Measurement of lung oxygenation by near-infrared spectroscopy in preterm infants with bronchopulmonary dysplasia.

INTRODUCTION: It has recently been reported that it is possible to monitor lung oxygenation (rSO2 L) by near-infrared spectroscopy (NIRS) in preterm infants with respiratory distress syndrome (RDS). Thus, our aim was to assess the possibility of monitoring rSO2 L in infants with evolving and established bronchopulmonary dysplasia (BPD) and to evaluate if rSO2 L correlates with BPD severity and other oxygenation indices. METHODS: We studied 40 preterm infants with gestational age ≤30 weeks at risk for BPD. Patients were continuously studied for 2 h by NIRS at 28 ± 7 days of life and 36 weeks ± 7 days of postmenstrual age. RESULTS: rSO2 L was similar at the first and second NIRS recordings (71.8 ± 7.2 vs. 71.4 ± 4.2%) in the overall population, but it was higher in infants with mild than in those with moderate-to-severe BPD at both the first (73.3 ± 3.1 vs. 71.2 ± 3.2%, p = .042) and second (72.3 ± 2.8 vs. 70.5 ± 2.8, p = .049) NIRS recording. A rSO2 L cutoff value of 71.6% in the first recording was associated with a risk for moderate-to-severe BPD with a sensitivity of 66% and a specificity of 60%. Linear regression analysis demonstrated a significant positive relationship between rSO2 L and SpO2 /FiO2 ratio (p = .013) and a/APO2 (p = .004). CONCLUSIONS: Monitoring of rSO2 L by NIRS in preterm infants with evolving and established BPD is feasible and safe. rSO2 L was found to be higher in infants with mild BPD, and predicts the risk for developing moderate-to-severe BPD and correlates with other indices of oxygenation.

A structured programme to promote breastfeeding improved the rates in very preterm infants at discharge.

AIM: We developed the Promotion of Breastfeeding (PROBREAST) programme and evaluated what effect it had on the breastfeeding rate in infants born at less than 32 weeks of gestation or weighing ≤1500 grams. METHODS: We compared the breastfeeding rate in two cohorts of patients who were born before (n = 72; January 2017 to June 2018) and after (n = 80; July 2018 to December 2019) the application of the programme. Moreover, we compared the correlation between type of feeding at discharge and post-discharge breastfeeding rate, between exclusive breastfeeding, postnatal growth and neurodevelopment. RESULTS: Infants in the PROBREAST group had an exclusive breastfeeding rate at discharge higher (42 vs. 16%, p < 0.001) than that in the historical control group. Exclusive breastfeeding was negatively correlated with weight z-score at discharge, but not at 12 and 24 months corrected age, and was positively correlated with cognitive score at 24 months corrected age. CONCLUSION: The application of a structured programme for the promotion of breastfeeding improved the breastfeeding rate in very preterm infants. We demonstrated that exclusive breastfeeding at discharge improved their neurodevelopment without impairing growth.

Nasal intermittent positive pressure ventilation during less invasive surfactant administration in preterm infants: An open-label randomized controlled study.

INTRODUCTION: Approximately half of very preterm infants with respiratory distress syndrome (RDS) fail treatment with nasal continuous positive airway pressure (NCPAP) and need mechanical ventilation (MV). OBJECTIVES: Our aim with this study was to evaluate if nasal intermittent positive pressure ventilation (NIPPV) during less invasive surfactant treatment (LISA) can improve respiratory outcome compared with NCPAP. MATERIALS AND METHODS: We carried out an open-label randomized controlled trial at tertiary neonatal intensive care units in which infants with RDS born at 25+0-31+6 weeks of gestation between December 1, 2020 and October 31, 2022 were supported with NCPAP before and after surfactant administration and received NIPPV or NCPAP during LISA. The primary endpoint was the need for a second dose of surfactant or MV in the first 72 h of life. Other endpoints were need and duration of invasive and noninvasive respiratory supports, changes in SpO2/FiO2 ratio after LISA, and adverse effect rate. RESULTS: We enrolled 101 infants in the NIPPV group and 99 in the NCPAP group. The unadjusted odds ratio for the composite primary outcome was 0.873 (95% confidence interval: 0.456-1.671; p = .681). We found that the SpO2/FiO2 ratio was transiently higher in the LISA plus NIPPV than in the LISA plus NCPAP group, while adverse effects of LISA had similar occurrence in the two arms. CONCLUSIONS: The application of NIPPV or NCPAP during LISA in very preterm infants supported with NCPAP before and after surfactant administration had similar effects on the short-term respiratory outcome and are both safe. Our study does not support the use of NIPPV during LISA.

Morphine exposure and prematurity affect flash visual evoked potentials in preterm infants.

Objective: The present study aimed to explore first the impact of perinatal risk factors on flash-VEP waves and morphology in a group of preterm infants studied at term equivalent age (TEA). Second, to correlate VEP morphology with neurological outcome at 2 years corrected age (CA). Methods: Infants with a gestational age (GA) at birth <32 weeks, without major brain injury, were enrolled. Multivariate regression analyses were performed, and the models were run separately for each dependent variable N2, P2, N3 latencies and P2 amplitude. Logistic regression was applied to study N4 component (present/absent) and VEP morphology (regular/irregular). The predictors were GA, bronchopulmonary dysplasia (BPD), postmenstrual age at VEP registration, cumulative morphine and fentanyl dose, and painful procedures. Lastly, linear regression models were performed to assess the relation between the Bayley-III cognitive and motor scores at 2 years CA and VEP morphology, in relation to GA, BPD, painful procedures and cumulative morphine dose. Results: Eighty infants were enrolled. Morphine was the predictor of N2 (R2 = 0.09, p = 0.006), P2 (R2 = 0.11, p = 0.002), and N3 (R2 = 0.13, p = 0.003) latencies. Younger GA was associated with lower amplitude (R2 = 0.05, p = 0.029). None of the independent variables predicted the presence of N4 component, nor VEP morphology in the logistic analysis. VEP morphology was not associated with cognitive and motor scores at 2 years. Conclusions: Morphine treatment and prematurity were risk factors for altered VEPs parameters at TEA. In our cohort VEP morphology did not predict neurological outcome. Significance: Morphine administration should be evaluated according to potential risks and benefits, and dosage individually accustomed, according to pain and comfort scores, considering the possible risk for neurodevelopmental impairment.

External Validation of a Multivariate Model for Targeted Surfactant Replacement.

INTRODUCTION: Early targeted surfactant therapy for preterm infants is recommended but the best criteria to personalize treatment are unclear. We validate a previously published multivariate prognostic model based on gestational age (GA), lung ultrasound score (LUS), and oxygen saturation to inspire oxygen fraction ratio (SatO2/FiO2) using an independent data set. METHODS: Pragmatic, observational study in 10 Italian and Spanish NICUs, including preterm babies (250 and 336 weeks divided into 3 GA intervals) with clinical signs of respiratory distress syndrome and stabilized on CPAP. LUS and SatO2/FiO2 were collected soon after stabilization. Their prognostic accuracy was evaluated on the subsequent surfactant administration by a rigorously masked physician. RESULTS: One hundred seventy-five infants were included in the study. Surfactant was given to 74% infants born at 25-27 weeks, 38.5% at 28-30 weeks, and 26.5% at 31-33 weeks. The calibration curve comparing the validation and the development populations showed significant overlap with an intercept = 0.08, 95% CI (-0.34; 0.5) and a slope = 1.53, 95% CI (1.07-1.98). The validation cohort had a high predictive accuracy. Its ROC curve showed an AUC = 0.95, 95% CI (0.91-0.99) with sensitivity = 0.93, 95% CI (0.83-0.98), specificity = 0.81, 95% CI (0.73-0.88), PPV = 0.76, 95% CI (0.65-0.84), NPV = 0.95, 95% CI (0.88-0.98). LUS ≥9 demonstrated the highest sensitivity (0.91, 95% CI [0.82-0.97]) and specificity = 0.81, 95% CI (0.72-0.88) as individual predictor. LUS and SatO2/FiO2 prognostic performances varied with GA. CONCLUSION: We validated a prognostic model based on LUS and Sat/FiO2 to facilitate early, customized surfactant administration that may improve respiratory management of preterm neonates.

Tissue-Tracking Mitral Annular Displacement in Neonates: A Novel Index of Left Ventricular Systolic Function.

OBJECTIVES: To assess the feasibility, accuracy, and reproducibility of tissue-tracking mitral annular displacement (TMAD) compared with other measures of left ventricular systolic function in healthy preterm and term neonates in the transitional period. METHODS: This was a prospective observational study. Two echocardiograms were performed at 24 and 48 hours of life. TMAD, shortening fraction (SF), ejection fraction (EF), s', and global longitudinal strain (GLS) were measured offline. Accuracy to detect impaired GLS was tested by ROC curve analysis. DeLong test was used to compare AUCs. Intra and interobserver reproducibility of the off-line analysis was calculated. RESULTS: Mean ± SD gestational age and weight were 34.2 ± 3.8 weeks and 2162 ± 833 g, respectively. TMAD was feasible in 168/180 scans (93%). At 24 hours the AUC (95% CI) of SF, EF, s', and TMAD (%) was 0.51 (0.36-0.67), 0.68 (0.54-0.82), 0.63 (0.49-0.77), and 0.89 (0.79-0.99) respectively. At 48 hours the AUC (95% CI) of SF, EF, s', and TMAD (%) was 0.64 (0.51-0.77), 0.59 (0.37-0.80), 0.70 (0.54-0.86), and 0.96 (0.91-1.00), respectively. The AUC of TMAD was superior to the AUC of SF, EF, s', at both timepoints (P < .02). Intraclass correlation coefficients (95% CI) of intra and interobserver reproducibility of TMAD were 0.97 (0.95-0.99) and 0.94 (0.88-0.97), respectively. CONCLUSION: TMAD showed improved accuracy and optimal reproducibility in neonates in the first 48 hours of life.

Lung UltrasouNd Guided surfactant therapy in preterm infants: an international multicenter randomized control trial (LUNG study).

BACKGROUND: The management of respiratory distress syndrome (RDS) in premature newborns is based on different types of non-invasive respiratory support and on surfactant replacement therapy (SRT) to avoid mechanical ventilation as it may eventually result in lung damage. European guidelines currently recommend SRT only when the fraction of inspired oxygen (FiO2) exceeds 0.30. The literature describes that early SRT decreases the risk of bronchopulmonary dysplasia (BPD) and mortality. Lung ultrasound score (LUS) in preterm infants affected by RDS has proven to be able to predict the need for SRT and different single-center studies have shown that LUS may increase the proportion of infants that received early SRT. Therefore, the aim of this study is to determine if the use of LUS as a decision tool for SRT in preterm infants affected by RDS allows for the reduction of the incidence of BPD or death in the study group. METHODS/DESIGN: In this study, 668 spontaneously-breathing preterm infants, born at 25+0 to 29+6 weeks' gestation, in nasal continuous positive airway pressure (nCPAP) will be randomized to receive SRT only when the FiO2 cut-off exceeds 0.3 (control group) or if the LUS score is higher than 8 or the FiO2 requirements exceed 0.3 (study group) (334 infants per arm). The primary outcome will be the difference in proportion of infants with BPD or death in the study group managed compared to the control group. DISCUSSION: Based on previous published studies, it seems that LUS may decrease the time to administer surfactant therapy. It is known that early surfactant administration decreases BPD and mortality. Therefore, there is rationale for hypothesizing a reduction in BPD or death in the group of patients in which the decision to administer exogenous surfactant is based on lung ultrasound scores. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT05198375 . Registered on 20 January 2022.

Comparison among three lung ultrasound scores used to predict the need for surfactant replacement therapy: a retrospective diagnostic accuracy study in a cohort of preterm infants.

Lung ultrasound (LU) has emerged as the imaging technique of choice for the assessment of neonates with respiratory distress syndrome (RDS) at the bedside. Scoring systems were developed to quantify RDS severity and to predict the need for surfactant administration. There is no data on the comparison of the three main LU scores (LUS) proposed by Brat, Raimondi and Rodriguez-Fanjul. Moreover, there is not enough evidence to recommend which score and which cut-off has the best ability to predict surfactant need. The three LUS were compared in terms of ability to predict the need for surfactant and reproducibility in a cohort of very preterm infants. This was an observational, retrospective, multicenter study. Neonates below 32 weeks of gestational age with RDS, on non-invasive ventilation with a LU performed prior to surfactant administration (1-3 h of life) were included. Brat, Raimondi, and Rodriguez-Fanjul's scores were calculated for each patient. Receiver-operating characteristic (ROC) curve analysis was used to assess the ability to predict surfactant administration. K-Cohen test, Bland-Altman, and intraclass correlation coefficients were used to assess the intra and interobserver variability. Fifty-four preterm infants were enrolled. Brat, Raimondi, and Rodriguez-Fanjul scores showed a strong ability to predict the need for surfactant: the AUCs were 0.85 (95% CI 0.74-0.96), 0.85 (95% CI 0.75-0.96), and 0.79 (95% CI 0.67-0.92), respectively. No significant differences have been found between the AUCs using the DeLong test. Brat and Raimondi's scores had an optimal cut-off value > 8, while the Rodriguez-Fanjul's score > 10. The k-Cohen values of intraobserver agreement for Brat, Raimondi, and Rodriguez-Fanjul's scores were 0.896 (0.698-1.000), 1.000 (1.000-1.000), and 0.922 (0.767-1.000), respectively. The k-Cohen values of interobserver agreement were 0.896 (0.698-1.000), 0.911 (0.741-1.000), and 0.833 (0.612-1.000), respectively.Conclusions: The three LUS had an excellent ability to predict the need for surfactant and an optimal intra and interobserver agreement. The differences found between the three scores are minimal with negligible clinical implications. Since the optimal cut-off value differed, the same score should be used consistently within the same center. What is Known: • Lung ultrasound is a useful bedside imaging tool that should be used in the assessment of neonates with RDS • Scoring systems or lung ultrasound scores allow to quantify the severity of the pulmonary disease and to predict the need for surfactant replacement therapy What is New: • The three lung ultrasound scores by Brat, Raimondi and Rodriguez-Fanjul have an excellent ability to predict the need for surfactant replacement therapy, although with different cut-off values • All three lung ultrasound scores had an excellent intra and interobserver reproducibility.

Prognostic accuracy of Neonatal SOFA score versus SIRS criteria in preterm infants with late-onset sepsis.

Neonatal SOFA score was reported as an accurate predictor of mortality while the prognostic accuracy of SIRS criteria is unknown. The aim was to compare neonatal SOFA and SIRS criteria for the prediction of late onset sepsis-related mortality in preterm newborns. Newborns ≤ 32 weeks with late onset sepsis were retrospectively studied. Neonatal SOFA and SIRS criteria were calculated at onset of sepsis (T0), and after 6 ± 1 (T1), 12 ± 3 (T2) and 24 ± 3 h (T3). Outcome was death during antibiotic treatment for late onset sepsis. We studied 112 newborns with gestational age 26.9 ± 2.3 weeks; 11% met the study outcome. Neonatal SOFA was significantly higher in non-survivors vs. survivors at all time intervals; SIRS criteria were significantly higher in non-survivors vs. survivors at T1, T2 and T3. Neonatal SOFA increased over time in non-survivors (p = 0.003). At T0, the area under receiver operating characteristics curve was significantly higher for neonatal SOFA score than SIRS criteria (0.950 vs. 0.569; p = 0.0002), and the best calculated cut-off for T0 neonatal SOFA score was 4. In multivariate analysis T0 and T1 neonatal SOFA were predictors of late onset sepsis-related mortality (p = 0.048 and p < 0.001).  Conclusion: Neonatal SOFA score showed greater discriminatory capacity for mortality than SIRS criteria and might be helpful to plan management for patients at higher risk of death. What is Known: • Neonatal SOFA score may be an accurate prognostic tool. • No prognostic score has been fully standardized for septic newborns in NICU. What is New: • Neonatal SOFA score outperformed SIRS criteria for the prediction of prognosis in preterm infants with late onset sepsis. • Neonatal SOFA score assessed at onset of sepsis and 6 hrs later is a predictor of mortality.

Association between immediate oxygenation response and survival in preterm infants receiving rescue inhaled nitric oxide therapy for hypoxemia from pulmonary hypertension: A systematic review and meta-analysis.

PURPOSE: To investigate whether immediate response to inhaled nitric oxide (iNO) therapy is associated with reduced mortality in preterm infants with hypoxemic respiratory failure (HRF) and pulmonary hypertension (PH). METHODS: A systematic review and meta-analysis of observational studies was conducted to examine the association between immediate response (improved oxygenation ≤6 h) compared to non-response, and all-cause mortality among preterm infants <34 weeks gestational age without congenital anomalies or genetic disorders who received iNO treatment. Adjusted and unadjusted odds ratio, were pooled using a random effects meta-analysis Hartung-Knapp-Sidik-Jonkman approach. Subgroup analyses were planned for infants with preterm premature rupture of membranes (PPROM) and those treated within 72 h after birth. RESULTS: The primary analysis included 5 eligible studies, a total of 400 infants (196 responders; 204 non-responders). The studies were rated as low to moderate risk of bias based on the Quality in Prognostic Studies tool. Immediate iNO responsiveness was associated with reduced odds of mortality [odds ratio (OR) 0.22, 95 % confidence interval (95 % CI) (0.10-0.49)]. Although there was insufficient data for a subgroup analysis of infants with PPROM, infants treated with iNO within 72 h demonstrated consistent findings of reduced mortality [OR 0.21 95 % CI (0.13-0.36)]. Based on the GRADE approach, considering the risk of bias of included studies, the overall strength of evidence was rated as moderate. CONCLUSION: There is evidence to suggest that immediate improvement in oxygenation following iNO therapy is associated with reduced odds of mortality before discharge in preterm infants with HRF and clinically suspected or confirmed PH.

Ethanol-induced AMPA alterations are mediated by mGLU5 receptors through miRNA upregulation in hippocampal slices.

Prenatal alcohol exposure (PAE) affects neuronal networks and brain development causing a range of physical, cognitive and behavioural disorders in newborns that persist into adulthood. The array of consequences associated with PAE can be grouped under the umbrella-term 'fetal alcohol spectrum disorders' (FASD). Unfortunately, there is no cure for FASD as the molecular mechanisms underlying this pathology are still unknown. We have recently demonstrated that chronic EtOH exposure, followed by withdrawal, induces a significant decrease in AMPA receptor (AMPAR) expression and function in developing hippocampus in vitro. Here, we explored the EtOH-dependent pathways leading to hippocampal AMPAR suppression. Organotypic hippocampal slices (2 days in cultures) were exposed to EtOH (150 mM) for 7 days followed by 24 h EtOH withdrawal. Then, the slices were analysed by means of RT-PCR for miRNA content, western blotting for AMPA and NMDA related-synaptic proteins expression in postsynaptic compartment and electrophysiology to record electrical properties from CA1 pyramidal neurons. We observed that EtOH induces a significant downregulation of postsynaptic AMPA and NMDA subunits and relative scaffolding protein expression and, accordingly, a decrease of AMPA-mediated neurotransmission. Simultaneously, we found that chronic EtOH induced-upregulation of miRNA 137 and 501-3p and decreased AMPA-mediated neurotransmission are prevented by application of the selective mGlu5 antagonist MPEP during EtOH withdrawal. Our data indicate mGlu5 via miRNA137 and 501-3p expression as key factors in the regulation of AMPAergic neurotransmission that may contribute, at least in part, to the pathogenesis of FASD.

Carboxyhemoglobin as biomarker of late-onset sepsis in preterm infants.

Carboxyhemoglobin (COHb) is considered a biomarker of oxidative stress and previous studies reported an increase in COHb levels in preterm infants who develop late-onset sepsis (LOS). Our aim was to assess the correlation between COHb levels and the risk for LOS development. We retrospectively studied 100 preterm infants, 50 in the LOS and 50 in the no LOS group. COHb levels were measured on the day of diagnosis of the first episode of LOS, 3, 2, and 1 days before and 1 and 4 days after the onset of LOS. Logistic regression analysis showed that a higher level of COHb 2 days before the diagnosis of LOS increases the risk for LOS development (OR 12.150, 95% Cl 1.311-12.605; P = 0.028). A COHb level of 1.55% measured 2 days before the diagnosis of LOS is the best predictive threshold for LOS with a sensitivity of 70% and a specificity of 70%.    Conclusion: Increased levels of COHb may predict the diagnosis of LOS in very preterm infants with a good accuracy. If further studies confirm our findings, this easy-to-measure biomarker could provide neonatologists with another tool for monitoring and early diagnosis of sepsis in high-risk patients. What is Known: • Carboxyhemoglobin (COHb) is a biomarker of oxidative stress. • Previous studies reported an increase in COHb levels in preterm infants who develop late-onset sepsis (LOS). What is New: • COHb levels increased two days before the diagnosis of LOS and this increase was associated with the risk for developing LOS. • ROC curve analysis for COHb measured two days before the diagnosis of LOS showed that 1.55% is the best predictive threshold for LOS with a sensitivity of 70% and a specificity of 70%.

Effect of Nasal Continuous Positive Airway Pressure vs Heated Humidified High-Flow Nasal Cannula on Feeding Intolerance in Preterm Infants With Respiratory Distress Syndrome: The ENTARES Randomized Clinical Trial.

Importance: Respiratory distress syndrome and feeding intolerance are common conditions that are often associated with preterm infants. Showing similar efficacy, nasal continuous positive airway pressure (NCPAP) and heated humidified high-flow nasal cannula (HHHFNC) are the most widespread noninvasive respiratory support (NRS) in neonatal intensive care units, but their effect on feeding intolerance is unknown. Objective: To evaluate the effect of NCPAP vs HHHFNC on high-risk preterm infants with respiratory distress syndrome. Design, Setting, and Participants: This multicenter randomized clinical trial involved infants who were born in 1 of 13 neonatal intensive care units in Italy between November 1, 2018, and June 30, 2021. Preterm infants with a gestational age of 25 to 29 weeks, who were suitable for enteral feeding and who proved to be medically stable on NRS for at least 48 hours were enrolled in the study within the first week of life and randomized to receive either NCPAP or HHHFNC. Statistical analysis was performed according to the intention-to-treat approach. Intervention: NCPAP or HHHFNC. Main Outcomes and Measures: The primary outcome was the time to full enteral feeding (FEF), defined as an enteral intake of 150 mL/kg per day. Secondary outcomes were the median daily increment of enteral feeding, signs of feeding intolerance, effectiveness of the assigned NRS, peripheral oxygen saturation (SpO2)-fraction of inspired oxygen (FIO2) ratio at changes of NRS, and growth. Results: Two-hundred forty-seven infants (median [IQR] gestational age, 28 [27-29] weeks; 130 girls [52.6%]) were randomized to the NCPAP group (n = 122) or the HHHFNC group (n = 125). There were no differences in the primary and secondary nutritional outcomes between the 2 groups. The median time to reach FEF was 14 days (95% CI, 11-15 days) in the NCPAP group and 14 days (95% CI, 12-18 days) in the HHHFNC group, and similar results were observed in the subgroup of infants with less than 28 weeks' gestation. On the first NRS change, higher SpO2-FIO2 ratio (median [IQR], 4.6 [4.1-4.7] vs 3.7 [3.2-4.0]; P < .001) and lower rate of ineffectiveness (1 [4.8%] vs 17 [73.9%]; P < .001) were observed in the NCPAP vs HHHFNC group. Conclusions and relevance: This randomized clinical trial found that NCPAP and HHHFNC had similar effects on feeding intolerance, despite different working mechanisms. Clinicians may tailor respiratory care by selecting and switching between the 2 NRS techniques on the basis of respiratory effectiveness and patient compliance, without affecting feeding intolerance. Trial Registration: ClinicalTrials.gov Identifier: NCT03548324.

Effect of fortification on the osmolality of human milk.

BACKGROUND: It is known that human milk fortifiers (HMF) increases osmolality of human milk (HM) but some aspects of fortification have not been deeply investigated. Our aim was to evaluate the effect of fortification on the osmolality of donor human milk (DHM) and mother's own milk (MOM) over 72 h of storage using two commercial fortifiers and medium-chain triglycerides (MCT) supplementation. METHODS: Pasteurized DHM and unpasteurized preterm MOM were fortified with 4% PreNAN FM85, 4% PreNAN FM85 plus 2% MCT, or 4% Aptamil BMF. Osmolality was measured in unfortified DHM and MOM and, moreover, just after fortification (T0), and after 6 (T6), 24 (T24) and 72 h (T72) to determine the effect of mixing and storage. RESULTS: Unfortified DHM and MOM did not show changes of osmolality. Fortification increased osmolality of DHM and MOM without changes during the study period, except for Aptamil BMF which increased osmolality of MOM. The addition of MCT to fortified human milk (FHM) did not affect its osmolality. CONCLUSIONS: Changes of osmolality in the 72 h following fortification of both DHM and MOM did not exceed the safety values supporting the theoretically possibility of preparing 72 h volumes of FHM. Supplementation with MCT of FHM does not change osmolality suggesting that increasing energy intake in preterm infants via this approach is safe.

New Antimicrobials for the Treatment of Neonatal Sepsis Caused by Multi-Drug-Resistant Bacteria: A Systematic Review.

BACKGROUND: Infections by multi-drug-resistant (MDR) organisms are sharply increasing in newborns worldwide. In low and middle-income countries, a disproportionate amount of neonatal sepsis caused by MDR Gram negatives was recently reported. Newborns with infections by MDR organisms with limited treatment options may benefit from novel antimicrobials. METHODS: We performed a literature search investigating the use in newborns, infants and children of novel antimicrobials for the treatment of MDR Gram negatives, namely ceftazidime/avibactam, ceftolozane/tazobactam, cefiderocol, meropenem/vaborbactam, imipenem/relebactam, and Gram positives with resistance of concern, namely ceftaroline and dalbavancin. PubMed, EMBASE, and Web of Science were searched. RESULTS: A total of 50 records fulfilled the inclusion criteria. Most articles were case reports or case series, and ceftazidime/avibactam was the most studied agent. All studies showed favorable efficacy and safety profile in newborns and across different age cohorts. CONCLUSIONS: novel antibiotics may be considered in newborns for the treatment of MDR Gram negatives with limited treatment options and for Gram positives with resistance concerns. Further studies are needed to address their effectiveness and safety in newborns.

Effects of caffeine on diaphragmatic activity in preterm infants.

BACKGROUND: Caffeine is the first-choice drug for the treatment for apnea of prematurity (AOP) in preterm infants and it has been reported that it improves the diaphragm activity. The aim of this study was to evaluate by ultrasound possible changes in diaphragm contractility and motility induced by caffeine. METHODS: We studied 26 preterm infants with gestational age ≤34 weeks treated with caffeine for the prevention or treatment of AOP. Diaphragmatic ultrasound was performed 15 min (T0 ) before and 60 min (T60 ) after the loading (20 mg/kg) or maintenance (5 mg/kg) dose of caffeine. RESULTS: Diaphragmatic excursion (DE) and thickness at the end of inspiration (DT-in) and expiration (DT-ex), as well as peak velocity of the excursion at the end of inspiration (DT-in) and expiration (DT-ex) increased after administration of both loading and maintenance dose of caffeine. CONCLUSIONS: Ultrasounds confirmed that caffeine improves the activity of diaphragm in preterm infants improving its thickness, amplitude of excursions, and contraction velocity. These results are consistent with the effectiveness of caffeine in treating AOP and decreasing the risk of failure of noninvasive respiratory support in preterm infants with respiratory distress syndrome (RDS).

Neonatal Outcomes of Term Infants Born with Meconium-Stained Amniotic Fluid.

Background Meconium-stained amniotic fluid (MSAF) is considered an alarming sign of possible fetal compromise and it has recently been reported that neonatal outcome correlates with the degree of meconium thickness. Methods We retrospectively studied 400 term infants allocated in clear amniotic fluid and grade 1, 2, and 3 MSAF groups on the basis of color and thickness of AF. Multivariable logistic regression analysis was performed to evaluate the potential independent effect of delivery with MSAF of different severity on the risk of a composite adverse neonatal outcome. Results We found that delivery with grade 2 (OR 16.82, 95% Cl 2.12-33.52; p = 0.008) and 3 (OR 33.79, 95% Cl 4.24-69.33; p < 0.001) MSAF is independently correlated with the risk of adverse neonatal outcome, such as the occurrence of at least one of the following: need of resuscitation in the delivery room, blood cord pH < 7.100, occurrence of meconium aspiration syndrome (MAS), persistent pulmonary hypertension (PPH), transient tachypnea of the newborn (TTN), acute respiratory distress syndrome (ARDS), hypoxic-ischemic encephalopathy (HIE), and sepsis. Conclusions There is a positive correlation between the severity of amniotic fluid meconium staining and thickness and the outcomes of term infants. Therefore, the evaluation and grading of MSAF during labor is useful in order to plan for the presence of a neonatologist at delivery for immediate and proper neonatal care.

Cardiac Hypertrophy Associated with Insulin Therapy in Extremely Preterm Infants.

BACKGROUND: In the neonatal period, cardiac hypertrophy (CH) has been commonly associated with hyperinsulinemic pathologies, and the first case of CH in an extremely preterm infant treated with insulin infusion has recently been reported. To confirm this association, we report a case series of patients who developed CH after insulin therapy. METHODS: Infants with gestational age < 30 weeks and birth weight < 1500 g, born from November 2017 to June 2022, were studied if they developed hyperglycemia requiring treatment with insulin and had echocardiographic diagnosis of CH. RESULTS: We studied 10 extremely preterm infants (24.3 ± 1.4 weeks) who developed CH at a mean age of 124 ± 37 h of life, 98 ± 24 h after the initiation of insulin therapy. All surviving patients had resolution of CH at discharge, while three of four (75%) of the deceased patients had persistent CH. CONCLUSIONS: Our case series supports the association between the development of CH and insulin therapy in extremely preterm infants and suggests further caution and the need for echocardiographic monitoring when treating these fragile patients with insulin.

Carboxyhemoglobin as biomarker of prematurity complications.

BACKGROUND: Carboxyhemoglobin (COHb) is considered a biomarker of oxidative stress and previous studies suggest a correlation between its blood level and prematurity complications. Our aim in this study was to assess the correlation between COHb levels and the risk for bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). METHODS: We retrospectively studied 178 preterm infants with gestational age of 27.0 ± 1.5 weeks, among which 121 (68 %) had BPD, 43 (24 %) IVH, and 33 (19 %) ROP. COHb levels measured during the first seven days of life were recorded. RESULTS: Logistic regression analysis showed that higher levels of COHb on the seventh day of life increases the risk for moderate-to-severe BPD (OR 4.552, 95 % Cl 1.220-16.997; P = 0.024), while higher levels of COHb on the fourth day of life increases the risk for grade 2-4 IVH (OR 5.537, 95 % Cl 1.602-19.134; P = 0.007). CONCLUSIONS: COHb measured in the first week of life can contribute to predicting the risk for BPD and IVH, but not for ROP, in very preterm infants. Since COHb can be readily measured, its assessment can be useful in clinical practice for early identification of preterm infants at high risk for oxidative stress related complications.