Furosemide and Ductus Arteriosus Closure in Very-Low-Birth-Weight Preterm Infants: A Comprehensive Retrospective Study.

Ductus arteriosus closure may be delayed in preterm infants, and prostaglandin, a vasodilator, can affect ductal patency. Furosemide can increase renal prostaglandin synthesis, so its net effect on patent ductus arteriosus (PDA) is uncertain. Our goal is to explore the relationship between furosemide and spontaneous ductal closure in very-low-birth-weight preterm infants. Our treatment for PDA involves fluid restriction initially and furosemide administration for hemodynamically significant PDA until closure is confirmed by the echocardiogram. We enrolled 105 infants from 1 January 2019 to 30 June 2022 and evaluated the impact of furosemide on ductal closure, including exposure duration and cumulative dose. There is no correlation between furosemide exposure and spontaneous ductal closure (p = 0.384). Furosemide exposure does not delay the postmenstrual age at which spontaneous ductal closure occurs (p = 0.558). The time for spontaneous ductal closure is positively associated with furosemide prescription days (coefficient value = 0.547, p = 0.026) and negatively with gestational age (coefficient value = -0.384, p = 0.062). The prescription of furosemide does not impact the probability or time duration of ductus arteriosus spontaneous closure. The cumulative dose of furosemide has minimal impact on ductal closure. The correlation between furosemide exposure duration and ductal patency duration is likely due to our treatment protocol, with gestational age being a significant factor.

The Outcomes of Preterm Infants with Neonatal Respiratory Distress Syndrome Treated by Minimally Invasive Surfactant Therapy and Non-Invasive Ventilation.

In recent years, the utilization of minimally invasive surfactant therapy (MIST) and Non-invasive ventilation (NIV) as the primary respiratory assistance has become increasingly prevalent among preterm infants with neonatal respiratory distress syndrome (RDS). This study aims to compare the outcomes between MIST administered with nasal continuous positive airway pressure (NCPAP) versus nasal intermittent positive pressure ventilation (NIPPV), with the objective of exploring the respiratory therapeutic benefits of these two approaches. This retrospective study collected data from the neonatal intensive care unit of Kaohsiung Medical University Hospital spanning from January 2016 to June 2021. Infants were divided into two groups based on the type of NIV utilized. The NCPAP group comprised 32 infants, while the NIPPV group comprised 22 infants. Statistical analysis revealed significant differences: the NIPPV group had a smaller gestational age, lower birth weight, higher proportion of female infants, and earlier initiation of MIST. Additionally, the NIPPV group exhibited higher incidence rates of retinopathy of prematurity, longer respiratory support duration, prolonged hospitalization, and mortality. However, upon adjustment, these differences were not statistically significant. Analysis of venous blood gas and respiratory parameter changes indicated that both the NCPAP and NIPPV groups experienced improvements in oxygenation and ventilation following MIST.

Relationship between orofacial dysfunction and orofacial features, oral function, and eating performance among preschool children.

Background/purpose: Orofacial (OF) development is influenced by multiple factors. This study aimed to explore the relationship between OF dysfunction (OFD) and OF features, oral function, and eating performance among preschool children. Materials and methods: There were 243 preschool children and their parents who participated in this cross-sectional study. Participant demographic information and eating performance were obtained from questionnaires completed by their mothers. OF features and functions were assessed using oral examinations. OFD assessments were performed using Nordic Orofacial Test-Screening (NOT-S). Results: Approximately 80% of participants had at least one domain of NOT-S affected. The main OFD in a structured interview was chewing and swallowing (64.61%). Dysarthria (40.38%), weak bite force (53.85%), inability to effectively chew (45.19%), and taking longer than 30 min to eat meals (75.00%) were significantly more prevalent among participants with OFD than among those without OFD (all P < 0.05). Also, compared with participants born full-term, those born prematurely and who had OFD had higher rates of V-shaped dental arch (42.11%), high-arched palate (31.58%), small mouth opening capacity (7.89%), dysarthria (65.79%), preference to eating soft-textured food (42.11%), and weak cough strength (21.05%). Taking longer than 30 min to eat meals (adjusted odds ratio (AOR = 8.87, P < 0.001) and not effectively chewing food (AOR = 8.81, P < 0.001) were significantly associated with OFD. Conclusion: Chewing and swallowing and habits are common among preschool children and associated with OFD. OFD is associated with OF features, and presented in oral function and eating performance.

Comparison of Two Methods for Weaning from Nasal Continuous Positive Airway Pressure via the Cyclic Use of High-Flow Nasal Cannula or Room Air in Preterm Infants.

Nasal continuous positive airway pressure (NCPAP) is extensively used for preterm infants experiencing respiratory distress syndrome (RDS). Weaning from NCPAP includes direct weaning or gradually extending room air exposure. However, a high-flow nasal cannula (HFNC) is an alternative weaning method. Therefore, this study evaluated the clinical outcomes of HFNC and progressively increasing room air duration as weaning strategies. This study enrolled 46 preterm infants with RDS receiving NCPAP support who underwent the cyclic use of NCPAP and HFNC weaning protocol as the HFNC group; a retrospective analysis included 87 preterm infants weaned from NCPAP by gradually extending room air duration as the room air group. Differences in clinical conditions, complications, and short-term outcomes between the weaning methods were compared. The mean post-menstrual age at initiating NCPAP weaning was lower in the room air group than in the HFNC group (mean ± SD, 35.2 ± 2.3 weeks vs. 33.2 ± 2.5 weeks, p < 0.001). Hospital stay duration and total respiratory therapy days were longer in the HFNC group (96 ± 38 days and 80 ± 37 days, respectively) than in the room air group (78 ± 28 days and 56 ± 25 days, respectively), with p-values of 0.006 and <0.001. In conclusion, employing HFNC for weaning from NCPAP resulted in longer hospital admissions and respiratory therapy days than the room air method. However, further studies with a larger sample size are warranted for a more comprehensive evaluation, given the limited number of enrolled patients.

Developing a practical neurodevelopmental prediction model for targeting high-risk very preterm infants during visit after NICU: a retrospective national longitudinal cohort study.

BACKGROUND: Follow-up visits for very preterm infants (VPI) after hospital discharge is crucial for their neurodevelopmental trajectories, but ensuring their attendance before 12 months corrected age (CA) remains a challenge. Current prediction models focus on future outcomes at discharge, but post-discharge data may enhance predictions of neurodevelopmental trajectories due to brain plasticity. Few studies in this field have utilized machine learning models to achieve this potential benefit with transparency, explainability, and transportability. METHODS: We developed four prediction models for cognitive or motor function at 24 months CA separately at each follow-up visits, two for the 6-month and two for the 12-month CA visits, using hospitalized and follow-up data of VPI from the Taiwan Premature Infant Follow-up Network from 2010 to 2017. Regression models were employed at 6 months CA, defined as a decline in The Bayley Scales of Infant Development 3rd edition (BSIDIII) composite score > 1 SD between 6- and 24-month CA. The delay models were developed at 12 months CA, defined as a BSIDIII composite score < 85 at 24 months CA. We used an evolutionary-derived machine learning method (EL-NDI) to develop models and compared them to those built by lasso regression, random forest, and support vector machine. RESULTS: One thousand two hundred forty-four VPI were in the developmental set and the two validation cohorts had 763 and 1347 VPI, respectively. EL-NDI used only 4-10 variables, while the others required 29 or more variables to achieve similar performance. For models at 6 months CA, the area under the receiver operating curve (AUC) of EL-NDI were 0.76-0.81(95% CI, 0.73-0.83) for cognitive regress with 4 variables and 0.79-0.83 (95% CI, 0.76-0.86) for motor regress with 4 variables. For models at 12 months CA, the AUC of EL-NDI were 0.75-0.78 (95% CI, 0.72-0.82) for cognitive delay with 10 variables and 0.73-0.82 (95% CI, 0.72-0.85) for motor delay with 4 variables. CONCLUSIONS: Our EL-NDI demonstrated good performance using simpler, transparent, explainable models for clinical purpose. Implementing these models for VPI during follow-up visits may facilitate more informed discussions between parents and physicians and identify high-risk infants more effectively for early intervention.

Mobile Device-Based Video Screening for Infant Head Lag: An Exploratory Study.

INTRODUCTION: Video-based automatic motion analysis has been employed to identify infant motor development delays. To overcome the limitations of lab-recorded images and training datasets, this study aimed to develop an artificial intelligence (AI) model using videos taken by mobile phone to assess infants' motor skills. METHODS: A total of 270 videos of 41 high-risk infants were taken by parents using a mobile device. Based on the Pull to Sit (PTS) levels from the Hammersmith Motor Evaluation, we set motor skills assessments. The videos included 84 level 0, 106 level 1, and 80 level 3 recordings. We used whole-body pose estimation and three-dimensional transformation with a fuzzy-based approach to develop an AI model. The model was trained with two types of vectors: whole-body skeleton and key points with domain knowledge. RESULTS: The average accuracies of the whole-body skeleton and key point models for level 0 were 77.667% and 88.062%, respectively. The Area Under the ROC curve (AUC) of the whole-body skeleton and key point models for level 3 were 96.049% and 94.333% respectively. CONCLUSIONS: An AI model with minimal environmental restrictions can provide a family-centered developmental delay screen and enable the remote monitoring of infants requiring intervention.

Feasibility of Endotracheal Extubation Evaluation Form in Predicting Successful Extubation in Neonatal Intensive Care Units: A Retrospective Study.

Given the limited availability of evidence-based methods for assessing the timing of extubation in intubated preterm infants, we aimed to standardize the extubation protocol in this single-center, retrospective study. To accomplish this, we established an extubation evaluation form to assess the suitability of extubation in preterm infants. The form comprises six indicators: improved clinical condition, spontaneous breath rate ≥ 30 breaths per minute, peak inspiratory pressure (PIP) ≤ 15 cmH2O, fraction of inspired oxygen (FiO2) ≤ 30%, blood pH ≥ 7.2, and mixed venous carbon dioxide tension (PvCO2) < 70 mmHg. Each positive answer is given one point, indicating a maximum of six points. We enrolled 41 intubated preterm infants (gestational age < 32 weeks, birth weight < 1500 g) who were receiving mechanical ventilation support for over 24 h. Among them, 35 were successfully extubated, and 6 were not. After completing the extubation evaluation form and adjusting for birth weight and postextubation device, we observed that the total score of the form was significantly associated with successful extubation; the higher the score, the greater the chance of successful extubation. Thus, we infer that the extubation evaluation form may provide a more objective standard for extubation assessment in preterm infants.

Clinical outcomes of different patent ductus arteriosus treatment in preterm infants born between 28 and 32 weeks in Taiwan.

BACKGROUND: The patent ductus arteriosus (PDA) treatment in very preterm infants is controversial. This study focused on preterm infants born at 28-32 weeks of gestation and analyzed the association between various PDA treatments and clinical outcomes. METHODS: We conducted a retrospective cohort study of infants born at 28-32 weeks of gestation between 2016 and 2019 at 22 hospitals in the Taiwan Premature Infant Follow-up Network. We categorized the infants into four groups according to treatment strategies: medication, primary surgery, medication plus surgery, or conservative treatment. RESULTS: A total of 1244 infants presented with PDA, and 761 (61.1%) were treated. Medication was the predominant treatment (50.0%), followed by conservative treatment (38.9%), medication plus surgery (7.6%), and primary surgery (3.5%). The risk of mortality was not reduced in the active treatment group compared to the conservative treatment group. There was a higher prevalence of severe intraventricular hemorrhage, necrotizing enterocolitis (NEC), and any degree of bronchopulmonary dysplasia (BPD) in both the primary surgery and medication plus surgery groups than in the conservative treatment group. After adjustment, both the primary surgery and medication plus surgery groups still had higher odds ratios for the occurrence of NEC and any degree of BPD. CONCLUSIONS: Compared with active PDA treatment, conservative treatment for PDA did not increase the risk of mortality and morbidity in very preterm infants born at 28-32 weeks of gestation. The risks and benefits of surgery (PDA ligation) in these infants must be considered cautiously.

Risks of attention-deficit/hyperactivity disorder, autism spectrum disorder, and intellectual disability in children delivered by caesarean section: A population-based cohort study.

This population-based study investigated the risks of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disabilities among children delivered by Cesarean section (CS) in comparison with those who were delivered by vaginal delivery (VD). The Taiwan Maternal and Child Health Database from 2004 to 2016 registered 675,718 and 1,208,983 children delivered by CS and by VD, respectively. The results of Cox proportional hazards regression model demonstrated that children delivered by CS had significantly higher risks of ADHD, ASD, and intellectual disability than those delivered by VD after the confounding effects of maternal and child factors were controlled for.

Congenital Surfactant C Deficiency with Pulmonary Hypertension-A Case Report.

Interstitial lung diseases in children are a diverse group in terms of etiology and pathogenesis. With advances in genetic testing, mutations in surfactant protein have now been identified as the etiology for childhood interstitial lung disease of variable onset and severity, ranging from fatal acute respiratory distress syndrome (RDS) in neonates to chronic lung disease in adults. We presented an 11-month-old girl with surfactant protein C deficiency and secondary pulmonary hypertension, successfully treated with hydroxychloroquine, and provided a detailed discussion of the clinical and diagnostic approach and management.

Effect of Small Volume Blood Sampling on the Outcomes of Very Low Birth Weight Preterm Infants.

Very low birth weight (VLBW) preterm infants universally experience anemia of prematurity (AOP) while growing up. The effects of reduced blood sample volume on AOP, packed red blood cell (PRBC) transfusion, and outcome in VLBW preterm infants were examined in this study. To reduce blood loss due to phlebotomy, we set up a small volume blood sampling procedure in VLBW infants. In this retrospective study, we compared the VLBW infants who had undergone standard blood sampling (control group, n = 20) with those who underwent small volume blood sampling (study group, n = 84), with both groups receiving PRBC transfusion under restrictive criteria. Blood loss from phlebotomy and PRBC transfusion volume over 30 days was significantly lower in the study group than in the control group. Compared to the control group, hematocrit, reticulocyte, and iron levels were significantly higher in the study group. There were no significant differences in the proportion of patent ductus arteriosus, severe intraventricular hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia between the two groups. The small volume blood sampling resulted in lower PRBC transfusion volume, less severe anemia, and greater bone marrow function at 30 days of age. This strategy can reduce potential adverse effects of PRBC transfusion in VLBW preterm infants.

Body Weight Gain Status during the Incubator Weaning Process in Very Low Birth Weight Premature Infants.

Incubator care is essential for premature infants during early hospitalization. As the infants' conditions improve, incubator weaning becomes necessary. This retrospective study aimed to evaluate the effect of body weight gain and status of intake-calorie gain on the incubator weaning process for very low birth weight (VLBW) premature infants. The study included 127 VLBW premature neonates. We analyzed data on clinical characteristics potentially associated with the weaning period and the end-weaning body weight (EWBW), including body weight gain status, intake-calorie gain status, and disease conditions. The neonates were weaned from the incubators at a mean postmenstrual age (PMA) of 35.1 ± 1.3 weeks; postnatal days, 37.7 ± 18.2 days; and body weight, 1882.8 ± 157.1 g. The total weaning period was 3.5 ± 3.1 days. Regarding the weaning period, there was a strong positive relationship only in the end-weaning PMA and the daily body weight within 3 days before incubator weaning. Further, regarding the factors associated with EWBW, only the end-weaning PMA and necrotizing enterocolitis had a significant positive impact. Body weight gain and the status of intake-calorie gain showed no association with either the weaning period or the EWBW and, thus, were not related to the incubator weaning process.

Unique Pulmonary Hypertension in Young Children: A Case Series Study.

Pediatric pulmonary hypertension (PH) has a similar clinical presentation to the adult disease but is associated with several additional disorders and challenges that require a specific approach for their fulminant course. With improved care for premature infants, various forms of pulmonary vascular disease have been found in children that did not previously exist. Pediatric PH can begin in utero, resulting in pulmonary vascularity growth abnormalities that may persist into adulthood. Here, we retrospectively reviewed several unique pediatric PH cases from 2000 to 2020 at Kaohsiung Medical University Hospital, Taiwan, a tertiary teaching hospital. Their comorbidities varied and included surfactant dysfunction, bronchopulmonary dysplasia, premature closure of the ductus arteriosus, high levels of renin and aldosterone, and Swyer-James-Macleod syndrome. Their clinical profiles, radiological characteristics, echocardiography, pulmonary angiogram, and therapeutic regimens were recorded. Further, because the underlying causes of pediatric PH were complex and markedly different according to age, adult PH classification may not be applicable to pediatric PH in all settings. We also classified these cases using different systems, including the Panama classification and the Sixth World Symposium on PH, and compared their advantages and disadvantages.

Impact of Illness Severity and Interventions on Successful Weaning from Nasal CPAP in Very Preterm Neonates: An Observational Study.

This study aims to identify clinical variables that could affect successful weaning from nasal continuous positive airway pressure (NCPAP) in very preterm infants. Infants born at a gestational age (GA) of <32 weeks were retrospectively enrolled. Weaning from NCPAP was initiated when the infants were clinically stable. In the univariate analysis, GA, birth weight, body weight (BW) z-score at the time of successful NCPAP weaning, intubation, total duration of intubation, respiratory distress syndrome grade, APGAR score at the 1 and 5 min, initial shock, anemia, bronchopulmonary dysplasia, number of blood transfusions, total duration of dopamine use, administration of more than two doses of surfactant, use of aminophylline, use of a diuretic, and total duration of total parenteral nutrition were significantly associated with postmenstrual age (PMA) at the time of successful NCPAP weaning. Multivariate analysis showed that the total duration of intubation, bronchopulmonary dysplasia, and administration of more than two doses of surfactant were positively associated with PMA at the time of successful NCPAP weaning. A reverse association was noted between BW z-score and PMA at the time of successful NCPAP weaning. Sufficient nutrition and avoidance of further ventilator-induced lung injury could decrease NCPAP duration in very preterm infants.

New developments in neonatal respiratory management.

Respiratory distress syndrome (RDS) is the major cause of respiratory failure in preterm infants due to immature lung development and surfactant deficiency. Although the concepts and methods of managing respiratory problems in neonates have changed continuously, determining appropriate respiratory treatment with minimal ventilation-induced lung injury and complications is crucially important. This review summarizes neonatal respiratory therapy's advances and available strategies (i.e., exogenous surfactant therapy, noninvasive ventilation, and different ventilation modes), focusing on RDS management.

Study of Orofacial Function in Preschool Children Born Prematurely.

Children born prematurely often exhibit orofacial dysfunction. We conducted Nordic Orofacial Test Screening and analyzed chewing and swallowing functions of 243 children aged 3−5 years, consisting of 142 and 101 children born full-term and preterm, respectively, to evaluate the orofacial function of preschool premature children. Categorical variables were analyzed using chi-square test for a comparison. The univariate analysis of variance was used to analyze the effects of birth weight, gestational age, intubation at birth, use of nasal continuous positive airway pressure support after birth, and use of nasogastric tube on the chewing and swallowing functions of children born prematurely. In this survey, term-born children had a higher incidence of bad oral habits, grinding teeth while sleeping, and abnormal gulping compared to preterm-born children. Preterm-born children had a higher incidence of choking, decreased mouth opening (<30 mm), abnormal dental arch form, abnormal palatal vault, and dysarthria compared to term-born children.

Risk of Respiratory Infectious Diseases and the Role of Methylphenidate in Children with Attention-Deficit/Hyperactivity Disorder: A Population-Based Cohort Study.

Children with attention-deficit/hyperactivity disorder (ADHD) are commonly affected by medical illness. The aim of the present study was to explore the risks of contracting respiratory infectious diseases (RIDs), including upper and lower RIDs and influenza, in children with ADHD. We also examined whether methylphenidate has a protective effect regarding the risk of contracting RIDs among children with ADHD who have a history of methylphenidate treatment. Children in the Taiwan Maternal and Child Health Database from 2004 to 2016 were included in the present study. Upper and lower RIDs, influenza, ADHD, age, sex, and records of methylphenidate prescription were identified. A Cox proportional hazards regression model was used to estimate the significance of the risk of RIDs among children with ADHD in comparison with that among children without ADHD after adjustment for sex and age. The self-controlled case series analysis was conducted to examine the protective effect of methylphenidate treatment against RIDs. In total, 85,853 children with ADHD and 1,458,750 children without ADHD were included in the study. After controlling for sociodemographic variables, we observed that children with ADHD had significantly higher risks of upper RIDs, lower RIDs, and influenza infection than did those without ADHD. Among the children with ADHD who had a history of methylphenidate treatment, the risk of contracting RIDs was lower during the methylphenidate treatment period than during the nontreatment period. Children with ADHD had a higher RID risk than those without ADHD. Methylphenidate might reduce the risk of RIDs among children with ADHD who have a history of methylphenidate treatment.

3-MCPD and glycidol coexposure induces systemic toxicity and synergistic nephrotoxicity via NLRP3 inflammasome activation, necroptosis, and autophagic cell death.

3-Monochloropropane-1,2-diol (3-MCPD), 2,3-epoxy-1-propanol (glycidol), and their esters are well-known food contaminants mainly formed by the heat processing of certain refined oils and coexist in various kinds of foodstuffs. However, the combined health effect and the underlying mechanism of 3-MCPD and glycidol coexposure are not well-understood. In this study, we investigated the systemic toxicity effects and the nephrotoxicity mechanisms of 3-MCPD and glycidol coexposure with in vitro and in vivo models, and next-generation sequencing (NGS) analysis. It was found that 3-MCPD and glycidol coexposure for 28 days synergistically induced toxicity in the kidney, lung, testis, and heart in C57BL/6 mice. Kidney was the most sensitive organ to coexposure, and the coexposure had a synergistic effect on inflammation and cytotoxicity through activation of the NLRP3 inflammasome, and the induction of necroptosis, and autophagic cell death in NRK-52E cells. Moreover, the NGS results revealed the genes changes associated with nephrotoxicity, inflammation and with the broad toxicity effects induced by 3-MCPD or glycidol alone or in combination, which were consistent with the results of in vitro and in vivo models. In summary, we report for the first time of the comprehensive toxicity effects and the mechanisms caused by 3-MCPD and glycidol coexposure.