High Early Parenteral Lipid in Very Preterm Infants: A Randomized-Controlled Trial.

OBJECTIVE: To determine whether high early parenteral soybean oil lipid intake in very low birth weight (VLBW) infants in the first week after birth decreases the proportion of weight loss and subsequently the incidence of extrauterine growth restriction (EUGR). STUDY DESIGN: This was a randomized controlled trial of appropriate for gestational- ge VLBW infants. Lipid intake in the control group started at 0.5-1 g/kg per day and increased daily by 0.5-1 g/kg per day till reaching 3 g/kg per day. The intervention group was started on 2 g/kg per day that increased to 3 g/kg per day the following day. RESULTS: Of the 176 infants assessed for eligibility, 83 were included in the trial. Infants in the intervention group were started on lipid sooner (13.8 ± 7.8 vs 17.5 ± 7.8 hour; P = .03) and had higher cumulative lipid intake in the first 7 days of age (13.5 ± 4.2 vs 10.9 ± 3.5 g/kg per day; P = .03). Infants in the intervention group had a lower percentage of weight loss (10.4 vs 12.7%; P = .02). The mean triglyceride level was higher in the intervention group (1.91 ± 0.79 vs 1.49 ± 0.54 mmol/L; P = .01), however, hypertriglyceridemia was similar between the 2 groups. The incidence of EUGR was lower in the intervention group (38.6% vs 67.6%; P = .01). Head circumference z score was higher in the intervention group (-1.09 ± 0.96 vs -1.59 ± 0.98; P = .04). CONCLUSIONS: In VLBW infants, provision of a high early dose of parenteral lipid in the first week of age results in less weight loss and lower incidence of EUGR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03594474.

A clinical audit of the growth of preterm infants fed predominantly pasteurised donor human milk v. those fed mother's own milk in the neonatal intensive care unit.

Preterm infants whose mothers are unable to produce sufficient breast milk are increasingly being supplemented with pasteurised donor human milk (PDHM) instead of commercial preterm infant formula. Concerns have been raised that this practice can result in reduced growth. This retrospective clinical audit collected data from the medical records of a cohort of preterm infants (≤30 weeks gestational age) receiving either ≥28 d of PDHM (n 53) or ≥28 d of their mother's own milk (MOM, n 43) with standard fortification supplied to both groups during admission. Weight growth velocity was assessed from regained birth weight to 34+1 weeks' postmenstrual age (PMA); and weight, length and head circumference were compared at discharge and 12 months (corrected age). At 34+1 weeks' PMA, the weight growth velocity (g/kg per d) was significantly lower in the PDHM group (15·4 g/kg per d, 95 % CI 14·6, 16·1) compared with the MOM group (16·9 g/kg per d, 95 % CI 16·1, 17·7, P=0·007). However, the increase was still within clinically acceptable limits (>15 g/kg per d) and no significant difference was observed in the weight between the two groups. There was no significant difference in weight between the groups at discharge or at the 12-month corrected gestational age review. Although we demonstrated a significant reduction in the weight growth velocity of preterm infants receiving PDHM at 34 weeks' PMA, this difference is not present at discharge, suggesting that the growth deficit is reduced by supplementation before discharge.

Body length and occipitofrontal circumference may be good indicators of neurodevelopment in very low birthweight infants - secondary publication.

AIM: The aim of this study was to predict the neurological prognosis of very low birthweight (VLBW) infants. We examined the relationship between nutritional status, brain volume measured by magnetic resonance imaging (MRI) and anthropometric measurements of VLBW infants at term-equivalent age (TEA). METHODS: We evaluated 27 VLBW infants, born at Showa University Hospital in Japan between April 2012 and August 2013, who underwent brain MRI at TEA. Based on their clinical data, we analysed their protein and energy intake. RESULTS: Median values for the 27 VLBW infants were as follows: gestational age, 29.7 weeks; birthweight 1117 g; protein intake 2.7 g/kg/day and energy intake 97.9 kcal/kg/day. At TEA, the standard deviation scores (SDSs) of body weight, body length and the occipitofrontal circumference (OFC) were -0.8, -1.4 and 0.7, respectively. Multiple regression analysis revealed that the SDSs of body length and the OFC at TEA were significant determinants of white matter volume, but that the SDS of body weight at TEA was not. CONCLUSION: Our findings suggest that the SDSs of body length and the OFC at TEA may be better indicators than body weight for predicting the development of the central nervous system in VLBW infants receiving nutritional management.

Nutritional intake and growth velocity in preterm extremely low-birthweight infants in Asia: Are we doing enough?

AIM: To describe nutritional practices among preterm extremely low-birthweight (ELBW) infants and their impact on growth and to compare differences in nutritional intervention and comorbidities between those with limited growth velocity (GV < 25th percentile) and those with GV > 25th percentile. METHODS: A prospective cohort study was conducted to assess total protein and energy intake for week 1, days 14, 21 and 28 of life. Post-natal growth was calculated by measuring GV using an exponential model. Univariable analysis was applied to identify the potential risk factors associated with poor GV at day 28 and at discharge from hospital. RESULTS: The median GV from birth to day 28 was 9.84 g/kg/day and 11.87 g/kg/day for GV from birth to discharge. Increased protein and energy intake was associated with higher GV at discharge. Hypotension needing inotropes, necrotising enterocolitis (NEC), patent ductus arteriosus and chronic lung disease were significantly associated with reduced GV at discharge. Infants with NEC, hypotension needing inotropes and sepsis took a significantly longer time to achieve full enteral nutrition. A longer time to attain full enteral feeds was associated with slower GV at discharge. Small-for-gestational-age babies increased from 22% at birth to 66.6% at discharge. CONCLUSIONS: GV at discharge was positively correlated with increasing protein and energy intake in the first 28 days and adversely affected by the presence of neonatal morbidities. There was strong evidence of extra-uterine growth restriction, with the majority of preterm ELBW infants having lower z scores at discharge compared to at birth.

An anthropometric survey of US pre-term and full-term neonates.

BACKGROUND: Anthropometric data prove valuable for screening and monitoring various medical conditions. In young infants, however, only weight, length and head circumference are represented in publicly accessible databases. AIM: To characterise length and circumferential measures in pre-term and full-term infants up to 90 days post-natal. SUBJECTS AND METHODS: In eight US medical centres, trained raters recorded humeral, ulnar, femoral, tibial and fibular lengths along with mid-upper arm, mid-thigh, chest, abdominal and neck circumference. Data were pooled by post-menstrual age into 1-week intervals and population curves created using the lambda, mu and sigma (LMS) method. Goodness-of-fit was assessed by examining de-trended quantile-quantile plots, Q statistics and fitted centiles overlaid on empirical centiles. RESULTS: In total, 2097 infants were enrolled in this study with a mean ± SD gestational age and post-natal age of 37.1 ± 3.3 weeks and 27.3 ± 25.3 days, respectively. A re-scale option was used to describe all curves. The resultant models reliably characterised anthropometric measures from 33-52 weeks PMA, with less certainty at the extremes (27-55 weeks). CONCLUSION: The population curves generated under this investigation expand existing reference data on a comprehensive set of anthropometric traits in infants through the first 90 days post-natal.

Extrauterine growth and adipocytokines in appropriate-for-gestational-age preterm infants.

BACKGROUND: Extra-uterine growth retardation in preterm infants is associated with an increased risk for cardiometabolic diseases later in life. Adipocytokines are also associated with the development of cardiometabolic diseases. We examined the relationship between extra-uterine growth and serum concentrations of adipocytokines and metabolic hormones in preterm infants. METHODS: Serum concentrations of leptin, adiponectin, insulin, IL-6, TNF-α, C-peptide, GIP, GLP-1 and glucagon were measured in 38 appropriate-for-gestational-age preterm infants at birth, and at 33 and 38 weeks of postmenstrual age using a Bio-Plex 200TM suspension array system. RESULTS: Serum concentrations of leptin were not correlated with body weight at any time point. However, serum concentrations of adiponectin were correlated with body weight at all time points. Serum concentrations of IL-6 were decreased from birth to 33 and 38 weeks. Serum concentrations of TNF-α were not changed. Serum concentrations of C-peptide, GIP and glucagon increased from birth to 33 weeks, and decreased from 33 to 38 weeks. Serum concentrations of insulin and GLP-1 were not changed. CONCLUSION: Changes in serum concentrations of leptin and adiponectin showed unique profiles, thereby suggesting maldevelopment of white adipose tissue. This may affect the future development of adipose tissue and lead to increased risk for cardio-metabolic disorders. This article is protected by copyright. All rights reserved.

Early Extra-Uterine Growth Restriction in Very-Low-Birth-Weight Neonates with Normal or Mildly Abnormal Brain MRI: Effects on a 2-3-Year Neurodevelopmental Outcome.

Extra-uterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very-low-birth-weight (VLBW) neonates. We report a population of 288 patients with no or with low-grade MRI lesions scanned at a term equivalent age (TEA) born between 2012 and 2018. Griffiths Mental Development Scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analyzed. EUGR was defined for weight z-score ˂ 10 percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point standard deviation (SDS) from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for the global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59-0.93; p = 0.01). EUGR at 6 months was associated with worse locomotor, personal/social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion, a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest that we should invest more into post-discharge nutrition, optimizing family nutritional education.

Improving growth in preterm infants through nutrition: a practical overview.

The primary purpose of this practical overview is to provide a practical update on appropriate nutritional strategies to improve growth in preterm infants. Current recommendations for improving preterm growth concern both macronutrients and micronutrients, with tailored nutrition since the first days of life, particularly when fetal growth restriction has been reported. Human milk is undoubtedly the best nutrition for all newborns, but, in some populations, if not adequately fortified, it does not adequately support their growth. In all preterms, growth should be correctly monitored weekly to intercept a negative trend of growth and implement nutritional strategies to avoid growth restriction. Similarly, growth should be accurately supported and monitored after discharge to improve long-term health consequences.

Does Early Fortification of Human Milk Decrease Time to Regain Birth Weight as Compared to Late Fortification Among Preterm Infants? - A Randomized Controlled Trial.

OBJECTIVES: To compare the duration required to regain birth weight following early fortification of human milk vs. late fortification among preterm infants. METHODS: This randomized controlled trial included hemodynamically stable 120 preterm infants (≤32 wk of gestation). The intervention and comparator groups received standard fortification with human milk fortifier when enteral feeds reached 30 ml/kg/d (early fortification) and 80 ml/kg/d (late fortification) respectively. Neonates in both the groups received feed increments as per standard NICU protocol. Anthropometric measurements (weight, length, and head circumference) at birth and during postnatal follow-up were done following standard precautions and plotted on the sex-specific Fenton growth charts. Primary outcome was the mean duration required to regain birth weight. Secondary outcomes included weight gain velocity, linear growth, increase in head circumference and occurrence of sepsis, feed intolerance and necrotizing enterocolitis. RESULTS: Preterm neonates who received early fortification regained birth weight earlier compared to those in the late fortification group (10.13 ± 2.90 vs. 11.26 ± 3.06, p <0.05). The weight gain velocity, linear growth and increase in head circumference were better in the early fortification group. There was no increased risk of culture proven sepsis, feed intolerance and necrotizing enterocolitis in the early fortification group compared to late fortification. CONCLUSIONS: Standard fortification with human milk fortifier when enteral feeds reach 30 ml/kg/d helps preterm neonates regain birth weight earlier. Early fortification is well tolerated and safe for the population studied.

Extrauterine Growth Restriction: Need for an Accurate Definition.

Neonates show considerable variation in growth that can be recognized through serial measurements of basic variables such as weight, length, and head circumference. If possible, measurement of subcutaneous and total body fat mass can also be useful. These biometric measurements at birth may be influenced by demographics, maternal and paternal anthropometrics, maternal metabolism, preconceptional nutritional status, and placental health. Subsequent growth may depend on optimal feeding, total caloric intake, total metabolic activity, genetic makeup, postnatal morbidities, medications, and environmental conditions. For premature infants, these factors become even more important; poor in utero growth can be an important reason for spontaneous or induced preterm delivery. Later, many infants who have had intrauterine growth restriction (IUGR) and are born small for gestational age (SGA) continue to show suboptimal growth below the 10th percentile, a condition that has been defined as extrauterine growth restriction (EUGR) or postnatal growth restriction (PNGR). More importantly, a subset of these growth-restricted infants may also be at high risk of abnormal neurodevelopmental outcomes. There is a need for well-defined criteria to recognize EUGR/PNGR, so that correctional steps can be instituted in a timely fashion.

Complex Perinatal Syndromes Affecting Early Human Growth and Development: Issues to Consider to Understand Their Aetiology and Postnatal Effects.

Complex perinatal syndromes (CPS) affecting pregnancy and childhood, such as preterm birth, and intra- and extra-uterine growth restriction, have multiple, diverse contexts of complexity and interaction that determine the short- and long-term growth, health and development of all human beings. Early in life, genetically-guided somatic and cerebral development occurs alongside a psychism "in statu nascendi," with the neural structures subjected to the effects of the intra- and extra-uterine environments in preparation for optimal postnatal functioning. Different trajectories of fetal cranial and abdominal growth have been identified before 25 weeks' gestation, tracking differential growth and neurodevelopment at 2 years of age. Similarly, critical time-windows exist in the first 5-8 months of postnatal life because of interactions between the newborn and their environment, mother/care-givers and feeding practices. Understanding these complex relational processes requires abandoning classical, linear and mechanistic interpretations that are placed in rigid, artificial biological silos. Instead, we need to conduct longitudinal, interdisciplinary research and integrate the resulting new knowledge into clinical practice. An ecological-systemic approach is required to understand early human growth and development, based on a dynamic multidimensional process from the molecular or genomic level to the socio-economic-environmental context. For this, we need theoretical and methodological tools that permit a global understanding of CPS, delineating temporal trajectories and their conditioning factors, updated by the incorporation of new scientific discoveries. The potential to optimize human growth and development across chronological age and geographical locations - by implementing interventions or "treatments" during periods of greatest instability or vulnerability - should be recognized. Hence, it is imperative to take a holistic view of reproductive and perinatal issues, acknowledging at all levels the complexity and interactions of CPS and their sensitive periods, laying the foundations for further improvements in growth and development of populations, to maximize global human potential. We discuss here conceptual issues that should be considered for the development and implementation of such a strategy aimed at addressing the perinatal health problems of the new millenium.

Challenges in the growth and development of newborns with extra-uterine growth restriction.

INTRODUCTION: Extra-uterine growth restriction (EUGR) is a condition caused by the failure of very preterm infants to reach their potential growth during the NICU hospital stay. Despite enormous improvements in nutritional support and strategies, the growth pattern of preterm infants is still far from the one expected. AREAS COVERED: This review focuses on what EUGR is, highlighting controversial aspects of this topic. EUGR is still missing a univocal definition, and the international debate is also open on what is the best growth chart to use. Moreover, professionals in NICU may not be trained on how to perform anthropometric measurements, increasing the risk of over- or underestimation, especially for length assessment. EUGR has recently been described as one of the main comorbidities in NICU, influencing growth, metabolism, and neurodevelopment later in life. EXPERT OPINION: There is still much to investigate about what the best growth pattern in the NICU should be. What is known so far is that the majority of preterm neonates develop EUGR, and this leads to several short- and long-term consequences. It is imperative that neonatologists and pediatric endocrinologists work together, to modulate growth in the NICU.

Extra-uterine growth restriction in preterm infants: Neurodevelopmental outcomes according to different definitions.

AIM: Extra-uterine Growth Restriction (EUGR) is common among preterm infants. Two types of EUGR definitions are still now available: cross-sectional definitions and longitudinal ones. In a cohort of very preterm infants, we aimed to evaluate which definition could better predict neurodevelopmental outcomes at 2 years of corrected age. We used Italian Neonatal Study Charts (INeS) growth charts and INTERGROWTH-21st (IG-21) standard charts and compared results. METHOD: We restrospectively collected data from clinical charts of 324 preterm newborns with a gestational age ≤30 weeks born from 2012 to 2017. Then we compared forty-eight definitions (24 cross-sectional and 24 longitudinal) of EUGR, in term of neurodevelopmental outcomes at 2 years of corrected age. RESULTS: We included in the study 254 preterm infants, whose clinical information met the enrolment criteria. Nineteen out of 48 definitions of EUGR were significantly predictive both for Griffith's Development Quotient (GDQ) and Neurodevelopment Impairment (NDI). Among these, longitudinal definitions appeared to have a higher negative predictive value for NDI than cross-sectional ones. Furthermore, infants with EUGR appeared to have a lower cognitive score than their peers without EUGR. INTERPRETATION: A loss of Zs > 1 SDS in weight and head circumference, calculated from when physiological weight loss is over and identified as soon as possible rather than at discharge, better predicts neurodevelopmental outcomes of preterm infants.

Crescimento de prematuros de muito baixo peso do nascimento até doze meses de idade corrigida / Growth of very low birth weight preterm until 12 months of corrected age

Facing the progressive increase in the survival of premature ta infants, a concern for health professionals would be related to the possible consequences arising from prematurity, among them the growth changes OBJECTIVES: to describe the anthropometric variables of newborns Premature Very Low Birth Weight in the follow-up monitoring METHODS: observational, longitudinal and retrospective study, involving 71 children who left Neonatal Intensive Care Unit (NICU), with a weight lower than 1500 g who were treated between 2006 and 2013. They should have at least three outpatient visits within twelve months of corrected age after NCAU discharge, in the following periods: period I up to 3 months of corrected age; period II between 4-6 months of corrected age and period III between 7-12 months of corrected age RESULTS: the mean Gestational Age (GA) was 29.4 weeks, 51% male, birth weight 1073.2 g, 70% with appropriate GA. The hospitalization stay was 68.73 days. Weight Z score at birth -0.95; at discharge -3.05; in period I -2.4; period II -1.8; period III -1.2. Height at birth -1.21, at discharge -2.23; -2.5; -1.8 and -1.1 for the periods I, II and III , respectively. Regarding the PT Z score at birth -0.71; at discharge -1.5; and monitoring -1.1; -0.8 and -0.5 respectively in the periods I, II and III CONCLUSIONS: despite of the great Z score reduction in NICU, there was a progressive improvement during follow-up in the Z score in the three anthropometric variables...

Frente ao progressivo aumento da sobrevida de recém-nascidos prematuros, uma preocupação para os profissionais de saúde deve ser em relação às possíveis sequelas advindas da prematuridade, dentre elas as alterações de crescimento OBJETIVOS: descrever variáveis antropométricas de recém-nascidos Prematuros de Muito Baixo Peso em acompanhamento de follow-up MÉTODO: estudo observacional, longitudinal e retrospectivo, em que participaram 71 crianças egressas da Unidade de Terapia Intensiva Neonatal, com peso menor de 1.500 g, atendidas entre 2006 e 2013 e, que realizaram pelo menos três consultas ambulatoriais até doze meses de Idade Corrigida (IC), nos seguintes períodos: período I (até 3 meses de IC); período II (entre 4 a 6 meses de IC) e período III (entre 7 a 12 meses de IC RESULTADOS: a Idade Gestacional média foi de 29,4 semanas, sendo 51% do sexo masculino, com peso médio de nascimento de 1073,2 g, sendo 70% adequados à IG. O tempo de internação médio foi de 68,73 dias. A média do escore Z do peso ao nascimento de -0,95; no momento da alta hospitalar, de -3,05; no período I -2,4; período II -1,8; período III -1,2. : -1,21 ao nascimento, -2,23 na alta, -2,5; -1,8 e -1,1 nos períodos I, II e III, respectivamente. Em relação ao PC: escore Z ao nascimento -0,71; alta -1,5; e seguimento -1,1; -0,8 e -0,5 respectivamente nos períodos I, II e III CONCLUSÕES: na descrição das variáveis antropométricas dos recém-nascidos prematuros durante a hospitalização até o terceiro período de seguimento observou-se retardo de crescimento extrauterino na internação e melhora progressiva nos índices de escore Z das três variáveis antropométricas durante o seguimento ambulatorial...