Anna Curley

How we decide when a neonate needs a transfusion

The decision to transfuse a neonate can be approached by addressing a series of questions that cover the cause of anaemia, alternatives to transfusion, the need for transfusion and the risks. Recent clinical trials of red cell transfusions have started to inform evidence‐based transfusion practice, but have raised uncertainties about neurological outcomes when policies advocating use of fewer red cell transfusions at lower haemoglobin concentration (Hb) thresholds were tested. Red cell transfusions should be considered when the Hb <120 g/l for premature neonates requiring mechanical ventilation support, with lower thresholds applying for oxygen‐dependent neonates not requiring ventilation or for late anaemia (Hb <70–100 g/l, depending on gestational and post‐natal age). There is no recent high quality evidence to inform thresholds for prophylactic platelet transfusions in stable non‐bleeding premature neonates with platelet count levels of 50 × 109/l, although common practice has become more restrictive, using lower safe thresholds for platelet transfusion between 20 and 30 × 109/l. A more appropriate transfusion strategy for fresh frozen plasma (FFP) in neonates is one that emphasizes the therapeutic use of FFP in the face of bleeding, rather than prophylactic use in stable non‐bleeding neonates who often have mild to moderate apparent abnormalities of standard coagulation tests, after allowing for appropriate reference ranges.

Severe thrombocytopenia and patterns of bleeding in neonates: results from a prospective observational study and implications for use of platelet transfusions

To describe patterns of clinical bleeding in neonates with severe thrombocytopenia (ST and platelet count <60 × 109 L−1), and to investigate the factors related to bleeding.

Use of premedication for intubation in tertiary neonatal units in the United Kingdom

Background:  Endotracheal intubation and laryngoscopy are frequently performed procedures in neonatal intensive care. These procedures represent profoundly painful stimuli and have been associated with laryngospasm, bronchospasm, hemodynamic changes, raised intracranial pressure and an increased risk of intracranial hemorrhage. These adverse changes can cause significant neonatal morbidity but may be attenuated by the use of suitable premedication.

The safety and efficacy of red cell transfusions in neonates: a systematic review of randomized controlled trials

Premature neonates commonly receive red blood cell (RBC) transfusions. This study systematically identified and appraised randomized controlled trials (RCTs) where the intervention was ‘transfusion of red blood cells’ from searches of multiple databases. Primary review outcomes were mortality, neurodevelopmental and respiratory endpoints. Two reviewers extracted data and assigned overall quality. Twenty‐seven RCTs were identified and grouped into four predefined categories: trials comparing RBC transfusion versus no transfusion/placebo (n = 3); different thresholds for transfusion (n = 6); differing doses or administration schedule (n = 4), or different types or products of RBC (n = 14). In the threshold group of trials, enrolling 679 neonates, no significant differences in mortality (relative risk 1·22, 95% confidence interval 0·84–1·75) or chronic lung disease were found. Only two trials assessed neurodevelopment outcomes, both within the threshold group, but with differing results. The largest subgroup of RCTs by number evaluated different media for storage of red cells (n = 7), enrolling 221 neonates. The methodological quality of many RCTs was poor. The design of future RCTs can be informed by the lessons from this review. Many trials failed to report on outcomes that would be considered of primary importance to clinicians. Consistent reporting of adverse events is required, and endpoints need to include neurodevelopmental outcomes.

A novel approach to standardised recording of bleeding in a high risk neonatal population

Background Bleeding assessment tools have been developed in other specialties to standardise the recording of bleeding for clinical haemostatic outcomes in transfusion trials, but such tools have not been developed for routine use in neonatology. Aim The objective of this study was to develop, refine and evaluate a neonatal bleeding assessment tool (NeoBAT) to standardise the clinical recording of bleeding in premature and term neonates in an intensive care setting. Methods This prospective neonatal international multicentre study included all episodes of bleeding in infants admitted to the intensive/high dependency care nursery over a 2–4-week period. The NeoBAT was developed to record neonatal bleeding episodes. We tested its reliability and reproducibility with duplicate assessments. Results Duplicate assessments revealed 98% concordance. Bleeding occurred in 25% (37/146) of infants overall and was most common in preterm infants. 11% (16/146) infants had major/severe bleeds, 1% (2/146) moderate and 13% (19/146) minor bleeds. Conclusions Bleeding is common in premature and term neonates admitted to intensive/high dependency care nurseries. This novel bleeding assessment tool facilitates prospective recording of bleeding events in neonatal intensive care settings and may allow standardised bleeding assessments in this high risk population.

Paraoxonase-3, a Putative Circulating Antioxidant, Is Systemically Up-Regulated in Late Gestation in the Fetal Rat, Sheep, and Human

CONTEXT Surfactant is a successful therapeutic based on supplementing preterm infants with a substance that would normally have been up-regulated in late gestation. Although prematurity is associated with oxidative stress, no effective antioxidant therapy has yet been identified. OBJECTIVE Our objective was to identify endogenous antioxidants involved in fetal preparation for birth. DESIGN We performed transcript profiling of fetal rat lung and intestine at 16 d gestational age (dGA) and 20 dGA with out-of-sample validation. Gene expression was then measured in fetal sheep tissues, comparing 1) advancing GA, 2) exogenous maternal dexamethasone (compared with saline, at 130 dGA), and 3) fetal adrenalectomy at 115-118 d on levels at term. Protein levels were compared in human umbilical cord serum using Western blot. RESULTS Four transcripts were up-regulated more than 20-fold on the array in both rat lung and intestine. One of these, paraoxonase-3 (Pon3), had been identified as a putative circulating antioxidant. Up-regulation of Pon3 mRNA in rat lung, intestine, and liver was confirmed in siblings (all P<0.001). Pon3 mRNA levels in fetal sheep lung and intestine increased 5.1- and 5.3-fold, respectively (both P<0.001) between 100 and 145 dGA and were strongly correlated with plasma cortisol (both P<0.001). Fetal sheep pulmonary Pon3 transcript level was increased 55% (P=0.01) by dexamethasone and reduced 74% (P<0.001) by adrenalectomy. Term human infants had more than 6-fold higher umbilical cord serum levels of Pon3 than preterm (24-28 wk GA) infants (P<0.001). CONCLUSIONS Pon3, a putative circulating antioxidant, was systemically up-regulated in late-gestation rat, sheep, and human fetuses and is a candidate therapeutic in preterm human infants.

Interpretation of clotting tests in the neonate

There are significant differences between the coagulation system in neonates compared with children and adults. Abnormalities of standard coagulation tests are common within the neonatal population. The laboratory tests of activated partial thromboplastin time (aPTT) and prothrombin time (PT) were developed to investigate coagulation factor deficiencies in patients with a known bleeding history, and their significance and applied clinical value in predicting bleeding (or thrombotic) risk in critically ill patients is weak. Routine screening of coagulation on admission to the neonatal intensive care unit leads to increased use of plasma for transfusion. Fresh frozen plasma (FFP) is a human donor plasma frozen within a short specified time period after collection (often 8 h) and then stored at −30°C. FFP has little effect on correcting abnormal coagulation tests when mild and moderate abnormalities of PT are documented in neonates. There is little evidence of effectiveness of FFP in neonates. A large trial by the Northern Neonatal Nursing Initiative assessed the use of prophylactic FFP in preterm infants and reported no improvement in clinical outcomes in terms of mortality or severe disability. An appropriate FFP transfusion strategy in neonates should be one that emphasises the therapeutic use in the face of bleeding rather than prophylactic use in association with abnormalities of standard coagulation tests that have very limited predictive value for bleeding.

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.

Using Measurements of Shunt and Ventilation-to-Perfusion Ratio to Quantify the Severity of Bronchopulmonary Dysplasia

Background: Classifying the severity of bronchopulmonary dysplasia (BPD) by continuous numerical variables would facilitate follow-up of disease progression and quantified analysis of disease determinants. Objectives: To non-invasively measure oxygenation impairment in BPD by the degree of right-to-left shunt, right shift of the oxyhaemoglobin dissociation curve and ventilation/perfusion (VA/Q) inequality and to explore their relation with clinical parameters. Methods: Prospective cohort study of 24 infants with a median (interquartile range, IQR) gestation of 25 weeks (24-27) and a birth weight of 0.70 kg (0.63-0.93), studied at 36 days (30-66), at a postmenstrual age (PMA) of 33 weeks (29-36). Inspired oxygen (FIO2) was varied to obtain three to five transcutaneous oxygen saturation (SpO2) values between 85 and 96%. Values of shunt, shift and VA/Q were obtained by plotting the paired data of SpO2 against FIO2 for each infant using a unique program. Right-to-left shunt, right shift of the oxyhaemoglobin dissociation curve and VA/Q were measured in infants born <32 weeks PMA receiving oxygen at 28 days. Results: The median (IQR) shunt was 8% (0.3-16.5), shift 14.5 kPa (10.9-19.4) and VA/Q 0.40 (0.30-0.48). Shunt, shift and VA/Q were significantly related to gestational age (GA) at birth, PMA at study, weight at study and weight gain per week. Conclusions: Severity of pulmonary oxygenation impairment in BPD can be quantified at the cot-side by non-invasive measurement of shunt, shift and VA/Q. Low GA at birth, low weight at birth and at the time of study and impaired weight gain are significantly associated with the severity of oxygen-exchange impairment in infants with BPD.

Skin colonisation at the catheter exit site is strongly associated with catheter colonisation and catheter-related sepsis

The commonest mode of catheter colonisation is via the extraluminal route with skin bacteria. Catheter‐related sepsis causes significant mortality and morbidity in neonates. Our aim was to study the relationships between culture‐positive catheter exit site skin swabs, percutaneous central venous catheter segments and blood to determine the magnitude of associations between exit site skin colonisation, catheter colonisation and catheter‐related sepsis.