Reduction in limb-movement complexity at term-equivalent age is associated with motor developmental delay in very-preterm or very-low-birth-weight infants.

Reduced complexity during the writhing period can be crucial in the spontaneous movements of high-risk infants for neurologic impairment. This study aimed to verify the association between quantified complexity of upper and lower-limb movements at term-equivalent age and motor development in very-preterm or very-low-birth-weight infants. Video images of spontaneous movements at term-equivalent age were collected from very-preterm or very-low-birth-weight infants. A pretrained pose-estimation model and sample entropy (SE) quantified the complexity of the upper- and lower-limb movements. Motor development was evaluated at 9 months of corrected age using Bayley Scales of Infant and Toddler Development, Third Edition. The SE measures were compared between infants with and without motor developmental delay (MDD). Among 90 infants, 11 exhibited MDD. SE measures at most of the upper and lower limbs were significantly reduced in infants with MDD compared to those without MDD (p < 0.05). Composite scores in the motor domain showed significant positive correlations with SE measures at most upper and lower limbs (p < 0.05). The results show that limb-movement complexity at term-equivalent age is reduced in infants with MDD at 9 months of corrected age. SE of limb movements can be a potentially useful kinematic parameter to detect high-risk infants for MDD.

Ongoing exposure to endocrine disrupting phthalates and alternative plasticizers in neonatal intensive care unit patients.

Due to endocrine disrupting effects, di-(2-ethylhexyl) phthalate (DEHP), a plasticizer used to soften plastic medical devices, was restricted in the EU Medical Devices Regulation (EU MDR 2017/745) and gradually replaced by alternative plasticizers. Neonates hospitalized in the neonatal intensive care unit (NICU) are vulnerable to toxic effects of plasticizers. From June 2020 to August 2022, urine samples (n = 1070) were repeatedly collected from premature neonates (n = 132, 4-10 samples per patient) born at <31 weeks gestational age and/or <1500 g birth weight in the Antwerp University Hospital, Belgium. Term control neonates (n = 21, 1 sample per patient) were included from the maternity ward. Phthalate and alternative plasticizers' metabolites were analyzed using liquid-chromatography coupled to tandem mass spectrometry. Phthalate metabolites were detected in almost all urine samples. Metabolites of alternative plasticizers, di-(2-ethylhexyl)-adipate (DEHA), di-(2-ethylhexyl)-terephthalate (DEHT) and cyclohexane-1,2-dicarboxylic-di-isononyl-ester (DINCH), had detection frequencies ranging 30-95 %. Urinary phthalate metabolite concentrations were significantly higher in premature compared to control neonates (p = 0.023). NICU exposure to respiratory support devices and blood products showed increased phthalate metabolite concentrations (p < 0.001). Phthalate exposure increased from birth until four weeks postnatally. The estimated phthalate intake exceeded animal-derived no-effect-levels (DNEL) in 10 % of samples, with maximum values reaching 24 times the DNEL. 29 % of premature neonates had at least once an estimated phthalate intake above the DNEL. Preterm neonates are still exposed to phthalates during NICU stay, despite the EU Medical Devices Regulation. NICU exposure to alternative plasticizers is increasing, though currently not regulated, with insufficient knowledge on their hazard profile.

Modeling Developmental Changes in Caffeine Clearance Considering Differences between Pre- and Postnatal Period.

Taguchi et al. reported that postmenstrual age (PMA) is a promising factor in describing and understanding the developmental change of caffeine (CAF) clearance. The aim of the present study was to quantify how developmental changes occur and to determine the effect of the length of the gestational period on CAF clearance. We performed a nonlinear mixed effect model (NONMEM) analysis and evaluated the fit of six models. A total of 115 samples were obtained from 52 patients with a mean age of 34.3 ± 18.2 d. The median values of gestational age (GA) and postnatal age (PNA) were 196 and 31 d, respectively. Serum CAF levels corrected for dose per body surface area (BSA) (C/D ratioBSA) were dependent on PMA rather than PNA, which supports the findings of a previous study. NONMEM analysis provided the following final model of oral clearance: CL/F = 0.00603∙WT∙∙0.877GA ≤ 196 L/h. This model takes into account developmental changes during prenatal and postnatal periods separately. The model successfully described the variation in clearance of CAF. Our findings suggest that the dosage of CAF in preterm infants should be determined based not only on body weight (WT) but also on both PNA and GA.

Non-surgical treatment of stage 4A retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a major cause of visual impairment in premature infants, often requiring surgical interventions in advanced stages. This retrospective case series study investigates non-surgical management for Stage 4A ROP, specifically the use of combined laser therapy and intravitreal anti-vascular endothelial growth factor (VEGF) injections. METHODS: Ten eyes from five infants with Stage 4A ROP were treated with a combined laser and anti-VEGF approach. Comprehensive follow-up examinations were conducted to evaluate the treatment outcomes. RESULTS: The study demonstrated successful retinal attachment without complications, showcasing the efficacy and safety of this non-surgical method. A comparison with surgical interventions highlighted the potential benefits in terms of reduced adverse effects. DISCUSSION: This combined treatment emerges as a promising first-choice option for Stage 4A ROP, offering rapid regression without surgical intervention, particularly in early stages. However, larger randomized clinical trials are necessary to validate these findings and establish definitive guidelines for managing this complex condition. CONCLUSION: Combined laser and anti-VEGF therapy proved to be an effective and safe non-surgical approach for Stage 4A ROP, with the potential to reduce the need for surgery, especially in its early presentation. Further research is required to confirm these findings and provide comprehensive recommendations for clinical practice.

Correlation of gestational age and age at death in sudden infant death syndrome: another pointer to the role of critical developmental period?

BACKGROUND: Filiano and Kinney proposed a triple-risk model for the sudden infant death syndrome (SIDS) that involves the intersection of three risks: (1) a vulnerable infant, (2) a critical developmental period in homeostatic control, and (3) an exogenous stressor(s). The primary evidence for the role of a critical developmental period in SIDS etiology is the peak of cases around the third month of life. Independently, several studies pointed to correlation between gestational age and age at death in SIDS, but used that to assess the SIDS risk for preterm infants, ignoring further ramifications. METHODS: We did a detailed analysis of CDC data spanning over two decades (1983-2011). We focused not only on the correlation between two age variables (gestational and age at death), but also on the possibility of misdiagnosis. Also, we attempted to account for potential biases in the data induced by the ICD-9/ICD-190 transition or the "Back to Sleep" campaign. RESULTS: The peak of deaths in the third month of life, that was the main argument for the role of the critical development period, wasn't unique to SIDS. However, we confirmed an almost linear and negative correlation between gestational age and the week of death due to SIDS. This pattern (slope of correlation < 0 and significance of correlation p < 0.05) is characteristic of SIDS among all diseases analyzed in the study. CONCLUSIONS: We interpret the results as the evidence of the role of the critical development period in SIDS etiology. Possibly more attention in the future research should be put to theories that are based on homeostatic control.

The impact of combined administration of surfactant and intratracheal budesonide compared to surfactant alone on bronchopulmonary dysplasia (BPD) and mortality rate in preterm infants with respiratory distress syndrome: a single-blind randomized clinical trial.

BACKGROUND: Respiratory distress syndrome (RDS) is one of the most important and common disorders among premature infants. OBJECTIVE: This study aimed to compare the effect of the combination of surfactant and budesonide with surfactant alone on Bronchopulmonary dysplasia (BPD) and mortality rate among premature infants with RDS. METHOD: An outcome assessor-blind randomized clinical trial was conducted on 134 premature infants with RDS who were born in Ayatollah Mousavi Hospital, Zanjan, Iran in 2021. The covariate adaptive randomization method was utilized to allocate participants into two groups (surfactant alone and a combination of surfactant and budesonide). The primary outcomes were BPD and Mortality rate from admission to hospital discharge. The data in this study were analyzed using SPSS software version 18. RESULTS: Overall the comparison of mortality rate and BPD between the two groups did not show a significant difference(p > 0.05). The subgroup results showed that administering surfactant with budesonide to infants under 30 weeks of age significantly reduced the number of deaths compared to using surfactant alone (5 vs. 17). Similar positive effects were observed for the occurrence of Pulmonary Hemorrhage, the need for a second dose of surfactant, oxygen index, mean blood pressure and mean arterial pressure (MAP) in infants under 34 weeks of age compared to more than 34 weeks (p < 0.05). CONCLUSION: These findings suggest that the combination therapy of surfactant and budesonide may be beneficial, particularly in preterm infants with less than 34 weeks gestational age and 1500 birth weight. However, further studies with larger sample sizes and longer follow-up periods are needed to confirm these results and assess long-term outcomes. TRIAL REGISTRATION: The study was registered at the Iranian Registry of Clinical Trials website under the code IRCT20201222049802N1. https://en.irct.ir/user/trial/48117/view . REGISTRATION DATE: 28/02/2021. PUBLIC REPOSITORY: DATA SET: This research data set link is displayed on the Zanjan-Iran Medical Sciences website: https://repository.zums.ac.ir/cgi/users/login? target=https%3 A%2 F/repository.zums.ac.ir/id/eprint .

Prechtl's method to assess general movements: Inter-rater reliability during the preterm period.

INTRODUCTION: Prechtl's method (GMA) is a test for the functional assessment of the young nervous system. It involves a global and a detailed assessment of the general movements (GMs) and has demonstrated validity. Data on the reliability of both assessments in the preterm period are scarce. This study aimed to evaluate the inter-rater reliability for the global and detailed assessments of the preterm writhing GMA. MATERIALS AND METHODS: The study participants were 69 infants born at <37 gestational weeks and admitted to the neonatal intensive care unit. They were randomly assigned to five pairs of raters. Raters assessed infants' GMs using preterm videos. Outcome variables were (a) the GMs classification (normal versus abnormal; normal versus abnormal subcategories) and (b) the general movements optimality score (GMOS), obtained through the global and detailed assessments. The Gwet's AC1 and the intraclass correlation coefficient (ICC) were calculated for the GMs classification and the GMOS, respectively. RESULTS: The global assessment presented an AC1 = 0.84 [95% CI = 0.54,1] for the GMs binary classification and an AC1 = 0.67 [95% CI = 0.38,0.89] for the GMs classification with abnormal subcategories. The detailed assessment presented an ICC = 0.72 [95% CI = 0.39,0.90] for the GMOS. CONCLUSIONS: Inter-rater reliability was high and substantial for the global assessment and good for the detailed assessment. However, the small sample size limited the precision of these estimates. Future research should involve larger samples of preterm infants to improve estimate precision. Challenging items such as assessing the neck and trunk, poor repertoire GMs, and tremulous movements may impact the preterm writhing GMA's inter-rater reliability. Therefore, ongoing training and calibration among raters is necessary. Further investigation in clinical settings can enhance our understanding of the preterm writhing GMA's reliability.

Mobile bedside ductus arteriosus closure in severely premature neonates using only echocardiographic guidance.

BACKGROUND: Transcatheter closure of the patent ductus arteriosus (PDA) in premature infants is currently dependent on fluoroscopic guidance and transportation to the catheterization laboratory. AIM: We describe a new echocardiographically guided technique to allow our team to move to the bedside at the neonatal intensive care unit (NICU) of the referring center for percutaneous treatment of PDA in premature infants. METHODS: This is a single-center, retrospective, primarily descriptive analysis. Clinical details about the procedure, its outcomes, and complications were collected. RESULTS: Fifty-eight neonates with a median weight of 1110 g (range 730-2800) and postnatal age of 28 days (range 9-95) underwent percutaneous PDA closure. Five of them were treated in our center with ultrasound guidance only and the other 53 in 18 different neonatology units in 12 towns. The median duration of the procedure was 40 min (range 20-195 min). There were no procedural deaths. There was one residual shunt for 3 weeks, in all other patients the duct closed completely in the first few hours after the intervention. In one patient the procedure had to be interrupted because of a pericardial effusion which had to be drained, the PDA was closed successfully interventionally 5 days later. One device-related aortic coarctation had to be stented. One embolization and one late migration occurred and required treatment. CONCLUSIONS: Echocardiographically guided transcatheter closure of the PDA in prematures was repeatedly possible and allowed that the procedure is performed at the bedside at the NICU with an acceptable rate of complications.

Inhaled bronchodilators for the prevention and treatment of chronic lung disease in preterm infants.

BACKGROUND: Chronic lung disease (CLD) occurs frequently in preterm infants and is associated with respiratory morbidity. Bronchodilators have the potential effect of dilating small airways with muscle hypertrophy. Increased compliance and tidal volume, and decreased airway resistance, have been documented with the use of bronchodilators in infants with CLD. Therefore, bronchodilators are widely considered to have a role in the prevention and treatment of CLD, but there remains uncertainty as to whether they improve clinical outcomes. This is an update of the 2016 Cochrane review. OBJECTIVES: To determine the effect of inhaled bronchodilators given as prophylaxis or as treatment for chronic lung disease (CLD) on mortality and other complications of preterm birth in infants at risk for or identified as having CLD. SEARCH METHODS: An Information Specialist searched CENTRAL, MEDLINE, Embase, CINAHL and three trials registers from 2016 to May 2023. In addition, the review authors undertook reference checking, citation searching and contact with trial authors to identify additional studies. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials involving preterm infants less than 32 weeks old that compared bronchodilators to no intervention or placebo. CLD was defined as oxygen dependency at 28 days of life or at 36 weeks' postmenstrual age. Initiation of bronchodilator therapy for the prevention of CLD had to occur within two weeks of birth. Treatment of infants with CLD had to be initiated before discharge from the neonatal unit. The intervention had to include administration of a bronchodilator by nebulisation or metered dose inhaler. The comparator was no intervention or placebo. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Critical outcomes included: mortality within the trial period; CLD (defined as oxygen dependency at 28 days of life or at 36 weeks' postmenstrual age); adverse effects of bronchodilators, including hypokalaemia (low potassium levels in the blood), tachycardia, cardiac arrhythmia, tremor, hypertension and hyperglycaemia (high blood sugar); and pneumothorax. We used the GRADE approach to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included two randomised controlled trials in this review update. Only one trial provided useable outcome data. This trial was conducted in six neonatal intensive care units in France and Portugal, and involved 173 participants with a gestational age of less than 31 weeks. The infants in the intervention group received salbutamol for the prevention of CLD. The evidence suggests that salbutamol may result in little to no difference in mortality (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.50 to 2.31; risk difference (RD) 0.01, 95% CI -0.09 to 0.11; low-certainty evidence) or CLD at 28 days (RR 1.03, 95% CI 0.78 to 1.37; RD 0.02, 95% CI -0.13 to 0.17; low-certainty evidence), when compared to placebo. The evidence is very uncertain about the effect of salbutamol on pneumothorax. The one trial with usable data reported that there were no relevant differences between groups, without providing the number of events (very low-certainty evidence). Investigators in this study did not report if side effects occurred. We found no eligible trials that evaluated the use of bronchodilator therapy for the treatment of infants with CLD. We identified no ongoing studies. AUTHORS' CONCLUSIONS: Low-certainty evidence from one trial showed that inhaled bronchodilator prophylaxis may result in little or no difference in the incidence of mortality or CLD in preterm infants, when compared to placebo. The evidence is very uncertain about the effect of salbutamol on pneumothorax, and neither included study reported on the incidence of serious adverse effects. We identified no trials that studied the use of bronchodilator therapy for the treatment of CLD. Additional clinical trials are necessary to assess the role of bronchodilator agents in the prophylaxis or treatment of CLD. Researchers studying the effects of inhaled bronchodilators in preterm infants should include relevant clinical outcomes in addition to pulmonary mechanical outcomes.

Balanced on the Biggest Wave: Nirsevimab for Newborns.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization in infancy in the United States. Nearly all infants are infected by 2 years of age, with bronchiolitis requiring hospitalization often occurring in previously healthy children and long-term consequences of severe disease including delayed speech development and asthma. Incomplete passage of maternal immunity and a high degree of genetic variability within the virus contribute to morbidity and have also prevented successful neonatal vaccine development. Monoclonal antibodies reduce the risk of hospitalization from severe RSV disease, with palivizumab protecting high-risk newborns with comorbidities including chronic lung disease and congenital heart disease. Unfortunately, palivizumab is costly and requires monthly administration of up to five doses during the RSV season for optimal protection.Rapid advances in the past two decades have facilitated the identification of antibodies with broad neutralizing activity and allowed manipulation of their genetic code to extend half-life. These advances have culminated with nirsevimab, a monoclonal antibody targeting the Ø antigenic site on the RSV prefusion protein and protecting infants from severe disease for an entire 5-month season with a single dose. Four landmark randomized controlled trials, the first published in July 2020, have documented the efficacy and safety of nirsevimab in healthy late-preterm and term infants, healthy preterm infants, and high-risk preterm infants and those with congenital heart disease. Nirsevimab reduces the risk of RSV disease requiring medical attention (number needed to treat [NNT] 14-24) and hospitalization (NNT 33-63) with rare mild rash and injection site reactions. Consequently, the Centers for Disease Control and Prevention has recently recommended nirsevimab for all infants younger than 8 months of age entering or born during the RSV season and high-risk infants 8-19 months of age entering their second season. Implementing this novel therapy in this large population will require close multidisciplinary collaboration. Equitable distribution through minimizing barriers and maximizing uptake must be prioritized.

Achieving optimal cord management: a multidisciplinary quality improvement initiative.

Optimal cord management (OCM), defined as waiting at least 60 seconds (s) before clamping the umbilical cord after birth, is an evidence-based intervention that improves outcomes for both term and preterm babies. All major resuscitation councils recommend OCM for well newborns.National Neonatal Audit Programme (NNAP) benchmarking data identified our tertiary neonatal unit as a negative outlier with regard to OCM practice with only 12.1% of infants receiving the recommended minimum of 60 s. This inspired a quality improvement project (QIP) to increase OCM rates of ≥ 60 s for infants <34 weeks. A multidisciplinary QIP team (Neonatal medical and nursing staff, Obstetricians, Midwives and Anaesthetic colleagues) was formed, and robust evidence-based quality improvement methodologies employed. Our aim was to increase OCM of ≥ 60 s for infants born at <34 weeks to at least 40%.The percentage of infants <34 weeks receiving OCM increased from 32.4% at baseline (June-September 2022) to 73.6% in the 9 months following QIP commencement (October 2022-June 2023). The intervention period spanned two cohorts of rotational doctors, demonstrating its sustainability. Rates of admission normothermia were maintained following the routine adoption of OCM (89.2% vs 88.5%), which is a complication described by other neonatal units.This project demonstrates the power of a multidisciplinary team approach to embedding an intervention that relies on collaboration between multiple departments. It also highlights the importance of national benchmarking data in allowing departments to focus QIP efforts to achieve long-lasting transformational service improvements.

Effects of human milk odor stimulation on feeding in premature infants: a systematic review and meta-analysis.

Previous studies suggested odor stimulation may influence feeding of premature neonates. Therefore, this systematic review and meta-analysis of randomized controlled trials was conducted to assess the effect of human milk odor stimulation on feeding of premature infants. All randomized controlled trials related to human milk odor stimulation on feeding in premature infants published in PubMed, Cochrane, Library, Medline, Embase, Web of science databases and Chinese biomedical literature databases, China National Knowledge Infrastructure, China Science and Technology Journal Database (VIP) and Wanfang Chinese databases were searched, and The Cochrane Handbook 5.1.0 was used to evaluate the quality and authenticity of the literature. Relevant information of the included studies was extracted and summarized, and the evaluation indexes were analyzed using ReviewManager5.3. The retrieval time was from the establishment of the database to July 28, 2022.12 articles were assessed for eligibility, and six randomized controlled studies were eventually included in the meta-analysis (PRISMA). A total of 6 randomized controlled studies with 763 patients were finally included in the study, and the quality evaluation of literatures were all grade B. Human milk odor stimulation reduced the transition time to oral feeding in premature infants [SMD = - 0.48, 95% CI (- 0.69, - 0.27), Z = 4.54, P < 0.00001] and shortened the duration of parenteral nutrition [MD = - 1.01, 95% CI (- 1.70, - 0.32), Z = 2.88, P = 0.004]. However, it did not change the length of hospitalization for premature infants [MD = - 0.03, 95% CI (- 0.41, 0.35), Z = 0.17, P = 0.86]. The implementation of human milk odor stimulation can reduce the transition time to oral feeding and the duration of parenteral nutrition in premature infants, but further studies are needed to determine whether it can reduce the length of hospital stay in premature infants. More high-quality, large-sample studies are needed to investigate the effect of human milk odor stimulation on the feeding process and other outcomes in premature infants.

Cost-utility analysis of palivizumab for preventing respiratory syncytial virus in preterm neonates and infants in Colombia.

AIM: Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations. METHODS: We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses. RESULTS: Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results. CONCLUSION: Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.

Development of a Web-Based Oxygenation Dashboard for Preterm Neonates: A Quality Improvement Initiative.

BACKGROUND: Preterm neonates are extensively monitored to require strict oxygen target attainment for optimal outcomes. In daily practice, detailed oxygenation data are hardly used and crucial patterns may be missed due to the snapshot presentations and subjective observations. This study aimed to develop a web-based dashboard with both detailed and summarized oxygenation data in real-time and to test its feasibility to support clinical decision making. METHODS: Data from pulse oximeters and ventilators were synchronized and stored to enable real-time and retrospective trend visualizations in a web-based viewer. The dashboard was designed based on interviews with clinicians. A preliminary version was evaluated during daily clinical rounds. The routine evaluation of the respiratory condition of neonates (gestational age < 32 weeks) with respiratory support at the NICU was compared to an assessment with the assistance of the dashboard. RESULTS: The web-based dashboard included data on the oxygen saturation (SpO2), fraction of inspired oxygen (FiO2), SpO2/FiO2 ratio, and area < 80% and > 95% SpO2 curve during time intervals that could be varied. The distribution of SpO2 values was visualized as histograms. In 65% of the patient evaluations (n = 86) the level of hypoxia was assessed differently with the use of the dashboard. In 75% of the patients the dashboard was judged to provide added value for the clinicians in supporting clinical decisions. CONCLUSIONS: A web-based customized oxygenation dashboard for preterm neonates at the NICU was developed and found feasible during evaluation. More clear and objective information was found supportive for clinicians during the daily rounds in tailoring treatment strategies.

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

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

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

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

Association of Caffeine Daily Dose With Respiratory Outcomes in Preterm Neonates: A Retrospective Cohort Study.

Apnea and poor respiratory drive increase the risk of extubation failure (EF) and prolonged invasive mechanical ventilation (IMV) in preterm neonates (pre-nates) with respiratory distress. Caffeine citrate (CC) is often prescribed for pre-nates in doses of 5-10 mg/kg in 24 h. This study aimed to evaluate the most effective dosage regimen (5 mg/kg/day vs >5-10 mg/kg/day) to prevent apnea and EF with minimal caffeine-associated potential side effects (CC-APSEs) in pre-nates. This one-year retrospective cohort study included all the eligible neonates admitted to NICU and received CC-therapy till 28 days of life (DOL) or discharge. Based on CC-daily dose formed LD-caffeine-group (5 mg/kg/day) and HD-caffeine-group (>5-10 mg/kg/day). Antenatal, prenatal, and postnatal characteristics, CC-regimen, comorbidities, and CC-APSEs were compared between the groups. Predictors of apnea and EF were analyzed through logistic regression. There were 181 and 72 neonates in the LD and HD-caffeine-groups respectively. In HD-caffeine-group daily CC-dose was 7 to 7.5 mg/kg/day in 93% of neonates and >7.5 to 10 mg/kg/day in only 7%. Significantly fewer neonates experienced apnea and EF in the HD-caffeine-group till 28DOL or discharge. This difference was even greater in the subgroup of ≤28 weeks GA (15.6% vs 40.0%; P < .01). In HD-caffeine-group the incidence of severe/moderate-BPD was significantly lower and the frequency of CC-APSEs was higher. Multivariate analysis showed that; the smaller the GA higher the risk of apnea (AOR = 0.510, 95% CI 0.483-0.999) and EF (AOR = 0.787, 95% CI 0.411-0.997). The HD-caffeine was inversely associated with developing apnea (AOR = 0.244, 95% CI 0.053-0.291) and EF (AOR = 0.103, 95% CI 0.098-2.976). IMV-duration before extubation (AOR = 2.229, 95% CI 1.672-2.498) and severe/moderate-BPD (AOR = 2.410, 95%CI 1.104-2.952) had a high risk of EF. Initiating early HD-caffeine may prevent apnea and extubation failure in preterm neonates. Optimization of caffeine initiation time and dosages can be a safe and feasible approach to decrease the burden of neonatal respiratory morbidities.

Nutritional support during the first week for infants with bronchopulmonary dysplasia and respiratory distress: a multicenter cohort study in China.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a major complication affecting the survival rate and long-term outcomes of preterm infants. A large, prospective, multicenter cohort study was conducted to evaluate early nutritional support during the first week of life for preterm infants with a gestational age < 32 weeks and to verify nutritional risk factors related to BPD development. METHODS: A prospective multicenter cohort study of very preterm infants was conducted in 40 tertiary neonatal intensive care units across mainland China between January 1, 2020, and December 31, 2021. Preterm infants who were born at a gestational age < 32 weeks, < 72 h after birth and had a respiratory score > 4 were enrolled. Antenatal and postnatal information focusing on nutritional parameters was collected through medical systems. Statistical analyses were also performed to identify BPD risk factors. RESULTS: The primary outcomes were BPD and severity at 36 weeks postmenstrual age. A total of 1410 preterm infants were enrolled in this study. After applying the exclusion criteria, the remaining 1286 infants were included in this analysis; 614 (47.7%) infants were in the BPD group, and 672 (52.3%) were in the non-BPD group. In multivariate logistic regression model, the following six factors were identified of BPD: birth weight (OR 0.99, 95% CI 0.99-0.99; p = 0.039), day of full enteral nutrition (OR 1.03, 95% CI 1.02-1.04; p < 0.001), parenteral protein > 3.5 g/kg/d during the first week (OR 1.65, 95% CI 1.25-2.17; p < 0.001), feeding type (formula: OR 3.48, 95% CI 2.21-5.49; p < 0.001, mixed feed: OR 1.92, 95% CI 1.36-2.70; p < 0.001; breast milk as reference), hsPDA (OR 1.98, 95% CI 1.44-2.73; p < 0.001), and EUGR ats 36 weeks (OR 1.40, 95% CI 1.02-1.91; p = 0.035). CONCLUSIONS: A longer duration to achieve full enteral nutrition in very preterm infants was associated with increased BPD development. Breastfeeding was demonstrated to have a protective effect against BPD. Early and rapidly progressive enteral nutrition and breastfeeding should be promoted in very preterm infants. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry (No. ChiCTR2000030125 on 24/02/2020) and in www.ncrcch.org (No. ISRCTN84167642 on 25/02/2020).

The effect of maternal voice and non-nutritional sucking on repeated procedural pain of heel prick in neonates: a quasi-experimental study.

BACKGROUND: Neonates in the neonatal intensive care unit undergo frequent painful procedures. It is essential to reduce pain using safe and feasible methods. PURPOSE: To evaluate the effects of non-nutritional sucking, mother's voice, or non-nutritional sucking combined with mother's voice on repeated procedural pain in hospitalized neonates. METHODS: A quasi-experimental study was conducted in which 141 neonates were selected in a hospital in Changsha, China. Newborns were divided into four groups: non-nutritional sucking (NNS) (n = 35), maternal voice (MV) (n = 35), NNS + MV (n = 34), and control (n = 37) groups. The Preterm Infant Pain Profile-Revised Scale (PIPP-R) was used to assess pain. RESULTS: During the heel prick, the heart rate value and blood oxygen saturation were significantly different between the groups (P < 0.05). Both non-nutritional sucking and maternal voice significantly reduced PIPP-R pain scores of hospitalized newborns (P < 0.05). The pain-relief effect was more robust in the combined group than in other groups. CONCLUSIONS: This study showed that both non-nutritional sucking and the mother's voice alleviated repeated procedural pain in neonates. Therefore, these interventions can be used as alternatives to reduce repeated procedural pain.