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1.
N Engl J Med ; 381(15): 1434-1443, 2019 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597020

RESUMO

BACKGROUND: Observational data have shown that slow advancement of enteral feeding volumes in preterm infants is associated with a reduced risk of necrotizing enterocolitis but an increased risk of late-onset sepsis. However, data from randomized trials are limited. METHODS: We randomly assigned very preterm or very-low-birth-weight infants to daily milk increments of 30 ml per kilogram of body weight (faster increment) or 18 ml per kilogram (slower increment) until reaching full feeding volumes. The primary outcome was survival without moderate or severe neurodevelopmental disability at 24 months. Secondary outcomes included components of the primary outcome, confirmed or suspected late-onset sepsis, necrotizing enterocolitis, and cerebral palsy. RESULTS: Among 2804 infants who underwent randomization, the primary outcome could be assessed in 1224 (87.4%) assigned to the faster increment and 1246 (88.7%) assigned to the slower increment. Survival without moderate or severe neurodevelopmental disability at 24 months occurred in 802 of 1224 infants (65.5%) assigned to the faster increment and 848 of 1246 (68.1%) assigned to the slower increment (adjusted risk ratio, 0.96; 95% confidence interval [CI], 0.92 to 1.01; P = 0.16). Late-onset sepsis occurred in 414 of 1389 infants (29.8%) in the faster-increment group and 434 of 1397 (31.1%) in the slower-increment group (adjusted risk ratio, 0.96; 95% CI, 0.86 to 1.07). Necrotizing enterocolitis occurred in 70 of 1394 infants (5.0%) in the faster-increment group and 78 of 1399 (5.6%) in the slower-increment group (adjusted risk ratio, 0.88; 95% CI, 0.68 to 1.16). CONCLUSIONS: There was no significant difference in survival without moderate or severe neurodevelopmental disability at 24 months in very preterm or very-low-birth-weight infants with a strategy of advancing milk feeding volumes in daily increments of 30 ml per kilogram as compared with 18 ml per kilogram. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; SIFT Current Controlled Trials number, ISRCTN76463425.).


Assuntos
Deficiências do Desenvolvimento/prevenção & controle , Nutrição Enteral/métodos , Fórmulas Infantis , Doenças do Prematuro/prevenção & controle , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Leite Humano , Pré-Escolar , Nutrição Enteral/efeitos adversos , Enterocolite Necrosante/prevenção & controle , Seguimentos , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Unidades de Terapia Intensiva Neonatal , Tempo de Internação , Sepse/prevenção & controle
2.
BMJ Open ; 7(12): e017727, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-29217722

RESUMO

OBJECTIVES: We aimed to improve the nutritional care of preterm infants by developing a complex (multifaceted) intervention intended to translate current evidence into practice. We used the sociological framework of Normalization Process Theory (NPT), to guide implementation in order to embed the new practices into routine care. DESIGN: A prospective interventional study with a before and after methodology. PARTICIPANTS: Infants <30 weeks gestation or <1500 g at birth. SETTING: Tertiary neonatal intensive care unit. INTERVENTIONS: The intervention was introduced in phases: phase A (control period, January-August 2011); phase B (partial implementation; improved parenteral and enteral nutrition solutions, nutrition team, education, August-December 2011); phase C (full implementation; guidelines, screening tool, 'nurse champions', January-December 2012); phase D (postimplementation; January-June 2013). Bimonthly audits and staff NPT questionnaires were used to measure guideline compliance and 'normalisation', respectively. NPT Scores were used to guide implementation in real time. Data on nutrient intakes and growth were collected continuously. RESULTS: There were 52, 36, 75 and 35 infants in phases A, B, C and D, respectively. Mean guideline compliance exceeded 75% throughout the intervention period, peaking at 85%. Guideline compliance and NPT scores both increased over time, (r=0.92 and 0.15, p<0.03 for both), with a significant linear association between the two (r=0.21, p<0.01). There were significant improvements in daily protein intake and weight gain between birth and discharge in phases B and Ccompared with phase A (p<0.01 for all), which were sustained into phase D. CONCLUSIONS: NPT and audit results suggest that the intervention was rapidly incorporated into practice, with high guideline compliance and accompanying improvements in protein intake and weight gain. NPT appears to offer an effective way of implementing new practices such that they lead to sustained changes in care. Complex interventions based on current evidence can improve both practice and clinical outcomes.


Assuntos
Assistência à Saúde/normas , Nutrição Enteral , Guias como Assunto , Recém-Nascido Prematuro/crescimento & desenvolvimento , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Terapia Intensiva Neonatal/métodos , Nutrição Parenteral , Dieta/normas , Proteínas na Dieta/administração & dosagem , Nutrição Enteral/métodos , Nutrição Enteral/normas , Fidelidade a Diretrizes/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Estado Nutricional , Nutrição Parenteral/métodos , Nutrição Parenteral/normas , Estudos Prospectivos , Melhoria de Qualidade/estatística & dados numéricos , Ganho de Peso
3.
BMC Pediatr ; 17(1): 39, 2017 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-28129748

RESUMO

BACKGROUND: In the UK, 1-2% of infants are born very preterm (<32 weeks of gestation) or have very low birth weight (<1500 g). Very preterm infants are initially unable to be fed nutritional volumes of milk and therefore require intravenous nutrition. Milk feeding strategies influence several long and short term health outcomes including growth, survival, infection (associated with intravenous nutrition) and necrotising enterocolitis (NEC); with both infection and NEC being key predictive factors of long term disability. Currently there is no consistent strategy for feeding preterm infants across the UK. The SIFT trial will test two speeds of increasing milk feeds with the primary aim of determining effects on survival without moderate or severe neurodevelopmental disability at 24 months of age, corrected for prematurity. The trial will also examine many secondary outcomes including infection, NEC, time taken to reach full feeds and growth. METHODS/DESIGN: Two thousand eight hundred very preterm or very low birth weight infants will be recruited from approximately 30 hospitals across the UK to a randomised controlled trial. Infants with severe congenital anomaly or no realistic chance of survival will be excluded. Infants will be randomly allocated to either a faster (30 ml/kg/day) or slower (18 ml/kg/day) rate of increase in milk feeds. Data will be collected during the neonatal hospital stay on weight, infection rates, episodes of NEC, length of stay and time to reach full milk feeds. Long term health outcomes comprising vision, hearing, motor and cognitive impairment will be assessed at 24 months of age (corrected for prematurity) using a parent report questionnaire. DISCUSSION: Extensive searches have found no active or proposed studies investigating the rate of increasing milk feeds. The results of this trial will have importance for optimising incremental milk feeding for very preterm and/or very low birth weight infants. No additional resources will be required to implement an optimal feeding strategy, and therefore if successful, the trial results could rapidly be adopted across the NHS at low cost. TRIAL REGISTRATION: ISRCTN Registry; ISRCTN76463425 on 5 March, 2013.


Assuntos
Deficiências do Desenvolvimento/prevenção & controle , Nutrição Enteral/métodos , Doenças do Prematuro/prevenção & controle , Terapia Intensiva Neonatal/métodos , Leite Humano , Nutrição Parenteral/métodos , Pré-Escolar , Protocolos Clínicos , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Masculino , Estudos Prospectivos , Fatores de Tempo
4.
Acta Paediatr ; 105(6): 587-99, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26813585

RESUMO

UNLABELLED: A systematic review with meta-analysis was carried out to investigate the effects of increased nutritional intake, via either macronutrient or multinutrient intervention, during the neonatal period on neurodevelopmental outcomes in infants born at <32 weeks of gestation or weighing <1501 g at birth. CONCLUSION: Although the relationship remains unclear, increased early nutrition may reduce neurodevelopmental impairment in this group of infants. Future research should focus on using standardised nutritional interventions and an agreed neurodevelopmental assessment battery.


Assuntos
Fenômenos Fisiológicos da Nutrição do Lactente , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Transtornos do Neurodesenvolvimento/epidemiologia , Humanos , Recém-Nascido
5.
Elife ; 42015 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-26182404

RESUMO

Appropriate physiological signaling by primary cilia depends on the specific targeting of particular receptors to the ciliary membrane, but how this occurs remains poorly understood. In this study, we show that D1-type dopaminergic receptors are delivered to cilia from the extra-ciliary plasma membrane by a mechanism requiring the receptor cytoplasmic tail, the intraflagellar transport complex-B (IFT-B), and ciliary kinesin KIF17. This targeting mechanism critically depends on Rab23, a small guanine nucleotide binding protein that has important effects on physiological signaling from cilia but was not known previously to be essential for ciliary delivery of any cargo. Depleting Rab23 prevents dopamine receptors from accessing the ciliary membrane. Conversely, fusion of Rab23 to a non-ciliary receptor is sufficient to drive robust, nucleotide-dependent mis-localization to the ciliary membrane. Dopamine receptors thus reveal a previously unrecognized mechanism of ciliary receptor targeting and functional role of Rab23 in promoting this process.


Assuntos
Proteínas de Transporte/metabolismo , Cílios/fisiologia , Cinesina/metabolismo , Receptores Dopaminérgicos/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Animais , Camundongos , Transporte Proteico
8.
Arch Dis Child Educ Pract Ed ; 100(3): 147-54, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25267876

RESUMO

Adequate nutrition and growth during the neonatal period are important, especially for preterm infants, for whom there is evidence of poor nutrient intakes and growth, and this has important implications for their health in later life. Increased nutritional support while on the neonatal intensive care unit has been shown to improve growth, but such support is not universally available. Being able to carry out and interpret a nutritional assessment is therefore an important skill for paediatricians caring for neonates. This article aims to explain how to use nutritional assessment in neonates and provides some tools to make this process as straightforward as possible.


Assuntos
Fenômenos Fisiológicos da Nutrição do Lactente , Doenças do Recém-Nascido/terapia , Doenças do Prematuro/terapia , Avaliação Nutricional , Apoio Nutricional/métodos , Antropometria/métodos , Desenvolvimento Infantil/fisiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro/crescimento & desenvolvimento
10.
World Rev Nutr Diet ; 110: 152-66, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24751627

RESUMO

There are 13 nutrients classified as vitamins: 4 'fat-soluble' and 9 'water-soluble'. All are essential to maintain healthy homeostasis and metabolic function. Preterm infants are born with low levels and reduced stores of fat-soluble vitamins. Active placental transfer of water-soluble vitamins ensures high levels at birth, but as they are not stored, levels fall rapidly. All VLBW and ELBW infants require vitamins to be provided soon after birth. Quantifying exact requirements of each vitamin which will meet the needs for all infants is difficult due to a limited evidence base. However, timely prescription of vitamin supplements and awareness of situations where delivery or uptake might be compromised will help to ensure that these vulnerable patients do not suffer from vitamin deficiencies. Multivitamin preparations are available for parenteral and enteral use. Vitamins A, C and E have important functions as antioxidants. Further research is required to understand optimal doses and routes of administration for initial and ongoing nutritional support.


Assuntos
Suplementos Nutricionais , Fenômenos Fisiológicos da Nutrição do Lactente , Vitaminas/administração & dosagem , Antioxidantes/administração & dosagem , Nutrição Enteral , Humanos , Lactente , Recém-Nascido Prematuro/crescimento & desenvolvimento , Recém-Nascido de muito Baixo Peso/crescimento & desenvolvimento , Micronutrientes/administração & dosagem , Leite Humano/química , Necessidades Nutricionais , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Arch Dis Child Fetal Neonatal Ed ; 99(1): F6-F11, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23973795

RESUMO

OBJECTIVE: To describe feeding and gastrointestinal outcomes in growth-restricted infants <29 weeks' gestation and to determine the rate of feed advancement which they tolerate. DESIGN: Analysis of prospectively collected data from a randomised feeding trial, the Abnormal Doppler Enteral Prescription Trial (ADEPT). SETTING: 54 neonatal units in the UK and Ireland. PARTICIPANTS: 404 preterm, growth-restricted infants with abnormal antenatal Doppler studies from ADEPT. 83 infants <29 weeks and 312 infants ≥ 29 weeks' gestation were included in this analysis. INTERVENTIONS: In ADEPT, infants were randomised to start milk 'early' on day 2 after birth, or 'late' on day 6. Subsequent feed advancement followed a regimen, which should have achieved full feeds by day 16 in the early and day 20 in the late group. MAIN OUTCOME MEASURES: Full feeds were achieved later in infants <29 weeks; median age 28 days {IQR 22-40} compared with 19 days {IQR 17-23} in infants ≥ 29 weeks (HR 0.35, 95% CI 0.3 to 0.5). The incidence of necrotising enterocolitis was also higher in this group; 32/83 (39%) compared to 32/312 (10%) in those ≥ 29 weeks (RR 3.7, 95% CI 2.4 to 5.7). Infants <29 weeks tolerated very little milk for the first 10 days of life and reached full feeds 9 days later than predicted from the trial regimen. CONCLUSIONS: Growth-restricted infants born <29 weeks' gestation with abnormal antenatal Doppler failed to tolerate even the careful feeding regimen of ADEPT. A slower advancement of feeds may be required for these infants. TRIAL REGISTRATION NUMBER: ISRCTN87351483.


Assuntos
Aleitamento Materno , Nutrição Enteral/efeitos adversos , Enterocolite Necrosante/etiologia , Retardo do Crescimento Fetal/terapia , Fórmulas Infantis/administração & dosagem , Doenças do Prematuro/terapia , Recém-Nascido Prematuro , Animais , Nutrição Enteral/métodos , Feminino , Retardo do Crescimento Fetal/diagnóstico por imagem , Idade Gestacional , Humanos , Recém-Nascido , Doenças do Prematuro/diagnóstico por imagem , Recém-Nascido de muito Baixo Peso , Irlanda , Masculino , Gravidez , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Pré-Natal , Reino Unido
12.
Am J Clin Nutr ; 97(4): 816-26, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23446896

RESUMO

BACKGROUND: The achievement of adequate nutritional intakes in preterm infants is challenging and may explain the poor growth often seen in this group. The use of early parenteral nutrition (PN) is one potential strategy to address this problem, although the benefits and harms are unknown. OBJECTIVE: We determined whether earlier administration of PN benefits growth outcomes in preterm infants. DESIGN: We conducted a systematic review of randomized controlled trials (RCTs) and observational studies. RESULTS: Eight RCTs and 13 observational studies met the inclusion criteria (n = 553 and 1796 infants). The meta-analysis was limited by disparate growth-outcome measures. An assessment of bias was difficult because of inadequate reporting. Results are given as mean differences (95% CIs). Early PN reduced the time to regain birth weight by 2.2 d (1.1, 3.2 d) for RCTs and 3.2 d (2.0, 4.4 d) in observational studies. The maximum percentage weight loss with early PN was lower by 3.1 percentage points (1.7, 4.5 percentage points) for RCTs and by 3.5 percentage points (2.6, 4.3 percentage points) for observational studies. Early PN improved weight at discharge or 36 wk postmenstrual age by 14.9 g (5.3, 24.5 g) (observational studies only), but no benefit was shown for length or head circumference. There was no evidence that early PN significantly affects risk of mortality, necrotizing enterocolitis, sepsis, chronic lung disease, intraventricular hemorrhage, or cholestasis. CONCLUSIONS: The results of this review, although subject to some limitations, show that early PN provides a benefit for some short-term growth outcomes. No evidence that early PN increases morbidity or mortality was found. Neonatal research would benefit from the development of a set of core growth outcome measures.


Assuntos
Peso ao Nascer , Crescimento , Recém-Nascido de Baixo Peso , Recém-Nascido Prematuro , Nutrição Parenteral , Nascimento Prematuro , Humanos , Recém-Nascido , Alta do Paciente , Perda de Peso
13.
Arch Dis Child Fetal Neonatal Ed ; 98(2): F166-9, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21930688

RESUMO

High osmolality of infant feed reflects a high concentration of solute particles and has been implicated as a cause of necrotising enterocolitis. Evidence for direct intestinal mucosal injury as a result of hyperosmolar feeds is scant, and no good evidence has been found to support such an association. High osmolality of enteral substrate may, however, slow down gastric emptying. Osmolality of current infant feeds ranges from around 300 mOsm/kg in human breast milk to just more than 400 mOsm/kg in fully fortified breast milk. Addition of mineral and vitamin supplements to small volumes of milk can increase osmolality significantly and should be avoided if possible.


Assuntos
Enterocolite Necrosante/etiologia , Leite/química , Animais , Trato Gastrointestinal/crescimento & desenvolvimento , Humanos , Lactente , Fórmulas Infantis/química , Recém-Nascido , Leite/efeitos adversos , Leite Humano/química , Concentração Osmolar
14.
Pediatrics ; 130(3): e640-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22891222

RESUMO

BACKGROUND AND OBJECTIVE: Infants born preterm are significantly lighter and shorter on reaching term equivalent age (TEA) than are those born at term, but the relation with body composition is less clear. We conducted a systematic review to assess the body composition at TEA of infants born preterm. METHODS: The databases MEDLINE, Embase, CINAHL, HMIC, "Web of Science," and "CSA Conference Papers Index" were searched between 1947 and June 2011, with selective citation and reference searching. Included studies had to have directly compared measures of body composition at TEA in preterm infants and infants born full-term. Data on body composition, anthropometry, and birth details were extracted from each article. RESULTS: Eight studies (733 infants) fulfilled the inclusion criteria. Mean gestational age and weight at birth were 30.0 weeks and 1.18 kg in the preterm group and 39.6 weeks and 3.41 kg in the term group, respectively. Meta-analysis showed that the preterm infants had a greater percentage total body fat at TEA than those born full-term (mean difference, 3%; P = .03), less fat mass (mean difference, 50 g; P = .03), and much less fat-free mass (mean difference, 460 g; P < .0001). CONCLUSIONS: The body composition at TEA of infants born preterm is different than that of infants born at term. Preterm infants have less lean tissue but more similar fat mass. There is a need to determine whether improved nutritional management can enhance lean tissue acquisition, which indicates a need for measures of body composition in addition to routine anthropometry.


Assuntos
Composição Corporal , Recém-Nascido Prematuro , Nascimento a Termo , Peso ao Nascer , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Gravidez
15.
Pediatrics ; 129(5): e1260-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22492770

RESUMO

BACKGROUND: Growth-restricted preterm infants are at increased risk of developing necrotizing enterocolitis (NEC) and initiation of enteral feeding is frequently delayed. There is no evidence that this delay is beneficial and it might further compromise nutrition and growth. METHODS: Infants with gestation below 35 weeks, birth weight below the 10th centile, and abnormal antenatal umbilical artery Doppler waveforms were randomly allocated to commence enteral feeds "early," on day 2 after birth, or "late," on day 6. Gradual increase in feeds was guided by a "feeding prescription" with rate of increase the same for both groups. Primary outcomes were time to achieve full enteral feeding sustained for 72 hours and NEC. RESULTS: Four hundred four infants were randomly assigned from 54 hospitals in the United Kingdom and Ireland (202 to each group). Median gestation was 31 weeks. Full, sustained, enteral feeding was achieved at an earlier age in the early group: median age was 18 days compared with 21 days (hazard ratio: 1.36 [95% confidence interval: 1.11-1.67]). There was no evidence of a difference in the incidence of NEC: 18% in the early group and 15% in the late group (relative risk: 1.2 [95% confidence interval: 0.77-1.87]). Early feeding resulted in shorter duration of parenteral nutrition and high-dependency care, lower incidence of cholestatic jaundice, and improved SD score for weight at discharge. CONCLUSIONS: Early introduction of enteral feeds in growth-restricted preterm infants results in earlier achievement of full enteral feeding and does not appear to increase the risk of NEC.


Assuntos
Nutrição Enteral/métodos , Retardo do Crescimento Fetal/terapia , Doenças do Prematuro/terapia , Fatores Etários , Estudos Transversais , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/prevenção & controle , Feminino , Retardo do Crescimento Fetal/epidemiologia , Humanos , Incidência , Recém-Nascido , Doenças do Prematuro/epidemiologia , Gravidez , Reino Unido
16.
BMC Pediatr ; 9: 63, 2009 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-19799788

RESUMO

BACKGROUND: Pregnancies complicated by abnormal umbilical artery Doppler blood flow patterns often result in the baby being born both preterm and growth-restricted. These babies are at high risk of milk intolerance and necrotising enterocolitis, as well as post-natal growth failure, and there is no clinical consensus about how best to feed them. Policies of both early milk feeding and late milk feeding are widely used. This randomised controlled trial aims to determine whether a policy of early initiation of milk feeds is beneficial compared with late initiation. Optimising neonatal feeding for this group of babies may have long-term health implications and if either of these policies is shown to be beneficial it can be immediately adopted into clinical practice. METHODS AND DESIGN: Babies with gestational age below 35 weeks, and with birth weight below 10th centile for gestational age, will be randomly allocated to an "early" or "late" enteral feeding regimen, commencing milk feeds on day 2 and day 6 after birth, respectively. Feeds will be gradually increased over 9-13 days (depending on gestational age) using a schedule derived from those used in hospitals in the Eastern and South Western Regions of England, based on surveys of feeding practice. Primary outcome measures are time to establish full enteral feeding and necrotising enterocolitis; secondary outcomes include sepsis and growth. The target sample size is 400 babies. This sample size is large enough to detect a clinically meaningful difference of 3 days in time to establish full enteral feeds between the two feeding policies, with 90% power and a 5% 2-sided significance level. Initial recruitment period was 24 months, subsequently extended to 38 months. DISCUSSION: There is limited evidence from randomised controlled trials on which to base decisions regarding feeding policy in high risk preterm infants. This multicentre trial will help to guide clinical practice and may also provide pointers for future research. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: 87351483.


Assuntos
Aleitamento Materno , Nutrição Enteral/métodos , Fórmulas Infantis/administração & dosagem , Ultrassonografia Doppler/métodos , Ultrassonografia Pré-Natal/métodos , Artérias Umbilicais/diagnóstico por imagem , Feminino , Seguimentos , Idade Gestacional , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Fatores de Risco , Fatores de Tempo
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