Ibuprofen enantiomers in premature neonates with patent ductus arteriosus: Preliminary data on an unexpected pharmacokinetic profile of S(+)-ibuprofen.

S(+)-ibuprofen (S-IBU) and R(-)-ibuprofen (R-IBU) concentrations were measured in 16 neonates with patent ductus arteriosus during a cycle of therapy (three intravenous doses of 10-5-5 mg kg-1 at 24-h intervals), at the end of the first infusion and 6, 24, 48, and 72 h later. Data were analyzed with a PK model that included enantiomer elimination rate constants and the R- to S-IBU conversion rate constant. The T½ of S-IBU in the newborn was much longer than in adults (41.8 vs. ≈2 h), whereas the T½ of R-IBU appeared to be the same (2.3 h). The mean fraction of R- to S-IBU conversion was much the same as in adults (0.41 vs. ≈0.60). S-IBU concentrations measured 6 h after the first dose were higher than at the end of the infusion in 10 out of 16 cases, and in five cases, they remained higher even after 24 h. This behavior is unprecedented and may be attributable to a rapid R-to-S conversion overlapping with a slow S-IBU elimination rate. In 13 of the 16 neonates, S-IBU concentrations at 48 and/or 72 h were lower than expected, probably due to the rapid postnatal maturation of the newborn's liver metabolism.

Update on Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a major complication of premature birth that significantly affects mortality and long-term morbidity in numerous immature infants. Corticosteroids are particularly suitable for treating BPD, as lung inflammation is central to its pathogenesis. Corticosteroids have considerable, fast beneficial effects on lung function in premature infants with lung disease, but they are also associated with several serious adverse effects, which may have a detrimental impact on long-term outcome. Dexamethasone is the most often used corticosteroid for systemic administration. Despite its value in preventing and treating BPD, its use is associated with several alarming short-term effects and, worst of all, with an increased rate of cerebral palsy in the long term. Dexamethasone nonetheless remains an important therapeutic option for infants with severe lung disease beyond the second to third week of life. Hydrocortisone is an important alternative to dexamethasone, as its use does not appear to be associated with any neurotoxic effects. Its efficacy in the prevention and treatment of BPD has yet to be clearly demonstrated, however. Inhaled corticosteroids might reduce lung inflammation with fewer systemic adverse effects; however, a recent, large randomized trial showed that inhaled budesonide was associated with an excess mortality, despite its beneficial respiratory effects. In another study, instilling budesonide together with surfactant in the trachea of intubated infants with severe respiratory distress appeared safe and achieved a significant reduction in the rate of BPD at 36 postmenstrual weeks. This important finding needs to be confirmed in a larger trial currently underway.

Early modifications of cardiac function in preterm neonates using speckle tracking echocardiography.

BACKGROUND AND AIMS: Preterm newborns undergo hemodynamic challenges in the postnatal period. The aim of this study was to investigate myocardial mechanics changes in the postnatal period in preterm infants using speckle tracking echocardiography (STE). MATERIAL AND METHODS: Thirty-nine preterm infants ≤34 weeks' gestation underwent cardiac ultrasound evaluation during the first 96 hours of life. A repeated echocardiogram at 3 weeks of age was performed. Echocardiographic assessment involved left ventricular ejection fraction, mitral E/A ratio, S' and E' velocities, E/E' ratio, tricuspid annular plane systolic excursion (TAPSE), left atrium-to-aorta ratio, ductal diameter and ductal shunt pattern. Left ventricular longitudinal, circumferential and radial strain, apex-basal rotation and twist were measured from the apical 4-chamber and short-axis views using STE. RESULTS: The mean gestational age was 30 ± 2.7 weeks with a mean birth weight of 1318 ± 485 g. Apical segments demonstrated higher longitudinal strain than basal and mid-ones. In all gestational ages, endocardial longitudinal strain was higher than the epicardial. Epicardial longitudinal strain significantly increased during the first 3 weeks, resulting in the change in basal rotation from counterclockwise to clockwise and thus in the acquisition of twist. Deformation parameters were higher in infants with a hemodynamic significant patents ductus arteriosus. CONCLUSIONS: Echocardiographic assessment of myocardial deformation parameters is feasible in preterm infants. Our data suggest that the maturational process of the myocardium is due to the development of the epicardial layer after birth, which allows the acquisition of the twist.

Analysis and interpretation of acylcarnitine profiles in dried blood spot and plasma of preterm and full-term newborns.

BACKGROUND: Acylcarnitines are biomarkers of fatty acid metabolism, and examining their patterns in preterm newborn may reveal metabolic changes associated with particular conditions related to prematurity. Isomeric acylcarnitines in dried blood spots (DBS) and plasma have never been assessed in preterm infants. METHODS: We studied 157 newborn divided into four groups by weeks of gestational age (GA), as follows: 22-27 wk in group 1; 28-31 wk in group 2; 32-36 wk in group 3; and 37-42 wk in group 4. Samples were collected on the third day of life. Acylcarnitines were separated and quantified using ultra-performance liquid chromatography tandem mass spectrometry. RESULTS: Acylcarnitine concentrations correlated significantly with GA and birth weight in both DBS and plasma samples. Concentrations were lower in preterm newborn, except for acylcarnitines derived from branched-chain amino acids, which were higher and correlated with enteral feeding. On day 3 of life, no correlations emerged with gender, respiratory distress syndrome, bronchopulmonary dysplasia, surfactant administration, or mechanical ventilation. CONCLUSION: We established GA-based reference ranges for isomeric acylcarnitine concentrations in preterm newborn, which could be used to assess nutritional status and the putative neuroprotective role of acylcarnitines.

Cardiac Mechanics Evaluation in Preschool-Aged Children with Preterm Birth History: A Speckle Tracking and 4D Echocardiography Study.

Background: The premature-born adult population is set to grow significantly, and prematurity has emerged as an important cardiovascular risk factor. We aimed to comprehensively assess cardiac mechanics and function in a cohort of ex-preterm preschoolers. Methods: Ex-preterm children (<30 weeks of gestation), aged 2 to 5 years, underwent transthoracic 2D, speckle-tracking, and 4D echocardiography. The findings were compared with 19 full-term children. Results: Our cohort of 38 children with prematurity history showed a normal morpho-functional echocardiographic assessment. However, compared to controls, the indexed 3D end-diastolic volumes of ventricular chambers were reduced (left ventricle 58.7 ± 11.2 vs. 67.2 ± 8.5 mL/m2; right ventricle 50.3 ± 10.4 vs. 57.7 ± 11 mL/m2; p = 0.02). Left ventricle global and longitudinal systolic function were worse in terms of fraction shortening (32.9% ± 6.8 vs. 36.5% ± 5.4; p = 0.05), ejection fraction (59.2% ± 4.3 vs. 62.3% ± 3.7; p = 0.003), and global longitudinal strain (-23.6% ± 2.4 vs. -25.5% ± 1.7; p = 0.003). Finally, we found a reduced left atrial strain (47.4% ± 9.7 vs. 54.9% ± 6.8; p = 0.004). Conclusions: Preschool-aged ex-preterm children exhibited smaller ventricles and subclinical impairment of left ventricle systolic and diastolic function compared to term children. Long-term follow-up is warranted to track the evolution of these findings.

Sonographic Evaluation of the Endotracheal Tube Position in the Neonatal Population: A Comprehensive Review and Meta-Analysis.

Background: Endotracheal intubation in neonates is challenging and requires a high level of precision, due to narrow and short airways, especially in preterm newborns. The current gold standard for endotracheal tube (ETT) verification is chest X-ray (CXR); however, this method presents some limitations, such as ionizing radiation exposure and delayed in obtaining the radiographic images, that point of care ultrasound (POCUS) could overcome. Primary Objective: To evaluate ultrasound efficacy in determining ETT placement adequacy in preterm and term newborns. Secondary Objective: To compare the time required for ultrasound confirmation vs. time needed for other standard of care methods. Search Methods: A search in Medline, PubMed, Google Scholar and in the Cochrane Central Register of Controlled Trials (CENTRAL) was performed. Our most recent search was conducted in September 2021 including the following keywords: "newborn", "infant", "neonate", "endotracheal intubation", "endotracheal tube", "ultrasonography", "ultrasound". Selection Criteria: We considered randomized and non-randomized controlled trials, prospective, retrospective and cross-sectional studies published after 2012, involving neonatal intensive care unit (NICU) patients needing intubation/intubated infants and evaluating POCUS efficacy and/or accuracy in detecting ETT position vs. a defined gold-standard method. Three review authors independently assessed the studies' quality and extracted data. Main Results: We identified 14 eligible studies including a total of 602 ETT evaluations in NICU or in the delivery room. In about 80% of cases the gold standard for ETT position verification was CXR. Ultrasound was able to identify the presence of ETT in 96.8% of the evaluations, with a pooled POCUS sensitivity of 93.44% (95% CI: 90.4-95.75%) in detecting an appropriately positioned ETT as assessed by CXR. Bedside ultrasound confirmation was also found to be significantly faster compared to obtaining a CXR. Conclusion: POCUS appears to be a fast and effective technique to identify correct endotracheal intubation in newborns. This review could add value and importance to the use of this promising technique.

Severe retinopathy of prematurity is associated with early post-natal low platelet count.

Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in "Group 1" (ROP needing treatment), "Group 2" (ROP spontaneously regressed) and "noROP" group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.

The "Hub and Spoke" (HandS) ECMO for "Resuscitating" Neonates with Respiratory Life-Threatening Conditions.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) implantation for neonates with severe cardiorespiratory life-threatening conditions is highly effective. However, since ECMO is a high-risk and complex therapy, this treatment is usually performed in centers with proven expertise. METHODS: A retrospective review of neonates, from January 2014 to January 2020, presenting with life-threatening conditions and treated by means of Hub and Spoke (HandS) ECMO in peripheral (spoke) hospitals. Data were retrieved from our internal ECMO registry. Protocols and checklists were revised and shared with all spoke hospitals located in North-Eastern Italy. RESULTS: Eleven neonates receiving maximal respiratory and cardiovascular support at a spoke hospital underwent HandS ECMO management. All but three patients were affected by life-threatening meconium aspiration syndrome (MAS). The median ECMO support duration and hospitalization were four (range 2-32) and 30 days (range 8-50), respectively. All but two patients (with congenital diaphragmatic hernia), were weaned off ECMO and discharged home. At a mean follow up of 33.7 ± 29.2 months, all survivors were alive and well, without medications, and normal somatic growth. All but one had normal neuropsychological development. CONCLUSION: HandS ECMO model for neonates with life-threatening conditions is effective and successful. A specialized multidisciplinary team and close cooperation between Hub and Spoke centers are essential for success.

Thrombocytopenia as Type 1 ROP Biomarker: A Longitudinal Study.

This study aimed to prospectively evaluate the association between the appearance and evolution of retinopathy of prematurity (ROP) and selected blood parameters, focusing on platelets count. In total, 157 preterm consecutive babies screened for ROP were included and classified in: ROP necessitating treatment (group ROP1), ROP regressed without therapy (group ROP2) and no ROP (group no-ROP), divided in two phases for each group depending on gestational age. Blood parameters were weekly gathered and referred to postmenstrual age, ROP severity and phase. Platelet count mean values were statistically lower (p < 0.001) during both phases in ROP1 group (179 × 109/L vs. 213 × 109/L in phase 1 and 2, respectively) vs. other groups (ROP2: 286 × 109/L vs. 293 × 109/L; no ROP: 295 × 109/L vs. 313 × 109/L). Platelet count at birth <181 × 109 was statistically associated with Type 1 ROP development and evolution (sensibility = 76.47%, 95% confidence interval 60.0-87.6; specificity = 66.12%, 95% confidence interval 57.3-73.9). In ROP 1 group, a platelets count mean value "spike" (392.6 × 109/L) was documented at 36 weeks of corrected gestational age, preceding the need for treatment performed at a median of 38.1 ± 3.2 weeks. Early birth thrombocytopenia is confirmed as a biomarker of development and progression of ROP requiring treatment. The increase of platelets count at 35-37 weeks of corrected gestational age can be considered a possible clinical biomarker anticipating Type 1 ROP progression in preterm infants.

Ultrasound for Endotracheal Tube Tip Position in Term and Preterm Infants.

BACKGROUND AND OBJECTIVE: Placing an endotracheal tube (ETT) in neonates is challenging and currently requires timely radiographic confirmation of correct tip placement. The objective was to establish the reliability of ultrasound (US) for assessing ETT position in the neonatal intensive care unit (NICU), time needed to do so, and patients' tolerance. METHODS: A prospective study on 71 newborns admitted to our NICU whose ETT placement was evaluated with US (ETT-echo) and confirmed on chest X-rays (CXR). Data were collected by 3 operators (2 neonatologists and a resident in pediatrics). The right pulmonary artery (RPA) was used as a landmark for US. The distance between the tip of the ETT and the upper margin of the RPA was measured using US and compared with the distance between the tube's tip and the carina on the CXR. RESULTS: Seventy-one intubated newborns were included in the study (n = 34 < 1,000 g, n = 18 1,000-2,000 g, n = 19 > 2,000 g). Statistical analysis (Bland-Altman plot and Lin's concordance correlation coefficient) showed an excellent consistency between ETT positions identified on US and chest X-ray. The 2 measures (ETT-echo and CXR) were extremely concordant both in the whole sample and in the subgroups. Minimal changes in patients' vital signs were infrequently observed during US, confirming the tolerability of ETT-echo. The mean time to perform US was 3.2 min (range 1-13). CONCLUSIONS: ETT-echo seems to be a rapid, tolerable, and highly reliable method worth further investigating for future routine use in neonatology with a view to reducing radiation exposure.

Intra-tracheal surfactant/budesonide versus surfactant alone: Comparison of two consecutive cohorts of extremely preterm infants.

OBJECTIVES: To compare the efficacy of intra-tracheal (IT) surfactant/budesonide (SB) with that of surfactant alone (S) in reducing the rate of bronchopulmonary dysplasia (BPD) at 36 weeks post-menstrual age (PMA), we included extremely preterm very low birth weight (VLBW) infants with severe respiratory distress syndrome (RDS) in our tertiary neonatal level of care unit (Padua, Italy). STUDY DESIGN: A retrospective chart review of two cohorts of extremely preterm VLBW neonates (<28+0 gestation weeks, birth weight [BW] < 1500 g) born in two consequent epochs (2017-2018/2018-2019) were compared. The SB group received surfactant (200 mg/kg 1st dose) and budesonide (0.25 mg/kg), while the S group received surfactant alone. RESULTS: Among 68 neonates with RDS Grades III-IV, FiO2 ≥ 0.3 within 12 h of life, 18 were included in each group after matching for perinatal, clinical, and laboratory characteristics. IT SB did not affect the rate of BPD (Vermont Oxford Network, Jensen's, and National Institute of Child Health and Human Development BPD Workshop 2018 definitions), death, BPD, or death at 36 weeks PMA. Hypotension requiring inotropic support within the first 5 days was lower in those receiving the combined treatment (p = .03). The SB group had fewer admissions to pediatric ward due to respiratory causes up to 12 months of corrected age (p = .03). CONCLUSION: The preliminary results of this retrospective study suggest that in extremely preterm VLBW infants, IT SB for severe RDS did not affect the incidence of BPD, death, and BPD or death at 36 weeks PMA, compared to surfactant alone. The combined therapy proved to be safe in this population. Further studies are warranted to explore the role of early IT steroids on respiratory morbidity in preterm infants.

Trends in respiratory management of transferred very preterm infants in the last two decades.

BACKGROUND: Among infants needing urgent transfer after birth, very preterm infants are a high-risk sub-group requiring special attention. This study aimed to assess trends in early respiratory management in a large series of very preterm infants undergoing postnatal transfer. METHODS: Trends in patient characteristics and early respiratory management were assessed in 798 very preterm infants who were transferred by the Eastern Veneto Neonatal Emergency Transport Service in 2000-2019. Trends were analyzed using joinpoint regression analysis and summarized as annual percentage changes (APCs). RESULTS: Proportion of neonates with birth weight less than 1 kg decreased from 33% to 16% (APC -3.82%). Use of nasal-continuous-positive-airway pressure increased (at call: APC 15.39%; during transfer: APC 15.60%), while use of self-inflating bag (at call: APC -12.09%), oxygen therapy (at call: APC -13.00%; during transfer: APC -23.77%) and mechanical ventilation (at call: APC -2.71%; during transfer: APC -2.99%) decreased. Use of oxygen concentrations at 21% increased (at call: APC 6.26%; during transfer: APC 7.14%), while oxygen concentrations above 40% decreased (at call: APC -5.73%; at transfer APC -8.89%). Surfactant administration at call increased (APC 3%-10%), while surfactant administration when arriving at referring hospital remained around 7-11% (APC 2.55%). CONCLUSION: Relevant trends toward "gentle" approaches in early respiratory management of very preterm infants undergoing postnatal transfer occurred during the last twenty years. In addition, the proportion of transferred extremely low birth weight infants halved. Clinicians and stakeholders should consider such information when allocating assets to both hospitals and transfer services and planning regional perinatal programs.

Innate immunity ascertained from blood and tracheal aspirates of preterm newborn provides new clues for assessing bronchopulmonary dysplasia.

AIM: The study aimed to establish how granulocytes, monocytes and macrophages contribute to the development of bronchopulmonary dysplasia (BPD). MATERIALS AND METHODS: Study A: samples of blood and tracheal aspirates (TAs) collected from preterm newborn infants during the first 3 days of life were investigated by flow cytometry, and testing for white blood cells (WBCs), neutrophils and neutrophil extracellular traps (NETs). Maternal blood samples were also collected. Study B: data from previously-tested samples of TAs collected from preterm newborn infants were re-analyzed in the light of the findings in the new cohort. RESULTS: Study A: 39 preterm newborn infants were studied. A moderate correlation emerged between maternal WBCs and neutrophils and those of their newborn in the first 3 days of life. WBCs and neutrophils correlated in the newborn during the first 8 days of life. Decision rules based on birth weight (BW) and gestational age (GA) can be used to predict bronchopulmonary dysplasia (BPD). Neutrophil levels were lower in the TAs from the newborn with the lowest GAs and BWs. Study B: after removing the effect of GA on BPD development, previously-tested newborn were matched by GA. Monocyte phenotype 1 (Mon1) levels were lower in the blood of newborn with BPD, associated with a higher ratio of Monocyte phenotype 3 (Mon3) to Mon1. Newborn infants from mothers with histological chorioamnionitis (HCA) had lower levels of classically-activated macrophages (M1) and higher levels of alternatively-activated macrophages (M2) in their TAs than newborn infants from healthy mothers. CONCLUSION: Immune cell behavior in preterm newborn infants was examined in detail. Surprisingly, neutrophil levels were lower in TAs from the newborn with the lowest GA and BW, and no correlation emerged between the neutrophil and NET levels in TAs and the other variables measured. Interestingly, monocyte phenotype seemed to influence the onset of BPD. The rise in the ratio of Mon 3 to Mon 1 could contribute to endothelial dysfunction in BPD.

Lung Ultrasonography Scores in Preterm Infants and Respiratory Outcomes at Age 2 Years.

This cohort study examines the role of lung ultrasonography score in estimating respiratory episodes needing drugs or hospitalization in premature infants.

Propranolol 0.2% Eye Micro-Drops for Retinopathy of Prematurity: A Prospective Phase IIB Study.

Background: Oral propranolol reduces retinopathy of prematurity (ROP) progression, although not safely. Propranolol 0.1% eye micro-drops administered to newborns with stage 2 ROP are well-tolerated, but not sufficiently effective. Methods: A multi-center open-label trial was conducted to assess the safety and efficacy of propranolol 0.2% eye micro-drops in newborns with stage 1 ROP. The progression of the disease was evaluated with serial ophthalmologic examinations. Hemodynamic, respiratory, biochemical parameters, and propranolol plasma levels were monitored. Demographic and perinatal characteristics, co-morbidities and co-intervention incidences, together with ROP progression, were compared with a historical control group in the same centers participating in the trial. Results: Ninety-eight newborns were enrolled and compared with the historical control group. Populations were not perfectly homogeneous (as demonstrated by the differences in the Apgar score and the different incidence rate in surfactant administration and oxygen exposure). The progression to ROP stage 2 or 3 plus was significantly lower than the incidence expected on the basis of historical data (Risk Ratio 0.521, 95% CI 0.297- 0.916). No adverse effects related to propranolol were observed and the mean propranolol plasma level was significantly lower than the safety cut-off of 20 ng/mL. Unexpectedly, three newborns treated with oral propranolol before the appearance of ROP, showed a ROP that was unresponsive to propranolol eye micro-drops and required laser photocoagulation treatment. Conclusion: Propranolol 0.2% eye micro-drops were well-tolerated and appeared to reduce the ROP progression expected on the basis of a comparison with a historical control group. Propranolol administered too early appears to favor a more aggressive ROP, suggesting that a ß-adrenoreceptor blockade is only useful during the proliferative phase. Further randomized placebo-controlled trials are required to confirm the current results. Clinical Trial Registration  The trial was registered at ClinicalTrials.gov with Identifier NCT02504944 and with EudraCT Number 2014-005472-29.

Incidence of metabolic bone disease in preterm infants of birth weight <1250 g and in those suffering from bronchopulmonary dysplasia.

BACKGROUND & AIMS: Preterm infants are exposed to a higher risk of developing Metabolic Bone Disease (MBD) with an increased bone fragility, a higher fracture risk and a long-term reduced linear growth and childhood height. Monitoring bone growth has become mandatory in neonatology. Several risk factors have been identified among the population of extremely low birth weight infants, but we still do not know which is the real incidence of MBD since its evaluation is not routinely performed worldwide. The aim of this study was to evaluate the incidence of MBD in preterm infants and in those suffering from bronchopulmonary dysplasia (BPD). METHODS: Prospective evaluation of patients who developed BPD (BPD group) versus infants who did not develop it (no-BPD group). We examined, in preterms <1.250 g, the metacarpus bone transmission time (mc-BTT) at birth, 21 days and 36 weeks of gestational age (GA) together with biochemical markers of bone status. RESULTS: We included 135 patients, 55 with BPD. BPD patients received less total proteins in the first two weeks and less energy in the first month of life (p = 0.007 and p < 0.001 respectively). BPD patients had a worse growth velocity at two weeks of age (12.36 ± 7.86 vs 16.59 ± 7.05 g/kg/day, p = 0.001). At 21 days, BPD patients had lower phosphatemia (1.65 ± 0.031 mmol/L vs 1.85 ± 0.034 mmol/L, p = 0.007) and higher alkaline phosphatase levels (411.62 ± 135.31 IU/l vs 338.98 ± 102.20 IU/l, p = 0.005). BPD patients had significantly worse mc-BTT at 36 weeks GA (0.45 ± 0.06 vs 0.50 ± 0.08 µsec, p < 0.001) and a higher incidence of MBD (60% vs 34%; p = 0.012). CONCLUSIONS: BPD infants are a special subset of patients among preterms who receive, in the first month of life, a lower energy intake than patients without BPD. BPD patients have a suboptimal bone growth and a higher incidence of MBD. Monitoring growth, bone status and optimizing nutritional intakes need to be further improved in preterm infants with BPD.

Tricuspid regurgitant velocity elevation in a three-year old child with sickle cell anemia and recurrent acute chest syndromes reversed not by hydroxyurea but by bone marrow transplantation.

Elevated Tricuspid Regurgitant Velocity (TRV) has been related to higher mortality in adults and to hemolysis, lower oxygen saturation during 6-minute walk test and acute chest syndrome (ACS) in children with sickle cell disease (SCD). Hydroxyurea (HU) has reduced TRV value in children and adults. We describe a three year old HbSS child with recurrent ACS, hypoperfusion of the left lung, mild hemolysis and persistent TRV elevation. TRV did not normalize after HU, despite improvement in clinical conditions and in baseline laboratory parameters related to hemolysis and blood viscosity, but normalized after bone marrow transplantation (BMT). Our experience suggests that in young patients, TRV reduction can be a positive concomitant effect of BMT.