High-risk Preterm Infants Research Articles

The Association between Ventricle Ratio in Preterm Infants and Motor Developmental Delay

Introduction: Early prediction and timely intervention are particularly essential for high-risk preterm infants. Brain magnetic resonance imaging (BMRI) is frequently used alongside functional evaluations to improve predictions of developmental outcomes. This study aimed to assess voxel-based brain volumetry in extremely preterm infants using BMRI at term equivalent age (TEA) and investigate its association with developmental outcomes. Methods: From March 2016 to December 2019, high-risk preterm infants (birth weight <1,500 g or gestational age <32 weeks) with BMRI at TEA and follow-up developmental data assessed by Bayley-III were included. For BMRI volumetry, manual tracing and segmentation were performed on T1-weighted scans, and after smoothing, voxels were calculated for each brain segment. Forty-seven subjects were enrolled and categorized into typical/delayed motor groups. Results: Results revealed a significant difference in ventricle size and ventricle ratio in BMRI at TEA between the groups. Even after controlling for other factors that could influence developmental outcomes, ventricle ratio emerged as a robust, single predictor for future motor development. Conclusion: This study suggests the potential clinical utility of BMRI volumetry in predicting motor development outcomes.

The Bronchopulmonary Dysplasia score: A predictive model for bronchopulmonary dysplasia or death in high-risk preterm infants.

Progressive respiratory deterioration in infants at high risk of bronchopulmonary dysplasia (BPD) is associated with patent ductus arteriosus (PDA) exposure. This study aimed to design an early predictive model for BPD or death in preterm infants using early echocardiographic markers and clinical data. Infants born with gestational age (GA) ≤ 29 weeks and/or birth weight (BW) < 1500 g at Cork University Maternity Hospital, Ireland were retrospectively evaluated. Those with echocardiography performed between 36 h and 7 days of life were eligible for inclusion. Exclusion criteria were pulmonary hypertension and major congenital anomalies. The primary outcome was a composite of BPD and death before discharge. The study included 99 infants. A predictive model for the primary outcome was developed, which included three variables (BW, Respiratory Severity Score and flow pattern across the PDA), and yielding an area under the curve of 0.98 (95% CI 0.96-1.00, p < 0.001). Higher scores were predictive of the primary outcome. A cut-off of -1.0 had positive and negative predictive values of 89% and 98%, and sensitivity and specificity of 98% and 88%, respectively. Our prediction model is an accessible bedside tool that predicts BPD or death in premature infants.

Retinopathy of Prematurity in Neonatal Intensive Care Unit at King Fahd University Hospital, Eastern Province: Prevalence, Risk Factors, and pattern of severity Seven years’ experience.

Background Premature newborns are susceptible to retinopathy of prematurity (ROP), a vasoproliferative disease of the developing retinal vessels, which is a major cause of potentially avoidable blindness. Due to geographical variations in newborn care, geographic variations in the epidemiology of ROP have been observed internationally during the last several decades. There was a correlation between the severity of the condition and the number of prenatal, postnatal, and other risk factors. This study aimed to examine the incidence and risk factors associated with retinopathy of prematurity in preterm infants. Methods A retrospective review of preterm newborns evaluated for retinopathy of prematurity between January 2016 and December 2022 was carried out at King Fahd Hospital of the University (KFHU), Khobar, Saudi Arabia. Infants who fulfilled the screening criteria (GA &lt; 34 or Birth Weight (WT) ≤ 1500 g) underwent the screening test, and the International Classification of Retinopathy of Prematurity was used to classify retinopathy of prematurity. Risk factors and demographic information regarding ROP were assessed. Statistical analysis was performed using SPSS (version 20) with a 95% confidence interval (CI). Statistical significance was set at p &lt; 0.05. Results Among the 200 preterm neonates that were evaluated and admitted to neonatal critical care units, 37% exhibited premature retinopathy, with 46.7% of those cases being in stage 1. The development of ROP was linked to gestational age, length of mechanical ventilation, septicemia, intraventricular hemorrhage, bronchopulmonary dysplasia, respiratory distress syndrome, and septicemia, according to univariate and multivariate logistic regression analyses. Conclusion The incidence of total retinopathy in premature infants in this population was 37%. Evaluating these risk factors during the screening of high-risk premature infants will help determine the appropriate timing of examinations and treatment.

CNN-Based Pattern Classifiers for Precise Identification of Perinatal EEG Biomarkers of Brain Injury in Preterm Neonates

Electroencephalographic (EEG) monitoring is important for the diagnosis of hypoxic-ischemic (HI) brain injury in high-risk preterm infants. EEG monitoring is limited by the reliance on expert clinical observation. However, high-risk preterm infants often do not present observable symptoms due to their frailty. Thus, there is an urgent need to find better ways to automatically quantify changes in the EEG these high-risk babies. This article is a first step towards this goal. This innovative study demonstrates the effectiveness of deep Convolutional Neural Networks (CNN) pattern classifiers, trained on spectrally-detailed Wavelet Scalograms (WS) images derived from neonatal EEG sharp waves—a potential translational HI biomarker, at birth. The WS-CNN classifiers exhibit outstanding performance in identifying HI sharp waves within an exclusive clinical EEG recordings dataset of preterm infants immediately after birth. The work has impact as it demonstrates exceptional high accuracy of 99.34 ± 0.51% cross-validated across 13,624 EEG patterns over 48 h raw EEG at low 256 Hz clinical sampling rates. Furthermore, the WS-CNN pattern classifier is able to accurately identify the sharp-waves within the most critical first hours of birth (n = 8, 4:36 ± 1:09 h), regardless of potential morphological changes influenced by different treatments/drugs or the evolutionary ‘timing effects’ of the injury. This underscores its reliability as a tool for the identification and quantification of clinical EEG sharp-wave biomarkers at bedside.

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.

Predictive and Diagnostic Values of Systemic Inflammatory Indices in Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) is the most common respiratory complication in preterm infants, and there is a lag in the diagnosis of BPD. Inflammation is a vital pathogenic factor for BPD; we aim to evaluate the predictive and diagnostic values of systemic inflammatory indices in BPD. Between 1 January 2019 and 31 May 2023, the clinical data of 122 premature infants with a gestational age of <32 weeks in the Department of Neonatology, the Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University, were retrospectively collected and classified into non-BPD (n = 72) and BPD (n = 50) groups based on the National Institute of Child Health and Human Development 2018 criteria. To compare the general characteristics of each group, we identified the independent risk variables for BPD using multivariate logistic regression analysis, compared the systemic inflammatory indices at birth, 72 h, 1 week, 2 weeks, and 36 weeks postmenstrual age (PMA), and constructed the receiver operating characteristic curves of neutrophil-to-lymphocyte ratio (NLR) diagnosis of BPD at different time points. ① The independent risk factors for BPD in preterm infants were birth weight, small for gestational age, and days of oxygen therapy (all p < 0.05). ② At 72 h and 1 week after birth, the serum NLR of the BPD group was higher than for the non-BPD group (p < 0.05). Furthermore, the neutrophil count (N), NLR, monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index, systemic inflammation response index (SIRI), and pan-immune-inflammation value of infants with BPD were higher than the non-BPD group at 3 weeks after birth (p < 0.05). Moreover, at 36 weeks of PMA, the serum N, NLR, MLR, and SIRI of BPD infants were higher than those of non-BPD infants (p < 0.05). ③ The NLR of infants with and without BPD gradually increased after birth, reaching a peak at 72 h and 1 week, respectively. At 3 weeks postnatal, the NLR had the highest predictive power for BPD, with an area under the curve (AUC) of 0.717 (p < 0.001); the sensitivity was 56% and specificity was 86.1%. In addition, the NLR at 36 weeks of PMA exhibited some diagnostic value for BPD. The AUC was 0.693 (p < 0.001), the sensitivity was 54%, and specificity was 83.3%. At 3 weeks after birth and 36 weeks of PMA, some systemic inflammation indices (like N, NLR, SIRI) of preterm infants with BPD have specific predictive and diagnostic values; these indices may help the management of high-risk preterm infants with BPD.

The Relation Between Oxygen Saturation Measured by Pulse Oximetry vs Near-infrared Spectroscopy Following Surfactant Therapy in Very Low-birth-weight Neonates

Background: Monitoring regional cerebral oxygen saturation (rScO2) and hemodynamic stability (eg, mean arterial blood pressure [MABP]) in high-risk premature infants is crucial to enhance daily clinical practices in neonatal intensive care units (NICUs). Objectives: This study aimed to investigate potential differences between oxygen saturation measurements obtained via near-infrared spectroscopy (NIRS) and pulse oximetry (PO). Methods: This pilot study enrolled 20 very low-birth-weight (VLBW) premature neonates through a non-random, available sampling approach. We gathered maternal and fetal demographic data along with clinical characteristics of the neonates. The study focused on assessing tissue and cerebral oxygenation using PO and NIRS. We specifically monitored changes in mean rScO2 and MABP at various time points: before, during, and 5 and 10 min after the administration of surfactant injection (SI) via the endotracheal tube. Results: The mean gestational age, neonatal birth weight, and Apgar scores at 1 and 5 min after birth were 28.44 ± 2.57 weeks, 1063 ± 246 g, 6.05 ± 2.57, and 7.94 ± 1.79, respectively. No significant differences were observed between mean rScO2 values measured by NIRS and PO before (P = 0.631), during (P = 0.722), and 5 min after (P = 0.783) SI. However, a significant difference between PO and NIRS-based rScO2 values was found 10 min after SI (96.95% vs 75.0%; P = 0.04). Additionally, there was no significant correlation between mean rScO2 and MABP recorded before, during, and after SI. Conclusions: There were no differences in oxygen saturation measurements (recorded by PO) and rScO2 values (recorded by NIRS) before, during, and immediately after SI. Therefore, using PO in NICUs to assess cerebral oxygenation, autoregulation, and hypoxia appears both reasonable and cost-effective. Further multicenter studies are needed to validate the practical advantages and cost-effectiveness of NIRS as an emerging monitoring system.

Patent Ductus Arteriosus and Bronchopulmonary Dysplasia–Associated Pulmonary Hypertension

Bronchopulmonary dysplasia (BPD) is often associated with pulmonary vascular disease and secondary pulmonary hypertension (PH). The pathogenesis of BPD-associated PH (BPD-PH) is complex and involves prenatal and postnatal factors that disrupt pulmonary vascular development, and patent ductus arteriosus (PDA) is a factor potentially associated with risk of BPD-PH that has been identified in very recent studies. To explore the association of PDA with BPD-PH using a bayesian model-averaged (BMA) meta-analysis of studies. PubMed and Embase were searched up to April 2023. Key search terms included BPD and PH. Studies examining infants with gestational age 32 weeks or less and reporting data on PDA and risk of BPD-PH. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the Meta-Analysis of Observational Studies in Epidemiology reporting guidelines. Two independent reviewers extracted data, with a third reviewer checking for accuracy and completeness. Data pooling and effect size calculations were performed by BMA. The primary outcome was BPD-PH. BMA was used to calculate Bayes factors (BFs). The BF10 is the ratio of the probability of the data under the alternative hypothesis (H1, association of PDA with BPD-HP) over the probability of the data under the null hypothesis (H0). A total of 32 studies (8513 infants) were included. BMA showed that the evidence in favor of H1 was weak for any PDA (BF10 = 2.90; 10 studies), moderate for hemodynamically significant PDA (BF10 = 3.77; 3 studies), and extreme for surgically ligated or catheter-occluded PDA (BF10 = 294.9; 16 studies). In contrast, the evidence in favor of H0 was weak for medically treated PDA (BF10 = 0.55; 6 studies). In addition, BMA found strong evidence in favor of H1 when prolonged exposure to PDA was analyzed as a dichotomous variable (BF10 = 11.80; 6 studies) and extreme evidence (BF10 = 113.60; 3 studies) when PDA exposure time was analyzed as a continuous variable. In this bayesian meta-analysis, the data suggest that prolonged exposure to PDA might be associated with increased risk of pulmonary vascular disease in extremely preterm infants. This highlights the need to monitor for PH in high-risk preterm infants with prolonged exposure to PDA and to incorporate PH risk into clinical decisions regarding PDA management.

Nearly Half of Extreme Preterm Infants Are Iron Deficient at 4-6 Months of Corrected Age Despite Prophylactic Iron Supplementation

Background: Iron deficiency (ID) is the most prevalent micronutrient deficiency globally and has been associated with negative neurodevelopmental and behavioral outcomes in infants and young children. Susceptibility to ID is heightened in preterm infants due to lower iron reserves at birth, rapid growth during the initial weeks of life, immature erythropoiesis, and frequent blood samplings during hospitalization. To mitigate this problem, international bodies recommend prophylactic iron therapy from 2-6 weeks of age until at least 6-12 months in preterm infants. Currently, the literature regarding iron status in extremely preterm infants (EPI, infants born less than 28 weeks gestational age) who receive prophylactic iron supplementation after birth is limited. Considering the potential long-term detrimental effects of ID on the developing brain of these high-risk preterm infants, examining the prevalence and risk factors for ID are crucial to implement prevention strategies. Objective: To investigate the prevalence and risk factors associated with ID in EPI Methods: A retrospective cohort study was conducted using a population-based Provincial Perinatal Follow-Up database on all live EPIs born in Nova Scotia between 2005 and 2018. Infants with congenital malformations, chromosomal anomalies, blood disorders or those who died before outcome assessment were excluded. Prophylactic iron supplementation (2-3 mg/kg/day) starting at 2-4 weeks of chronological age was a standard of care for all included infants. Further, the dosage of iron was adjusted regularly during the hospital stay based on serum ferritin (SF) levels. Discharge instructions recommended continuing iron prophylaxis until 9-12 months corrected age (CA). At 4-6 months CA, all infants underwent blood tests to evaluate hemoglobin, and SF levels. ID was defined as SF levels below 20g/L or 12g/L at 4 and 6 months CA, respectively. A univariate analysis was performed by using a series of single-variable logistic regression models to identify the factors associated with presence of ID. Factors with a p-value &amp;lt; 0.20 in the univariate analysis were entered into a multivariable risk model using a backward selection procedure. Variables with a p-value &amp;lt; 0.05 were retained. Results: Among 146 infants, 67 (45.9%) had ID. Ferritin (16.4 µg/L vs 50.0 µg/L, p &amp;lt; .001) and reticulocyte hemoglobin equivalent (28.4pg vs 31.6pg, p &amp;lt; .001) were significantly lower in the ID group than non-ID group. The prevalence of ID decreased over time, from 59.7% in 2005-2011 to 40.3% in 2012-2018 (p = 0.52). Table 1 compares the antenatal and neonatal characteristics of the ID and non-ID groups. Table 2 compares sociodemographic variables and clinical variables at 4-6 months CA between two groups. Breastfeeding (exclusive or partial) versus formula alone at a 4-6 months CA was identified as an independent factor protective for ID (Odds: 0.2 (0.1 - 0.6), p = 0.003). Iron therapy at follow-up was also protective for ID but did not remain significant in the final model. Of note, iron therapy was stopped in 40 (27.4%) EPI before 4-6 months CA. Supplemental iron intake at 4-6 months CA was significantly lower in the infants receiving exclusive formula feeding (66.1%) compared with those breastfed (99.1%, p = 0.006). Conclusion(s): Despite prophylactic iron supplementation, nearly half of the EPI had ID at 4-6 months CA, and iron therapy was discontinued in roughly a quarter of all EPI before 4-6 months CA. Breastfeeding at 4-6 months follow-up was found to be protective for ID. High prevalence of ID in EPI highlights the need for further research in this area to avert the negative neurodevelopmental consequences of ID on the developing brain of these high-risk infants. Closer monitoring of iron status and early identification of children at high risk for ID is imperative to maximize the benefits of prophylactic iron supplementation in EPI. Further, there is lack of sufficient data for iron requirements in EPI leading to a variability in iron therapy recommendations by different professional organizations. Future prospective studies to investigate specific iron requirements of EPI as well as risk factors for ID in this high-risk vulnerable population are essential to optimize their neurodevelopmental outcomes.

Noninvasive Monitoring Strategies for Bronchopulmonary Dysplasia or Post-Prematurity Respiratory Disease: Current Challenges and Future Prospects.

Definitions of bronchopulmonary dysplasia (BPD) or post-prematurity respiratory disease (PPRD) aim to stratify the risk of mortality and morbidity, with an emphasis on long-term respiratory outcomes. There is no univocal classification of BPD due to its complex multifactorial nature and the substantial heterogeneity of clinical presentation. Currently, there is no definitive treatment available for extremely premature very-low-birth-weight infants with BPD, and challenges in finding targeted preventive therapies persist. However, innovative stem cell-based postnatal therapies targeting BPD-free survival are emerging, which are likely to be offered in the first few days of life to high-risk premature infants. Hence, we need easy-to-use noninvasive tools for a standardized, precise, and reliable BPD assessment at a very early stage, to support clinical decision-making and to predict the response to treatment. In this non-systematic review, we present an overview of strategies for monitoring preterm infants with early and evolving BPD-PPRD, and we make some remarks on future prospects, with a focus on near-infrared spectroscopy (NIRS).

Cost minimization analysis of a hexavalent vaccine in Argentina

BackgroundArgentina currently uses a pentavalent vaccine containing diphtheria, tetanus, pertussis (whole cell), Haemophilus influenza type b and hepatitis B antigens, administered concomitantly with the inactivated polio vaccine (IPV) (DTwP-Hib-HB plus IPV) in its childhood vaccination schedule. However, hexavalent vaccines containing acellular pertussis antigens (DTaP-Hib-HB-IPV) and providing protection against the same diseases are also licensed, but are only available with a private prescription or for high-risk pre-term infants in the public health program. We analyzed the cost of switching from the current schedule to the alternative schedule with the hexavalent vaccine in Argentina, assuming similar levels of effectiveness.MethodsThe study population was infants ≤ 1 year of age born in Argentina from 2015 to 2019. The analysis considered adverse events, programmatic, logistic, and vaccine costs of both schemes from the societal perspective. The societal costs were disaggregated to summarize costs incurred in the public sector and with vaccination pre-term infants in the public sector. Costs were expressed in 2021 US Dollars (US$).ResultsAlthough the cost of vaccines with the alternative scheme would be US$39.8 million (M) more than with the current scheme, these additional costs are in large part offset by fewer adverse event-associated costs and lower programmatic costs such that the overall cost of the alternative scheme would only be an additional US$3.6 M from the societal perspective. The additional cost associated with switching to the alternative scheme in the public sector and with the vaccination of pre-term infants in the public sector would be US$2.1 M and US$84,023, respectively.ConclusionsThe switch to an alternative scheme with the hexavalent vaccine in Argentina would result in marginally higher vaccine costs, which are mostly offset by the lower costs associated with improved logistics, fewer separate vaccines, and a reduction in adverse events.

Development and validation of an artificial intelligence based screening tool for detection of retinopathy of prematurity in a South Indian population.

The primary objective of this study was to develop and validate an AI algorithm as a screening tool for the detection of retinopathy of prematurity (ROP). Images were collected from infants enrolled in the KIDROP tele-ROP screening program. We developed a deep learning (DL) algorithm with 227,326 wide-field images from multiple camera systems obtained from the KIDROP tele-ROP screening program in India over an 11-year period. 37,477 temporal retina images were utilized with the dataset split into train (n = 25,982, 69.33%), validation (n = 4,006, 10.69%), and an independent test set (n = 7,489, 19.98%). The algorithm consists of a binary classifier that distinguishes between the presence of ROP (Stages 1-3) and the absence of ROP. The image labels were retrieved from the daily registers of the tele-ROP program. They consist of per-eye diagnoses provided by trained ROP graders based on all images captured during the screening session. Infants requiring treatment and a proportion of those not requiring urgent referral had an additional confirmatory diagnosis from an ROP specialist. Of the 7,489 temporal images analyzed in the test set, 2,249 (30.0%) images showed the presence of ROP. The sensitivity and specificity to detect ROP was 91.46% (95% CI: 90.23%-92.59%) and 91.22% (95% CI: 90.42%-91.97%), respectively, while the positive predictive value (PPV) was 81.72% (95% CI: 80.37%-83.00%), negative predictive value (NPV) was 96.14% (95% CI: 95.60%-96.61%) and the AUROC was 0.970. The novel ROP screening algorithm demonstrated high sensitivity and specificity in detecting the presence of ROP. A prospective clinical validation in a real-world tele-ROP platform is under consideration. It has the potential to lower the number of screening sessions required to be conducted by a specialist for a high-risk preterm infant thus significantly improving workflow efficiency.

Respiratory management and outcomes in high-risk preterm infants with development of a population outcome dashboard

IntroductionBronchopulmonary dysplasia (BPD) is associated with adverse long-term respiratory and neurodevelopmental outcomes. No recent studies examined the changing respiratory management and outcomes, particularly severe BPD, across a whole population.PurposeEvaluate the...

Impact of postnatal dexamethasone timing on preterm mortality and bronchopulmonary dysplasia: a propensity score analysis.

Postnatal dexamethasone (PND) is used in high-risk preterm infants after the first week of life to facilitate extubation and prevent bronchopulmonary dysplasia (BPD) but the optimal treatment timing remains unclear. Our objective was to explore the association between the timing of PND commencement and mortality and respiratory outcomes. This was a retrospective National Neonatal Research Database study of 84 440 premature infants born <32 weeks gestational age from 2010 to 2020 in England and Wales. Propensity score weighting analysis was used to explore the impact of PND commenced at three time-points (2-3 weeks (PND2/3), 4-5 weeks (PND4/5) and after 5 weeks (PND6+) chronological age) on the primary composite outcome of death before neonatal discharge and/or severe BPD (defined as respiratory pressure support at 36 weeks) alongside other secondary respiratory outcomes. 3469 infants received PND. Compared with PND2/3, infants receiving PND6+ were more likely to die and/or develop severe BPD (OR 1.68, 95% CI 1.28-2.21), extubate at later postmenstrual age (mean difference 3.1 weeks, 95% CI 2.9-3.4 weeks), potentially require respiratory support at discharge (OR 1.34, 95% CI 1.06-1.70) but had lower mortality before discharge (OR 0.38, 95% CI 0.29-0.51). PND4/5 was not associated with severe BPD or discharge respiratory support. PND treatment after 5 weeks of age was associated with worse respiratory outcomes although residual bias cannot be excluded. A definitive clinical trial to determine the optimal PND treatment window, based on early objective measures to identify high-risk infants, is needed.

Impact of the COVID-19 Pandemic on a Clinical Trial: A Quantitative Report on Study Engagement and Strategies.

The COVID-19 pandemic impacted clinical research worldwide potentially altering research findings. The study purpose was to measure the effect of the pandemic on recruitment, retention, assessment, and intervention completion rates. Enrollment and participation data from a clinical trial evaluating efficacy of a physical therapy intervention for high-risk preterm infants were compared across 3 pandemic periods (February 2019 through November 2021). Recruitment, retention, assessment, and intervention completion rates were lowest during the peak pandemic period. In compliance with the Human Subjects Review Board, and for the participants' and staff safety, transition from in-person to telehealth or hybrid visits was required to continue this longitudinal study. Despite the negative effect of the pandemic, parental resilience and commitment to the study was clear. Flexibility, quick action, dedication, and efficiency of the research team were key elements enabling study continuation with successful transition to telehealth assessments/interventions during the peak pandemic period.

Antibiotics Use and Its Effects on the Establishment of Feeding Tolerance in Preterm Neonates.

Antibiotics are one of the most widely used medications in today's neonatal intensive care units. Indiscriminate antibiotic usage persists in preterm newborns who are symptomatic due to factors linked to prematurity rather than being septic. Previous studies in older infants suggest that prior antibiotic administration is associated with possible dysmotility and microbial dysbiosis in the intestinal tract. We hypothesize that early antibiotic administration impacts high-risk preterm infants' tolerance to enteral feeding advancement. As part of the Routine Early Antibiotic Use in SymptOmatic Preterm Neonates study, symptomatic preterm newborns without maternal infection risk factors were randomized to receive or not receive antibiotics, with C1 receiving antibiotics and C2 not. Of the 55 newborns that underwent pragmatic randomization, 28 preterm neonates in group C1 received antibiotics. The premature neonates in the randomized groups who received antibiotics and those who did not showed no differences in sustained feeding tolerance. Our investigation of the risk of feeding issues in babies who get antibiotics early in life revealed no differences between neonates who received antibiotics and those who did not when the randomized controlled trial data alone was reviewed. Given the sample sizes, it is uncertain if the preceding analysis is powerful enough to detect differences (a significant percentage of neonates who were randomly assigned to NOT get antibiotics subsequently received early treatment due to changing clinical conditions). This affirms the requirement for a meticulously designed prospective randomized study. · Defining feeding tolerance for the first time in neonates.. · Patients from the REASON trial were evaluated.. · Preterm neonates were the focus of this study..

Effect of Nasal Continuous Positive Airway Pressure vs Heated Humidified High-Flow Nasal Cannula on Feeding Intolerance in Preterm Infants With Respiratory Distress Syndrome

Respiratory distress syndrome and feeding intolerance are common conditions that are often associated with preterm infants. Showing similar efficacy, nasal continuous positive airway pressure (NCPAP) and heated humidified high-flow nasal cannula (HHHFNC) are the most widespread noninvasive respiratory support (NRS) in neonatal intensive care units, but their effect on feeding intolerance is unknown. To evaluate the effect of NCPAP vs HHHFNC on high-risk preterm infants with respiratory distress syndrome. This multicenter randomized clinical trial involved infants who were born in 1 of 13 neonatal intensive care units in Italy between November 1, 2018, and June 30, 2021. Preterm infants with a gestational age of 25 to 29 weeks, who were suitable for enteral feeding and who proved to be medically stable on NRS for at least 48 hours were enrolled in the study within the first week of life and randomized to receive either NCPAP or HHHFNC. Statistical analysis was performed according to the intention-to-treat approach. NCPAP or HHHFNC. The primary outcome was the time to full enteral feeding (FEF), defined as an enteral intake of 150 mL/kg per day. Secondary outcomes were the median daily increment of enteral feeding, signs of feeding intolerance, effectiveness of the assigned NRS, peripheral oxygen saturation (SpO2)-fraction of inspired oxygen (FIO2) ratio at changes of NRS, and growth. Two-hundred forty-seven infants (median [IQR] gestational age, 28 [27-29] weeks; 130 girls [52.6%]) were randomized to the NCPAP group (n = 122) or the HHHFNC group (n = 125). There were no differences in the primary and secondary nutritional outcomes between the 2 groups. The median time to reach FEF was 14 days (95% CI, 11-15 days) in the NCPAP group and 14 days (95% CI, 12-18 days) in the HHHFNC group, and similar results were observed in the subgroup of infants with less than 28 weeks' gestation. On the first NRS change, higher SpO2-FIO2 ratio (median [IQR], 4.6 [4.1-4.7] vs 3.7 [3.2-4.0]; P < .001) and lower rate of ineffectiveness (1 [4.8%] vs 17 [73.9%]; P < .001) were observed in the NCPAP vs HHHFNC group. This randomized clinical trial found that NCPAP and HHHFNC had similar effects on feeding intolerance, despite different working mechanisms. Clinicians may tailor respiratory care by selecting and switching between the 2 NRS techniques on the basis of respiratory effectiveness and patient compliance, without affecting feeding intolerance. ClinicalTrials.gov Identifier: NCT03548324.

Increasing the dose of ibuprofen with postnatal age to close a hemodynamically significant patent ductus arteriosus in very preterm infants.

Patent ductus arteriosus (PDA) is associated with neonatal morbidities in high-risk preterm infants. Early neonatal treatment by ibuprofen induces the ductus arteriosus (DA) closure in approximatively 60% of infants. Dose escalation of ibuprofen according to postnatal age has been suggested for improving the DA closure rate. The aim of this study was to assess the efficacy and tolerance of an increasing dose regimen of ibuprofen. This single-center retrospective cohort study involved infants hospitalized from 2014 to 2019 in our neonatal unit. Selection criteria were gestational age < 30weeks, birth weight < 1000g, and treatment by ibuprofen. Three dose levels were used and consisted of a daily intravenous injection of ibuprofen-tris-hydroxymethyl-aminomethane (ibuprofen-THAM) for three consecutive days: (i) 10 -5 -5mg/kg before the 70th h of life (H70) (dose level 1), (ii) 14 -7 -7mg/kg between H70 and H108 (dose level 2), (iii) 18 -9 -9mg/kg after H108 (dose level 3). The ibuprofen-induced DA closure was compared between ibuprofen schedules, and the Cox proportional-hazard regression was performed to identify factors associated with the ibuprofen efficacy. Tolerance was assessed through renal function, acidosis, and platelet count. One hundred forty-three infants met the inclusion criteria. The ibuprofen-induced DA closure was observed in 67 infants (46.8%). One course of ibuprofen at dose level 1 was more efficient in closing the DA than other schedules (dose level 1, one course (n = 70): 71%, dose level 2 or 3, one course (n = 20): 45%, two-course schedules (n = 53): 15%, p < 0.0001). Independent factors associated with ibuprofen-induced DA closure were a complete antenatal schedule of steroids (p = 0.001), a lower CRIB II score (p = 0.009), and a lower and earlier exposure to ibuprofen (p < 0.0001 and p = 0.002). No severe side effects were observed. Neonatal mortality and morbidities were similar regardless of the infant's response to ibuprofen. Conclusion: Increasing ibuprofen doses with postnatal age failed to reach an efficacy similar to earlier treatment. Although the infant response to ibuprofen was likely to depend on multiple factors, the optimal use of ibuprofen included its early initiation. What is Known: • Ibuprofen is the current first-line treatment for patent ductus arteriosus during the early neonatal period in very preterm infants. • However, the ibuprofen efficacy rapidly declined with postnatal age during the first week of life. A dose escalation of ibuprofen according to postnatal age has been suggested to improve the ibuprofen-induced ductus arteriosus closure. What is New: • The rapid drop of ibuprofen's ability to close hemodynamically significant patent ductus arteriosus persisted beyond the postnatal day 2 despite the dose adjustment arguing for an early initiation to optimize its efficacy. • The early selection of patients who will suffer from patent ductus arteriosus-related morbidities and who will positively respond to ibuprofen is an issue that could determine the future place of ibuprofen in the patent ductus arteriosus management.

Assessment of role of cranial ultrasound (CUS) in the evaluation of high-risk preterm and term neonates

BackgroundCranial ultrasonography (CUS) has become an important tool to depict normal brain anatomy and to detect the ischemic and hemorrhagic brain injury patterns in high-risk neonates. The present study aimed to assess the utility of CUS to diagnose the spectrum of brain injury patterns in high-risk preterm and term neonates admitted to the neonatal intensive care unit (NICU) and to find the association of CUS findings in various adverse antenatal and perinatal feto-maternal factors.ResultsOut of the 200 neonates, 76 (38%) neonates had abnormal CUS findings and 124 (62%) had a normal CUS. Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) (28/76; 36.8 %) was the commonest abnormality with GMH (grade 1) in 14/76 (18.4%), grade 2 in 7 (9.2%), grade 3 in 5 (6.5%), and grade 4 in 2 (2.63%). The other findings observed were cerebral edema (14/76; 18.4%), thalamic hyperechogenicity (10/76; 13.1%), periventricular leukomalacia (PVL) (4/76; 5.2%), and congenital anomalies (8; 10.5%). Abnormal CUS findings had a statistically significant association with birth weight <2000 g, prematurity, Apgar score <7, and adverse peri-natal fetal and maternal factors (all p-values <0.05). Abnormal CUS findings had a statistically significant association with poor cry, poor activity, abnormal tone, and presence of cyanosis (all p-values <0.05).ConclusionIn this cohort study of high-risk preterm and term infants GMH-IVH, cerebral edema, thalamic hyperechogenicity, PVL, and congenital malformations were the commonest lesions detected on CUS. Abnormal CUS findings were found to have a statistically significant association with various adverse peri-natal fetal and maternal factors.

Protective Effects of Early Caffeine Administration in Hyperoxia-Induced Neurotoxicity in the Juvenile Rat.

High-risk preterm infants are affected by a higher incidence of cognitive developmental deficits due to the unavoidable risk factor of oxygen toxicity. Caffeine is known to have a protective effect in preventing bronchopulmonary dysplasia associated with improved neurologic outcomes, although very early initiation of therapy is controversial. In this study, we used newborn rats in an oxygen injury model to test the hypothesis that near-birth caffeine administration modulates neuronal maturation and differentiation in the hippocampus of the developing brain. For this purpose, newborn Wistar rats were exposed to 21% or 80% oxygen on the day of birth for 3 or 5 days and treated with vehicle or caffeine (10 mg/kg/48 h). Postnatal exposure to 80% oxygen resulted in a drastic reduction of associated neuronal mediators for radial glia, mitotic/postmitotic neurons, and impaired cell-cycle regulation, predominantly persistent even after recovery to room air until postnatal day 15. Systemic caffeine administration significantly counteracted the effects of oxygen insult on neuronal maturation in the hippocampus. Interestingly, under normoxia, caffeine inhibited the transcription of neuronal mediators of maturing and mature neurons. The early administration of caffeine modulated hyperoxia-induced decreased neurogenesis in the hippocampus and showed neuroprotective properties in the neonatal rat oxygen toxicity model.