Best evidence summary of sleep protection in premature infants in the neonatal intensive care unit: a narrative review.

Background and Objective: Sleep influences the interaction between infants and their environment, as well as the achievement of crucial milestones in motor and language development. This is particularly significant for preterm infants in vulnerable positions. However, prematurely born infants in the neonatal intensive care unit (NICU) are exposed to various stimuli such as noise and light, which disrupt their normal sleep patterns. This study assesses and consolidates the existing evidence on non-pharmacological strategies for protecting and promoting sleep in preterm infants. By providing an evidence-based data repository, it offers a valuable reference for clinical interventions. Methods: We conducted computer-based searches using various databases and resources, including UpToDate, BMJ Best Practice, Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), National Guideline Clearinghouse (NGC), Registered Nurses Association of Ontario (RNAO), Joanna Briggs Institute (JBI), World Health Organization (WHO), Cochrane Library, Web of Science, PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data, and China Biology Medicine disc (CBM). The search period spanned from January 2014 to May 2024. Key Content and Findings: We have included a total of 22 articles in our review, comprising two guidelines, 11 systematic reviews, 1 evidence summary, 1 technical report, 2 practice recommendations, and 5 randomized controlled trials. The evidence was synthesized from eight domains: sleep team construction, risk factor assessment, sleep assessment tools, positional management, noise control, light management, sensory stimulation, and hospital-home transition sleep management, resulting in 27 pieces of evidence. Conclusions: This study summarizes the optimal evidence for the management of sleep in premature infants, providing empirical support for standardizing the management of sleep in premature infants. It is recommended that healthcare professionals judiciously apply the best evidence while considering the clinical context, thus promoting safe sleep for premature infants.

Association of Shift-Level Organizational Factors with Nosocomial Infection in the Neonatal Intensive Care Unit.

Objective: To evaluate the association between shift-level organizational data (unit occupancy, nursing overtime ratios [OTRs], and nursing provision ratios [NPRs]) with nosocomial infection (NI) among infants born very preterm in the neonatal intensive care unit (NICU). Study design: This was a multicenter, retrospective cohort study, including 1921 infants 230/7-326/7 weeks of gestation admitted to 3 tertiary-level NICUs in Quebec between 2014 and 2018. Patient characteristics and outcomes (NIs) were obtained from the Canadian Neonatal Network database and linked to administrative data. For each shift, unit occupancy (occupied/total beds), OTR (nursing overtime hours/total nursing hours), and NPR (number of actual/number of recommended nurses) were calculated. Mixed-effect logistic regression models were used to calculate aOR for the association of organizational factors (mean over 3 days) with the risk of NI on the following day for each infant. Results: Rate of NI was 11.5% (220/1921). Overall, median occupancy was 88.7% [IQR 81.0-94.6], OTR 4.4% [IQR 1.5-7.6], and NPR 101.1% [IQR 85.5-125.1]. A greater 3-day mean OTR was associated with greater odds of NI (aOR 1.08, 95% CI 1.02-1.15), a greater 3-day mean NPR was associated lower odds of NI (aOR 0.96, 95% CI 0.95-0.98), and occupancy was not associated with NI (aOR, 0.99, 95% CI 0.96-1.02). These findings were consistent across multiple sensitivity analyses. Conclusions: Nursing overtime and nursing provision are associated with the adjusted odds of NI among infants born very preterm in the NICU. Further interventional research is needed to infer causality.

Provision of bubble continuous positive airway pressure for the stabilisation of extremely and very preterm infants after birth: A single-centre experience.

AIM: To describe the effect of resuscitation with bubble CPAP (bCPAP) versus T-piece device at birth on early clinical parameters and hospital outcomes in infants born <32 weeks gestation. METHODS: This is a single-centre pre- and post-implementation study comparing outcomes in two epochs. In epoch 1 (1 July 2013-31 December 2014), infants were managed with non-humidified gas using Neopuff® T-piece devices to support breathing after birth. In epoch 2 (1 March 2020-31 December 2021), routine application of bCPAP with humidified gas was introduced at birth. RESULTS: Three hundred fifty-seven patients were included (176 epoch 1, 181 epoch 2). The mean gestational age was 28 ± 2 weeks. The demographics of the two epochs were comparable. There were significant improvements in outcomes of infants in epoch 2 with less infants intubated at delivery (16% vs. 4%, P ≤ 0.001), improved 5 min Apgar (7 vs. 8, P ≤ 0.001), reduced need for ventilation (21% vs. 8.8%, P ≤ 0.001), duration of ventilation in the first 72 h (9.6 vs. 4.6 h) and mortality (10.8% vs. 1.7%, P ≤ 0.001). There was, increased incidence of chronic lung disease (30% vs. 55%, P = 0.02) but no increase in infants discharged on oxygen (3.8% vs. 5%, P = 0.25). Similar findings were observed in a subgroup of infants born <25 weeks' gestation with no increase in the incidence of CLD. CONCLUSION: Introducing application of bCPAP from the first breaths in infants <32 weeks' gestation was associated with better short-term outcomes and mortality, albeit with increased incidence of CLD. The subgroup of infants born <25 weeks' gestation showed similar change in outcomes, with no increase in CLD.

Exploring the thalamus L-sign: initial findings and associations with white matter injury in premature infants.

BACKGROUND: The thalamus L-sign, characterized by damage to the lateral and posterior parts of the thalamus, has recently been identified as a potential marker of partial prolonged hypoxic-ischemic injury (HII). Although prematurity-related thalamic injury is well documented, its association with the thalamus L-sign is infrequently described. OBJECTIVE: The primary objective of this study was to further investigate the thalamus L-sign in premature birth and white matter injury. MATERIALS AND METHODS: A retrospective analysis of 246 brain magnetic resonance imaging (MRI) scans from preterm infants born before 37 weeks of gestation was conducted to explore the occurrence, characteristics, and associations of the thalamus L-sign with white matter injury. RESULTS: The L-sign was detected in 12.6% of patients with periventricular leukomalacia (PVL), primarily in severe cases (57.9% of severe PVL). All cases were associated with posterior parieto-occipital PVL. Four patients exhibited unilateral or asymmetric L-signs, which were linked to high-grade intraventricular hemorrhage (IVH) or periventricular hemorrhagic infarction on the ipsilateral side, with the most severe white matter injury occurring on that side. No significant differences were observed regarding gestational age at birth, duration of neonatal intensive care unit hospitalization, percentage of IVH, hypoglycemia, or jaundice between patients with moderate-to-severe PVL with and without the thalamus L-sign. CONCLUSION: The thalamus L-sign may serve as a marker for severe parieto-occipital PVL and may be exacerbated and appear asymmetric in cases of ipsilateral IVH or periventricular hemorrhagic infarction.

Early Parenting Interventions to Enhance Development in Infants and Children Born Prematurely: A Systematic Review and Meta-Analysis.

INTRODUCTION: Parenting interventions have the potential to become effective strategies for improving the developmental trajectories of infants and children born prematurely. However, the effectiveness of parenting interventions is not well understood. METHODS: A literature search was conducted in five databases. A total of 24 studies involving 3,636 participants were included for review. RESULTS: The results showed a significant effect in cognition, language, motor development, and behavioral problems of children born prematurely. Parenting stress, anxiety, and interactive behaviors showed significant effect size. DISCUSSION: This review focuses on interventions that employ scaffolding parenting strategies to enhance the development of children born prematurely. Efforts should continue to empower parents through effective and sustainable parenting interventions to improve the quality of life of preterm children.

Case Report: Micafungin for treating Candida glabrata urinary infection: a clinical case in a premature neonate.

Urinary tract infections (UTIs) associated with indwelling urinary catheterization (IUC) in premature newborns (PNBs) pose a significant challenge in neonatal intensive care units (NICUs) due to the vulnerability of this population to infections and the necessity of invasive procedures. While bacterial UTIs have historically been predominant, there is a rising incidence of fungal pathogens, particularly non-albicans Candida strains like Candida glabrata and Candida tropicalis, attributed to broad-spectrum antibiotic use. Diagnosis of fungal UTIs in a PNB relies on culturing Candida spp. from properly collected urine samples, particularly critical in very low birth weight (VLBW) PNBs because of the risk of invasive candidiasis and associated complications. We present a case of an extremely premature newborn (EPNB) successfully treated for a UTI caused by C. glabrata with micafungin. Our case exhibits micafungin as a potentially safe and effective alternative for treating C. glabrata UTIs in neonates.

Hyperoxia-Induced miR-195 Causes Bronchopulmonary Dysplasia in Neonatal Mice.

Background: Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the pathogenesis of BPD and provide a potential therapeutic target. Methods: This study was conducted utilizing a postnatal animal model of experimental hyperoxia-induced murine BPD to investigate the expression and function of miR-195 as well as its molecular signaling targets within developing mouse lung tissue. Results: miR-195 expression levels increased in response to hyperoxia in male and female lungs, with the most significant elevation occurring in 40% O2 (mild) and 60% O2 (moderate) BPD. The inhibition of miR-195 improved pulmonary morphology in the hyperoxia-induced BPD model in male and female mice with females showing more resistance to injury and better recovery of alveolar chord length, septal thickness, and radial alveolar count. Additionally, we reveal miR-195-dependent signaling pathways involved in BPD and identify PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) as a novel specific target protein of miR-195. Conclusions: Our data demonstrate that high levels of miR-195 in neonatal lungs cause the exacerbation of hyperoxia-induced experimental BPD while its inhibition results in amelioration. This finding suggests a therapeutic potential of miR-195 inhibition in preventing BPD.

Effects of vanilla odor on hypoxia-related periodic breathing in premature newborns: A pilot study.

BACKGROUND: Periodic breathing (PB)-related intermittent hypoxia can have long-lasting deleterious consequences in preterm infants. Olfactory stimulation using vanilla odor is beneficial for apnea of prematurity in the first postnatal days/weeks. We aimed to determine for the first time whether vanilla odor can also decrease PB-related intermittent hypoxia. METHOD: This pilot study was a balanced crossover clinical trial including 27 premature infants born between 30 and 33+6 weeks of gestation. We performed 12-h recordings on two nights separated by a 24-h period. All infants were randomly exposed to vanilla odor on the first or second study night. The primary outcome was the desaturation index, defined as the number per hour of pulse oximetry (SpO2) values <90 % for at least 5 s, together with a drop of ≥5 % from the preceding value. Univariate mixed linear models were used for the statistical analysis. RESULTS: Overall, exposure to vanilla odor did not significantly decrease the desaturation index (52 ± 22 events/h [mean ± SD] on the intervention night vs. 57 ± 26, p = 0.2); furthermore, it did not significantly alter any secondary outcome. In a preliminary post hoc subgroup analysis, however, the effect of vanilla odor was statistically significant in infants with a desaturation index of ≥70/h (from 86 ± 12 to 65 ± 23, p = 0.04). CONCLUSION: In this pilot study, vanilla odor overall did not decrease PB-related intermittent hypoxia in infants born at 30-33+6 weeks of gestation, which is when they are close to term. Preliminary results suggesting a beneficial effect in infants with the highest desaturation index, however, justify further studies in the presence of PB-related intermittent hypoxia as well as in infants born more prematurely.

Current anesthesia practice for preterm infants undergoing surgery for necrotizing enterocolitis: A European survey.

STUDY OBJECTIVE: Necrotizing enterocolitis (NEC) is a life-threatening intestinal illness mostly affecting preterm infants, which commonly requires surgery. Anesthetic care for these patients is challenging, due to their prematurity and critical illness with hemodynamic instability. Currently, there are no guidelines for anesthetic care for these vulnerable patients. Therefore, this study aimed to describe current anesthesia practices across Europe for infants undergoing surgery for NEC. DESIGN: Cross-sectional survey study. PARTICIPANTS: Anesthesiologists working in centers where surgery for NEC is performed across Europe. MEASUREMENTS: A 46-item questionnaire assessing protocols for anesthesia practice, preoperative care, intraoperative care, postoperative care, and the respondent's opinion on the adequacy of anesthetic care for patients with NEC in their center. MAIN RESULTS: Out of the 173 responding anesthesiologists from 31 countries, approximately a third had a written standard protocol for anesthetic care in infants. Three quarters of the respondents screened all patients with NEC preoperatively, and a third structurally performed preoperative multidisciplinary consultation. For induction of general anesthesia, most respondents opted for intravenous anesthesia (n = 73, 43%) or a combination of intravenous and inhalation anesthesia (n = 57, 33%). For intravenous induction, they mostly used propofol (n = 58, 44%), followed by midazolam (n = 43, 33%) and esketamine (n = 42, 32%). For maintenance of anesthesia, inhalation anesthetic agents were more commonly used (solely: n = 71, 41%; in combination: n = 37, 22%), almost exclusively with sevoflurane. Postoperative analgesics mainly included paracetamol and/or morphine. Sixty percent of the respondents (n = 104) considered their anesthetic care for patients with NEC adequate. Suggestions for further improvement mainly revolved around monitoring, protocols, and collaboration. CONCLUSIONS: Anesthesia practice for infants undergoing surgery for NEC was highly variable. Most respondents considered the provided anesthetic care for patients with NEC adequate, but also recognized opportunities for further improvement, especially with regards to monitoring, protocols, and interdisciplinary collaboration.

Discharge preparation experiences and needs of intergenerational caregivers of neonatal intensive care unit preterm: A qualitative study.

PURPOSE: This study aimed to explore the real experiences and needs of neonatal intensive care unit (NICU) preterm intergenerational caregivers for discharge preparation and provide a basis for nursing staff to formulate systemic and personalized health education plans and continuous nursing plans for preterm discharge. DESIGN AND METHODS: This was a descriptive qualitative study. An objective sampling method was used to select 16 intergenerational caregivers of preterm infants admitted to the NICU of tertiary obstetrics and gynecology hospitals in Zhejiang and Jilin provinces from December 2023 to February 2024. Semi-structured interviews were conducted on the day of discharge of the preterm infants and six weeks after discharge. Colaizzi's seven-step analysis method was used to analyze the interview data. RESULTS: Based on the existence, relatedness, and growth (ERG) theory, the discharge preparation experiences and needs of neonatal intergenerational caregivers in the NICU were summarized into three themes: psychological condition, care capacity condition, and multi-party support needs. CONCLUSIONS: In the process of hospital discharge preparation, intergenerational caregivers of premature infants in NICU have multiple needs, including enhancing nursing ability and obtaining psychological and multi-party support. It is helpful to take effective interventions to improve their readiness for discharge. PRACTICE IMPLICATIONS: The nursing staff should develop personalized discharge health education plans and continuous nursing plans to improve the level of discharge preparation. PATIENT OR PUBLIC CONTRIBUTIONS: There were no patient or public contributions.

A cost-effectiveness analysis for high versus standard (low) dose caffeine for the treatment of apnea in neonatal intensive care unit.

Objective: Preterm babies are prone to experiencing apnea of prematurity (AOP), mostly characterised by a pause in breathing lasting a minimum of 20 seconds. Recent literature supported higher maintenance doses of caffeine, indicating benefits. This study evaluated the cost-effectiveness of high maintenance dose (HD) versus low maintenance dose (LD) caffeine for AOP in neonates. Methods: From the hospital perspective of Hamad Medical Corporation (HMC), Qatar, a cost-effectiveness decision-analytic model was constructed to follow the use of a HD maintenance caffeine of 20 mg/kg/dose versus a LD maintenance caffeine of 10 mg/kg/dose, in a simulated cohort of AOP neonates, over a therapy follow-up duration of six weeks, until neonatal intensive care (NICU) discharge. The clinical inputs were primarily literature-based, while the resource cost and utilisation were locally extracted in HMC. The cost-effectiveness outcome measure was calculated per therapy success, defined as survival with no apnea and successful extubation removal within 72 hours, with or without adverse events. One-way and multivariate sensitivity analyses were performed to confirm the robustness of the results. Results: With 0.23 (95% CI, 0.23-0.23) enhancement in success rate, at United States dollar (US$) 3869 (95% CI, US$ 3823-3915) added infant cost, the HD caffeine was between dominant (34.8%) and cost-effective (63.7%), with an average incremental cost-effectiveness ratio of US $16,895 (95% CI, US$ 15,242-18,549) relative to LD caffeine per additional case of success. The hospitalisation contributed the most to the total infant cost, and the probability of patent ductus arteriosus was the model input that influenced the results most. Conclusion: This is the first literature economic evaluation of caffeine for AOP. Despite increasing the cost of therapy, HD maintenance caffeine seems to be a cost-effective alternative to LD caffeine in Qatar. Our results support the recent global trends of increased use of HD caffeine for AOP in NICU.

Combination Therapy for OXA-48 Carbapenemase-Producing Klebsiella Pneumoniae Bloodstream Infections in Premature Infant: A Case Report and Literature Review.

The prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has been increasing in recent years. Chinese Infectious Disease Surveillance of Pediatrics (ISPED) showed that in 2022, its resistance rate to meropenem was 18.5%. However, there is limited data available on the treatment of CRKP infection in neonates. In this study, we present a case involving a premature infant infected with OXA-48-producing Klebsiella pneumoniae. The combined susceptibility test revealed a significant synergistic effect between ceftazidime-avibactam(CAZ-AVI), and aztreonam(ATM). The infection was successfully treated with a combination of CAZ-AVI, ATM, and fosfomycin. This case represents the first reported instance of sepsis in a premature infant caused by OXA-48-producing Klebsiella pneumoniae in China. The objective of our study is to evaluate the effectiveness and safety of combination therapy in treating CRKP infections in premature infants. We hope that the findings of this study will provide valuable insights for clinicians in their treatment approach.

Association of Standardized Parenteral Nutrition with Early Neonatal Growth of Moderately Preterm Infants: A Population-Based Cohort Study.

In preterm infants, early nutrient intake during the first week of life often depends on parenteral nutrition. This study aimed to evaluate the influence of standardized parenteral nutrition using three-in-one double-chamber solutions (3-in-1 STD-PN) on early neonatal growth in a cohort of moderately preterm (MP) infants. This population-based, observational cohort study included preterm infants admitted to neonatal centers in the southeast regional perinatal network in France. During the study period, 315 MP infants with gestational ages between 320/7 and 346/7 weeks who required parenteral nutrition from birth until day-of-life 3 (DoL3) were included; 178 received 3-in-1 STD-PN solution (56.5%). Multivariate regression was used to assess the factors associated with the relative body-weight difference between days 1 and 7 (RBWD DoL1-7). Infants receiving 3-in-1 STD-PN lost 36% less body weight during the first week of life, with median RBWD DoL1-7 of -2.5% vs. -3.9% in infants receiving other PN solutions (p < 0.05). They also received higher parenteral energy and protein intakes during the overall first week, with 85% (p < 0.0001) and 27% (p < 0.0001) more energy and protein on DoL 3. After adjusting for confounding factors, RBWD DoL1-7 was significantly lower in the 3-in-1 STD-NP group than in their counterparts, with beta (standard deviation) = 2.08 (0.91), p = 0.02. The use of 3-in-1 STD-PN provided better energy and protein intake and limited early weight loss in MP infants.

Efficacy and safety of different inhaled corticosteroids for bronchopulmonary dysplasia prevention in preterm infants: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of inhaled corticosteroids (budesonide, beclomethasone, or fluticasone propionate) in preventing bronchopulmonary dysplasia (BPD) for premature infants. METHOD: Electronic databases, including PubMed, EMBASE, Web of science, Scopus, and Cochrane library, were searched from databases inception to January 2022 for eligible randomized controlled trials. Clinical outcomes such as BPD, mortality, BPD or death, adverse events, and neurodevelopmental outcomes were assessed. RESULTS: Overall, budesonide was significantly associated with a reduction in BPD at 36 weeks' postmenstrual age (RR 0.48; 95 % CI [0.38, 0.62]) and patent ductus arteriosus (PDA) (RR 0.75; 95 % CI [0.63, 0.89]) compared with control treatments. Early longer duration inhalation of budesonide alone was associated with a lower risk of BPD at 36 weeks' postmenstrual age and PDA compared with controls. Early shorter duration intratracheal instillation of budesonide with surfactant as vehicle was associated with a lower risk of BPD at 36 weeks' postmenstrual age and all-cause mortality compared with surfactant. There was no statistically significant difference between budesonide and control groups regarding neurodevelopmental impairment. Beclomethasone and fluticasone propionate did not show any superior or inferior effect on clinical outcomes compared to control treatments. CONCLUSION: These findings suggest that budesonide, especially intratracheal instillation of budesonide using surfactant as a vehicle, is a safe and effective option in preventing BPD for preterm infants. More well-design large-scale trials with long-term follow-ups are necessary to verify the present findings.

Neonatal neurobehavior associated with developmental changes from age 2 to 3 in very preterm infants.

OBJECTIVE: Understand how high-risk infants' development changes over time. Examine whether NICU Network Neurobehavioral Scale (NNNS) profiles are associated with decrements in developmental outcomes between ages 2 and 3 years in infants born very preterm. STUDY DESIGN: The Neonatal Outcomes for Very preterm Infants (NOVI) cohort is a multisite prospective study of 704 preterm infants born <30 weeks' gestation across nine university and VON affiliated NICUs. Data included infant neurobehavior measured by NNNS profiles at NICU discharge and the Bayley Scales of Infant and Toddler Development (BSID-III) at ages 2 and 3 years. Generalized estimating equations tested associations between NNNS profiles and BSID-III composite score changes between ages 2 and 3 years. RESULTS: The final study sample included 433 infants with mean gestational age of 27 weeks at birth. Infants with dysregulated NNNS profiles were more likely to have decreases in BSID-III Cognitive (OR = 2.66) and Language scores (OR = 2.53) from age 2 to 3 years compared to infants with more well-regulated neurobehavioral NNNS profiles. Further, infants with more well-regulated NNNS profiles were more likely to have increases in BSID-III Cognitive scores (OR = 2.03), rather than no change, compared to infants with dysregulated NNNS profiles. CONCLUSIONS AND RELEVANCE: Prior to NICU discharge, NNNS neurobehavioral profiles identified infants at increased risk for developing later language and cognitive challenges. Findings suggests that neonatal neurobehavior provides a unique, clinically significant contribution to the evaluation of very preterm infants to inform treatment planning for the most vulnerable.

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The UK screening and treatment of retinopathy of prematurity (ROP) updated 2022 guidelines were developed by a multidisciplinary guideline development group from the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists, following the standards of the National Institute for Health and Care Excellence. They were published on the websites of the Royal College of Paediatrics and Child Health and the Royal College of Ophthalmologists in March 2022, and formally published in Early Human Development in March 2023. The guidelines provide evidence-based recommendations for the screening and treatment of ROP. The most significant change in the 2022 updated version compared to the previous guidelines is the lowering of the gestational age screening criterion to below 31 weeks. The treatment section covers treatment indications, timing, methods, and follow-up visits of ROP. This article interprets the guidelines and compares them with ROP guidelines/consensus in China, providing a reference for domestic peers.

Prolonged pain in premature neonates hospitalised in neonatal intensive care units: A scoping review.

BACKGROUND: Exposure to repetitive pain during the neonatal period has been shown to have important short and long-term effects on the neurodevelopment of the premature neonate and can contribute to experienced prolonged pain. A uniform taxonomy of neonatal prolonged pain is still lacking to this day which contributes to suboptimal prolonged pain management in neonatal intensive care units. Accordingly, a scoping review exploring the state of knowledge about prolonged pain in preterm neonates hospitalised in the neonatal intensive care unit will contribute to the developing field of neonatal prolonged pain and provide recommendations for clinical prolonged pain management. OBJECTIVE: To determine the scope, extent, and nature of the available literature on prolonged pain in premature neonates hospitalised in neonatal intensive care units. DESIGN: Scoping review. METHODS: An electronic search was conducted from inception to November 2023 in the databases of CINAHL, PubMed, Medline, Web of Science, GeryLit.org and Grey Source Index. Included studies discussed concepts related to neonatal prolonged pain such as definitions of prolonged pain, indicators of prolonged pain, contexts that result in prolonged pain, prolonged pain evaluation tools, consequences of prolonged pain and interventions for prolonged pain management. RESULTS: Key concepts of neonatal prolonged pain were identified in the 86 included articles of this scoping review such as definitions (n = 26), indicators (n = 39), contexts (n = 49), scales (n = 56), consequences of prolonged pain (n = 30) and possible interventions for prolonged pain management (n = 22). Whilst a consensus on a definition has yet to be achieved, no proximate event was shown to cause prolonged pain and a time criterion was identified by authors as being relevant in defining prolonged pain. Interestingly, the context of hospitalisation was identified as being the most indicative of prolonged pain in premature neonates and should guide its evaluation and management, whilst only limited pain management interventions and consequences were discussed. CONCLUSION: The findings of this scoping review contribute to the foundation of growing knowledge in neonatal prolonged pain and shed light on the ambiguity that currently exists on this topic in the scientific literature. This review summarises knowledge of key concepts necessary for a better understanding of prolonged pain and stresses the importance of considering contexts of hospitalisation for prolonged pain evaluation and management in neonatal intensive care units, with the objective of improving developmental outcomes of premature neonates. TWEETABLE ABSTRACT: A scoping review reveals that the contexts of prolonged pain in premature neonates hospitalised in the neonatal intensive care unit are essential in guiding its evaluation and management.

Implications of maternal vitamin D administration for the neonatal respiratory distress syndrome: A randomized clinical trial.

BACKGROUND: Vitamin D deficiency has been suggested to be a risk factor for neonatal respiratory distress syndrome (RDS). This study aimed to evaluate the effect of 25 (OH) D administrations in pregnant women with findings of preterm labor on the incidence of RDS in their preterm neonates. MATERIALS AND METHODS: A randomized controlled clinical trial was conducted on pregnant mothers with gestational age (GA) of less than 34 weeks at risk of preterm delivery. 175 subjects were randomly assigned into two groups, including intervention (intramuscular injection of 50,000 units of 25(OH) D during 72 hours before delivery) and control (no injections). Serum concentrations of 25(OH) D were measured shortly after birth in both mothers and neonates. Then, clinical and laboratory results of mothers and their offspring were recorded (in a checklist). Short-term outcomes and the need for respiratory support were also assessed. Data were analyzed by independent t-test, Mann-Whitney U test, Fisher's exact test, and chi-square test. RESULTS: Even though gestational age, birth weight, delivery method, and serum vitamin D levels are consistent among both groups, 45% of neonates in the control group and 20% in the intervention group developed respiratory distress syndrome (P = 0.05). The mean 25(OH) D level in neonates was 17.7±10.5 and 19.29±9.94 ng/mL in the intervention and control groups, respectively (P > 0.05). CONCLUSION: A single dose of 50,000 units of intramuscular 25(OH)D in pregnant women at risk of preterm labor can lower the risk of RDS in the infant.

Trends in Amplitude-Integrated Electroencephalography in the Smallest Preterm Neonates.

BACKGROUND: Amplitude-integrated electroencephalography is increasingly used for the neuromonitoring of premature infants. However, it is still not clear how bioelectrical activity changes in the smallest gestational age newborns. The aim of our study was to evaluate the bioelectrical activity of amplitude-integrated electroencephalograms in premature newborns of different gestational age to assess how gestational age and postnatal age influence patterns of amplitude-integrated electroencephalograms and to test the hypothesis of whether the bioelectrical activity of the brain matures faster after the birth of premature newborns than in utero. METHODS: We prospectively included infants born before 32 weeks of gestational age between June 2020 and July 2022. Serial recordings of amplitude-integrated electroencephalograms were performed at three time points of age (days 1-3, 13-15, and 27-29). Recordings were analyzed for background patterns, the onset and appearance of cyclicity, and lower amplitude border and bandwidth, which were used to derive a composite Burdjalov score. RESULTS: In total, 140 premature neonates were included in the study, and 112 of them completed the study. The median gestational age of the newborns enrolled in the study was 29 (27-30) weeks, and the mean weight was 1206 (350) g. Burdjalov scores increased with increasing gestational age. Higher scores were observed in every dimension of the amplitude-integrated electroencephalograms for newborns of lower gestational age when compared to newborns of higher gestational age of the same postmenstrual age. There was a significant correlation between gestational age and parameters of amplitude-integrated electroencephalograms at all time points. CONCLUSIONS: A higher gestational age has a positive effect on the bioelectrical activity of amplitude-integrated electroencephalograms. Increasing postnatal age affected amplitude-integrated electroencephalograms more than gestational age. Our hypothesis that the bioelectrical activity of the brain matures faster for premature newborns after birth than in the womb was confirmed.