Nutrition and Growth of Preterm Neonates during Hospitalization: Impact on Childhood Outcomes.

The Special Issue has been completed with the publication of 13 review and research articles [...].

Extrauterine Growth Restriction and Optimal Growth of Very Preterm Neonates: State of the Art.

Over the last few decades, there has been an ongoing debate over both the optimal feeding mode for very premature neonates (VPN) as well as what their optimal growth should be. Despite the American Academy of Pediatric declaring since 1997 that the growth of VPN should follow the trajectory of intrauterine fetal growth, differences of opinion persist, feeding policies keep changing, and the growth and development of VPN remains extremely variable not only between countries, but even between neighboring neonatal units. Even the appropriate terminology to express poor postnatal growth (extrauterine growth restriction (EGR) and postnatal growth failure (PGF)) remains a subject of ongoing discussion. A number of recent publications have shown that by implementing breast milk fortification and closely following growth and adjusting nutrition accordingly, as per the consensus guidelines of the major Neonatal Societies, we could achieve growth that closely follows birth centiles. A recent position paper from EPSGAN recommending targeted nutritional support to cover the energy and protein deficits sustained by VPN during periods of critical illness further strengthens the above findings. Conclusion: We can promote better growth of VPN by ensuring a stable administration of sufficient calories and protein, especially in the first 2 weeks of life, implementing breast milk fortification, covering energy and protein deficits due to critical illness, and increasing feeding volumes as per the latest guidelines. The adoption of universal protocol for nutrition and growth of VPN is essential and will enable better monitoring of long-term outcomes for this population.

Are the current feeding volumes adequate for the growth of very preterm neonates?

Postnatal growth failure, a common problem in very preterm neonates associated with adverse neurodevelopmental outcome, has recently been shown not to be inevitable. There is a wide discussion regarding feeding practices of very preterm neonates, specifically regarding feeding volumes and nutrients supply to avoid postnatal growth failure. Current guidelines recommend an energy intake of 115­140 kcal /kg per d with a considerably higher upper limit of 160 kcal/kg per d. The feeding volume corresponding to this energy supply is not higher than 200 ml/kg in most cases. From the other side, randomised and observational studies used higher feeding volumes, and these were associated with better weight gain and growth, while no complications were noted. Taking into account the above, nutritional practices should be individualised in each very and extremely preterm infant trying to reduce postnatal growth failure, pointing out that available data are inconclusive regarding the effect of high-volume feeds on growth. Large clinical trials are necessary to conclude in the best feeding practices of very preterm neonates.

"Aggressive" Feeding of Very Preterm Neonates and Body Mass Index at School Age.

INTRODUCTION: The effects of "aggressive" neonatal feeding policies of very preterm neonates (VPN) and the risk of metabolic syndrome later in life remain questionable. We aimed to evaluate the effect of our "aggressive" nutrition policies of VPN during hospitalisation on body mass index (BMI) at ages 2 and 8 years. MATERIALS AND METHODS: Eighty four VPN, who received "aggressive" nutrition during hospitalisation in an effort to minimise postnatal growth restriction (PGR) (group A), and 62 term neonates, as controls (group B), were enrolled in the study. Group A was further divided in four subgroups depending on the type (A1: fortified expressed breast milk and preterm formula; A2: exclusively preterm formula) and quantity of milk received (A3: maximum feeds 180-210 mL/kg/day; A4: maximum feeds 210 and up to 260 mL/kg/day). BMI was calculated at ages 2 and 8 years and plotted on the centile charts. RESULTS: There was no significant difference in BMI between groups A and B at 2 and 8 years, respectively, in both absolute BMI values and their centile chart distribution. There was no significant difference in BMI at 2 and 8 years either between subgroups A1 and A2 or between subgroups A3 and A4. CONCLUSIONS: "Aggressive" and individualised feeding policy for VPN did not affect the BMI and obesity rates at ages of 2 and 8 years in our study population. The type and quantity of milk feeds had no impact on their BMI at school age. Further larger studies are needed to confirm our results.

Gastric Volume Changes in Preterm Neonates during Intermittent and Continuous Feeding-GRV and Feeding Mode in Preterm Neonates.

Background: We aimed to evaluate gastric volume changes during intermittent milk feeds (IMF) and continuous milk feeds (CMF) in very premature neonates (VPN), with gastric residual volume (GRV) based on antral cross-sectional area (ACSA) measurements and to examine if there were differences in GRV between the two feeding methods. Methods: A randomized prospective clinical trial with crossover design was conducted in 31 preterm neonates (gestational age < 30 weeks). Gastric volume was assessed twice in each neonate (during IMF and CMF feeding), at 7 specific time points during a 2-h observation period by measuring ACSA changes via the ultrasound (U/S) method. Results: There was a significantly different pattern of gastric volume changes between the two feeding methods. GRV, expressed as the median percentage of ACSA measurement at 120 min relative to the higher ACSA measurement during IMF, was found to be 3% (range 0-25%) for IMF and 50% (range 15-80%) for CMF. Neonates fed with IMF had a shorter mean gastric emptying time compared to those fed with CMF (p = 0.0032). No signs of feeding intolerance were recorded in either group during the period of observation. Conclusions: Our results showed that gastric volume changes and gastric emptying time in VPN, based on ACSA measurement changes, depend on the milk feeding method. No gastrointestinal complications/adverse events were noted with GRV up to 80% with CMF.

Caffeine and Gastric Emptying Time in Very Preterm Neonates.

BACKGROUND: Caffeine has been commonly used for prevention and treatment of apnea-related symptoms in premature infants. However, its side effects have not been thoroughly studied. We investigated whether caffeine affects gastric motility in very-preterm (VP) neonates. METHODS: The study is a randomized crossover clinical trial. Twenty-two neonates with mean birth weight (BW) (standard deviation-SD) 1077 (229) g and mean gestational age (GA) (SD) 28.6 (2.1) weeks were recruited. Each neonate had its gastric emptying time checked twice with ultrasound assessment of changes in antral cross sectional area (ACSA). All neonates were sequentially allocated to the caffeine group (A) and the control group (B). Complications from the gastrointestinal tract were documented throughout the study. RESULTS: Statistically significant difference was found with regards to the gastric emptying time [median, (range)] between caffeine and control group (p = 0.040). Additionally, in the neonates with BW 1000-1500 g and GA ≥ 28 weeks, the gastric emptying time (minutes) was significantly longer during caffeine treatment [44.5 (36-68.2)] and [40 (34.5-66.5)] respectively, as compared to the gastric emptying time during no caffeine treatment [27 (24.2-30)] (p = 0.002) and [27 (24.5-30)] (p = 0.001). The incidence of gastrointestinal (GI) complications was significantly greater in neonates receiving caffeine [6 (27.%)] as compared with those without caffeine treatment [1 (4.6%)] (p = 0.039). CONCLUSIONS: During caffeine treatment, a significantly delayed gastric emptying time was noted in all study neonates, especially in these with BW 1000-1500 g and those with GA ≥ 28 weeks. Further larger studies are necessary in order to confirm this interesting finding.

Thromboelastometry Variables in Neonates with Perinatal Hypoxia.

Perinatal hypoxia is associated with an increased risk of coagulation disorders by enhancing the consumption of platelets and some clotting factors due to the associated severe hypoxemia, acidemia, and compromised oxygen and blood supply to the neonatal liver and bone marrow. Thromboelastometry (TEM), which estimates the dynamics of blood coagulation, may represent an attractive tool for studying the coagulation status of these neonates. We aimed at assessing the hemostatic profile of neonates with perinatal hypoxia using the standard extrinsically activated TEM (ex-TEM) assay. In total, 164 hospitalized neonates with perinatal asphyxia and/or fetal distress comprised the study subjects, and 273 healthy neonates served as controls. Ex-TEM assay was performed, SNAPPE (Score for Neonatal Acute Physiology Perinatal Extension) was calculated, and clinical findings and laboratory results were recorded in all study subjects. Hypoxic neonates expressed a prolonged clotting time (CT) and clot formation time (CFT) and reduced amplitude at 10 minutes (A10), α-angle, and maximum clot firmness compared with healthy neonates. Furthermore, asphyxiated neonates had a significantly prolonged CT and CFT and reduced A10 and α-angle compared with neonates with fetal distress. Hypoxic neonates demonstrate a hypocoagulable ex-TEM profile relative to healthy neonates, indicating a potential role of TEM in the early detection of coagulation derangement in perinatal hypoxia.

It is Time for a Universal Nutrition Policy in Very Preterm Neonates during the Neonatal Period? Comment on: "Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm Infants" Nutrients 2019, 11, 2772.

We have read the article entitled "Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm infants" by Montserrat Izquierdo Renau et al [...].

Very preterm neonates receiving "aggressive" nutrition and early nCPAP had similar long-term respiratory outcomes as term neonates.

BACKROUND: The impact of the consistent implementation of "aggressive" nutrition by means of intensive early neonatal nutritional support up to 40-44 weeks postmenstrual age and the use of nasal continuous positive airway pressure (nCPAP) within the first hour of life on the respiratory function of very premature neonates (VPN) at school age is unclear. METHOD: Respiratory function was evaluated in 108 VPN and 70 term controls. Growth, frequency of lower respiratory tract infections, re-hospitalization, and spirometry were recorded up to 8-10 years of age. Comparison was carried out between the two study groups. RESULTS: There was no significant difference in forced expiratory volume in 1 s and forced vital capacity at 8 years of age, and also in lower respiratory tract infections and re-hospitalization due to them, up to 8 years of age between preterm and term neonates. No significant difference was found in spirometry measurements neither between premature neonates with and without BPD nor between the two subgroups of preterms and term neonates. CONCLUSION: "Aggressive" nutrition, persistent nCPAP use, and their impact on early postnatal growth probably positively affect the respiratory function of our study population. These very encouraging results need to be confirmed by larger studies.

Umbilical Venous Catheters and Peripherally Inserted Central Catheters: Are They Equally Safe in VLBW Infants? A Non-Randomized Single Center Study.

Background and Objective: Peripherally inserted central catheters (PICC) and umbilical venous catheters (UVC) are frequently used for vascular access in neonatal intensive care units (NICUs). While there is a significant need for these devices for critically ill neonates, there are many complications associated with their use. We aimed at investigating the incidence of UVC and PICC complications in very low birth weight (VLBW) infants. Materials and Methods: This is an observational study performed with neonates of the tertiary General Hospital of Piraeus, Greece, during an 18 month-period. Seventy-one neonates were recruited and divided into two groups: 34 neonates with PICC and 37 neonates with UVC. We recorded: Catheter dwell time, the causes of catheter removal, other complications, infections, and catheter tip colonization rates. Results: No significant statistical differences were noticed between the 2 study groups with regards to demographic characteristics, causes for catheter removal, catheter indwelling time or the incidence of nosocomial infection. Eleven UVC tips and no PICC tips were proved colonized (p = 0.001) following catheter removal. Conclusions: The incidence of complications associated with the use of UVCs and PICCs in VLBW infants did not significantly differ in our study. Their use seems to be equally safe. Further studies, with larger samples, are necessary to confirm our results.

Clinical Application of Thromboelastography/Thromboelastometry (TEG/TEM) in the Neonatal Population: A Narrative Review.

Hemostasis is a dynamic age-related process, which gradually evolves from fetal life throughout childhood until adulthood. Although at birth there is a hemostatic deficit of most coagulation factors, studies have shown that this "hemostatic immaturity" is functionally counterbalanced in healthy term or preterm newborns. This delicate hemostatic balance is, however, deranged in sick neonates, resulting in an enhanced risk of hemorrhage and/or thrombosis. In critically ill neonates, conventional coagulation tests do not seem to provide reliable information or indications regarding the functional status of platelets or fibrinolysis. In contrast, viscoelastic tests, namely thromboelastography/thromboelastometry (TEG/TEM) hold promise for rapid assessment of the whole hemostatic potential, allowing immediate intervention should this be required. However, neonatal data are limited due to lack of reference values, especially in premature neonates. In this narrative review, we provide some insights around current knowledge regarding TEG/TEM applications in healthy and sick newborns. Overall, the use of viscoelastic tests in diagnosis and management of coagulation disorders in neonates is definitely worth further exploration. Consideration should be made to include these tests in the routine laboratory investigation of neonates and specific transfusion algorithms should also be developed in order to avoid treatment pitfalls.

Thromboelastometry: studying hemostatic profile in small for gestational age neonates-a pilot observational study.

Scarce data exists about the hemostatic status of small for gestational age (SGA) neonates. We aimed at evaluating the hemostatic profile of SGA neonates, using thromboelastometry (TEM). This is an observational study performed in a Greek tertiary General Hospital during an 18-month period. Ninety-three neonates were included in the study: 48 appropriate for gestational age weight (AGA) neonates and 45 SGA neonates Extrinsically activated TEM (ex-TEM) parameters, such as clotting time, clot formation time, amplitude recorded at 5 and 10 min, a angle, maximum clot firmness, lysis index at 60 min, and also platelet count, were used for the evaluation of the hemostatic profile in all neonates. No statistically significant differences were noticed regarding all ex-TEM parameters between AGA and SGA neonates, while no event of hemorrhage or thrombosis was noticed in the study population.Conclusions: The coagulation system of SGA neonates seems to be fully functional, with no evident tendency toward coagulopathy or thrombosis, when compared with AGA neonates. TEM seems to provide a promising and valid assessment of coagulation and fibrinolysis systems and may be used as a valuable biomarker, in the future. Further studies, with large samples, are necessary to confirm our results. What is Known: • SGA neonates may present coagulation disorders mainly due to hepatic dysfunction, polycythemia, and thrombocytopenia owing to long-term intrauterine hypoxia. • In the literature, despite the statistically significant differences in laboratory results between SGA and AGA neonates, no clinical manifestations of significantly altered hemostasis were recorded. Data of TEM interpretation of hemostasis in SGA neonates are not available. What is New: • TEM seems to interpret coagulation mechanism of preterm and full-term SGA neonates and confirm previous relevant literature findings regarding hemostasis in these neonates.

The Association Between Retinopathy of Prematurity and Ocular Growth.

Purpose: The purpose of this study was to prospectively investigate the association between retinopathy of prematurity (ROP) and ocular growth in premature infants during the earliest weeks of life. Methods: Premature infants in the national ROP screening program were recruited and examined at 1- or 2-week intervals between 30 and 38 weeks of postmenstrual age. One hundred infants with gestational age (GA) between 24 and 35 weeks (30.04 + 2.13), and birth weight (BW) between 550 and 2060 g (1251.45 + 317.19) were included in the study. At each examination, the presence, stage, and zone of ROP were recorded along with axial length (AL), central corneal thickness (CCT), and weight gain. Biometric parameters were measured by A-scan biometry. Study variables included GA, BW, AL, CCT, weight gain, relative weight (RW), and dif_AL, dif_CCT, and dif_weight, which are the differences between two consecutive recordings of the same infant. Multiple regression analysis models were used to determine the association between the study variables and ROP. Results: dif_AL, dif_CCT, and RW were the most appropriate variables to detect the optimal threshold points that discriminate ROP: weekly increase of AL < 0.095 mm, weekly reduction of CCT < 0.5 µm, or weekly weight gain < 7% is associated with ROP development. Conclusions: ROP is associated with delayed ocular development, as eyes of premature infants with ROP have shorter axial lengths and thicker corneas than eyes of premature infants without ROP. The association of AL, CCT, and weight gain with ROP could be of value for future development of predictive models for ROP.

MBL2 genotypes and their associations with MBL levels and NICU morbidity in a cohort of Greek neonates.

The objective of this study was to assess the frequency of MBL2 genotypes and their associations with MBL levels and various morbidities of a neonatal intensive care unit (NICU). One hundred and thirty-four (134) NICU (83 term and 51 preterm) and 150 healthy neonates were enrolled in the study. MBL2 genotype and MBL serum levels at birth were determined prospectively by PCR-RFLP-sequencing and enzyme-linked immunosorbent assay, respectively. NICU neonates displayed significantly lower MBL serum levels compared to healthy ones. MBL deficiency, defined as the low MBL2 expression group (XA/O and O/O), was significantly associated with an increased risk of respiratory morbidity, especially transient tachypnea of the newborn and respiratory distress syndrome (RDS). Moreover, an increase of 100 ng/mL of serum MBL levels decreases by 5% the risk of total respiratory morbidity and by 7% the risk of RDS, after correction for prematurity and sex and regardless of the presence of infections. Our study further supports the notion that neonates with MBL deficiency and low MBL serum levels at birth may be at higher risk of developing severe respiratory complications.

Successful control of a neonatal outbreak caused mainly by ST20 multidrug-resistant SHV-5-producing Klebsiella pneumoniae, Greece.

BACKGROUND: Extended spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-Kp) infection can cause significant morbidity and mortality in neonates. We investigated a nosocomial ESBL-Kp outbreak in a neonatal intensive care unit (NICU) of the University Hospital of Larissa (UHL), Central Greece. METHODS: A total of sixty-four ESBL-Kp were studied; twenty six isolates were recovered from the NICU and were compared with thirty-eight randomly selected isolates from different wards of the hospital during the period March- December 2012. All isolates were characterized by antimicrobial susceptibility testing, ESBL-production by double-disk synergy test, molecular typing using BOX-PCR, whereas selected isolates were further characterized by beta lactamase and virulence gene content, multilocus sequence typing and phylogenetic analysis. All neonates affected by ESBL-Kp were put under strict contact isolation, along with appropriate infection control measures. RESULTS: The outbreak strain of ST20 multidrug-resistant SHV-5-producing K. pneumoniae was identified in all infected (n = 13) and three colonized neonates. A novel ST (ST1114) was also identified among SHV-5 producers (n = 10) recovered from nine colonized infants, but it was not related with ST20. Both STs were identified only in the NICU and not in other wards of the hospital. No ESBL-Kp were isolated from the hands of the nursing staff and the environment. Although we were not able to identify the source of the outbreak, no ESBL-Kp were isolated in the NICU after this period and we assumed that the outbreak was successfully controlled. All neonates received parenteral nutrition and most of them were delivered by caesarean section and showed low gestational age (<32 weeks) and low birth weights (<1500 g). CONCLUSION: According to our knowledge, this is the first description of an outbreak of multidrug-resistant SHV-5 producing K. pneumoniae assigned to ST20.

Successful control of an echovirus 6 meningitis outbreak in a neonatal intensive care unit in central Greece.

We report an outbreak of echovirus 6 meningitis in a neonatal intensive care unit in central Greece from July to August 2011. The most probable source of the outbreak was a mother; during hospitalization, her neonate was initially infected, followed by 7 more. Stricter infection control measures were implemented, and no other cases have been observed.

Two cases of severe sepsis caused by Bacillus pumilus in neonatal infants.

Bacillus pumilus is an environmental contaminant that has been rarely associated with clinical infections. Here, two cases of severe sepsis caused by B. pumilus are described in two full-term neonates; one in a female infant with no factors predisposing her to infection and the other in a male infant requiring mechanical ventilation and an intravenous catheter. In both cases, the micro-organism was recovered from repeated blood cultures and was identified using biochemical assays and 16S rRNA gene sequencing. Both infants were successfully treated with vancomycin. This report reveals the potential role of B. pumilus as a bloodstream pathogen during infancy.