Neonatal hypoglycaemia.

Low blood concentrations of glucose (hypoglycaemia) soon after birth are common because of the delayed metabolic transition from maternal to endogenous neonatal sources of glucose. Because glucose is the main energy source for the brain, severe hypoglycaemia can cause neuroglycopenia (inadequate supply of glucose to the brain) and, if severe, permanent brain injury. Routine screening of infants at risk and treatment when hypoglycaemia is detected are therefore widely recommended. Robust evidence to support most aspects of management is lacking, however, including the appropriate threshold for diagnosis and optimal monitoring. Treatment is usually initially more feeding, with buccal dextrose gel, followed by intravenous dextrose. In infants at risk, developmental outcomes after mild hypoglycaemia seem to be worse than in those who do not develop hypoglycaemia, but the reasons for these observations are uncertain. Here, the current understanding of the pathophysiology of neonatal hypoglycaemia and recent evidence regarding its diagnosis, management, and outcomes are reviewed. Recommendations are made for further research priorities.

Current management of surgical neonates: is it optimal or do we need to improve? A national survey of the Italian Society of Neonatology.

PURPOSE: Few guidelines exist for the perioperative management (PM) of neonates with surgical conditions (SC). This study examined the current neonatal PM in Italy. METHODS: We invited 51 neonatal intensive care units with pediatric surgery in their institution to participate in a web-based survey. The themes included (1) the involvement of the neonatologist during the PM; (2) the spread of bedside surgery (BS); (3) the critical issues concerning the neonatal PM in operating rooms (OR) and the actions aimed at improving the PM. RESULTS: Response rate was 82.4%. The neonatologist is involved during the intraoperative management in 42.9% of the responding centers (RC) and only when the surgery is performed at the patient's bedside in 50.0% of RCs. BS is reserved for extremely preterm (62.5%) or clinically unstable (57.5%) infants, and the main barrier to its implementation is the surgical-anesthesiology team's preference to perform surgery in a standard OR (77.5%). Care protocols for specific SC are available only in 42.9% of RCs. CONCLUSION: Some critical issues emerged from this survey: the neonatologist involvement in PM, the spread of BS, and the availability of specific care protocols need to be implemented to optimize the care of this fragile category of patients.

A Proof-of-Concept Model for Implementing a "Smart-NICU" to Improve Infant Mortality.

Low- and middle-income countries face limited critical care capacity due to constraints in staffing, resources, and technology. "Smart ICUs" that integrate telehealth to augment care delivery, communication, and data integration have the potential to bridge these gaps and reduce preventable morbidity and mortality. While their efficacy has been well validated in adult populations, applications of Smart-ICU services in the neonatal population have not been studied. Neonatal intensive care units (NICUs) in India using a common Smart-NICU platform, developed by CloudPhysician, utilize a hub-and-spokes framework along with locally designed technology to facilitate remote patient care in collaboration with local health systems. In this article, we investigate the operational characteristics and performance outcomes for Smart-NICU deployment from the 18 NICUs and 214 beds deployed to date. These findings highlight the potential impact of Smart-NICUs and establish generalizable principles for implementation in low-resource settings.

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.

Syndecan-1 Level, a Marker of Endothelial Glycocalyx Degradation, Is Associated With Fetal Exposure to Chorioamnionitis and Is a Potential Biomarker for Early-Onset Neonatal Sepsis.

The goal of this investigation was to identify the association between Syndecan-1 (S1) serum levels in preterm newborns exposed to chorioamnionitis (CA) in utero and the potential of S1 as a biomarker of early-onset neonatal sepsis. A cohort of preterm newborns born <33 weeks gestational age was recruited. Within 48 hours of birth, 0.5 mL of blood was drawn to obtain S1 levels, measured via ELISA. Placentas were examined and classified as having (1) no CA, (2) CA without umbilical cord involvement, or (3) CA with inflammation of the umbilical cord (funisitis). S1 levels were compared between preterm newborns without exposure to CA verus newborns with exposure to CA (including with and without funisitis). Preterm newborns exposed to CA were found to have significantly elevated S1 levels compared to those unexposed. Although S1 levels could not differentiate fetal exposure to CA from exposure to CA with funisitis, the combined CA groups had significantly higher S1 levels compared to those not exposed to CA. S1 level has the potential to become a clinically useful biomarker that could assist in the management of mothers and preterm newborns with CA and funisitis. Furthermore, S1 level could aid in the diagnosis and treatment of early-onset neonatal sepsis.

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.

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.

Parent screening questionnaires to detect cognitive and language delay at 2 years in high-risk infants: an analysis from the Victorian Infant Collaborative Study 2016-2017 cohort.

OBJECTIVE: To determine the accuracy of two developmental screening questionnaires to detect cognitive or language delay, defined using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III), in children born extremely preterm (EP: <28 weeks' gestation) or extremely low birth weight (ELBW: <1000 g). DESIGN: Prospective cohort study. SETTING: State of Victoria, Australia. PATIENTS: 211 infants born EP/ELBW assessed at 2 years' corrected age (mean 2.2, SD 0.2). MAIN OUTCOME MEASURES: Cognitive and language delay (<-1 SD) on the Bayley-III. The screening questionnaires were the Parent Report of Children's Abilities-Revised (PARCA-R) and the Ages & Stages Questionnaires Third Edition (ASQ-3). RESULTS: The PARCA-R performed better than the ASQ-3, but neither questionnaire had substantial agreement with the Bayley-III to detect cognitive delay; kappa (95% CI): PARCA-R 0.43 (0.23, 0.63); ASQ-3 0.15 (-0.05, 0.35); sensitivity (95% CI): PARCA-R 70% (53%, 84%) ASQ-3 62% (47%, 76%); specificity (95% CI): PARCA-R 73% (60%, 84%) ASQ-3 53% (38%, 68%). When both tools were used in combination (below cut-off on at least one assessment), sensitivity increased to 78% (60%, 91%) but specificity fell to 45% (29%, 62%). Similar trends were noted for language delay on the Bayley-III, although kappa values were better than for cognitive delay. CONCLUSIONS: Neither screening questionnaire identified cognitive delay well, but both were better at identifying language delay. The PARCA-R detects delay on the Bayley-III more accurately than the ASQ-3. Sensitivity for detecting delay is greatest when the PARCA-R and ASQ-3 were used in combination, but resulted in lower specificity.

Are toddlers with neurosensory impairment more difficult to follow up? A secondary analysis of the hPOD follow-up study.

OBJECTIVE: To describe strategies used to maximise follow-up after a neonatal randomised trial, how these differed for families of different ethnicity, socioeconomic status and urban versus rural residence and investigate relationships between the difficulty of follow-up and rate of neurosensory impairment. METHOD: hPOD was a multicentre randomised trial assessing oral dextrose gel prophylaxis for neonatal hypoglycaemia. Follow-up at 2 years was conducted from 2017 to 2021. We analysed all recorded contacts between the research team and participants' families. Neurosensory impairment was defined as blindness, deafness, cerebral palsy, developmental delay or executive function impairment. RESULTS: Of 1321 eligible participants, 1197 were assessed (91%) and 236/1194 (19.8%) had neurosensory impairment. Participants received a median of five contacts from the research team (range 1-23). Those from more deprived areas and specific ethnicities received more contacts, particularly home tracking visits and home assessments. Impairment was more common among participants receiving more contacts (relative risk 1.81, 95% CI 1.34 to 2.44 for ≥7 contacts vs <7 contacts), and among those assessed after the intended age (76/318, 23.9% if >25 months vs 160/876, 18.3% if ≤25 months). CONCLUSIONS: Varied contact strategies and long timeframes are required to achieve a high follow-up rate. Without these, the sociodemographics of children assessed would not have been representative of the entire cohort, and the rate of neurosensory impairment would have been underestimated. To maximise follow-up after randomised trials, substantial effort and resources are needed to ensure that data are useful for clinical decision-making.

Maternal and infant outcomes in women with sickle cell disease: a matched cohort study.

OBJECTIVE: Women with sickle cell disease (SCD) have adverse maternal and infant outcomes. Our aim was to determine whether the outcomes of SCD mothers and their infants differed from African or Caribbean women not affected by SCD and whether there were differences between SCD individuals with the haemoglobin SS (HbSS) or haemoglobin SC (HbSC) genotypes. Furthermore, we wished to determine if any differences related to deprivation. DESIGN: A matched cohort study. SETTING: Tertiary perinatal centre in London PATIENTS: 4964 African or Caribbean women without SCD and 148 with SCD. MAIN OUTCOME MEASURES: Mode of delivery, maternal exchange transfusion, birthweight, neonatal unit admission, neonatal death and deprivation indices RESULTS: SCD women were more likely to be delivered by caesarean section (p<0.001) and had babies of lower birthweight (p<0.001). Their infants were no more likely to be admitted to neonatal intensive care unit or suffer a neonatal death. There were no significant differences between the SCD women and those without SCD in their deprivation index or deprivation decile. The women with the HbSS genotype compared to those with the HbSC genotype were more anaemic (p<0.02), required more exchange transfusions (p<0.001) and were more likely to be delivered by caesarean section (p=0.008). The infant outcomes did not differ significantly between the genotypes. CONCLUSIONS: Although, the SCD women, particularly those with the HbSS genotype, had greater morbidity, infant morbidity, and mortality was similar in mothers with the HbSS or HbSC genotypes and those without SCD.

Use of neonatal lung ultrasound in European neonatal units: a survey by the European Society of Paediatric Research.

OBJECTIVE: Regarding the use of lung ultrasound (LU) in neonatal intensive care units (NICUs) across Europe, to assess how widely it is used, for what indications and how its implementation might be improved. DESIGN AND INTERVENTION: International online survey. RESULTS: Replies were received from 560 NICUs in 24 countries between January and May 2023. LU uptake varied considerably (20%-98% of NICUs) between countries. In 428 units (76%), LU was used for clinical indications, while 34 units (6%) only used it for research purposes. One-third of units had <2 years of experience, and only 71 units (13%) had >5 years of experience. LU was mainly performed by neonatologists. LU was most frequently used to diagnose respiratory diseases (68%), to evaluate an infant experiencing acute clinical deterioration (53%) and to guide surfactant treatment (39%). The main pathologies diagnosed by LU were pleural effusion, pneumothorax, transient tachypnoea of the newborn and respiratory distress syndrome. The main barriers for implementation were lack of experience with technical aspects and/or image interpretation. Most units indicated that specific courses and an international guideline on neonatal LU could promote uptake of this technique. CONCLUSIONS: Although LU has been adopted in neonatal care in most European countries, the uptake is highly variable. The main indications are diagnosis of lung disease, evaluation of acute clinical deterioration and guidance of surfactant. Implementation may be improved by developing courses and publishing an international guideline.

Can transcutaneous bilirubinometry safely be used to monitor rebound hyperbilirubinaemia after phototherapy in neonates ≥35 weeks' gestation? A prospective, comparative study.

INTRODUCTION: There is insufficient evidence to determine if non-invasive transcutaneous bilirubin (TcB) measurement can replace serum bilirubin (SBR) in assessing rebound hyperbilirubinaemia after phototherapy. OBJECTIVE: To investigate if TcB can safely guide management of neonates after phototherapy. SUBJECTS: 100 well neonates ≥35 weeks' gestation who had received inpatient phototherapy. METHOD: Measurement of both helix (manufacturer's recommendation) and earlobe TcB coincidentally with routine SBR 12 hours after cessation of phototherapy. All mothers gave written informed consent. RESULTS: Gestation ranged from 35+0 to 41+5 (median 37+6) weeks; birth weight 2018-4566 (median 3230) g; age 55-222 (median 109) hours at testing. 86% neonates were Caucasian. Outcomes determined by SBR included restarting phototherapy (n=0), repeat SBR next day (n=29), no further routine follow-up (n=71).TcB and SBR measurements were unpredictably inconsistent. Helix TcB tended to underestimate SBR (mean difference 50.1 (95% CI 113.9 to -13.7) µmols/L); for earlobe TcB mean difference was -13.4 (95% CI 46.3 to -73.2) µmols/L (overestimate), but bias was greater over the range of mean differences. No demographic factor predicted consistency between TcB and SBR. TcB was 25% (helix) and 76% (earlobe) sensitive in predicting repeat phototherapy and/or repeat SBR; specificities were 92% and 58%, respectively. Adding a safety margin of 120 µmols/L to helix TcB value could have safely avoided invasive SBR measurement in 50/98 (51%) babies. CONCLUSIONS: Consistency between TcB and rebound SBR is unpredictable in well neonates >35 weeks' gestation but adopting a wide safety margin has potential to reduce blood sampling. Recommencement of phototherapy is uncommon in this population.

Mortality in the neonatal intensive care setting: Do benchmarks tell the whole story?

AIM: Australian neonatal mortality data are collected and shared within collaborative networks. Individual unit outcomes are benchmarked between units and presented in quarterly or yearly reports. Low mortality is commonly interpreted as optimal performance. However, current collected data do not differentiate between death due to severe illness and death following treatment limitation. This study aims to explore the physiological condition immediately before death, and the proportion of deaths attributed to treatment limitation. METHODS: This retrospective single centre study of 100 consecutive deaths classified the physiological condition 12 h prior to death as stable or unstable using a clinical illness score based upon pH, oxygen saturation index, medications and blood product use. Documented discussions regarding expected outcomes and goals of management were reviewed for agreed upon treatment limitations and analysed against physiological stability. RESULTS: Causes of death were sepsis (n = 24), congenital anomalies (n = 20), extreme prematurity (n = 19), hypoxic ischaemic encephalopathy (n = 18), intraventricular haemorrhage (n = 11) and other (n = 8). Forty-eight infants were physiologically stable at 12 h before death. In infants classified as physiologically stable, 90% of deaths were in a scenario where palliative care was discussed and intensive care treatment was ceased. These deaths accounted for 43% of total mortality in our unit. CONCLUSION: A large portion of mortality in our unit could be attributed to treatment limitations in physiologically stable infants with high risk of neurodevelopmental impairment. Our study emphasises the need to consider the physiological status around time of death for optimal benchmarking of mortality between neonatal units.