Is targeted fortification of human breast milk an optimal nutrition strategy for preterm infants? An interventional study

BACKGROUND: Fortifying human milk contributes to the prevention of postnatal growth failure in preterm infants. Because of the natural variability of human milk, targeted fortification of human milk has been advocated. However, data regarding the efficacy and safety of prolonged targeted fortification are scarce. We aimed to assess the safety of targeted fortification of human milk in preterm infants compared with standard fortification, as well as the effects on infant growth. METHODS: We conducted an interventional study during hospital stay in healthy very low birth weight preterm infants who were exclusively fed human milk. Pools of human milk collected for 24 h were analysed using mid-infrared transmission spectroscopy. Targeted fortification of human milk was performed by adding macronutrients to native human milk to obtain optimal ratios of fat (4.4 g), carbohydrates (8.8 g), and protein (3 g) per 100 ml. The intervention period lasted 4-7 weeks. Weekly weight and daily growth rates were compared with those of a standardized fortification group of very low birth weight preterm infants who received standard fortified human milk (n = 10). The osmolality as well as the metabolic and gastrointestinal tolerance were monitored. Intergroup differences were evaluated using the Mann-Whitney U-test. RESULTS: A total of 10 preterm infants (birth weight 1223 \ub1 195 g; gestational age 29.1 \ub1 1.03 weeks) were enrolled and 118 samples of pooled milk were analysed. On average, 1.4 \ub1 0.1 g of protein, 2.3 \ub1 0.5 g of carbohydrate, and 0.3 \ub1 0.1 g of fat per 100 ml were added to the milk. Osmolality values after target fortification were within recommended limits (376 \ub1 66 mOsml/kg). Weekly weight gain (205.5 g; 95 % CI 177-233 vs 155 g; 95 % CI 132-178; p = 0.025) and daily growth rates (15.7 g/kg/day; 95 % CI 14.5-16.9 vs 12.3 g/kg/day; 95 % CI 10.7-13.9; p = 0.005) were higher in infants receiving target fortification than in infants receiving standardized fortification. The infants receiving targeted fortified milk consumed similar volumes as infants in the standardized fortification group (148 \ub1 4.5 vs 146 \ub1 4 ml/kg/day). No signs of either gastrointestinal or metabolic intolerance were observed. CONCLUSIONS: Target fortification appears to promote growth in very low birth weight preterm infants without any detrimental effects. Trial registration NCT02716337

Bronchoalveolar Lavage-microRNAs Are Potential Novel Biomarkers of Outcome after Lung Transplantation

Background. Primary graft dysfunction, infections, and acute rejection (AR) worsen lung transplantation (LTx) outcome and patient survival. Despite significant efforts, reliable biomarkers of acute lung allograft dysfunction are lacking. To address this issue, we profiled the bronchoalveolar lavage (BAL) miRNome in LTx patients. Methods. BAL-microRNAs (miRNAs) from 16 patients were collected 7 days (T0), 15 days (T1), and 3 months (T2) after bilateral LTx and profiled on low-density array. Unsupervised and supervised analyses were used to identify miRNAs associated with clinical features, pneumonia, or AR. Prognostic markers were identified using the Cox model. Targeted signaling pathways were predicted in silico. A second series of 11 patients were used to validate AR-associated miRNAs. Results. Variation in BAL-miRNAs was associated with acute lung allograft dysfunction. Increased levels of miR-23b-3p at T2 were detected in patients with pneumonia, whereas let-7f-5p, miR-146b-3p, miR-22-5p, miR-29c-5p, miR-362-5p, and miR-452-5p were upregulated at T2 in patients with AR. miR-148b-5p and miR-744-3p distinguished LTx patients with AR in both cohorts. Low miR-148b-5p and high miR-744-3p expression levels were significantly associated with a shorter time to AR either within the first year after LTx or during follow-up. Combination of the 2 miRNAs identified LTx patients with higher AR risk independently of clinical variables. Conclusions. Our data provide new insights into the roles of BAL-miRNAs in regulating the pulmonary environment after transplantation and suggest that these miRNAs could serve as biomarkers of early- or mid-stage events. If validated, these findings could pave the way to a personalized clinical approach in LTx patients

Does human milk modulate body composition in late preterm infants at term-corrected age?

(1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content \u3b2 = - 47.9, 95% confidence interval (CI) = -95.7; p = 0.18; p = -0.049; = \u3b2=-89.6, 95% CI = -131.5; -47.7; p < 0.0001; - = -104.1, 95% CI = -151.4; -56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants

Clinical evaluation of two different protein content formulas fed to full-term healthy infants: A randomized controlled trial

Background: A high early protein intake is associated with rapid postnatal weight gain and altered body composition. We aimed to evaluate the safety of a low-protein formula in healthy full-term infants. Methods: A randomized controlled trial was conducted. A total of 118 infants were randomized to receive two different protein content formulas (formula A or formula B (protein content: 1.2 vs. 1.7g/100mL, respectively)) for the first 4 months of life. Anthropometry and body composition by air displacement plethysmography were assessed at enrolment and at two and 4 months. The reference group comprised 50 healthy, exclusively breastfed, full-term infants. Results: Weight gain (g/day) throughout the study was similar between the formula groups (32.5\ub16.1 vs. 32.8\ub16.8) and in the reference group (30.4\ub15.4). The formula groups showed similar body composition but a different fat-free mass content from breastfed infants at two and 4 months. However, the formula A group showed a fat-free mass increase more similar to that of the breastfed infants. The occurrence of gastrointestinal symptoms or adverse events was similar between the formula groups. Conclusions: Feeding a low-protein content formula appears to be safe and to promote adequate growth, although determination of the long-term effect on body composition requires further study

Growth and Fat Mass in Preterm Infants Fed A Protein-Enriched Postdischarge Formula (PDF): A Randomized Controlled Trial

Background and aims: Male infants with BW< 1250 g benefit from PDF. Fetal growth seems to influence growth recovery whereas fat restoration occurs irrespective of BW. To evaluate whether being fed a PDF determines a growth benefit in two subgroups of infants. Methods: 123 preterm infants born AGA (BW=1193.4\ub1 230 g; GA=29\ub11.9 wks) and 84 born SGA (BW=1127\ub1 262g; GA=31.3\ub11.9 wks) were randomized at term corrected age (CA) in G1: 59 AGA fed PDF (2.9 g/100 kcal), G2: 64 AGA fed term formula (TF) (2.1 g/100 kcal), G3: 41 SGA fed PDF, G4: 43 SGA fed TF. From 6 months infants were fed a follow on formula and weaned according to ESPGHAN recommendations. Growth and body composition were assessed by an air displacement plethysmography system at term, 1, 3, 5, 6, 12 months. ANOVA, regression analysis. Results: G1 and G3 protein intakes were higher than those of G2 (p< 0.005) and G4(p< 0.05), respectively, whereas weight, length and fat mass were similar at each study point. G1 mean HC (cm) was bigger than that of G2 at six months (43.5\ub1 1.9 vs 42.6\ub11.6, p=0.03) whereas at 12 months no difference was found (45.4\ub11.6 vs 46\ub11.6). In AGA infants being fed a PDF formula, being male, not having a postnatal growth retardation at term correlated with bigger HC at six months [(p< 0.001), unstandardized B coefficient (SE) 0.9 (0.36); 1.2 (0.36); 1.2 (0.37), respectively]. Conclusions: Male AGA without postnatal growth retardation at term but not SGA infants appear to benefit from being fed PDF

Sympatho-Vagal Dysfunction in Patients with End-Stage Lung Disease Awaiting Lung Transplantation

Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx; 19 men, age 38 \ub1 15 years) and 49 healthy non-smoking controls (HC; 22 men, age 40 \ub1 16 years) were enrolled in a case-control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients

Determinants of breastfeeding discontinuation in an Italian cohort of mother-infant dyads in the first six months of life: A randomized controlled trial

Background: Among breastfeeding determinants, the marketing of breast milk substitutes might contribute to suboptimal breastfeeding rates. The aim of this study was to investigate the effect of receiving information on breast milk substitutes on breastfeeding rates. Methods: We conducted a randomized, single-blind, controlled trial from 2012 to 2014 in a northern Italian maternity ward. We enrolled 802 Caucasian mothers who gave birth to healthy, full-term singletons with a birth weight > 2500 g and who were exclusively breastfeeding from delivery to discharge. Mothers who gave birth to infants with congenital diseases, chromosomal abnormalities, perinatal infections and/or cardio-respiratory instability and/or mothers being affected by endocrine and/or metabolic and/or gastrointestinal and/or renal diseases were excluded. Mothers were randomized to either receive (group A, n = 405) or not (group B, n = 397) written information on a breast milk substitute at discharge. Breastfeeding was promoted and supported in all mother-infant pairs equally. The mode of feeding for up to 6 months after delivery was determined by phone interview. To detect a 10% difference between groups in the discontinuation rate of exclusive breastfeeding at three months of age at 5% significance and 80% power, a total of 356 mother-infant pairs per group were needed. Results: The exclusive breastfeeding prevalence was 91% and 92% at 7 days, 79% and 70% at 1 month, 75% and 66% at 2 months, 72% and 62% at 3 months, and 3% and 2% at 6 months in groups A and B, respectively. The relative risk (95% confidence interval) of exclusive breastfeeding (group A vs B) at 7 days and at 1, 2, 3 and 6 months was as follows: 0.99 (0.95-1.03), 1.12 (1.03-1.21), 1.13 (1.03-1.24), 1.15 (1.04-1.27), and 1.49 (0.62-3.61). Nutritional, lifestyle and lactational factors were the primary contributing determinants to early breastfeeding discontinuation. Conclusions: The present findings indicate that receiving written information on breast milk substitutes at hospital discharge, provided that breastfeeding support and education are offered, does not negatively affect breastfeeding rates. Trial registration: NCT03208114. Registered 5 July 2017

Is nutritional support needed in late preterm infants?

Background: Late preterm birth accounts for 70 % of all preterm births. While the impact of feeding problems in very preterm infants has been widely investigated, data on late preterm infants' feeding issues are scarce. The aim of the present study was to investigate the need of nutritional support during hospital stay in a cohort of late preterm infants and to identify the factors that most contribute to its occurrence. Methods: We analyzed the medical records of late preterm infants, born 2011-2013, admitted to a single institution. Neonatal data, the need for nutritional support, defined as the need for parenteral nutrition or intravenous fluids or tube feeding, and the feeding status at discharge were retrieved. The occurrence of respiratory distress syndrome, congenital malformations/chromosomal diseases, cardiac diseases, sepsis, hypoglycemia, poor feeding and the need for surgical intervention were also collected. Results: A total of 1768 late preterm infants were included. Among the 592 infants requiring a nutritional support, 228 developed a respiratory distress syndrome, two developed a sepsis, one presented with a cardiac disease, 24 underwent a surgical intervention, eight had a chromosomal disease/congenital malformation, 80 had hypoglycemia. In addition, 100 infants required nutritional support due to poor feeding and 149 were born small for gestational age. Birth weight 642000 g (adjusted OR = 12.2, 95 % CI 7.5-19.9, p < 0.0001), gestational age of 34 weeks (adjusted OR = 4.08, 95 % CI 2.8-5.9, p < 0.0001), being small for gestational age (adjusted OR = 2.17, 95 % CI 2.8-5.9, p=0.001), having a respiratory distress syndrome (adjusted OR = 79.6, 95 % CI 47.2-134.3, p < 0.0001) and the need of surgical intervention (adjusted OR = 49.4, 95 % CI 13.9-174.5, p < 0.0001) were associated with a higher risk of need of nutritional support during hospital stay. Conclusions: Late preterm infants are at relatively high risk of requiring nutritional support during hospital stay, especially if they have a birth weight 642000 g, a gestational age of 34 weeks, are born small for gestational age, develop a respiratory distress syndrome and require a surgical intervention. The present findings add to the knowledge of late preterm infants' feeding issues and may contribute to tailoring nutritional approaches for these infants

Serum and exhaled breath condensate inflammatory cytokines in community-acquired pneumonia: a prospective cohort study

Background The role and relationship between pro- and anti-inflammatory cytokines represents one of the least studied aspects of the pathogenesis of community-acquired pneumonia (CAP). The aim of the present study was to evaluate pro- and anti-inflammatory cytokines at both local (lung) and systemic (blood) levels and their relationship with the severity of the disease on admission and time for a patient to reach clinical stability during hospitalisation. Methods This was an observational, prospective, cohort study of hospitalised patients with a diagnosis of CAP at the IRCCS Policlinico Hospital, Milan, Italy, between April 2010 and January 2012. Ten pro-inflammatory cytokines (interleukin [IL]-1, IL-1\u3b1, IL-1\u3b2, IL-2, IL-6, IL-8, tumor necrosis factor [TNF]\u3b1 and interferon [IFN]\u3b3) and anti-inflammatory cytokines (IL-4 and IL-10) were measured in both serum and exhaled breath condensate within 24 h after hospital admission. Results A total of 74 patients (median age: 76 years; gender: 61 % male) were enrolled. The anti- to pro-inflammatory cytokine ratio was reduced in patients with severe disease on admission and prolonged time to reach clinical stability. This was due to lower levels of anti-inflammatory cytokines in the exhaled breath condensate and higher levels of pro-inflammatory cytokines in serum. Conclusions Dis-regulation between pro- and anti-inflammatory pathways might be a part of the pathogenic mechanisms that lead to severe infection and worse early clinical outcomes in CAP patients

Regional analysis with quantitative computed tomography after lung transplantation

Regional analysis with quantitative computed tomography (CT) of graft could be an attractive technique to interpret lung patterns after transplantation. Aim of this study was the definition of lung regional patterns in the early post-transplantation period. We prospectively collected the CT scans at end-expiration (EXP) and full-inspiration (INSP) of patients at 3 months after lung transplantation (LT). Lungs were segmented from both scans. INSP images were registered to EXP by optical flow to obtain maps of density variation (\u394HU) with pixel-by-pixel subtraction. We evaluated a classification of the pixels from maps of \u394HU in low ventilation (LV), consolidation (C), air trapping (AT) and healthy parenchyma (H). Patients who experienced uneventful early postoperative course after bilateral LT were enrolled. The figure shows the resulted composition of the parenchyma in 20 patients: LV=59.6\ub15.4%, C=1.7\ub10.4%, AT=0.06\ub10.05%, H=38.7\ub15.6%. To note that low ventilation pattern still affected the majority of lung tissue while consolidation and air trapping were negligible. Quantitative CT regional analysis may provide a significant advance in the interpretation of ventilation abnormalities after LT