Differences in Cerebral Tissue Oxygenation in Preterm Neonates Receiving Adult or Cord Blood Red Blood Cell Transfusions.

Importance: Repeated transfusions in preterm neonates with anemia of prematurity replace fetal hemoglobin (HbF) with adult Hb (HbA), which has a low oxygen affinity. The reduction of HbF is associated with a higher incidence of retinopathy of prematurity (ROP). Objective: To assess whether HbF and HbA are differently associated with cerebral tissue oxygenation in preterm neonates. Design, Setting, and Participants: This cohort study was a single-center, pilot study on cerebral oxygenation kinetics in preterm neonates with a gestational age between 24.0 weeks and 27.9 weeks who were admitted to the neonatal intensive care unit of Policlinico Universitario A. Gemelli IRCCS from December 27, 2021, to May 15, 2023. This study was ancillary to the ongoing, double-blind, multicenter Umbilical or Adult Donor Red Blood Cells in Extremely Low Gestational Age Neonates and Retinopathy of Prematurity (BORN) randomized clinical trial. The BORN trial outcome was ROP severity in neonates randomized to receive standard packed red blood cell (PRBC) transfusions obtained from RBCs of adult donors (A-RBCs) or from cord blood (CB-RBCs). According to standard procedures at the institute's neonatal intensive care unit, patients concurrently received continuous cerebral near-infrared spectroscopy (NIRS) monitoring. This cohort study was not prespecified in the trial protocol. Exposure: Transfusion with A-RBCs or CB-RBCs. Main Outcomes and Measures: The main outcome was the kinetics of cerebral regional oxygen saturation (crSO2) and cerebral fraction of tissue oxygen extraction (cFTOE) associated with A-RBC or CB-RBC transfusions. Cerebral NIRS monitoring was performed by neonatologists and nurses, who were blinded to the PRBC type. The NIRS monitoring was conducted starting with the blood product order, during transfusion, and for the subsequent 24 hours after transfusion completion. The mean treatment effects of A-RBCs or CB-RBCs were quantified using a linear mixed model for repeated measures. Results: Of 23 randomized neonates, 17 (11 male [64.7%]; median gestational age at birth, 25.6 weeks [IQR, 25.3-26.1 weeks]) with a median birth weight of 840 g (IQR, 580-900 g) were included in the study; NIRS was evaluated for 42 transfusion episodes, of which 22 were A-RBCs and 20 were CB-RBCs. Globally considering all posttransfusion time points, the overall crSO2 covariate-adjusted mean after CB-RBC transfusions was 5.27% lower (95% CI, 1.20%-9.34%; P = .01) than that after A-RBC transfusions, while the cFTOE after CB-RBC transfusions was 6.18% higher (95% CI, 1.66%-10.69%; P = .009) than that after A-RBCs. Conclusions and Relevance: The findings of this cohort study suggest that A-RBC transfusions may be associated with more oxygen delivery to cerebral tissues of preterm neonates than transfusions from CB-RBCs. This finding may explain the previously observed association between low HbF and high ROP risk. It also suggests that use of CB to meet the RBC transfusion needs of neonates with a gestational age of less than 28 weeks may protect cerebral tissues from overexposure to oxygen.

Allogenic Cord Blood Transfusion in Preterm Infants.

Repeated red blood cell (RBC) transfusions in preterm neonates cause the progressive displacement of fetal hemoglobin (HbF) by adult hemoglobin. The ensuing increase of oxygen delivery may result at the cellular level in a dangerous condition of hyperoxia, explaining the association between low-HbF levels and retinopathy of prematurity or bronchopulmonary dysplasia. Transfusing preterm neonates with RBC concentrates obtained from allogeneic umbilical blood is a strategy to increase hemoglobin concentration without depleting the physiologic HbF reservoir. This review summarizes the mechanisms underlying a plausible beneficial impact of this strategy and reports clinical experience gathered so far in this field.

BORN study: a multicenter randomized trial investigating cord blood red blood cell transfusions to reduce the severity of retinopathy of prematurity in extremely low gestational age neonates.

BACKGROUND: Extremely low gestational age neonates (ELGANs, i.e., neonates born before 28 weeks of gestation) are at high risk of developing retinopathy of prematurity (ROP), with potential long-life visual impairment. Due to concomitant anemia, ELGANs need repeated red blood cell (RBC) transfusions. These produce a progressive replacement of fetal hemoglobin (HbF) by adult hemoglobin (HbA). Furthermore, a close association exists between low levels of HbF and severe ROP, suggesting that a perturbation of the HbF-mediated oxygen release may derange retinal angiogenesis and promote ROP. METHODS/DESIGN: BORN (umBilical blOod to tRansfuse preterm Neonates) is a multicenter double-blinded randomized controlled trial in ELGANs, to assess the effect of allogeneic cord blood RBC transfusions (CB-RBCs) on severe ROP development. Recruitment, consent, and randomization take place at 10 neonatology intensive care units (NICUs) of 8 Italian tertiary hospitals. ELGANs with gestational age at birth comprised between 24+0 and 27+6 weeks are randomly allocated into two groups: (1) standard RBC transfusions (adult-RBCs) (control arm) and (2) CB-RBCs (intervention arm). In case of transfusion need, enrolled patients receive transfusions according to the allocation arm, unless an ABO/RhD CB-RBC is unavailable. Nine Italian public CB banks cooperate to make available a suitable amount of CB-RBC units for all participating NICUs. The primary outcome is the incidence of severe ROP (stage 3 or higher) at discharge or 40 weeks of postmenstrual age, which occurs first. DISCUSSION: BORN is a groundbreaking trial, pioneering a new transfusion approach dedicated to ELGANs at high risk for severe ROP. In previous non-randomized trials, this transfusion approach was proven feasible and able to prevent the HbF decrease in patients requiring multiple transfusions. Should the BORN trial confirm the efficacy of CB-RBCs in reducing ROP severity, this transfusion strategy would become the preferential blood product to be used in severely preterm neonates. TRIAL REGISTRATION: ClinicalTrials.gov NCT05100212. Registered on October 29, 2021.

Transfusion-Free Survival Predicts Severe Retinopathy in Preterm Neonates.

Repeated red blood cell (RBC) transfusions are thought to increase the risk for retinopathy of prematurity (ROP), likely due to a critical fetal hemoglobin (HbF) reduction. In this study, we investigated if the postmenstrual age (PMA) of neonates at transfusion influences the risk for ROP. We estimated the cumulative transfusion-free survival (TFS) in a series of 100 preterm neonates receiving one or more RBC units. TFS was calculated by censoring patients at first transfusion and expressing the time between birth and transfusion as either PMA or postnatal day. Then, we investigated if TFS predicted the occurrence of severe ROP, defined as ROP stage 3 or higher. We found that neonates with severe ROP displayed a significantly shorter TFS expressed according to their PMA (p = 0.001), with similar TFS according to postnatal days. At receiver operating characteristic (ROC) curve analysis, receiving an RBC unit before week 28 of PMA predicted severe ROP with a sensitivity of 64% and a specificity of 78%. In addition, receiving a second RBC unit before the PMA of 29 weeks predicted severe ROP with a sensitivity of 75% and a specificity of 69%. At multivariate analysis, PMA at the second transfusion was even more informative than at first transfusion and outperformed all other variables in predicting severe ROP, with an odds ratio of 4.554 (95% CI 1.332-15.573, p = 0.016). Since HbF decrease is greater after multiple RBC transfusions, it is conceivable that neonates receiving more than one unit before the PMA of 29 weeks may be exposed to a greater disturbance of retinal vascularization. Any strategy aimed at preventing the critical HbF decrease at this low age might potentially reduce the risk for severe ROP.

Lutein supplementation and retinopathy of prematurity: a meta-analysis.

BACKGROUND: Retinopathy of prematurity (ROP) is a multifactorial retinal disorder characterized by an abnormal vascular development of the retina of the preterm infants. Carotenoids are natural pigments that are synthesized by all plants and some microorganisms where they play a role in photoprotection and coloration. Lutein and zeaxanthin (L/Z) are two carotenoids identified as the major components of the macular pigment. Recently it has been suggested that lutein and its isomer zeaxanthin may act as antioxidant agents and that they may prevent ROP. OBJECTIVE: The primary objective of this study is to assess the safety and effectiveness of oral lutein in the prevention of retinopathy of prematurity in preterm neonates. STUDY DESIGN: We conducted a systematic search for randomized or quasi-randomized controlled trials without any language or publication year restriction. The studies have to recruit preterm neonates ≤32 completed weeks of gestation and to compare the administration of oral L/Z at any dosage or duration, versus placebo in order to prevent ROP. RESULT: Data from three RCT with a total of 406 participants failed to show any reduction in ROP incidence nor the risk of BPD, sepsis, NEC and mortality. It may reduce the number of transfusions but this result has to be assessed in a separate ad hoc trial.

Allogeneic cord blood transfusions prevent fetal haemoglobin depletion in preterm neonates. Results of the CB-TrIP study.

Repeated red blood cell (RBC) transfusions in preterm neonates are associated with poor outcome and increased risk for prematurity-associated diseases. RBC transfusions cause the progressive replacement of fetal haemoglobin (HbF) by adult haemoglobin (HbA). We monitored HbF levels in 25 preterm neonates until 36 weeks of post-menstrual age (PMA); patients received RBC units from allogeneic cord blood (cord-RBCs) or from adult donors (adult-RBCs), depending on whether cord-RBCs were available. Primary outcome was HbF level at PMA of 32 weeks. Twenty-three neonates survived until this age: 14 received no transfusions, two only cord-RBCs, three only adult-RBCs and four both RBC types. HbF levels in neonates transfused with cord-RBCs were significantly higher than in neonates receiving adult-RBCs (P < 0·0001) or both RBC types (P < 0·0001). Superimposable results were obtained at PMA of 36 weeks. Every adult-RBCs transfusion increased the risk for an HbF in the lowest quartile by about 10-fold, whereas this effect was not evident if combined adult- and cord-RBCs were evaluated. Overall, these data show that transfusing cord-RBCs can limit the HbF depletion caused by conventional RBC transfusions. Transfusing cord blood warrants investigation in randomised trials as a strategy to mitigate the severity of retinopathy of prematurity (NCT03764813).

rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial.

OBJECTIVE: To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. STUDY DESIGN: This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 230/7 weeks to 276/7 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 296/7 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 404/7 weeks. Target exposure was ≥70% IGF-1 measurements within 28-109 µg/L and ≥70% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. RESULTS: Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3% treated vs 44.9% standard care), and an 89% decrease in the evaluable set (4.8% vs 44.9%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3-4 intraventricular hemorrhage in the full analysis set (13.1% vs 23.3%) and in the evaluable set (8.3% vs 23.3%). Fatal serious adverse events were reported in 19.7% of treated infants (12/61) and 11.7% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. CONCLUSIONS: rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3-4 intraventricular hemorrhage. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01096784.

Effect of Early Expressed Human Milk on Insulin-Like Growth Factor 1 and Short-Term Outcomes in Preterm Infants.

AIMS: Preterm breast milk contains high levels of bioactive components, including insulin-like growth factor 1 (IGF-1), that are reduced by Holder pasteurization. Animal studies have shown that milk-borne IGF-1 is likely absorbed intact in a bioactive form by the intestines. The aim of this study was to assess if early non-pasteurized expressed breast milk nutrition may affect IGF-1 plasma levels in premature infants. We also investigated the possible association between early expressed milk nutrition and short-term outcomes. METHODS: Fifty-two preterm infants with gestational age < 31 weeks were divided into two groups according to expressed breast milk intake (< or ≥ 50 mL/Kg/day) until 32 weeks of postmenstrual age when blood sampling for IGF-1 analysis was performed. RESULTS: In our population, early expressed breast milk does not affect IGF-1 plasma levels (p 0.48). An association was observed between early expressed milk nutrition and a lower incidence of bronchopulmonary dysplasia, sepsis, feeding intolerance, need for parenteral nutrition and length of hospitalization. CONCLUSIONS: Contrary to the results in some animal studies, our results did not seem to show that early expressed breast milk can help to maintain postnatal IGF-1 near foetal levels in preterm infants. The observed protective effect of expressed breast milk on short-term outcomes can be the starting point for further study of the effects of non-pasteurized human milk in preterm infants.

Allogeneic umbilical cord blood red cell concentrates: an innovative blood product for transfusion therapy of preterm infants.

BACKGROUND: Preterm infants often receive blood transfusions early in life. In this setting, umbilical cord blood (UCB) might be safer than adult blood (A) with respect to infectious and immunologic threats. OBJECTIVES: To evaluate, as a first objective, the feasibility of fulfilling transfusion needs of preterm infants with allogeneic UCB red blood cell (RBC) concentrates and, as a secondary objective, to assess the safety of allogeneic cord blood transfusions. METHODS: At the Neonatal Intensive Care Unit and the UNICATT Cord Blood Bank of 'A. Gemelli' Hospital in Rome, a prospective study was carried out over a 1-year period, enrolling newborns with gestational age ≤30 weeks and/or birth weight ≤1,500 g requiring RBC transfusions within the first 28 days of life. At first transfusion, patients were assigned to receive UCB-RBCs or A-RBCs depending on the availability of ABO-Rh(D)-matched UCB-RBC units. The same regimen (UCB-RBC or A-RBC units) was thereafter maintained, unless ABO-Rh(D)-matched UCB-RBC units were not available. RESULTS: Overall, 23 UCB-RBC units were transfused to 9 patients; the requests for UCB-RBC units were met in 45% of patients at the first transfusion and in 78% at the subsequent transfusions. At a median follow-up of 57 days (range 6-219), no acute or delayed transfusion-related adverse events occurred. Hematocrit gain after transfusion and time intervals between transfusions were similar in the UCB-RBC and A-RBC group, as well. CONCLUSIONS: Transfusing allogeneic UCB-RBC units in preterm infants appears a feasible and safe approach, although the transfusion needs of our study population were not completely covered. More data are necessary to validate this novel transfusion practice.

Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings.

PURPOSE: To compare the structural outcome at 9 months of eyes treated with intravitreal injection of bevacizumab with fellow eyes treated with conventional laser photoablation in zone I type 1 retinopathy of prematurity (ROP). DESIGN: Single randomized controlled trial. PARTICIPANTS: All inborn babies with type 1 zone I ROP at a single institution were included in the study. One eye was randomized to receive an intravitreal injection of 0.5 mg bevacizumab; the fellow eye received conventional laser photoablation. METHODS: Digital fundus photographs and fluorescein angiography (FA) using the RetCam (Clarity Medical Systems Inc., Pleasanton, CA) were performed before treatment and 9 months after treatment. MAIN OUTCOME MEASURES: Presence of retinal and choroidal abnormalities on FA at 9 months. RESULTS: Thirteen infants were enrolled; 1 died 3 months after birth. One laser-treated eye progressed to stage 5 retinal detachment. The remaining 23 eyes had favorable structural results at the 9-month follow-up and provided FA results. At 9 months of age, all eyes treated with a bevacizumab injection were noted to have abnormalities at the periphery (large avascular area, abnormal branching, shunt) or the posterior pole (hyperfluorescent lesion, absence of foveal avascular zone). These posterior and peripheral lesions were not observed in the majority of the lasered eyes. CONCLUSIONS: This study documents significant vascular and macular abnormalities of eyes in the bevacizumab group. Long-lasting implications of these abnormalities for visual function of the child need to be studied.

Effects of lutein supplementation on biological antioxidant status in preterm infants: a randomized clinical trial.

OBJECTIVE: To test the hypothesis that lutein, compared to the placebo, would enhance the total antioxidant status (TAS) in the preterm infants. METHODS: Infants with gestational age (GA) ≤34 weeks were randomly assigned to receive a daily dose of lutein and zeaxanthin (0.5 mg + 0.02 mg/kg/d) or placebo from the 7th day of life until 40th week of postmenstrual age or until discharge. RESULTS: Seventy-seven preterm infants were randomized (38 in the Lutein group and 39 in the Placebo group) with mean GA of 30.4 (±2.3) weeks and the mean birth weight of 1415 (±457) grams. The TAS did not result statistically different between the two groups during all the study period, but a significant linear correlation was evidenced between plasma lutein concentration and TAS (r = 0.14, p = 0.012) and between plasma zeaxanthin concentration and TAS (r = 0.13, p = 0.02). CONCLUSIONS: Supplementation of preterm infants with orally lutein was ineffective in enhancing biological antioxidant capacity. Further studies need to better understand the bioavailability of lutein in the neonatal period in order to identify any best form of supplementation. TRIAL REGISTRATION NUMBER: UMIN000007041.

Fluorescein angiography and retinal vascular development in premature infants.

OBJECTIVE: To investigate the role of fluorescein angiography (FA) in the management of retinopathy of prematurity (ROP) in preterm newborns. METHODS: An observational case series of 13 extremely low birth weight infants. From September 2009 to March 2010, 13 newborn infants with a gestational age <29 weeks end/or birth weight <1000 g underwent serial fluorescein angiography with RetCam (Clarity, Pleasanton, CA) every 2 weeks. The fluorescein angiograms were examined to optimize the timing of diagnosis of ROP and to investigate development of retinal and choroidal vascularization. RESULTS: There were no side effects related to FA. Variable features of retinal and choroidal circulation in preterm infants with a high risk of developing ROP were noted. FA allows vessels branching at the junction between vascular and avascular retina (V-Av junction) to be viewed easily and shows the ROP findings that sometimes cannot be seen by indirect ophthalmoscopy. Dye leakage is the most significant sign of progression to severe ROP or the need for surgery in newborn babies with ROP. CONCLUSIONS: RetCam-assisted intravenous FA is safe and allows a more objective assessment of the ROP stage and zone.

Renal failure of the surviving fetus after intrauterine death of the co-twin.

Twin pregnancies are considered at a higher risk for fetal mortality than singleton pregnancies. The antenatal death of one of the twins is associated with an increasing rate of cerebral impairment and lesions in other organs in the surviving fetus, especially if the pregnancy is monochorionic. We describe a case of isolate renal failure becoming evident gradually after birth in a surviving twin after the antenatal death of the co-twin. Considering the deleterious effects of vascular disruption in a surviving twin, our findings suggest careful investigation of renal function, even if no intrauterine signs of diminished renal function were previously detected.

Analysis of risk factors for progression to treatment-requiring ROP in a single neonatal intensive care unit: is the exposure time relevant?

OBJECTIVE: Retinopathy of prematurity (ROP) is a multifactorial disease whose pathogenesis is organized in two phases. We hypothesized that postnatal risk factors may differently exert their effect in a phase dependent way. METHODS: Data obtained from medical records of 93 very low birth weight neonates with stage ≥ 3 ROP were analyzed. Perinatal ROP risk factors were compared between infants with stage 3 ROP not requiring surgery and infants with treatment-requiring ROP with relation to newborn's lifetime exposure. RESULTS: In the first two weeks and in the whole first month of life length of oxygen administration was an independent risk factor for treatment-requiring ROP. In the first month of life also sepsis was identified as independent risk factor for surgical ROP. Sepsis and Candida pneumonia in the time frame from birth to ROP diagnosis and prolonged mechanical ventilation from diagnosis to prethreshold ROP were associated to treatment-requiring ROP. Blood transfusions are the only risk factor for treatment-requiring ROP identified in all the periods analyzed. CONCLUSION: Risk factors for ROP play their role since birth. Beside scrupulous oxygen-administration monitoring and prevention of infections, blood transfusions are of primary importance in the development of treatment-requiring ROP.

A prospective, randomized, double blind study comparing lutein to placebo for reducing occurrence and severity of retinopathy of prematurity.

Lutein has been shown to have antioxidant functions in newborns and with zeaxantin selectively taken up into the macula of the eye. We hypothesize that lutein administration may contribute to reducing the incidence of Retinopathy of Prematurity (ROP). This was a single center, double-blind randomized controlled study. Preterm infants with gestational age (GA) ≤ 32 weeks able to tolerate minimal enteral feeding before the seventh day of life (DOL) were enrolled; lutein and zeaxantin plasma concentrations and ROP occurrence and severity were evaluated. Sixty-three newborns were enrolled, 31 in the lutein group and 32 in the placebo group (one died before ROP assessment). The mean GA was 29.9 (± 1.9) weeks and the mean birth weight was 1331 (± 415) grams. There were no differences in the incidence of ROP at any stage between groups. Oxidative injury is probably an additional mechanism of damage of the developing retinal vessels, and it probably plays only a minor role in the pathogenesis of ROP. Supplementation with antioxidant substances might have beneficial effects noticeable only on larger samples of high risk neonates or at very high dosage. Further investigations would be needed to evaluate whether lutein supplementation can influence functional rather than anatomical outcomes in preterm infants.

Effectiveness of ketorolac tromethamine in prevention of severe retinopathy of prematurity.

PURPOSE: This study assessed the effectiveness of the use of ketorolac tromethamine to reduce retinopathy of prematurity (ROP) incidence and its progression to more severe forms. METHODS: Forty-seven preterm newborn infants with a birth weight (BW) of 1,000 grams or less and/or a gestational age (GA) of 29 weeks or less were enrolled in the study when avascular retina zone I or ROP any stage were diagnosed at screening. Studied infants were randomized to receive ketorolac tromethamine ophthalmic solution in one eye and a drop of placebo in the other eye, until ROP requiring treatment or full retinal vascularization was diagnosed. RESULTS: Only 2 newborn infants did not develop ROP. Among 45 newborn infants who developed ROP, 6 showed different ROP staging between the two eyes, 4 of which had a better outcome in the eye receiving ketorolac tromethamine. The differences between ROP stagings were not significant even when analyzed by GA and BW subgroups. No significant treatment-related side effects occurred. CONCLUSION: This report suggests that ketorolac tromethamine ophthalmic solution cannot reduce the risk of developing severe ROP in preterm infants.

Chest physiotherapy in preterm infants with lung diseases.

BACKGROUND: In neonatology the role of chest physiotherapy is still uncertain because of the controversial outcomes. METHODS: The aim of this study was to test the applicability in preterm infants of 'reflex rolling', from the Vojta method, in preterm neonates with lung pathology, with particular attention to the effects on blood gases and oxygen saturation, on the spontaneous breathing, on the onset of stress or pain. The study included 34 preterm newborns with mean gestational age of 30.5 (1.6) weeks - mean (DS) - and birth weight of 1430 (423) g - mean (DS) -, who suffered from hyaline membrane disease, under treatment with nasal CPAP (continuous positive airways pressure), or from pneumonia, under treatment with oxygen-therapy. The neonates underwent phase 1 of 'reflex rolling' according to Vojta method three times daily. Respiratory rate, SatO2, transcutaneous PtcCO2 e PtcO2 were monitored; in order to evaluate the onset of stress or pain following the stimulations, the NIPS score and the PIPP score were recorded; cerebral ultrasound scans were performed on postnatal days 1-3-5-7, and then weekly. RESULTS: In this population the first phase of Vojta's 'reflex rolling' caused an increase of PtcO2 and SatO2 values. No negative effects on PtcCO2 and respiratory rate were observed, NIPS and PIPP stress scores remained unmodified during the treatment; in no patient the intraventricular haemorrhage worsened in time and none of the infants developed periventricular leucomalacia. CONCLUSIONS: Our experience, using the Vojta method, allows to affirm that this method is safe for preterm neonates, but further investigations are necessary to confirm its positive effects and to evaluate long-term respiratory outcomes.

Maternal and neonatal characteristics of an immigrant population in an Italian hospital.

OBJECTIVE: The objective of this study was to evaluate clinical and epidemiological characteristics of the maternal and neonatal immigrant population and to compare it with the Italian population in the Agostino Gemelli Hospital (Rome). METHODS: This study was a prospective population-based study. We compared 595 newborns from immigrant mothers with 2413 newborns from Italian mothers. Neonatal characteristics included in this study were sex, gestational age, birth weight, Apgar score, transfer to pathology units, minor pathologies, and type of breastfeeding at discharge. Maternal characteristics included nationality, age, parity, type of delivery, twin birth, and pathology during the pregnancy. RESULTS: Immigrant newborns comprised 20% of the total births included in the study. No statistically significant differences were found between immigrant and Italian newborns in gestational age, birth weight, or Apgar score. Immigrant newborns were transferred to the Paediatric Infectious Disease Unit more frequently than Italian newborns, had a significantly higher incidence of hyperbilirubinemia and a higher rate of exclusive and prevalent breastfeeding at discharge. Immigrant mothers came predominantly from Eastern Europe, were younger and had caesarean sections less frequently than Italian mothers. CONCLUSION: No significant differences in biological and clinical characteristics or in medical practice were found between groups, except for a higher frequency of neonatal hyperbilirubinemia and an inclination among immigrant mothers toward breastfeeding.

Remifentanil analgosedation in preterm newborns during mechanical ventilation.

AIM: To assess efficacy of remifentanil in preterm newborns during mechanical ventilation. METHODS: Remifentanil was administered by continuous intravenous infusion to provide analgesia and sedation in 48 preterm infants who developed respiratory distress and required mechanical ventilation. We examined the doses needed to provide adequate analgesia, extubation time after the discontinuation of opioid infusion, the presence of side effects and safety of the use. RESULTS: Remifentanil provided adequate analgesia, with a significant reduction of NIPS and COMFORT score since 1 h after starting the infusion of remifentanil. The drug was initially administered at a dose of 0.075 microg/kg/min, but in 73% of newborns the latter had to be increased; at a dose of 0.094 +/- 0.03 (mean +/- standard deviation) microg/kg/min, 97% of the newborns received adequate analgesia and sedation. The time elapsed between the discontinuation of remifentanil infusion and extubation was 36 +/- 12 min. Treatment was started between the 1st and the 17th day of life. The mean duration of therapy was 5.9 +/- 5.7 days. No side effects on the respiratory or cardiovascular system were observed. CONCLUSION: Remifentanil is a manageable and effective opioid in the newborn undergoing mechanical ventilation, though randomized controlled trials and information about long-term outcomes are necessary.

Neonatal colour Doppler ultrasound study: normal values of abdominal blood flow velocities in the neonate during the first month of life.

BACKGROUND: Doppler US to measure abdominal blood flow velocities (ABFV) is increasingly used to investigate intestinal haemodynamics in several clinical conditions in neonates. Studies that provide reference values of ABFV during the entire neonatal period are currently lacking. OBJECTIVE: To make available normal reference values of ABFV and Doppler indices in the coeliac trunk and superior mesenteric artery during the first month of life in term and healthy preterm infants. MATERIALS AND METHODS: ABFV were obtained with colour Doppler US in 69 neonates (12 term, 57 preterm) divided into four gestational age groups (25-28 weeks, 29-32 weeks, 33-36 weeks, and 37-41 weeks). RESULTS: ABFV increased with increasing gestational and postnatal age. We also provide normal reference values of ABFV and Doppler indices to compare with measurements of abdominal blood flow changes during the neonatal period for diagnostic, therapeutic and prognostic purposes. CONCLUSION: These longitudinal reference values provide a useful tool for assessing possible alteration in ABFV secondary to neonatal pathologies.