Treatment Of Preterm Neonates Research Articles

A Survey of the Prevalence Rate and Antibiotic Resistance Pattern of Microbial Agents in Preterm Neonatal Sepsis

Background: Sepsis is one of the most dangerous neonatal infections. Bacterial causes of neonatal septicemia are different. Objectives: This study aimed to investigate the prevalence and antibiotic resistance pattern of microbial agents causing preterm neonatal sepsis. Methods: This descriptive study was performed on 1000 infants admitted to neonatal intensive care units 1 and 2 and the neonatal ward of Al-Zahra Medical Center in Tabriz, Iran, from March 2019 to June 2020. Sampling was completed through the convenience sampling method. Data were collected using a researcher-made questionnaire after evaluating its validity and reliability. The questionnaire included personal information of neonates, causes of infection, antibiotic use, hospitalization time, and medication resistance pattern. Antibiotic susceptibility testing was performed by disk diffusion technique according to the Clinical and Laboratory Standards Institute guidelines. SPSS software version 22 was used for data analysis. Results: Among all studied neonates, 78 cases (7.8%) had positive blood cultures. The most common cause of neonatal infection was preterm birth (80.8%), and the most common bacterial causes of sepsis were coagulase-negative Staphylococcus (46.15) and Klebsiella pneumonia (28.2%). The highest antibiotic susceptibility of Gram-positive (coagulase-negative Staphylococcus) and Gram-negative bacteria was to ceftriaxone (47.3%) and piperacillin/tazobactam (100%), respectively, and the highest antibiotic resistance was to ampicillin and gentamicin (nearly 100%). Conclusions: Resistance to antibiotics used to treat sepsis has increased, which will cause irreparable problems in the treatment of preterm neonates if not addressed. Due to different microbial agents and drug resistance patterns in distinct regions, annual surveys should be conducted to determine drug resistance patterns, emphasizing preventive measures.

Surfactant administration via laryngeal mask or supraglottic airway

Surfactant therapy has been the mainstay of treatment in preterm neonates with respiratory distress syndrome. Delivery of surfactant through endotracheal intubation has been the commonly used technique. Intubation requires expertise and is associated with complications. In addition, there is also an increased future risk of chronic lung disease. Newer techniques of surfactant delivery abating the need of intubation have been reported. One such minimally invasive technique is surfactant administration through a supraglottic airway device. In this report, we describe the delivery of surfactants using this technique.

Predictive Factors for Surgery in Preterm Neonates with Necrotizing Enterocolitis: A Retrospective Cohort Study

Objectives: Necrotizing enterocolitis (NEC) is a severe neonatal condition. This study aimed to assess predictive factors for surgical treatment in preterm neonates with NEC in a Tunisian center. Methods: We present a retrospective study including all neonates treated for NEC between January 01, 2010 and March 31, 2022. Results: Within the study period, 102 patients were included, with an overall survival of 47%. Most of our patients were male (64.7%), with low birth weight or less (100%), 5-min Apgar score ?8 (79.4%), and Bell’s stage II (66.7%). Multivariate logistic analyses demonstrated that gestational age <30 weeks (p=0.002, odds ratio [OR]=4.544), birth weight <1000 g (p=0.001, OR=5.750), NEC onset <7 days (p<0.001, OR=5.667), not being breastfed (p=0.019, OR=3.026), and C-reactive protein level >20 mg/L (p=0.020, OR=2.942) were associated with the need for surgical treatment in neonates with NEC. Conclusion: Our findings would be helpful in refining treatment modalities for better disease outcomes. Keywords: Bell's staging criteria, breastfeeding, C-reactive protein, Necrotizing enterocolitis, surgery

Predictive factors for surgical treatment in preterm neonates with necrotizing enterocolitis: a multicenter case-control study

Necrotizing enterocolitis (NEC) is one of the most common and lethal gastrointestinal diseases in preterm infants. Early recognition of infants in need for surgical intervention might enable early intervention. In this multicenter case-control study, performed in nine neonatal intensive care units, preterm born infants (< 30 weeks of gestation) diagnosed with NEC (stage ≥ IIA) between October 2014 and August 2017 were divided into two groups: (1) medical (conservative treatment) and (2) surgical NEC (sNEC). Perinatal, clinical, and laboratory parameters were collected daily up to clinical onset of NEC. Univariate and multivariate logistic regression analyses were applied to identify potential predictors for sNEC. In total, 73 preterm infants with NEC (41 surgical and 32 medical NEC) were included. A low gestational age (p value, adjusted odds ratio [95%CI]; 0.001, 0.91 [0.86–0.96]), no maternal corticosteroid administration (0.025, 0.19 [0.04–0.82]), early onset of NEC (0.003, 0.85 [0.77–0.95]), low serum bicarbonate (0.009, 0.85 [0.76–0.96]), and a hemodynamically significant patent ductus arteriosus for which ibuprofen was administered (0.003, 7.60 [2.03–28.47]) were identified as independent risk factors for sNEC.Conclusions: Our findings may support the clinician to identify infants with increased risk for sNEC, which may facilitate early decisive management and consequently could result in improved prognosis.What is Known:• In 27–52% of the infants with NEC, a surgical intervention is indicated during its disease course.• Absolute indication for surgical intervention is bowel perforation, whereas fixed bowel loop or clinical deterioration highly suggestive of bowel perforation or necrosi, is a relative indication.What is New:• Lower gestational age, early clinical onset, and no maternal corticosteroids administration are predictors for surgical NEC.• Low serum bicarbonate in the 3 days prior clinical onset and patent ductus arteriosus for which ibuprofen was administered predict surgical NEC.

Association between changes in urine output and successful indomethacin treatment for patent ductus arteriosus in preterm neonates.

To investigate the relationship between changes in urine output during indomethacin treatment and ductal closure in preterm neonates. It is a retrospective study in neonates ≤32 weeks who had received two courses of indomethacin for PDA treatment over a 5-year period. Indomethacin courses with pre- and post-echocardiography confirmation of PDA status were included. Various urine output indices were collected and compared between successful versus unsuccessful indomethacin courses. Indomethacin treatment success was defined as: (i) where PDA closed or became haemodynamically insignificant (hisPDA) after treatment and (ii) only including neonates where PDA had complete closure after treatment. ROC analysis was performed to examine predictive ability of urine output during indomethacin for treatment success. One hundred and eight indomethacin courses (first course: 52, second course: 56) in 80 neonates were included. The mean gestational age and birthweight were 25.4 ± 1.3 weeks and 762 ± 165 g, respectively. Irrespective of the definition used, there was no significant differences seen in any of urine output parameters between groups, except for a higher urine output during indomethacin associated with complete PDA closure (3.6 ± 1.3 vs. 3.0 ± 1.0 mL/kg/h, P = 0.02). The incidence of significant oliguria, hyponatraemia and need to withhold/delay indomethacin doses were also similar across groups. Urine output was not a useful predictor of ductal response to indomethacin treatment in preterm neonates.

Platelets and platelet derived growth factor and ductus arteriosus in preterm neonates

BackgroundPlatelets and platelet derived growth factor (PDGF) play an important role in persistence and closure of ductus arteriosus (DA) in preterm neonates. AimTo study the effect of Platelets count and PDGF on DA patency in preterm neonates. MethodsIn a prospective study, performed in the neonatal intensive care unit (NICU) of Fayoum University Hospital, 75 preterm neonates with gestational age >33 weeks were assessed by Doppler echocardiography after 72 h of birth and classified into two groups (group 1: patent ductus arteriosus (PDA) group which included 40 preterm neonates and group 2: non-PDA group which included 35 preterm neonates). For all of them, complete blood count (CBC), C reactive protein (CRP) and serum PDGF were assessed. ResultsTwenty six preterm neonates of group1 had hemodynamically significant PDA and received medical treatment in the form of an oral course of ibuprofen. Platelets count was significantly lower among PDA group, platelet distribution width (PDW) was significantly higher among PDA group, and platelets mass index (PMI) was significantly lower among PDA group. PDGF was significantly lower among PDA group on day 2 in comparison to non-PDA group and increased significantly from day 2 to day 5 in cases of PDA with spontaneous closure. ConclusionsLow platelets count and PMI and high PDW are associated with persistence of PDA and poor response to medical treatment, while up trending of PDGF level is associated with spontaneous PDA closure and good response to medical treatment in preterm neonates.

Patent ductus arteriosus treatment in preterm neonates, which is the drug of choice paracetamol vs ibuprofen?

Background Patent ductus arteriosus (PDA) is one of the most prevalent problems in preterm infants. Although ibuprofen represents one of the choices for the closure of PDA, this treatment can cause severe gastrointestinal and adverse renal effects and worsen platelet function. Effective therapy for PDA had been suggested as paracetamol. Aim Our study is aiming to compare the efficacy and safety of paracetamol and ibuprofen. Patients and methods A prospective observational, single-center study was performed from December 2016 until August 2017, at ElGalaa Teaching Hospital in Cairo. In this study we included neonates with a gestational age of 28–36 weeks, diagnosed with a significant hemodynamically PDA using clinical and ultrasonographic cardiac evaluation. The pediatric cardiologist performed an echocardiographic examination before the start of the treatment and after seven days. Results We found that paracetamol had good efficacy on PDA in preterm infants, and the closure rate of paracetamol was comparable to that of ibuprofen. Conclusion Paracetamol may confer comparable treatment efficacy for the closure of PDA to ibuprofen, although paracetamol is associated with lower risk of adverse events.

Study on therapeutic effectiveness of continuous positive airway pressure compared to mechanical ventilation in preterm babies with respiratory distress

Background: Previously mechanical ventilation was primary modality of treatment in preterm neonates with respiratory distress. With the introduction of continuous positive airway pressure (CPAP), the need of mechanical ventilation is reduced. The present study was done to know the therapeutic effects of CPAP as compared to mechanical ventilation in preterm neonates with respiratory distress. To study the duration of oxygen requirement and duration of hospitalisation in preterm neonates treated with CPAP compared to invasive mechanical ventilationMethods: Hospital based prospective study was conducted from November 2013 to November 2014 in Dr. B. R. Ambedkar medical college, Bangalore. All the preterm babies admitted in neonatal intensive care unit with respiratory distress requiring CPAP or mechanical ventilation during study period were included. Total 50 cases were included, out of which 20 (40%) were on CPAP treatment and 30 (60%) were on mechanical ventilation. Outcome was assessed by reduction of respiratory distress with SpO2 more than 88% with FiO2 of 21%.Results: Out of 50 preterm neonates studied, 20 (40%) were on CPAP treatment and 30 (60%) were on mechanical ventilation. Mean duration of oxygen treatment was less in neonates on CPAP (4.8±0.9 days) compared to mechanical ventilated neonates (7.12±0.8days) and it is statistically significant (p value&lt;0.05). Mean duration of hospitalisation was less in neonates on CPAP (19.3±0.76 days) compared to mechanical ventilated neonates (21±1.2 days) but it was statistically not significant (P value &gt;0.05).Conclusions: CPAP as a mode of treatment for preterm babies with respiratory distress reduces the duration of oxygen dependency compared to invasive mechanical ventilation. Difference in duration of hospital stay was statistically not significant in these neonates treated with CPAP and mechanical ventilation.

Role of Melatonin in Treatment of Necrotizing Enterocolitis in Preterm Neonates

AbstractBackground: Necrotizing enterocolitis (NEC) is one of the most dangerous gastrointestinal diseases that affects the neonates especially preterm neonates. It can lead to severe morbidity and even mortality, so early detection of NEC would give us good chance for early prevention and treatment with better prognosis. Free radicals play a significant role in the pathogenesis of neonatal sepsis and NEC. It has been suggested that melatoninas an antioxidant can be used to counteract the toxicity of oxygen radicals that are released during neonatal illness.Aim of Study: Is to Determine the role of melatonin as an adjuvant therapy in treating necrotizing enterocolitis (NEC) in preterm neonates.Patients and Methods: A prospective clinical trial study was conducted on 20 preterm neonates which suffer from NEC diagnosed on the basis of both clinical and laboratory criteria. group (G I) (n=10) received melatonin and antibiotics, while the control group (G II) (n=10) was treated with antibi-otics only. Melatonin was administered as 20 mg for 3 con-secutive days and antibiotics were administered according to a standard protocol protocol and followed-up of symptoms and signs of NEC after 5,10 and 15 days of starting treatment.Results: As regard outcome of NEC, In group I there were 9 (90%) cases improved and 1 (10%) case not improved but In group II there were 5 (50%) cases improved and 5 (50%) cases not improved, so more cases in group I who received melatonin showed improvement of NEC than group II. As regard mortality, one baby (10%) died and 9 (90%) survived in group I compared to 3 babies (30%) died and 7 babies (70%) survived in group II.As regard length of NICU stay the patients who received melatonin (group I) stay for a shorter period in NICU compared to group II who received traditional therapy only.Conclusion: Melatonin administration as an adjuvant therapy in NEC treatment in preterm neonates is associated with improvement of clinical and laboratory outcome.

Dobutamine treatment reduces inflammation in the preterm fetal sheep brain exposed to acute hypoxia.

Impaired cerebral autoregulation in preterm infants makes circulatory management important to avoid cerebral hypoxic-ischemic injury. Dobutamine is frequently used as inotropic treatment in preterm neonates, but its effects on the brain exposed to cerebral hypoxia are unknown. We hypothesized that dobutamine would protect the immature brain from cerebral hypoxic injury. In preterm (0.6 gestation) fetal sheep, dobutamine (Dob, 10 μg/kg/min) or saline (Sal) was infused intravenously for 74 h. Two hours after the beginning of the infusion, umbilical cord occlusion (UCO) was performed to produce fetal asphyxia (Sal+UCO: n = 9, Dob+UCO: n = 7), or sham occlusion (Sal+sham: n = 7, Dob+sham: n = 6) was performed. Brains were collected 72 h later for neuropathology. Dobutamine did not induce cerebral changes in the sham UCO group. UCO increased apoptosis and microglia density in white matter, hippocampus, and caudate nucleus, and astrocyte density in the caudate nucleus. Dobutamine commenced before UCO reduced microglia infiltration in the white matter, and microglial and astrocyte density in the caudate. In preterm hypoxia-induced brain injury, dobutamine decreases neuroinflammation in the white matter and caudate, and reduces astrogliosis in the caudate. Early administration of dobutamine in preterm infants for cardiovascular stabilization appears safe and may be neuroprotective against unforeseeable cerebral hypoxic injury.

Impact on the intestinal microbiota of early antibiotic treatment in preterm neonates

Objective: To investigate the impact of early antibiotics treatment on intestinal microbiota in preterm infants. Methods: The cohort study was performed from January 2015 to June 2015 in Neonatal Intensive Care Unit of Peking University Third Hospital. A total of 33 preterm infants were enrolled, among whom 25 were antibiotics-exposure group, and 8 were non-exposure group. Serial stool samples were collected on the first day, 14th and 30th days of life and analyzed by high-throughput sequencing. In exposure group, intestinal microbiota was also analyzed at 8 months to 1 year of age. Categorical variables were analyzed with χ(2) test, and continuous variables were analyzed with t test or non-parametric test. Results:Proteobacteria was the most prominent flora after birth in all cases (exposure group 69.6%, non-exposure group 83.7%) . In exposure group, at the phylum level, Proteobacteria was the dominant bacteria within the first 30 days, followed by Firmicutes after 30 days of life. At the genus level, Escherichia was the most abundant genera within 30 days after birth, while Veillonella became dominant after 8 months to 1 year of life. In non-exposure group, at the phylum level, Proteobacteria was the dominant phylum within the first 30 days. At the genus level, Actinobacteria (37.5%) was the dominant genus after birth, followed by Escherichia within the first month. Intestinal bacterial abundance and diversity were lower in exposure group, which was most significant on 30th day of life (shannon index 2.6 vs.3.4, ACE index 563.9 vs.591.6) . The influence of single antibiotics was less significant than combined treatment (shannon index 2.7 vs.2.5, ACE index 727.3 vs.492.9) . At the genus level, compared to non-exposure group, there were significant decrease of Escherichia (9.3% vs. 54.3%, Z=-2.830, P=0.005), Klebsiella (0.03% vs.12.4%,Z=-2.240, P=0.025), and Clostridium (0.2% vs. 4.8%, Z=-2.979, P=0.003) in exposure group on 14 days of life. Bifidobacterium (0.1% vs.2.0%, Z=-2.349, P=0.019) in cases treated with combined antibiotics was lower than that treated with antibiotic monotherapy on 30 days of life. Conclusions: Early application of combined antibiotics impacts on the intestinal microbiome of preterm infants significantly. The infants who have received antibiotic after birth have lower quantity and diversity of Clostridium, Lactobacillus, Bacteroides and Bifidobacterium.

Predictors of PDA Treatment in Preterm Neonates Who Had Received Prophylactic Indomethacin.

To identify clinical factors those predict the need for patent ductus arteriosus (PDA) treatment in preterm neonates who had received prophylactic indomethacin. Preterm neonates with <28 weeks' gestational age admitted to level III neonatal intensive care units (NICUs) in Canada between 2010 and 2015 and who had received prophylactic indomethacin were included. Primary outcome was surgical ligation of PDA, while secondary outcomes were any PDA treatment and common neonatal morbidities. Of the 7,024 eligible neonates, 843 (12%) neonates had received prophylactic indomethacin. Of them, 84 neonates (10%) required surgical ligation while 367 neonates (44%) received medical or surgical treatment for PDA. Logistic regression analyses identified gestational age (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.58-0.87) and outborn status (OR: 2.07, 95% CI: 1.09-3.93) as predictors for surgical ligation. Maternal hypertension (OR: 0.57, 95% CI: 0.37-0.89), rupture of membranes (ROM) ≥24 hours (OR: 0.68, 95% CI: 0.48-0.96), and surfactant treatment (OR: 1.70, 95% CI: 1.09-2.66) were predictors for medical or surgical treatment of PDA. In extremely preterm neonates who had received prophylactic indomethacin, gestational age and outborn status were predictors for surgical ligation of PDA, while maternal hypertension, ROM ≥24 hours, and surfactant treatment were associated with the medical or surgical treatment of PDA.

Antibiotic Treatment Preventing Necrotising Enterocolitis Alters Urinary and Plasma Metabolomes in Preterm Pigs.

Necrotising enterocolitis (NEC) is a serious gut inflammatory condition in premature neonates, onset and development of which depend on the gut microbiome. Attenuation of the gut microbiome by antibiotics can reduce NEC incidence and severity. However, how the antibiotics-suppressed gut microbiome affects the whole-body metabolism in NEC-sensitive premature neonates is unknown. In formula-fed preterm pigs, used as a model for preterm infants, plasma and urinary metabolomes were investigated by LC-MS and 1H NMR, with and without antibiotic treatment immediately after birth. While it reduced the gut microbiome density and NEC lesions as previously reported, the antibiotic treatment employed in the current study affected the abundance of 44 metabolites in different metabolic pathways. In antibiotics-treated pigs, tryptophan metabolism favored the kynurenine pathway, relative to the serotonin pathway, as shown by specific metabolites. Metabolites associated with the gut microbiome, including 3-phenyllactic acid, 4-hydroxyphenylacetic acid, and phenylacetylglycine, all from phenylalanine, and three bile acids showed lower levels in the antibiotics-treated pigs where the gut microbiome was extensively attenuated. Findings in the current study warrant further investigation of metabolic and developmental consequences of antibiotic treatment in preterm neonates.

The burden of inflammatory stress and antibiotic treatment in preterm neonates and neuro-developmental outcome

Objective: To evaluate the possible association between antibiotic treatment in preterm infants and the occurrence of adverse radiologic and neurologic outcomes. We hypothesize that antibiotic treatment may represent inflammation and thus be associated with adverse outcomes. Methods: Preterm infants (≤ 36 weeks gestational age), hospitalized in the Neonatal Intensive Care Unit (NICU) were eligible for inclusion. Follow-up performed by a pediatric neurologist included assessment by the Griffiths Mental Developmental Scales (GMDS–ER). NICU admission history was retrospectively reviewed. Extended antibiotic treatment was defined as treatment for a duration greater than 72 hours. Infants were further categorized by the number of antibiotic treatment courses given. Adverse neurologic outcome was defined as DQ < 55. Adverse radiological outcome included any of the following: intraventricular hemorrhage grade 2 or above, periventricular leukomalacia or post-hemorrhagic hydrocephalus. Statistical analysis included univariate and multivariate analyses. Results: Included were 203 patients. Adverse radiologic and neurologic outcomes were present in 46 of 203 (22.7%) and 21 of 203 (10.3 %) preterm infants, respectively. Maternal infection or antibiotic treatment were associated significantly with adverse radiological outcome, as were extended antibiotic therapy or multiple antibiotic treatment courses (p<0.001). Unadjusted analysis showed that extended antibiotic therapy (OR 5.03, 95% CI, 2.23, 11.33) and repeated antibiotic courses (two courses OR 2.81, 95% CI, 1.1, 7.8, three courses or more OR 9.44, 95% CI, 3.50, 25.49) were associated with adverse radiological outcome, A non-significant trend remained after adjustment to other known risk factors. Among 46 neonates with adverse radiologic outcome, 16 (34.8%) had an adverse neurological outcome. The most significant risk factors were NICU length of stay, duration of mechanical ventilation and culture-proven sepsis. Conclusion: Our sample despite its small size, suggests an association between prolonged antibiotic treatment and neonatal brain injury. These findings need further investigation using larger cohorts.

Factors associated with non-response to second course indomethacin for PDA treatment in preterm neonates

Background: Failure of first course of indomethacin (FCI) for patent ductus arteriosus (PDA) treatment in preterm neonates often prompts clinicians to consider a second course (SCI).Objective: To identify factors including baseline characteristics and response to FCI that are associated with non-response to SCI for PDA treatment in preterm neonates.Methods: In this retrospective observational study, neonates ≤32 weeks admitted to a tertiary NICU over 5 years who received two indomethacin courses for PDA treatment were reviewed. Only neonates with echocardiograms (ECHO) immediately before and after receipt of each indomethacin course were included. Primary outcome was non-response to SCI. Baseline characteristics and response to FCI were compared between responders and non-responders of SCI.Results: Of the 98 neonates enrolled, 47 (48%) had non-response to SCI. Of them, 27 patients (57%) had prior non-response to FCI, while of the 51 neonates who responded to SCI, 24 neonates (47%) had prior non-response to FCI. The adjusted risk of non-response to SCI in patients who had non-response to FCI was 37% higher (relative risk = 1.37, 95%CI: 0.87–1.80; p = .07) compared to those who had response to FCI. Multivariable analysis showed that increasing gestational age (AOR: 1.6, 95%CI: 1.1–2.3, p = .03) was associated with a higher odds of non-response to SCI while the odds of non-response to SCI increased by 90% in patients with non-response to FCI (AOR: 1.9, 95%CI: 0.8–4.5; p = .15) compared to those with success of FCI, although no statistical significance was observed.Conclusions: Advanced gestational age was the predictor of non-response to SCI in preterm neonates.

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect the Fetal Brain After Hypoxia-Ischemia.

Preterm neonates are susceptible to perinatal hypoxic-ischemic brain injury, for which no treatment is available. In a preclinical animal model of hypoxic-ischemic brain injury in ovine fetuses, we have demonstrated the neuroprotective potential of systemically administered mesenchymal stromal cells (MSCs). The mechanism of MSC treatment is unclear but suggested to be paracrine, through secretion of extracellular vesicles (EVs). Therefore, we investigated in this study the protective effects of mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) in a preclinical model of preterm hypoxic-ischemic brain injury. Ovine fetuses were subjected to global hypoxia-ischemia by transient umbilical cord occlusion, followed by in utero intravenous administration of MSC-EVs. The therapeutic effects of MSC-EV administration were assessed by analysis of electrophysiological parameters and histology of the brain. Systemic administration of MSC-EVs improved brain function by reducing the total number and duration of seizures, and by preserving baroreceptor reflex sensitivity. These functional protections were accompanied by a tendency to prevent hypomyelination. Cerebral inflammation remained unaffected by the MSC-EV treatment. Our data demonstrate that MSC-EV treatment might provide a novel strategy to reduce the neurological sequelae following hypoxic-ischemic injury of the preterm brain. Our study results suggest that a cell-free preparation comprising neuroprotective MSC-EVs could substitute MSCs in the treatment of preterm neonates with hypoxic-ischemic brain injury, thereby circumventing the potential risks of systemic administration of living cells. Bone marrow-derived mesenchymal stromal cells (MSCs) show promise in treating hypoxic-ischemic injury of the preterm brain. Study results suggest administration of extracellular vesicles, rather than intact MSCs, is sufficient to exert therapeutic effects and avoids potential concerns associated with administration of living cells. The therapeutic efficacy of systemically administered mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) on hypoxia-ischemia-induced injury was assessed in the preterm ovine brain. Impaired function and structural injury of the fetal brain was improved following global hypoxia-ischemia. A cell-free preparation of MSC-EVs could substitute for the cellular counterpart in the treatment of preterm neonates with hypoxic-ischemic brain injury. This may open new clinical applications for "off-the-shelf" interventions with MSC-EVs.

Surfactant Replacement Therapy Beyond Respiratory Distress Syndrome in Neonates.

Surfactant replacement therapy is an established modality of treatment in preterm neonates with respiratory distress syndrome. In addition, there are various neonatal respiratory disorders which are characterized by surfactant deficiency in which surfactant therapy can be a feasible and safe option. To collate the literature on the use of surfactant replacement therapy in neonates beyond respiratory distress syndrome and examine the evidence and newer developments. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, and EMBASE up to June 2015; and previous reviews, including cross-references, abstracts, and conference proceedings. Evidence supports surfactant administration via bolus route in neonates with meconium aspiration syndrome, but additional robust evidence is required before its adoption in clinical practice. There is limited evidence to support surfactant therapy in neonates with pneumonia, pulmonary hemorrhage and bronchopulmonary dysplasia. Large multicenter randomized trials are needed to cement or refute the role of surfactant therapy in these disorders.

Outcomes of inhaled nitric oxide in preterm neonates - a five-year experience in a tertiary neonatal centre

To review the outcome of preterm neonates treated with iNO. The neonatal electronic database was reviewed between April 1, 2009 and March 31, 2014. In the five-year period, 142 babies were treated with iNO. Forty-two preterm neonates <34(+0) weeks were included in this review. During this period, the use of iNO in preterm neonates <26(+0) weeks rose from 1.4% to 4.8% and the mortality was significantly higher in this group (69%). There is an increasing trend in using iNO as a rescue treatment in preterm neonates. The outcomes were very poor in the preterm neonates <26(+0) weeks. A cautious approach is warranted in the absence of robust evidence to support the use of iNO, in preterm neonates <26(+0) weeks.

CP-069 Quality of antibiotic treatment in preterm neonates: a ready-to-use formulation of gentamicin sulphate

Background Intravenous (IV) drug treatment of preterm neonates is affected by: clinical status (i.e. sepsis/infections, immature physiology, pharmacokinetic/pharmacodynamic variation), shortage of ready-to-use formulations, small doses of drug required and the dangers of the IV route. Purpose To identify the most prescribed IV antibiotics so that ready-to-use formulations can be prepared with standard concentrations (SCs) of drug avoiding handling (reconstitution/dilution) in the ward. Material and methods The Hospital Pharmacy, Neonatology and Hygiene Department of “Azienda Ospedali Riuniti-Ancona” conducted this multiphase study. Phase I: a review of IV antibiotics prescribed to preterm (24 +0 –31 +6 weeks) Neonatology inpatients from 2004–2013. Phase II: study of pharmaceutical quality and stability of SC (2 mg/ml) gentamicin sulphate (the gold standard in sepsis/infections). Aqueous solutions were prepared by pharmacists in two different ways: with and without filtration. Both batches were stored in polyethylene syringes for 90 days at 2–8°C and 25°C and were examined for: endotoxin absence with the LAL test (Limulus amoebocyte lysate, Endosafe Portable Test System) in accordance with the Italian Pharmacopoeia 12th edition (kinetic-chromogenic technique); sterility test (BacT/ALERT FA, six days of incubation at 36°C) for aerobic bacteria/fungi; quantification with HPLC-MS/MS technique of gentamicin components (C 1 , C 2 , C 1a ) at 0–3–7–14–21–28–60–90 days. Limits of detection (LOD) and quantitation (LOQ) were 0.25 ng. The SC was derived from the usual dose (2.5 mg/kg/12 h) for a 1,000 g patient. Results Phase I studies found: 1,011 preterm inpatients (521 males, 420 females), 222 cases of sepsis (52 early, 170 late) and 102 infections. Gentamicin was the most used antibiotic with 1,126 doses for 88 patients per year. Phase II studies certified: sterility (no microbiological growth), absence of endotoxins and stability of GS 2 mg/ml stored 90 days at 2–8°C and 25°C. No significant changes in concentration of gentamicin components: P not significant, t-test >0.05. Conclusion After this “pilot study” the next target could be to provide standard concentration unit dose treatments direct from the pharmacy to paediatric patients. References and/or Acknowledgements No conflict of interest.

Hypertrophic intraventricular flow obstruction after very-low-dose dexamethasone (Minidex) in preterm infants: case presentation and review of the literature

The use of dexamethasone in preterm infants developing bronchopulmonary dysplasia has been proven to be effective. Hypertrophic cardiomyopathy is a frequently reported, although transient, side effect of high-dose dexamethasone administration. The recent introduction of very low dexamethasone dose, called 'Minidex', promised equal effectiveness compared to high-dose dexamethasone without relevant side effects. Our study presents two patients developing hypertrophic cardiomyopathy with intraventricular cardiac obstruction after administration of 'Minidex'. Marked cardiac side effects may occur even during very-low-dose dexamethasone treatment in preterm neonates. Betablocker and discontinuation of dexamethasone seem to allow spontaneous reversal of myocardial hypertrophy and obstruction. After all, systematic surveys of the incidence of cardiac complications in a larger population of preterm infants treated with very low doses of dexamethasone are needed.