Maintaining optimal circulatory status is a key component of preterm neonatal care. Low-cardiac output (CO) in the preterm neonate leads to inadequate perfusion of vital organs and has been linked to ...a variety of adverse outcomes with heightened acute morbidity and mortality and adverse neurodevelopmental outcomes. Having technology available to monitor CO allows us to detect low-output states and potentially intervene to mitigate the unwanted effects of reduced organ perfusion. There are many technologies available for the monitoring of CO in the preterm neonatal population and while many act as useful adjuncts to aid clinical decision-making no technique is perfect. In this review, we discuss the relative merits and limitations of various common methodologies available for monitoring CO in the preterm neonatal population. We will discuss the ongoing challenges in monitoring CO in the preterm neonate along with current gaps in our knowledge. We conclude by discussing emerging technologies and areas that warrant further study.
Neonatologists have begun using superior vena cava flow as assessed by functional echocardiography to facilitate real‐time decision‐making on cardiovascular care. This review aims to describe the ...basis of the technique, summarise the evidence for its use and compare the technique to existing clinical, biochemical and radiological techniques for assessing neonatal circulatory status.
Conclusion
Although echocardiographic measurements of superior vena cava flow, like other measures of perfusion, are not perfect, their noninvasive nature and ability to facilitate real‐time decision‐making means that at present, they remain the best available methodology of monitoring central perfusion in the neonatal population.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aim
From birth to old age, males generally have poorer disease outcomes compared to females. Preterm infants display a marked gender disparity in disease outcomes, and the underlying mechanisms are ...not well delineated. Our aim was to review the literature on clinical outcomes between preterm infants of different genders and discuss the potential mechanisms underlying the differences observed.
Methods
A literature review was undertaken for experimental and clinical research related to gender differences in preterm outcomes.
Results
Preterm male infants appear to have consistently worse outcomes compared to females, and the aetiology of these differences, while mostly undetermined, is likely multifactorial.
Conclusion
The male disadvantage in preterm outcomes is likely multifactorial with hormonal, genetic and immunological differences likely playing key roles. Gender is an important variable in preterm outcome and should be considered when designing clinical and experimental research.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
AimsMale neonates appear to be more susceptible to infection than females. The immunological reasons for this are poorly understood. Our aim was to compare the immune response of healthy term male ...and female neonates using flow cytometry and cytokine analysis.MethodologyWhole blood was collected with routine phlebotomy in healthy, term infants on the postnatal ward within 48 hours of delivery. Samples were processed for flow cytometry and cytokine analysis. Whole blood was treated with endotoxin (LPS; 10 ng/mL) for 1 hour at 37°C before subsequent analysis. Granulocytes and monocytes were identified by flow cytometry based on light scattering properties and cell surface markers. Multiplex ELISA was undertaken using a multisport 96-well plate customised for the experiment.ResultsIn total 26 neonates were analysed (13 of each sex) with 20 having flow cytometry analysis and 6 undergoing ELISA. Female monocytes had higher CD11B expression than males following endotoxin stimulation. GM-CSF, IL-10, IL-1RA and IL-8 increased significantly following endotoxin stimulation in females but not males (p<0.05)ConclusionMale and female neonates mount different immune responses following septic challenge. Results suggest that females mount a more robust immune response and may be better able to modulate the immune response resulting from infectious stimuli.
Sepsis remains a leading cause of morbidity and mortality in the neonatal population, and at present, there is no unified definition of neonatal sepsis. Existing consensus sepsis definitions within ...paediatrics are not suited for use in the NICU and do not address sepsis in the premature population. Many neonatal research and surveillance networks have criteria for the definition of sepsis within their publications though these vary greatly and there is typically a heavy emphasis on microbiological culture. The concept of organ dysfunction as a diagnostic criterion for sepsis is rarely considered in neonatal literature, and it remains unclear how to most accurately screen neonates for organ dysfunction. Accurately defining and screening for sepsis is important for clinical management, health service design and future research. The progress made by the Sepsis-3 group provides a roadmap of how definitions and screening criteria may be developed. Similar initiatives in neonatology are likely to be more challenging and would need to account for the unique presentation of sepsis in term and premature neonates. The outputs of similar consensus work within neonatology should be twofold: a validated definition of neonatal sepsis and screening criteria to identify at-risk patients earlier in their clinical course. IMPACT: There is currently no consensus definition of neonatal sepsis and the definitions that are currently in use are varied.A consensus definition of neonatal sepsis would benefit clinicians, patients and researchers.Recent progress in adults with publication of Sepsis-3 provides guidance on how a consensus definition and screening criteria for sepsis could be produced in neonatology.We discuss common themes and potential shortcomings in sepsis definitions within neonatology.We highlight the need for a consensus definition of neonatal sepsis and the challenges that this task poses.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Neonatal sepsis is a leading cause of infant mortality worldwide with non-specific and varied presentation. We aimed to catalogue the current definitions of neonatal sepsis in published randomised ...controlled trials (RCTs).
A systematic search of the Embase and Cochrane databases was performed for RCTs which explicitly stated a definition for neonatal sepsis. Definitions were sub-divided into five primary criteria for infection (culture, laboratory findings, clinical signs, radiological evidence and risk factors) and stratified by qualifiers (early/late-onset and likelihood of sepsis).
Of 668 papers screened, 80 RCTs were included and 128 individual definitions identified. The single most common definition was neonatal sepsis defined by blood culture alone (n = 35), followed by culture and clinical signs (n = 29), and then laboratory tests/clinical signs (n = 25). Blood culture featured in 83 definitions, laboratory testing featured in 48 definitions while clinical signs and radiology featured in 80 and 8 definitions, respectively.
A diverse range of definitions of neonatal sepsis are used and based on microbiological culture, laboratory tests and clinical signs in contrast to adult and paediatric sepsis which use organ dysfunction. An international consensus-based definition of neonatal sepsis could allow meta-analysis and translate results to improve outcomes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
OBJECTIVESScientific evidence provides a widened view of differences in immune response between male and female neonates. The X-chromosome codes for several genes important in the innate immune ...response and neonatal innate immune cells express receptors for, and are inhibited by, maternal sex hormones. We hypothesized that sex differences in innate immune responses may be present in the neonatal population which may contribute to the increased susceptibility of premature males to sepsis. We aimed to examine the in vitro effect of pro-inflammatory stimuli and hormones in neutrophils and monocytes of male and female neonates, to examine the expression of X-linked genes involved in innate immunity and the miRNA profiles in these populations.METHODSPreterm infants (n = 21) and term control (n = 19) infants were recruited from the Coombe Women and Infants University Hospital Dublin with ethical approval and explicit consent. The preterm neonates (eight female, 13 male) were recruited with a mean gestation at birth (mean ± SD) of 28 ± 2 weeks and corrected gestation at the time of sampling was 30 + 2.6 weeks. The mean birth weight of preterm neonates was 1084 ± 246 g. Peripheral blood samples were used to analyze immune cell phenotypes, miRNA human panel, and RNA profiles for inflammasome and inflammatory genes.RESULTSDividing neutrophil results by sex showed no differences in baseline CD11b between sexes among either term or preterm neonates. Examining monocyte CD11b by sex shows, that at baseline, total and classical monocytes have higher CD11b in preterm females than preterm males. Neutrophil TLR2 did not differ between sexes at baseline or following lipopolysaccharide (LPS) exposure. CD11b expression was higher in preterm male non-classical monocytes following Pam3CSK treatment when compared to females, a finding which is unique to our study. Preterm neonates had higher TLR2 expression at baseline in total monocytes, classical monocytes and non-classical monocytes than term. A sex difference was evident between preterm females and term females in TLR2 expression only. Hormone treatment showed no sex differences and there was no detectable difference between males and females in X-linked gene expression. Two miRNAs, miR-212-3p and miR-218-2-3p had significantly higher expression in preterm female than preterm male neonates.CONCLUSIONSThis study examined immune cell phenotypes and x-linked gene expression in preterm neonates and stratified according to gender. Our findings suggest that the responses of females mature with advancing gestation, whereas male term and preterm neonates have very similar responses. Female preterm neonates have improved monocyte activation than males, which likely reflects improved innate immune function as reflected clinically by their lower risk of sepsis. Dividing results by sex showed changes in preterm and term infants at baseline and following LPS stimulation, a difference which is reflected clinically by infection susceptibility. The sex difference noted is novel and may be limited to the preterm or early neonatal population as TLR2 expression on monocytes of older children does not differ between males and females. The differences shown in female and male innate immune cells likely reflect a superior innate immune defense system in females with sex differences in immune cell maturation. Existing human studies on sex differences in miRNA expression do not include preterm patients, and most frequently use either adult blood or cord blood. Our findings suggest that miRNA profiles are similar in neonates of opposite sexes at term but require further investigation in the preterm population. Our findings, while novel, provide only very limited insights into sex differences in infection susceptibility in the preterm population leaving many areas that require further study. These represent important areas for ongoing clinical and laboratory study and our findings represent an important contribution to exiting literature.
Neonatal chest-Xray (CXR)s are commonly performed as a first line investigation for the evaluation of respiratory complications. Although lung area derived from CXRs correlates well with functional ...assessments of the neonatal lung, it is not currently utilised in clinical practice, partly due to the lack of reference ranges for CXR-derived lung area in healthy neonates. Advanced MR techniques now enable direct evaluation of both fetal pulmonary volume and area. This study therefore aims to generate reference ranges for pulmonary volume and area in uncomplicated pregnancies, evaluate the correlation between prenatal pulmonary volume and area, as well as to assess the agreement between antenatal MRI-derived and neonatal CXR-derived pulmonary area in a cohort of fetuses that delivered shortly after the antenatal MRI investigation.
Fetal MRI datasets were retrospectively analysed from uncomplicated term pregnancies and a preterm cohort that delivered within 72 h of the fetal MRI. All examinations included T2 weighted single-shot turbo spin echo images in multiple planes. In-house pipelines were applied to correct for fetal motion using deformable slice-to-volume reconstruction. An MRI-derived lung area was manually segmented from the average intensity projection (AIP) images generated. Postnatal lung area in the preterm cohort was measured from neonatal CXRs within 24 h of delivery. Pearson correlation coefficient was used to correlate MRI-derived lung volume and area. A two-way absolute agreement was performed between the MRI-derived AIP lung area and CXR-derived lung area.
Datasets from 180 controls and 10 preterm fetuses were suitable for analysis. Mean gestational age at MRI was 28.6 ± 4.2 weeks for controls and 28.7 ± 2.7 weeks for preterm neonates. MRI-derived lung area correlated strongly with lung volumes (p < 0.001). MRI-derived lung area had good agreement with the neonatal CXR-derived lung area in the preterm cohort both lungs = 0.982.
MRI-derived pulmonary area correlates well with absolute pulmonary volume and there is good correlation between MRI-derived pulmonary area and postnatal CXR-derived lung area when delivery occurs within a few days of the MRI examination. This may indicate that fetal MRI derived lung area may prove to be useful reference ranges for pulmonary areas derived from CXRs obtained in the perinatal period.
•Refrence ranges were derived from segmentation of fetal lung areas on AIP-MRI images and correlates with CXR-derived data in preterm infants•Fetal MRI-derived lung area correlated well with fetal MR pulmonary volume and postnatal CXR-lung area. This may prove to be a useful reference range for pulmonary areas derived from CXRs obtained in the perinatal period.•The findings suggest that fetal MRI measurements can serve as useful reference points for assessing lung area in high-risk neonatal CXRs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP