Gender and sex hormone effects on neonatal innate immune function.

OBJECTIVES: Scientific 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. METHODS: Preterm 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. RESULTS: Dividing 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. CONCLUSIONS: This 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.

The hidden benefits of patient encounters.

BACKGROUND: Whilst it is widely acknowledged that health care professionals (HCPs) learn from patient encounters, research exploring what HCPs learn from their meetings with patients is relatively sparse, particularly in the context of postgraduate training. Moreover, there are few research studies that examine the contribution of patient encounters to HCP education from both HCP and patient perspectives. This study set out to explore HCPs learning from patient encounters from both HCP and patient perspectives. METHODS: Qualitative descriptive design was used to conduct this study. Using purposive sampling, we recruited participants from three different groups in a single department of paediatrics in a teaching hospital. Data was collected through interviews, which were transcribed and analysed for key themes. FINDINGS: Patients felt that they played a central role in clinical education and highlighted their ability to educate postgraduate HCPs about their lived experiences of disease. HCPs highlighted the unique insight into a chronic illness gained from patient accounts, essential to developing patient and family orientated approaches to care. HCPs reported that they developed professionally, learning to adapt their negotiation and educational strategies. CONCLUSIONS: This study highlights the importance of patient encounters as critical contributors to HCPs understanding of the lived experiences of patients with chronic disease, and offers insights into how parents view their contribution to clinical education. Much of this learning is embedded and implicit, which suggests that HCP trainees need to develop better in the moment awareness of what they are learning from their meetings with patients and their families.

Exploring parental experiences of virtual paediatric neurodevelopmental consultations.

OBJECTIVE: The coronavirus pandemic resulted in dramatic changes and challenges to healthcare practices. We endeavoured to establish the experiences of families of children attending a neurodevelopmental service after a transition to virtual consultations. METHODS: Anonymous questionnaires were posted to parents of children registered in virtual clinics over a 10-week period. RESULTS: Thirty parental questionnaires were completed. Parents reported a very high level of satisfaction (8.2/10) with previous face-to-face clinic appointments and virtual consultations (8.2/10). Individual aspects of virtual consultations received very positive ratings. Overall, 77% of parents highlighted a future preference for a combined service of both virtual and face-to-face consultations. CONCLUSIONS: This study highlights the high level of parental satisfaction with the service, but especially satisfaction with the unplanned transition to virtual clinics. Virtual clinics cannot replace the holistic approach gained from face-to-face consultations; however, we identified their benefits of convenience and accessibility for our vulnerable population. In response, we have developed an integrated outpatient service involving both forms of consultation to potentiate satisfaction and adapt to meet the needs of our patients. The suggested proforma that has been developed offers a simple structure for undertaking a virtual consultation that can be adapted to different specialities, integrating the suggestions provided by our service users.

Paediatric management of a tuberculosis outbreak in an Irish Direct Provision Centre.

Direct Provision in Ireland provides basic needs of food and shelter to asylum seekers while their refugee status is processed. There are a number of issues associated with living conditions in these centres including overcrowding, nutrition and play facilities (1,2). This article outlines the protocol of contact tracing and management of latent tuberculosis infection in the paediatric setting after a confirmed adult case of tuberculosis within a Direct Provision centre in Ireland. This is a retrospective case series of 82 children living in the centre. Twenty-two children were deemed at risk of infection, all asymptomatic. Sixteen children (20%) were treated for possible latent tuberculosis infection with isoniazid for 6-9 months; compliance was good with no side effects reported. This article highlights the risk to vulnerable populations, especially children, when residing in Direct Provision facilities. Initial migrant screening on entry is essential, in addition to improving living conditions and time spent by families in this living environment.

Challenges in developing a consensus definition of neonatal sepsis.

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.