Interdisciplinary collaborative eye examinations to protect preterm infant neurodevelopment: a quality improvement project.

Introduction: Infants born <31 weeks gestational age with birth weight ≤ 1,500 grams receive routine eye examinations to screen for Retinopathy of Prematurity (ROP) while in the Neonatal Intensive Care Unit (NICU) to help prevent vision threatening complications; however, preterm infants' sensory systems are underdeveloped, and repeated exposure to painful stimuli is associated with worse developmental outcomes. Methods: An interdisciplinary NICU team designed a collaborative eye exam model (CEEM) incorporating best practice recommendations for infant pain control during exams. Pain scores and vital signs were recorded before, during, and after exams. Two sets of mixed-effects regression models with a random intercept on infants were established to investigate relationships between the intervention, birth gestational age (BGA), postmenstrual age (PMA), and outcomes associated with painful stimuli. Survey feedback was elicited from NICU stakeholders about the CEEM. Results: Thirty standard of care (SC) and 35 CEEM exams of 37 infants were included in final analysis. In infants of the same BGA, the number of desaturation events was significantly reduced in the CEEM group (p = 0.003) and became 1.53 times smaller with each additional week of BGA (p = 0.009). Probability of heart rate recovery within 15 min lowered significantly in the CEEM group (p = 0.04). In SC or CEEM or between infants of the same PMA, no differences were observed for bradycardia, heart rate range, chance of heart rate recovery, or pain scores. Increases in tachycardia (p < 0.001) events and desaturations p = 0.006 were discovered in the CEEM group. When considering interaction effects, the CEEM appeared to reduce the number of desaturations to a greater degree for infants at earliest BGAs with attenuation of this effect with greater BGA. Regarding PMA, bradycardia and tachycardia events were reduced for infants across PMAs in the CEEM, but the effect for tachycardia improves with age, while the effect for bradycardia diminishes with age. Stakeholders agreed that the infant's eye exam experience and the staff experience was "very much" improved by the CEEM. Discussion: Despite variable findings in selected outcome measures, the CEEM was positively viewed by staff. Infants may benefit from the CEEM differently based on BGA and PMA.

Evaluating the Clinical Risk Index for Babies (CRIB) II Score for Mortality Prediction in Preterm Newborns: A Prospective Observational Study at a Tertiary Care Hospital.

INTRODUCTION: Neonatal mortality is an issue that affects both the developed and developing world. It is very important in the neonatal intensive care unit (NICU) to do the assessment of the severity of neonatal illness, which in turn helps in estimating and preventing mortality in the NICU by improving healthcare control and by rational use of resources. This research was carried out to evaluate how effectively the Clinical Risk Index for Babies (CRIB) II score can predict mortality rates among newborns treated in our NICU.  Methodology: This prospective observational study spanned one year, commencing in October 2021 and concluding in September 2022, within the confines of our NICU. The CRIB II score calculation was performed for included newborns, and the outcomes of the newborns were compared. A receiver operating characteristic (ROC) curve was obtained to ascertain the optimal CRIB II cut-off score for predicting mortality. RESULTS: Within the designated research timeframe, 292 neonates were admitted to the NICU. Forty-four newborns were enrolled in the study. Preterm neonates who died had higher CRIB II scores than those who survived, and their median (IQR) was 6 (1-12) vs. 9.5 (5-14) (p=0.0003). The estimate for the area under the curve was 0.83 (95% CI 0.68-0.92), and the odds ratio of 2.56 suggests neonates with a higher CRIB II score have higher chances of mortality. CONCLUSION: The CRIB II score is very good at predicting mortality in preterm newborns.

Retrospective analysis of efgartigimod use in patients with double-seronegative generalized myasthenia gravis: a case series.

The effect of treatment with efgartigimod in seronegative myasthenia gravis (MG) remains unclear. This retrospective study aimed to evaluate symptomatic changes and safety of treatment with efgartigimod in patients with generalized MG (gMG) double-seronegative for acetylcholine receptor antibody and muscle-specific kinase antibody. We reviewed the medical records of double-seronegative gMG treated with 10 mg/kg efgartigimod once/week per cycle (4 weeks) from June 2022 to June 2023. A total of 16 patients were included. MG-activities of daily living (ADL) scores improved from 9.2 to 7.4. Mean prednisolone dose was reduced from 5.4 to 4.1 mg/day. The duration before MG-ADL deterioration after the end of a cycle was 6.1 weeks. Five patients had mild adverse events. This retrospective study revealed no significant treatment benefit in the outcomes of patients with double-seronegative gMG treated with efgartigimod.

Transplantation of Alveolar Macrophages Improves the Efficacy of Endothelial Progenitor Cell Therapy in Mouse Model of Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is a severe complication of preterm births, which develops due to exposure to supplemental oxygen and mechanical ventilation. Published studies demonstrated that the number of endothelial progenitor cells (EPC) is decreased in mouse and human BPD lungs and that adoptive transfer of EPC is an effective approach in reversing the hyperoxia-induced lung damage in mouse model of BPD. Recent advancements in macrophage biology identified the specific sub-types of circulating and resident macrophages mediating the developmental and regenerative functions in the lung. Several studies reported the successful application of macrophage therapy in accelerating regenerative capacity of damaged tissues and enhancing the therapeutic efficacy of other transplantable progenitor cells. In the present study, we explored the efficacy of combined cell therapy with EPC and resident alveolar macrophages (rAM) in hyperoxia-induced BPD mouse model. rAM and EPC were purified from neonatal mouse lungs and used for adoptive transfer to the recipient neonatal mice exposed to hyperoxia. Adoptive transfer of rAM alone did not result in engraftment of donor rAM into the lung tissue, but increased the mRNA level and protein concentration of proangiogenic CXCL12 chemokine in recipient mouse lungs. Depletion of rAM by chlodronate-liposomes decreased the retention of donor EPC after their transplantation into hyperoxia-injured lungs. Adoptive transfer of rAM in combination with EPC enhanced the therapeutic efficacy of EPC as evidenced by increased retention of EPC, increased capillary density, improved arterial oxygenation and alveolarization in hyperoxia-injured lungs. Dual therapy with EPC and rAM has promise in human BPD.

Risks of congenital malformations and neonatal intensive care unit admissions with gabapentin use in pregnancy: A cohort study and scoping review with meta-analysis.

BACKGROUND: The increasing and prevalent use of gabapentin among pregnant people highlights the necessity to assess its neonatal safety. OBJECTIVES: This study aimed to investigate the foetal safety of gabapentin during pregnancy using a cohort study and scoping review with a meta-analysis of published evidence. METHODS: We conducted a population-based cohort study using the Manitoba health databases between 1995 and 2019. We examined the association between gabapentin use during pregnancy and the prevalence of major congenital malformations, cardiac and orofacial malformations, and neonatal intensive care unit (NICU) admissions using multivariate regression models. We searched the literature in MEDLINE and EMBASE databases from inception to October 2022 to identify relevant observational studies and conducted a meta-analysis using random-effects models, including our cohort study results. RESULTS: Of the 289,227 included pregnancies, 870 pregnant people were exposed to gabapentin. Gabapentin exposure during the First trimester was not associated with an increased risk of any malformations (adjusted relative risk [aRR]) 1.16 (95% confidence interval [CI] 0.92, 1.46), cardiac malformations (aRR 1.29, 95% CI 0.72, 2.29), orofacial malformations (aRR 1.37, 95% CI 0.50, 3.75), and major congenital malformations (aRR 1.00, 95% CI 0.73, 1.36). whereas exposure during any trimester was associated with an increased NICU admission risk (aRR, 1.99 [95% CI 1.70, 2.32]). The meta-analysis of unadjusted results revealed an increased risk of major congenital malformations (RR 1.44, 95% CI 1.28, 1.61, I2 = 0%), cardiac malformations (RR 1.66, 95% CI 1.11, 2.47, I2 = 68%), and NICU admissions (RR 3.15, 95% CI 2.90, 3.41, I2 = 10%), and increased trend of orofacial malformations (RR 1.98, 95% CI 0.79, 5.00, I2 = 0%). CONCLUSIONS: Gabapentin use was associated with an increased risk of NICU admissions in the cohort study and pooled meta-analysis. Clinicians should prescribe gabapentin with caution during pregnancy and further studies are warranted.

Melatonin reduces brain injury following inflammation-amplified hypoxia-ischemia in a translational newborn piglet study of neonatal encephalopathy.

There is a need to develop therapies for neonatal encephalopathy (NE) in low- and middle-income countries (LMICs) where the burden of disease is greatest and therapeutic hypothermia (HT) is not effective. We aimed to assess the efficacy of melatonin following inflammation-amplified hypoxia-ischaemia (IA-HI) in the newborn piglet. The IA-HI model accounts for the contribution of infection/inflammation in this setting and HT is not cytoprotective. We hypothesised that intravenous melatonin (5% ethanol, at 20 mg/kg over 2 h at 1 h after HI + 10 mg/kg/12 h between 24 and 60 h) is safe and associated with: (i) reduction in magnetic resonance spectroscopy lactate/N-acetylaspartate (MRS Lac/sNAA); (ii) preservation of phosphorus MRS phosphocreatine/phosphate exchange pool (PCr/Epp); (iii) improved aEEG/EEG recovery and (iv) cytoprotection on immunohistochemistry. Male and female piglets underwent IA-HI by carotid artery occlusion and reduction in FiO2 to 6% at 4 h into Escherichia coli lipopolysaccharide sensitisation (2 µg/kg bolus + 1 µg/kg/h over 12 h). At 1 h after IA-HI, piglets were randomised to HI-saline (n = 12) or melatonin (n = 11). There were no differences in insult severity between groups. Target melatonin levels (15-30 mg/L) were achieved within 3 h and blood ethanol levels were <0.25 g/L. At 60 h, compared to HI-saline, melatonin was associated with a reduction of 0.197 log10 units (95% CrI [-0.366, -0.028], Pr(sup) 98.8%) in basal-ganglia and thalamic Lac/NAA, and 0.257 (95% CrI [-0.676, 0.164], Pr(sup) 89.3%) in white matter Lac/NAA. PCr/Epp was higher in melatonin versus HI-saline (Pr(sup) 97.6%). Melatonin was associated with earlier aEEG/EEG recovery from 19 to 24 h (Pr(sup) 95.4%). Compared to HI-saline, melatonin was associated with increased NeuN+ cell density (Pr(sup) 99.3%) across five of eight regions and reduction in TUNEL-positive cell death (Pr(sup) 89.7%). This study supports the translation of melatonin to early-phase clinical trials. Melatonin is protective following IA-HI where HT is not effective. These data guide the design of future dose-escalation studies in the next phase of the translational pipeline.

Volumetric apparent diffusion coefficient histogram analysis in term neonatal asphyxia treated with hypothermia.

OBJECTIVES: Our aim is to estimate the long-term neurological sequelae and prognosis in term neonatal asphyxia treated with hypothermia via volumetric apparent diffusion coefficient (ADC) map histogram analysis (HA). METHODS: Brain MRI studies of eighty-three term neonates with asphyxia who received whole-body hypothermia treatment and examined between postnatal (PN) 4 to 6th days were retrospectively re-evaluated by two radiologists. Volumetric HA was performed for the areas frequently affected in deep and superficial asphyxia (thalamus, lentiform nucleus, posterior limb of internal capsule, corpus callosum forceps major and perirolandic cortex-subcortical white matter) on ADC map. The quantitative ADC values were obtained separately for each region. Qualitative-visual (conventional) MRI findings were also re-evaluated. Neonates were examined neurodevelopmentally according to the Revised Brunet-Lezine scale. The distinguishability of long-term neurodevelopmental outcomes was statistically investigated. RESULTS: With HA, the adverse neurodevelopmental outcomes could only be distinguished from mild-moderated impairment and normal development at the thalamus with 10th percentile ADC (p = 0.02 and p = 0.03; respectively) and ADCmin (p = 0.03 and p = 0.04; respectively). Also with the conventional MRI findings, adverse outcome could be distinguished from mild-moderated impairment (p = 0.04) and normal development (p = 0.04) via cytotoxic edema of the thalamus, corpus striatum and diffuse cerebral cortical. CONCLUSION: The long-term adverse neurodevelopmental outcomes in newborns with asphyxia who received whole-body hypothermia treatment can be estimate similarly with volumetric ADC-HA and the conventional assessment of the ADC map. ADVANCES IN KNOWLEDGE: This study compare early MRI ADC-HA with neurological sequelae in term newborns with asphyxia who received whole-body hypothermia treatment. We couldn't find any significant difference in predicting adverse neurological sequelae between the visual-qualitative evaluation of the ADC map and HA.

Neonatal Outcomes of Early Term Versus Late-Term Births in a University Teaching Hospital in Lagos, Nigeria.

BACKGROUND: There is increasing evidence of an association between early term birth and adverse neonatal outcomes. However, there is a paucity of data on the true neonatal outcomes following term deliveries in lower-income countries, including Nigeria. OBJECTIVES: This study compared the neonatal outcomes of early and late-term deliveries in a tertiary hospital in Lagos, Nigeria. METHODS: This was a five-year retrospective cohort study of all term deliveries between January 2013 and December 2017. Data were obtained from the labour ward and neonatal ward admission registers and medical records of the hospital. Descriptive and inferential statistics were computed for all relevant data. Statistical significance was reported at a p-value < 0.05. RESULTS: Of the 1,001 deliveries reviewed and analysed for this study, 215 recorded adverse neonatal events, with a significantly higher proportion of these occurring in early term compared to late-term delivered pregnancies (75.8% versus 24.2%, p < 0.001). There was a statistically higher rate of NICU admission in early term neonates than in late-term neonates (14.3 versus 3.9%, p < 0.001). Respiratory complications were the most common adverse outcomes experienced by neonates in both groups. However, the early term neonates had a higher risk even when adjusted for sex, birth weight, and mode of delivery. CONCLUSION: Our study highlights the substantial impact of gestational age on neonatal outcomes, with early term neonates at a significantly higher risk of adverse events compared to late-term neonates. Strategies aimed at reducing the rates of elective early term induction of labour and caesarean deliveries may help minimize the occurrence of adverse neonatal outcomes in our setting.

Clinical and Paraclinical Features in Pregnancies Associated With Renal Impairment Due to Hypertensive Complications.

Background An association between renal impairment and hypertensive complications occurring during pregnancy has been shown in a limited number of studies. As a consequence of a lack of clear criteria for diagnostic certainty, acute renal failure during pregnancy is a challenging pathology to diagnose, mainly due to the physiological reduction of nitrogen retention parameters. In light of the fact that renal injury is associated with a poor maternal and fetal prognosis, this study aims to determine the maternal demographic features and the cut-off of serum creatinine that can lead to a heightened risk of prematurity, stillbirth, intrauterine growth restriction, or the necessity of neonatal intensive care. Methods We performed a study that included a cohort of 45 pregnant women with acute renal injury who delivered in the Department of Obstetrics and Gynecology of the University Emergency Hospital in Bucharest between January 1, 2017, and December 31, 2022, a cohort of 45 pregnant women with a value of serum creatinine between 0.8 and 1 mg/dL, and a cohort of 45 pregnant women, selected at random, with a value of serum creatinine under 0.8 mg/dL, who delivered in the same period in the aforementioned unit. The analysis included neonatal outcomes (preterm birth, intrauterine growth restriction, stillbirth, Apgar score calculated at one minute, the need for neonatal intensive care), maternal demographic features, medical and obstetrical history, and paraclinical parameters. Results The incidence of acute renal injury was 0.33% for the entire cohort of patients who gave birth in our hospital. Out of that lot, 65.21% of the cases of acute renal impairment associated with pregnancy were caused by hypertensive complications. The mean age of patients with acute kidney injury (AKI) was 29.4 ± 6.66, preponderantly primiparous. The majority of the neonates from patients with AKI (62.22%) were born with a birth weight under 2.500 grams. Preterm deliveries were preponderant (66.66%) in patients with AKI, while in the control group, the incidence of preterm deliveries was 48.88%. Stillbirth in the AKI group had an incidence of 13.33%, while in the control group, there were none. Due to these neonatal complications, most of the newborns in the AKI group needed neonatal intensive care. An important percentage of the patients who developed AKI (40%) did not benefit from proper medical care during pregnancy or before admission to our unit. The cutoff of 1.09 mg/dL of serum creatinine level was established following receiver operating characteristic curve analysis. Conclusion AKI during pregnancy is associated with hypertensive disorders, low birth weight, and preterm deliveries.

Validity of Umbilical Cord Blood Procalcitonin in the Diagnosis of Early-Onset Neonatal Infection.

INTRODUCTION: Early-onset neonatal infection (EONI) poses significant risks to neonatal health, necessitating reliable diagnostic markers for early detection. This study aims to evaluate the diagnostic validity of procalcitonin (PCT) concentration in umbilical cord blood as a biomarker for EONI. METHODS: This prospective study was conducted at Ho Chi Minh University Medical Center from April 2022 to September 2022. The PCT level was measured in umbilical cord blood at birth. Based on clinical, laboratory, and microbiologic results, neonates were classified into infected and non-infected groups. RESULTS: One hundred eighty neonates with risk factors for EONI were recruited. Among the neonates studied, 22 (12.2%) were classified as infected and 158 (87.8%) as non-infected by the classification criteria of clinical manifestations, laboratory tests, and blood culture. The median PCT in the infected group was significantly higher than that in the non-infected group (0.389 ng/mL vs. 0.127 ng/mL, p = 0.007). The optimal PCT cut-off was found by receiver operating characteristic (ROC) to be 0.23 ng/mL, with an area under the curve (AUC) of 0.87. The results were 59.1%, 98.7%, 86.2%, 94%, 45, and 0.41 for sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios, respectively. The post-test probability was 86% if the test was positive and 5% if it was negative. CONCLUSION: Umbilical cord blood PCT might be a reliable marker in the diagnosis of EONI, and its value helps limit the harmful effects of unnecessary prescriptions in non-infected neonates. However, considering the low sensitivity of procalcitonin, further research is necessary to fully integrate this biomarker into clinical practice.

Generalized cutis marmorata telangiectatica congenita or neonatal lupus? A case report and literature review.

Cutis marmorata telangiectatica congenita (CMTC) presents as marbled erythema and may exhibit diverse associated anomalies. Thorough multidisciplinary evaluation is crucial. Treatment varies with inconclusive evidence, necessitating further research. Our case underscores CMTC's rarity and heterogeneous nature, advocating for comprehensive management approaches and ongoing research.

Maternal and fetal outcomes after planned cesarean or vaginal delivery in twin pregnancy: a comparison between 2 third level birth centers.

BACKGROUND: Twin pregnancy is associated with higher risks of adverse perinatal outcomes for both the mother and the babies. Among the many challenges in the follow-up of twin pregnancies, the mode of delivery is the last but not the least decision to be made, with the main influencing factors being amnionicity and fetal presentation. The aim of the study was to compare perinatal outcomes in two European centers using different protocols for twin birth in case of non-cephalic second twin; the Italian patients being delivered mainly by cesarean section with those in Belgium being routinely offered the choice of vaginal delivery (VD). METHODS: This was a dual center international retrospective observational study. The population included 843 women with a twin pregnancy ≥ 32 weeks (dichorionic or monochorionic diamniotic pregnancies) and a known pregnancy outcome. The population was stratified according to chorionicity. Demographic and pregnancy data were reported per pregnancy, whereas neonatal outcomes were reported per fetus. We used multiple logistic regression models to adjust for possible confounding variables and to compute the adjusted odds ratio (adjOR) for each maternal or neonatal outcome. RESULTS: The observed rate of cesarean delivery was significantly higher in the Italian cohort: 85% for dichorionic pregnancies and 94.4% for the monochorionic vs 45.2% and 54.4% respectively in the Belgian center (p-value < 0.001). We found that Belgian cohort showed significantly higher rates of NICU admission, respiratory distress at birth and Apgar score of < 7 after 5 min. Despite these differences, the composite severe adverse outcome was similar between the two groups. CONCLUSION: In this study, neither the presentation of the second twin nor the chorionicity affected maternal and severe neonatal outcomes, regardless of the mode of delivery in two tertiary care centers, but VD was associated to a poorer short-term neonatal outcome.

Vortioxetine Exposure During Pregnancy and Lactation: A Japanese Case Study of Neonatal Implications and Quantitative Milk and Plasma Analyses.

Background: Information about influences of vortioxetine on pregnant women and neonates during perinatal period is almost unknown. Case Presentation: The case was a 28-year-old Japanese woman in her first pregnancy, treated for depression with vortioxetine (20 mg daily) among other medications. At 36 weeks of gestation, she was admitted for premature rupture of the membranes and delivered a girl with no apparent congenital anomalies. Immediately after birth, the neonate required brief respiratory support due to her dyspnea and poor muscle tone. Her respiratory condition improved in 6 days after delivery, and she demonstrated normal developmental progress afterward. Maternal plasma and breast milk samples, collected 4 days postpartum, revealed vortioxetine concentrations of 11.4 ng/mL and 9.3 ng/mL, respectively. The calculated relative infant dose (RID) was estimated at 0.32%. After discharge from hospital, the infant presented no detectable drug-related adverse effects, with over 50% of nutrition derived from breastfeeding. Conclusion: This case showed minimal transfer of vortioxetine into breast milk, reflected in a low RID. The findings suggest limited neonatal exposure to the drug, with no adverse developmental effects observed in the infant. However, the case also indicated the potential for vortioxetine use during pregnancy to contribute to the onset of severe neonatal asphyxia. Further research is needed for a comprehensive understanding of its impact on neonatal health.

Molecular characterization of emerging Echovirus 11 (E11) shed light on the recombinant origin of a variant associated with severe hepatitis in neonates.

Echovirus 11 (E11) has gained attention owing to its association with severe neonatal infections. Due to the limited data available, the World Health Organization (WHO) considers public health risk to the general population to be low. The present study investigated the genetic variation and molecular evolution of E11 genomes collected from May to December 2023. Whole genome sequencing (WGS) was performed for 16 E11 strains. Phylogenetic analysis on WG showed how all Italian strains belonged to genogroup D5, similarly to other E11 strains recently reported in France and Germany all together aggregated into separate clusters. A cluster-specific recombination pattern was also identified using phylogenetic analysis of different genome regions. Echovirus 6 was identified as the major recombinant virus in 3Cpro and 3Dpol regions. The molecular clock analysis revealed that the recombination event probably occurred in June 2018 (95% HPD interval: Jan 2016-Jan 2020). Shannon entropy analyses, within P1 region, showed how 11 amino acids exhibited relatively high entropy. Five of them were exposed on the canyon region which is responsible for receptor binding with the neonatal Fc receptor. The present study showed the recombinant origin of a new lineage of E11 associated with severe neonatal infections.

Oxygen in the neonatal ICU: a complicated history and where are we now?

Despite major advances in neonatal care, oxygen remains the most commonly used medication in the neonatal intensive care unit (NICU). Supplemental oxygen can be life-saving for term and preterm neonates in the resuscitation period and beyond, however use of oxygen in the neonatal period must be judicious as there can be toxic effects. Newborns experience substantial hemodynamic changes at birth, rapid energy consumption, and decreased antioxidant capacity, which requires a delicate balance of sufficient oxygen while mitigating reactive oxygen species causing oxidative stress. In this review, we will discuss the physiology of neonates in relation to hypoxia and hyperoxic injury, the history of supplemental oxygen in the delivery room and beyond, supporting clinical research guiding trends for oxygen therapy in neonatal care, current practices, and future directions.

Why do women choose home births.

In recent years, the US has seen a significant rise in the rate of planned home births, with a 60 % increase from 2016 to 2023, reaching a total of 46,918. This trend positions the US as the leading developed country in terms of home birth prevalence. The American College of Obstetricians and Gynecologists (ACOG) suggests stringent criteria for selecting candidates for home births, but these guidelines have not been adopted by home birth midwives leading to poor outcomes including increased rates of neonatal morbidity and mortality. This paper explores the motivations behind choosing home births in the US despite the known risks. Studies highlight factors such as the desire for a more natural birth experience, previous negative hospital experiences, and the influence of the COVID-19 pandemic on perceptions of hospital safety. We provide new insights into why women choose home births by incorporating insights from Nobel laureate Daniel Kahneman's theories on decision-making, suggesting that cognitive biases may significantly influence these decisions. Kahneman's work provides a framework for understanding how biases and heuristics can lead to the underestimation of risks and overemphasis on personal birth experiences. We also provide recommendations ("nudges according to Richard Thaler") to help ensure women have access to clear, balanced information about home births. The development of this publication was assisted by OpenAI's ChatGPT-4, which facilitated the synthesis of literature, interpretation of data, and manuscript drafting. This collaboration underscores the potential of integrating advanced computational tools in academic research, enhancing the efficiency and depth of our analyses.

Comparison of different promoters to improve AAV vector-mediated gene therapy for neuronopathic Gaucher disease.

Gaucher Disease (GD) is an inherited metabolic disorder caused by mutations in the GBA1 gene. It can manifest with severe neurodegeneration and visceral pathology. The most acute neuronopathic form (nGD), for which there are no curative therapeutic options, is characterised by devastating neuropathology and death during infancy. In this study, we investigated the therapeutic benefit of systemically delivered AAV9 vectors expressing the human GBA1 gene at two different doses comparing a neuronal-selective promoter with ubiquitous promoters. Our results highlight the importance of a careful evaluation of the promoter sequence used in gene delivery vectors, suggesting a neuron-targeted therapy leading to high levels of enzymatic activity in the brain but lower GCase expression in the viscera, might be the optimal therapeutic strategy for nGD.

The Effect of Neonatal Intensive Care Nurses' Attitudes Towards Palliative Care on Death Anxiety and Burnout: An Analytic Cross-Sectional Study.

This study aimed to determined the effect of neonatal intensive care nurses' attitudes towards palliative care on death anxiety and burnout. This was an analytic cross-sectional study conducted with 215 neonatal intensive care nurses working a children's hospital with Turkey's largest NICU bed capacity. The mean Neonatal Palliative Care Attitude Scale total score was 3.04 ± 0.78, and the mean scores of the organization, resources, and clinician subscales were 3.16 ± 0.86, 2.87 ± 0.80, and 3.10 ± 0.97, respectively. The participants' mean Death Anxiety Scale score was 57.65 ± 21.46, and the mean Burnout Inventory score was 39.21 ± 17.61. The organization subscale explained 17% of the variance in death anxiety, and the organization and resources subscales explained 31% of the variance in burnout. Neonatal intensive care nurses' palliative care attitudes are moderate; they face obstacles in providing and improving their attitudes in this field. The high level of obstacles increases nurses' death anxiety and burnout.

Factors associated with posttraumatic stress and anxiety among the parents of babies admitted to neonatal care: a systematic review.

BACKGROUND: Posttraumatic stress (PTS) and anxiety are common mental health problems among parents of babies admitted to a neonatal unit (NNU). This review aimed to identify sociodemographic, pregnancy and birth, and psychological factors associated with PTS and anxiety in this population. METHOD: Studies published up to December 2022 were retrieved by searching Medline, Embase, PsychoINFO, Cumulative Index to Nursing and Allied Health electronic databases. The modified Newcastle-Ottawa Scale for cohort and cross-sectional studies was used to assess the methodological quality of included studies. This review was pre-registered in PROSPERO (CRD42021270526). RESULTS: Forty-nine studies involving 8,447 parents were included; 18 studies examined factors for PTS, 24 for anxiety and 7 for both. Only one study of anxiety factors was deemed to be of good quality. Studies generally included a small sample size and were methodologically heterogeneous. Pooling of data was not feasible. Previous history of mental health problems (four studies) and parental perception of more severe infant illness (five studies) were associated with increased risk of PTS, and had the strongest evidence. Shorter gestational age (≤ 33 weeks) was associated with an increased risk of anxiety (three studies) and very low birth weight (< 1000g) was associated with an increased risk of both PTS and anxiety (one study). Stress related to the NNU environment was associated with both PTS (one study) and anxiety (two studies), and limited data suggested that early engagement in infant's care (one study), efficient parent-staff communication (one study), adequate social support (two studies) and positive coping mechanisms (one study) may be protective factors for both PTS and anxiety. Perinatal anxiety, depression and PTS were all highly comorbid conditions (as with the general population) and the existence of one mental health condition was a risk factor for others. CONCLUSION: Heterogeneity limits the interpretation of findings. Until clearer evidence is available on which parents are most at risk, good communication with parents and universal screening of PTS and anxiety for all parents whose babies are admitted to NNU is needed to identify those parents who may benefit most from mental health interventions.