The role of nutritional interventions in the prevention and treatment of chronic lung disease of prematurity.

Chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Nutrition may affect incidence and severity of BPD. In this context, the Section on Nutrition, Gastroenterology and Metabolism, the Pulmonary Section of the European Society for Paediatric Research (ESPR) and SPR have joined forces to review the current knowledge on nutritional issues related to BPD. The aim of this narrative review is to discuss the clinical implications for nutritional practice. Nutrient deficiencies may influence pathogenesis of BPD. Adequate nutrition and growth can play a crucial role in the prevention of and recovery from BPD. Optimal nutrition strategy is an important principle, especially in the early postnatal period. As optimal energy intake in infants at risk of BPD or with evolving BPD is not yet defined, further research with well-designed studies on nutritional strategies for preterm infants with BPD is urgently needed. IMPACT: Based on current evidence it seems reasonable to recommend that BPD diagnosed infants should receive an energy supply ranging from 120 to 150 Kcal/kg/d. Exclusive MOM feed with adequate fortification should be encouraged as this is associated with a significant reduction in the risk of BPD. Suboptimal nutritional delivery is often seen in preterm infants with BPD compared to controls.

Nutritional interventions to prevent retinopathy of prematurity.

Very preterm infants are at high risk of growth failure. Poor weight gain is a prominent risk factor for retinopathy of prematurity (ROP) and optimizing nutrition could potentially promote growth and reduce ROP. Most infants at risk of ROP need parenteral nutrition initially and studies of enhanced parenteral provision of lipids and amino acids have suggested a beneficial effect on ROP. Higher amino acid intake was associated with lower incidence of hyperglycemia, a risk factor for ROP. For very preterm infants, providing unpasteurized fortified raw maternal breast milk appears to have a dose-dependent preventive effect on ROP. These infants become deficient in arachidonic acid (ArA) and docosahexaenoic acid (DHA) after birth when the maternal supply is lost. Earlier studies have investigated the impact of omega-3 fatty acids on ROP with mixed results. In a recent study, early enteral supplementation of ArA 100 mg/kg/d and DHA 50 mg/kg/d until term equivalent age reduced the incidence of severe ROP by 50%. IMPACT: Previous reviews of nutritional interventions to prevent morbidities in preterm infants have mainly addressed bronchopulmonary dysplasia, brain lesions and neurodevelopmental outcome. This review focusses on ROP. Neonatal enteral supplementation with arachidonic acid and docosahexaenoic acid, at levels similar to the fetal accretion rate, has been found to reduce severe ROP by 50% in randomized controlled trials.

Dietitian-nutritionist incorporation in a university hospital: position statement of the Commission on Nutrition, Hospital Universitario La Paz.

Introduction: The present document has the objective of justifying the incorporation of a dietician/nutritionist to the multidisciplinary teams of specialized care that provide education, food anamnesis, nutritional recommendations, treatment and follow up of those patients in risk of malnutrition in Madrid. The appropriate nutritional status of hospitalized patients bears a close relationship with the existence of dieticians at hospitals. Dieticians use nutrition therapy as a cost-effective means to achieve significant health benefits by preventing or altering the course of diabetes, obesity, hypertension, lipid metabolism disorders, heart failure, osteoporosis, celiac disease, and chronic kidney disease, among other diseases.

Introducción: El presente documento tiene como objetivo plantear y justificar la incorporación del dietista-nutricionista en los equipos multidisciplinares de atención integrada en la educación, el tratamiento y el seguimiento de aquellos pacientes con patologías que cursen con alteraciones del estado nutricional, tanto en su defecto como en su exceso, en el área sanitaria de la Comunidad Autónoma de Madrid. El estado nutricional de los pacientes hospitalizados se beneficiará de la incorporación del dietista-nutricionista al equipo multidisciplinar que, actualmente, se ocupa de la atención de estos. El manejo de la terapia nutricional por dietistas-nutricionistas ha demostrado ser costo-efectiva, habida cuenta de la repercusión sanitaria que tiene el estado nutricional en la evolución clínica y prevención de enfermedades como la diabetes, los trastornos de la conducta alimentaria, la obesidad, el cáncer, la insuficiencia cardiaca, la osteoporosis, la enfermedad celiaca y la enfermedad renal crónica, entre otras.

Exclusive Fish Oil Lipid Emulsion Rescue Strategy Improves Cholestasis in Neonates on Partially Fish Oil-Based Lipid Emulsion: A Pilot Study.

Resolution of parenteral nutrition-associated liver disease has been identified in infants receiving SMOFlipid™ or a 100% fish oil lipid emulsion (FOLE). However, the effect of FOLE is unknown when the previous emulsion received is a mixed lipid emulsion containing fish oil. This observational pilot study reports data regarding the use of Omegaven™ after the diagnosis of cholestasis while receiving SMOFlipid™. We conducted a retrospective review of medical charts of neonates in which a partially fish oil-based lipid emulsion was replaced by a fish oil lipid emulsion at 1 g/kg/day due to cholestasis. Thirty-eight infants (92.1% preterm, being 44.7% born below 28 weeks' gestation), received FOLE. Birth weight was 1390 (743.0; 2298) grams. The age that cholestasis diagnosed was 15.0 (10.0; 24.8) days. The fish oil emulsion was administered for 38.5 (11.2; 51.8) days. In 73.7% (28/38) of the neonates, the cholestasis was resolved. In 34.2% (13/38), resolution happened before FOLE discontinuation. In addition, in the rest of the neonates (15) in whom cholestasis resolved, resolution occurred after FOLE discontinuation. Nine of the neonates died. In conclusion, the use of a 100% fish oil-based emulsion in neonates afflicted with cholestasis developed while on a partially fish oil-based emulsion is associated with a bilirubin decrease.

Survival and Survival without Major Morbidity Seem to Be Consistently Better throughout Gestational Age in 24- to 30-Week Gestational Age Very-Low-Birth-Weight Female Infants Compared to Males.

INTRODUCTION: Several studies showed advantages in outcomes for very-low-birth-weight (VLBW) female infants. It has been suggested that recent advances in perinatal care might have benefited boys relatively more than girls, making differences disappear. OBJECTIVES: The aims of the study were (1) to determine if sex differences in survival and survival without morbidity in VLBW infants are still present in the context of more advanced perinatal care and (2) to know whether these differences are consistent throughout gestational age (GA). METHODS: Retrospective cohort study in seven countries participating in the Spanish SEN1500 and the South American NEOCOSUR neonatal networks. We included VLBW infants 24-30 weeks' GA, born alive without major congenital anomalies (2013-2016). Major morbidity, survival, and survival without morbidity were compared between male and female infants overall and stratified by GA. RESULTS: 10,565 patients were included: 5,620 (53.2%) males and 4,945 (46.8%) females. Female infants exhibited a lower incidence rate ratio (95% CI) of respiratory distress syndrome: 0.91 (0.88, 0.94), necrotizing enterocolitis: 0.83 (0.74, 0.93), major brain damage: 0.79 (0.72, 0.86), moderate-severe bronchopulmonary dysplasia (BPD): 0.77 (0.72, 0.83), higher survival: 1.03 (1.01, 1.05), survival without BPD: 1.11 (1.07, 1.16), survival without major brain damage: 1.05 (1.02, 1.08), and survival without major morbidity: 1.14 (1.07, 1.21). Survival and survival without morbidity were almost consistently favourable to females throughout GA. CONCLUSIONS: Our findings suggest that perinatal results continue to be favourable for VLBW female infants in the context of current perinatology, and that they are almost consistent throughout GA.

Gut microbes and health. / Microbiota intestinal y salud.

The human body is populated by myriads of microorganisms throughout its surface and in the cavities connected to the outside. The microbial colonisers of the intestine (microbiota) are a functional and non-expendable part of the human organism: they provide genes (microbiome) and additional functions to the resources of our species and participate in multiple physiological processes (somatic development, nutrition, immunity, etc.). Some chronic non-communicable diseases of developed society (atopias, metabolic syndrome, inflammatory diseases, cancer and some behaviour disorders) are associated with dysbiosis: loss of species richness in the intestinal microbiota and deviation from the ancestral microbial environment. Changes in the vertical transmission of the microbiome, the use of antiseptics and antibiotics, and dietary habits in industrialised society appear to be at the origin of dysbiosis. Generating and maintaining diversity in the microbiota is a new clinical target for health promotion and disease prevention.

Influence of Maternal Age and Gestational Age on Breast Milk Antioxidants During the First Month of Lactation.

Breast milk (BM) is beneficial due to its content in a wide range of different antioxidants, particularly relevant for preterm infants, who are at higher risk of oxidative stress. We hypothesize that BM antioxidants are adapted to gestational age and are negatively influenced by maternal age. Fifty breastfeeding women from two hospitals (Madrid, Spain) provided BM samples at days 7, 14 and 28 of lactation to assess total antioxidant capacity (ABTS), thiol groups, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase activities, lipid peroxidation (malondialdehyde, MDA + 4-Hydroxy-Trans-2-Nonenal, HNE), protein oxidation (carbonyl groups) (spectrophotometry) and melatonin (ELISA). Mixed random-effects linear regression models were used to study the influence of maternal and gestational ages on BM antioxidants, adjusted by days of lactation. Regression models evidenced a negative association between maternal age and BM melatonin levels (ß = -7.4 ± 2.5; p-value = 0.005); and a negative association between gestational age and BM total antioxidant capacity (ß = -0.008 ± 0.003; p-value = 0.006), SOD activity (ß = -0.002 ± 0.001; p-value = 0.043) and protein oxidation (ß = -0.22 ± 0.07; p-value = 0.001). In conclusion, BM antioxidants are adapted to gestational age providing higher levels to infants with lower degree of maturation; maternal ageing has a negative influence on melatonin, a key antioxidant hormone.

Incidence, Treatment, and Outcome Trends of Necrotizing Enterocolitis in Preterm Infants: A Multicenter Cohort Study.

Background: Data regarding the incidence and mortality of necrotizing enterocolitis trends are scarce in the literature. Recently, some preventive strategies have been confirmed (probiotics) or increased (breastfeeding rate). This study aims to describe the trends of necrotizing enterocolitis incidence, treatment, and mortality over the last decade in Spain. Methods: Multicenter cohort study with data from the Spanish Neonatal Network-SEN1500 database. The study period comprised from January 2005 to December 2017. Preterm infants <32 weeks of gestational age at birth without major congenital malformations were included for analysis. The main study outcomes were necrotizing enterocolitis incidence, co-morbidity (bronchopulmonary dysplasia, late-onset sepsis, cystic periventricular leukomalacia, retinopathy of prematurity, acute kidney injury), mortality, and surgical/non-surgical treatment. Results: Among the 25,821 included infants, NEC incidence was 8.8% during the whole study period and remained stable when comparing 4-year subperiods. However, more cases were surgically treated (from 48.8% in 2005-2008 to 70.2% in 2015-2017, p < 0.001). Mortality improved from 36.7% in the 2005-2008 to 26.6% in 2015-2017 (p < 0.001). Breastfeeding rates improved over the studied years (24.3% to 40.5%, p < 0.001), while gestational age remained invariable (28.5 weeks, p = 0.20). Prophylactic probiotics were implemented during the study period in some units, reaching 18.6% of the patients in 2015-2017. Conclusions: The incidence of necrotizing enterocolitis remained stable despite the improvement regarding protective factors frequency. Surgical treatment became more frequent over the study period, whereas mortality decreased.

[Prevention, diagnosis and treatment of necrotising enterocolitis in newborns less than 32 weeks at birth in Spain]. / Prevención, diagnóstico y tratamiento de la enterocolitis necrosante en recién nacidos menores de 32 semanas al nacimiento en España.

OBJECTIVES: To describe preventive, diagnostic and therapeutic strategies regarding necrotising enterocolitis in Spain and to identify the strengths, areas of further improvement, and future research lines. METHODS: Two questionnaires on the management of preterm infants less than 32 weeks, at risk of, or with diagnosed necrotising enterocolitis, were distributed among selected representatives of the surgeons and neonatologists of the Spanish Neonatal Network (SEN1500) participant hospitals with a Paediatric Surgery Department. RESULTS: Percentage of response was 77.1% of contacted surgeons and 88.6% of neonatologists. There is a written protocol on the diagnosis and medical management of necrotising enterocolitis in 52% of the hospitals, and as regards surgical treatment in 33%. There is wide access to donor bank milk and to staff dedicated to breastfeeding promotion (87%). On the contrary, only 52% of the centres perform delayed cord clamping, and probiotics are used in just 23%. The use of abdominal ultrasound is increasing. There are no large differences as regards duration of antibiotic use and bowel rest, whereas there was as regards antibiotic selection, surgical indication, and type of intervention. CONCLUSIONS: As regards prevention, delayed cord clamping and extended access to donor milk are two possible aspects of further improvement. The observed discrepancies noted in diagnostic and therapeutic aspects are common in precisely the areas where evidence in the literature is weakest.

The Impact of Postnatal Systemic Steroids on the Growth of Preterm Infants: A Multicenter Cohort Study.

Postnatal steroids, often used to prevent and treat bronchopulmonary dysplasia, may influence the growth of preterm infants, although data are scarce in the literature. This is a multicenter cohort study including surviving preterm infants <32 weeks at birth (n = 17,621) from the Spanish Neonatal Network SEN1500 database, without major congenital malformations. Linear regression models were adjusted for postnatal steroids, respiratory severity course (invasive mechanical ventilation at 28 days), progression to moderate-severe bronchopulmonary dysplasia (O2 at 36 weeks), length of stay, sex, gestational age and z-scores at birth. A subgroup analysis depending on the timing of administration, ventilation status at 28 days and moderate-severe BPD diagnosis was also performed. Overall, systemic postnatal steroids were not independently associated with poorer weight gain (0.1; 95% CI: -0.05 to 0.2 g/kg/day), linear growth (0; 95% CI: -0.03 to 0.01 cm/week) or head circumference growth (-0.01; 95% CI: -0.02 to 0 cm/week). Patients who received steroids after 28 days or who were not O2 dependent at 36 weeks after having received steroids gained more weight (0.22; 95% CI: 0.04 to 0.4 and 0.2; 95% CI: 0.004 to 0.5 g/kg/day, respectively). Globally, systemic postnatal steroids had no significant adjusted effect on postnatal growth.

The Effect of Morbidity and Sex on Postnatal Growth of Very Preterm Infants: A Multicenter Cohort Study.

BACKGROUND: Extrauterine growth restriction is common in the preterm infant, and it is associated with poor neurodevelopment. Nutrition plays an important role in postnatal growth, but growth is also influenced by other factors like co-morbidity, and, also, there might be sex differences. METHODS: This is a cohort study including preterm infants < 32 weeks at birth (n = 21,825) from the Spanish Neonatal Network database. The effect of sex and morbidity (patent ductus arteriosus, bronchopulmonary dysplasia, necrotizing enterocolitis and late-onset sepsis) on weight gain as well as linear and head growth from birth to discharge/death was assessed with linear regression models adjusted by gestational age and Z-scores at birth. RESULTS: The 4 selected morbidities had an independent effect on all 6 growth parameters studied, which was greater in the case of necrotizing enterocolitis: changes in weight, length and head Z-scores were -0.60 (95% CI: -0.66 to -0.55), -0.62 (95% CI: -0.70 to -0.54) and -0.63 (95% CI: -0.71 to -0.56), respectively. Weight gain and linear growth were overall more affected than head growth. Girls lost slightly more weight Z-scores (-0.03; 95% CI: -0.06 to -0.002) than boys after adjustment by morbidity. There were no significant gender differences regarding linear and head growth velocity (cm/week), although girls lost more head Z-scores (-0.14; 95% CI: -0.18 to -0.10). CONCLUSIONS: Main co-morbidities associated with prematurity have an impact on postnatal growth. Head growth is less affected than length and weight. Girls are at slightly higher risk of postnatal weight and head restriction after adjustment by morbidity.

Nutritional practices in very low birth weight infants: a national survey.

BACKGROUND: Significant efforts have been made to improve the nutritional support of very preterm infants. Large surveys may help to know the nutritional practices for preterm infants in neonatal units and identify if they are in line with the current guidelines. METHODS: A multicentre nationwide web-based survey on clinical feeding practices in very low birth weight (VLBW) infants was conducted in tertiary neonatal hospitals that admit infants with a birth weight < 1,500 g and/or a gestational age of < 32 weeks. RESULTS: The questionnaire was completed by 53 units (response rate, 59%). Over 90% of the units surveyed start amino-acid administration immediately after birth and more than half use novel intravenous fish oil-based lipid emulsions. Enteral nutrition is started within 24 hours of birth in 65% of units and 86% of these are medium-sized or large. Feeding volumes are increased at a rate of 10-30 ml/kg/day in > 90% of units. Monitoring of serum phosphorus was measured more frequently than albumin (p = 0.009) or triglycerides (p = 0.037), but only 28% of centres regularly measure pre-albumin as a nutritional biomarker. Human milk fortification and iron supplementation, starting at four weeks of age, are almost universal. However, only 30% of units administer 800 IU/day of vitamin D. Nearly 50% of the units discharge infants on preterm formula. CONCLUSION: Most Spanish neonatology units use early amino-acid supplementation and over half use novel fish oil-based lipid emulsions. Post-discharge nutrition practices and vitamin administration vary greatly.

Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism.

OBJECTIVE: To determine the influence of gestational age and fetal growth restriction on the cord blood adipokine profile, IGF1, and ghrelin levels, and their relationship with glucose metabolism. STUDY DESIGN: One hundred and ninety newborns (99 preterm and 91 full term) were studied and, according to their anthropometry at birth, classified as small (SGA) or adequate for gestational age (AGA). METHODS: Venous cord blood serum levels of IGF1, IGF binding protein 3 (IGFBP-3), adiponectin, resistin, leptin, soluble leptin receptor (sOB-R), tumoral necrosis factor-alpha, interleukin 6 (IL-6), total ghrelin, and acylated ghrelin were determined and compared between preterm and full-term, as well as between SGA and AGA, newborns. Correlations with newborn weight, gestational age, and homeostatic model assessment (HOMA) index, as an index of insulin resistance, were determined. RESULTS: Preterm newborns had higher HOMA, sOB-R, resistin, and IL-6 and lower IGF1, IGFBP-3, leptin, and adiponectin levels than full-term newborns. SGA had lower IGF1, IGFBP-3, leptin, IL-6, and adiponectin and higher sOB-R and total ghrelin than AGA newborns. Adiponectin and HOMA showed independent positive and negative correlations with gestational age respectively, but not with neonatal weight. Birth weight was correlated positively with IGF1 and leptin levels and negatively with total ghrelin ones. CONCLUSIONS: Our findings suggest that the lack of proper acquisition of adipose tissue by the fetus either due to prematurity or to fetal growth restriction is associated with changes in the cord blood adipokine profile that may contribute to the impairment of glucose metabolism.

Intussusception in a preterm neonate; a very rare, major intestinal problem--systematic review of cases.

Intussusception is an extremely rare disorder in preterm infants and it is often misdiagnosed as necrotizing enterocolitis. We report a case of intussusception in a 30-day-old preterm infant of 26 weeks of gestational age and a birthweight of 610 g who was diagnosed via abdominal ultra sonography. A systematic review of the literature was performed and reports on 23 previous cases were found. The presence of recognizable causes of intussusception in preterms, such as Meckel's diverticulum, bowel polypus, etc. was very infrequent. Comorbidity before and after intussusception is heterogeneous and related to prematurity. The intussusception is predominantly located in the small bowel (91.6%)--ileal or jejunal. The condition is misdiagnosed as NEC and managed conservatively until clinical deterioration occurs. A definitive diagnosis is thus established during abdominal surgery, which is usually delayed an average of 9.5 days from the onset of symptoms. Our case illustrates the capability of abdominal ultrasonography to establish early diagnosis of intussusception in the premature newborn.