Safe and efficient practice of parenteral nutrition in neonates and children aged 0-18 years - The role of licensed multi-chamber bags.

Parenteral nutrition (PN) is recognized as a complex high-risk therapy. Its practice is highly variable and frequently suboptimal in pediatric patients. Optimizing care requires evidence, consensus-based guidelines, audits of practice, and standardized strategies. Several pediatric scientific organizations, expert panels, and authorities have recently recommended that standardized PN should generally be used over individualized PN in the majority of pediatric patients including very low birth weight premature infants. In addition, PN admixtures produced and validated by a suitably qualified institution are recommended over locally produced PN. Licensed multi chamber bags are standardized PN bags that comply with Good Manufacturing Practice and high-quality standards for the finished product in the frame of their full manufacturing license. The purpose of this article is to review the practical aspects of PN and the evidence for using such multi-chamber bags in pediatric patients. It highlights the safety characteristics and the limitations of the different PN practices and provides some guidance for ensuring safe and efficient therapy in pediatric patients.

Mother's own milk and bronchopulmonary dysplasia in appropriate for gestational age preterm infants.

OBJECTIVE: To evaluate the association between mother's own milk (MOM) and bronchopulmonary dysplasia (BPD) in appropriate for gestational age (AGA) preterm infants <32 weeks. METHODS: Clinical data of AGA preterm infants (24+0/7-31+6/7 weeks) were reviewed. Infants with ≥66% of cumulative prescribed enteral volumes as MOM from birth to 36 weeks were allocated to the high provision of MOM group (H-MOM), whereas those with <66% were assigned to the low provision of MOM group (L-MOM). Multiple regressions were used to assess the association of H-MOM with BPD and oxygen saturation to fraction inspired oxygen ratio (SFR) at 36 weeks. RESULTS: A total of 1041 infants met the inclusion criteria, with a median provision of cumulative enteral nutrition volumes of 5721 (IQR 2616) mL/kg. Among them, 517 (49.7%) were H-MOM and 524 (50.3%) L-MOM infants. H-MOM showed a reduction in the incidence of BPD to 31.6% compared to L-MOM infants. H-MOM had a lower risk of BPD than L-MOM infants after the adjustment for gestational age, sex, cesarean section, mean SFR at the first hours of life, surfactant administration, patent ductus arteriosus, sepsis, prolonged ventilatory supports/oxygen exposure, and cumulative energy intakes from birth to 36 weeks [aOR: 0.613, p = 0.047]. H-MOM was also associated with a lower risk of SFR in the first quartile at 36 weeks [aOR: 0.616, p = 0.028] than L-MOM. CONCLUSION: A high provision (≥66%) of enteral volume as MOM from birth to 36 weeks is associated with a reduced risk of both BPD and low SFR at 36 weeks in AGA preterm infants <32 weeks.

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.

Incidence and two-year neurodevelopmental outcomes of small-for-gestational-age preterm infants: how do they relate to using different neonatal anthropometric charts?

BACKGROUND: The effect of different neonatal anthropometric charts on the incidence and neurodevelopmental outcomes at two years (Y) corrected age of small-for-gestational-age (SGA) preterm infants has still not been fully explored. METHODS: All preterm infants with a gestational age (GA) between 24.0 and 31.6 weeks (W), born from Jan-2004 to Dec-2017 in the Marche region (Italy) were studied. Intergrowth-21st, Beeby, Fenton, and Bertino anthropometric charts were used to classify infants with a birth weight less than 10th centile as SGA. Disabilities and neurodevelopmental scores assessed by Bayley-III Test were recorded at the 2Y follow-up visit. RESULTS: One thousand one hundred forty-seven preterm infants were evaluated. The incidence of SGA was significantly different among the study charts (from 12.9 to 17.5%). Nine hundred and twenty-seven study infants were assessed for neurodevelopmental outcomes at 2Y corrected age. The incidence of SGA with moderate cognitive impairment (COG Score: 70-84) and mild neurodevelopmental disability (NDD) were significantly different between the Intergrowth-21st and Bertino charts (31.7% vs. 19.6%, P=0.042; 30.8 vs. 19.2%, P=0.036; respectively). A statistically significant difference in COG Score was found between SGA preterm infants overlapping in all study charts and those classified as SGA only by the Intergrowth-21st chart (89.1±15.7 vs. 99.2±19.8; P=0.038). CONCLUSIONS: In a large cohort of preterm infants with a GA between 24.0 and 31.6W, the incidence and neurodevelopmental outcomes at 2Y corrected age of SGAs were significantly different depending on the anthropometric charts. These differences, albeit small, should be considered both in clinical practice and trials on SGA preterm infants.

Reduced pulmonary oxygen diffusion at 36 weeks of postmenstrual age in small-for-gestational-age preterm infants of less than 32 weeks without bronchopulmonary dysplasia.

BACKGROUND: Small-for-gestational-age (SGA) preterm infants are at increased risk of developing bronchopulmonary dysplasia (BPD). There is limited information on pulmonary oxygen diffusion of SGA preterm infants, particularly in those without BPD. OBJECTIVE: To compare the pulmonary oxygen diffusion of SGA to that of appropriate-for-gestational-age (AGA) preterm infants without BPD. STUDY DESIGN: Preterm infants with a gestational age (GA) between 24.0 and 31.6 weeks were studied. The oxygen saturation (SpO2 ), fraction to inspired oxygen (FiO2 ), and the SpO2 to FiO2 ratio (SFR) were compared between SGA and AGA infants. The association between SGA and SFR at 36 weeks was assessed using a multiple regression analysis. In the subgroup without BPD, SGA were match-paired for GA and gender with AGA infants. RESULTS: We analyzed 1189 infants surviving at 36 weeks: 194 (16%) were SGA and 995 (84%) AGA. The incidence of BPD was significantly higher in SGA than AGA infants (32% vs. 13%; p = .000). Out of the 995 infants without BPD, 132 (13%) were SGA and 863 (87%) AGA. SGA was negatively associated with the SFR value at 36 weeks, independently from BPD. SGA infants without BPD had significantly higher (better) SFR at birth, but lower (worse) SpO2 and SFR and from 33 to 36 weeks than their matched AGA counterpart. At 36 weeks, median SpO2 and SFR values were 97.7 versus 98.4 (p = .006) and 465 versus 468 (p = .010) in match-paired SGA and AGA, respectively. CONCLUSION: Among preterm infants of less than 32 weeks and without BPD, SGA infants had a reduced pulmonary oxygen diffusion at 36 weeks in comparison with AGA infants.

Who Needs a Second Dose of Exogenous Surfactant?

OBJECTIVE: To identify prenatal and postnatal risk factors associated with surfactant redosing. STUDY DESIGN: Retrospective, single-regional center study including all infants born from 24 + 0 to 31 + 6 weeks of gestation in the Marche Region, Italy, and admitted to a single level III regional NICU from January 1, 2004, to February 28, 2021. Clinical factors associated with surfactant redosing were identified through logistic regression analysis. RESULTS: Of 1615 consecutive admissions, 662 infants were treated with exogenous surfactant: 462 (70%) received a single dose and 200 (30%) received more than 1 dose (25.5% two doses and 4.5% three doses). Risk of redosing was higher for infants born to mothers with hypertension in pregnancy (OR 3.95, P < .001), for small for gestational age (SGA) infants (OR 3.93, P < .001) and when the first surfactant dose was 100 mg/kg instead of 200 mg/kg (OR 4.56/4.61, P < .001). Infants with greater GA, delayed first surfactant administration, and milder respiratory distress syndrome had reduced risk of redosing. Infants who required multiple surfactant doses had a higher rate of bronchopulmonary dysplasia and mortality, as well as longer duration of respiratory support than patients that received 1 dose. CONCLUSIONS: Hypertension in pregnancy and SGA status were found to be statistically and clinically significant predictors of surfactant redosing. Understanding the pathophysiology of these conditions requires further investigation.

Effect of preoperative pulmonary hemodynamic and cardiopulmonary bypass on lung function in children with congenital heart disease.

In children with congenital heart disease (CHD), pulmonary blood flow (Qp) contributes to alterations of pulmonary mechanics and gas exchange, while cardiopulmonary bypass (CPB) induces lung edema. We aimed to determine the effect of hemodynamics on lung function and lung epithelial lining fluid (ELF) biomarkers in biventricular CHD children undergoing CPB. CHD children were classified as high Qp (n = 43) and low Qp (n = 17), according to preoperative cardiac morphology and arterial oxygen saturation. We measured ELF surfactant protein B (SP-B) and myeloperoxidase activity (MPO) as indexes of lung inflammation and ELF albumin as index of alveolar capillary leak in tracheal aspirate (TA) samples collected before surgery and in 6 hourly intervals within 24 h after surgery. At the same time points, we recorded dynamic compliance and oxygenation index (OI). The same biomarkers were measured in TA samples collected from 16 infants with no cardiorespiratory diseases at the time of endotracheal intubation for elective surgery. Preoperative ELF biomarkers in CHD children were significantly increased than those found in controls. In the high Qp, ELF MPO and SP-B peaked 6 h after surgery and tended to decrease afterward, while they tended to increase within the first 24 h in the low Qp. ELF albumin peaked 6 h after surgery and decreased afterwards in both CHD groups. Dynamic compliance/kg and OI significantly improved after surgery only in the High Qp.  Conclusion: In CHD children, lung mechanics, OI, and ELF biomarkers were significantly affected by CPB, according to the preoperative pulmonary hemodynamics. What is Known: • Congenital heart disease children, before cardiopulmonary run, exhibit changes in respiratory mechanics, gas exchange, and lung inflammatory biomarkers that are related to the preoperative pulmonary hemodynamics. • Cardiopulmonary bypass induces alteration of lung function and epithelial lining fluid biomarkers according to preoperative hemodynamics. What is New: • Our findings can help to identify children with congenital heart disease at high risk of postoperative lung injury who may benefit of tailored intensive care strategies, such as non-invasive ventilation techniques, fluid management, and anti-inflammatory drugs that can improve cardiopulmonary interaction in the perioperative period.

Systematic Review on Individualized Versus Standardized Parenteral Nutrition in Preterm Infants.

The need for high quality evidence is recognized for optimizing practices of parenteral nutrition (PN). The purpose of the present systematic review is to update the available evidence and investigate the effect of standardized PN (SPN) vs. individualized PN (IPN) on protein intake, immediate morbidities, growth, and long-term outcome in preterm infants. A literature search was performed on articles published in the period from 1/2015 to 11/2022 in PubMed and Cochrane database for trials on parenteral nutrition in preterm infants. Three new studies were identified. All new identified trials were nonrandomized observational trials using historical controls. SPN may increase weight and occipital frontal circumference gain and lower the value of maximum weight loss. More recent trials suggest that SPN may easily increase early protein intake. SPN may reduce the sepsis incidence, but overall, no significant effect was found. There was no significant effect of standardization of PN on mortality or stage ≥2 necrotizing enterocolite (NEC) incidence. In conclusion SPN may improve growth through higher nutrient (especially protein) intake and has no effect on sepsis, NEC, mortality, or days of PN.

European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update.

Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of "European Guidelines for the Management of RDS" by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12, 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS).

Early postnatal weight loss does not affect the 2-year neurodevelopment in preterm infants of less than 32 weeks.

AIM: It is still unclear if the magnitude of early postnatal weight loss (PWL) could be associated with neurodevelopmental outcomes in preterm infants. We studied the association between PWL and neurodevelopment at 2-year corrected age in preterm infants. METHODS: We retrospectively reviewed data of preterm infants with a gestational age between 24 + 0 and 31 + 6 weeks/days, admitted at the G.Salesi Children's Hospital, Ancona, Italy, between 1 January 2006 and 31 December 2019. Infants with PWL greater than or equal to 10% (PWL ≥ 10%) were compared with those with PWL of less than 10% (PWL < 10%). A matched cohort analysis was also performed using gestational age and birth weight as matching variables. RESULTS: We analysed 812 infants: 471 (58%) PWL ≥ 10% and 341 (42%) PWL < 10%. A subgroup of 247 PWL ≥ 10% was closely match-paired with 247 PWL < 10% infants. There were no differences in amino acid and energy intakes from birth to day 14 of life and from birth to 36 weeks. Although at 36 weeks, body weight and total length were lower in PWL ≥ 10% than PWL < 10%, anthropometry and neurodevelopment at 2 years were similar between groups. CONCLUSION: Given similar amino acid and energy intakes on PWL ≥ 10% and PWL < 10% preterm infants of less than 32 + 0 weeks/days, PWL does not affect 2-year neurodevelopment.

UPDATE - 2022 Italian guidelines on the management of bronchiolitis in infants.

Bronchiolitis is an acute respiratory illness that is the leading cause of hospitalization in young children. This document aims to update the consensus document published in 2014 to provide guidance on the current best practices for managing bronchiolitis in infants. The document addresses care in both hospitals and primary care. The diagnosis of bronchiolitis is based on the clinical history and physical examination. The mainstays of management are largely supportive, consisting of fluid management and respiratory support. Evidence suggests no benefit with the use of salbutamol, glucocorticosteroids and antibiotics with potential risk of harm. Because of the lack of effective treatment, the reduction of morbidity must rely on preventive measures. De-implementation of non-evidence-based interventions is a major goal, and educational interventions for clinicians should be carried out to promote high-value care of infants with bronchiolitis. Well-prepared implementation strategies to standardize care and improve the quality of care are needed to promote adherence to guidelines and discourage non-evidence-based attitudes. In parallel, parents' education will help reduce patient pressure and contribute to inappropriate prescriptions. Infants with pre-existing risk factors (i.e., prematurity, bronchopulmonary dysplasia, congenital heart diseases, immunodeficiency, neuromuscular diseases, cystic fibrosis, Down syndrome) present a significant risk of severe bronchiolitis and should be carefully assessed. This revised document, based on international and national scientific evidence, reinforces the current recommendations and integrates the recent advances for optimal care and prevention of acute bronchiolitis.

Which birth weight threshold to start parenteral nutrition? A single center experience.

OBJECTIVES: To analyze the need for parenteral nutrition (PN) in infants with a birth weight (BW) between 1250 and 1499 g. METHODS: Retrospective evaluation of clinical, nutritional, growth and neurodevelopmental data of infants with a BW between 1250 and 1499 g consecutively admitted to our institution between 2004 and 2020. RESULTS: Of the 503 infants admitted during the study period, 130 (26%) received PN: in 97 (19%) PN was medically indicated, while in 33 (7%) there was no clear indication. Patients who received medically indicated PN were younger, smaller, and sicker than the 373 infants who were managed with enteral nutrition, and their weight gain was lower (14.6 ± 4.1 vs 16.9 ± 4.2 g∙kg-1 ∙ d-1, p = 0.000). Body size at 36 weeks and 2-year anthropometry and neurodevelopment of the infants managed with enteral nutrition were not different from our reference values. CONCLUSIONS: After lowering the BW threshold for bridging PN from 1500 to 1250 g, we found that PN was started in only 20% of infants with a BW between 1250 and 1500 g. Withholding PN if not medically indicated did not result neither in growth faltering nor in reduced neurodevelopment.

Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts.

OBJECTIVES: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g. METHODS: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-to-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached. RESULTS: In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier. CONCLUSIONS: We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants.

Evolution of Ultrasound-Assessed Lung Aeration and Gas Exchange in Respiratory Distress Syndrome and Transient Tachypnea of the Neonate.

OBJECTIVE: To use clinical, lung ultrasound, and gas exchange data to clarify the evolution of lung aeration and function in neonates with respiratory distress syndrome (RDS) and transient tachypnea of the neonate (TTN), the most common types of neonatal respiratory failure. STUDY DESIGN: In this prospective observational cohort study, lung aeration and function were measured with a semiquantitative lung ultrasound score (LUS) and transcutaneous blood gas measurement performed at 1 hour (time point 0), 6 hours (time point 1), 12 hours (time point 2), 24 hours (time point 3) and 72 hours (time point 4) of life. Endogenous surfactant was estimated using lamellar body count (LBC). LUS, oxygenation index (OI), oxygen saturation index (OSI), and transcutaneous pressure of carbon dioxide (PtcCO2) were the primary outcomes. All results were adjusted for gestational age. RESULTS: Sixty-nine neonates were enrolled in the RDS cohort, and 58 neonates were enrolled in the TTN cohort. LUS improved over time (within-subjects, P < .001) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001). Oxygenation improved over time (within-subjects, P = .011 for OI, P < .001 for OSI) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001 for OI and OSI). PtcCO2 improved over time (within-subjects, P < .001) and was similar in the RDS and TTN cohorts at all time points. Results were unchanged after adjustment for gestational age. LBC was associated with RDS (ß = -0.2 [95% CI, -0.004 to -0.0001]; P = .037) and LUS (ß = -3 [95% CI, -5.5 to -0.5]; P = .019). CONCLUSIONS: For the first 72 hours of life, the RDS cohort had worse lung aeration and oxygenation compared with the TTN cohort at all time points. CO2 clearance did not differ between the cohorts, whereas both lung aeration and function improved in the first 72 hours of life.

A novel deuterium-based model for measurement of exogenous surfactant using deuterium-depleted water.

Stable isotope tracers, like 13 C, can be used for the measurement of the partition between the endogenous and exogenous pulmonary disaturated-phosphatidylcholine (DSPC). Deuterium labeling methods are still not fully explored. Our aim was to investigate the feasibility of using deuterium-depleted water (DDW) and deuterium-enriched water (DEW) to measure endogenous and exogenous pulmonary DSPC in a rabbit model of surfactant depletion. Data obtained from the 13 C dilution method were used as a reference. We studied 9 adult rabbits: 4 drank DDW and 5 DEW for 5 days. Lung surfactant depletion was induced at Day 5 by repeated saline bronchoalveolar lavages (BAL), which were stored as a pool (BAL pool). After endogenous surfactant depletion, rabbits received exogenous surfactant followed by a second BAL depletion procedure (End-Experiment Pool). DSPC quantity, and palmitic acid (PA)-DSPC 2 H/1 H (δ2 H) and 13 C/12 C ratios (δ13 C) of exogenous surfactant batches and of BAL pools were measured by High-Resolution Mass Spectrometry. The amount of exogenous surfactant recovered from the lungs ranged from 45% to 81% and, it was highly correlated with those obtained with the use of the 13 C (r = 0.9844, p < 0.0001). We demonstrated that commercially available purified DDW and even low doses of DEW can be used to modify the deuterium background of endogenous surfactants with the purpose of measuring the contribution of exogenous surfactants to the endogenous alveolar surfactant pool.

Respiratory distress syndrome in preterm infants of less than 32 weeks: What difference does giving 100 or 200 mg/kg of exogenous surfactant make?

BACKGROUND: Surfactant dosing and effective delivery could affect continuous positive airways pressure (CPAP)-failure. Nevertheless, information on exogenous surfactant dosing with current administration methods is limited. OBJECTIVE: To describe the effect of 100 or 200 mg/kg of surfactant as first-line treatment of respiratory distress syndrome in preterm infants of less than 32 weeks gestation. STUDY DESIGN: A retrospective single-center cohort study comparing two epochs, before and after switching from 100 to 200 mg/kg surfactant therapy. RESULTS: Six hundred and fifty-eight of the 1615 infants of less than 32 weeks were treated with surfactant: 282 received 100 mg/kg (S-100) and 376 received 200 mg/kg (S-200). There were no differences between S-100 and S-200 in perinatal data including prenatal corticosteroids, medication use, age at first surfactant administration and respiratory severity before surfactant. The S-200 vs. S-100 had fewer retreatments (17.0% vs. 47.2%, p < 0.001) and a shorter duration of oxygen therapy and mechanical ventilation (315 vs. 339 h, p = 0.018; 37 vs. 118 h, p = 0.000, respectively). There was no difference in postnatal corticosteroid use (S-200 10.0% vs. S-100 11.0%, p = 0.361). Bronchopulmonary dysplasia (BPD) was significantly lower in S-200 vs. S-100 when comparing either the 4 and 6-year periods before and after the dose switch (29.4% vs. 15.7%, p = 0.003, and 18.7% vs. 27.3%, p = 0.024, respectively) CONCLUSIONS: The switch from 100 to 200 mg/kg was associated with a marked reduction in the need for surfactant redosing, respiratory support, and BPD. This information could be important when designing a study in the modern era of less invasive administration as surfactant dosing and its effective delivery may affect the outcome.

DHA turnover in pregnant women using the natural abundance variation of 13C: a pilot study.

The importance of DHA intake to support fetal development and maternal health is well established. In this pilot study we applied the natural abundance approach to determine the contribution of 200 mg/day of DHA supplement to the plasma DHA pool in 19 healthy pregnant women on a free diet.Women received DHA, from pregnancy week 20 until delivery, from an algal source (N=13, Algae group) or from fish oil (N=6, Fish group) with slightly different content of 13C.We measured plasma phospholipids DHA 13C:12C ratio (reported as δ13C) prior to supplementation (T0), after 10 (T1) and 90 days (T2) and prior to delivery (T3).The δ13C of DHA in algae and fish supplements were -15.8±0.2 mUr and -25.3±0.2 mUr (p<0.001).DHA δ13C in the Algae group increased from -27.7±1.6 mUr (T0) to -21.9±2.2 mUr (T3) (p<0.001), whereas there were not significant changes in the Fish group (-27.8±0.9 mUr at T0 and -27.3±1.1 mUr at T3, p=0.09).In the Algae group 200 mg/day of DHA contributed to the plasma phospholipid pool by a median value of 53% (31-75% minimum and maximum). This estimation was not possible in the fish group.Our results demonstrate the feasibility of assessing the contribution of DHA from an algal source to the plasma DHA pool in pregnant women by the natural abundance approach. Plasma δ13C DHA did not change when consuming DHA of fish origin, with almost the same δ13C value of that of the pre-supplementation plasma δ13C DHA.

Is low cerebral near infrared spectroscopy oximetry associated with neurodevelopment of preterm infants without brain injury?

OBJECTIVES: To evaluate the association between low regional cerebral oxygen saturation (rScO2) and neurodevelopment in preterm infants classified as no brain injury (NBI). METHODS: We retrospectively reviewed data of rScO2 monitoring during the first 3 days of life of infants with a gestational age (GA)<28 weeks or birth weight (BW)<1,000 g, with and without brain injury (BI). BI was defined as intraventricular haemorrhage, cystic periventricular leukomalacia or cerebellar haemorrhage. Univariate and multivariate analyses were used to study the association of rScO2<55% for more than 10 h in the first 3 days of life (NIRS<55%>10H) and the 24 months neurodevelopment. RESULTS: Of the 185 patients who met the inclusion criteria, 31% were classified as BI infants and 69% NBI. BI compared to NBI infants had a significantly lower GA and a higher incidence of complications of prematurity. Mean rScO2 in the first 72 h of life was significantly lower in BI than NBI. NIRS<55%>10H in NBI patients was negatively associated with neurodevelopmental scores both at the univariate and multivariate analysis (p<0.05). NBI infants with NIRS<55%>10H were found to have lower systemic oxygenation than their counterparts with rScO2<55% for less than 10 h. CONCLUSIONS: NIRS<55%>10H in NBI small preterm infants was found to be an independent predictor of neurodevelopment at 24 months and it was associated with low systemic saturation values.

Efficacy and Safety of Enteral Recombinant Human Insulin in Preterm Infants: A Randomized Clinical Trial.

IMPORTANCE: Feeding intolerance is a common condition among preterm infants owing to immaturity of the gastrointestinal tract. Enteral insulin appears to promote intestinal maturation. The insulin concentration in human milk declines rapidly post partum and insulin is absent in formula; therefore, recombinant human (rh) insulin for enteral administration as a supplement to human milk and formula may reduce feeding intolerance in preterm infants. OBJECTIVE: To assess the efficacy and safety of 2 different dosages of rh insulin as a supplement to both human milk and preterm formula. DESIGN, SETTING, AND PARTICIPANTS: The FIT-04 multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 46 neonatal intensive care units throughout Europe, Israel, and the US. Preterm infants with a gestational age (GA) of 26 to 32 weeks and a birth weight of 500 g or more were enrolled between October 9, 2016, and April 25, 2018. Data were analyzed in January 2020. INTERVENTIONS: Preterm infants were randomly assigned to receive low-dose rh insulin (400-µIU/mL milk), high-dose rh insulin (2000-µIU/mL milk), or placebo for 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome was time to achieve full enteral feeding (FEF) defined as an enteral intake of 150 mL/kg per day or more for 3 consecutive days. RESULTS: The final intention-to-treat analysis included 303 preterm infants (low-dose group: median [IQR] GA, 29.1 [28.1-30.4] weeks; 65 boys [59%]; median [IQR] birth weight, 1200 [976-1425] g; high-dose group: median [IQR] GA, 29.0 [27.7-30.5] weeks; 52 boys [55%]; median [IQR] birth weight, 1250 [1020-1445] g; placebo group: median [IQR] GA, 28.8 [27.6-30.4] weeks; 54 boys [55%]; median [IQR] birth weight, 1208 [1021-1430] g). The data safety monitoring board advised to discontinue the study early based on interim futility analysis (including the first 225 randomized infants), as the conditional power did not reach the prespecified threshold of 35% for both rh-insulin dosages. The study continued while the data safety monitoring board analyzed and discussed the data. In the final intention-to-treat analysis, the median (IQR) time to achieve FEF was significantly reduced in 94 infants receiving low-dose rh insulin (10.0 [7.0-21.8] days; P = .03) and in 82 infants receiving high-dose rh insulin (10.0 [6.0-15.0] days; P = .001) compared with 85 infants receiving placebo (14.0 [8.0-28.0] days). Compared with placebo, the difference in median (95% CI) time to FEF was 4.0 (1.0-8.0) days for the low-dose group and 4.0 (1.0-7.0) days for the high-dose group. Weight gain rates did not differ significantly between groups. Necrotizing enterocolitis (Bell stage 2 or 3) occurred in 7 of 108 infants (6%) in the low-dose group, 4 of 88 infants (5%) in the high-dose group, and 10 of 97 infants (10%) in the placebo group. None of the infants developed serum insulin antibodies. CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial revealed that enteral administration of 2 different rh-insulin dosages was safe and compared with placebo, significantly reduced time to FEF in preterm infants with a GA of 26 to 32 weeks. These findings support the use of rh insulin as a supplement to human milk and preterm formula. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02510560.