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Cyclic phototherapy (cPT) can achieve a reduction in total serum bilirubin comparable to that achieved with standard continuous PT in preterm infants. Our aim was to assess the effect of cPT on splanchnic (rSO2S) and cerebral (rSO2C) oxygenation measured by near-infrared spectroscopy (NIRS). We prospectively studied 16 infants with a gestational age of 25–34 weeks with hyperbilirubinemia requiring PT. Splanchnic regional oxygenation (rSO2S), oxygen extraction fraction (FOES), and cerebro-splanchnic oxygenation ratio (CSOR) were recorded before, during, and after cPT discontinuation. We found that rSO2S, FOES, and CSOR did not change during the study period. The overall duration of single or multiple courses of PT was 6.5 (6.0–13.5) h, but by cycling PT, the actual exposure was 3.0 (1.5–4.9) h. Twelve patients (75%) required 15 min/h cPT, and four (25%) required prolonging cPT to 30 min/h. None of the patients developed enteral feeding intolerance. Conclusions: cPT treatment of hyperbilirubinemia in preterm infants does not affect splanchnic oxygenation or intestinal oxygen blood extraction, likely due to the short exposure to PT light, and it could contribute to decreasing the risk of feeding intolerance. What is Known: • The assumption that phototherapy (PT) is innocuous with no serious adverse effects has been questioned. • Cyclic phototherapy (cPT) can achieve a reduction in total serum bilirubin comparable to that achieved with standard continuous PT in preterm infants. What is New: • Splanchnic and cerebral oxygenation measured by near-infrared spectroscopy did not change during KMC. • cPT can contribute to decrease the risk of feeding intolerance likely due to the short exposure to PT light. [ABSTRACT FROM AUTHOR]

Lung function has never been assessed during kangaroo mother care (KMC) in preterm infants. We measured lung (rSO2L) and cerebral (rSO2C) oxygenation by near-infrared spectroscopy (NIRS) in infants born at less than 32 weeks of gestation or weighing ≤ 1500 g during KMC. rSO2L, rSO2C, and pulmonary (FOEL) and cerebral (FOEC) tissue oxygen extraction fraction were measured in 20 preterm infants before, during, and after a 2-h period of KMC at a mean postnatal age of 36 ± 21 days of life. We found that rSO2L, rSO2C, FOEL, and FOEC did not change in our patients. After 120 min of KMC, rSO2L was lower (71.3 ± 1.4 vs. 76.7 ± 4.6%; P = 0.012) in infants with BPD (n = 6; 30%) than in infants without BPD (n = 14 = 60%), while FOEL was higher (0.26 ± 0.02 vs. 0.20 ± 0.05; P = 0.012). Conclusion: Cerebral and lung oxygenation did not change in preterm infants during KMC. A transient decrease in lung oxygenation was offset by the increase in oxygen extraction, but these changes were clinically insignificant. These results confirm the safety of KMC in preterm infants who are in stable clinical conditions. What is Known • Kangaroo mother care (KMC) is widely used to improve the care of preterm newborns since it improves their outcome. • KMC is safe as patients' vital parameters, are not negatively affected, but lung function has never been directly assessed. What is New • Cerebral and lung oxygenation measured by near-infrared spectroscopy did not change during KMC. • A transient decrease in lung oxygenation compensated for by the increase in oxygen extraction occurred only in infants with BPD, but these changes were clinically insignificant. [ABSTRACT FROM AUTHOR]

Background: Preterm infants are at high risk for retinopathy of prematurity (ROP), with potential life-long visual impairment. Low fetal hemoglobin (HbF) levels predict ROP. It is unknown if preventing the HbF decrease also reduces ROP. Methods: BORN is an ongoing multicenter double-blinded randomized controlled trial investigating whether transfusing HbF-enriched cord blood-red blood cells (CB-RBCs) instead of adult donor-RBC units (A-RBCs) reduces the incidence of severe ROP (NCT05100212). Neonates born between 24 and 27 + 6 weeks of gestation are enrolled and randomized 1:1 to receive adult donor-RBCs (A-RBCs, arm A) or allogeneic CB-RBCs (arm B) from birth to the postmenstrual age (PMA) of 31 + 6 weeks. Primary outcome is the rate of severe ROP at 40 weeks of PMA or discharge, with a sample size of 146 patients. A prespecified interim analysis was scheduled after the first 58 patients were enrolled, with the main purpose to evaluate the safety of CB-RBC transfusions. Results: Results in the intention-to-treat and per-protocol analysis are reported. Twenty-eight patients were in arm A and 30 in arm B. Overall, 104 A-RBC units and 49 CB-RBC units were transfused, with a high rate of protocol deviations. A total of 336 adverse events were recorded, with similar incidence and severity in the two arms. By per-protocol analysis, patients receiving A-RBCs or both RBC types experienced more adverse events than non-transfused patients or those transfused exclusively with CB-RBCs, and suffered from more severe forms of bradycardia, pulmonary hypertension, and hemodynamically significant patent ductus arteriosus. Serum potassium, lactate, and pH were similar after CB-RBCs or A-RBCs. Fourteen patients died and 44 were evaluated for ROP. Ten of them developed severe ROP, with no differences between arms. At per-protocol analysis each A-RBC transfusion carried a relative risk for severe ROP of 1.66 (95% CI 1.06–2.20) in comparison with CB-RBCs. The area under the curve of HbF suggested that HbF decrement before 30 weeks PMA is critical for severe ROP development. Subsequent CB-RBC transfusions do not lessen the ROP risk. Conclusions: The interim analysis shows that CB-RBC transfusion strategy in preterm neonates is safe and, if early adopted, might protect them from severe ROP. Trial registration: Prospectively registered at ClinicalTrials.gov on October 29, 2021. Identifier number NCT05100212. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

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%. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The effectiveness of repeated drug course to close or constrict a hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants has not been studied extensively. Our aim was to assess the effectiveness of a second or third course of treatment with ibuprofen and/or paracetamol in 107 infants with gestational age < 29 weeks. Infants with echocardiographic diagnosis of hsPDA were treated with ibuprofen, paracetamol, or with ibuprofen plus paracetamol between 24 and 72 h of life. Echocardiography was repeated at the end of each pharmacological course. The failure rate of the first, second and third course of drug treatment was 38% (41/107), 76% (31/41), and 92% (24/26), respectively. Among 24 infants who failed treatment, 8 (31%) had closure or constriction of the hsPDA after >3 drug courses, 15 (57%) received surgical closure, and 3 (12%) died with hsPDA. Logistic regression analyses did not show independent risk factors for the failure of the second and third course of treatment. We found a higher failure rate of the second and third courses of drug treatment than previously reported. Planning the third and additional pharmacological courses at centers where the failure rate is very high may prolong the exposure of very preterm infants to the adverse effects of hsPDA. • We assessed the effectiveness of a second or third course of treatment with ibuprofen and/or paracetamol in a cohort of extremely preterm infants. • We found a higher failure rate of the second (76%) and third (92%) courses of drug treatment than previously reported. • Additional pharmacological courses may prolong the exposure of very preterm infants to the adverse effects of hsPDA. [ABSTRACT FROM AUTHOR]

Background: Early treatment with caffeine in the delivery room (DR) has been proposed to decrease the need for mechanical ventilation (MV) by limiting episodes of apnoea and improving respiratory mechanics in preterm infants. Our aim was to verify the hypothesis that intravenous or enteral administration of caffeine can be performed in the preterm infant in the DR. Methods: Infants with 25±0–29±6 weeks of gestational age were enrolled and randomised to receive 20 mg/kg of caffeine citrate intravenously, via the umbilical vein, or enterally, through an orogastric tube, within 10 min of birth. Caffeine blood level was measured at 60 ± 15 min after administration and 60 ± 15 min before the next dose (5 mg/kg). The primary endpoint was evaluation of the success rate of intravenous and enteral administration of caffeine in the DR. Results: Nineteen patients were treated with intravenous caffeine and 19 with enteral caffeine. In all patients the procedure was successfully performed. Peak blood level of caffeine 60 ± 15 min after administration in the DR was found to be below the therapeutic range (5 µg/mL) in 25 % of samples and above the therapeutic range in 3%. Blood level of caffeine 60 ± 15 min before administration of the second dose was found to be below the therapeutic range in 18% of samples. Conclusions: Intravenous and enteral administration of caffeine can be performed in the DR without interfering with infants' postnatal assistance. Some patients did not reach the therapeutic range, raising the question of which dose is the most effective to prevent MV. Clinical Trial Registration: ClinicalTrials.gov identifier NCT04044976; EudraCT number 2018-003626-91. [ABSTRACT FROM AUTHOR]

Objective Many very preterm infants are treated with phototherapy (PT) for hyperbilirubinemia and it has been reported that PT can negatively affect gut perfusion. Thus, our aim was to evaluate the occurrence of feeding intolerance in the course of PT in these patients. Methods We retrospectively studied infants born at 25+0–31+6 weeks from November 2017 to April 2020 who required PT during the first two weeks of life. Patients were used as their own controls recording for each one the occurrence of feeding intolerance after starting PT and the resumption of feeding tolerance after its termination. Results We studied 125 preterm infants of whom 58 (46%) developed a feeding intolerance which disappeared in 47 (81%) of them at the end of PT. Regression analysis showed a trend toward a not significant decrease of risk of feeding intolerance in infants with higher birth weight and age at the start of the first course of PT. Conclusion We found that about half of our patients developed a transient feeding intolerance during PT that ceased in the vast majority of them after termination of the therapy. Further studies are necessary to confirm the correlation between PT and feeding intolerance. [ABSTRACT FROM AUTHOR]

The aim of this study is to report our experience in the management of type 1 retinopathy of prematurity (ROP) or aggressive posterior retinopathy of prematurity (APROP) in premature infants, who received intravitreal bevacizumab (IVB) injections either as first-line monotherapy or as rescue therapy following laser therapy. Single-center retrospective study on 37 patients (74 eyes) affected by sight-threatening ROP that underwent treatment either with IVB alone or laser photocoagulation followed by IVB at the Neonatal Intensive Care Unit of Careggi University Hospital of Florence, between 2008 and 2015. Seventeen patients were males (45.9%) and 20 were females (54.1%). The mean gestational age was 24 weeks and the mean birth weight was 610 g. Fifty-six eyes (75.7%) of 28 patients were diagnosed as type 1 ROP and 18 eyes (24.3%) of nine patients as APROP. Sixty-six eyes of 33 patients received IVB as first-line monotherapy, eight eyes of four patients were treated with IVB after laser photocoagulation treatment, as rescue therapy. The mean postmenstrual age at treatment was 33.9 weeks. All the patients received bilateral injections. None of the infants required repeat injections. The mean follow-up time was 59.6 months. All the patients achieved a good response to treatment, showing the regression of the proliferative phase and a complete peripheral retinal vascularization within 2 months from the injection of bevacizumab. One patient with a bilateral ROP had only a partial resolution of a vitreous hemorrhage in the left eye. The procedures were well tolerated without local or systemic adverse events during the follow-up. No infants showed recurrences. Ocular motility alterations appeared in four patients (10.8%), with the absence of stereopsis in six cases (16.20%). After treatment, spherical equivalent values in cycloplegic refraction ranged from −4.0 D to +5.0 D, with a mean value of +1.75 D. All the patients showed a normal neuropsychomotor development. Our study confirms the effectiveness and safety of IVB in the treatment of ROP, both as monotherapy and rescue therapy after laser photocoagulation, according to the published literature. [ABSTRACT FROM AUTHOR]

the importance of sucking milk directly at the mother's breast is often underestimated and many aspects of direct breastfeeding of very preterm infants are not investigated. The primary endpoint of the study was to identify maternal and infant clinical predictors of direct breastfeeding in a cohort of infants born at <32 weeks of gestation or weighing <1500 g. The secondary endpoint was to evaluate the possible effects of direct breastfeeding on infant neurodevelopment. Seventy-two infants born between July 2018 and December 2019 were divided into the subgroup that were directly breastfed (n = 42) and not directly breastfed (n = 30) at discharge. Maternal and infant characteristics were compared, and differences were analysed. Logistic regression analysis demonstrated that the percentage of maternal milk taken during hospitalization, maternal age, and weight (z-score) at discharge were positively correlated with the likelihood of direct breastfeeding at discharge. Direct breastfeeding was not correlated with the cognitive score at 24 months corrected age. Direct breastfeeding at discharge is more probable in infants of older mothers who receive more breastmilk and who experience greater weight gain. Direct breastfeeding is not correlated with the cognitive score at 24 months corrected age. • We identified clinical predictors of direct breastfeeding in very preterm infants. • The volume of maternal milk taken during hospitalization, maternal age, and weight at discharge were positively correlated with the likelihood of direct breastfeeding • We evaluated possible effects of direct breastfeeding on neurodevelopment at 24 months corrected age. • We found that direct breastfeeding was not correlated with the cognitive score at 24 months corrected age. [ABSTRACT FROM AUTHOR]

Objective: Non-negligible differences in retinopathy of prematurity (ROP) and its risk factors between different neonatal intensive care units (NICUs) are reported. Our aim was to assess the incidence and risk factors for ROP development in a large cohort of very preterm infants who were assisted in two Italian NICUs. Methods: Preterm infants with gestational age between 23+ 0 and 29+ 6 weeks were stratified into subgroups of infants who developed ROP and those who did not; their clinical characteristics were compared with univariate and multivariable logistic regression analyses. Results: We studied a total of 178 infants of whom 67 (38%) developed ROP (stage 1: n = 12; stage 2: n = 41; stage 3: n = 14). Regression analysis demonstrated that maternal milk (OR 0.979, 95% Cl 0.961–0.998) decreased the risk of developing ROP, while intraventricular hemorrhage (IVH) (OR 2.055, 95% Cl 1.120–3.772) increased it. Moreover, maternal milk was found to decrease (OR 0.981, 95% Cl 0.964–0.997) the risk of ROP at discharge, while RBC transfusion increased it (OR 1.522, 95% Cl 1.208–1.916). Conclusions: In our cohort the occurrence of ROP was similar to that previously reported. Strategies for promoting the use of mother's own milk, preventing IVH, and standardizing the approach to RBC transfusions could contribute to decreasing the risk of ROP in very preterm infants. [ABSTRACT FROM AUTHOR]

Our aim was to assess the efficacy and safety of intravenous (i.v.) paracetamol vs. i.v. ibuprofen for the treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. This is a multicenter randomized controlled study. Infants with a gestational age of 25+0–31+6 weeks were randomized to receive i.v. paracetamol (15 mg/kg/6 h for 3 days) or i.v. ibuprofen (10-5-5 mg/kg/day). The primary outcome was the closure rate of hsPDA after the first treatment course with paracetamol or ibuprofen. Secondary outcomes included the constriction rate of hsPDA, the re-opening rate, and the need for surgical closure. Fifty-two and 49 infants received paracetamol or ibuprofen, respectively. Paracetamol was less effective in closing hsPDA than ibuprofen (52 vs. 78%; P = 0.026), but the constriction rate of the ductus was similar (81 vs. 90%; P = 0.202), as confirmed by logistic regression analysis. The re-opening rate, the need for surgical closure, and the occurrence of adverse effects were also similar. Conclusions: Intravenous paracetamol was less effective in closing hsPDA than ibuprofen, but due to a similar constriction effect, its use was associated with the same hsPDA outcome. These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA. Trial registration:Clinicaltrials.gov: NCT02422966, Date of registration: 04/09/2015; EudraCT no: 2013-003883-30. What is Known: • The successful closure of patent ductus arteriosus with oral paracetamol has been recently reported in several preterm infants, but only one randomized controlled study investigated the efficacy of intravenous paracetamol. What is New: • Intravenous paracetamol is less effective in closing hsPDA than ibuprofen, but have a similar constriction effect. • These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA. [ABSTRACT FROM AUTHOR]

Background: Preterm infants and infants with perinatal brain injury show a higher incidence of neurodevelopmental disorders (NDD). The Infant Motor Profile (IMP) is a clinical assessment which evaluates the complexity of early motor behaviour. More data are needed to confirm its predictive ability and concurrent validity with other common and valid assessments such as the Alberta Infant Motor Scale (AIMS) and Prechtl's General Movement Assessment (GMA). The present study aims to evaluate the concurrent validity of the IMP with the AIMS, to assess its association with the GMA, to evaluate how the IMP reflects the severity of the brain injury and to compare the ability of the IMP and the AIMS to predict an abnormal outcome in 5-month-old infants at risk of NDD.Methods: 86 infants at risk of NDD were retrospectively recruited among the participants of two clinical trials. Preterm infants with or without perinatal brain injury and term infants with brain injury were assessed at 3 months corrected age (CA) using the GMA and at 5 months CA using the IMP and the AIMS. The neurodevelopmental outcome was established at 18 months.Results: Results confirm a solid concurrent validity between the IMP Total Score and the AIMS (Spearman's ρ 0.76; p < .001) and a significant association between IMP Total Score and the GMA. Unlike the AIMS, the IMP Total score accurately reflects the severity of neonatal brain injury (p < .001) and proves to be the strongest predictor of NDD (p < .001). The comparison of areas under receiver operating characteristic curves (AUC) confirms that the IMP Total score has the highest diagnostic accuracy at 5 months (AUC 0.92). For an optimal IMP Total Score cut-off value of 70, the assessment shows high sensitivity (93%) and specificity (81%) (PPV 84%; NPV 90%).Conclusions: Early motor behaviour assessed with the IMP is strongly associated with middle-term neurodevelopmental outcome. The present study confirms the concurrent validity of the IMP with the AIMS, its association with the GMA and its ability to reflect brain lesion load, hence contributing to the construct validity of the assessment.Trial Registration: NCT01990183 and NCT03234959 (clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

This correction notice addresses an error in the affiliation details of the authors Maria Della Bona and Giancarlo la Marca in an article titled "Enteral and Parenteral Treatment with Caffeine for Preterm Infants in the Delivery Room: A Randomised Trial." The original article incorrectly listed their affiliation as the 'Laboratory of Clinical Chemistry and Pharmacology of the A. Meyer Pediatric Hospital of Florence, Florence, Italy,' when it should have been 'Laboratory of Clinical Chemistry and Pharmacology of the Meyer Children's Hospital IRCCS, Florence, Italy.' The original article has been corrected. [Extracted from the article]

Background: Infants born at 23-24 weeks' gestation have the highest risk of developing a hemodynamically significant patent ductus arteriosus (hsPDA), that is refractory to pharmacological closure requiring surgical ligation. Thus, these patients might have the greatest benefits from hsPDA closure, although previous studies on PDA closure were not focused on this population.Aim: To compare the occurrence of hsPDA, failure rate of the first course of ibuprofen in closing hsPDA, and need of surgical closure in infants born at 23+0-24+6 weeks' gestation to those in infants born at 25+0-28+6 weeks' gestation.Study Design: This is a retrospective multicenter study including infants born at 23+0-28+6 weeks of gestation admitted to the neonatal care units from January 2013 to December 2017. All infants underwent echocardiographical assessment for hsPDA diagnosis and eventually pharmacological treatment, and surgical closure.Results: We studied a total of 842 infants of which 562 (67%) developed a PDA. Among those with PDA, 511 (91%) received a pharmacological treatment for a hsPDA. We found that a hsPDA occurred in 70% (106/151) of infants born at 23-24 weeks and in 59% (405/691) of infants born at 25-28 weeks of gestation (P < 0.001). Failure of closure with the first-treatment cycle (69 vs. 40%; P < 0.001) and need of surgical closure (19 vs 10%) were more frequent (P < 0.011) in infants born at 23-24 than 25-28 gestational weeks. Paracetamol vs. ibuprofen treatment and gestational age of 23-24 versus 25-28 weeks increased closure failure, while less severe RDS and maternal clinical chorioamnionitis decreased it.Conclusions: Among extremely preterm infants, infants born at 23-24 weeks of gestation have the highest risk of developing a hsPDA refractory to pharmacological treatment requiring surgical closure. Our findings support the need of individualized more careful strategies for hsPDA management in this special population. [ABSTRACT FROM AUTHOR]

Abstract Background There is no standardized method for total serum bilirubin (TSB) monitoring during phototherapy for neonatal hyperbilirubinemia and national guidelines give heterogeneous indications. Aim To assess the hypothesis that TSB values do not exceed exsanguino-transfusion (EXT) threshold during phototherapy and that it is possible to decrease its monitoring frequency in jaundiced infants. Study design We carried out a prospective observational study in which changes in TSB during phototherapy for non-haemolytic hyperbilirubinemia were recorded in a cohort of late preterm and term infants. TSB values after 6, 12, 18, and 24 h of phototherapy were compared to the EXT threshold matched to infants' gestational and postnatal age according to the specific nomogram of the Italian Society of Neonatology guidelines. Results We studied 105 infants who started phototherapy at a mean age of 89 ± 37 h when mean TSB was 17.1 ± 2.5 mg/dL. We found that TSB decreased during phototherapy and the difference between mean TSB and EXT threshold progressively increased during phototherapy; TSB exceeded EXT threshold in none of our patients (0%). Conclusions Our study demonstrates that differences between mean TSB and EXT threshold increased during phototherapy in late preterm and term infants with non-haemolytic hyperbilirubinemia; in none of our patients TSB exceeded EXT threshold. Our findings support the possibility of safely decreasing TSB monitoring during phototherapy, thus limiting noxious painful stimuli in neonates. Highlights • Differences between mean TSB and EXT threshold increased during phototherapy in late preterm and term infants with hyperbilirubinemia. • In none of our patients TSB exceeded EXT threshold. • It is possible to decrease TSB monitoring during phototherapy, limiting noxious painful stimuli in neonates. [ABSTRACT FROM AUTHOR]

Hyperbilirubinemia is the most frequent clinical problem neonatologists must deal with during the newborn period. It has been suggested that bilirubin is involved in the balance between antioxidant and pro-oxidant agents due to its antioxidant properties. However, the relevance of these effects in vivo in term and preterm infants is still debated. We performed a literature review of studies that investigated the association between total serum bilirubin (TSB) and oxidative stress in newborn infants. We found that studies in term infants give contradictory results, while studies in preterm infants suggest that the TSB increase is associated with an oxidative stress increase due to concurrent factors other than bilirubin level, such as heme oxygenase (HO) activity. Moreover, it could be speculated that low physiologic TSB values are associated with antioxidant effects, while high pathologic TSB values are associated with pro-oxidant effects. Literature data do not allow the establishment of whether if the antioxidant properties of bilirubin are important from a clinical point of view and can affect the outcome in ill infants. [ABSTRACT FROM AUTHOR]

Objective: To evaluate surfactant effectiveness for the treatment of respiratory distress syndrome (RDS) in late preterm infants.Methods: We performed a retrospective cohort study of infants born between 34+0 and 36+6  weeks of gestation admitted for respiratory failure in seven perinatal centers from January 2010 to December 2014. We evaluated changes of FiO2, PaO2 and a/APO2 in surfactant-treated patients, and the need and duration of MV, the duration of noninvasive respiratory support, stay in NICU and in hospital in surfactant-treated and untreated late preterm infants with RDS alone.Results: We studied 562 infants with RDS, 252 (45%) were treated with surfactant and 310 (55%) were not. FiO2, PaO2 and a/APO2 significantly improved after surfactant treatment. The adjusted odds ratio for the need of MV and the adjusted differences of duration of noninvasive respiratory support, and of NICU and hospital stay were not different in the surfactant and non-surfactant groups.Conclusions: Surfactant therapy was followed by a quick and persisting significant improvement of respiratory function in late preterm infants with RDS. Surfactant did not improve short-term outcomes in our population probably because other factors such as the gestational age, occurrence of complications and poor feeding play a relevant role. [ABSTRACT FROM AUTHOR]

Paracetamol seems to have similar success rates compared with indomethacin and ibuprofen in closing patent ductus arteriosus (PDA) in preterm infants, but with a better safety profile. The aim of our study was to evaluate the possible effects of paracetamol on cerebral oxygenation and cerebral blood flow velocity (CBFV). Infants with gestational age < 32 weeks with hemodynamically significant PDA (hsPDA) were prospectively studied by near infrared spectroscopy (NIRS) after the first dose of paracetamol (15 mg/kg) or ibuprofen (10 mg/kg). Cerebral regional oxygenation (rSO2C) and fractional oxygen extraction ratio (FOEC) were recorded 30 min before (T0) and 60 ± 20 min (T1), 180 ± 30 min (T2), and 360 ± 30 min (T3) after the beginning of drug infusion. Moreover, mean flow velocity (Vmean) and resistance index (RI = PSV-DV/PSV) measured with Doppler ultrasound in pericallosal artery were recorded at the same times. Significant changes in rSO2C and FOEC were not found during the study period within and between the groups. Similarly, Vmean did not vary in infants treated with paracetamol or ibuprofen, while RI decreased in the ibuprofen group.Conclusion: The treatment of hsPDA with paracetamol does not affect cerebral oxygenation in very preterm infants; there were no differences in cerebral oxygenation in infants treated with paracetamol or ibuprofen, although in the ibuprofen group, the possible closure progression of PDA was associated to changes of RI. What is Known: • Paracetamol has similar success rates to indomethacin and ibuprofen in closing PDA with a better safety profile since previous studies did not report adverse effects. What is New: • Paracetamol does not affect cerebral oxygenation and perfusion in very preterm infants with PDA and this confirms its good safety profile. [ABSTRACT FROM AUTHOR]

Background: The risk of developing red blood cell (RBC) transfusion-associated necrotizing enterocolitis (TANEC) in preterm infants has recently been emphasized. Our aim was to assess changes in cytokine serum levels after RBC transfusions in a cohort of very preterm infants to evaluate their possible proinflammatory effect.Study Design and Methods: We carried out a prospective observational study. One transfusion event was studied in infants less than 32 weeks' gestation and more than 7 days old (n = 20) admitted to a tertiary neonatal intensive care unit. Interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, interferon-γ (IFN-γ), IL-17, monocyte chemoattractant protein-1 (MCP-1), interferon-γ-induced protein 10 (IP-10), intracellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule serum levels were measured in enrolled patients within 120 minutes before (T0 ) the RBC transfusion and then within 120 minutes (T1 ), 12 ± 3 hours (T2 ), 24 ± 6 hours (T3 ), and 48 ± 6 hours (T4 ) after the end of RBC transfusion.Results: Infants received 19.8 ± 3.0 mL of RBCs at the mean age of 50 ± 18 days. Their hematocrit level increased from 24.1 ± 1.2% to 39.4 ± 2.9%. IL-1β, IL-8, IFN-γ, IL-17, MCP-1, IP-10, and ICAM-1 increased significantly after RBC transfusions.Conclusion: Proinflammatory cytokines are increased after RBC transfusion. These findings may contribute to explaining the pathogenesis of TANEC and suggest the opportunity of adopting wise transfusion guidelines that would help to avoid detrimental risks of transfusion-related immunomodulation and of undertransfusion. [ABSTRACT FROM AUTHOR]

Background: We studied late preterm and term infants who were admitted to our neonatal care unit in a tertiary hospital for unexpected episodes of cyanosis that occurred during rooming-in for evaluation of their frequency, most frequent associated diseases, and documentation of the diagnostic clinical approach. Methods: We carried out a retrospective study of infants with a gestational age ≥35 weeks who were admitted from the nursery with the diagnosis of cyanosis from January 2009 to December 2016. Exclusion criteria were the occurrence of acrocyanosis and the diagnosis of sudden unexpected postnatal collapse (SUPC). Results: We studied 49 infants with a mean gestational age of 38 ± 2 weeks. The frequency of admission for cyanosis was 1.8/1000 live births and was similar (p = 0.167) in late preterm and term infants. The majority of episodes occurred during the first 24 h of life (57%). Only 16 infants (33%) were discharged with a diagnosis, that was mostly (n = 5;10%) gastro-esophageal reflux. Conclusions: Unexpected episodes of cyanosis caused admission of 1.8/1000 live births to the neonatal care unit without differences between late preterm and term infants. These episodes occurred mainly during the first day of life and infants were mostly discharged without a known diagnosis. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to compare the effects on cerebral oxygenation in preterm infants of two different procedures for surfactant administration: the LISA (low-invasive method of surfactant administration) and the InSurE (Intubation, SURfactant administration, Extubation). Study Design Twenty premature infants with respiratory distress syndrome were assigned to receive surfactant either by "LISA" (n = 10) or "InSurE" (n = 10) procedure. Patients were continuously studied by near-infrared spectroscopy (NIRS) for the measurement of cerebral regional oxygenation (rSO2C) and calculation of cerebral fractional oxygen extraction rate (cFTOE), and NIRS data were recorded 30 minutes before (T0) surfactant administration, during the procedure (Tproc), and 30 (T1), 60 (T2T2), and 120 minutes (T3) afterward. Cerebral blood flow velocity (CBFV) was studied in the anterior cerebral artery at T0, T1, and T3. Results SpO2 significantly decreased at Tproc in comparison with T0, T1, T2, and T3 and the decrease was higher in the LISA than in the InSurE group. rSO2C was lower at tproc and T3 in the LISA than in the InSurE group. cFTOE was higher at tproc, t2, and t3 in the LISA group than in the InSurE group. CBFV did not change during the study periods in both groups. Conclusions The LISA and InSurE procedures transiently decreased rSO2C in our population, and the decrease was higher in the LISA group. Consistently, there was a contemporary increase in cFTOE that was higher in the LISA than in the InSurE group, suggesting that it represents a compensatory mechanism. [ABSTRACT FROM AUTHOR]

• Carboxyhemoglobin early predicts the risk for bronchopulmonary dysplasia. • Carboxyhemoglobin early predicts the risk for intraventricular hemorrhage. • Carboxyhemoglobin does not predict the risk for retinopathy of prematurity. 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). 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. 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). 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. [ABSTRACT FROM AUTHOR]

Although surfactant is the most studied drug in the preterm infant, the best criteria for treatment of preterm infants with respiratory distress syndrome (RDS) with surfactant have been not extensively investigated. We assessed the criteria used for deciding the rescue surfactant treatment of preterm infants with RDS in combination with nasal continuous positive airway pressure as reported by the main recent randomized controlled trials. We evaluated 10 studies and found that the criteria chosen for administering selective surfactant were very heterogeneous, different types and doses of surfactant were used, and this limits their applicability in the clinical practice. In conclusion, although current data seem to suggest that low threshold is better than high threshold, additional studies are necessary to identify the most effective criteria for selective surfactant treatment of preterm infants with RDS. [ABSTRACT FROM AUTHOR]

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria.Methods/design: In this study, 206 spontaneously breathing infants born at 24(+0)-27(+6) weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation.Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge.Trial Registration: ClinicalTrials.gov identifier: NCT02482766 . Registered on 1 June 2015. [ABSTRACT FROM AUTHOR]

Objective: To describe morbidity in neonates born by cesarean section (CS) before labor between 34(+0) and 38(+6) weeks, stratified by gestational age.Methods: Cohort study from five Italian tertiary care hospitals. Consecutive singleton pregnancies delivered by CS before labor between 34(+0) and 38(+6) weeks of gestation from January 2010 to August 2011 were included. Women in labor, with premature rupture of membranes, or with previous administration of steroids were excluded. The incidence of neonatal complication by gestational week was calculated.Results: A total of 1135 cases were analyzed. Composite adverse neonatal outcomes, respiratory distress syndrome, transient tachypnea and use of continuous airway positive pressure decreased from 50%, 28%, 5% and 22% at 34 weeks of gestation, to 4.7%, 1.0%, 0.9% and 0.3% at 38 weeks of gestation. Multivariate analysis showed that the only variable independently associated with composite adverse neonatal outcome was gestational age at delivery (adjusted odds ratio 0.49; 95% confidence interval 0.39-0.61).Conclusions: The prevalence of neonatal complications in newborns delivered by CS before labor halves at each week of gestation from 34 to 38 weeks. Nonetheless complications, and mainly respiratory problems, are still present at early term gestation. [ABSTRACT FROM AUTHOR]

Background: Patent ductus arteriosus (PDA) is one of most common complications in preterm infants. Although ibuprofen represents the first choice for the closure of PDA, this treatment can cause severe gastrointestinal and adverse renal effects and worsen platelet function. The successful closure of the PDA with paracetamol has been recently reported in several preterm infants, and the safety of paracetamol for this use has been suggested by the available data. Methods/design: We present the design of a randomized, multicenter, controlled study, whose aim is to assess the effectiveness and safety of intravenous paracetamol in comparison to intravenous ibuprofen for the treatment of PDA in preterm infants. A total of 110 infants born at 25(+0) to 31(+6) weeks of gestational age will be enrolled and randomized to receive paracetamol or ibuprofen (55 patients per group) starting at 24-72 h of life. The primary endpoint of the study is the comparison of the PDA closing rate observed after a 3-day course with paracetamol or ibuprofen. The secondary endpoints include the closure rate of PDA after the second course of treatment with ibuprofen, the re-opening rate of the PDA, the incidence of surgical ligation, and the occurrence of adverse effects. Discussion: The results of this study will provide new information about the possible use of paracetamol in the treatment of PDA. Paracetamol could offer several important therapeutic advantages over current treatment options, and it could become the treatment of choice for the management of PDA, mainly due to its more favorable side effect profile. Trial Registration: Clinicaltrials.gov NCT02422966 . Eudract no. 2013-003883-30. [ABSTRACT FROM AUTHOR]

Hyperbilirubinemia is a frequent condition affecting newborns during the first two weeks of life and when it lasts more than 14 days it is defined as prolonged jaundice. This condition requires differential diagnosis between the usually benign unconjugated hyperbilirubinemia and the pathological conjugated hyperbilirubinemia, that is mainly due to neonatal cholestasis. It is important that the diagnosis of neonatal cholestasis be well-timed to optimize its management, prevent worsening of the patient's outcome, and to avoid premature, painful, expensive, and useless tests. Unfortunately, this does not always occur and, therefore, the Task Force on Hyperbilirubinemia of the Italian Society of Neonatology presents these shared Italian guidelines for the management and treatment of neonatal cholestasis whose overall aim is to provide a useful tool for its assessment for neonatologists and family pediatricians. [ABSTRACT FROM AUTHOR]

Phototherapy is standard care for treatment of neonatal hyperbilirubinemia. Our aim was to compare the effectiveness of broad-spectrum light (BSL) to that of blue light emitting diodes (LED) phototherapy for the treatment of jaundiced late preterm and term infants. Infants with gestational age from 35+0 to 41+6 weeks of gestation and nonhemolytic hyperbilirubinemia were randomized to treatment with BSL phototherapy or blue LED phototherapy. A total of 20 infants were included in the blue LED phototherapy group and 20 in the BSL phototherapy group. The duration of phototherapy was lower in the BSL than in the blue LED phototherapy group (15.8 ± 4.9 vs. 20.6 ± 6.0 hours; p = 0.009), and infants in the former group had a lower probability (p = 0.015) of remaining in phototherapy than infants in the latter. We concluded that BSL phototherapy is more effective than blue LED phototherapy for the treatment of hyperbilirubinemia in late preterm and term infants. Our data suggest that these results are not due to the different irradiance of the two phototherapy systems, but probably depend on their different peak light emissions. [ABSTRACT FROM AUTHOR]

Pneumomediastinum (PM) occurs in approximately 0.1% of newborns. Its diagnosis is usually followed by admission of the infant to a neonatal care unit for treatment and monitoring. We report the outcome of a cohort of late preterm and term infants who developed PM in our center, and review the literature on this topic. We describe the course of 10 cases of PM, five asymptomatic and five with respiratory failure. Asymptomatic infants had an uncomplicated course, but received a similar number of chest X-rays and had a slightly shorter hospitalization compared to symptomatic infants. PM generally has a benign course. Fewer chest X-rays are warranted when it is asymptomatic. [ABSTRACT FROM AUTHOR]

Aim: We aimed to identify specific polymorphisms of genes encoding for vascular endothelial growth factor A (VEGFA), endothelial nitric oxide synthase (eNOS), renin-angiotensin system (angiotensinogen gene [AGT], angiotensinogen type 1 receptor [AGTR1], angiotensin-converting enzyme [ACE]), and heme oxygenase-1 (HMOX-1) in a cohort of preterm infants and correlate their presence with the development of respiratory distress syndrome (RDS) requiring mechanical ventilation (MV), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH) and retinopathy of prematurity (ROP). Study Design: We carried out a retrospective study to evaluate the allele frequency and genotype distribution of polymorphisms of VEGFA, eNOS, AGT, AGTR1, ACE, and HMOX-1 in a population of preterm neonates (n=342) with a gestational age ≤28 weeks according to the presence or absence of RDS requiring MV, BPD, IVH, or ROP. Moreover, we evaluated through the haplotype reconstruction analysis whether combinations of the selected polymorphisms are related to the occurrence of RDS, BPD, IVH and ROP. Results: In our population 157 infants developed RDS requiring MV, 71 BPD, 70 IVH, and 43 ROP. We found that TC+CC rs2070744 eNOS (41.7 vs. 25.4%, p=0.01) and GT+TT rs1799983 eNOS (51.8 vs. 35.2%, p=0.01) polymorphisms are independent risk factors for BPD. Haplotype reconstruction showed that haplotypes in VEGF and eNOS are significantly associated with different effects on RDS, BPD, IVH, and ROP in our population. Conclusions: We found that TC+CC rs2070744 eNOS and GT+TT rs1799983 eNOS polymorphisms are independent predictors of an increased risk of developing BPD. Haplotypes of VEGFA and eNOS may be independent protective or risk markers for prematurity complications. [ABSTRACT FROM AUTHOR]

It has been reported that preterm infants can develop feeding intolerance during phototherapy (PT) and that PT can affect mesenteric perfusion in these patients. Our aim was to assess if PT can decrease regional splanchnic oxygenation (rSO 2 S) measured by near infrared spectroscopy (NIRS). We prospectively studied infants with gestational age of 25–34 weeks with hyperbilirubinemia requiring PT. Splanchnic regional oxygenation (rSO 2 S), oxygen extraction fraction (FOES), and cerebrosplanchnic oxygenation ratio (CSOR) were recorded before, during, and after PT discontinuation. During PT rSO 2 S and CSOR significantly decreased and this effect lasted for some hours after its interruption. FOES contemporary increased, although this effect was not statistically significant. PT treatment decreases splanchnic oxygenation in preterm infants likely due to peripheral vasodilation which triggers a redistribution of blood flow. These results can help explain the association between PT and the development of feeding intolerance in preterm infants. • We measured regional splanchnic oxygenation during phototherapy. • Splanchnic oxygenation decreased and blood oxygen extraction increased. • Peripheral vasodilation and redistribution of blood flow may explain this effect. • These results help explain association between phototherapy and feeding intolerance. [ABSTRACT FROM AUTHOR]

Background The best criteria for surfactant treatment in the perinatal period are unknown and this makes it of interest to consider the possible economic implications of lessening the use of more restrictive criteria. Objective The objective of this study is the evaluation of the costs of respiratory care for preterm infants with Respiratory Distress Syndrome (RDS) treated with "early rescue" surfactant compared to a "late rescue" strategy. Methods The study was carried out applying the costs of materials used, of staff and pharmacological therapy calculated in the Neonatal Intensive Care Unit (NICU) of an Italian hospital to the Verder et al. study (Pediatrics 1999) clinical data. Results The cost for patients treated with early strategy was slightly lower than for patients treated with late strategy (Euro 4,901.70 vs. Euro 4,960.07). The cost of treatment with surfactant was greater in the early group (Euro 458.49 vs. Euro 311.74), but this was compensated by the greater cost of treatment with Mechanical Ventilation (MV) in the late group (respectively Euro 108.85 vs. Euro 259.25). Conclusions The cost-effectiveness analysis performed in this study shows how early treatment with surfactant in preterm infants with RDS, as well as being clinically more effective, is associated with a slightly lower cost. [ABSTRACT FROM AUTHOR]

It has been reported that low platelet count may increase the risk of patent ductus arteriosus (PDA) in preterm infants. Moreover, high mean platelet volume (MPV) has been found to be associated with the development of prematurity complications due to enhanced platelet reactivity. Our aim was to assess the relationship between platelet count and MPV and the occurrence of PDA and its resistance to ibuprofen closure in a cohort of extremely preterm infants. Platelet count <100 (x 103/mm3; odds ratio 4.50; 95% confidence limits 1.39 to 14.61) at birth is an independent risk factor for PDA but does not affect its response to ibuprofen. MPV values did not influence PDA fate. Low platelet count increases the risk of developing a hemodynamically significant PDA but does not affect the ibuprofen closure rate. MPV is unrelated to the DA outcome. [ABSTRACT FROM AUTHOR]

Background: Some studies have suggested that the early sustained lung inflation (SLI) procedure is effective in decreasing the need for mechanical ventilation (MV) and improving respiratory outcome in preterm infants. We planned the present randomized controlled trial to confirm or refute these findings. Methods/Design: In this study, 276 infants born at 25+0 to 28+6 weeks' gestation at high risk of respiratory distress syndrome (RDS) will be randomized to receive the SLI maneuver (25 cmH2O for 15 seconds) followed by nasal continuous positive airway pressure (NCPAP) or NCPAP alone in the delivery room. SLI and NCPAP will be delivered using a neonatal mask and a T-piece ventilator. The primary endpoint is the need for MV in the first 72 hours of life. The secondary endpoints include the need and duration of respiratory support (NCPAP, MV and surfactant), and the occurrence of bronchopulmonary dysplasia (BPD). [ABSTRACT FROM AUTHOR]

Objectives: Our aim was to assess whether non-invasive ventilation with heliox may decrease the incidence of extubation failure in preterm infants with RDS. Methods: Infants <29 weeks of gestation were treated immediately after extubation with heliox combined with nasal continuous airway pressure (Hx-NCPAP) or bilevel NCPAP (Hx-BiPAP) for 24 h, while infants in the control groups were treated with conventional NCPAP or BiPAP. The primary endpoint was the comparison of the extubation failure rate in the two groups, where failure was defined as the need for MV during the 24 h following extubation. Results: Eighteen infants were assigned to the heliox group and 18 to the control group. The extubation failure rate was similar ( p = 0.249) in the heliox ( n = 6; 33%) and in the control group ( n = 9; 50%), but required mean airway pressure (MAP: 4.0 +1.0 vs. 4.8 +1.2 cm H2O; p = 0.037) and PaCO2 (39+8 mmHg vs. 52+7 mmHg; p < 0.001) at 24 h of treatment were lower in the heliox group. Conclusions: Non-invasive ventilation with heliox was not effective in decreasing extubation failure in preterm infants with RDS, but did improve their respiratory function. Our findings might support the planning of large randomized controlled studies to evaluate the effectiveness of heliox non-invasive ventilation for decreasing extubation failure in premature infants. [ABSTRACT FROM AUTHOR]

Background Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Very different models using clinical parameters at an early postnatal age to predict BPD have been developed with little extensive quantitative validation. The objective of this study is to review and validate clinical prediction models for BPD. Methods We searched the main electronic databases and abstracts from annual meetings. The STROBE instrument was used to assess the methodological quality. External validation of the retrieved models was performed using an individual patient dataset of 3229 patients at risk for BPD. Receiver operating characteristic curves were used to assess discrimination for each model by calculating the area under the curve (AUC). Calibration was assessed for the best discriminating models by visually comparing predicted and observed BPD probabilities. Results We identified 26 clinical prediction models for BPD. Although the STROBE instrument judged the quality from moderate to excellent, only four models utilised external validation and none presented calibration of the predictive value. For 19 prediction models with variables matched to our dataset, the AUCs ranged from 0.50 to 0.76 for the outcome BPD. Only two of the five best discriminating models showed good calibration. Conclusions External validation demonstrates that, except for two promising models, most existing clinical prediction models are poor to moderate predictors for BPD. To improve the predictive accuracy and identify preterm infants for future intervention studies aiming to reduce the risk of BPD, additional variables are required. Subsequently, that model should be externally validated using a proper impact analysis before its clinical implementation. [ABSTRACT FROM AUTHOR]

We aimed to identify specific polymorphisms of genes encoding for superoxide dismutase (SOD) 1 (cytoplasmic Cu/ZnSOD), SOD2 (mitochondrial MnSOD), SOD3 (extracellular Cu/ZnSOD) and CAT in a cohort of preterm infants and correlate their presence to the development of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH) and retinopathy of prematurity (ROP). We carried out a retrospective study to evaluate the allele frequency and the genotype distribution of polymorphisms of SODs and CAT in a population of preterm neonates (n = 152) with a gestational age ≤ 28 weeks according to the presence or absence of RDS, BPD, IVH and ROP. Moreover, we evaluated through the haplotype reconstruction analysis whether combinations of the selected polymorphisms are related to the occurrence of RDS, BPD, IVH and ROP. We found that rs8192287 SOD3 polymorphism is an independent protective factor for all grade IVH, while rs4880 and rs5746136 SOD2 polymorphisms are associated with a lower gestational age (rs4880, rs5746136) and birth weight (rs4880). Haplotypes reconstruction showed that SOD1 (GG) decreased the risk of RDS, IVH and ROP; SOD2 (GT) increased the risk of BPD and decreased the risk of RDS, IVH and ROP; SOD3 (TGC) decreased the risk of BPD and IVH; and 4) CAT (CTC) decreased the risk of RDS. The rs8192287 SOD3 polymorphism is per se an independent predictor of a decreased risk of developing IVH. Different SOD2 polymorphisms are associated per se with a lower gestational age and/or birth weight, and haplotypes of SOD1, SOD3 and CAT genes may be independent protecting or risk markers for prematurity complications. [ABSTRACT FROM AUTHOR]

Objectives: Lutein and its isomer zeaxanthin (L/Z) function in the eye as antioxidant agents and blue-light filters. Our aim was to evaluate whether their administration could help decrease the occurrence of retinopathy of prematurity (ROP) in preterm infants. Methods: Infants with gestational age ≤32 weeks were randomly assigned to receive a daily dose of L/Z (0.14 ++ 0.006 mg) or placebo until discharge. Results: ROP occurrence was similar in the L/Z (11/58; 19%) and placebo (15/56; 27%) groups, as the occurrence of ROP at each stage and the need of eye surgery. Conclusion: L/Z supplementation was ineffective in preventing ROP in preterm infants and did not affect the outcome at discharge of our patients. [ABSTRACT FROM AUTHOR]

Background: Natural surfactant combined with beclomethasone decreases pulmonary oxidative stress in preterm lambs with respiratory distress syndrome (RDS). Objectives: To test the hypothesis that this occurs through a decrease in pulmonary inflammation. Methods: Preterm lambs received 200 mg/kg of natural surfactant or 200 mg/kg of natural surfactant combined with 400 or 800 μg/kg of beclomethasone. Interleukin 8 (IL-8) and macrophage migration inhibitory factor (MIF) were assayed in bronchial aspirate samples and lung mechanics were evaluated. Results: IL-8 increased in all the groups, but the increase was lower in the groups treated with surfactant plus 400 and 800 μg/kg of beclomethasone. MIF decreased in the surfactant group, did not vary in the surfactant plus 400 μg/kg beclomethasone group, and decreased in the surfactant plus 800 μg/kg beclomethasone group. MIF concentration was higher in the surfactant plus 800 μg/kg beclomethasone group than in the other groups. Conclusions: Natural surfactant combined with beclomethasone at 800 μg/kg is effective in reducing lung inflammation in an animal model of RDS, thus explaining the associated decrease in lung oxidative stress. The increase in MIF in animals treated with surfactant plus 800 μg/kg of beclomethasone might be an important maturative and protective factor for neonatal lungs. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The possible correlation between the mean platelet volume (MPV) and the occurrence of bronchopulmonary dysplasia (BPD) and intraventricular hemorrhage (IVH) in a cohort of preterm infants was assessed. We studied infants with gestational age <30 weeks. Enrolled infants were divided into BPD and no-BPD groups and IVH and no-IVH groups. MPV was evaluated at birth and at 24 to 48 hours of life. MPV measured at birth was similar in BPD and no-BPD groups, but at 24 to 48 hours of life was higher in the BPD than in the no-BPD group (11.1±0.9 versus 10.8±0.9 fL, p=0.033) and multivariate analysis demonstrated that MPV >11 fL increases (relative risk 1.40, 95% confidence interval 1.08 to 1.80) the risk of developing BPD. MPV was similar in infants with or without IVH. We concluded that high MPV in the first days of life is a risk factor for the development of BPD in extremely preterm infants. This might be because high MPV could favor inflammatory and oxidative lung damage. On the contrary, our data indicate that MPV is not associated with the development of IVH in our population. [ABSTRACT FROM AUTHOR]

Objectives. It has been reported that caesarean delivery (CD) protects against intraventricular haemorrhage (IVH) in the extremely preterm infant, but it is not known whether this effect involve the more severe grades of IVH. Thus, our aim was to confirm the correlation between the occurrence of IVH and the mode of delivery, and to evaluate this correlation for each grade of IVH. Methods. All infants with gestational age (GA) ≤ 28 weeks admitted to the neonatal intensive care unit of a tertiary hospital were studied for each grade IVH and major complications rate. Results. We found that vaginally born infants had a higher rate of each grade of IVH, but the increase was statistically significant only for grade 3 IVH (18% vs. 2%, p < 0.0001) and all grades IVH (45% vs. 20%, p < 0.0001). Multivariate analysis demonstrated that CD (RR: 0.42, 95% CI 0.28-0.63), birth weight ≥ 800 g (RR: 0.48, 95% CI 0.32-0.73), 27-28 weeks of GA (RR: 0.38, 95% CI 0.25-0.60) and antenatal steroids (0.66, 95% CI 0.22-0.46) decrease independently the risk of developing IVH. Conclusions. Our study demonstrates that CD decreases the risk of developing IVH in extremely preterm infants including the most severe grades of IVH. [ABSTRACT FROM AUTHOR]

Objectives. Our aim was to identify the clinical characteristics which could distinguish infants who can be managed with INSURE (intubatio-surfactant-extubation) method for preventing mechanical ventilation (MV) and which could predict INSURE success or failure. Methods. Inborn infants with gestational age <30 weeks were Infants were categorised into three groups: (1) infants who needed MV in the delivery room; (2) infants spontaneously breathing who were treated only with NCPAP; (3) infants who were treated with INSURE method. Results. We studied 125 infants: 30 (24%) required MV, 75 (60%) received INSURE treatment, and 20 (16%) were treated with NCPAP. Sixty-eight (91%) infants were successfully treated with the INSURE method. Infants in the success group had less severe RDS and less occurrence of sepsis and pneumothorax, lower mortality, and shorter duration of stay in the NICU than infants in the failure group. A birth weight <750 g, pO2/FiO2 <218, and a/ApO2 <0.44 at the first blood gas analysis were independent risk factor for INSURE failure. Conclusions. The INSURE method can be applied to the majority of extremely preterm infants and is followed by a high percentage of success. [ABSTRACT FROM AUTHOR]

Our aim was to evaluate the literature on survival and major disability rate in preterm infants born at 22– 25 weeks of gestational age (GA). Thirty-three studies were identified and reviewed. Survival was lower in population-based studies (2% at 22, 13% at 23, 35% at 24, and 56% at 25 weeks) than in center-based study (15% at 22, 41% at 23, 58% at 24, and 74% at 25 weeks). The severe disability rate was slightly higher in population-based studies than in center-based studies at 23 (29 vs. 32%) and at 24 (30 vs. 27%) week of GA, whereas it was similar in population and center-based studies at 25 (21 vs. 22%) weeks of GA. Survival rate seems to improve with time, whereas the change of severe disability rate cannot be adequately evaluated due to the paucity of available data. We conclude that the survival of infants born at 22 weeks is still an uncommon event, whereas the survival of infants born at 23, and mostly at 24 and 25 weeks of GA is significant in the majority of studies. [ABSTRACT FROM AUTHOR]

BACKGROUND: More than 90 percent of extremely low-birth-weight infants receive one or more transfusions of red blood cells (RBCs). The objective was to assess if RBC transfusions may induce significant changes of plasma acid-base, electrolyte, and glucose status in extremely preterm infants. STUDY DESIGN AND METHODS: Records of infants with gestational age of less than 31 weeks who were transfused with RBCs during the first week of life were reviewed (n = 61). Blood samples were collected from infants before and after transfusions to evaluate hemoglobin (Hb) level, hematocrit, acid-base, electrolyte, and glucose status. Then infants were stratified into four groups that received a RBC volume of less than 15, 15 to 20, more than 20 to 25, or more than 25 mL per kg. RESULTS: Infants received 20.7 (±1.5) mL per kg RBCs. After transfusions, a significant increase of pO2 (p < 0.0001) and decrease of Ca2+ (p = 0.047) and glycemia (p < 0.0001) were observed. Infants who were transfused with more than 25 mL per kg were significantly less immature, heavier, and more anemic than infants in other groups. A positive relationship was found between changes of patients' potassium plasma level and K+ intake through RBC transfusion (r = 0.442, p = 0.008). Three (4.9%) infants developed hyperkalemia, one (1.6%) had an exacerbation of his hypocalcemia, and another (1.6%) of his hypoglycemia. CONCLUSIONS: RBC transfusions were effective in correcting anemia in our patients and induced a slight increase of pH and pO2 and decrease of Ca2+ and glycemia, which were not clinically relevant. A linear direct correlation was observed between potassium intake by RBC transfusions and changes of kalemia in our infants, but there was not an increase of K+ plasma level after transfusions. [ABSTRACT FROM AUTHOR]