How delayed full enteral feeding could affect extrauterine growth restriction in a neonatal intensive care unit: a retrospective, short-term, observational single-center study.

BACKGROUND: Achieving adequate growth in preterm newborns through enteral feeding is one of the most important aspects of providing medical assistance in neonatal intensive care units due to not only improved outcomes (the prevention of complications such as necrotizing enterocolitis) but also the evaluation of the well-known consequences of adequate weight gain beyond metabolism and cognitive abilities later in life. METHODS: In our study, we evaluated how the impact of delayed full enteral feeding could influence the entity of extrauterine growth restriction. We retrospectively analyzed the data of preterm subjects from a neonatal intensive care unit anonymous database. RESULTS: We detected significant correlations between delayed full enteral feeding as well as prolonged parenteral nutrition and extrauterine growth restriction. CONCLUSIONS: The achievement of full enteral feeding in the shortest possible time may be reasonably considered an important aspect in preterm newborn care.

Perinatal asphyxia partly affects presepsin urine levels in non-infected term infants.

OBJECTIVES: Standard of care sepsis biomarkers such as C-reactive protein (CRP) and procalcitonin (PCT) can be affected by several perinatal factors, among which perinatal asphyxia (PA) has a significant role. In this light, new early sepsis biomarkers such as presepsin (P-SEP) are needed to enact therapeutic strategies at a stage when clinical and laboratory patterns are still silent or unavailable. We aimed at investigating the potential effects of PA on longitudinal P-SEP urine levels. METHODS: We conducted an observational case-control study in 76 term infants, 38 with PA and 38 controls. Standard clinical, laboratory, radiological monitoring procedures and P-SEP urine measurement were performed at four time-points (first void, 24, 48, 96 h) after birth. RESULTS: Higher (p<0.05) CRP and PCT blood levels at T1-T3 were observed in PA than control infants whilst no differences (p>0.05, for all) at T0 were observed between groups. P-SEP urine levels were higher (p<0.05) in PA at first void and at 24 h while no differences (p>0.05) at 48 and 96 h were observed. No significant correlations were found (p>0.05) between P-SEP and urea (R=0.11) and creatinine (R=0.02) blood levels, respectively. CONCLUSIONS: The present results, showed that PA effects on P-SEP were limited up to the first 24 h following birth in absence of any kidney function bias. Data open the way to further investigations aimed at validating P-SEP assessment in non-invasive biological fluids as a reliable tool for early EOS and LOS detection in high-risk infants.

Pediatric Use of Recombinant Human Nerve Growth Factor 20 µg/mL Eye Drops (Cenegermin) for Bilateral Neurotrophic Keratopathy in Congenital Corneal Anesthesia.

PURPOSE: This study aimed to present the efficacy and safety of cenegermin eye drop (Oxervate; Dompè Farmaceutici, Milan, Italy) treatment in a pediatric patient affected by neurotrophic keratopathy (NK) with Goldenhar syndrome. METHODS: This case reports an infant presenting ulceration and a small central opacity in the cornea of the right and left eyes, respectively. The NK bilaterally worsened despite the use of therapeutic contact lenses and temporary partial tarsorrhaphy. Magnetic resonance imaging showed absence and hypoplasia of the right and left trigeminal nerves, respectively. Cenegermin eye drops were administered 1 drop/each eye, 6 times daily for 8 weeks to promote corneal healing. RESULTS: Complete healing was achieved in both eyes after treatment. During the 16-month follow-up period, no epithelial defect, recurrence, or complications were noticed, whereas corneal opacities progressively became clearer, although insignificant improvements in corneal sensitivity or in the reflex tearing were observed. CONCLUSIONS: Cenegermin was effective in treating NK in an infant with Goldenhar syndrome.

A retrospective analysis of the occurrence of accidents during 20 years of neonatal transport in Liguria region, Italy.

Our article focuses on a retrospective analysis of the occurrence of accidents relating to 20 years of activity of Neonatal Emergency Transport Service (NETS) in Liguria region, Italy. The objective of this study is to determine the vehicle accident rate for a specialized emergency medical services-NETS transport system between 1995 and 2015. We reviewed 5035 medical records related to the activity of our NETS from its beginning, in February 1995 to June 2015. We identified the occurrence of three road accidents (rate ∼1 : 1600 transports; 1 : 170 000 driven km), no helicopter accidents and only one technical problem during helicopter use; our service was not involved in any crashes resulting in injury. We discussed some reasons possibly explaining these good results.

Incidental findings on routine brain MRI scans in preterm infants.

OBJECTIVE: Many neonatal intensive care units (NICUs) have adopted the practice of performing routine brain MRI in very low birth weight (VLBW) infants at term-equivalent age in order to better evaluate prematurity-related acquired lesions. A number of unexpected brain abnormalities of potential clinical significance can be visualised on routine scans as well. The aim of our study was to describe these incidental findings (IFs) in a VLBW population and to assess their clinical significance. STUDY DESIGN: We retrospectively reviewed a series of brain MRI scans performed in VLBW infants consecutively admitted to our NICU between November 2011 and November 2014. IFs on brain MRI, which were not detected by cranial ultrasound nor suspected clinically, were registered. Clinical significance of IF was assessed in terms of need of further diagnostic or therapeutic interventions. RESULTS: IFs were detected in 28 out of 276 VLBW infants (10.1%). In total, 21 cases (7.6%) required an intervention, which was only diagnostic in 16 cases, and both diagnostic and therapeutic in 5 cases. In the remaining seven cases (2.5%), no further action was considered necessary. CONCLUSIONS: This study suggests that IFs on brain MRI of VLBW infants are not rare. In our population, most of them required a diagnostic or therapeutic intervention. The need and appropriateness of routine MRI scanning in VLBW at term-equivalent age are still subject of debate, and we believe our data can contribute meaningfully to this discussion.

Accuracy of ultrasound in assessing cerebellar haemorrhages in very low birthweight babies.

OBJECTIVE: To assess diagnostic accuracy of cranial ultrasound (CUS) performed through the anterior fontanelle (AF) and mastoid fontanelle (MF) in detecting cerebellar haemorrhages (CBH) in very low birthweight (VLBW) infants. SETTING: Third-level neonatal intensive care unit (NICU). DESIGN: VLBW infants consecutively admitted at Gaslini Children's Hospital between February 2012 and September 2013 underwent both CUS and MR susceptibility-weighted imaging (SWI). CUS was performed at days 1, 2, 3 and 7 after birth, then weekly until term-equivalent age. All CUS examinations were performed through AF and MF using an 8 Mhz convex probe. Depending on the size, CBHs were classified as massive, limited or microhaemorrhages. Diagnostic accuracy of CUS through AF and MF in detecting all types of CBHs was assessed by comparing it with SWI, used as the gold-standard technique. RESULTS: 140 VLBW infants were included. CUS sensitivity in detecting massive CBH through both AF and MF was excellent (100%). However, CUS sensitivity through AF dropped down to 16.7% (95% CI 1% to 46%) in cases of limited CBH, with sensitivity through MF remaining good (83.3%; 95% CI 53% to 100%). None of the microhaemorrhages diagnosed by SWI was identified by CUS, despite the use of MF. Specificity of CUS in detecting all degrees of CBH through both AF and MF was excellent (100%). CONCLUSIONS: Routine use of MF allows a better detection of limited CBH when compared with AF. Overall sensitivity of CUS in detecting CBH is low when microhaemorrhages are included. In other words, microhaemorrhages proved to be undetectable by CUS.

Neurological abnormalities in full-term asphyxiated newborns and salivary S100B testing: the "Cooperative Multitask against Brain Injury of Neonates" (CoMBINe) international study.

BACKGROUND: Perinatal asphyxia (PA) is a leading cause of mortality and morbidity in newborns: its prognosis depends both on the severity of the asphyxia and on the immediate resuscitation to restore oxygen supply and blood circulation. Therefore, we investigated whether measurement of S100B, a consolidated marker of brain injury, in salivary fluid of PA newborns may constitute a useful tool for the early detection of asphyxia-related brain injury. METHODS: We conducted a cross-sectional study in 292 full-term newborns admitted to our NICUs, of whom 48 suffered PA and 244 healthy controls admitted at our NICUs. Saliva S100B levels measurement longitudinally after birth; routine laboratory variables, neurological patterns, cerebral ultrasound and, magnetic resonance imaging were performed. The primary end-point was the presence of neurological abnormalities at 12-months after birth. RESULTS: S100B salivary levels were significantly (P<0.001) higher in newborns with PA than in normal infants. When asphyxiated infants were subdivided according to a good (Group A; n = 15) or poor (Group B; n = 33) neurological outcome at 12-months, S100B was significantly higher at all monitoring time-points in Group B than in Group A or controls (P<0.001, for all). A cut-off >3.25 MoM S100B achieved a sensitivity of 100% (CI5-95%: 89.3%-100%) and a specificity of 100% (CI5-95%: 98.6%-100%) as a single marker for predicting the occurrence of abnormal neurological outcome (area under the ROC curve: 1.000; CI5-95%: 0.987-1.0). CONCLUSIONS: S100B protein measurement in saliva, soon after birth, is a useful tool to identify which asphyxiated infants are at risk of neurological sequelae.

Low-grade intraventricular hemorrhage: is ultrasound good enough?

OBJECTIVE: To assess diagnostic accuracy of cranial ultrasonography (CUS) in detecting low-grade (i.e. grade I and grade II) germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) in very low birth weight (VLBW) infants. METHODS: Among VLBW infants who were admitted to Gaslini Children's Hospital neonatal intensive care unit between January and November 2012, patients who underwent both serial CUS since birth and magnetic resonance susceptibility-weighted imaging (SWI) at term-equivalent age were included in this retrospective study. Diagnostic accuracy of CUS in detecting low-grade GMH-IVH was assessed in terms of sensitivity and specificity by comparing it to SWI, which was used as the gold-standard technique. RESULTS: Sixty VLBW infants were included in the study. Sensitivity of CUS in detecting low-grade GMH-IVH was low (60%), whilst specificity was 100%. CONCLUSIONS: In the present study, CUS sensitivity in detecting grade I-II GMH-IVH proved to be surprisingly low, in contrast with specificity. In other words, we suggest that low-grade GMH-IVH may be underdiagnosed in VLBW infants when assessed exclusively with CUS.

Different gestational ages and changing vulnerability of the premature brain.

In recent decades, there has been a general increase in survival rates of preterm and low birth weight infants, but this overall decrease in perinatal mortality has not been accompanied by a decrease in long-term physical and mental disability. In order to reduce the long-term sequelae of prematurity and to establish preventive measures, it is important to identify risk factors since the main determinant of specific vulnerability to different types of lesions is gestational age. The regional tissue vulnerability at a given gestational age is probably determined by the local metabolic requirements together with specific cell characteristics and their level of maturation. In this article, we discuss the most common neonatal cerebral lesions (cerebellar haemorrhage, germinal matrix intraventricular haemorrhage, periventricular leukomalacia, arterial ischaemic stroke, cerebral vein sinus thrombosis and hypoxic-ischaemic encephalopathy) related to the gestational age-dependent vulnerability of the premature brain.

From germinal matrix to cerebellar haemorrhage.

For many years cerebellar development after preterm birth has been poorly investigated and has been studied without taking germinal matrix-intraventricular haemorrhage into account. Advanced neuroimaging techniques like magnetic resonance imaging, as well as the use of various acoustic windows (mastoid fontanelle, occipital foramen) have allowed for in vivo diagnosis of acquired focal haemorrhagic lesions in the cerebellum of very preterm babies. The vulnerability of the cerebellum also seems to be related to specific gestational ages, i.e., between 23 and 27 weeks, when rapid growth in cerebellar volume occurs and at a much faster rate than mean brain volume increase. In this paper, the contribution of the cerebellum in long-term motor cognitive, learning and behavioural functions, including psychiatric ones, is discussed.

Early surfactant for respiratory distress syndrome in premature infants.

Effects of early surfactant administration to premature newborns have been widely investigated in several RCTs. Furthermore, recent studies and metanalysis have compared early with delayed administration as well as selective and prophylactic use of surfactant. These data from the literature are discussed in the present review together with the factors that may argue against the standardization of respiratory care at birth. A tailored approach based on the stratification of risk factors may be appropriate in the so heterogeneous population of premature newborns.

Elevated Activin A urine levels are predictors of intraventricular haemorrhage in preterm newborns.

AIM: Intraventricular haemorrhage (IVH) is the most common variety of cerebral haemorrhage and cause of neurological disabilities in preterm newborns. We evaluated the usefulness of urine Activin A concentrations for the early detection of perinatal IVH. METHODS: We conducted a case-control study on 100 preterm newborns (20 with IVH and 80 without IVH) in whom urine Activin A was measured at five predetermined time-points in the first 72 h after birth. IVH diagnosis and the extension of the lesion were performed by ultrasound scanning within the first 72 h and at 1 week after birth, respectively. RESULTS: Urine Activin A in infants who developed IVH was significantly higher than in controls at all monitoring time-points (p < 0.01 for all), increasing progressively from first urination to 24 h when it reached the highest peak (p < 0.001). At a cut-off 0.08 ng/L, at the first void, Activin A sensitivity and specificity were 68.7% (CI: 41.3-89%) and 84.5% (CI: 75-91.5%). CONCLUSION: Activin A measurements in urine soon after birth can constitute a promising tool for identifying preterm infants at risk of IVH.

S100B urine concentrations in late preterm infants are gestational age and gender dependent.

BACKGROUND: Late preterm deliveries (LP, between 34 and 36wks), have considerably increased in the last decades. About 20-25% of LP infants who require intensive care and morbidity on public health are of great magnitude. Therefore, we aimed at offering a reference curve in LP period of a well-established neurotrophic and brain damage marker namely S100B protein. METHODS: We collected, between December 2009 and March 2012, urine samples, at first void (within 6-hours from birth) for S100B assessment, in 277 healthy LP infants consecutively admitted to our units. Standard clinical and laboratory monitoring parameters were also recorded. S100B was measured by using a commercially available immunoluminometric assay. RESULTS: S100B pattern in LP infants was characterized by a slight decrease in protein's concentration from 34 to 35wks. From 35wks onwards S100B started to increase reaching a significant difference (P=0.008) at 36wks. When corrected for gender, significantly higher (P<0.01, for all) S100B concentrations in female were observed from 34 to 36wks. Polynomial type-1 regression analysis showed a significant correlation (R=-0.05; P<0.001) between gestational age and S100B in LP infants considering either the whole study population or when corrected for gender. CONCLUSIONS: S100B in LP infants is gestational age and gender dependent. The present reference curve, for S100B in LP period, offers additional support to protein's neurotrophic role and suggests that gestational age and gender have to be taken into due account, whenever S100B is measured, in order to avoid bias factors.

Biomarkers of brain damage in preterm infants.

OBJECTIVE: There is growing evidence on the usefulness of biomarkers in the early detection of preterm infants at risk for brain damage. However, among different tools Activin A, S100B protein and adrenomedullin assessment offer the possibility to investigate brain/multiorgan function and development. This could be especially useful in perinatal medicine that requires even more non-invasive techniques in order to fulfill the minimal handling in diagnostic and therapeutic strategy performance. MATERIALS AND METHODS: The concept of Unconventional Biological Fluid (UBF: urine and saliva) is becoming even stronger and regards the assessment in non-invasive biological fluids of biochemical markers involved in the cascade of events leading to brain damage. RESULTS: Activin A, S100B protein and adrenomedullin in UBF were increased in preterm newborns developing brain damage and/or ominous outcome. CONCLUSIONS: The present manuscript offers an update on the usefulness of Activin A, S100B protein an adrenomedullin in UBF as brain damage markers. The findings open a new cue on the use of these markers in daily neonatal intensive care unit (NICU) activities.

Preterm and term newborn: primary investigations.

The present overview is aimed at reporting the standard primary investigations that are mandatory in preterm and term newborns at admission to neonatal unit in the first hours after birth. Herein, the main neonatal screening tests for early detection of metabolic diseases are described as well as laboratory standard procedures (glycaemia, bilirubin, blood gas, infectious diseases analyses) monitoring parameters (vital signs recordings, blood and transcutaneous gas assessment, blood pressure recordings) and ultrasound pattern (cranial and cardiac).

Reference values of blood cell counts in the first days of life.

The lack of updated neonatal reference values for hematological parameters impacts significantly with clinical management of both healthy and sick newborns. The present pilot study was thus aimed at assessing updated hematological Italian reference values in late preterm and term newborns. From January 2004 to December 2008 hematological laboratory tests were performed in 1175 newborns (820 healthy and 355 sick controls) between 33-41 weeks of gestation, during the first four days after birth. Hematological parameters were sorted for gender and gestational age and statistically analyzed. No gender-related differences were observed at different weeks of gestation and no significant differences were found when study population was sub-grouped for late preterm and term newborns. During the first 4 days of life erythrocytes and platelets remained stable whilst white blood cell counts and differentials were significantly modified. This study shares updated reference values for hematological parameters in the early phases after birth and offers additional support for improving the management of sick infants.

S100B protein maternal and fetal bloodstreams gradient in healthy and small for gestational age pregnancies.

BACKGROUND: Brain S100B assessment in maternal blood has been proposed as a useful tool for early perinatal brain damage detection. Among potential confounding factors the possibility of a protein gradient between maternal and fetal bloodstreams under pathophysiological conditions is consistent. The present study investigates in healthy and small gestational age fetuses (SGA) whether S100B concentrations differ among fetal and maternal bloodstreams. METHODS: We conducted a case-control study in 160 pregnancies (SGA: n=80; healthy: n=80), in which standard monitoring parameters were recorded. S100B was assessed in arterial cord and in maternal blood samples at birth. Eighty non pregnant women (NP), matched for age at sampling, served as controls (1 SGA vs. 1 healthy vs. 1 NP). RESULTS: Fetal S100B in SGA and healthy groups was significantly higher (P<0.01) than that detected in the maternal district and in NP women groups, respectively. No differences in protein's gradient between fetal and maternal bloodstreams (P>0.05) were observed between groups. No differences (P>0.05) in fetal S100B have been found between the studied groups. Maternal S100B of SGA and healthy groups was significantly higher (P<0.01) than that detected in NP women. No differences in maternal S100B concentrations (P>0.05) were observed between SGA and control groups. CONCLUSION: The present study shows that S100B is pregnancy-dependent with the presence of a protein's gradient between fetal and maternal bloodstreams. The present data suggests that non-invasive fetal brain monitoring is becoming possible in opening a new cue on further investigations on S100B fetal/maternal gradient changes under pathological conditions.

Antenatal glucocorticoid treatment affects preterm infants' S100B urine concentration in a dose-dependent manner.

BACKGROUND: Maternal glucocorticoid (GC) treatment is widely used to prevent lung immaturity in preterm infants. There is growing evidence that GCs may be detrimental to the Central Nervous System (CNS). We investigated whether antenatal GC administration affects CNS function in a dose-dependent manner by measuring urine concentrations of a well-established brain damage marker, S100B. METHODS: We conducted a case-control-study in 70 preterm infants (1 GC vs 1 control) whose mothers received a complete GC-course (GC2, n=16), half-course (GC1, n=19), and controls (n=35). At four predetermined time-points, in the first 72 h from birth, we assessed S100B urine concentrations, using a commercially available immunoluminometric assay (Lia-mat Sangtec 100, AB Sangtec Medical, Bromma, Sweden). Data were correlated with primary neonatal outcomes (incidence of respiratory distress syndrome, length of ventilatory support and hospital stay, incidence of intraventricular hemorrhage, adverse 7th day neurological follow-up and neonatal death). RESULTS: S100B in GC2 group at all monitoring time-points was significantly lower (P<0.01) than controls and GC1 group, while no differences (P>0.05) were evident between controls and GC1 group. No significant differences (P>0.05) were shown in primary outcomes between half or complete GC-course treated groups. CONCLUSION: S100B levels of infants antenatally treated with GCs differed in a dose-dependent manner. Data on primary outcomes suggest that lowering antenatal GC-course may be less detrimental for brain without affecting lung maturation. Further clinical trials are needed to elucidate the low GC-course issue.