Tertiary Neonatal Intensive Care Unit Research Articles

Clinical profile and risk factors associated with Elizabethkingia anophelis infection in neonates born in a tertiary care hospital-a case-control study and outbreak investigation.

The objective of this study was to determine the risk factors associated with Elizabethkingia anophelis infection in neonates admitted to a tertiary care neonatal intensive care unit (NICU). A case-control study was undertaken as part of the outbreak investigation for E. anophelis sepsis in a tertiary care NICU in South India. Thirty-eight neonates with E. anophelis bloodstream infection (BSI) between January 2021 and February 2022 were enrolled as cases, and 38 neonates symptomatic with other BSIs, were selected as controls, and risk factors analysed. The 38 cases were relatively stable neonates, likely to be admitted to level 1 and level 2 NICU, unlike the controls, who were sicker and required level 3 NICU care. Only a third of neonates with Elizabethkingia sepsis had traditional risk factors like central lines, need for respiratory support or perinatal risk factors. Multiple logistic regression analysis revealed that neonates with E. anophelis infection were more likely to be stable and on only enteral feeds, cared in level 1 or 2 of the NICU. This observation, combined with isolation of Elizabethkingia meningosepticum from breast pumps earlier, led us to autoclave the feeding vessels and milk containers along with provision of hot water for cleaning breast pumps, and adoption of general infection control measures, after which incident cases declined. Sanger sequencing of 10 representative isolates obtained from the neonates showed 100% sequence identity to E. anophelis. Infection due to E. anophelis affects relatively stable neonates without traditional risk factors for sepsis. Adherence to asepsis routines and housekeeping protocols helps to prevent the spread of infection.

Early hypophosphataemia and refeeding syndrome in extremely low birthweight babies and outcomes to 2 years of age: secondary cohort analysis from the ProVIDe trial

ObjectiveTo investigate in extremely low birthweight (ELBW; <1000 g) babies the associations between refeeding syndrome (serum phosphate <1.4 mmol·L-1 and serum total calcium>2.8 mmol·L-1) and hypophosphataemia in the first week...

Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) in the neonatal intensive care unit (NICU): an Australian NICU experience

BackgroundPreterm infants often require non-invasive breathing support while their lungs and control of respiration are still developing. Non-invasive neurally adjusted ventilatory assist (NIV-NAVA) is an emerging technology that allows infants to breathe spontaneously while receiving support breaths proportional to their effort. This study describes the first Australian Neonatal Intensive Care Unit (NICU) experience of NIV-NAVA.MethodsRetrospective cohort study of infants admitted to a major tertiary NICU between October 2017 and April 2021 supported with NIV-NAVA. Infants were divided into three groups based on the indication to initiate NIV-NAVA (post-extubation; apnoea; escalation). Successful application of NIV-NAVA was based on the need for re-intubation within 48 h of application.ResultsThere were 169 NIV-NAVA episodes in 122 infants (82 post-extubation; 21 apnoea; 66 escalation). The median (range) gestational age at birth was 25 + 5 weeks (23 + 1 to 43 + 3 weeks) and median (range) birthweight was 963 g (365–4320 g). At NIV-NAVA application, mean (SD) age was 17 days (18.2), and median (range) weight was 850 g (501–4310 g). Infants did not require intubation within 48 h in 145/169 (85.2%) episodes [72/82 (87.8%) extubation; 21/21 (100%) apnoea; 52/66 (78.8%) escalation).ConclusionNIV-NAVA was successfully integrated for the three main indications (escalation; post-extubation; apnoea). Prospective clinical trials are still required to establish its effectiveness versus other modes of non-invasive support.

Neonatal acuity tool-defined staffing ratios in a tertiary Australian neonatal intensive care unit.

There is well-established data linking the adequacy of nurse staffing to patient outcomes. Evidence-based standards for staffing are therefore critical to drive improvements in clinical care. One such evidence-based approach is the use of patient acuity-based tools. The objective of this study is to determine the performance of a neonatal acuity tool in an Australian tertiary neonatal health-care setting, focusing on the classification of patient acuity and nursing:patient staffing ratios compared to current practice. Acuity data were collected in a neonatal intensive care unit (NICU) and special care baby unit (SCBU) over a 10-week period in 2023. Patient data were scored in the 16 domains at two time points (prior to morning and evening nursing shift changeover) for all admitted newborns. For ventilated newborns nursed with a nurse:patient staffing ratio of 1:1, 78% of scores were within the L4-high acuity (score ≥ 26) band, with the remaining scores within the L3-high acuity (18-25) band. For newborns on non-invasive respiratory support in NICU staffed 1:1, the proportion scoring within the L4 acuity band was higher in the nasal high-flow group compared to the nasal continuous positive airway pressure group (P = 0.032), an effect not seen for those nursed 1:2 in NICU or for those on nasal high-flow nursed in SCBU either 1:2 or 1:3. This study of how a neonatal acuity classification system compares with current nurse:patient staffing allocations in an Australian tertiary NICU, suggests refinements in staffing ratios for specific patient groups on respiratory support are possible.

Glucose disturbances in very low-birthweight infants-Results from the prospective LIGHT study.

To describe glucose homeostasis disturbances (dysglycaemia) in very low-birthweight infants (<1500 g) during the admission period and explore associated risk factors. The LIGHT (very low-birthweight infants - glucose and hormonal profile over time) study was a prospective observational cohort study that included 49 very low-birthweight infants admitted to the tertiary neonatal intensive care unit in Umeå, Sweden, during 2016-2019. All glucose concentrations (n = 3515) sampled during the admission period were registered. Hyperglycaemia >10 mmol/L and hypoglycaemia <2.6 mmol/L were registered in 63% and 55% of the infants, respectively. Onset of dysglycaemia occurred almost exclusively in the first postnatal week. Hyperglycaemia followed 15% of corticosteroid doses given; all were preceded by pre-existing hyperglycaemia. Pre-existing hyperglycaemia was found in 66.7% of hyperglycaemic infants who received inotrope treatment. Upon commencement, 72.5% of antimicrobial treatments given were neither preceded nor followed by hyperglycaemia. Dysglycaemia was common in very low-birthweight infants. Daily means of glucose concentrations seemed to follow a postmenstrual age-dependent pattern, decreasing towards term age suggesting a postmenstrual age-dependent developmental mechanism. The primary mechanism causing hyperglycaemia was independent of sepsis, and corticosteroid and inotrope treatments. No hypoglycaemia was registered during ongoing insulin treatment.

Affordable Implementation of a Point-of-Care Ultrasound Program in a Large Tertiary Neonatal Intensive Care Unit to Assess Umbilical Venous Catheter Tips and Aid Central Placement.

This study aimed to implement a point-of-care ultrasound (POCUS) program into a large neonatal intensive care unit (NICU) to enhance care by improving (1) umbilical venous catheter (UVC) tip identification and (2) central placement. A POCUS program was established with core providers who received training from external and internal experts. A prospective study (n = 94) compared the accuracy of UVC identification between neonatology-performed ultrasound (NeoUS) and X-ray relative to a referent of radiology-interpreted ultrasound. Finally, an ultrasound-guided UVC insertion protocol was introduced to rescue noncentral traditionally placed catheters (n = 37). Program implementation trained six providers for a total cost of approximately $10,500 USD. NeoUS was more accurate than X-ray at identifying UVC location (81.9 vs. 60.6%) with improved sensitivity and specificity (80.0 and 84.6 vs. 52.5 and 66.7%, respectively). POCUS guidance was able to rescue 89.2% of catheters that were originally noncentral. POCUS implementation in a large NICU is feasible, affordable, and can improve quality of care. · POCUS implementation is feasible and affordable.. · POCUS is more accurate than X-ray at monitoring UVCs.. · Central UVC placement can be increased with POCUS..

Parent and staff focus groups to address NICU racial inequities: "There's radical optimism in that we're in a different time and we're not doing it alone".

To understand local mechanisms of racial inequities and generate recommendations from community members regarding how to promote racial equity in the Neonatal Intensive Care Unit (NICU). In an urban tertiary care NICU, 4 semi-structured in-person focus groups with follow-up audio diaries were conducted with NICU parents and staff from 2022-2023 with support from interpreters, a psychologist, and a family advocate. Researchers coded transcripts independently and thematic analysis was utilized to generate and refine themes. 16 racially diverse and multidisciplinary staff and parents participated, and six themes emerged from the data. Mechanisms of racial inequities included power dynamics, interpersonal and institutional dehumanization, and societal inequities. Recommendations included redistributing power, transforming space and staff to promote humanism, and mitigating harm through peer support and resource allocation. Focus groups are a promising strategy to identify interventions to address racial inequities. Future research should focus on intervention implementation and evaluation.

Less Invasive Surfactant Administration in Preterm Infants in Tertiary Neonatal Intensive Care Units in Germany: A Survey

Introduction: The European guideline for treatment of respiratory distress syndrome recommends less invasive surfactant administration (LISA) as the preferred method of surfactant administration in spontaneously breathing preterm infants. However, there is limited evidence on practical aspects such as sedation and catheter types, leading to considerable variability between centers. Methods: An anonymous online survey (www.soscisurvey.de) was sent to 164 tertiary neonatal intensive care units (NICUs) in Germany including 43 questions on practical aspects of LISA. Results: Of 122 (74%) participating NICUs, 117 (96%) reported experience with LISA with 82% of those reporting LISA as their preferred method of surfactant administration. Indications for surfactant administration differed widely between NICUs. Most (89%) used FiO2-thresholds only or in combination with other criteria, such as Silverman score/signs of dyspnea (41%) or lung ultrasound findings (3%). Prophylactic surfactant was administered by 42%. Differences in use of LISA in extremely immature infants were reported (e.g., 36% did not perform LISA in infants below 24–26 weeks). Preferred drugs for sedation were (Es-)Ketamine, followed by Propofol and Midazolam. Minimum time interval between subsequent LISA procedures was 4 (2–6) h. Catheters specifically designed for LISA were used by most NICUs (69%). Conclusion: This survey shows that LISA is common practice in German NICUs, but with considerable variability in practical aspects. These data may serve as a guidance for NICUs that have not yet implemented LISA and might be helpful design clinical trials with the aim to standardize and/or optimize LISA.

Written information about retinopathy of prematurity in Aotearoa New Zealand: identification, review and opportunities for improvement.

The aims of this research include adapting a patient information tool for whānau (extended family) Māori needs, identifying and reviewing written information provided for the retinopathy of prematurity eye examination (ROPEE) and identifying improvements to ROPEE written information. ROPEE patient information (printed leaflets, website, app) was obtained from all tertiary neonatal intensive care units in Aotearoa New Zealand (Aotearoa). Information was reviewed using an adapted "20 good-design principles" guide and given a star rating and Flesch-Kincaid readability score to identify acceptability and usability for patients. Seven ROPEE information materials were reviewed and varied in alignment with the adapted good-design principles tool. Based on the adapted good-design principles, opportunities were identified in many aspects of the written information for improvement, including words and language, tone and meaning, content and design. The Flesch-Kincaid grade level reading scores ranged from 12-22 years reading age. Written information also did not use te reo Māori (Aotearoa Indigenous language) or extensively use Māori imagery. Opportunities exist to improve ROPEE whānau information, including making content more readable, understandable and visually appealing. Optimising the clinical information on ROPEE nationally for Aotearoa will support whānau decision making, and aligning written information with Māori (Indigenous peoples of Aotearoa) is a priority.

Exploring Current Practices, Challenges, and Innovations in the Nutrition and Feeding of Neonates, Including the Use of Human Milk, Fortifiers, and Formula: A Clinical Study

ABSTRACT Background: Neonatal nutrition plays a crucial role in the growth and development of infants, particularly in the neonatal intensive care unit (NICU) where specialized care is essential. This study aims to explore current practices, challenges, and innovations in the nutrition and feeding of neonates, focusing on the utilization of human milk, fortifiers, and formula. Materials and Methods: A retrospective clinical study was conducted at a tertiary care NICU over a period of two years. Data were collected from medical records of neonates admitted to the unit. Information regarding feeding practices, types of milk (human milk, fortified human milk, or formula), fortification protocols, and associated clinical outcomes were analyzed. Results: A total of 150 neonates were included in the study. The majority (85%) received some form of human milk during their NICU stay, with 60% exclusively receiving human milk. Among those receiving human milk, 40% required fortification with a human milk fortifier due to inadequate growth parameters. Formula supplementation was necessary in 25% of cases due to maternal lactation insufficiency or medical contraindications to human milk. The mean duration of parenteral nutrition was 10 days, with a median time to full enteral feeds of 14 days. Infants receiving exclusively human milk demonstrated a lower incidence of necrotizing enterocolitis (NEC) compared to those receiving formula (5% vs. 12%, P &lt; 0.05). Conclusion: Human milk remains the preferred source of nutrition for neonates in the NICU setting, associated with lower rates of NEC and improved clinical outcomes. However, fortification with human milk fortifiers or supplementation with formula is often necessary to meet the nutritional requirements of preterm infants. Further research is needed to optimize fortification protocols and improve long-term outcomes in this vulnerable population.

Randomised crossover study on pulse oximeter readings from different sensors in very preterm infants

ObjectiveIn extremely preterm infants, different target ranges for pulse oximeter saturation (SpO2) may affect mortality and morbidity. Thus, the impact of technical changes potentially affecting measurements should be assessed. We...

Early and exclusive enteral nutrition in infants born very preterm

ObjectiveTo characterise the effects of early and exclusive enteral nutrition with either maternal or donor milk in infants born very preterm (280/7–326/7 weeks of gestation).DesignParallel-group, unmasked randomised controlled trial.SettingRegional, tertiary...

Mortality and extrauterine growth restriction of necrotizing enterocolitis in very preterm infants with heart disease: a multi-center cohort study.

Congenital heart disease (CHD) and patent ductus arteriosus (PDA) are risk factors of necrotizing enterocolitis (NEC) in infants. However, it is unclear whether the prognosis of NEC is different between very preterm infants (VPIs) with and without heart diseases. This was an observational cohort study that enrolled VPIs (born between 24+0 and 31+6weeks) admitted to 79 tertiary neonatal intensive care units (NICU) in the Chinese Neonatal Network (CHNN) between 2019 and 2021. The exposure was CHD or isolated PDA, and VPIs with NEC were divided into three groups: complicated with CHD, with isolated PDA, and without heart diseases. The primary outcomes were NEC-related adverse outcomes (death or extrauterine growth restriction (EUGR)). Logistic regression models were used to adjust potential confounders and calculate the odds ratios (ORs) and 95% confidential intervals (CIs) for each outcome. A total of 1335 VPIs with NEC were enrolled in this study, including 65 VPIs with CHD and 406 VPIs with isolated PDA. The VPIs with heart diseases had smaller gestational ages and lower body weights at birth, more antenatal steroids use, and requiring inotrope prior to the onset of NEC. While suffering from NEC, there was no significant increased risks in NEC-related death in VPIs with either CHD (adjusted OR [aOR]: 1.10; 95% CI: 0.41-2.50) or isolated PDA (aOR: 1.25; 95% CI 0.82-1.87), and increased risks in EUGR were identified in either survival VPIs with CHD (aOR: 2.35; 95% CI: 1.31-4.20) or isolated PDA (aOR: 1.53; 95% CI: 1.16-2.01) in survivors. The composite outcome (death or EUGR) was also more often observed in VPIs with either CHD (aOR: 2.07; 95% confidence interval [CI]: 1.20-3.60) or isolated PDA (aOR: 1.51; 95% CI: 1.17-1.94) than that without heart diseases. VPIs with either CHD or isolated PDA were associated with significantly prolonged duration of fasting, extended time to achieve full enteral feeding, and longer ventilation duration and hospitalization duration. Similar characteristics were also seen in VPIs with isolated PDA, with the exception that VPIs with CHD are more likely to undergo surgical intervention and maintain a prolonged fast after NEC. Conclusion: In VPIs with NEC, CHD and isolated PDA are associated with an increased risk in worse outcomes. We recommend that VPIs with cardiac NEC be managed with aggressive treatment and nutrition strategies to prevent EUGR. What is Known: • CHD and PDA are risk factors for NEC in infants, which can lead to adverse outcomes such as death and EUGR. • NEC in infants with heart disease differs clinically from that in infants without heart disease and should be recognized as a separate disease process. What is New: • CHD and isolated PDA are associated with increased risks of EUGR in VPIs with NEC. • Risk factors associated with VPIs with cardiac NEC suggested these patients should be managed with aggressive treatment and nutrition strategies to adverse outcomes.

A Decade of Invasive Candida Infection in Neonates: A Retrospective Study at a Tertiary Neonatal Intensive Care Unit in Thailand (2008–2018)

A Decade of Invasive Candida Infection in Neonates: A Retrospective Study at a Tertiary Neonatal Intensive Care Unit in Thailand (2008–2018)

Neonatal Endotracheal Intubation: Comparison of Existing Formulae for Accuracy

Background There are several formulae proposed to calculate the ideal depth of insertion of the endotracheal tube (ETT) in neonates, none of which are universally accurate. Our objective is to identify the most accurate of these formulae and to determine the most suitable formula for babies weighing less than 1 kg. Methods This is a retro-prospective observational study conducted in a tertiary neonatal intensive care unit. All intubated babies, irrespective of their gestational age, were included in this study. Those with congenital airway anomalies or syndromes with involvement of the upper airway and those who required short-term ventilation restricted to the theatre complex were excluded. The ideal insertion depth was determined via a chest X-ray (CXR) with the ETT projecting between thoracic vertebrae 2 and 3. Predictions from eight formulae investigated in the Indian population were analysed using paired Wilcoxon tests and Bland–Altman plots. Results The sample size was 83, of which 16 weighed less than 1 kg. Neither weight-based nor naso-tragal length (NTL)-based formulae were universally accurate in the prediction of the ideal depth of insertion, and using either of the formulae resulted in a high rate of malpositioning. Amongst the NTL-based formulae, Tatwavedi and Singh’s adjustments worked better than the original. Conclusion The currently available formulae remain inaccurate in the prediction of the ideal length of insertion of ETT, more so in babies less than 1 kg in our study population.

Quantitative Lung Ultrasonography to Guide Surfactant Therapy in Neonates Born Late Preterm and Later

Surfactant administration may be needed in late preterm through full-term neonates, but the pathophysiology of their respiratory failure can be different from that of early preterm neonates. The lung ultrasonography score (LUS) is accurate to guide surfactant replacement in early preterm neonates, but to our knowledge, it has not yet been studied in the late preterm through full-term neonatal population. To assess whether LUS is equally accurate to predict surfactant need in late preterm through full-term neonates as in early preterm neonates. This prospective, international, multicenter diagnostic study was performed between December 2022 and November 2023 in tertiary academic neonatal intensive care units in France, Italy, Spain, and the US. Late preterm through full-term neonates (≥34 weeks' gestation) with respiratory failure early after birth were enrolled. Point-of-care lung ultrasonography to calculate the neonatal LUS (range, 0-18, with higher scores indicating worse aeration), which was registered in dedicated research databases and unavailable for clinical decision-making. The main outcomes were the area under the curve (AUC) in receiver operating characteristic analysis and derived accuracy variables, considering LUS as a replacement for other tests (ie, highest global accuracy) and as a triage test (ie, highest sensitivity). Sample size was calculated to assess noninferiority of LUS to predict surfactant need in the study population compared with neonates born more prematurely. Correlations of LUS with the ratio of hemoglobin oxygen saturation as measured by pulse oximetry (SpO2) to fraction of inspired oxygen (FiO2) and with the oxygen saturation index (OSI) were assessed. A total of 157 neonates (96 [61.1%] male) were enrolled and underwent lung ultrasonography at a median of 3 hours (IQR, 2-7 hours) of life; 32 (20.4%) needed surfactant administration (pretest probability, 20%). The AUC was 0.87 (95% CI, 0.81-0.92). The highest global accuracy and sensitivity were reached for LUS values higher than 8 or 4 or lower, respectively. Subgroup analysis gave similar diagnostic accuracy in neonates born late preterm (AUC, 0.89; 95% CI, 0.81-0.97; n = 111) and early term and later (AUC, 0.84; 95% CI, 0.73-0.96; n = 46). After adjusting for gestational age, LUS was significantly correlated with SpO2:FiO2 (adjusted β, -10.4; 95% CI, -14.0 to -6.7; P < .001) and OSI (adjusted β, 0.2; 95% CI, 0.1-0.3; P < .001). In this diagnostic study of late preterm through full-term neonates with respiratory failure early after birth, LUS accuracy to predict surfactant need was not inferior to that observed in earlier preterm neonates. An LUS higher than 8 was associated with highest global accuracy (replacement test), suggesting that it can be used to guide surfactant administration. An LUS value of 4 or lower was associated with the highest sensitivity (triage test), suggesting it is unlikely for this population to need surfactant.

Intervention Bundle for Optimization of Procedural Sedation for Newborns Undergoing Magnetic Resonance Imaging: A Single-Center Quality Improvement Project in Qatar

Introduction: Magnetic resonance imaging (MRI) is a common procedure in tertiary care neonatal intensive care units (NICUs). MRIs aid in detailing structural anatomy and are increasingly utilized for prognostication. Keeping babies calm and motion-free in the MRI suite is challenging, and various approaches have been adopted to obtain the best image quality. We share our experience of intervention bundle for procedural sedation with the novel use of buccal midazolam in our NICU for babies undergoing MRI. Methods: This single-center quality improvement project comprised two epochs. Epoch 1 from April 2018 to December 2020 provided baseline data regarding sedation use and helped identify causes for suboptimal images and the adverse event rate. Following the implementation of an interventional bundle comprising specific midazolam dose recommendations tailored to background risk factors and streamlining the procedural sedation process, similar comparative data were collected in epoch 2 (May 2021 to December 2022) after a washout period. Results: Of 424 patients, 238 and 108 had MRI done under either procedural sedation protocol or feed and wrap technique in epoch 1 and 2, respectively. After excluding babies whose MRIs were performed under sedative infusions, 30 (13%) babies had adverse events in epoch 1, while only 8 (7%) events occurred in epoch 2. There was also a 37% improvement in the documentation of procedural sedation between the two epochs. Conclusion: Procedural sedation with buccal midazolam under neonatologist supervision is safe, efficient, and effective in babies undergoing MRI in this single-center study. More extensive studies may be warranted to assess the suitability of this sedation modality for broader use.

Umbilical arterial catheter duration as risk factor for Bell's Stage III necrotizing enterocolitis in preterm neonates.

To explore risk factors for Stage-III necrotizing enterocolitis (NEC-III) in preterm neonates. This was a retrospective case-control study of neonates born <33 weeks gestational age (GA) who were admitted to a tertiary neonatal intensive care unit, between 2015 and 2018. NEC-III cases were compared with Stage-II NEC (NEC-II) and non-NEC controls. Two to four non-NEC controls were matched by GA ± 1 week and date of birth ± 3 months, to one NEC-III case. Univariate and multivariate analyses were used to examine risk factors for NEC-III. Of 1360 neonates born <33 weeks, 71 (5.2%) had NEC-II and above, with 46% being NEC-III. Mean age of onset of NEC-III was 13.7 days versus 23.9 days for NEC-II (p = 0.01). Neonates with NEC-III were of lower GA (NEC-III 25.4 weeks, NEC-II 27.3 weeks, and non-NEC 26 weeks; p = 0.0008) and had higher Score for Neonatal Acute Physiology Perinatal Extension-II scores (NEC-III 47.5, NEC-II 28.4 and non-NEC 37, p = 0.003). Multivariate analysis showed duration of umbilical arterial catheter (UAC) >5 days was significantly associated with the development of NEC-III with adjusted odds ratio (AOR) 3.8; 95% confidence interval (CI) (1.05-13.66) for NEC-III versus non-NEC and AOR 5.57; 95% CI (1.65-18.73), p = 0.006 for NEC-III versus NEC-II. Rupture of membranes (ROM) >1 week was associated with NEC-III (AOR 6.93; 95% CI [1.56-30.69] vs. non-NEC and AOR 11.74; 95% CI [1.14-120.34] vs. NEC-II). The increased association of NEC-III with duration of UAC and ROM could be further examined in prospective studies, and an upper limit for UAC duration could be considered in NEC prevention bundles.

Whole-Body Hypothermia vs Targeted Normothermia for Neonates With Mild Encephalopathy

Although whole-body hypothermia is widely used after mild neonatal hypoxic-ischemic encephalopathy (HIE), safety and efficacy have not been evaluated in randomized clinical trials (RCTs), to our knowledge. To examine the effect of 48 and 72 hours of whole-body hypothermia after mild HIE on cerebral magnetic resonance (MR) biomarkers. This open-label, 3-arm RCT was conducted between October 31, 2019, and April 28, 2023, with masked outcome analysis. Participants were neonates at 6 tertiary neonatal intensive care units in the UK and Italy born at or after 36 weeks' gestation with severe birth acidosis, requiring continued resuscitation, or with an Apgar score less than 6 at 10 minutes after birth and with evidence of mild HIE on modified Sarnat staging. Statistical analysis was per intention to treat. Random allocation to 1 of 3 groups (1:1:1) based on age: neonates younger than 6 hours were randomized to normothermia or 72-hour hypothermia (33.5 °C), and those 6 hours or older and already receiving whole-body hypothermia were randomized to rewarming after 48 or 72 hours of hypothermia. Thalamic N-acetyl aspartate (NAA) concentration (mmol/kg wet weight), assessed by cerebral MR imaging and thalamic spectroscopy between 4 and 7 days after birth using harmonized sequences. Of 225 eligible neonates, 101 were recruited (54 males [53.5%]); 48 (47.5%) were younger than 6 hours and 53 (52.5%) were 6 hours or older at randomization. Mean (SD) gestational age and birth weight were 39.5 (1.1) weeks and 3378 (380) grams in the normothermia group (n = 34), 38.7 (0.5) weeks and 3017 (338) grams in the 48-hour hypothermia group (n = 31), and 39.0 (1.1) weeks and 3293 (252) grams in the 72-hour hypothermia group (n = 36). More neonates in the 48-hour (14 of 31 [45.2%]) and 72-hour (13 of 36 [36.1%]) groups required intubation at birth than in the normothermic group (3 of 34 [8.8%]). Ninety-nine neonates (98.0%) had MR imaging data and 87 (86.1%), NAA data. Injury scores on conventional MR biomarkers were similar across groups. The mean (SD) NAA level in the normothermia group was 10.98 (0.92) mmol/kg wet weight vs 8.36 (1.23) mmol/kg wet weight (mean difference [MD], -2.62 [95% CI, -3.34 to -1.89] mmol/kg wet weight) in the 48-hour and 9.02 (1.79) mmol/kg wet weight (MD, -1.96 [95% CI, -2.66 to -1.26] mmol/kg wet weight) in the 72-hour hypothermia group. Seizures occurred beyond 6 hours after birth in 4 neonates: 1 (2.9%) in the normothermia group, 1 (3.2%) in the 48-hour hypothermia group, and 2 (5.6%) in the 72-hour hypothermia group. In this pilot RCT, whole-body hypothermia did not improve cerebral MR biomarkers after mild HIE, although neonates in the hypothermia groups were sicker at baseline. Safety and efficacy of whole-body hypothermia should be evaluated in RCTs. ClinicalTrials.gov Identifier: NCT03409770.

The effect of developmental care on the length of hospital stay and family centered care practice for very low birth weight infants in neonatal intensive care units: A cluster randomized controlled trial

BackgroundDespite previous studies suggesting that developmental care can provide benign stimulation to promote neural development of newborns, more evidence is needed regarding the other clinical benefits of developmental care. ObjectiveTo evaluate the effect of implementing developmental care on the length of hospital stay, the improvement of care practice in neonatal intensive care units, as well as the short-term outcome of very low birth weight infants. DesignCluster-randomized controlled trial. Setting(s) and participantsFrom March 1, 2021 to March 1, 2022, 1400 very low birth weight infants were recruited from 14 tertiary neonatal intensive care units in China. MethodsWe assigned 14 neonatal intensive care units to either developmental care or standard care. The length of hospital stay of the infants was the primary outcome analyzed at the individual level. Secondary outcomes were family centered care practice including parental involvement, the skin to skin care, exclusive breast milk, oral immune therapy and breastfeeding. The environmental management (noise and light) and the short-term outcomes were also evaluated. ResultsThe length of hospital stay for the developmental care group was 65 % as long as that for the control group (HR: 0.65, 95 % CI, 0.451–0936, p = 0.021). After controlling the covariables, the adjusted HR = 0.755 (95 % CI, 0.515 to 1.107, p = 0.150). When compared to the control group, the developmental care group had greater access to SSC, with 22 infants (3.8 %) in the developmental care group compared to 13 infants (1.7 %) in the standard care group (p = 0.013). A greater proportion of infants in the developmental care group were fed at the breast, than those in the standard care group (136 [23.6 %] vs 9 [1.1 %]; p = 0.029). Compared to the control group, exclusively breast milk was significantly more favorable in the developmental care group (435 [75.6 %] vs 114 [15.0 %]; p = 0.001). The difference remained significant even after adjusting for covariates. However, the rate of oral immune therapy and parental involvement was similar in the two groups. The average noise and light levels in the developmental care group were significantly lower than those in the standard care group. After adjusting for confounders, the difference remained significant. There were no significant differences among groups in the mortality and major morbidity. ConclusionsDevelopmental care might have developed an accumulated effect over time on the length of hospital stay among very low birth weight infants. The implementation of developmental care can greatly improve family centered care practices and the neonatal intensive care unit environment. RegistrationClinicalTrials.govNCT05166720. Registration date: 1 March, 2021.