Publications by authors named "Sabita Uthaya"

27 Publications

  • Page 1 of 1

Early versus later initiation of parenteral nutrition for very preterm infants: a propensity score-matched observational study.

Arch Dis Child Fetal Neonatal Ed 2021 Nov 18. Epub 2021 Nov 18.

Department of Neonatal Medicine, Imperial College London, London, UK.

Objective: To evaluate the impact of timing of initiation of parenteral nutrition (PN) after birth in very preterm infants.

Design: Propensity-matched analysis of data from the UK National Neonatal Research Database.

Patients: 65 033 babies <31 weeks gestation admitted to neonatal units in England and Wales between 2008 and 2019.

Interventions: PN initiated in the first 2 days (early) versus after the second postnatal day (late). Babies who died in the first 2 days without receiving PN were analysed as 'late'.

Main Outcome Measures: The main outcome measure was morbidity-free survival to discharge. The secondary outcomes were survival to discharge, growth and other core neonatal outcomes.

Findings: No difference was found in the primary outcome (absolute rate difference (ARD) between early and late 0.50%, 95% CI -0.45 to 1.45, p=0.29). The early group had higher rates of survival to discharge (ARD 3.3%, 95% CI 2.7 to 3.8, p<0.001), late-onset sepsis (ARD 0.84%, 95% CI 0.48 to 1.2, p<0.001), bronchopulmonary dysplasia (ARD 1.24%, 95% CI 0.30 to 2.17, p=0.01), treated retinopathy of prematurity (ARD 0.50%, 95% CI 0.17 to 0.84, p<0.001), surgical procedures (ARD 0.80%, 95% CI 0.20 to 1.40, p=0.01) and greater drop in weight z-score between birth and discharge (absolute difference 0.019, 95% CI 0.003 to 0.035, p=0.02). Of 4.9% of babies who died in the first 2 days, 3.4% were in the late group and not exposed to PN.

Conclusions: Residual confounding and survival bias cannot be excluded and justify the need for a randomised controlled trial powered to detect differences in important functional outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2021-322383DOI Listing
November 2021

Changes in neonatal admissions, care processes and outcomes in England and Wales during the COVID-19 pandemic: a whole population cohort study.

BMJ Open 2021 10 1;11(10):e054410. Epub 2021 Oct 1.

Section of Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, UK

Objectives: The COVID-19 pandemic instigated multiple societal and healthcare interventions with potential to affect perinatal practice. We evaluated population-level changes in preterm and full-term admissions to neonatal units, care processes and outcomes.

Design: Observational cohort study using the UK National Neonatal Research Database.

Setting: England and Wales.

Participants: Admissions to National Health Service neonatal units from 2012 to 2020.

Main Outcome Measures: Admissions by gestational age, ethnicity and Index of Multiple Deprivation, and key care processes and outcomes.

Methods: We calculated differences in numbers and rates between April and June 2020 (spring), the first 3 months of national lockdown (COVID-19 period), and December 2019-February 2020 (winter), prior to introduction of mitigation measures, and compared them with the corresponding differences in the previous 7 years. We considered the COVID-19 period highly unusual if the spring-winter difference was smaller or larger than all previous corresponding differences, and calculated the level of confidence in this conclusion.

Results: Marked fluctuations occurred in all measures over the 8 years with several highly unusual changes during the COVID-19 period. Total admissions fell, having risen over all previous years (COVID-19 difference: -1492; previous 7-year difference range: +100, +1617; p<0.001); full-term black admissions rose (+66; -64, +35; p<0.001) whereas Asian (-137; -14, +101; p<0.001) and white (-319; -235, +643: p<0.001) admissions fell. Transfers to higher and lower designation neonatal units increased (+129; -4, +88; p<0.001) and decreased (-47; -25, +12; p<0.001), respectively. Total preterm admissions decreased (-350; -26, +479; p<0.001). The fall in extremely preterm admissions was most marked in the two lowest socioeconomic quintiles.

Conclusions: Our findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2021-054410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488283PMC
October 2021

Better preterm parenteral nutrition practice.

Authors:
Sabita Uthaya

Early Hum Dev 2021 Nov 14;162:105468. Epub 2021 Sep 14.

Department of Neonatal Medicine, School of Public Health, Imperial College London, UK. Electronic address:

At birth preterm babies are unable to tolerate sufficient enteral nutrition to support growth and development. Parenteral nutrition provides a means to bridge the transition from placental transfer of nutrients to the establishment of enteral feeds. Despite preterm babies being one of the highest users of parenteral nutrition amongst all patient groups and that it has been in use in preterm infants for several decades, the evidence base for its use remains weak. There are several areas of uncertainty in practice, including the optimal and relative intakes of macronutrients and the optimal timing of initiation of parenteral nutrition after birth. High quality randomised controlled trials powered to detect differences in long term functional outcomes are needed to determine best practice in preterm parenteral nutrition practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.earlhumdev.2021.105468DOI Listing
November 2021

Outcomes in relation to early parenteral nutrition use in preterm neonates born between 30 and 33 weeks' gestation: a propensity score matched observational study.

Arch Dis Child Fetal Neonatal Ed 2021 Sep 21. Epub 2021 Sep 21.

Neonatal Medicine, Imperial College London, London, UK.

Objective: To evaluate whether in preterm neonates parenteral nutrition use in the first 7 postnatal days, compared with no parenteral nutrition use, is associated with differences in survival and other important morbidities. Randomised trials in critically ill older children show that harms, such as nosocomial infection, outweigh benefits of early parenteral nutrition administration; there is a paucity of similar data in neonates.

Design: Retrospective cohort study using propensity matching including 35 maternal, infant and organisational factors to minimise bias and confounding.

Setting: National, population-level clinical data obtained for all National Health Service neonatal units in England and Wales.

Patients: Preterm neonates born between 30 and 32 weeks.

Interventions: The exposure was parenteral nutrition administered in the first 7 days of postnatal life; the comparator was no parenteral nutrition.

Main Outcome Measures: The primary outcome was survival to discharge from neonatal care. Secondary outcomes comprised the neonatal core outcome set.

Results: 16 292 neonates were compared in propensity score matched analyses. Compared with matched neonates not given parenteral nutrition in the first postnatal week, neonates who received parenteral nutrition had higher survival at discharge (absolute rate increase 0.91%; 95% CI 0.53% to 1.30%), but higher rates of necrotising enterocolitis (absolute rate increase 4.6%), bronchopulmonary dysplasia (absolute rate increase 3.9%), late-onset sepsis (absolute rate increase 1.5%) and need for surgical procedures (absolute rate increase 0.92%).

Conclusions: In neonates born between 30 and 32 weeks' gestation, those given parenteral nutrition in the first postnatal week had a higher rate of survival but higher rates of important neonatal morbidities. Clinician equipoise in this area should be resolved by prospective randomised trials.

Trial Registration Number: NCT03767634.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2021-321643DOI Listing
September 2021

Birthweight and patterns of postnatal weight gain in very and extremely preterm babies in England and Wales, 2008-19: a cohort study.

Lancet Child Adolesc Health 2021 10 25;5(10):719-728. Epub 2021 Aug 25.

School of Public Health, Faculty of Medicine, Imperial College London, London, UK; Section of Neonatal Medicine, Chelsea and Westminster Hospital, London, UK. Electronic address:

Background: Intrauterine and postnatal weight are widely regarded as biomarkers of fetal and neonatal wellbeing, but optimal weight gain following preterm birth is unknown. We aimed to describe changes over time in birthweight and postnatal weight gain in very and extremely preterm babies, in relation to major morbidity and healthy survival.

Methods: In this cohort study, we used whole-population data from the UK National Neonatal Research Database for infants below 32 weeks gestation admitted to neonatal units in England and Wales between Jan 1, 2008, and Dec 31, 2019. We used non-linear Gaussian process to estimate monthly trends, and Bayesian multilevel regression to estimate unadjusted and adjusted coefficients. We evaluated birthweight; weight change from birth to 14 days; weight at 36 weeks postmenstrual age; associated Z scores; and longitudinal weights for babies surviving to 36 weeks postmenstrual age with and without major morbidities. We adjusted birthweight for antenatal, perinatal, and demographic variables. We additionally adjusted change in weight at 14 days and weight at 36 weeks postmenstrual age, and their Z scores, for postnatal variables.

Findings: The cohort comprised 90 817 infants. Over the 12-year period, mean differences adjusted for antenatal, perinatal, demographic, and postnatal variables were 0 g (95% compatibility interval -7 to 7) for birthweight (-0·01 [-0·05 to 0·03] for change in associated Z score); 39 g (26 to 51) for change in weight from birth to 14 days (0·14 [0·08 to 0·19] for change in associated Z score); and 105 g (81 to 128) for weight at 36 weeks postmenstrual age (0·27 [0·21 to 0·33] for change in associated Z score). Greater weight at 36 weeks postmenstrual age was robust to additional adjustment for enteral nutritional intake. In babies surviving without major morbidity, weight velocity in all gestational age groups stabilised at around 34 weeks postmenstrual age at 16-25 g per day along parallel percentile lines.

Interpretation: The birthweight of very and extremely preterm babies has remained stable over 12 years. Early postnatal weight loss has decreased, and subsequent weight gain has increased, but weight at 36 weeks postmenstrual age is consistently below birth percentile. In babies without major morbidity, weight velocity follows a consistent trajectory, offering opportunity to construct novel preterm growth curves despite lack of knowledge of optimal postnatal weight gain.

Funding: UK Medical Research Council.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-4642(21)00232-7DOI Listing
October 2021

Review of guidelines and recommendations from 17 countries highlights the challenges that clinicians face caring for neonates born to mothers with COVID-19.

Acta Paediatr 2020 Nov 20;109(11):2192-2207. Epub 2020 Aug 20.

Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Aim: This review examined how applicable national and regional clinical practice guidelines and recommendations for managing neonates born to mothers with COVID-19 mothers were to the evolving pandemic.

Methods: A systematic search and review identified 20 guidelines and recommendations that had been published by May 25, 2020. We analysed documents from 17 countries: Australia, Brazil, Canada, China, France, India, Italy, Japan, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, the UK and the United States.

Results: The documents were based on expert consensus with limited evidence and were of variable, low methodological rigour. Most did not provide recommendations for delivery methods or managing symptomatic infants. None provided recommendations for post-discharge assimilation of potentially infected infants into the community. The majority encouraged keeping mothers and infants together, subject to infection control measures, but one-third recommended separation. Although breastfeeding or using breastmilk was widely encouraged, two countries specifically prohibited this.

Conclusion: The guidelines and recommendations for managing infants affected by COVID-19 were of low, variable quality and may be unsustainable. It is important that transmission risks are not increased when new information is incorporated into clinical recommendations. Practice guidelines should emphasise the extent of uncertainty and clearly define gaps in the evidence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apa.15495DOI Listing
November 2020

Association of Use of the Neonatal Early-Onset Sepsis Calculator With Reduction in Antibiotic Therapy and Safety: A Systematic Review and Meta-analysis.

JAMA Pediatr 2019 Nov;173(11):1032-1040

Department of Pediatrics, Tergooi Hospital, Blaricum, the Netherlands.

Importance: The neonatal early-onset sepsis (EOS) calculator is a clinical risk stratification tool increasingly used to guide the use of empirical antibiotics for newborns. Evidence on the effectiveness and safety of the EOS calculator is essential to inform clinicians considering implementation.

Objective: To assess the association between management of neonatal EOS guided by the neonatal EOS calculator (compared with conventional management strategies) and reduction in antibiotic therapy for newborns.

Data Sources: Electronic searches in MEDLINE, Embase, Web of Science, and Google Scholar were conducted from 2011 (introduction of the EOS calculator model) through January 31, 2019.

Study Selection: All studies with original data that compared management guided by the EOS calculator with conventional management strategies for allocating antibiotic therapy to newborns suspected to have EOS were included.

Data Extraction And Synthesis: Following PRISMA-P guidelines, relevant data were extracted from full-text articles and supplements. CHARMS (Checklist for Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modeling Studies) and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) tools were used to assess the risk of bias and quality of evidence. Meta-analysis using a random-effects model was conducted for studies with separate cohorts for EOS calculator and conventional management strategies.

Main Outcomes And Measures: The difference in percentage of newborns treated with empirical antibiotics for suspected or proven EOS between management guided by the EOS calculator and conventional management strategies. Safety-related outcomes involved missed cases of EOS, readmissions, treatment delay, morbidity, and mortality.

Results: Thirteen relevant studies analyzing a total of 175 752 newborns were included. All studies found a substantially lower relative risk (range, 3%-60%) for empirical antibiotic therapy, favoring the EOS calculator. Meta-analysis revealed a relative risk of antibiotic use of 56% (95% CI, 53%-59%) in before-after studies including newborns regardless of exposure to chorioamnionitis. Evidence on safety was limited, but proportions of missed cases of EOS were comparable between management guided by the EOS calculator (5 of 18 [28%]) and conventional management strategies (8 of 28 [29%]) (pooled odds ratio, 0.96; 95% CI, 0.26-3.52; P = .95).

Conclusions And Relevance: Use of the neonatal EOS calculator is associated with a substantial reduction in the use of empirical antibiotics for suspected EOS. Available evidence regarding safety of the use of the EOS calculator is limited, but shows no indication of inferiority compared with conventional management strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamapediatrics.2019.2825DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724419PMC
November 2019

Outcomes following early parenteral nutrition use in preterm neonates: protocol for an observational study.

BMJ Open 2019 07 9;9(7):e029065. Epub 2019 Jul 9.

Section of Neonatal Medicine, Imperial College London, London, UK.

Introduction: Preterm babies are among the highest users of parenteral nutrition (PN) of any patient group, but there is wide variation in commencement, duration, and composition of PN and uncertainty around which groups will benefit from early introduction. Recent studies in critically unwell adults and children suggest that harms, specifically increased rates of nosocomial infection, outweigh the benefits of early administration of PN. In this study, we will describe early PN use in neonatal units in England, Wales and Scotland. We will also evaluate if this is associated with differences in important neonatal outcomes in neonates born between 30 and 32 weeks gestation.

Methods And Analysis: We will use routinely collected data from all neonatal units in England, Wales and Scotland, available in the National Neonatal Research Database (NNRD). We will describe clinical practice in relation to any use of PN during the first 7 postnatal days among neonates admitted to neonatal care between 1 January 2012 and 31 December 2017. We will compare outcomes in neonates born between 30 and 32 weeks gestation who did or did not receive PN in the first week after birth using a propensity score-matched approach. The primary outcome will be survival to discharge home. Secondary outcomes will include components of the neonatal core outcome set: outcomes identified as important by former patients, parents, clinicians and researchers.

Ethics And Dissemination: We have obtained UK National Research Ethics Committee approval for this study (Ref: 18/NI/0214). The results of this study will be presented at academic conferences; the UK charity Bliss will aid dissemination to former patients and parents.

Trial Registration Number: NCT03767634.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2019-029065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615825PMC
July 2019

Impact of breast milk intake on body composition at term in very preterm babies: secondary analysis of the Nutritional Evaluation and Optimisation in Neonates randomised controlled trial.

Arch Dis Child Fetal Neonatal Ed 2019 May 14;104(3):F306-F312. Epub 2018 Jul 14.

Neonatal Medicine, Chelsea and Westminster National Health Service Foundation Trust, London, UK.

Objective: To investigate the impact of breast milk (BM) intake on body composition at term in very preterm infants.

Design: Preplanned secondary analysis of the Nutritional Evaluation and Optimisation in Neonates Study, a 2-by-2 factorial randomised controlled trial of preterm parenteral nutrition (PN).

Setting: Four National Health Service hospitals in London and South-East England.

Patients: Infants born at <31 weeks of gestation; infants with life-threatening congenital abnormalities and those unable to receive trial PN within 24 hours of birth were ineligible. 133 infants survived and underwent whole-body MRI at term (37-44 weeks postmenstrual age).

Main Outcome Measures: Non-adipose tissue mass (non-ATM), ATM and ATM as a percentage of body weight (% ATM) at term.

Results: Compared with the exclusively BM group (proportion of BM=100% milk, n=56), predominantly formula-fed infants (BM ≤50%, n=38) weighed 283.6 g (95% CI 121.6 to 445.6) more, had 257.4 g (139.1-375.7) more non-ATM and a greater positive weight Z-score change between birth and term. There were no significant differences in weight, non-ATM and weight Z-score change between the exclusively and predominantly BM (BM 51%-99%, n=39) groups. Compared with the exclusively BM group no significant differences were observed in ATM and %ATM in the predominantly BM and predominantly formula-fed groups.

Conclusions: The slower weight gain of preterm infants fed BM appears to be due to a deficit in non-ATM and may reflect lower protein intake. Whether this pattern persists into childhood, is altered by BM fortification or later diet, or relates to functional outcomes, are important research questions.

Clinical Trial Registration: ISRCTN29665319, post results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2017-314625DOI Listing
May 2019

Body Composition following Necrotising Enterocolitis in Preterm Infants.

Neonatology 2018 23;113(3):242-248. Epub 2018 Jan 23.

Section of Neonatal Medicine, Department of Medicine, Imperial College London, Chelsea and Westminster Campus, London, United Kingdom.

Background: The optimal nutritional regimen for preterm infants, including those that develop necrotising enterocolitis (NEC), is unknown.

Objective: The objective here was to evaluate body composition at term in infants following NEC, in comparison with healthy infants. The primary outcome measure was non-adipose tissue mass (non-ATM).

Methods: We compared body composition assessed by magnetic resonance imaging at term in infants born <31 weeks of gestational age that participated in NEON, a trial comparing incremental versus immediate delivery of parenteral amino acids on non-ATM, and SMOF versus intralipid on intrahepatocellular lipid content. There were no differences in the primary outcomes. We compared infants that received surgery for NEC (NEC-surgical), infants with medically managed NEC (NEC-medical), and infants without NEC (reference).

Results: A total of 133 infants were included (8 NEC-surgical; 15 NEC-medical; 110 reference). In comparison with the reference group, infants in the NEC-surgical and NEC-medical groups were significantly lighter [adjusted mean difference (95% CI) NEC-surgical: -630 g (-1,010, -210), p = 0.003; NEC-medical: -440 g (-760, -110), p = 0.009] and the total adipose tissue volume (ATV) was significantly lower [NEC-surgical: -360 cm3 (-516, -204), p < 0.001; NEC-medical: -127 cm3 (-251, -4); p = 0.043]. There were no significant differences in non-ATM [adjusted mean difference (95% CI) NEC-surgical: -46 g (-281, 189), p = 0.70; NEC-medical: -122 g (-308, 63), p = 0.20].

Conclusion: The lower weight at term in preterm infants following surgically and medically managed NEC, in comparison to preterm infants that did not develop the disease, was secondary to a reduction in ATV. This suggests that the nutritional regimen received was adequate to preserve non-ATM but not to support the normal third-trimester deposition of adipose tissue in preterm infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000485827DOI Listing
September 2019

Methylene blue-induced Heinz body hemolytic anemia in a premature neonate.

Am J Hematol 2018 05 27;93(5):716-717. Epub 2018 Jan 27.

Department of Haematology, St Mary's Hospital, London, W2 1NY, United Kingdom.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.25028DOI Listing
May 2018

Neonatal brain injuries in England: population-based incidence derived from routinely recorded clinical data held in the National Neonatal Research Database.

Arch Dis Child Fetal Neonatal Ed 2018 Jul 22;103(4):F301-F306. Epub 2017 Oct 22.

Section of Neonatal Medicine, Department of Medicine, Imperial College London, Chelsea and Westminster Hospital campus, London, UK.

Objective: In 2015, the Department of Health in England announced an ambition to reduce 'brain injuries occurring during or soon after birth'. We describe the development of a pragmatic case definition and present annual incidence rates.

Design: Retrospective cohort study using data held in the National Neonatal Research Database (NNRD) extracted from neonatal electronic patient records from all National Health Service (NHS) neonatal units in England, Wales and Scotland. In 2010-2011, population coverage in the NNRD was incomplete, hence rate estimates are presented as a range; from 2012, population coverage is complete, and rates (95% CIs) are presented. Rates are per 1000 live births.

Setting: NHS neonatal units in England.

Patients: Infants admitted for neonatal care; denominator: live births in England.

Main Outcome Measure: 'Brain injuries occurring at or soon after birth' defined as infants with seizures, hypoxic-ischaemic encephalopathy, stroke, intracranial haemorrhage, central nervous system infection and kernicterus and preterm infants with cystic periventricular leucomalacia.

Results: In 2010, the lower estimate of the rate of 'Brain injuries occurring at or soon after birth' in England was 4.53 and the upper estimate was 5.19; in 2015, the rate was 5.14 (4.97, 5.32). For preterm infants, the population incidence in 2015 was 25.88 (24.51, 27.33) and 3.47 (3.33, 3.62) for term infants. Hypoxic-ischaemic encephalopathy was the largest contributor to term brain injury, and intraventricular/periventricular haemorrhage was the largest contributor to preterm brain injury.

Conclusions: Annual incidence rates for brain injuries can be estimated from data held in the NNRD; rates for individual conditions are consistent with published rates. Routinely recorded clinical data can be used for national surveillance, offering efficiencies over traditional approaches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2017-313707DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047140PMC
July 2018

Reply to P Mainie.

Am J Clin Nutr 2016 12;104(6):1721-1722

From the Chelsea and Westminster NHS Foundation Trust, London, United Kingdom (SU, e-mail: NM); and the Section of Neonatal Medicine, Department of Medicine (SU, NM) and Imperial Clinical Trials Unit, School of Public Health (XL), Imperial College London, London, United Kingdom.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3945/ajcn.116.139782DOI Listing
December 2016

Nutritional Evaluation and Optimisation in Neonates: a randomized, double-blind controlled trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition.

Am J Clin Nutr 2016 Jun 20;103(6):1443-52. Epub 2016 Apr 20.

Chelsea and Westminster National Health Service Foundation Trust, London, United Kingdom; Section of Neonatal Medicine, Department of Medicine, Imperial College London.

Background: Parenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intakes and fish oil-containing lipid emulsions.

Objective: The aim of this trial was to compare 1) the effects of high [immediate recommended daily intake (Imm-RDI)] and low [incremental introduction of amino acids (Inc-AAs)] parenteral amino acid delivery within 24 h of birth on body composition and 2) the effect of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil (SMOF) with that of soybean oil (SO)-based lipid emulsion on intrahepatocellular lipid (IHCL) content.

Design: We conducted a 2-by-2 factorial, double-blind, multicenter randomized controlled trial.

Results: We randomly assigned 168 infants born at <31 wk of gestation. We evaluated outcomes at term in 133 infants. There were no significant differences between Imm-RDI and Inc-AA groups for nonadipose mass [adjusted mean difference: 1.0 g (95% CI: -108, 111 g; P = 0.98)] or between SMOF and SO groups for IHCL [adjusted mean SMOF:SO ratio: 1.1 (95% CI: 0.8, 1.6; P = 0.58]. SMOF does not affect IHCL content. There was a significant interaction (P = 0.05) between the 2 interventions for nonadipose mass. There were no significant interactions between group differences for either primary outcome measure after adjusting for additional confounders. Imm-RDI infants were more likely than Inc-AA infants to have blood urea nitrogen concentrations >7 mmol/L or >10 mmol/L, respectively (75% compared with 49%, P < 0.01; 49% compared with 18%, P < 0.01). Head circumference at term was smaller in the Imm-RDI group [mean difference: -0.8 cm (95% CI: -1.5, -0.1 cm; P = 0.02)]. There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, incidence of conjugated hyperbilirubinemia, weight, length, mortality, and brain volumes.

Conclusion: Imm-RDI of parenteral amino acids does not benefit body composition or growth to term and may be harmful. This trial was registered at www.isrctn.com as ISRCTN29665319 and at eudract.ema.europa.eu as EudraCT 2009-016731-34.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3945/ajcn.115.125138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880995PMC
June 2016

A randomised controlled trial of high vs low volume initiation and rapid vs slow advancement of milk feeds in infants with birthweights ≤ 1000 g in a resource-limited setting.

Paediatr Int Child Health 2016 Nov 1;36(4):288-295. Epub 2016 Jun 1.

a Division of Neonatal Medicine, Department of Paediatrics , University of Cape Town , South Africa.

Background: Optimal feeding regimens for infants ≤ 1000 g have not been established and are a global healthcare concern.

Aims And Objectives: A controlled trial to establish the safety and efficacy of high vs low volume initiation and rapid vs slow advancement of milk feeds in a resource-limited setting was undertaken.

Methods: Infants ≤ 1000 g birthweight were randomised to one of four arms, either low (4 ml/kg/day) or high (24 ml/kg/day) initiation and either slow (24 ml/kg/day) or rapid (36 ml/kg/day) advancement of exclusive feeds of human milk (mother's or donor) until a weight of 1200 g was reached. After this point, formula was used to supplement insufficient mother's milk. The primary outcome was time to reach 1500 g.

Results: infants were recruited (51: low/slow; 47: low/rapid; 52: high/slow; 50: high/rapid). Infants on rapid advancement regimens reached 1500 g most rapidly (hazard ratio 1.48, 95% CI 1.05-2.09, P=0.03). The rapid advancement groups also regained birthweight more rapidly (hazard ratio 1.77, 95% CI 1.26-2.50, P=0.001). There was no apparent effect of high vs low initiation volumes but there was some evidence of interaction between interventions. There were no significant differences in other secondary outcomes, including necrotising enterocolitis, feed intolerance and late-onset sepsis.

Conclusions: In this small pilot study, higher initiation feed volumes and larger daily increments appeared to be well tolerated and resulted in more rapid early weight gain. These data provide justification for a larger study in resource-limited settings to address mortality, necrotising enterocolitis and other important outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1179/2046905515Y.0000000056DOI Listing
November 2016

Managing palliation in the neonatal unit.

Arch Dis Child Fetal Neonatal Ed 2014 Sep 4;99(5):F349-52. Epub 2014 Jun 4.

Chelsea and Westminster NHS Foundation Trust, London, UK Imperial College London, London, UK Royal College of Paediatrics and Child Health, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2013-305845DOI Listing
September 2014

Adiposity and hepatic lipid in healthy full-term, breastfed, and formula-fed human infants: a prospective short-term longitudinal cohort study.

Am J Clin Nutr 2014 May 26;99(5):1034-40. Epub 2014 Feb 26.

Section of Neonatal Medicine, Chelsea and Westminster Hospital Campus, Imperial College London, London, United Kingdom (CG, SJ, KML, JRCP, SU, SS, and NM); the Metabolic and Molecular Imaging Group, Medical Research Council Clinical Sciences Centre, Hammersmith Campus, Imperial College London, London, United Kingdom (ELT and JDB); and the Robert Steiner MRI Unit, Hammersmith Campus, Imperial College London, London, United Kingdom (GD).

Background: The effect of mode of infant feeding on adiposity deposition is not fully understood.

Objective: The objective was to test the hypothesis that differences in total and regional adipose tissue content and intrahepatocellular lipid (IHCL) arise in early infancy between breast- and formula-fed infants and to describe longitudinal changes.

Design: This prospective longitudinal cohort study was performed in 2 hospitals in the United Kingdom. Healthy, full-term, appropriate weight-for-gestational age infants were recruited; adipose tissue volume and distribution were directly quantified by using whole-body magnetic resonance imaging; IHCL was assessed by in vivo proton magnetic resonance spectroscopy. Measurements were performed after birth (median age: 13 d) and at 6-12 wk of age. Method of infant feeding was recorded prospectively by using maternally completed feeding diaries. Breastfed was defined as >80% of feeds consisting of breast milk at both points; formula-fed was defined as >80% of feeds consisting of formula milk at both points.

Results: Longitudinal results were obtained from 70 infants (36 breastfed, 9 mixed-fed, and 25 formula-fed). No differences were found in total or regional adipose tissue or IHCL between breastfed and formula-fed infants. In pooled analyses including all feeding groups, IHCL and total adipose tissue approximately doubled between birth and 6-12 wk: IHCL after birth (median: 0.949; IQR: 0.521-1.711) and at 6-12 wk (1.828; 1.376-2.697; P < 0.001) and total adipose tissue after birth (0.749 L; 0.620-0.928 L) and at 6-12 wk (1.547 L; 1.332-1.790 L; P < 0.001). Increasing adiposity was characterized by greater relative increases in subcutaneous than in internal adipose tissue depots.

Conclusions: No differences were detectable in adipose tissue or IHCL accretion between breastfed and formula-fed infants up to 2 mo. The substantial increase in IHCL seen over this period in both breastfed and formula-fed infants is a novel observation, which suggests that hepatic storage of lipids may be physiologic up to 2 mo. This trial was registered at www.clinicaltrials.gov as NCT02033005.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3945/ajcn.113.080200DOI Listing
May 2014

GATA1-mutant clones are frequent and often unsuspected in babies with Down syndrome: identification of a population at risk of leukemia.

Blood 2013 Dec 10;122(24):3908-17. Epub 2013 Sep 10.

Centre for Haematology, Hammersmith Campus, Imperial College London, London, United Kingdom;

Transient abnormal myelopoiesis (TAM), a preleukemic disorder unique to neonates with Down syndrome (DS), may transform to childhood acute myeloid leukemia (ML-DS). Acquired GATA1 mutations are present in both TAM and ML-DS. Current definitions of TAM specify neither the percentage of blasts nor the role of GATA1 mutation analysis. To define TAM, we prospectively analyzed clinical findings, blood counts and smears, and GATA1 mutation status in 200 DS neonates. All DS neonates had multiple blood count and smear abnormalities. Surprisingly, 195 of 200 (97.5%) had circulating blasts. GATA1 mutations were detected by Sanger sequencing/denaturing high performance liquid chromatography (Ss/DHPLC) in 17 of 200 (8.5%), all with blasts >10%. Furthermore low-abundance GATA1 mutant clones were detected by targeted next-generation resequencing (NGS) in 18 of 88 (20.4%; sensitivity ∼0.3%) DS neonates without Ss/DHPLC-detectable GATA1 mutations. No clinical or hematologic features distinguished these 18 neonates. We suggest the term "silent TAM" for neonates with DS with GATA1 mutations detectable only by NGS. To identify all babies at risk of ML-DS, we suggest GATA1 mutation and blood count and smear analyses should be performed in DS neonates. Ss/DPHLC can be used for initial screening, but where GATA1 mutations are undetectable by Ss/DHPLC, NGS-based methods can identify neonates with small GATA1 mutant clones.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2013-07-515148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995281PMC
December 2013

Ultrasound estimates of visceral and subcutaneous-abdominal adipose tissues in infancy.

J Obes 2013 17;2013:951954. Epub 2013 Apr 17.

MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, P.O. Box 285, Cambridge CB2 0QQ, UK.

Other imaging techniques to quantify internal-abdominal adiposity (IA-AT) and subcutaneous-abdominal adiposity (SCA-AT) are frequently impractical in infants. The aim of this study was twofold: (a) to validate ultrasound (US) visceral and subcutaneous-abdominal depths in assessing IA-AT and SCA-AT from MRI as the reference method in infants and (b) to analyze the association between US abdominal adiposity and anthropometric measures at ages 3 months and 12 months. Twenty-two infants underwent MRI and US measures of abdominal adiposity. Abdominal US parameters and anthropometric variables were assessed in the Cambridge Baby Growth Study (CBGS), n = 487 infants (23 girls) at age 3 months and n = 495 infants (237 girls) at 12 months. US visceral and subcutaneous-abdominal depths correlated with MRI quantified IA-AT (r = 0.48, P < 0.05) and SCA-AT (r = 0.71, P < 0.001) volumes, respectively. In CBGS, mean US-visceral depths increased by ~20 % between ages 3 and 12 months (P < 0.0001) and at both ages were lower in infants breast-fed at 3 months than in other infants. US-visceral depths at both 3 and 12 months were inversely related to skinfold thickness at birth (P = 0.03 and P = 0.009 at 3 and 12 months, resp.; adjusted for current skinfold thickness). In contrast, US-subcutaneous-abdominal depth at 3 months was positively related to skinfold thickness at birth (P = 0.004). US measures can rank infants with higher or lower IA-AT and SCA-AT. Contrasting patterns of association with visceral and subcutaneous-abdominal adiposities indicate that they may be differentially regulated in infancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2013/951954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654330PMC
December 2013

Avoiding sedation in research MRI and spectroscopy in infants: our approach, success rate and prevalence of incidental findings.

Arch Dis Child Fetal Neonatal Ed 2013 May 26;98(3):F267-8. Epub 2012 Sep 26.

Section of Neonatal Medicine, Department of Medicine, Imperial College London, Chelsea and Westminster Hospital campus, 369 Fulham Road, London, SW10 9NH, UK.

Performing magnetic resonance investigations in a paediatric population can be difficult; image acquisition is commonly complicated by movement artefact and non-compliance. Sedation is widely used for clinically indicated investigations, but there is controversy when used for research imaging. Over a 10-year period we have performed whole body MRI on over 450 infants and hepatic magnetic resonance spectroscopy on over 270 infants. These investigations have been accomplished without the use of sedation in infants up to 3 months of age. Our overall success rate in achieving good quality images free of movement artefact is 94%. The prevalence of incidental findings on whole body (excluding brain) MRI in our cohort was 0.8%. We conclude that the use of sedation for research MRI in this group is not necessary. Our approach to MRI in infancy is also described.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2012-302536DOI Listing
May 2013

A randomized, double-blind, controlled trial of the effect of prebiotic oligosaccharides on enteral tolerance in preterm infants (ISRCTN77444690).

Pediatr Res 2010 Nov;68(5):440-5

Division of Medicine, Section of Neonatal Medicine, Chelsea and Westminster Hospital Campus, Imperial College London, London SW10 9NH, United Kingdom.

Breast milk prebiotic oligosaccharides are believed to promote enteral tolerance. Many mothers delivering preterm are unable to provide sufficient milk. We conducted a multicenter, randomized, controlled trial comparing preterm formula containing 0.8 g/100 mL short-chain galacto-oligosaccharides/long-chain fructo-oligosaccharides in a 9:1 ratio and an otherwise identical formula, using formula only to augment insufficient maternal milk volume. Infants were randomized within 24 h of birth. The primary outcome (PO) was time to establish a total milk intake of 150 mL/kg/d PO and the principal secondary outcome (PSO) was proportion of time between birth and 28 d/discharge that a total milk intake of ≥ 150 mL/kg/d was tolerated. Other secondary outcomes included growth, fecal characteristics, gastrointestinal signs, necrotizing enterocolitis, and bloodstream infection. Outcomes were compared adjusted for prespecified covariates. We recruited 160 infants appropriately grown for GA <33 wk. There were no significant differences in PO or PSOs. After covariate adjustment, we showed significant benefit from trial formula in PSO with increasing infant immaturity (2.9% improved tolerance for a baby born at 28-wk gestation and 9.9% at 26-wk gestation; p < 0.001) but decreased or no benefit in babies >31-wk gestation. Prebiotic supplementation appears safe and may benefit enteral tolerance in the most immature infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1203/PDR.0b013e3181f1cd59DOI Listing
November 2010

Whole body magnetic resonance imaging of healthy newborn infants demonstrates increased central adiposity in Asian Indians.

Pediatr Res 2009 May;65(5):584-7

Section of Neonatal Medicine, Division of Medicine, Chelsca & Westminister Hospital Campus, Imperial College London, London SW10 9NH, UK.

Abdominal adiposity and metabolic ill health in Asian Indians are a growing public health concern. Causal pathways are unknown. Preventive measures in adults have had limited success. The aim of this observational case-control study was to compare adipose tissue partitioning in 69 healthy full term Asian Indian and white European newborns born in Pune, India and London, UK, respectively. The main outcome measures were total and regional adipose tissue content measured by whole body magnetic resonance imaging. Although smaller in weight (95% CI for difference -0.757 to -0.385 kg, p < 0.001), head circumference (-2.15 to -0.9 cm, p < 0.001), and length (-2.9 to -1.1 cm p < 0.001), the Asian Indian neonates had significantly greater absolute adiposity in all three abdominal compartments, internal (visceral) (0.012-0.023 L, p < 0.001), deep s.c. (0.003-0.017 L, p = 0.006) and superficial s.c. (0.006-0.043 L, p = 0.011) and a significant reduction in nonabdominal superficial s.c. adipose tissue (-0.184 to -0.029 L, p = 0.008) in comparison to the white European babies despite similar whole body adipose tissue content (-0.175 to 0.034 L, p = 0.2). We conclude that differences in adipose tissue partitioning exist at birth. Investigative, screening, and preventive measures must involve maternal health, intrauterine life, and infancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1203/pdr.0b013e31819d98beDOI Listing
May 2009

Determinants of adiposity during preweaning postnatal growth in appropriately grown and growth-restricted term infants.

Pediatr Res 2006 Sep 20;60(3):345-8. Epub 2006 Jul 20.

Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London SW10 9NH, UK.

The distribution and quantity of adipose tissue are markers of morbidity risk in children and adults. Poor intrauterine growth and accelerated postnatal growth are believed to add to these risks. The aim of this study was to assess adipose tissue content and distribution at birth and 6 wk in relation to intrauterine growth restriction, postnatal growth, and infant diet. We measured weight, length, and head circumference and adipose content and distribution using magnetic resonance imaging at 6 wk of age in appropriately grown for gestational age (AGA) and growth-restricted (GR) infants and compared this with birth data. By 6 wk, GR infants showed complete catch-up in comparison to AGA infants in relation to head growth and adiposity. Catch-up in length and weight was not complete. Accelerated linear growth, but not accelerated weight gain, was associated with a highly significant increase in adiposity (r = 0.57, p = 0.001) regardless of AGA/GR status. The highest adiposity at 6 wk, allowing for baseline variables and linear growth, was seen in exclusively breast-fed GR infants (mean, 95% confidence interval: 33.5%, 29.51-37.5). Adipose tissue distribution remained constant and was unrelated to growth and diet. Reduced birth adiposity (B = -0.185, p = 0.003), but not low birth head size (B = 0.32, p = 0.093), was a significant predictor of accelerated postnatal head growth (R(2) = 0.29, adjusted R(2) = 0.23, p = 0.012). Increasing adiposity appears to be an inevitable accompaniment of accelerated linear growth. Low total adipose tissue quantity at birth appears to direct nutrition toward head growth. Adipose tissue may be involved in the signaling of catch-up growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1203/01.pdr.0000232732.93000.52DOI Listing
September 2006

Altered adiposity after extremely preterm birth.

Pediatr Res 2005 Feb 20;57(2):211-5. Epub 2004 Dec 20.

Division of Paediatrics, Obstetrics & Gynaecology, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, 369 Fulham Rd., London SW10 9NH, UK.

The quantity and distribution of adipose tissue are markers of morbidity risk. The third trimester of human development is a period of rapid adipose tissue deposition. Preterm infants may be at risk of altered adiposity. We measured anthropometric indices and quantified total, subcutaneous, and intraabdominal adipose tissue volumes using whole-body magnetic resonance adipose tissue imaging in 38 infants born at <32 wk gestational age, when they reached term, and 29 term-born infants. The preterm infants at term were significantly lighter and shorter than the term-born infants, but there was no significant difference in head circumference SD score or total adiposity. The preterm infants had a highly significant decrease in subcutaneous adipose tissue and significantly increased intraabdominal adipose tissue. Accelerated postnatal weight gain was accompanied by increased total and subcutaneous adiposity. Illness severity was the principal determinant of increased intraabdominal adiposity. Our data provide evidence of causal pathways linking accelerated postnatal growth with increased total and subcutaneous adiposity, and illness severity with altered adipose tissue partitioning. We suggest that these observations may in part explain the associations between small size at birth and later disease. Preterm infants may be at risk in later life of metabolic complications through increased and aberrant adiposity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1203/01.PDR.0000148284.58934.1CDOI Listing
February 2005

Adipose tissue magnetic resonance imaging in the newborn.

Horm Res 2004 ;62 Suppl 3:143-8

Division of Paediatrics, Obstetrics and Gynaecology, Chelsea and Westminster Hospital, Imperial College London, UK.

Infancy is a period of rapid adipose tissue accumulation, and influences during early development are plausible determinants of altered adiposity. The distribution, as well as the quantity of adipose tissue, is a marker of health and disease. Previous methods for the assessment of body composition in infants have been indirect and thus unable to determine adipose quantity reliably, nor assess adipose tissue distribution. Adipose tissue magnetic resonance imaging is direct, non-invasive, radiation free and suitable for serial examinations in infancy. Adipose tissue depots are quantified individually and summated to provide an accurate measure of depot-specific and total adiposity. We have adapted this technique for application to newborns and, to date, have imaged over 100 term and preterm infants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000080517DOI Listing
June 2005
-->