tools used to assess the preterm infant's growth status. Several growth curves for preterm infants were developed in the past decade. To use them effectively, clinicians need to understand how each growth curve was developed; the underlying reference population; intended use; and strengths and limitations. Intrauterine growth curves are references that use size at birth to represent healthy fetal growth. These curves serve 2 purposes-to assign size classifications at birth and to monitor postnatal growth. The INTERGROWTH-21 st preterm postnatal growth standards were developed to compare the postnatal growth of preterm infants to that of healthy preterm infants rather than the fetus. Individualized weight growth curves account for the water weight loss that frequently occurs after birth. In addition, body mass index (BMI) curves are now available. In this review, we discuss the main characteristics of growth curves used for preterm infants as well as the use of percentiles, z scores, and their change over time to evaluate size and growth status. We also review the differences in body composition between preterm infants at term-equivalent age and term-born infants and the potential role of monitoring proportionality of growth using BMI curves.