The current clinical landscape of neonatal respiratory failure in Jiangsu Province of China: patient demographics, NICU treatment interventions, and patient outcomes.

INTRODUCTION: Neonatal respiratory failure (NRF) is a serious condition that often has high mortality and morbidity, effective interventions can be delivered in the future by identifying the risk factors associated with morbidity and mortality. However, recent advances in respiratory support have improved neonatal intensive care units (NICUs) care in China. We aimed to provide an updated review of the clinical profile and outcomes of NRF in the Jiangsu province. METHODS: Infants treated for NRF in the NICUs of 28 hospitals between March 2019 and March 2022 were retrospectively reviewed. Data collected included baseline perinatal and neonatal parameters, NICU admission- and treatment-related data, and patient outcomes in terms of mortality, major morbidity, and survival without major morbidities. RESULTS: A total of 5548 infants with NRF were included in the study. The most common primary respiratory disorder was respiratory distress syndrome (78.5%). NRF was managed with non-invasive and invasive respiratory support in 59.8% and 14.5% of patients, respectively. The application rate of surfactant therapy was 38.5%, while that of neonatal extracorporeal membrane oxygenation therapy was 0.2%. Mortality and major morbidity rates of 8.5% and 23.2% were observed, respectively. Congenital anomalies, hypoxic-ischemic encephalopathy, invasive respiratory support only and inhaled nitric oxide therapy were found to be significantly associated with the risk of death. Among surviving infants born at < 32 weeks of gestation or with a birth weight < 1500 g, caffeine therapy and repeat mechanical ventilation were demonstrated to significantly associate with increased major morbidity risk. CONCLUSION: Our study demonstrates the current clinical landscape of infants with NRF treated in the NICU, and, by proxy, highlights the ongoing advancements in the field of perinatal and neonatal intensive care in China.

CLSI-based verification and de novo establishment of reference intervals for common biochemical assays in Croatian newborns.

Introduction: This study aimed to examine whether the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) reference intervals for 19 commonly used biochemical assays (potassium, sodium, chloride, calcium, magnesium, inorganic phosphorous, glucose, urea, creatinine, direct and total bilirubin, C-reactive protein (CRP), total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and lactate dehydrogenase (LD)) could be applied to the newborn population of one Croatian clinical hospital. Materials and methods: Reference interval verification was performed according to the CLSI EP28-A3c guidelines. Samples of healthy newborns were selected using the direct a posteriori sampling method and analyzed on the Beckman Coulter AU680 biochemical analyzer. If verification wasn't satisfactory, further procedure included de novo determination of own reference intervals by analyzing 120 samples of healthy newborns. Results: After the first set of measurements, 14/19 tested reference intervals were adopted for use: calcium, inorganic phosphorous, glucose, urea, creatinine, total bilirubin, CRP, total protein, albumin, AST, ALT, GGT, ALP and LD. A second set of samples was tested for 5 analytes: potassium, sodium, chloride, magnesium and direct bilirubin. The verification results of the additional samples for sodium and chloride were satisfactory, while the results for potassium, magnesium and direct bilirubin remained unsatisfactory and new reference intervals were determined. Conclusions: The CALIPER reference intervals can be implemented into routine laboratory and clinical practice for the tested newborn population for most of the analyzed assays, while own reference intervals for potassium, magnesium and direct bilirubin have been determined.

Two cases with discrepancy in the quantitative cytological assessment of cerebrospinal fluid in neonatal samples using light microscopy in comparison with Sysmex XN-1000.

We present two cases from the neonatal department with cerebrospinal fluid examination. We revealed a striking discrepancy in polymorphonuclear (PMN) and mononuclear (MN) cell counts using conventional light microscopy in comparison with automated analyzer Sysmex XN-1000 (PMNs - 13 vs. 173x106/L, MNs - 200 vs. 67x106/L in case 1 and PMNs - 13 vs. 372x106/L, MNs - 411 vs. 179x106/L in case 2). We revealed the dominant presence of hemosiderophages in both cases in cytospin slide. Even though Sysmex XN-1000 offers fast examination with a low sample volume, there is possibility of misdiagnosis, with negative impact on the patient.

Comparison of singleton and twin birth weight reference percentile curves by gestational age and sex in extremely preterm infants: a population-based study.

BACKGROUND: With the increasing survival rate of smaller newborns and twins, previous growth curves may not accurately assess the growth of extremely preterm infants (EPIs). Our study aimed to establish birth weight percentile curves for singletons and twins in EPIs from China and the USA and compare the differences between them. METHODS: In China, EPIs were from 31 provinces, from 2010 to 2021. The collected information was sex, gestational age, birth weight, singletons and twins. We used the generalised additive models for location scale and shape method to construct the birth weight percentile curves by gestational age and sex for EPIs. The National Vital Statistics System database from 2016 to 2021 was also analysed. We compared the differences between the 50th birth weight percentile curves of the two databases. RESULTS: We identified 8768 neonates in China (5536 singletons and 3232 twins) and 121 933 neonates in the USA (97 329 singletons and 24 604 twins). We established the 3rd, 10th, 25th, 50th, 75th, 90th and 97th birth weight reference curves for China and the USA. The results showed that males had higher birth weights than females. In China, for the same gestational age and sex, birth weights in singletons and twins were found to be similar, though singleton males born in China had slightly higher birth weights than male twins. In the USA, birth weights were also similar for females and males, with the same gestational age in singletons and twins. CONCLUSION: We established birth weight reference percentile curves by gestational age and sex for singletons and twins among EPIs in China and the USA.

Survival status and predictors of mortality among preterm neonates admitted in Bench Sheko Zone, Sheka Zone and Keffa Zone Governmental Hospitals, Southwest Ethiopia (2021): prospective follow-up study.

INTRODUCTION: Prematurity presents a significant challenge to the global community due to the rapid increase in its incidence and its disproportionate contribution to increased infant mortality rates. OBJECTIVE: To assess the survival status and predictors of mortality among preterm neonates. DESIGN: A multicentre prospective follow-up study was used. SETTING: 625 preterm neonates were admitted to hospitals for secondary level of care. The study covers the Bench Maji Zone, Keffa Zone, Sheka Zone, nearby woredas and portions of the Gambella area in Southwest Ethiopia. PARTICIPANTS: 614 preterm neonates with gestational age less than 37 weeks were entered for follow-up and 400 neonates were censored. Neonates with severe fetal malformations and neonates who need urgent referral were excluded from the study. RESULTS: Overall, 200 (32.57%) participants died with an incidence rate of 61.69 deaths per 1000 person-day observations (95% CI: 53.71 to 70.86). Poor kangaroo mother care (KMC) services (adjusted HR (AHR)=0.19, 95% CI: 0.12 to 0.29), sex (AHR=0.66, 95%, CI: 0.47 to 0.94), not initiating breast feeding (HR=2.78, 95% CI: 1.8 to 4.28), hypothermia (AHR=0.63, 95% CI: 0.44 to 0.92), anaemia (AHR=6.2, 95% CI: 2.34 to 16.43) and gestational age less than 28 weeks (AHR=9.28, 95% CI: 1.78 to 48.42) were independent predictors. CONCLUSION AND RECOMMENDATION: The rate of preterm neonatal mortality was high compared with the Ethiopia Demographic and Health Survey report nationally. Healthcare workers should encourage KMC services and breastfeeding initiation and prevent preterm neonates from being anaemic to increase their chances of survival.

Safety of different concentrations of glycerine enema for meconium evacuation in preterm infants: study protocol for a randomised controlled trial.

INTRODUCTION: Various approaches are employed to expedite the passage of meconium in preterm infants within the neonatal intensive care unit (NICU), with glycerine enemas being the most frequently used. Due to the potential risk of high osmolality-induced harm to the intestinal mucosa, diluted glycerine enema solutions are commonly used in clinical practice. The challenge lies in the current lack of knowledge regarding the safest and most effective concentration of glycerine enema. This research aims to ascertain the safety of different concentrations of glycerine enema solution in preterm infants. METHODS AND ANALYSIS: This study protocol is for a single-centre, two-arm, parallel-group, double-blind and non-inferiority randomised controlled trial. Participants will be recruited from a NICU in a teriary class A hospital in China, and eligible infants will be randomly allocated to either the glycerine (mL): saline (mL) group in a 3:7 ratio or the 1:9 ratio group. The enema procedure will adhere to the standardised operational protocols. Primary outcomes encompass necrotising enterocolitis and rectal bleeding, while secondary outcomes encompass feeding parameters, meconium passage outcomes and splanchnic regional oxygen saturation. Analyses will compare the two trial arms based on an intention-to-treat allocation. ETHICS AND DISSEMINATION: This trial is approved by the ethics committee of the Medical Ethics Committee of West China Second University Hospital of Sichuan University. The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ChiCTR2300079199.

Neurally adjusted ventilatory assist in preterm infants: A systematic review and meta-analysis.

To compare the effects of neurally adjusted ventilatory assist (NAVA) with other forms of synchronized artificial ventilation in preterm infants. A systematic review of randomized and quasi-randomized controlled trials with individual group allocation, both parallel-group trials as well as crossover trials, that included preterm infants born at less than 37 weeks gestational age and compared NAVA with any other form of synchronized mechanical ventilation with or without volume guarantee. Primary outcomes were death or bronchopulmonary dysplasia (BPD) at 36 weeks, total duration of respiratory support and neurodevelopmental outcome at 2 years. Secondary outcomes consisted of important procedural and clinical outcomes. Seven studies with a total of 191 infants were included, five randomized crossover trials and two parallel group randomized trials. No significant difference in the primary outcome of death or BPD (RR: 1.08, 95% CI: 0.33-3.55) was found. Peak inspiratory pressures were significantly lower with NAVA than with other forms of ventilation (MD -1.83 cmH2O [95% CI: -2.95 to -0.71]). No difference in any other clinical or ventilatory outcome was detected. Although associated with lower peak inspiratory pressures, the use of NAVA does not result in a reduced risk of death or BPD as compared to other forms of synchronized ventilation in preterm infants. However, the certainty of evidence is low due to imprecision of the effect estimate. Larger studies are needed to detect possible short- and long-term differences between ventilation modes.

Inter-facility transfers for emergency obstetrical and neonatal care in rural Madagascar: a cost-effectiveness analysis.

CONTEXT: There is a substantial lack of inter-facility referral systems for emergency obstetrical and neonatal care in rural areas of sub-Saharan Africa. Data on the costs and cost-effectiveness of such systems that reduce preventable maternal and neonatal deaths are scarce. SETTING: We aimed to determine the cost-effectiveness of a non-governmental organisation (NGO)-run inter-facility referral system for emergency obstetrical and neonatal care in rural Southern Madagascar by analysing the characteristics of cases referred through the intervention as well as its costs. DESIGN: We used secondary NGO data, drawn from an NGO's monitoring and financial administration database, including medical and financial records. OUTCOME MEASURES: We performed a descriptive and a cost-effectiveness analysis, including a one-way deterministic sensitivity analysis. RESULTS: 1172 cases were referred over a period of 4 years. The most common referral reasons were obstructed labour, ineffective labour and eclampsia. In total, 48 neonates were referred through the referral system over the study period. Estimated cost per referral was US$336 and the incremental cost-effectiveness ratio (ICER) was US$70 per additional life-year saved (undiscounted, discounted US$137). The sensitivity analysis showed that the intervention was cost-effective for all scenarios with the lowest ICER at US$99 and the highest ICER at US$205 per additional life-year saved. When extrapolated to the population living in the study area, the investment costs of the programme were US$0.13 per person and annual running costs US$0.06 per person. CONCLUSIONS: In our study, the inter-facility referral system was a very cost-effective intervention. Our findings may inform policies, decision-making and implementation strategies for emergency obstetrical and neonatal care referral systems in similar resource-constrained settings.

Reporting interhospital neonatal intensive care transport: international five-step Delphi-based template.

OBJECTIVE: To develop a general and internationally applicable template of data variables for reporting interhospital neonatal intensive care transports. DESIGN: A five-step Delphi method. SETTING: A group of experts was guided through a formal consensus process using email. SUBJECTS: 12 experts in neonatal intensive care transports from Canada, Denmark, Norway, the UK and the USA. Four women and eight men. The experts were neonatologists, anaesthesiologists, intensive care nurse, anaesthetic nurse, medical leaders, researchers and a parent representative. MAIN OUTCOME MEASURES: 37 data variables were included in the final template. RESULTS: Consensus was achieved on a template of 37 data variables with definitions. 30 variables to be registered for each transport and 7 for annual registration of the system of the transport service. 11 data variables under the category structure, 20 under process and 6 under outcome. CONCLUSIONS: We developed a template with a set of data variables to be registered for neonatal intensive care transports. To register the same data will enable larger datasets and comparing services.

The influence of chorioamnionitis on respiratory drive and spontaneous breathing of premature infants at birth: a narrative review.

Most very premature infants breathe at birth but require respiratory support in order to stimulate and support their breathing. A significant proportion of premature infants are affected by chorioamnionitis, defined as an umbrella term for antenatal inflammation of the foetal membranes and umbilical vessels. Chorioamnionitis produces inflammatory mediators that potentially depress the respiratory drive generated in the brainstem. Such respiratory depression could maintain itself by delaying lung aeration, hampering respiratory support at birth and putting infants at risk of hypoxic injury. This inflammatory-mediated respiratory depression may contribute to an association between chorioamnionitis and increased requirement of neonatal resuscitation in premature infants at birth. This narrative review summarises mechanisms on how respiratory drive and spontaneous breathing could be influenced by chorioamnionitis and provides possible interventions to stimulate spontaneous breathing.  Conclusion: Chorioamnionitis could possibly depress respiratory drive and spontaneous breathing in premature infants at birth. Interventions to stimulate spontaneous breathing could therefore be valuable. What is Known: • A large proportion of premature infants are affected by chorioamnionitis, antenatal inflammation of the foetal membranes and umbilical vessels. What is New: • Premature infants affected by chorioamnionitis might be exposed to higher concentrations of respiratory drive inhibitors which could depress breathing at birth. • Premature infants affected by chorioamnionitis seem to be associated with a higher and more extensive requirement of resuscitation at birth.

Impact of restrictive platelet transfusion strategies on transfusion rates: A cohort study in very preterm infants.

BACKGROUND: Evidence supports a restrictive platelet transfusion threshold in preterm neonates. We aimed to describe the effect of implementing this threshold on transfusion rates. STUDY DESIGN AND METHODS: This retrospective observational cohort study included all very preterm infants (born <32 weeks' gestation) admitted to a neonatal intensive care unit between 2004 and 2022, divided into three epochs. Platelet transfusion thresholds changed from 30 × 109/L for stable neonates and 50 × 109/L for unstable neonates (January 2004 to December 2009) to 20 × 109/L for stable neonates and 50 × 109/L for unstable neonates (January 2010 to June 2019) to 25 × 109/L for non-bleeding neonates and 50 × 109/L for neonates with major bleeding (July 2019 to July 2022). The primary outcome was the percentage of transfused neonates in each epoch. Secondary outcomes included the median number of transfusions per neonate, the percentage of transfusions given above 25 or 50 × 109/L, and major bleeding and mortality rates. RESULTS: The percentage of neonates transfused was 12.2% (115/939), 5.8% (96/1660), and 4.8% (25/525) in Epoch I, II, and III, respectively (p < .001), a relative reduction of 61%. The median number of transfusions per transfused neonate was 2.0 (interquartile range [IQR]: 1.0-3.0) in Epoch I, and 1.0 (IQR: 1.0-2.0) in subsequent Epochs (p = .04). The percentage of infants receiving at least one transfusion above 50 × 109/L in Epoch I, II, and III was 51.3% (59/115), 17.7% (17/96), and 20.0% (5/25; p < .001). Mortality and bleeding rates did not significantly differ between epochs. DISCUSSION: Implementation of restrictive platelet guidelines led to reduction of the rate and number of platelet transfusions.

Pharmacokinetics of amikacin after intravenous, intra-articular, and combined intravenous and intra-articular administration in healthy neonatal foals.

BACKGROUND: Pharmacokinetics of amikacin administered IV to neonatal foals are described, but little data are available regarding the plasma concentrations contributed by concurrent intra-articular (IA) administration. HYPOTHESIS/OBJECTIVES: Compare the pharmacokinetics of amikacin when the total dose is administered IV compared to being divided between IV and IA routes of administration in neonatal foals and predict the plasma concentrations from various combined IV and IA dosing regimens. ANIMALS: Eight healthy neonatal foals. METHODS: Foals received 3 amikacin treatment protocols: (1) IV-only (25 mg/kg q24h IV), (2) concurrent IV and IA (16.7 mg/kg q24h IV and 8.3 mg/kg q24h into 1 tarsocrural joint), and (3) IA-only (8.3 mg/kg q24h into 1 tarsocrural joint). Protocols were administered for 3 days beginning at 7, 14, and 21 days of age. Plasma concentrations ≥53 µg/mL at 30 minutes were considered therapeutic for isolates with intermediate susceptibility. RESULTS: Foal age was a significant variable. The IV-only protocol met or exceeded the 30-minute plasma concentrations considered therapeutic (mean µg/mL [95% confidence interval, CI]) in 7- to 9-day-old (54.0 [52.2-56.9]), 14- to 16-day-old (58.1 [55.2-61.0]), and 21- to 23-day-old (66.6 [63.7-69.6]) foals. Concurrent IV and IA protocol did not reach the 30-minute concentration considered therapeutic in 7- to 9-day-old foals (46.5 [43.6-49.4]) but did in 14- to 16-day-old (62.9 [60.0-65.8]) and 21-to 23-day-old (62.6 [59.7-65.6]) foals. CONCLUSIONS AND CLINICAL IMPORTANCE: Concurrent IV and IA administration of amikacin produces 30-minute plasma concentrations considered therapeutic in foals 14 to 23 days old, but concentrations observed in younger foals might be below those considered therapeutic for isolates with intermediate susceptibility to amikacin.

Anorectal malformation and Hirschsprung's disease: a cross-sectional multicentre comparison of quality of life and bowel function to a healthy population.

PURPOSE: Children with anorectal malformation (ARM) and Hirschsprung's disease (HD) often experience bowel symptoms into adulthood, despite definitive surgery. This study evaluates the quality of life (QOL) and bowel functional outcome of children treated for ARM and HD in comparison to healthy controls. METHODS: Between December 2020 and February 2023, we recruited patients with ARM and HD aged 3-17 years at four tertiary referral centres, who had primary corrective surgery done >12 months prior. Healthy controls were age-matched and sex-matched. All participants completed the Pediatric Quality of Life Inventory Generic Core Scales 4.0, General Well-Being (GWB) Scale 3.0 and Family Impact (FI) Module 2.0 Questionnaires. Bowel Function Score (BFS) Questionnaires were also administered. We also performed subgroup analysis according to age categories. Appropriate statistical analysis was performed with p<0.05 significance. Ethical approval was obtained. RESULTS: There were 306 participants: 101 ARM, 87 HD, 118 controls. Patients with ARM and HD had significantly worse Core and FI Scores compared with controls overall and in all age categories. In the GWB Scale, only ARM and HD adolescents (13-17 years) had worse scores than controls. ARM and HD had significantly worse BFSs compared with controls overall and in all age categories. There was significant positive correlation between BFS and Core Scores, GWB Scores and FI Scores. CONCLUSION: Patients with ARM and HD had worse QOL than controls. Lower GWB Scores in adolescents suggests targeted interventions are necessary. Bowel function influences QOL, indicating the need for continuous support into adulthood.

Gastrointestinal effects of caffeine in preterm infants: a systematic review and Bayesian meta-analysis.

OBJECTIVE: Caffeine is widely used in preterm infants to prevent or treat apnoea of prematurity. Adverse gastrointestinal effects of caffeine have not been thoroughly researched in preterm infants. With this systematic review and meta-analysis, we aim to summarise the results of trials on the gastrointestinal effects of caffeine in preterm infants. DESIGN: We searched MEDLINE, Web of Science, Scopus and ClinicalTrials.gov up to 21 April 2023. We included randomised controlled trials assessing caffeine versus placebo in preterm neonates and reporting gastrointestinal side effects. Risk of bias was assessed using the Cochrane Risk of Bias tool. A Bayesian meta-analysis was performed to estimate the pooled OR of gastrointestinal side effects. RESULTS: Nine trials involving 2746 preterm infants were analysed. Seven trials assessing necrotising enterocolitis and four trials assessing feeding intolerance in our meta-analysis found no differences between caffeine and placebo (OR=1.007 (95% credible interval 0.021, 5.462), I2=97.4%, and OR=1.266 (95% credible interval 0.064, 28.326), I2=84.8%, respectively). Four trials assessed the outcomes spontaneous intestinal perforation, constipation, gastrointestinal disorder (composite outcome: gastro-oesophageal regurgitation or dilated bowel loops), age at oral feeding and cholestasis syndrome and found no differences between groups. One trial assessed the outcomes gastro-oesophageal symptoms and duration of tube feeding and found that caffeine was associated with a reduced burden of gastro-oesophageal reflux symptoms at 2 weeks (p<0.05), but not at term. CONCLUSIONS: According to this systematic review and meta-analysis, the use of caffeine at usual doses in preterm infants does not seem to be associated with significant gastrointestinal adverse effects.

COMFORTneo scale in preterm infants during live performed music therapy-Difference between close physical contact and hand touch contact.

There is evidence that music therapy combined with physical contact to parents stabilizes the vital signs of hospitalized preterm infants. Yet, there is no evidence for the difference between simple contact by touching the infant in the incubator or cod, or close physical contact during music therapy sessions (MT). Behavioral effects of the various forms of attention toward the infant during therapy need to be elucidated. Our study aimed to quantify the effects of hand touch contact (HTC) and close physical contact (CPC) during live performed MT in preterm infants regardless of gestational age on behavioral state (assessed via COMFORTneo scale) and vital signs. A maximum of ten live music therapy sessions were delivered three to four times a week until hospital discharge to 50 stable infants. Pre-, during- and post-therapy heart rates, respiratory rates, oxygen saturations and COMFORTneo scores were recorded for each session. A total of 486 sessions was performed with 243 sessions using HTC and CPC each. The mean gestational age was 33 + 3 weeks, with 27 (54%) infants being male. We observed lower COMFORTneo scores, heart and respiratory rates and higher oxygen saturation during and after live performed music therapy independent of the kind of physical contact than before therapy. While pre-therapy values were better in the CPC group for all four variables, a higher mean response on COMFORTneo scale and vital signs was observed for HTC (COMFORTneo score -5.5, heart rate -12.4 beats per min., respiratory rate -8.9 breaths per min, oxygen saturation + 1.5%) compared to CPC (COMFORTneo score -4.6, heart rate -9.6 beats per min., respiratory rate -7.0 breaths per min, oxygen saturation + 1.1%). Nonetheless, post-therapy values were better for all four measures in the CPC group. Regression modeling with correction for individual responses within each patient also yielded attenuated effects of MT in the CPC group compared to HTC, likely caused by the improved pre-therapy values. Live performed music therapy benefits preterm infants' vital signs and behavioral state. During CPC with a parent, the absolute therapeutic effect is attenuated but resulting post-therapy values are nonetheless better for both the COMFORTneo scale and vital signs.