Patient blood management, what does this actually mean for neonates and infants?

Patient blood management (PBM) refers to an evidence-based package of care that aims to improve patient outcomes by optimal use of transfusion therapy, including managing anaemia, preventing blood loss and improving anaemia tolerance in surgical and other patients who may need transfusion. In adults, PBM programmes are well established, yet the definition and implementation of PBM in neonates and children lags behind. Neonates and infants are frequently transfused, yet they are often under-represented in transfusion trials. Adult PBM programmes may not be directly applicable to these populations. We review the literature in neonatal (and applicable paediatric) transfusion medicine and propose specific neonatal PBM definitions and elements.

Maintaining normothermia immediately after birth in preterm infants <34 weeks' gestation: A systematic review and meta-analysis.

AIM: To evaluate delivery room (DR) interventions to prevent hypothermia and improve outcomes in preterm newborn infants <34 weeks' gestation. METHODS: Medline, Embase, CINAHL and CENTRAL were searched till 22nd July 2022. Randomized controlled trials (RCTs), non-RCTs and quality improvement studies were considered. A random effects meta-analysis was performed, and the certainty of evidence was evaluated using GRADE guidelines. RESULTS: DR temperature of ≥23 °C compared to standard care improved temperature outcomes without an increased risk of hyperthermia (low certainty), whereas radiant warmer in servo mode compared to manual mode decreased mean body temperature (MBT) (moderate certainty). Use of a plastic bag or wrap (PBW) improved normothermia (low certainty), but with an increased risk of hyperthermia (moderate certainty). Plastic cap improved normothermia (moderate certainty) and when combined with PBW improved MBT (low certainty). Use of a cloth cap decreased moderate hypothermia (low certainty). Though thermal mattress (TM) improved MBT, it increased risk of hyperthermia (low certainty). Heated-humidified gases (HHG) for resuscitation decreased the risk of moderate hypothermia and severe intraventricular hemorrhage (very low to low certainty). None of the interventions was shown to improve survival, but sample sizes were insufficient. CONCLUSIONS: DR temperature of ≥23 °C, radiant warmer in manual mode, use of a PBW and a head covering is suggested for preterm newborn infants <34 weeks' gestation. HHG and TM could be considered in addition to PBW provided resources allow, in settings where hypothermia incidence is high. Careful monitoring to avoid hyperthermia is needed.

Maintaining normal temperature immediately after birth in late preterm and term infants: A systematic review and meta-analysis.

AIM: Prevention of hypothermia after birth is a global problem in late preterm and term neonates. The aim of this systematic review and meta-analysis was to evaluate delivery room strategies to maintain normothermia and improve survival in late preterm and term neonates (≥34 weeks' gestation). METHODS: Medline, Embase, CINAHL, CENTRAL and international clinical trial registries were searched. Randomized controlled trials (RCTs), quasi-RCTs and observational studies were eligible for inclusion. Risk of bias for each study and GRADE certainty of evidence for each outcome were assessed. RESULTS: 25 RCTs and 10 non-RCTs were included. Room temperature of 23 °C compared to 20 °C improved normothermia [Risk Ratio (RR), 95% Confidence Interval (CI): 1.26, 1.11-1.42)] and body temperature [Mean Difference (MD), 95% CI: 0.30 °C, 0.23-0.37 °C), and decreased moderate hypothermia (RR, 95% CI: 0.26, 0.16-0.42). Skin to skin care (SSC) compared to no SSC increased body temperature (MD, 95% CI: 0.32, 0.10-0.52), reduced hypoglycemia (RR, 95% CI: 0.16, 0.05-0.53) and hospital admission (RR, 95% CI: 0.34, 0.14-0.83). Though plastic bag or wrap (PBW) alone or when combined with SSC compared to SSC alone improved temperatures, the risk-benefit balance is uncertain. Clinical benefit or harm could not be excluded for the primary outcome of survival for any of the interventions. Certainty of evidence was low to very low for all outcomes. CONCLUSIONS: Room temperature of 23 °C and SSC soon after birth may prevent hypothermia in late preterm and term neonates. Though PBW may be an effective adjunct intervention, the risk-benefit balance needs further investigation.

First outbreak of PVL-positive nonmultiresistant MRSA in a neonatal ICU in Australia: comparison of MALDI-TOF and SNP-plus-binary gene typing.

The purpose of this brief report is to describe the first outbreak of a community-associated nonmultiresistant and PVL-positive MRSA strain (CC30) in a neonatal intensive care unit in Australia. The utility of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) for microbial typing is compared with single nucleotide polymorphism (SNP) plus binary gene analysis. The composite correlation index analysis of the MALDI-TOF-MS data demonstrated the similar inter-strain relatedness found with the SNP-plus-binary gene typing used to confirm the outbreak. The evolving spread of MRSA emphasizes the importance of surveillance, infection control vigilance and the ongoing investigation of rapid typing methods for MRSA.

The effect of breastmilk and saliva combinations on the in vitro growth of oral pathogenic and commensal microorganisms.

Neonates are exposed to microbes in utero and at birth, thereby establishing their microbiota (healthy microbial colonisers). Previously, we reported significant differences in the neonatal oral microbiota of breast-fed and formula-fed babies after first discovering a primal metabolic mechanism that occurs when breastmilk (containing the enzyme xanthine oxidase) and neonatal saliva (containing highly elevated concentrations of the substrates for xanthine oxidase: xanthine and hypoxanthine). The interaction of neonatal saliva and breast milk releases antibacterial compounds including hydrogen peroxide, and regulates the growth of bacteria. Using a novel in vitro experimental approach, the current study compared the effects of this unique metabolic pathway on a range of bacterial species and determined the period of time that microbial growth was affected. We demonstrated that microbial growth was inhibited predominately, immediately and for up to 24 hr following breastmilk and saliva mixing; however, some microorganisms were able to recover and continue to grow following exposure to these micromolar amounts of hydrogen peroxide. Interestingly, growth inhibition was independent of whether the organisms possessed a catalase enzyme. This study further confirms that this is one mechanism that contributes to the significant differences in the neonatal oral microbiota of breast-fed and formula-fed babies.

Regulation of messenger RNAs for the hydrophobic surfactant proteins in human lung.

The pulmonary surfactant proteins SP-B (8,000 D) and SP-C (4,000 D) accelerate surface film formation by surfactant phospholipids. We used cDNA probes to examine regulation of these proteins in human fetal lung. The mRNAs were detectable at 13 wk gestation and increased to approximately 50% (SP-B) and approximately 15% (SP-C) of adult levels at 24 wk. The mRNAs were detected only in lung of 11 dog tissues examined. When human fetal lung was cultured as explants without hormones, SP-B mRNA increased and SP-C mRNA decreased. Exposure for 48 h to glucocorticoids, but not other steroids, increased both SP-B mRNA (approximately 4-fold) and SP-C mRNA (approximately 30-fold) vs. controls. Half-maximal stimulation occurred with 1 nM dexamethasone and 300 nM cortisol for SP-B mRNA and at three- to fivefold higher concentrations for SP-C mRNA. Both stimulation and its reversal on removal of hormone were more rapid for SP-B than for SP-C. Terbutaline and forskolin increased SP-B mRNA but not SP-C mRNA. Levels of both mRNAs were much higher in type II cells than fibroblasts prepared from explants. Thus, the genes for SP-B and SP-C are expressed in vivo before synthesis of both SP-A (28,000-36,000 D) and surfactant lipids. Glucocorticoid induction of SP-B and SP-C mRNAs in type II cells appears to be receptor mediated but may involve different mechanisms.

The cognitive aids in medicine assessment tool (CMAT) applied to five neonatal resuscitation algorithms.

OBJECTIVE: The International Liaison Committee on Resuscitation (ILCOR) provides recommendations on neonatal resuscitation training and practice, which includes a template for a decision-making algorithm. We evaluated the design properties of the ILCOR algorithm and four adaptations by member resuscitation organizations using the validated Cognitive Aids in Medicine Assessment Tool (CMAT). STUDY DESIGN: Two experts rated five neonatal resuscitation algorithms against the CMAT and against medical device design criteria. RESULTS: The ILCOR algorithm scored 32 of a possible 60 CMAT points, showing an adherence rate to CMAT of 53%. The ILCOR algorithm scored higher than the design variations by member organizations. Nonetheless, there are design limitations in the ILCOR algorithm. CONCLUSION: In principle, cognitive aids can improve neonatal resuscitation team performance; however, a considered design process that incorporates the full complexity of the 'procedure as performed' is needed to improve future versions of the algorithm for incorporation in international guidelines.

Deep sequencing of the 16S ribosomal RNA of the neonatal oral microbiome: a comparison of breast-fed and formula-fed infants.

In utero and upon delivery, neonates are exposed to a wide array of microorganisms from various sources, including maternal bacteria. Prior studies have proposed that the mode of feeding shapes the gut microbiota and, subsequently the child's health. However, the effect of the mode of feeding and its influence on the development of the neonatal oral microbiota in early infancy has not yet been reported. The aim of this study was to compare the oral microbiota of healthy infants that were exclusively breast-fed or formula-fed using 16S-rRNA gene sequencing. We demonstrated that the oral bacterial communities were dominated by the phylum Firmicutes, in both groups. There was a higher prevalence of the phylum Bacteroidetes in the mouths of formula-fed infants than in breast-fed infants (p = 0.01), but in contrast Actinobacteria were more prevalent in breast-fed babies; Proteobacteria was more prevalent in saliva of breast-fed babies than in formula-fed neonates (p = 0.04). We also found evidence suggesting that the oral microbiota composition changed over time, particularly Streptococcus species, which had an increasing trend between 4-8 weeks in both groups. This study findings confirmed that the mode of feeding influences the development of oral microbiota, and this may have implications for long-term human health.

Isolation and characterization of differentiated alveolar type II cells from fetal human lung.

A method has been developed for isolating differentiated type II cells from human lung of 18-24-week gestation. The procedure involves an initial 4-day culture of lung explants in the presence of dexamethasone (10 nM) and triiodothyronine (2 nM). Type II cells (and fibroblasts) are isolated by trypsin digestion of the explants, two differential adherence steps and incubation overnight in primary culture. This method provides a high yield of type II cells ((50 +/- 15) X 10(6) cells/g wet weight of explant) with a purity of 85 +/- 5% in 16 experiments. The type II cells contain numerous perinuclear granules which stain darkly with toluidine blue and Papanicolaou stain; electron microscopy showed these inclusions to be lamellar bodies with tightly stacked, well defined lamellae. Type II cells, but not fibroblasts, were positive by immunofluorescence histology for surfactant apoprotein and binding of Maclura pomifera lectin which binds to the surface of type II but not type I cells in vivo. The rate of both [3H]acetate and [3H]choline incorporation into phosphatidylcholine (PC) was several-fold greater in type II cells than fibroblasts; the saturation of PC was 36.2 and 25.9%, respectively. Release of saturated PC was stimulated by terbutaline, the ionophore A23187, and tetradecanoyl phorbol acetate in type II cells but not fibroblasts. We conclude that differentiated type II cells can be isolated in relatively high yield and purity from hormone-treated explants of fetal human lung.

Synthesis of surfactant components by cultured type II cells from human lung.

We examined the effect of monolayer culture on surfactant phospholipids and proteins of type II cells isolated from human adult and fetal lung. Type II cells were prepared from cultured explants of fetal lung (16-24 weeks gestation) and from adult surgical specimens. Cells were maintained for up to 6 days on plastic tissue culture dishes. Although incorporation of [methyl-3H]choline into phosphatidylcholine (PC) by fetal cells was similar on day 1 and day 5 of culture, saturation of PC fell from 35 to 26%. In addition, there was decreased distribution of labeled acetate into PC, whereas distribution into other phospholipids increased or did not change. The decrease in saturation of newly synthesized PC was not altered by triiodothyronine (T3) and dexamethasone treatment or by culture as mixed type II cell/fibroblast monolayers. The content of surfactant protein SP-A (28-36 kDa) in fetal cells, as measured by ELISA and immunofluorescence microscopy, rose during the first day and then fell to undetectable levels by the fifth. Synthesis of SP-A, as measured by [35S]methionine labeling and immunoprecipitation, was detectable on day 1 but not thereafter. Levels of mRNAs for SP-A and for the two lipophilic surfactant proteins SP-B (18 kDa) and SP-C (5 kDa) fell with half-times of maximally 24 h. In contrast, total protein synthesis measured by [35S]methionine incorporation increased and then plateaued. In adult cells, the content of SP-A and its mRNA decreased during culture, with time-courses similar to those for fetal cells. We conclude that in monolayer culture on plastic culture dishes, human type II cells lose their ability to synthesize both phospholipids and proteins of surfactant. The control of type II cell differentiation under these conditions appears to be at a pretranslational level.