Luca Maggio

Progression of renal function in preterm neonates with gestational age < or = 32 weeks.

Abstract Serum creatinine (SeCr), creatinine clearance (CrCl), and fractional excretion of sodium (FeNa) were measured in 83 preterm neonates divided into four groups according to gestational age (GA). At birth, there were no differences in mean SeCr values in the four groups nor any significant correlation between initial values and GA. In all groups there was an initial SeCr increase; an inverse correlation between SeCr and GA was observed from the 3rd day of life to the 5th week (p<0.001). CrCl showed a positive correlation to GA from the first week onwards (p<0.001); in each group CrCl values correlated positively to days of life (p=0.0001). Rate of CrCl increase correlated positively to GA(p=0.0005). FeNa showed an inverse correlation to GA from the first week (p<0.001). In each group, the FeNa value correlated negatively to postnatal age (p<0.001) and the velocity of decrease was directly correlated to GA (p=0.0358). Our findings indicate that glomerular function shows a progression directly correlated to GA and postnatal age, while tubular function correlates inversely to the same parameters. The values reported could be useful for following renal function in very low birth weight infants.

Probiotics for prevention of atopic diseases in infants: systematic review and meta‐analysis

Growing evidence underlines the pivotal role of infant gut colonization in the development of the immune system. The possibility to modify gut colonization through probiotic supplementation in childhood might prevent atopic diseases. The aim of the present systematic review and meta‐analysis was to evaluate the effect of probiotic supplementation during pregnancy and early infancy in preventing atopic diseases. PubMed, Embase and Cochrane Library were searched for randomized controlled trials evaluating the use of probiotics during pregnancy or early infancy for prevention of allergic diseases. Fixed‐effect models were used, and random‐effects models where significant heterogeneity was present. Results were expressed as risk ratio (RR) with 95% confidence interval (CI). Seventeen studies, reporting data from 4755 children (2381 in the probiotic group and 2374 in the control group), were included in the meta‐analysis. Infants treated with probiotics had a significantly lower RR for eczema compared to controls (RR 0.78 [95% CI: 0.69–0.89], P = 0.0003), especially those supplemented with a mixture of probiotics (RR 0.54 [95% CI: 0.43–0.68], P < 0.00001). No significant difference in terms of prevention of asthma (RR 0.99 [95% CI: 0.77–1.27], P = 0.95), wheezing (RR 1.02 [95% CI: 0.89–1.17], P = 0.76) or rhinoconjunctivitis (RR 0.91 [95% CI: 0.67–1.23], P = 0.53) was documented. The results of the present meta‐analysis show that probiotic supplementation prevents infantile eczema, thus suggesting a new potential indication for probiotic use in pregnancy and infancy.

Effects of high versus standard early protein intake on growth of extremely low birth weight infants.

Objectives: Early provision of protein has been shown to limit catabolism and could improve growth. Our objective was to determine whether early aggressive protein intake improved growth outcomes of extremely low birth weight (ELBW) infants. Patients and Methods: ELBW infants were included in the study if they had no major congenital anomalies or renal failure and were still hospitalized at 36 weeks postmenstrual age. In 25 infants (HP) the early protein intake was planned to be 20% greater than in 31 historical controls (SP). Results: The 2 groups were similar in the baseline characteristics. The mean protein intake during the first 14 days of life was significantly greater in the HP group (3.1 ± 0.2 vs 2.5 ± 0.2 g/kg/d; P<0.0001). HP group showed lower postnatal weight loss (−3.1%; 95% confidence interval [CI] −5.9, −0.2) and earlier regain of birth weight (−4.1 days; 95% CI −6.6, −1.7). Mean blood urea nitrogen and bicarbonate levels were similar; mean serum glucose level was lower in the HP group (−21,7 mg/dL; 95% CI −41.9,−1.5). HP infants had a reduced fall in weight z score (−0.57; 95% CI −1.01, −0.12) and in length z score (−0.51; 95% CI −0.97, −0.05) from birth to discharge. Conclusion: Early high protein intake was associated with improved weight and length growth outcomes at discharge. These findings highlight the benefits of aggressive protein intake immediately after birth.

Higher urinary excretion of essential amino acids in preterm infants fed protein hydrolysates

Aim: Protein hydrolysates have been introduced in preterm formulae, but it is not clear whether they are needed for the feeding of preterm infants. We designed a randomized, controlled trial to test the effects of a preterm formula with hydrolysed cows milk proteins on short‐term growth and urinary and plasma amino acids levels. Methods: Infants with a birthweight 1750 g and gestational age 34 wk fed a conventional preterm infant formula (formula B) or a hydrolysed formula (formula A). Weight was measured daily; length, head circumference, mid‐arm circumference and total skinfold thickness were measured weekly. Blood and urine were analysed for amino acid concentrations at start, 14 and 28 d. Results: Twenty‐one infants met the criteria for randomization. The daily feeding volumes were: formula A 172.8±5.6 vs formula B 170.1±2.8 ml/kg/d. Infants fed with formula A showed slower weight gain (17.4±3.4 vs 20.5±3.3 g/kg/d; p=0.045) and lower mean change in Z‐scores for weight (−0.18±0.16 vs 0.00±0.09; p=0.009) and for head circumference (−0.06±0.13 vs 0.06±0.13; p=0.049). After 14 d, infants receiving formula A had statistically significant higher urinary levels of essential amino acids compared to infants receiving formula B.

Cardiac Adverse Effects of Early Dexamethasone Treatment in Preterm Infants: A Randomized Clinical Trial

This study evaluates the effects of early administration of dexamethasone on left ventricle dimensions and their clinical significance in preterm infants. Fifty preterm infants with birth weight ≤ 1250 g and gestational age ≤ 30 weeks were randomly assigned after 72 hours of life to the dexamethasone group (n = 25) or to the control group (n = 25). The treated infants received dexamethasone intravenously from the 4th day of life for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the 7th day). Serial echocardiographic measurements of end systolic interventricular septum thickness, end diastolic interventricular septum thickness, end systolic left ventricle posterior wall thickness, end diastolic left ventricle posterior wall thickness, left ventricle end diastolic diameter, and left ventricle end systolic diameter were taken before starting dexamethasone, on days 3 and 7 of treatment, 7 days after the interruption of treatment, and at the 28th day of life. Five infants of each group were excluded by the final analysis because of the lack of a complete cardiac evaluation, leaving 20 treated and 20 control infants. Infants receiving dexamethasone had a significantly larger increase in mean septal and left posterior wall thickness during the treatment and 7 days after the dexamethasone weaning. The mean left ventricle diameter of treated infants was significantly lower than that of control infants from the 7th day of treatment to the 28th day of life. Four neonates (20%) in the dexamethasone group developed left ventricular myocardial hypertrophy without left ventricle outflow tract obstruction, showing signs of decreased cardiac output and ischemic changes on ECG. The daily fluid intake was increased to 200 ml/kgto ensure an adequate preload volume, and the complete resolution of left ventricle hypertrophy was obtained within the 2nd to 3rd week after dexamethasone weaning. Preterm infants receiving an early (< 96 hours of life) short course of dexamethasone develop a left ventricular myocardial hypertrophy that can be symptomatic and clinically significant. Preterm infants included in future studies with the goal to find the minimum dose and duration of dexamethasone treatment should be strictly monitored echocardiographically for this side effect.

Preterm Small for Gestational Age Infants Are Not at Higher Risk for Parenteral Nutrition–Associated Cholestasis

OBJECTIVE To assess if being small for gestational age impacts parenteral nutrition-associated cholestasis (PNAC) development. STUDY DESIGN We reviewed all the very low-birth weight infants exposed to parenteral nutrition for >14 days from 1996 to 2006, comparing auxological and clinical data, as well as nutritional history, during the first 4 weeks of life of infants with cholestasis and control subjects. RESULTS Of 445 very low-birth weight infants, 55 had development of PNAC. Infants with cholestasis had lower birth weight and gestational age but similar birth weight z-score compared with infants without cholestasis, and they received a lower amount of enteral feeds (25.8 +/- 20.7 vs 67.9 +/- 33.0 mL/kg, P < .001), a greater amount of intravenous glucose (10.6 +/- 1.3 vs 7.5 +/- 2.5 g/kg, P < .0001), lipids (1.8 +/- 0.4 vs 1.3 +/- 0.5, P < .0001) and proteins (2.7 +/- 0.5 vs 1.9 +/- 0.7, P < .0001), and needed a higher number of days of fasting (13.2 +/- 6.7 vs 6.5 +/- 4.8, P < .001). Enteral intake between 0 and 21 days of life (OR 0.66; 95% CI 0.53, 0.81, P < .0001) and oxygen therapy (OR 1.05; 95% CI 1.01, 1.09; P = .030) were identified as the best independent predictors of PNAC. CONCLUSIONS Enteral feeding remains the main factor for the prevention of PNAC, whereas small for gestational age infants do not have a higher risk of PNAC.

Effect on growth of two different dexamethasone courses for preterm infants at risk of chronic lung disease. A randomized trial.

A randomized study was designed to evaluate the effects of two different dexamethasone courses on the growth of preterm infants. The first phase included 30 preterm infants at high risk for chronic lung disease (CLD). 15 babies (moderately early dexamethasone group) were treated with dexamethasone for 14 days, from the 10th day of life, and received a total dose of 4.75 mg/kg; 15 babies were assigned to the control group. The second phase included 30 preterm infants at high risk for CLD. 15 babies (early dexamethasone group) were treated with dexamethasone for 7 days, from the 4th day of life, and received a total dose of 2.38 mg/kg; 15 babies were assigned to the control group. All the main clinical baseline characteristics were similar between the groups both in the first and in the second phase. Infants given the two dexamethasone courses showed significantly reduced weight gain during the period of treatment when compared to the respective control group, but they had a weight catch-up soon after the end of treatment. At 30 days of life the weight and length gain of each treated group were similar to those of control infants, but the moderately early dexamethasone group showed a significantly poorer head growth. No differences between the groups were observed at discharge. Dexamethasone treatment induces a slower weight gain which is time-limited to the period of treatment and is followed by a body weight catch-up. However, the poorer head growth detected at 30 days of life in the infants who received a higher dose of dexamethasone could indicate important adverse effects, possibly dose-related, on postnatal brain growth and development.

rhBSSL Improves Growth and LCPUFA Absorption in Preterm Infants Fed Formula or Pasteurized Breast Milk

Objectives: Preterm infants often experience suboptimal growth, which can affect organ development. The aim of this study was to improve growth by treatment with bile salt–stimulated lipase (BSSL), naturally present in breast milk, but lost after pasteurization, and absent in formula. Methods: Two clinical trials were performed with a predefined analysis of combined data to investigate the effects of recombinant human BSSL (rhBSSL) treatment on growth velocity and fat absorption in preterm infants. The studies were randomized and double-blinded comparing 7-day treatment with rhBSSL and placebo, administered in pasteurized breast milk or formula, using a crossover design. Results: Sixty-three infants were evaluated for safety. At randomization, the mean (standard deviation) weight was 1467 (193) g and mean postmenstrual age was 32.6 (0.5) weeks. Sixty and 46 infants were evaluated for growth velocity and fat absorption, respectively. rhBSSL treatment significantly improved mean growth velocity by 2.93 g · kg−1 · day−1 (P < 0.001) compared with placebo (mean 16.86 vs 13.93 g · kg−1 · day−1) and significantly decreased the risk of suboptimal growth (<15 g · kg−1 · day−1) (30% vs 52%, P = 0.004). rhBSSL significantly increased absorption of the long-chain polyunsaturated fatty acids, docosahexaenoic acid, and arachidonic acid by 5.76% (P = 0.013) and 8.55% (P = 0.001), respectively, but had no significant effect on total fat absorption. The adverse-event profile was similar to placebo. Conclusions: In preterm infants fed pasteurized breast milk or formula, 1 week of treatment with rhBSSL was well tolerated and significantly improved growth and long-chain polyunsaturated fatty acid absorption compared to placebo. This publication presents the first data regarding the use of rhBSSL in preterms and the results have led to further clinical studies.

Human milk fortifiers in very low birth weight infants

The use of HMF remains an important option and has become common practice in all neonatal intensive care units. However, optimal composition of fortifiers is still undefined and more data are needed on safety and long-term benefits. Further research should be directed toward comparisons between different proprietary preparations, evaluating both short-term and long-term outcomes and adverse effects, in search of the best method of fortification.

Effect of Dexamethasone on Tracheobronchial Aspirate Fluid Cytology and Pulmonary Mechanics in Preterm Infants

The changes induced on respiratory mechanics and on tracheobronchial aspirate fluid (TAF) cytology by dexamethasone courses started at two different postnatal ages in preterm infants at risk of chronic lung disease (CLD) were reported in this clinical trial designed in two phases. The first phase of the study included 20 neonates with birth weight ≤1,250 g and gestational age ≤32 weeks, who were oxygen and ventilator dependent on the 10th day of life. They were randomly assigned to the moderately early dexamethasone (MED) group or to the control group. The second phase of the study included 20 neonates with the same characteristics, oxygen and ventilator dependent on the 4th day of life, randomly assigned to the early dexamethasone (ED) group or to the control group. Both treated groups received dexamethasone intravenously for 7 days (0.5 mg/kg/day for the first 3 days, 0.25 mg/kg/day for the next 3 days, and 0.125 mg/kg/day for the last day of treatment). The control groups received no steroid treatment. A significantly lower absolute cell count and percentage of neutrophils (PMN) in the TAF and significantly higher dynamic lung compliance (Cdyn) values were observed in both the MED treated compared to the untreated infants and the ED treated infants compared to the control group. Moreover these changes were more precocious in the ED Group compared to the MED Group. Our study suggests that dexamethasone could be more efficacious in reducing effects of ventilator-induced lung injury in preterm infants at high risk of CLD when started earlier.