Two-year outcomes following a randomised platelet transfusion trial in preterm infants

Objective: Assess mortality and neurodevelopmental outcomes at 2 years of corrected age in children who participated in the PlaNeT-2/MATISSE (Platelets for Neonatal Transfusion - 2/Management of Thrombocytopenia in Special Subgroup) study, which reported that a higher platelet transfusion threshold was associated with significantly increased mortality or major bleeding compared to a lower one. Design: Randomised clinical trial, enrolling from June 2011 to August 2017. Follow-up was complete by January 2020. Caregivers were not blinded; however, outcome assessors were blinded to treatment group. Setting: 43 level II/III/IV neonatal intensive care units (NICUs) across UK, Netherlands and Ireland. Patients: 660 infants born at less than 34 weeks' gestation with platelet counts less than 50×109/L. Interventions: Infants were randomised to undergo a platelet transfusion at platelet count thresholds of 50×109/L (higher threshold group) or 25×109/L (lower threshold group). Main outcomes measures: Our prespecified long-term follow-up outcome was a composite of death or neurodevelopmental impairment (developmental delay, cerebral palsy, seizure disorder, profound hearing or vision loss) at 2 years of corrected age. Results: Follow-up data were available for 601 of 653 (92%) eligible participants. Of the 296 infants assigned to the higher threshold group, 147 (50%) died or survived with neurodevelopmental impairment, as compared with 120 (39%) of 305 infants assigned to the lower threshold group (OR 1.54, 95% CI 1.09 to 2.17, p=0.017). Conclusions: Infants randomised to a higher platelet transfusion threshold of 50×109/L compared with 25×109/L had a higher rate of death or significant neurodevelopmental impairment at a corrected age of 2 years. This further supports evidence of harm caused by high prophylactic platelet transfusion thresholds in preterm infants. Trial registration number: ISRCTN87736839

Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia

Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p<0.001). Infants treated with TH had lower peak Alanine aminotransferase (ALT) concentrations (p=0.025) and delay in reaching peak CRP concentration (p<0.001).  Conclusion: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury

Skin antisepsis in the neonate:What should we use?

PURPOSE OF REVIEW: Neonates in intensive care are more susceptible to sepsis. Infection is commonly acquired via the transcutaneous portal. It is necessary to identify the most effective yet safest topical antiseptics for use in neonates to reduce nosocomial sepsis. RECENT FINDINGS: Recent national surveys indicate that a wide range of topical antiseptic preparations are used in the neonatal nursery. There are very few comparative studies in neonates and no robust evidence in favour of any particular antiseptic. There are significant safety and potential toxicity issues for neonates with all the commonly used antiseptics, particularly in very small immature babies. There are no convincing roles for routine application of emollient creams on the skin, topical antiseptics on the umbilical stump, or maternal vaginal washes with chlorhexidine for the prevention of neonatal infection. SUMMARY: Large multicentre trials are needed to determine the optimal antiseptic to use for neonates undergoing intensive care, especially for extremely preterm infants

Segmental percutaneous central venous line cultures for diagnosis of catheter-related sepsis

Objective: Culture of percutaneous central venous line (PCVL) segments may assist the diagnosis of line colonisation and catheter-related sepsis (CRS). The authors aimed to determine if the diagnosis of CRS and colonisation of PCVLs in neonates is improved by the culture of the proximal and middle segments of the line in addition to the tip. Patients and methods: In a prospective study, proximal, middle and tip segments of PCVLs indwelling for more than 24 h in term and preterm infants were sent for culture at line removal. Definite CRS was considered as a positive peripheral blood culture plus any line segment growing the same organism in an infant with clinical signs of sepsis. Results: 189 lines were removed from 143 neonates: 142 (75%) were from well infants and 47 (25%) were from neonates with suspected clinical sepsis. The overall CRS rate was 7.9% (15 of 189 line episodes). In well infants, bacterial colonisation rates were significantly higher for proximal segments than for tips (p=0.004). Comparative rates of segmental culture positivity and their positive predictive values for definite CRS were similar for all segments. The diagnosis of CRS was not improved beyond a sole line tip culture by additional middle or proximal segmental cultures or by combinations of the three segments. Conclusion: In well infants, the proximal segments of PCVLs were more often colonised than line tips, but in clinically septic infants preferential culture of proximal or middle segments or combinations of the three segments did not permit better prediction of definite CRS than the culture of the line tip alone. Further studies prior to antibiotic therapy are indicated in babies with suspected CRS

Endotracheal intubation in a neonatal population remains associated with a high risk of adverse events

Introduction: There has been a significant increase in premedication use for neonatal intubation in the UK over the past decade. We aimed to determine the adverse events during neonatal intubation using the most commonly used premedication regimen in the UK. Discussion: We prospectively studied all intubations performed using morphine, suxamethonium and atropine during a 3-month period in three UK tertiary neonatal units. Premedication was administered for 87/93 (94%) of intubations. Median time taken to prepare premedication was 16 min (IQR 10-35). Median time to successful intubation was 5 min (IQR 2-9) following premedication. Median lowest recorded oxygen saturation after administration of premedication was 65% (IQR 39-85). A bradycardia in the range 61-99/min accompanied the procedure in 24/93 (26%) intubations, with a median duration of bradycardia of 8 s (IQR 1-10). Conclusion: Despite the widespread move to premedication for neonatal intubation, many deficiencies in everyday practice remain. The rate of haemodynamic complications is high in this commonly used premedication regimen. This study shows that there are important factors to control at the local level in terms of timely preparation and administration of premedication drugs, training and supervision of staff carrying out this high-risk procedure

Platelets for neonatal transfusion - Study 2:A randomised controlled trial to compare two different platelet count thresholds for prophylactic platelet transfusion to preterm neonates

Introduction: Neonatal thrombocytopenia is a common and important clinical problem in preterm neonates. A trial assessing clinically relevant outcomes in relation to the different platelet count thresholds used to trigger transfusion has never been undertaken in preterm neonates with severe thrombocytopenia. Objectives: Platelets for Neonatal Transfusion - Study 2 (PlaNeT-2) aims to assess whether a higher prophylactic platelet transfusion threshold is superior to the lower thresholds in current standard practice in reducing the proportion of patients who have a major bleed or die up to study day 28. Methods: PlaNeT-2 is a two-stage, randomised, parallel-group, superiority trial. PlaNet-2 compares clinical outcomes in preterm neonates (<34 weeks' gestation at birth) randomised to receive prophylactic platelet transfusions to maintain platelet counts at or above either 25 × 109/l or 50 × 10 9/l. The primary outcome measure is the proportion of patients who either die or experience a major bleed up to and including study day 28. A total of 660 infants will be randomised. Results and Conclusions: This trial will help define optimal platelet transfusion support for severely thrombocytopenic preterm neonates by evaluating the risks and benefits of two different prophylactic neonatal platelet transfusion thresholds