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1.
Pediatr Res ; 93(7): 1927-1935, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36183005

RESUMEN

BACKGROUND: Late and moderate preterm (LMPT) infants are at risk for adverse later life outcomes. We determined the association between feeding method at enrolment and growth and body composition of LMPT infants until 3 months corrected age (3mCA). METHODS: Infants born between 32+0 and 36+6 weeks of gestation (n = 107) were enrolled up to 4 weeks corrected age and stratified according to feeding at enrolment. We performed anthropometric measurements at enrolment, term equivalent age (TEA) and 3mCA, including skinfold measurements and body composition using dual X-ray absorptiometry (DEXA). RESULTS: Feeding method at enrolment was associated with fat mass (FM) (breast 554.9 g, mixed 716.8 g, formula 637.7 g, p = 0.048), lean body mass (LM) (2512 g, 2853 g, 2722 g, respectively, p = 0.009) and lean mass index (LMI) (10.6 kg/m2, 11.6 kg/m2,11.2 kg/m2 respectively, p = 0.008) at TEA, but not 3mCA. Breastfed infants demonstrated greater increase in LM (breast 1707 g, mixed 1536 g, formula 1384 g, p = 0.03) and LMI (1.23 kg/m2, 0.10 kg/m2, 0.52 kg/m2, respectively, p = 0.022) between TEA and 3mCA. CONCLUSIONS: Breastfed LMPT infants have lower FM and greater LM increase and LMI increase up to 3mCA compared to formula or mixed-fed infants. These findings stress the importance of supporting breastfeeding in this population. IMPACT: Infants born late and moderate preterm age who are exclusively breastfed soon after birth gain more lean mass up to 3 months corrected age compared to mixed- or formula-fed infants. Breastfed infants have lower lean and fat mass at term equivalent age compared to mixed- and formula-fed infants. This is the first study exploring this population's growth and body composition in detail at 3 months corrected age. Our results underline the importance of supporting mothers to initiate and continue breastfeeding at least until 3 months corrected age.


Asunto(s)
Lactancia Materna , Leche Humana , Recién Nacido , Femenino , Lactante , Humanos , Composición Corporal , Fórmulas Infantiles
2.
N Engl J Med ; 381(15): 1434-1443, 2019 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-31597020

RESUMEN

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.).


Asunto(s)
Discapacidades del Desarrollo/prevención & control , Nutrición Enteral/métodos , Fórmulas Infantiles , Enfermedades del Prematuro/prevención & control , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Leche Humana , Preescolar , Nutrición Enteral/efectos adversos , Enterocolitis Necrotizante/prevención & control , Estudios de Seguimiento , Humanos , Recién Nacido , Recien Nacido Prematuro/crecimiento & desarrollo , Recién Nacido de muy Bajo Peso/crecimiento & desarrollo , Unidades de Cuidado Intensivo Neonatal , Tiempo de Internación , Sepsis/prevención & control
3.
Exp Physiol ; 107(5): 415-421, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35041771

RESUMEN

NEW FINDINGS: What is the topic of this review? The importance of the early life gut microbiome, with a focus on preterm infants and microbially related diseases. Current techniques to study the preterm gut microbiome are appraised, and the potential of recent methodological advancements is discussed. What advances does it highlight? Recent findings in the field achieved by the application of advanced technologies, the applicability of intestinally derived organoid models to study host-microbiome interactions in the preterm gut, and recent developments in enhancing the physiological relevance of such models. Preterm intestinally derived organoids may provide novel insights into the mechanisms underlying preterm disease, as well as diagnosis and treatment opportunities. These models have huge translational potential, offering a step towards precision medicine. ABSTRACT: Accumulating evidence affirms the importance of the gut microbiome in both health and disease. In early life, there exists a critical period in which the composition of gut microbes is particularly malleable and subject to a wide range of influencing factors. Disturbances to microbial communities during this time may be beneficial or detrimental to short and long-term health outcomes. For infants born prematurely, naïve immune systems, immature gastrointestinal tracts and additional clinical needs put this population at high risk of abnormal microbial colonisation, resulting in increased susceptibility to diseases including necrotising enterocolitis (NEC) and late-onset sepsis (LOS). Traditional cell culture methods, gnotobiotic animals, molecular sequencing techniques (16S rRNA gene sequencing and metagenomics) and advanced 'omics' technologies (transcriptomics, proteomics and metabolomics) have been fundamental in exploring the associations between diet, gut microbes, microbial functions and disease. Despite significant investment and ongoing research efforts, prevention and treatment strategies in NEC and LOS remain limited. Recent endeavours have focused on searching for new, more physiologically relevant models to simulate the preterm intestine. Preterm intestinally derived organoids represent a promising in vitro approach in the study of host-microbiome interactions in the preterm infant gut, offering new and exciting possibilities in this field.


Asunto(s)
Enterocolitis Necrotizante , Microbioma Gastrointestinal , Heces , Humanos , Recién Nacido , Recien Nacido Prematuro , ARN Ribosómico 16S/genética
4.
Pediatr Res ; 92(4): 979-986, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-34952939

RESUMEN

BACKGROUND: IgA and its secretory form sIgA impact protection from infection and necrotising enterocolitis but little is known about quantities in preterm mums own milk (MOM) or infant stool, onset of endogenous production in the preterm gut, and what affects these. METHODS: We measured by ELISA in MOM and stool from healthy preterm infants total IgA and sIgA longitudinally and additionally in MOM fresh, refrigerated, frozen, and after traversing feeding systems. RESULTS: In 42 MOM (median gestation 26 weeks), we showed total IgA levels and sIgA were highest in colostrum, fell over 3 weeks, and were not impacted by gestation. Median IgA values matched previous term studies (700 mcg/ml). In MOM recipients stool IgA was detected in the first week, at around 30% of MOM quantities. Formula fed infants did not have detectable stool IgA until the third week. Levels of IgA and sIgA were approximately halved by handling processes. CONCLUSIONS: MOM in the 3 weeks after preterm delivery contains the highest concentrations of IgA and sIgA. Endogenous production after preterm birth occurs from the 3 week meaning preterm infants are dependent on MOM for IgA which should be optimised. Routine NICU practices halve the amount available to the infant. IMPACT: (Secretory) Immunoglobulin A (IgA) is present in colostrum of maternal milk from infants as preterm as 23-24 weeks gestational age, falling over the first 3 weeks to steady levels similar to term. Gestation at birth does not impact (secretory) IgA levels in breast milk. IgA is present in very preterm infant stools from maternal milk fed infants from the first week of life, but not in formula milk fed preterm infants until week three, suggesting endogenous production from this point. Refrigeration, freezing, and feeding via plastic tubing approximately halved the amount of IgA available.


Asunto(s)
Leche Humana , Nacimiento Prematuro , Lactante , Femenino , Recién Nacido , Humanos , Leche Humana/química , Recien Nacido Prematuro , Inmunoglobulina A Secretora , Valores de Referencia , Plásticos , Lactancia Materna
5.
J Biomed Inform ; 128: 104031, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35183765

RESUMEN

Preterm birth affects more than 10% of all births worldwide. Such infants are much more prone to Growth Faltering (GF), an issue that has been unsolved despite the implementation of numerous interventions aimed at optimizing preterm infant nutrition. To improve the ability for early prediction of GF risk for preterm infants we collected a comprehensive, large, and unique clinical and microbiome dataset from 3 different sites in the US and the UK. We use and extend machine learning methods for GF prediction from clinical data. We next extend graphical models to integrate time series clinical and microbiome data. A model that integrates clinical and microbiome data improves on the ability to predict GF when compared to models using clinical data only. Information on a small subset of the taxa is enough to help improve model accuracy and to predict interventions that can improve outcome. We show that a hierarchical classifier that only uses a subset of the taxa for a subset of the infants is both the most accurate and cost-effective method for GF prediction. Further analysis of the best classifiers enables the prediction of interventions that can improve outcome.


Asunto(s)
Microbiota , Nacimiento Prematuro , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Aprendizaje Automático
6.
Am J Perinatol ; 39(S 01): S68-S72, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36470294

RESUMEN

OBJECTIVE: Bionutrients (or immunonutrients) are dietary components present in milk, or supplements that could be added to milk diets, that impact health and disease. With few exceptions, most of these are present in human breastmilk and the majority are also present in amniotic fluid. STUDY DESIGN: Bionutrients can be proteins and peptides including enzymes, hormones, immunoglobulins, and growth factors and can also be molecules such as human milk oligosaccharides, amino acids, or lipids such as docosahexaenoic acid. Many of these have ancient origins, are found in other species, and existed before mammalian lactation evolved. Bionutrients may act in diverse ways when administered enterally: they may impact gut bacterial communities or epithelial cell metabolism, or they may pass into the lamina propria where they interact with the gut and systemic immune systems. Clinical trials have often used bovine analogs such as lactoferrin or may use artificially synthesized or recombinant compounds including insulin, bile salt stimulated lipase, or oligosaccharides. RESULTS: Challenges arise because the bioactivity of proteins, such as lactoferrin, may be affected by processing and pasteurization meaning that the impacts of commercial products may differ. The challenge of determining the optimal bioactivity of any single preparation may be even greater in complex compounds such as milk fat globule membrane. It is also possible that bioactivity is affected by the milk matrix, that is, may differ between formula and human milk. CONCLUSION: Finally, it is important to appreciate that nutrients do not function in isolation, and most will not act like drugs, that is, they may take several days or longer to exert an affect. KEY POINTS: · Breastmilk contains high concentrations of bionutrients and provides more than macro- and micronutrients.. · Bionutrients can be proteins (e.g. enzymes, hormones, or immunoglobulins) or molecules (e.g. human milk oligosaccharides or amino acids).. · Bionutrients can be added to milk feeds but high quality trials are needed..


Asunto(s)
Recien Nacido Prematuro , Lactoferrina , Leche Humana , Humanos , Lactante , Recién Nacido , Aminoácidos , Hormonas , Lactoferrina/análisis , Leche Humana/química , Oligosacáridos/análisis
7.
Gut ; 70(12): 2273-2282, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33328245

RESUMEN

OBJECTIVE: Necrotising enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm infants. The underlying mechanisms are poorly understood: mother's own breast milk (MOM) is protective, possibly relating to human milk oligosaccharide (HMO) and infant gut microbiome interplay. We investigated the interaction between HMO profiles and infant gut microbiome development and its association with NEC. DESIGN: We performed HMO profiling of MOM in a large cohort of infants with NEC (n=33) with matched controls (n=37). In a subset of 48 infants (14 with NEC), we also performed longitudinal metagenomic sequencing of infant stool (n=644). RESULTS: Concentration of a single HMO, disialyllacto-N-tetraose (DSLNT), was significantly lower in MOM received by infants with NEC compared with controls. A MOM threshold level of 241 nmol/mL had a sensitivity and specificity of 0.9 for NEC. Metagenomic sequencing before NEC onset showed significantly lower relative abundance of Bifidobacterium longum and higher relative abundance of Enterobacter cloacae in infants with NEC. Longitudinal development of the microbiome was also impacted by low MOM DSLNT associated with reduced transition into preterm gut community types dominated by Bifidobacterium spp and typically observed in older infants. Random forest analysis combining HMO and metagenome data before disease accurately classified 87.5% of infants as healthy or having NEC. CONCLUSION: These results demonstrate the importance of HMOs and gut microbiome in preterm infant health and disease. The findings offer potential targets for biomarker development, disease risk stratification and novel avenues for supplements that may prevent life-threatening disease.


Asunto(s)
Enterocolitis Necrotizante/microbiología , Enterocolitis Necrotizante/prevención & control , Heces/microbiología , Leche Humana/química , Oligosacáridos/metabolismo , Estudios de Casos y Controles , Femenino , Microbioma Gastrointestinal , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino
8.
Biochem Cell Biol ; 99(1): 1-6, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32830532

RESUMEN

Results from previous studies have suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32 weeks gestation) reduces late-onset sepsis (LOS) and necrotising enterocolitis (NEC). The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the UK, aimed to further address this issue with a well powered double-blind placebo controlled trial of >2200 preterm infants. The results from ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. Of the 1093 infants, 316 (29%) in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group, with an adjusted risk ratio of 0.95 (95% CI = 0.86-1.04; p = 0.233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungal prophylaxis in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in the different trials. The UK National Institutes for Health Research funded "Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials" (MAGPIE) study is further exploring the use of lactoferrin, and the results should be available soon.


Asunto(s)
Enterocolitis Necrotizante/prevención & control , Lactoferrina/metabolismo , Sepsis/prevención & control , Administración Oral , Método Doble Ciego , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Lactoferrina/administración & dosificación , Reino Unido
9.
Acta Paediatr ; 110(2): 450-457, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33245565

RESUMEN

AIM: This narrative review summarises the benefits of maternal breastmilk to both the infant and the mother, specifically the benefits that relate to modification of the infant microbiome, and how this might vary in the preterm infant. METHODS: We used PubMed to primarily identify papers, reviews, case series and editorials published in English until May 2020. Based on this, we report on the components of breastmilk, their associated hypothesised benefits and the implications for clinical practice. RESULTS: Breastmilk is recommended as the exclusive diet for newborn infants because it has numerous nutritional and immunological benefits. Additionally, exposure to the maternal breastmilk microbiome may confer a lasting effect on gut health. In the preterm infant, breastmilk is associated with a significant reduction in necrotising enterocolitis, an inflammatory gastrointestinal disease and reduction in other key morbidities, together with improved neurodevelopmental outcomes. CONCLUSION: These impacts have long-term benefits for the child (and the mother) even after weaning. This benefit is likely due, in part, to modification of the infant gut microbiome by breastmilk microbes and bioactive components, and provide potential areas for research and novel therapies in preterm and other high-risk infants.


Asunto(s)
Enterocolitis Necrotizante , Microbioma Gastrointestinal , Niño , Enterocolitis Necrotizante/prevención & control , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Leche Humana , Madres
10.
Molecules ; 26(11)2021 Jun 02.
Artículo en Inglés | MEDLINE | ID: mdl-34199338

RESUMEN

The fecal metabolome in early life has seldom been studied. We investigated its evolution in pre-term babies during their first weeks of life. Multiple (n = 152) stool samples were studied from 51 babies, all <32 weeks gestation. Volatile organic compounds (VOCs) were analyzed by headspace solid phase microextraction gas chromatography mass spectrometry. Data were interpreted using Automated Mass Spectral Deconvolution System (AMDIS) with the National Institute of Standards and Technology (NIST) reference library. Statistical analysis was based on linear mixed modelling, the number of VOCs increased over time; a rise was mainly observed between day 5 and day 10. The shift at day 5 was associated with products of branched-chain fatty acids. Prior to this, the metabolome was dominated by aldehydes and acetic acid. Caesarean delivery showed a modest association with molecules of fungal origin. This study shows how the metabolome changes in early life in pre-term babies. The shift in the metabolome 5 days after delivery coincides with the establishment of enteral feeding and the transition from meconium to feces. Great diversity of metabolites was associated with being fed greater volumes of milk.


Asunto(s)
Heces/química , Metabolómica/métodos , Compuestos Orgánicos Volátiles/análisis , Cesárea/estadística & datos numéricos , Nutrición Enteral , Femenino , Cromatografía de Gases y Espectrometría de Masas , Edad Gestacional , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Modelos Lineales , Embarazo , Microextracción en Fase Sólida
11.
J Pediatr ; 227: 128-134.e2, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32553865

RESUMEN

OBJECTIVE: To determine whether commencement of antibiotics within 3 postnatal days in preterm, very low birth weight (VLBW; ≤1500 g) infants is associated with the development of necrotizing enterocolitis (NEC). STUDY DESIGN: Preplanned statistical analyses were done to study the association between early antibiotic treatment and later NEC development, using the NEOMUNE-NeoNutriNet cohort of VLBW infants from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2831). NEC incidence was compared between infants who received early antibiotics and those who did not, with statistical adjustments for NICU, gestational age, birth weight, sex, delivery mode, antenatal steroid use, Apgar score, and type and initiation of enteral nutrition. RESULTS: The incidence of NEC was 9.0% in the group of infants who did not receive early antibiotics (n = 269), compared with 3.9% in those who did receive early antibiotics (n = 2562). The incidence remained lower in the early antibiotic group after stepwise statistical adjustments for NICU (OR, 0.57; 95% CI, 0.35-0.94, P < .05) and other potential confounders (OR, 0.25; 95% CI, 0.12-0.47; P < .0001). CONCLUSIONS: In this large international cohort of preterm VLBW infants, a small proportion of infants did not receive antibiotics just after birth, and these infants had a higher incidence of NEC. It is important to better understand the role of such variables as time, type, and duration of antibiotic treatment on NEC incidence, immune development, gut colonization, and antibiotic resistance in the NICU.


Asunto(s)
Antibacterianos/administración & dosificación , Enterocolitis Necrotizante/epidemiología , Estudios de Casos y Controles , Estudios de Cohortes , Bases de Datos Factuales , Enterocolitis Necrotizante/prevención & control , Femenino , Humanos , Incidencia , Recién Nacido , Enfermedades del Recién Nacido/epidemiología , Enfermedades del Recién Nacido/prevención & control , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Masculino
12.
J Pediatr Gastroenterol Nutr ; 70(1): 12-19, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31714477

RESUMEN

OBJECTIVES: Microbial communities influencing health and disease are being increasingly studied in preterm neonates. There exists little data, however, detailing longitudinal microbial acquisition, especially in the most extremely preterm (<26 weeks' gestation). This study aims to characterize the development of the microbiota in this previously under-represented cohort. METHODS: Seven extremely preterm infant-mother dyads (mean gestation 23.6 weeks) were recruited from a single neonatal intensive care unit. Oral and endotracheal secretions, stool, and breast milk (n = 157 total), were collected over the first 60 days of life. Targeted 16S rRNA gene sequencing identified bacterial communities present. RESULTS: Microbiota of all body sites were most similar immediately following birth and diverged longitudinally. Throughout the sampling period Escherichia, Enterococcus, Staphylococcus, and an Enterobacteriaceae were dominant and well dispersed across all sites. Temporal divergence of the stool from other microbiota was driven by decreasing diversity and significantly greater proportional abundance of Bifidobacteriaceae compared to other sites. CONCLUSIONS: Four taxa dominated all anatomical sampling sites. Rare taxa promoted dissimilarity. Cross-seeding between upstream communities and the stool was demonstrated, possibly relating to buccal colostrum/breast milk exposure and indwelling tubes. Given the importance of dysbiosis in health and disease of extremely preterm infants, better understanding of microbial acquisition within this context may be of clinical benefit.


Asunto(s)
Secreciones Corporales/microbiología , Heces/microbiología , Recien Nacido Extremadamente Prematuro , Microbiota , Leche Humana/microbiología , Femenino , Humanos , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Masculino , ARN Ribosómico 16S/análisis , Tráquea/microbiología
13.
Pediatr Res ; 82(6): 958-963, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28738027

RESUMEN

BackgroundTo validate the findings of a single-center pilot study showing elevated urinary N-terminal B-type natriuretic peptide (NTproBNP) concentrations in preterm infants subsequently developing severe retinopathy of prematurity (ROP) in a multicenter setting across eight European and Middle East countries.MethodsProspective observational study in 967 preterm infants <30 weeks' gestational age assessing the capacity of urinary NTproBNP on days of life (DOLs) 14 and 28 to predict ROP requiring treatment.ResultsUrinary NTproBNP concentrations were markedly elevated in infants who developed ROP requiring treatment (n=94) compared with survivors without ROP treatment (n=837), at both time points (median (interquartile range) DOL14: 8,950 (1,925-23,783) vs. 3,083 (1,193-17,393) vs. 816 (290-3,078) pg/ml, P<0.001) and DOL28 (2,203 (611-4,063) vs. 1,671 (254-11,340) vs. 408 (162-1,126) pg/ml, P<0.001). C-statistic of NTproBNP for treated ROP or death was 0.731 (95% confidence interval 0.654-0.774) for DOL14 and 0.683 (0.622-0.745) for DOL28 (P<0.001). Threshold scores were calculated, potentially enabling around 20% of infants with low NTproBNP scores never to be screened with ophthalmoscopy.ConclusionThere is a strong association between early urinary NTproBNP and subsequent ROP development, which can be used to further refine subgroups of patients with high or low risk of severe ROP.


Asunto(s)
Péptido Natriurético Encefálico/orina , Retinopatía de la Prematuridad/orina , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Masculino , Proyectos Piloto , Estudios Prospectivos , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/fisiopatología , Análisis de Supervivencia
14.
BMC Pediatr ; 17(1): 39, 2017 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-28129748

RESUMEN

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.


Asunto(s)
Discapacidades del Desarrollo/prevención & control , Nutrición Enteral/métodos , Enfermedades del Prematuro/prevención & control , Cuidado Intensivo Neonatal/métodos , Leche Humana , Nutrición Parenteral/métodos , Preescolar , Protocolos Clínicos , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Masculino , Estudios Prospectivos , Factores de Tiempo
16.
Curr Opin Infect Dis ; 29(3): 256-61, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27023404

RESUMEN

PURPOSE OF REVIEW: Few areas in neonatal medicine have generated as much discussion and controversy as the use of prophylactic probiotics for the prevention of necrotizing enterocolitis. We summarize recent studies from the last 1-2 years. RECENT FINDINGS: Systematic reviews show that probiotics reduce the risk of necrotizing enterocolitis but there are methodological limitations to all the published trials, and the largest trial to date is at odds with the conclusions of the meta-analyses. Trials have used a range of commercially available products with differing species, and administered these at different times to heterogeneous populations of preterm babies. Although there is strong evidence to show that 'probiotics' are likely to represent a major advance for neonatal care, it is increasingly clear that not all species have beneficial effects in preterm infants. This makes interpretation of meta-analyses complex, and the determination of a single 'risk reduction' potentially flawed. SUMMARY: Despite current uncertainties, it is difficult for clinicians to ignore the current data, and increasing numbers now use commercially available products. It remains a matter of concern that many products lack the robust quality control most clinicians and parents would consider important for use in vulnerable populations. Head-to-head trials are needed.


Asunto(s)
Enterocolitis Necrotizante , Probióticos , Sepsis , Enterocolitis Necrotizante/dietoterapia , Enterocolitis Necrotizante/prevención & control , Humanos , Recién Nacido , Recien Nacido Prematuro , Probióticos/administración & dosificación , Probióticos/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Sepsis/dietoterapia , Sepsis/prevención & control
18.
Pediatr Res ; 79(3): 425-31, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26571220

RESUMEN

BACKGROUND: Necrotising enterocolitis (NEC) and late-onset sepsis (LOS) are the leading causes of death among preterm infants in the developed world. This study aimed to explore the serum proteome and metabolome longitudinally in preterm infants with NEC or LOS, matched to controls. METHODS: Nineteen patients (10 cases, 9 controls) were included. A sample 14 d prior to and following, as well as at disease diagnosis, was included for cases. Controls had serum matched at diagnosis for corresponding case. All samples (n = 39) underwent shotgun proteomic analysis, and 37 samples also underwent metabolomics analysis using ultra performance liquid chromatography-tandem mass spectrometry. RESULTS: The proteomic and metabolomic profiles of serum were comparable between all infants. Eight proteins were associated with NEC and four proteins were associated with LOS. C-reactive protein was increased in all NEC patients at diagnosis. CONCLUSION: No single protein or metabolite was detected in all NEC or LOS cases which was absent from controls; however, several proteins were identified which were associated with disease status. The differing expression of these proteins between diseased infants potentially relates to differing pathophysiology of disease. Thus, it is unlikely a single biomarker exists for NEC and/or LOS.


Asunto(s)
Enterocolitis Necrotizante/sangre , Enfermedades del Prematuro/sangre , Metaboloma , Proteoma/metabolismo , Sepsis/sangre , Biomarcadores/sangre , Proteínas Sanguíneas/química , Estudios de Casos y Controles , Cromatografía Liquida , Perfilación de la Expresión Génica , Humanos , Recién Nacido , Recien Nacido Prematuro , Espectrometría de Masas en Tándem
19.
Acta Paediatr ; 105(1): 50-2, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26148222

RESUMEN

AIM: Changes in gut microbiota may contribute to NEC, but most studies focus on bacteria. Case reports suggest a link between cytomegalovirus (CMV) or other enteric viruses and NEC, but there are few case series systematically looking at common potential viral causes. We aimed to assess the presence of candidate viruses in blood or stool of a case series of infants with NEC managed in one surgical centre. METHODS: We identified 22 infants diagnosed with NEC (from November 2011 to March 2014): 17 had suitable blood stored, of whom 14 also had suitable stool samples stored. Blood was analysed with polymerase chain reaction (PCR) for CMV, Epstein-Barr virus (EBV) and adenovirus, and stool by PCR for norovirus, sappovirus, astrovirus, adenovirus and rotavirus. RESULTS: All samples were negative. CONCLUSION: Although case reports indicate an episodic association of enteric viruses in NEC, the inability to detect any of these viruses in our 17 NEC infants suggests that a viral aetiology is unlikely to be causative for most sporadic forms of NEC.


Asunto(s)
Infecciones por Citomegalovirus/complicaciones , Enterocolitis Necrotizante/virología , Enfermedades del Prematuro/virología , Infecciones por Citomegalovirus/sangre , Infecciones por Citomegalovirus/diagnóstico , Enterocolitis Necrotizante/sangre , Heces/virología , Femenino , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/sangre , Masculino , Virosis/sangre , Virosis/complicaciones , Virosis/diagnóstico
20.
Eur J Pediatr ; 174(8): 1117-21, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25743117

RESUMEN

UNLABELLED: Congenital cytomegalovirus (cCMV) accounts for 20% of all childhood sensorineural hearing loss (SNHL) but is not routinely tested for at birth. Valganciclovir has been shown to prevent hearing deterioration and improve neurocognitive outcomes if started in the first month of life. This study aimed to assess the feasibility of integrating testing for cCMV using salivary swabs into the Newborn Hearing Screening Programme (NHSP). Parents of newborns <22 days old in South West London, who were referred after their initial newborn hearing screen for further audiological testing, were approached by hearing screeners to obtain a saliva sample for CMV DNA polymerase chain reaction (PCR). Eighty percent (203/255) of newborns who were eligible had a saliva swab taken by the hearing screener. Over 99% of results were delivered within the first month of life. Two newborns were identified with cCMV and both seen on day 10 of life by the paediatric specialist. All saliva samples tested delivered a result using real-time PCR. CONCLUSION: It is feasible for hearing screeners to obtain saliva swabs to test for CMV DNA using real-time PCR in newborns referred after their initial hearing screen. Rapid diagnostic testing for cCMV needs a more detailed clinical and cost-effectiveness analysis.


Asunto(s)
Infecciones por Citomegalovirus/diagnóstico , Citomegalovirus/genética , Pruebas Auditivas/métodos , Tamizaje Neonatal/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa , Saliva/química , Análisis Costo-Beneficio , Femenino , Humanos , Recién Nacido , Londres , Masculino
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