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Background/Objectives: Very low birth weight (VLBW) infants may require enhanced nutrition, even during complementary feeding. However, there are limited data on macronutrient intake during this period, particularly concerning the individual timing of the introduction of solid foods in a representative VLBW infant population. Methods: This prospective observational study analyzed macronutrient intake in VLBW infants with a gestational age < 32 weeks based on whether solid foods were introduced early (<17 weeks corrected age (CA)) or late (≥17 weeks corrected age) Nutritional intake was analyzed using a 24 h recall at 6 weeks CA and 3-day dietary records at 12 weeks, 6, 9, and 12 months CA. Results: In total, 115 infants were assigned to the early and 82 to the late group. The timing of solid food introduction did not affect macronutrient intake, except for a lower fat and higher carbohydrate intake (% of energy) in the early group at 12 weeks and 6 months CA: early vs. late, fat—12 weeks: 47.0% vs. 49.0%, 6 months: 39.2% vs. 43.3%; carbohydrates—12 weeks: 44.9% vs. 43.2%, 6 months: 51.3% vs. 48.0%. Apart from docosahexaenoic acid (DHA) and arachidonic acid (AA), dietary intake recommendations were met in both groups. While nutrient intakes varied significantly between breastfed and formula-fed infants, those with comorbidities exhibited similar nutrient intake levels compared to those without. Conclusions: Our findings suggest adequate macronutrient intakes in VLBW infants irrespective of the timing of solid introduction. However, there is a notable need to enhance dietary intakes of DHA and AA. Future research is crucial to assess whether current nutrient intakes are sufficient for VLBW infants with comorbidities. [ABSTRACT FROM AUTHOR]

Abstract Background Establishing successful lactation in mothers of very low birth weight (VLBW,

Background: Establishing successful lactation in mothers of very low birth weight (VLBW, <1500g) infants requires structured lactation support. Little is known about mothers' perspectives on lactation support in German neonatal intensive care units (NICUs). Methods: This paper features a convergent mixed-method approach that includes a retrospective, cross-sectional questionnaire and interview data to showcase mothers' perceptions of lactation support in NICUs. Content analysis of the interviews (n = 12) and a descriptive analysis of quantitative data (n = 533) were performed to illustrate the current status and need for lactation support in German NICUs. Results: The results show that lactation support in German NICUs is often inadequate and does not comply with recommendations based on the existing literature to encourage pumping and breastfeeding in mothers. The data imply that even if lactation is successfully initiated in most cases, it is often not maintained over time, which may be due to a lack of personal support and consistent information. Conclusion: The overall structures and institutional guidelines for lactation support should be encouraged to promote nutrition with mother´s own milk in German NICUs. [ABSTRACT FROM AUTHOR]

Background: Using soybean oil–based lipid emulsions (Intralipid), which contain higher amounts of ω‐6 fatty acids and phytosterols in parenteral nutrition, is a risk factor for cholestasis (parenteral nutrition–associated cholestasis [PNAC]). An alternative form of a mixed lipid emulsion (SMOFlipid) has been developed to reduce the risk of PNAC, but significant benefits over Intralipid in very low birth weight (VLBW) infants have yet to be demonstrated. The aim of this study was to compare the differences in PNAC incidence in VLBW infants receiving SMOFlipid vs Intralipid. Methods: The study was conducted in Sir Run Run Shaw Hospital of the Zhejiang University School of Medicine, Hangzhou, China, from January 2016 to March 2022. In total, 235 VLBW infants were administered SMOFlipid or Intralipid for ≥21 days and were included in the study. The primary outcome was the incidence of PNAC. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, late‐onset sepsis, length of stay, weight 28 days after birth, severity of PNAC, and the time to reversal of PNAC. Results: Forty‐four VLBW infants (35.5%) in the SMOFlipid group vs 41 (36.9%) in the Intralipid group achieved PNAC (P = 0.817). The subgroup analysis showed that the peak direct bilirubin level was lower (median [interquartile range] 55.6 [36.4] vs 118.4 [77.2] μmol/L; P < 0.001), and the time to reversal of PNAC was shorter (44 [49] vs 96 [61]; P < 0.001) in the SMOFlipid group than in the Intralipid group. Conclusion: SMOFlipid may represent a better alternative for VLBW infants who require prolonged parenteral nutrition. [ABSTRACT FROM AUTHOR]

Background: The use of diuretics is extremely common in infants cared for in neonatal wards, despite the lack of proven efficacy for many conditions. The main objective of this study was to assess the rate of diuretics exposure in a multicenter French cohort. The secondary objectives were to describe the evolution of this exposure over time, the indications, the prescription practices, and the exposure rates among centers. Methods: An observational study was conducted in 40 Level 3 French neonatal intensive care units using the same computerized order-entry system. Neonates hospitalized between January 2017 to December 2021 with a corrected age between 24 and 44 weeks of gestation at admission were eligible. Results: A total of 86,032 patients were included. The exposure rate was 8.5%, more specifically 29.4% for children born at < 32 weeks of gestation and 3.7% for neonates born at term. There was no significant variation over the study period, but the exposure ranged from 2.4% to 26.5% depending on the center. The main drugs prescribed were furosemide, spironolactone and dopamine with a diuretic purpose. The main indications were "fluid retention," and to a lesser extent "bronchopulmonary dysplasia" and "post-transfusion." For furosemide, the first exposure occurred in mean at 16.5 (±17.8) days of life, mean duration of exposure was 6.2 (±9.5) days, and the cumulative dose was in mean 10.7 (23.9) mg/kg. Conclusion: Diuretic prescription practices vary between centers. The administration of these drugs is often non-evidence based, doses and duration of treatment easily exceed toxic thresholds. [ABSTRACT FROM AUTHOR]

Aim: To compare two commonly used methods for expression of breastmilk, namely hand expression and manual pump electric, for the expression of milk and assess which method would be more successful in achieving the volumes of milk required. Study design: Randomised trial. Setting: Neonatal Intensive Care Unit (NICU). Methods: Mothers who delivered very-low-birth-weight infants (VLBW, birth weight <1500 grams) were randomly placed into two groups using block method of randomisation. In both the groups, Group I (hand expression, HE) and Group II (Medela Lactina Electric Plus breast pump, Electric Pump (EP) the expression of milk began within 24 hours of delivery. The volumes of expressed breast milk (EBM) were compared between the two groups. Results: The volumes of milk expressed were compared over a period of 10 days. The difference in volumes was found to be significant from Day 2 onwards, with mothers in Group II (EP) expressing more milk than mothers in Group I (HE) (p<0.001). This difference in volumes of milk expressed continued to remain significant throughout the entire duration of the study, i.e. until day 10. Conclusions: Thus, the EP method is superior compared to the HE method for producing adequate EBM in mothers of VLBW infants. Future implications: Early expression of breastmilk using electric pump (EP) may help to meet breastmilk demands of VLBW infants in the NICU. [ABSTRACT FROM AUTHOR]

Background/Objectives: Very low birth weight (VLBW) infants may require enhanced nutrition, even during complementary feeding. However, there are limited data on macronutrient intake during this period, particularly concerning the individual timing of the introduction of solid foods in a representative VLBW infant population. Methods: This prospective observational study analyzed macronutrient intake in VLBW infants with a gestational age < 32 weeks based on whether solid foods were introduced early (Results: In total, 115 infants were assigned to the early and 82 to the late group. The timing of solid food introduction did not affect macronutrient intake, except for a lower fat and higher carbohydrate intake (% of energy) in the early group at 12 weeks and 6 months CA: early vs. late, fat—12 weeks: 47.0% vs. 49.0%, 6 months: 39.2% vs. 43.3%; carbohydrates—12 weeks: 44.9% vs. 43.2%, 6 months: 51.3% vs. 48.0%. Apart from docosahexaenoic acid (DHA) and arachidonic acid (AA), dietary intake recommendations were met in both groups. While nutrient intakes varied significantly between breastfed and formula-fed infants, those with comorbidities exhibited similar nutrient intake levels compared to those without. Conclusions: Our findings suggest adequate macronutrient intakes in VLBW infants irrespective of the timing of solid introduction. However, there is a notable need to enhance dietary intakes of DHA and AA. Future research is crucial to assess whether current nutrient intakes are sufficient for VLBW infants with comorbidities.

Background: We aimed to assess prevalence and clinical characteristics of newborns receiving kidney replacement therapy (KRT). Methods: We used the National Inpatient Sample (NIS) dataset for the years 2000–2017. Newborns treated with peritoneal dialysis (PD), hemodialysis (HD), and continuous KRT (CKRT) were included. Trend analysis using the Cochran-Armitage test was used to assess prevalence over the years. Results: A total of 64,532,552 hospitalized newborns were included. Among the 4281 infants treated with KRT, 2501 (58.4%) were treated with PD, 997 (23.3%) had HD, and 783 (18.3%) used CKRT. Associated diagnoses included congenital kidney anomalies (37.4% vs. 15% vs. 9.5%), urinary tract anomalies (35% vs. 12.5% vs. 6.3%), and congenital heart disease (68% vs. 25.7% vs. 72.3%). Median length of stay was longest in PD patients (39 days vs. 18 days vs. 26 days), respectively. However, cost of hospitalization was greatest in CKRT patients (US $490,916 vs. US $218,514 vs. US $621,554), respectively. In the entire cohort, 54,424 newborns had acute kidney injury (AKI); of them 16,999 (31%) died. KRT was used in 2,688 (4.9%) of infants with AKI. Over the study period, trends for utilization of PD (from 0.042 to 0.06%) and CKRT (from 0.03 to 0.21%) increased whereas the hemodialysis trend decreased (from 0.021 to 0.013%). Conclusions: Congenital heart disease (CHD) and congenital anomalies of the kidneys and urinary tract (CAKUT) are the major diagnoses in newborns receiving KRT. Utilization of PD was greater than HD and CKRT. Trends of PD and CKRT utilization increased over time. Less than 5% of infants diagnosed with AKI received KRT. [ABSTRACT FROM AUTHOR]

This randomized study investigates whether feeding very low birth weight (VLBW) infants with mother's own milk (MOM) supplemented with either preterm (PDM) or term donor milk (TDM), when MOM is insufficient, has a positive impact on infants' protein intake and growth. A hundred and twenty VLBW infants were randomized into two groups. Group A (43 infants) received MOM supplemented with PDM, whereas Group B (77 infants) was fed with MOM supplemented with TDM, for the first three weeks of life (donor milk period). Breast milk fortifier was added when milk feeds exceeded 50 mL/Kg/day. After the donor milk period, both groups were fed with formula when MOM was not available or the milk bank was unable to provide TDM. Protein intake was higher in Group A than in Group B at initiation of milk fortification (p = 0.006), as well as during the 3-week donor milk period (p = 0.023) and throughout hospitalization (p = 0.014). Moreover, Group A presented higher Δz-score for body weight (p = 0.019) and head circumference (p = 0.001) from birth to the end of donor milk period, and higher mean body weight at discharge (p = 0.047) compared to Group B. In conclusion, when donor milk is required, PDM positively impacts protein intake and growth in VLBW infants (NCT05675397). [ABSTRACT FROM AUTHOR]

Background Human milk consumption is a protective factor against infection. However, the high variability of human milk composition makes it difficult for clinicians and researchers to assess the adequacy of nutritional intake. Objective To identify the nutritional profiles and composition of premature human milk and dietary intake of breastfeeding mother. Methods Human milk specimens were collected from mothers who gave birth to very premature and/or very low birth weight infants. Infants had been admitted to the Neonatology Unit of Dr. Cipto Mangunkusumo Hospital, Jakarta. The milk specimens were analyzed with a mid-infrared milk analyzerTM (MIRIS) for four weeks, and maternal dietary macronutrient intake was determined with food record questionnaires on food consumption frequency and food recall. Results Significant changes in nutritional composition of human milk were observed, with the fat concentration and calories increasing with time, and protein concentration decreasing with time. There were no significant differences observed in carbohydrate concentration of milk over the four weeks (P=0.447). Maternal intake of protein, carbohydrates, fat and calories was lower than the recommended values for breastfeeding women. Conclusion The macronutrient (protein and fat) and energy contents of human milk change weekly. Dietary intake of breastfeeding women are lower than recommended values.

Wasim Khasawneh, Mohammad Khassawneh, Mai Mazin, Muath Al-Theiabat, Tuka Alquraan Department of Pediatrics and Neonatology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, JordanCorrespondence: Wasim KhasawnehDepartment of Pediatrics and Neonatology, Jordan University of Science and Technology, PO Box 3030, Irbid 22110, JordanTel +962 796041117Fax +962 27095777Email wakhasawneh@just.edu.joPurpose: To identify the clinical and nutritional factors associated with extrauterine growth restriction (EUGR) among very low birth weight infants (VLBW) in a tertiary hospital in Jordan.Patients and Methods: We conducted a retrospective analysis of all VLBW infants admitted at King Abdullah University Hospital between July 2015 and June 2020. Clinical factors, nutritional intake, and growth parameters were collected and analyzed. A multilogistic regression model was applied to identify factors associated with EUGR.Results: Of the 247 VLBW infants included in analysis, 112 (45%) were males, 30 (12%) were below 1000 g, and 72 (29%) were small for gestational age (SGA). EUGR was diagnosed in 198 (80%) at discharge. The rates of EUGR among SGA and non-SGA infants were 97% and 73%, respectively. The EUGR infants had a higher gestational age (30.7 vs 29.8 weeks, p= 0.04), a lower birth weight (1209 vs 1300 g, p= 0.005), a longer ventilatory support (5.7 vs 2.2 days, p= 0.03), a higher incidence of sepsis (23% vs 10%, p= 0.05), and a longer hospitalization (46 vs 38 days, p= 0.03). With multilogistic regression model, the factors associated with EUGR include small-for-gestational age (AOR 9, 95% C.I. 2, 50), > 3-day delay in feeding initiation (AOR 3.8, 95% C.I. 1.2,10), > 14-day delay in achieving full feeds (AOR 3.3, 95% C.I. 1.2, 8), < 3 g/kg of protein intake on the 8th day (AOR 2.1, 95% C.I. 1.1, 4.1), < 100 kcal/kg of total caloric intake on the 15th day (AOR 3.8, 95% C.I. 1.6, 8.9), and occurrence of sepsis (AOR 3, 95% C.I. 1.1, 9).Conclusion: The rate of EUGR in our unit is high. In addition to being SGA at birth, sepsis and suboptimal protein and caloric intake in the first two weeks of life were significantly associated with this complication. A more aggressive enteral and parenteral nutritional approach is needed to minimize postnatal growth delay.Keywords: neonatal nutrition, EUGR, Jordan, VLBW infants

This randomized study investigates whether feeding very low birth weight (VLBW) infants with mother’s own milk (MOM) supplemented with either preterm (PDM) or term donor milk (TDM), when MOM is insufficient, has a positive impact on infants’ protein intake and growth. A hundred and twenty VLBW infants were randomized into two groups. Group A (43 infants) received MOM supplemented with PDM, whereas Group B (77 infants) was fed with MOM supplemented with TDM, for the first three weeks of life (donor milk period). Breast milk fortifier was added when milk feeds exceeded 50 mL/Kg/day. After the donor milk period, both groups were fed with formula when MOM was not available or the milk bank was unable to provide TDM. Protein intake was higher in Group A than in Group B at initiation of milk fortification (p = 0.006), as well as during the 3-week donor milk period (p = 0.023) and throughout hospitalization (p = 0.014). Moreover, Group A presented higher Δz-score for body weight (p = 0.019) and head circumference (p = 0.001) from birth to the end of donor milk period, and higher mean body weight at discharge (p = 0.047) compared to Group B. In conclusion, when donor milk is required, PDM positively impacts protein intake and growth in VLBW infants (NCT05675397).

Background: To assess prevalence and outcomes of acute kidney injury (AKI) in very-low-birth-weight infants. Methods: This cross-sectional study utilized the National Inpatient Sample (NIS) dataset for years 2000–2017. All premature infants with birth weight (BW) <1500g and/or gestational age (GA) ≤32 weeks were included. Analyses were conducted for overall population and two BW categories: <1000g and 1000–1499g. Adjusted odds ratios were calculated after controlling for confounding variables in logistic regression analysis. Cochrane–Armitage test was used to assess for statistically significant trends in AKI frequency over the years. Results: In total, 1,311,681 hospitalized premature infants were included; 19,603 (1.5%) were diagnosed with AKI. The majority (74.3%) were BW <1000g and 63.9% ≤28 weeks gestation. Prevalence of AKI differed by ethnicity; White had significantly less AKI than Black (OR=0.79, p<0.001) and Hispanic (OR=0.83, p<0.001). AKI was significantly associated with higher mortality compared to controls (35.1 vs. 3.0%, p<0.001). AKI was associated with comorbidities such as necrotizing enterocolitis, patent ductus arteriosus, bronchopulmonary dysplasia, intraventricular hemorrhage, and septicemia. In a regression model, AKI was associated with higher mortality after controlling confounding factors (aOR=7.79, p<0.001). AKI was associated with significant increase in length of stay (p<0.001) and cost of hospitalization in survivors (p<0.001). There is a significant trend for increased AKI frequency over the years (Z score=4.33, p<0.001). Conclusion: AKI is associated with increased mortality and comorbidities in preterm infants, especially in infants with BW <1000g. Further studies are needed to understand precipitating factors and assess preventative measures for this serious complication. [ABSTRACT FROM AUTHOR]

Serial body site swabbing is used to monitor horizontal spread of aggressive bacterial species in the neonatal intensive care unit (NICU). Since colonization/carriage is thought to precede systemic infection, one might expect to retrieve colonizing pathogens from blood cultures. This hypothesis, however, has not been fully investigated in very low birth weight (VLBW) infants that are at high sepsis' risk. The primary outcome was, in a population of VLBW infants with late-onset sepsis, the matching between blood culture results and pathogens isolated from rectal and nose/pharyngeal surveillance swabs in the preceding 2 weeks. The secondary outcomes were the site of swabbing and time interval from colonization to blood culture positivity. Out of 333 VLBW neonates, 80 (24%) were diagnosed with bacterial sepsis. In 46 (57%) neonates, the blood culture showed the same pathogen species cultured from a swab. Of these, 30 were isolated from infants with both body sites colonized with an average time interval of 3.5 days; 2/16 were isolated from rectal swabs and 14 /16 from nose/pharyngeal samples. Conclusion: Our data show a fair correspondence between bacteria colonizing the nasopharynx and/or the rectum and pathogens later isolated from blood cultures. This association depends on the swabbing site, number of sites, and pathogen species. Although these data constitute valuable results, they are not sufficient for providing the sole base of a thoughtful clinical decision. What is Known: • Body site's colonization may precede systemic infection. • Little is known on this mechanism in VLBW infants that are at higher sepsis' risk. What is New: •Colonizing bacteria partially correspond to pathogens of blood cultures in VLBW infants with sepsis. • Correspondence depends on swabbing site, number of sites, and pathogen species. [ABSTRACT FROM AUTHOR]

Background Human milk consumption is a protective factor against infection. However, the high variability of human milk composition makes it difficult for clinicians and researchers to assess the adequacy of nutritional intake. Objective To identify the nutritional profiles and composition of premature human milk and dietary intake of breastfeeding mothers. Methods Human milk specimens were collected from mothers who gave birth to very premature and/or very low birth weight infants. Infants had been admitted to the Neonatology Unit of Dr. Cipto Mangunkusumo Hospital, Jakarta. The milk specimens were analyzed with a midinfrared milk analyzerTM (MIRIS) for four weeks, and maternal dietary macronutrient intake was determined with food record questionnaires on food consumption frequency and food recall. Results Significant changes in nutritional composition of human milk were observed, with the fat concentration and calories increasing with time, and protein concentration decreasing with time. There were no significant differences observed in carbohydrate concentration of milk over the four weeks. Maternal intake of protein, carbohydrates, fat, and calories were lower than the recommended values for breastfeeding women. Conclusion The macronutrient (protein and fat) and energy contents of human milk change weekly. Dietary intake of breastfeeding women are lower than recommended values. [ABSTRACT FROM AUTHOR]

Objective: To assess the evolution of the prevalence of late-onset sepsis (LOS) and meningitis and its predictors in a Portuguese tertiary level Neonatal Intensive Care Unit (NICU) during its participation in the Vermont Oxford Network (VON) between 2000 and 2013. Methods: Descriptive retrospective study of all very low birth weight infants admitted to a level-III NICU between 2000 and 2013. Outborn infants, infants who died in the delivery room and neonates who died during the first 12 hours in NICU were excluded. Patients’ demographic characteristics and clinical data were collected. Data from neonates with and without LOS were compared. Results: The prevalence of LOS significantly decreased from 56.3% between 2000 and 2004 to 26.5% between 2010 and 2013. Infants with a gestational age of 22-27 weeks had more LOS (65.6%) than neonates with 32-36 weeks (20.9%). Similarly, smaller infants (weighing ≤ 1,000 g) had more LOS (59.4%) than babies with a weight > 1,000 g (33.3%). LOS was significantly associated with a gestational age between 22 and 27 weeks, mechanical ventilation (MV), nasal CPAP, necrotizing enterocolitis and the use of steroids for bronchopulmonary dysplasia. Conclusions: Preterm infants require many invasive devices to ensure their survival, such as MV, which greatly increases their infection risk. To minimize this risk, it is crucial to guarantee that better practices are followed, necessitating the use of regular audits. It is really important to know the data about LOS from our NICU, which allows sharing and comparison with peers in order to improve nosocomial infection prevention and control practices.

Abstract Background Fortification of human milk is a standard practice for feeding very low birth weight infants. However, preterm infants often still experience suboptimal growth and feeding intolerance. New fortification strategies and different commercially available fortifiers have been developed. Commercially available fortifiers are constituted by a blend of ingredients from different sources, including plant oils and bovine milk proteins, thus presenting remarkable differences in the quality of macronutrients with respect to human milk. Based on the consideration that donkey milk has been suggested as a valid alternative for children allergic to cow’s milk proteins, due to its biochemical similarity to human milk, we hypothesized that donkey milk could be a suitable ingredient for developing an innovative human milk fortifier. The aim of the study is to evaluate feeding tolerance, growth and clinical short and long-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk, in comparison to an analogous population fed with traditional fortifier and protein supplement containing bovine milk proteins. Methods The study has been designed as a randomized, controlled, single-blind clinical trial. Infants born

OBJECTIVE Administration of fluid bolus in very low birth weight (VLBW) infants is a common practice in the NICU, but one without clear evidence demonstrating benefits in clinical outcomes. On the contrary, recent observational studies have suggested a potential detrimental effect of empiric fluid bolus in preterm infants, especially in the absence of clear indications. The aim of this study was to assess the impact of fluid bolus on various clinical outcomes in VLBW infants. METHODS Retrospective cohort study of VLBW infants born at ≤34 weeks' gestation and/or ≤1500-g birth weight at a single level III NICU from January 1, 2008, to December 31, 2013, and who received at least one fluid bolus within the first 48 hours of life. Outcomes studied were in-hospital mortality, need for home oxygen, incidence of chronic lung disease (CLD), prevalence of patent ductus arteriosus (PDA), and intraventricular hemorrhage (IVH). RESULTS Of 516 infants, 112 (21.7%) received a fluid bolus within the first 48 hours of life for various indications. Propensity models suggested no statistical difference for CLD or mortality, but exposed infants had an increased incidence of home on oxygen (p = 0.018), PDA prevalence (p = 0.008), and IVH prevalence (p = 0.038). CONCLUSIONS Fluid bolus in the first 48 hours of life may be associated with increased incidence of need for home oxygen and higher prevalence of PDA and IVH in VLBW infants. Future studies are needed to address these important adverse outcomes. ABBREVIATIONS BP, blood pressure; BW, birth weight; CLD, chronic lung disease; GA, gestational age; IVH, intraventricular hemorrhage; MAP, mean arterial pressure; NICU, neonatal intensive care unit; PDA, patent ductus arteriosus; PIH, pregnancy-induced hypertension; VLBW, very low birth weight [ABSTRACT FROM AUTHOR]

Aim: To correlate nucleated red blood cell counts and serum lactate concentrations on day 2 and 5 of life with morbidity and mortality in very low birth weight infants and to determine corresponding cutoff values.Methods: Retrospective analysis in a cohort of very low birth weight infants.Results: 250 very low birth weight infants were included in this study. Gestational age ranged from 23 to 35 weeks (mean 29.04) and birth weight was 320-1500 g (mean 1047.9). 55 (22%) patients developed intraventricular hemorrhage, 55 (22%) bronchopulmonary dysplasia, 12 (4.8%) periventricular leukomalacia, 93 (37.2%) retinopathy of prematurity, and 1 (0.4%) necrotizing enterocolitis. Mortality rate was 25/250 (10%). Nucleated red blood cells and serum lactate on day 2 of life were associated with mortality (p < 0.001). Serum lactate on day 5 of life demonstrated an association with retinopathy of prematurity (p = 0.017), bronchopulmonary dysplasia (p = 0.044), and intraventricular hemorrhage (p < 0.001). Cutoff values predicting mortality were >89.5 nucleated red blood cells/100 leucocytes (sensitivity 68.2%, specificity 89.0%) and serum lactate concentrations >8.5 mmol/l (sensitivity 69.6%, specificity 93.5%) on day 2 of life.Conclusion: We conclude that both nucleated red blood cell count and serum lactate concentration are valuable biomarkers in predicting important outcome parameters in very low birth weight infants. [ABSTRACT FROM AUTHOR]

Human milk fortification is a routine clinical practice for feeding preterm infants. We hypothesized that donkey milk can be a suitable basis for developing an innovative human milk fortifier. Our randomized controlled single-blind clinical trial, named “Fortilat”, evaluated the feeding tolerance, growth and clinical short-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk. The aim of the current study is to extend the previous findings and to evaluate the auxological outcomes of the infants enrolled in the “Fortilat” trial at 18 months of age. In the previous trial “Fortilat”, the fortification protocol followed was the same for the two groups, and the two diets were designed to be isoproteic and isocaloric. All infants enrolled in the trial were included in a premature infant developmental evaluation program consisting of hospital visits at 40 ± 1 weeks of postmenstrual age, and at 6, 12 and 18 months of corrected age. Weight, head circumference and length were expressed in z-score using neonatal Intergrowth21st and INeS charts at birth, and WHO 0–5 years growth charts at 18 months. 122 children (Bovine-arm = 62, Donkey-arm = 60) were included in this study. All the observations were recorded in the interval of 18 ± 3 months of the correct age. The two groups did not differ for head circumference, length or weight at 18 months of age. Our data show that fortifiers derived from donkey milk had not different long term auxological outcomes of standard bovine-derived fortifier, but the new donkey milk fortifier was well tolerated in our population.

Adequate nutrition is fundamental to neonatal survival and short-term outcomes, but it also has long-term consequences on quality of life and neurologic development of preterm infants. Donkey milk has been suggested as a valid alternative for children allergic to cows’ milk proteins, due to its biochemical similarity to human milk; we, hence, hypothesized that donkey milk could be a suitable basis for developing an innovative human milk fortifier for feeding preterm infants. The aim of the current study was to extend the findings and to evaluate the neurodevelopmental outcomes at 18 months of corrected age of the infants enrolled in the clinical trial named “Fortilat”. Infants born ≤1500 g and

Background: Fortification of human milk is a standard practice for feeding very low birth weight infants. However, preterm infants often still experience suboptimal growth and feeding intolerance. New fortification strategies and different commercially available fortifiers have been developed. Commercially available fortifiers are constituted by a blend of ingredients from different sources, including plant oils and bovine milk proteins, thus presenting remarkable differences in the quality of macronutrients with respect to human milk. Based on the consideration that donkey milk has been suggested as a valid alternative for children allergic to cow's milk proteins, due to its biochemical similarity to human milk, we hypothesized that donkey milk could be a suitable ingredient for developing an innovative human milk fortifier. The aim of the study is to evaluate feeding tolerance, growth and clinical short and long-term outcomes in a population of preterm infants fed with a novel multi-component fortifier and a protein concentrate derived from donkey milk, in comparison to an analogous population fed with traditional fortifier and protein supplement containing bovine milk proteins.Methods: The study has been designed as a randomized, controlled, single-blind clinical trial. Infants born <1500 g and <32 weeks of gestational age were randomized to receive for 21 days either a combination of control bovine milk-based multicomponent fortifier and protein supplement, or a combination of a novel multicomponent fortifier and protein supplement derived from donkey milk. The fortification protocol followed is the same for the two groups, and the two diets were designed to be isoproteic and isocaloric. Weight, length and head circumference are measured; feeding tolerance is assessed by a standardized protocol. The occurrence of sepsis, necrotizing enterocolitis and adverse effects are monitored.Discussion: This is the first clinical study investigating the use of a human milk fortifier derived from donkey milk for the nutrition of preterm infants. If donkey milk derived products will be shown to improve the feeding tolerance or either of the clinical, metabolic, neurological or auxological outcomes of preterm infants, it would be an absolute innovation in the field of feeding practices for preterm infants.Trial Registration: ISRCTN - ISRCTN70022881 . [ABSTRACT FROM AUTHOR]

Purpose: To investigate the association of a standardized rapid enteral feeding strategy (established in 2011 in our unit) with intestinal morbidity in very low birth weight (VLBW) infants. Methods: A total of 301 inborn VLBW infants were included in this single-centre retrospective cohort study. We compared the incidence of intestinal morbidity (defined as necrotizing enterocolitis or intestinal perforation) in slowly enterally fed infants in 2008-2010 (10 ml/kg/day increase of milk feeds) to a corresponding cohort of rapidly enterally fed infants in 2011-2013 (20 ml/kg/day increase of milk feeds). Univariate and multivariable logistic and linear regression analyses, respectively, were performed to control for confounding variables. Results: Both groups were similar regarding baseline demographic and perinatal characteristics. In univariate modeling, intestinal morbidity did not significantly differ between the two groups (p = 0.25), neither did all-cause mortality nor incidence of late onset sepsis in multivariable modeling. In contrast, length of hospital stay (HS) and duration of parenteral nutrition (PEN) were significantly shorter in the rapid group (HS: -8.35 days, p = 0.012 and PEN: -7.13 days, p<0.001). Conclusions: Implementation of a more rapid enteral feeding regime is safe in VLBW infants and may significantly shorten length of HS and PEN in this cohort. [ABSTRACT FROM AUTHOR]

Objective: We aimed to find out the incidence and risk factors of nosocomial infections in VLBW neonates and to explore the microbiologic flora, sensitivity pattern and outcome. Methods: A prospective, observational study was performed in a neonatal intensive care unit of a teaching hospital. VLBW infants excluding those diagnosed with early onset sepsis, admitted to the unit between August 2012 and March 2013 were followed up for evidence of nosocomial sepsis. Results: Of 92 VLBW infants, 23 developed nosocomial sepsis, incidence rate being 25%. Decreasing birth weight (1251-1500 g, 10.9%; 1001-1250 g, 28%; 751-1000 g, 50%; P<.001) and gestational age (>33wks, 0%; 29-32wks, 21.3%; 26-28 wks, 66.7%; p<.001) were found to be associated with statistically significant increase in nosocomial sepsis rate. On multivariate logistic regression, only peripherally inserted central catheter (PICC) line was independently associated with increased risk of nosocomial sepsis (aOR 13.33, 95% CI 3.58-49.5) in VLBW. A predominance of Gram negative over Gram positive nosocomial sepsis (75% vs. 25%) with higher mortality in the Gram negative group (55% vs. 0%) was observed. Klebsiella pneumoniae was the predominant microbe (33.4%). All microbes were sensitive to first line antibiotics except Elizabeth kingia meningoseptica and one episode of K. pneumoniae. Seven (30.4%) VLBW neonates with nosocomial sepsis died. Conclusions: Among VLBW infants, the incidence of nosocomial sepsis was 25%. Lower birth weight, lesser gestational age and PICC line were important risk factors. Gram negative nosocomial sepsis was associated with higher mortality compared to Gram positive sepsis. [ABSTRACT FROM AUTHOR]

Study Purpose: To provide reference values for nucleated red blood cells and serum lactate concentrations in very and extremely low birth weight (VLBW/ELBW) infants in the first week of life.Patients and Methods: Retrospective data analysis of serial, daily measurements of NRBC counts and serum lactate during the first 6days of life in VLBW and ELBW infants.Results: In total, 250 infants<1500g were included in this study. Intrauterine growth retardation (IUGR) was seen in 87 (34.8%) patients. Gestational age (GA) ranged from 23 to 35weeks (mean 29.0weeks) and birth weight (BW) was 320-1499g (mean 1047.9g). During hospital stay, 55 (22%) patients developed IVH and 55 children (22%) BPD. PVL was seen in 12 (4.8%) cases, ROP in 93 (37.2%) and NEC in only 1 (0.4%) patient. NRBC counts as well as serum lactate concentrations depended significantly on birth weight (p<0.01) and presence respectively absence of IUGR (p<0.01). Both NRBC counts and serum lactate concentrations declined constantly during the 6-day period (p<0.01), and both were highly inter-correlated (p<0.01).Conclusions: This is one of only a very few studies that systematically and serially evaluated both NRBC counts and serum lactate concentration in VLBW and ELBW infants in the first 6days of life. Both parameters were significantly dependent on birth weight and the presence of IUGR. Moreover, a significant correlation between NRBC counts and serum lactate concentrations in this early period of life could be demonstrated. In future studies, the role of these readily available biomarkers in predicting important neonatal outcome parameters needs to be evaluated in a prospective manner. [ABSTRACT FROM AUTHOR]

Background: The indications and strategies for treatment of patent ductus arteriosus (PDA) are controversial, and the safety and long-term benefits of surgical PDA closure remain uncertain. The aim of this study was to compare the lung function of very low birth weight (VLBW) infants after successful PDA treatment with a cyclooxygenase inhibitor or secondary surgical ligation.Methods: A total of 114 VLBW infants (birth weight < 1500 g), including 94 infants (82%) with a birth weight < 1000 g, who received treatment for hemodynamically significant PDA (hsPDA), were examined at a median postmenstrual age of 48 weeks. All infants were initially given pharmacological treatment, and 40 infants (35%) required PDA ligation. Lung function testing (LFT) included tidal breathing measurements, measurement of respiratory mechanics assessed by the occlusion test, whole-body plethysmography, SF6 multiple breath washout, forced expiratory flow (V'maxFRC) by the rapid thoracoabdominal compression technique, exhaled NO (FeNO), and arterialized capillary blood gas analysis.Results: On the day of the LFT, the 2 groups had similar postconceptional age and body weight. However, the PDA ligation group was more immature at birth (p < 0.001) and had reduced respiratory compliance (p < 0.001), lower V'maxFRC (p = 0.006), increased airway resistance (Raw) (p < 0.001), and impaired blood gases (p < 0.001). Multivariate analysis showed that PDA surgery was an independent risk factor for increased Raw.Conclusion: PDA ligation after failed pharmacological treatment is associated with impaired lung function as compared to successful pharmacological closure in infants at a postmenstrual age of 48 weeks. However, only Raw was independently affected by PDA ligation, while all other differences were merely explained by patient characteristics. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine whether patient loads, infant status on admission and treatment interventions were significantly associated with inter-institutional variations in sepsis rates in very-low-birth-weight (VLBW) infants in the Malaysian National Neonatal Registry (MNNR).Methods: This was a retrospective study of 3,880 VLBW (≤ 1,500 g) infants admitted to 34 neonatal intensive care units (NICUs) in the MNNR. Sepsis was diagnosed in symptomatic infants with positive blood culture.Results: Sepsis developed in 623 (16.1%) infants; 61 (9.8%) had early-onset sepsis (EOS) and 562 (90.2%) had late-onset sepsis (LOS). The median EOS rate of all NICUs was 1.0% (interquartile range [IQR] 0%, 2.0%). Compared with NICUs reporting no EOS (n = 14), NICUs reporting EOS (n = 20) had significantly higher patient loads (total live births, admissions, VLBW infants, outborns); more mothers with a history of abortions, and antenatal steroids and intrapartum antibiotic use; more infants requiring resuscitation procedures at birth; higher rates of surfactant therapy, pneumonia and insertion of central venous catheters. The median LOS rate of all NICUs was 14.5% (IQR 7.8%, 19.2%). Compared with NICUs with LOS rates below the first quartile (n = 8), those above the third quartile (n = 8) used less intrapartum antibiotics, and had significantly bigger and more mature infants, more outborns, as well as a higher number of sick infants requiring ventilator support and total parenteral nutrition.Conclusion: Patient loads, resuscitation at birth, status of infants on admission and treatment interventions were significantly associated with inter-institutional variations in sepsis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of fluconazole prophylaxis on invasive fungal infection (IFI) in very low birth weight (VLBW) infants in the Neonatal Intensive Care Unit (NICU).Methods: VLBW infants receiving antibiotics for more than 3 days were randomized to receive either fluconazole (6 mg/kg) or placebo, every other day for 7 days followed by everyday till day 28 or discharge whichever was earlier. The primary outcome was IFI, and secondary outcome was fungal attributable mortality and all-cause mortality.Results: The incidence of IFI was significantly lower (21%) in the fluconazole group compared to the control group (43.2%, 95%CI 0.09-0.37, p < 0.05). The ARR (absolute risk reduction) was 22.2% and the NNT (number needed to treat) was 5. Fungal attributable mortality was also lower in the fluconazole group (2.6% versus 18.9%, 95%CI 0.003-0.52, p < 0.05).Conclusion: In VLBW neonates on the NICU, use of fluconazole prophylaxis decreases IFI and fungal attributable mortality. [ABSTRACT FROM AUTHOR]

Background and Study Purpose: Intraventricular hemorrhage (IVH) is a major complication in preterm neonates with significant long-term morbidity and an increased mortality rate. The role of the immature coagulation system in the pathogenesis of IVH in these infants is still under debate. The aim of this study was to provide reference values for coagulation studies within the first 24h of life, and to relate these findings to the incidence of IVH.Patients and Methods: In this retrospective study, a total of 250 (male: 123/female: 127; VLBW: 150 and ELBW: 100) infants were included over a 4-year-period. Coagulation studies were performed within the first 24h of life in all infants. Multiple regression analysis was employed to demonstrate a potential association between IVH and a number of known risk and protective factors for IVH (antenatal steroids, birth weight, gender, IUGR, APGAR score at 10minutes, platelet count, INR, PTT, fibrinogen).Results: Mean birth weight was 1047.9±305.6 (range: 320-1490g). Both cellular (platelets, nucleated red blood cells) and plasmatic coagulation parameters (INR, fibrinogen and antithrombin III) were dependent on birth weight. Moreover, INR levels (p<0.05) were significantly increased in neonates with IVH of any grade. Also, INR was positively correlated with the severity of IVH (Spearman's correlation coefficient: 0.193; p=0.003). While overall fibrinogen levels were not associated with IVH, a fibrinogen level<100mg/dL significantly increased the risk for IVH (p<0.01).Conclusions: Our data provide a robust set of reference values for both cellular and humoral coagulation studies in VLBW and ELBW infants for the first 24h of life. The results of our study indicate that abnormal INR levels and fibrinogen levels<100mg/dL are significantly associated with the occurrence of IVH in this susceptible cohort. [ABSTRACT FROM AUTHOR]

Unlabelled: Finding the optimal pharmacological treatment of a patent ductus arteriosus (PDA) in preterm neonates remains challenging. There is a growing interest in paracetamol as a new drug for PDA closure. In this prospective observational cohort study, we evaluated the effectiveness of intravenous paracetamol in closing a PDA in very low birth weight infants with a hemodynamically significant PDA who either did not respond to ibuprofen or had a contraindication for ibuprofen. They received high-dose paracetamol therapy (15 mg/kg/6 h intravenous) for 3-7 days. Cardiac ultrasounds were performed before and 3 and 7 days after treatment. Thirty-three patients were included with a median gestational age of 25(1/7) weeks (IQR 1.66), a median birth weight of 750 g (IQR 327), and a median postnatal age of 14 days (IQR 12). Paracetamol was ineffective in 27/33 patients (82 %). Even more, after previous exposure to ibuprofen, this was even 100 %.Conclusion: In this study, paracetamol after ibuprofen treatment failure was not effective for PDA closure in VLBW infants. From the findings of this study, paracetamol treatment for PDA closure cannot be recommended for infants with a postnatal age >2 weeks. Earlier treatment with paracetamol for PDA might be more effective. [ABSTRACT FROM AUTHOR]