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Aims We tested the hypothesis that the known reduction in myocardial functional reserve in preterm-born young adults is an independent predictor of exercise capacity (peak VO2) and heart rate recovery (HRR). Methods and results We recruited 101 normotensive young adults (n = 47 born preterm; 32.8 ± 3.2 weeks’ gestation and n = 54 term-born controls). Peak VO2 was determined by cardiopulmonary exercise testing (CPET), and lung function assessed using spirometry. Percentage predicted values were then calculated. HRR was defined as the decrease from peak HR to 1 min (HRR1) and 2 min of recovery (HRR2). Four-chamber echocardiography views were acquired at rest and exercise at 40% and 60% of CPET peak power. Change in left ventricular ejection fraction from rest to each work intensity was calculated (EFΔ40% and EFΔ60%) to estimate myocardial functional reserve. Peak VO2 and per cent of predicted peak VO2 were lower in preterm-born young adults compared with controls (33.6 ± 8.6 vs. 40.1 ± 9.0 mL/kg/min, P = 0.003 and 94% ± 20% vs. 108% ± 25%, P = 0.001). HRR1 was similar between groups. HRR2 decreased less in preterm-born young adults compared with controls (−36 ± 13 vs. −43 ± 11 b.p.m., P = 0.039). In young adults born preterm, but not in controls, EFΔ40% and EFΔ60% correlated with per cent of predicted peak VO2 (r2 = 0.430, P = 0.015 and r2 = 0.345, P = 0.021). Similarly, EFΔ60% correlated with HRR1 and HRR2 only in those born preterm (r2 = 0.611, P = 0.002 and r2 = 0.663, P = 0.001). Conclusions Impaired myocardial functional reserve underlies reductions in peak VO2 and HRR in young adults born moderately preterm. Peak VO2 and HRR may aid risk stratification and treatment monitoring in this population.

Infants born prematurely are often discharged from hospital before 37 weeks post-menstrual age. While breastfeeding will meet all the nutritional requirements of full-term infants, these preterm infants may need enhanced levels of protein, minerals and possibly energy to ensure optimum growth, bone mineralisation and neurological development. To meet these additional nutrient needs in the neonatal unit, it is currently recommended that multinutrient breast milk fortifier is added to maternal breast milk. There may also be benefits in continuing to provide fortified milk after discharge, potentially including improved growth and preserving breastfeeding, and this is increasingly becoming a recognised practice in some neonatal units. This article presents the discussion and consensus of a multidisciplinary panel of neonatologists, neonatal dietitians, a GP and a neonatal outreach sister. The aim is to develop guidance on providing safe and effective nutritional supplementation for preterm infants after discharge in order to maintain optimal growth. This guidance is aimed at community healthcare staff and is based on the limited evidence available, using shared best practice and expertise.

Aim Measure weight gain in preterm infants after introduction of a nutritional care bundle. Methods 509 infants less than 32 weeks gestation were studied until discharge home from the tertiary unit or their local neonatal unit. Growth and feeding data were prospectively collected for 18 months before and after the intervention. The intervention consisted of increasing the urgency of parenteral nutrition, routine introduction of enteral feeds from the first day of life, standardised weight-based daily increments of enteral feeds, use of donor human milk until at least 34 weeks corrected gestation (if insufficient mothers’ own milk) and routine fortification of human milk from 120 ml/kg/day. Results After the intervention, growth velocity by discharge home increased by 1 g/kg/day to 12.7 ± 2.2 g/kg/day (p Conclusion Introduction of a simple nutritional bundle was associated with improved weight gain, particularly in those fed exclusive human milk at discharge. In order to achieve international growth recommendations further intensification of macronutrient provision may be required.

Background Pregnancy complications such as preterm birth and fetal growth restriction are associated with altered prenatal and postnatal cardiac development. We studied whether there were changes related specifically to pregnancy hypertension. Methods and Results Left and right ventricular volumes, mass, and function were assessed at birth and 3 months of age by echocardiography in 134 term‐born infants. Fifty‐four had been born to mothers who had normotensive pregnancy and 80 had a diagnosis of preeclampsia or pregnancy‐induced hypertension. Differences between groups were interpreted, taking into account severity of pregnancy disorder, sex, body size, and blood pressure. Left and right ventricular mass indexed to body surface area ( LVMI and RVMI ) were similar in both groups at birth ( LVMI 20.9±3.7 versus 20.6±4.0 g/m 2 , P =0.64, RVMI 17.5±3.7 versus 18.1±4.7 g/m 2 , P =0.57). However, right ventricular end diastolic volume index was significantly smaller in those born to hypertensive pregnancy (16.8±5.3 versus 12.7±4.7 mL/m 2 , P =0.001), persisting at 3 months of age (16.4±3.2 versus 14.4±4.8 mL/m 2 , P =0.04). By 3 months of age these infants also had significantly greater LVMI and RVMI ( LVMI 24.9±4.6 versus 26.8±4.9 g/m 2 , P =0.04; RVMI 17.1±4.2 versus 21.1±3.9 g/m 2 , P RVMI and right ventricular end diastolic volume index at 3 months, but not left ventricular measures, correlated with severity of the hypertensive disorder. No differences in systolic or diastolic function were evident. Conclusions Infants born at term to a hypertensive pregnancy have evidence of both prenatal and postnatal differences in cardiac development, with right ventricular changes proportional to the severity of the pregnancy disorder. Whether differences persist long term as well as their underlying cause and relationship to increased cardiovascular risk requires further study.

ObjectiveTo evaluate the cost-effectiveness of two rates of enteral feed advancement (18 vs 30 mL/kg/day) in very preterm and very low birth weight infants.DesignWithin-trial economic evaluation alongside a multicentre, two-arm parallel group, randomised controlled trial (Speed of Increasing milk Feeds Trial).Setting55 UK neonatal units from May 2013 to June 2015.PatientsInfants born InterventionsWhen clinicians were ready to start advancing feed volumes, infants were randomised to receive daily increments in feed volume of 30 mL/kg (intervention) or 18 mL/kg (control).Main outcome measureCost per additional survivor without moderate to severe neurodevelopmental disability at 24 months of age corrected for prematurity.ResultsAverage costs per infant were slightly higher for faster feeds compared with slower feeds (mean difference £267, 95% CI −6928 to 8117). Fewer infants achieved the principal outcome of survival without moderate to severe neurodevelopmental disability at 24 months in the faster feeds arm (802/1224 vs 848/1246). The stochastic cost-effectiveness analysis showed a likelihood of worse outcomes for faster feeds compared with slower feeds.ConclusionsThe stochastic cost-effectiveness analysis shows faster feeds are broadly equivalent on cost grounds. However, in terms of outcomes at 24 months age (corrected for prematurity), faster feeds are harmful. Faster feeds should not be recommended on either cost or effectiveness grounds to achieve the primary outcome.

The implementation of video-based non-contact technologies to monitor the vital signs of preterm infants in the hospital presents several challenges, such as the detection of the presence or the absence of a patient in the video frame, robustness to changes in lighting conditions, automated identification of suitable time periods and regions of interest from which vital signs can be estimated. We carried out a clinical study to evaluate the accuracy and the proportion of time that heart rate and respiratory rate can be estimated from preterm infants using only a video camera in a clinical environment, without interfering with regular patient care. A total of 426.6 h of video and reference vital signs were recorded for 90 sessions from 30 preterm infants in the Neonatal Intensive Care Unit (NICU) of the John Radcliffe Hospital in Oxford. Each preterm infant was recorded under regular ambient light during daytime for up to four consecutive days. We developed multi-task deep learning algorithms to automatically segment skin areas and to estimate vital signs only when the infant was present in the field of view of the video camera and no clinical interventions were undertaken. We propose signal quality assessment algorithms for both heart rate and respiratory rate to discriminate between clinically acceptable and noisy signals. The mean absolute error between the reference and camera-derived heart rates was 2.3 beats/min for over 76% of the time for which the reference and camera data were valid. The mean absolute error between the reference and camera-derived respiratory rate was 3.5 breaths/min for over 82% of the time. Accurate estimates of heart rate and respiratory rate could be derived for at least 90% of the time, if gaps of up to 30 seconds with no estimates were allowed.

Non-contact vital sign monitoring enables the estimation of vital signs, such as heart rate, respiratory rate and oxygen saturation (SpO2), by measuring subtle color changes on the skin surface using a video camera. For patients in a hospital ward, the main challenges in the development of continuous and robust non-contact monitoring techniques are the identification of time periods and the segmentation of skin regions of interest (ROIs) from which vital signs can be estimated. We propose a deep learning framework to tackle these challenges. Approach: This paper presents two convolutional neural network (CNN) models. The first network was designed for detecting the presence of a patient and segmenting the patient’s skin area. The second network combined the output from the first network with optical flow for identifying time periods of clinical intervention so that these periods can be excluded from the estimation of vital signs. Both networks were trained using video recordings from a clinical study involving 15 pre-term infants conducted in the high dependency area of the neonatal intensive care unit (NICU) of the John Radcliffe Hospital in Oxford, UK. Main results: Our proposed methods achieved an accuracy of 98.8% for patient detection, a mean intersection-over-union (IOU) score of 88.6% for skin segmentation and an accuracy of 94.5% for clinical intervention detection using two-fold cross validation. Our deep learning models produced accurate results and were robust to different skin tones, changes in light conditions, pose variations and different clinical interventions by medical staff and family visitors. Significance: Our approach allows cardio-respiratory signals to be continuously derived from the patient’s skin during which the patient is present and no clinical intervention is undertaken.

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. opens in new tab.)

AIM To measure growth outcomes in preterm infants after introduction of a nutritional care bundle. METHODS A total of 509 infants of less than 32 weeks' gestation in a level III neonatal intensive care unit in the UK were studied until they were discharged home. Growth and feeding data were extracted from a prospective data registry for 18 months before and after the intervention. The intervention consisted of earlier routine bovine-derived multi-component fortification once the infant has reached 120ml/kg/day of enteral feed from the first day of life and an exclusive human milk diet with routine bovine-derived multi-component fortification of 120 mL/kg/day. RESULTS After the intervention, growth velocity between birth and 28 days increased from 9.7 ± 4.1 to 12.2 ± 4.6 g/kg/day (mean ± standard deviation), and weight z score change decreased from -1.06 ± 0.56 to -0.76 ± 0.59 (P

Knowledge of the pathological instabilities in the breathing pattern can provide valuable insights into the cardiorespiratory status of the critically-ill infant as well as their maturation level. This paper is concerned with the measurement of respiratory rate in premature infants. We compare the rates estimated from the chest impedance pneumogram, the ECG-derived respiratory rhythms, and the PPG-derived respiratory rhythms against those measured in the reference standard of breath detection provided by attending clinical staff during 165 manual breath counts. We demonstrate that accurate RR estimates can be produced from all sources for RR in the 40-80 bpm (breaths per min) range. We also conclude that the use of indirect methods based on the ECG or the PPG poses a fundamental challenge in this population due to their poor behavior at fast breathing rates (upward of 80 bpm).

AimsWe aim to evaluate the efficacy and safety of Numeta G13%E preterm neonatal parenteral nutrition (PN) in our neonatal population.In September 2017 a National Patient Safety Alert (NPSA) highlighted the risk of harm to babies when lipid was mistakenly run at the rate intended for the aqueous component resulting in significant lipid overdose.Although we have worked to implement many of the alert’s recommendations, we feel we can avoid this risk further by using an all-in-one PN solution.1Numeta meets current nutritional guidelines as per British Association of Perinatal Medicine (BAPM) but this project allows comparison of outcomes important to both patient and service between those achieved with our current regimen and those with the all-in-one regimen.2MethodsWe carried out a quality improvement project from April 2018 to April 2019. We collected data from 330 babies in our neonatal unit during six months before (154 babies) and after (176 babies) the adoption of the all-in-one solution.Our previous PN regimen consisted of a ‘menu’ of aqueous bags (starter, maintenance, ‘light’ and bespoke) and a separate lipid solution. All of them were suitable for peripheral or central administration. Numeta came with similar choices: starter, maintenance -for central administration only- and ‘lite’ and Numeta peripheral, suitable for peripheral administration. Bespoke bags were also available if clinically indicated. We set out our desired outcomes and measured parameters accordingly:Patient outcomesMetabolic stability: electrolyte, glucose, bilirubin and lipid measurements summarised by the need to change from standard PN regimen and/or requirement for insulin.Fluid balance summarised by the lowest weight during the first two weeks of life and time taken to regain birth weight.Growth summarised by change of standard deviation score of weight and head circumference between birth and discharge or transfer back to local hospital.Liver tolerance of lipid solutions summarised by incidence of cholestasis (>25 μmol/l conjugated fraction of serum bilirubin)Days and type of PNSepsisService outcomesNursing time taken to prepare PNCostWastageAccess to productResultsAlthough we finished collecting the data in April 2019, we are still in the process of analysing it and evaluating the final results. There have been no cases of lipid overdose and our neonates (including the preterm ones) have so far tolerated well the new parenteral nutrition solution. Average nursing time preparing Numeta went down from 18.5 minutes to 8 minutes and comparison of cost came in favour of Numeta. PN wastage was higher with Numeta (4.7% Maintenance, 10% ‘light’, peripheral 50%) especially in the first month during the transition phase. There was no significant increase of bespoke bags when Numeta was introduced.ConclusionsIn summary, so far we have not identified significant clinical differences between the first six months of the project -using our old standardised nutrition regimen- and the last months -on the new all-in-one solution. We have continued with Numeta preterm solution on the basis of assumed safety.ReferencesRisk of severe harm and death from infusing total parenteral nutrition too rapidly in babies. NHS improvement patient safety alert September 2017.The Provision of Parenteral Nutrition within Neonatal Services – A Framework for Practice. British Association of Perinatal Medicine (BAPM) April 2016 www.bapm.org

Non-contact vital-sign estimation allows the monitoring of physiological parameters (such as heart rate, respiratory rate, and peripheral oxygen saturation) without contact electrodes or sensors. Our recent work has demonstrated that a convolutional neural network (CNN) can be used to detect the presence of a patient and segment the patient’s skin area for vital-sign estimation, thus enabling the automatic continuous monitoring of vital signs in a hospital environment. In a study approved by the local Research Ethical Committee, we made video recordings of pre-term infants nursed in a Neonatal Intensive Care Unit (NICU) at the John Radcliffe Hospital in Oxford, UK. We extended the CNN model to detect the head, torso and diaper of the infants. We extracted multiple photoplethysmographic imaging (PPGi) signals from each body part, analysed their signal quality, and compared them with the PPGi signal derived from the entire skin area. Our results demonstrated the benefits of estimating heart rate combined from multiple regions of interest using data fusion. In the test dataset, we achieved a mean absolute error of 2.4 beats per minute for 80% (31.1 hours) from a total recording time of 38.5 hours for which both reference heart rate and video data were valid.

Background Heart rate variability (HRV) has emerged as a predictor of later cardiac risk. This study tested whether pregnancy complications that may have long-term offspring cardiac sequelae are associated with differences in HRV at birth, and whether these HRV differences identify abnormal cardiovascular development in the postnatal period. Methods Ninety-eight sleeping neonates had 5-min electrocardiogram recordings at birth. Standard time and frequency domain parameters were calculated and related to cardiovascular measures at birth and 3 months of age. Results Increasing prematurity, but not maternal hypertension or growth restriction, was associated with decreased HRV at birth, as demonstrated by a lower root mean square of the difference between adjacent NN intervals (rMSSD) and low (LF) and high-frequency power (HF), with decreasing gestational age (p Conclusions Altered cardiac autonomic function at birth relates to prematurity rather than other pregnancy complications and does not predict cardiovascular developmental patterns during the first 3 months post birth. Long-term studies will be needed to understand the relevance to cardiovascular risk.

Preterm-born individuals have elevated blood pressure. We tested the hypothesis that this associates with an enhanced antiangiogenic circulating profile and that this association is mediated by variations in capillary density. We studied 204 adults aged 25 years (range, 20–30 years), of which 102 had been followed up prospectively since very preterm birth (mean gestational age, 30.3±2.5 weeks) and 102 were born term to uncomplicated pregnancies. A panel of circulating biomarkers, including soluble endoglin and soluble fms-like tyrosine kinase-1, were compared between groups and related to perinatal history and adult cardiovascular risk. Associations with cardiovascular phenotype were studied in 90 individuals who had undergone detailed assessment of microvascular, macrovascular, and cardiac structure and function. Preterm-born individuals had elevations in soluble endoglin (5.64±1.03 versus 4.06±0.85 ng/mL; P P P P =0.002). Other circulating biomarkers, including those of inflammation and endothelial activation, were not related to blood pressure. There was a specific graded association between soluble endoglin and degree of functional and structural capillary rarefaction ( P =0.002 and P

Experimental and clinical studies show that prematurity leads to altered left ventricular (LV) structure and function with preserved resting LV ejection fraction (EF). Large-scale epidemiological data now links prematurity to increased early heart failure risk.The authors performed echocardiographic imaging at prescribed exercise intensities to determine whether preterm-born adults have impaired LV functional response to physical exercise.We recruited 101 normotensive young adults born preterm (n = 47; mean gestational age 32.8 ± 3.2 weeks) and term (n = 54) for detailed cardiovascular phenotyping. Full clinical resting and exercise stress echocardiograms were performed, with apical 4-chamber views collected while exercising at 40%, 60%, and 80% of peak exercise capacity, determined by maximal cardiopulmonary exercise testing.Preterm-born individuals had greater LV mass (p = 0.015) with lower peak systolic longitudinal strain (p = 0.038) and similar EF to term-born control subjects at rest (p = 0.62). However, by 60% exercise intensity, EF was 6.7% lower in preterm subjects (71.9 ± 8.7% vs 78.6 ± 5.4%; p = 0.004) and further declined to 7.3% below the term-born group at 80% exercise intensity (69.8 ± 6.4% vs 77.1 ± 6.3%; p = 0.004). Submaximal cardiac output reserve was 56% lower in preterm-born subjects versus term-born control subjects at 40% of peak exercise capacity (729 ± 1,162 ml/min/mPreterm-born young adults had impaired LV response to physiological stress when subjected to physical exercise, which suggested a reduced myocardial functional reserve that might help explain their increased risk of early heart failure. (Young Adult Cardiovascular Health sTudy [YACHT]; NCT02103231).

There is no consensus regarding how the growth of preterm infants should be monitored or what constitutes their ideal pattern of growth, especially after term-corrected age. The concept that the growth of preterm infants should match that of healthy fetuses is not substantiated by data and, in practice, is seldom attained, particularly for very preterm infants. Hence, by hospital discharge, many preterm infants are classified as postnatal growth–restricted. In a recent systematic review, 61 longitudinal reference charts were identified, most with considerable limitations in the quality of gestational age estimation, anthropometric measures, feeding regimens, and how morbidities were described. We suggest that the correct comparator for assessing the growth of preterm infants, especially those who are moderately or late preterm, is a cohort of preterm newborns (not fetuses or term infants) with an uncomplicated intrauterine life and low neonatal and infant morbidity. Such growth monitoring should be comprehensive, as recommended for term infants, and should include assessments of postnatal length, head circumference, weight/length ratio, and, if possible, fat and fat-free mass. Preterm postnatal growth standards meeting these criteria are now available and may be used to assess preterm infants until 64 weeks’ postmenstrual age (6 months’ corrected age), the time at which they overlap, without the need for any adjustment, with the World Health Organization Child Growth Standards for term newborns. Despite remaining nutritional gaps, 90% of preterm newborns (ie, moderate to late preterm infants) can be monitored by using the International Fetal and Newborn Growth Consortium for the 21st Century Preterm Postnatal Growth Standards from birth until life at home.

An abnormal respiratory rhythm is an early indicator of physiological deterioration. It is of critical importance in the clinical management of critically-ill or premature infants, for whom apnoea of prematurity is a major concern. Nevertheless, respiratory signals are still largely disregarded in neonatal intensive care units due to the high prevalence of noise and high false alarm rates in conventional monitoring. To address this, we present a novel method for the extraction of respiration from camera-based measurements taken from the top-view of an incubator. A total of 107 events from 30 neonatal admissions were annotated by three clinical reviewers as either true cessations of breathing (physiologically relevant) or false (artefact-related). The events were divided into two independent groups for training and validation and our algorithm was trained to classify true cessations. We achieved a good classification performance with 9 out of 10 cessations and 7 out of 10 artefactual events correctly identified in the training set, and with 7 out of 10 cessations and 34 out of 44 artefactual events correctly identified in the out-of-sample test set. A reduction in false alarm rate of 77.3% was achieved.

Patient detection and skin segmentation are important steps in non-contact vital sign monitoring as skin regions contain pulsatile information required for the estimation of vital signs such as heart rate, respiratory rate and peripheral oxygen saturation (SpO 2 ). Previous methods based on face detection or colour-based image segmentation are less reliable in a hospital setting. In this paper, we develop a multi-task convolutional neural network (CNN) for detecting the presence of a patient and segmenting the patient’s skin regions. The multi-task model has a shared core network with two branches: a segmentation branch which was implemented using a fully convolutional network, and a classification branch which was implemented using global average pooling. The whole network was trained using images from a clinical study conducted in the neonatal intensive care unit (NICU) of the John Radcliffe hospital, Oxford, UK. Our model can produce accurate results and is robust to changes in different skin tones, pose variations, lighting variations, and routine interaction of clinical staff.

Current technologies to allow continuous monitoring of vital signs in pre-term infants in the hospital require adhesive electrodes or sensors to be in direct contact with the patient. These can cause stress, pain, and also damage the fragile skin of the infants. It has been established previously that the colour and volume changes in superficial blood vessels during the cardiac cycle can be measured using a digital video camera and ambient light, making it possible to obtain estimates of heart rate or breathing rate. Most of the papers in the literature on non-contact vital sign monitoring report results on adult healthy human volunteers in controlled environments for short periods of time. The authors' current clinical study involves the continuous monitoring of pre-term infants, for at least four consecutive days each, in the high-dependency care area of the Neonatal Intensive Care Unit (NICU) at the John Radcliffe Hospital in Oxford. The authors have further developed their video-based, non-contact monitoring methods to obtain continuous estimates of heart rate, respiratory rate and oxygen saturation for infants nursed in incubators. In this Letter, it is shown that continuous estimates of these three parameters can be computed with an accuracy which is clinically useful. During stable sections with minimal infant motion, the mean absolute error between the camera-derived estimates of heart rate and the reference value derived from the ECG is similar to the mean absolute error between the ECG-derived value and the heart rate value from a pulse oximeter. Continuous non-contact vital sign monitoring in the NICU using ambient light is feasible, and the authors have shown that clinically important events such as a bradycardia accompanied by a major desaturation can be identified with their algorithms for processing the video signal.

Background Adults born very preterm have increased cardiac mass and reduced function. We investigated whether a hypertrophic phenomenon occurs in later preterm infants and when this occurs during early development. Methods Cardiac ultrasound was performed on 392 infants (33% preterm at mean gestation 34±2 weeks). Scans were performed during fetal development in 137, at birth and 3 months of postnatal age in 200, and during both fetal and postnatal development in 55. Cardiac morphology and function was quantified and computational models created to identify geometric changes. Results At birth, preterm offspring had reduced cardiac mass and volume relative to body size with a more globular heart. By 3 months, ventricular shape had normalized but both left and right ventricular mass relative to body size were significantly higher than expected for postmenstrual age (left 57.8±41.9 vs. 27.3±29.4%, P

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.

Background— Young adults born preterm have distinct differences in left ventricular mass, function, and geometry. Animal studies suggest that cardiomyocyte changes are evident in both ventricles after preterm birth; therefore, we investigated whether these young adults also have differences in their right ventricular structure and function. Methods and Results— We studied 102 preterm-born young adults followed up prospectively since birth and 132 term-born control subjects born to uncomplicated pregnancies. We quantified right ventricular structure and function by cardiovascular magnetic resonance on a 1.5-T Siemens scanner using Argus and TomTec postprocessing software. Preterm birth was associated with a small right ventricle (end diastolic volume, 79.8±13.2 versus 88.5±11.8 mL/m 2 ; P 2 ; P r =−0.47, P P =0.006). Indeed, 21% had values below the lower limit observed in the term-born adults and 6% had mild systolic dysfunction ( Conclusions— Preterm birth is associated with global myocardial structural and functional differences in adult life, including smaller right ventricular size and greater mass. The changes are greater in the right ventricle than previously observed in the left ventricle, with potentially clinically significant impairment in right ventricular systolic function.

We have shown that preterm infants fed a preterm formula grow better than those fed a standard term infant formula after hospital discharge. The purpose of this follow-up study was to determine whether improved early growth was associated with later growth and development. Preterm infants (< or =1750 g birth weight, < or =34 wk gestation) were randomized to be fed either a preterm infant formula (discharge to 6 mo corrected age), or a term formula (discharge to 6 mo), or the preterm (discharge to term) and the term formula (term to 6 mo). Anthropometry was performed at 12 wk and 6, 12, and 18 mo. Mental and psychomotor development were assessed using the Bayley Scales of Infant Development II at 18 mo. Differences in growth observed at 12 wk were maintained at 18 mo. At 18 mo, boys fed the preterm formula were 1.0 kg heavier, 2 cm longer, and had a 1.0 cm greater occipitofrontal circumference than boys fed the term formula. Boys fed the preterm formula were also 600 g heavier and 2 cm longer than girls fed the preterm formula. However, no differences were noted in MDI or PDI between boys fed the preterm formula and boys fed the term formula or between the boys fed preterm formula and girls fed the preterm formula. Overall, boys had significantly lower MDI than girls (mean difference, 6.0; p < 0.01), primarily reflecting lower scores in boys fed the term formula. Thus, early diet has long-term effects on growth but not development at 18 mo of age. Sex remains an important confounding variable when assessing growth and developmental outcome in these high-risk infants.

Background— Preterm birth leads to an early switch from fetal to postnatal circulation before completion of left ventricular in utero development. In animal studies, this results in an adversely remodeled left ventricle. We determined whether preterm birth is associated with a distinct left ventricular structure and function in humans. Methods and Results— A total of 234 individuals 20 to 39 years of age underwent cardiovascular magnetic resonance. One hundred two had been followed prospectively since preterm birth (gestational age=30.3±2.5 week; birth weight=1.3±0.3 kg), and 132 were born at term to uncomplicated pregnancies. Longitudinal and short-axis cine images were used to quantify left ventricular mass, 3-dimensional geometric variation by creation of a unique computational cardiac atlas, and myocardial function. We then determined whether perinatal factors modify these left ventricular parameters. Individuals born preterm had increased left ventricular mass (66.5±10.9 versus 55.4±11.4 g/m 2 ; P r = −0.22, P =0.03). Preterm-born individuals had short left ventricles with small internal diameters and a displaced apex. Ejection fraction was preserved ( P >0.99), but both longitudinal systolic (peak strain, strain rate, and velocity, P P P =0.05 and P =0.006; net twist angle, P =0.02) movement were significantly reduced. A diagnosis of preeclampsia during the pregnancy was associated with further reductions in longitudinal peak systolic strain in the offspring ( P =0.02, n=29). Conclusions— Individuals born preterm have increased left ventricular mass in adult life. Furthermore, they exhibit a unique 3-dimensional left ventricular geometry and significant reductions in systolic and diastolic functional parameters. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01487824.

BACKGROUND AND OBJECTIVE: Preeclampsia is an independent cardiovascular risk factor for the mother, and recent studies reveal that offspring of affected pregnancies also may have an increased cardiovascular risk. Our objective was to examine evidence for increased cardiovascular risk factors in children exposed to preeclampsia in utero. METHODS: We performed a systematic review and meta-analysis on studies reporting traditional cardiovascular risk factors in those exposed to preeclampsia compared to controls. Information was extracted on the classic cardiovascular risk factors, including blood pressure, lipid profile, glucose metabolism, and BMI from articles published between 1948 and August 2011 in Medline and Embase. RESULTS: Eighteen studies provided cumulated data on 45 249 individuals. In utero exposure to preeclampsia was associated with a 2.39 mm Hg (95% confidence interval: 1.74–3.05; P < .0001) higher systolic and a 1.35 mm Hg (95% confidence interval: 0.90–1.80; P < .00001) higher diastolic blood pressure during childhood and young adulthood. BMI was increased by 0.62 kg/m2 (P < .00001). Associations were similar in children and adolescents, for different genders, and with variation in birth weight. There was insufficient evidence to identify consistent variation in lipid profile or glucose metabolism. CONCLUSIONS: Young offspring of pregnancies complicated by preeclampsia already have increased blood pressure and BMI, a finding that may need to be considered in future primary prevention strategies for cardiovascular disease.

Parenteral nutrition (PN) is an important and widely used component in the care of neonates and children when gastrointestinal immaturity or disease precludes nutritional needs being met via the enteral route. The process of providing PN is complex, technically demanding, requires skill and judgement, and is fraught with the risk of complications. The National Confidential Enquiry into Patient Outcome and Death (NCEPOD), an independent charity, has recently completed a case-based observational peer review of PN clinical practice in England, Wales and Northern Ireland—the first large-scale review of this type conducted in the UK.1 Based on the findings of the studies undertaken, NCEPOD makes recommendations to clinicians and management aimed at improving the quality of patient care. While undoubtedly this current report identifies evidence of good clinical practice it also highlights deficiencies that need careful evaluation by the healthcare community. Patients of all ages who received PN between 1 January and 31 March 2008 were identified from local pharmacy records in hospitals in England, Wales and Northern Ireland and Offshore Islands. A random selection of these cases was chosen for inclusion using Access (Microsoft, Redmond, Washington). For each patient a confidential questionnaire was sent to the consultant in charge with a limit of two cases per consultant. The questionnaire was returned to NCEPOD with copied extracts of the case notes. The case notes were anonymised and peer-reviewed by a multidisciplinary group of advisors. For neonates and children, this group comprised neonatologists, gastroenterologists, dietitians, nutrition nurses and clinical pharmacists. A total of 1211 cases were reviewed: 877 adults, 70 children and 264 neonates. Much of the report focuses on PN in neonatal practice. Overall ‘good practice’ in PN care, defined for the Advisors as a ‘standard that you would accept from yourself, your trainees and your institution,’ was identified in only …

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

Aim The aim of this study is to prospectively assess the effect of using standardised parenteral nutrition (TPN) in comparison to individualised TPN in neonates managed postoperatively for gastroschisis. Method All neonates who had undergone surgical management for gastroschisis and received TPN were included in the study. Data was taken from a database system registered as a service evaluation tool with the local hospital. Data on sixty one neonates (born with gastroschisis between Jan 2009 to Jun 2014) was recorded of which 30 had been on individualised TPN and 31 on standardised TPN. The standardised TPN was introduced as an equal alternative option to individualised TPN beginning of Dec 2011 with a starter formulation containing lower amount of electrolytes for first two days of life and a maintenance formulation with a fixed content per 100 ml of glucose 12 g to 12.5 g and amino acid 3 g, electrolytes, trace elements and vitamins. A standardised SMOF-lipid formulation with fat soluble vitamins was provided in a separate bag. The standardised TPN formulation had a stability of 21days, and was accessible on the ward 24 hours a day, 7 days a week. All neonates (33 boys and 28 girls) had treatment with the above TPN (standardised 885 TPN days, median 15 days (range 7–66 days) of a total 1823 TPN days for a median of 30 days (range 7–199 days). The treatment started at median postnatal age of 24 hours (1 to 3 days). The median post-conceptual age was 35 weeks (28 to 37 weeks) and median birth weight was 2 kg (1.0 to 3.46 kg). All neonates were monitored for continuous regular weight gain. All the babies were also initially on antibiotics. 14 babies were on Intralipid (from which later 9 have been switched to Clinoleic, and 4 to SMOF), 2 on Clinoleic, and 45 on SMOF as lipid source. Results from routine blood samples for electrolytes, alanine transferase (ALT), alkaline phosphatase (ALP), bilirubin, albumin, raised C reactive protein (CRP) and blood stream infections were documented from the day of TPN initiation up to the establishing of oral feeds. Results Five (17%) neonates on standardised TPN needed to be managed temporarily with individualised TPN formulation (mean 4 days, range 1–14 days). 12 (19.6%) temporarily had a growth of an organism (8 with coagulase negative staphylococcus) in the blood stream (5 on standardised TPN). 23 (37%) neonates had temporarily raised CRP (equal number on standardised and individual TPN). 5 (8%) had temporarily increased ALT (3 on standardised TPN). ALP increased during the TPN course for all neonates, 10 (17%) beyond the factor of 4 (equal number on standardised and individual TPN, mean 7.6 range 4.4–11.8). One neonate had brief post-operative acute renal impairment but not related to TPN. Levels for sodium, potassium, phosphate, urea and albumin have not been significantly out of normal range for age for any neonate during the management with either individualised or standardised TPN. 8 (13%) had increasing bilirubin (>100umol/L) after first week (equal number on standardised and individual TPN). Conclusion Standardised parenteral nutrition provision in neonates managed postoperatively for gastroschisis is a promising safe option and does not seem to adversely affect monitored parameters any more than individualised TPN.

The objective of this study was to compare formula intake, the time of weaning, and growth in preterm infants (or = 1750-g birth weight,or = 34-wk gestation) fed a standard term or preterm infant formula after initial hospital discharge. Infants were randomized at hospital discharge to be fed a preterm infant formula from discharge to 6 mo corrected age (group A), a term formula from discharge to 6 mo (group B), or the preterm formula (discharge to term) and the term formula (term to 6 mo (group C). Infants were seen biweekly (discharge to term) and monthly (term to 6 mo), when intake was measured and anthropometry and blood sampling were performed. The results were analyzed using ANOVA. Although nutrient intake was similar, at 6 mo girls were lighter (6829 versus 7280 g) and shorter (64.4 versus 66.0 cm) than boys (p0.05). Patient characteristics were similar between the treatment groups. Although the volume of intake differed (BCA; p0.001), energy intake was similar in the groups. Because of differences in formula composition, protein, calcium, and phosphorus intakes differed (BCA; p0.001). Lower protein intakes were related to lower blood urea nitrogen levels (BCA; p0.001). At 6 mo, infant boys in B and C were lighter (6933, 66607949 g), shorter (65.3, 64.967.1 cm), and had a smaller head circumference (43.7, 43.744.8 cm; p0.05) than infants in group A. Preterm infants were found to increase their volume of intake to compensate for differences in energy density between formulas. After hospital discharge, infant boys fed a preterm formula grew faster than infant girls fed a preterm formula or infant boys fed a term formula.

Background Abnormal antenatal Dopplers with intrauterine growth restriction (IUGR) are associated with increased adverse outcomes in premature infants. Anxiety about necrotising enterocolitis (NEC) often results in delay in enteral feeding. Babies of less than 35-week gestation with IUGR and abnormal antenatal Dopplers were randomised to early (24–48 h) or late (120–144 h) initiation of milk feeds, with protocol for increasing feed volume the same in both groups. Data collected included daily milk intake, evidence of gut pathology, sepsis and need for parenteral nutrition. Primary end points were days to full feeds (150 ml/kg/day) sustained for 3 days and NEC. Secondary end points included death, sepsis, growth and duration of parenteral nutrition and hospital stay.1 Results 404 babies were randomised – 202 in each group. Data are presented on 372 completed outcome sets to date. Conclusion Preterm infants with absent or reversed end-diastolic flow velocity on umbilical Doppler who were fed on Day 2 of life achieved full feeds earlier than those commenced on Day 6, with no difference in the incidence of NEC or sepsis.

Aim Pregnancies complicated by abnormal antenatal Doppler blood flow often result in the preterm delivery of a growth restricted baby. These babies have a high risk of milk intolerance and necrotising enterocolitis (NEC), and introduction of milk feeds is frequently delayed. The authors9 aim was to determine the effect of early or late introduction on the time to successful establishment of full enteral feeding and on adverse outcomes including NEC. Methods Babies with birth weight below 10th centile and gestation below 34+6 weeks, born after abnormal antenatal Dopplers, were randomised between 20 and 48 h to either early (24–48 h) or late (120–144 h) introduction of milk feeds. Written, informed parental consent was obtained. Babies with major congenital anomaly, in utero transfusion, multiorgan failure or need for inotropes were excluded. Feed volumes and rate of increase were standardised and were the same for both groups. Daily feed logs were kept. Results 404 babies were randomised from 54 hospitals in the UK and Ireland (202 in each group) between 1 April 2006 and 31 May 2009. There were no important differences between groups at randomisation. Outcome data have been received on 372 babies to date and are presented below. Conclusion Growth-restricted preterm infants born after absent or reversed end-diastolic flow in the umbilical artery who are fed from the second day after birth achieve full feeds earlier than those commencing feeds on day 6. No difference has been seen to date in the incidence of NEC or sepsis.

Feeding Preterm Infants After Hospital Discharge: 2. Effect of Diet on Nutrient Intake and Body Composition 1507a

Feeding Preterm Infants After Hospital Discharge: 1. Effect of Diet on Nutrient Intake and Growth 1507