Cooling Under a Blanketrol System Versus Cooling With an Arctic Sun Thermoregulation System (CATS) for Neonates Undergoing Therapeutic Hypothermia.

Background Despite evidence suggesting improved outcomes in neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH), data on the impact of temperature variability during cooling and its association with clinical outcomes remain limited. Objective To compare the efficacy and ease of use of two different cooling systems, the Arctic Sun (Medivance, Inc., Louisville, CO) vs. the Blanketrol III (Gentherm Medical, Cincinnati, OH) on achieving TH, temperature variability, and clinical outcomes in neonates with HIE undergoing TH. Methods This study was conducted at the Baylor Scott and White Medical Center's Level IV NICU. The study employed a retrospective cohort design, comparing infants treated with the Arctic Sun device (from December 2020 to August 2021) to a historical cohort treated with the Blanketrol system (from January 2017 to November 2020). Both groups were evaluated for clinical characteristics, patients' outcomes, and ease of use of the cooling devices. Ease of use was assessed through a self-developed survey administered to NICU nurses. Core body temperatures throughout the cooling course were documented at four-hour intervals, including induction, maintenance, and rewarming phases. Results Twenty-two infants were cooled using the Arctic Sun system, and 44 infants were cooled with the Blanketrol device. Median birth weight and gestational age were comparable. There were no significant differences in one-minute and five-minute appearance, pulse, grimace, activity, and respiration (APGAR) scores. The Arctic Sun group had a significantly higher rate of maternal morbidities, including diabetes and placental abruption. Although the median temperature achieved with both devices was 33.5°C, temperature variability was significantly greater with the Blanketrol device (p = 0.03). Thrombocytopenia rates were statistically different between the groups (9% in Arctic Sun vs. 38% in Blanketrol, p = 0.001). Although the Blanketrol group had higher rates of disseminated intravascular coagulation (48% vs. 37%), hypercalcemia (23% vs. 5%), and subcutaneous fat necrosis (7% vs. 5%), these differences were not statistically significant. A nurses' survey on ease of use revealed a strong preference for the Arctic Sun cooling system. Over 85% of nurses found it easier to learn and set up and required less manual intervention than the Blanketrol device. Conclusions Gel adhesive pad-based TH is a potentially superior modality to traditional water-circulating cooling devices. These pads offer advantages in user-friendliness, improved temperature control precision, and potentially reduced adverse event profiles.

Pre-Medications for Non-Emergency Tracheal Intubation in the United States Neonatal Intensive Care Units.

BACKGROUND: Premedication in neonates undergoing elective intubation effectively minimizes the negative physiological events of bradycardia, systemic hypertension, intracranial hypertension, and hypoxia. Premedication decreases procedure-related pain and discomfort. This study aimed to evaluate the current practice of pre-intubation medications for non-emergent intubations in preterm and term neonates in the United States. STUDY DESIGN: A cross-sectional survey (Appendix) was sent via e-mail to all level 3 and 4 Neonatal Intensive Care Units (NICUs) of the Organization of Neonatal Perinatal Medicine Training Program Directors (ONTPD), NICU directors with pediatric residency only, and Baylor Scott and White Health, Mednax, and Envision health services systems. RESULTS: Of 170 responses, 41% (69/168) routinely premedicate, 38% (64/168) premedicate under specific circumstances, and 21% (35/168) do not administer any routine pre-intubation medications. Only 46% (77/168) of units had a written policy. The most frequently used drugs were fentanyl (68%, 116/170), atropine (39%, 66/170), midazolam (38%, 64/170), and morphine (26%, 45/170). 21% (36/170) used a two-drug combination, and 38% (64/170) used a three-drug combination. The most commonly used two-drug combination was atropine and fentanyl, and the most common three-drug combination was atropine, fentanyl, and a paralytic agent. CONCLUSION:  Despite the well-documented benefits of premedication for NICU intubations, as aligned with AAP recommendations, the US lags behind other nations, with stagnant rates since 2006. This disparity persists despite a rise in written policies, which exhibit significant content variations. The authors advocate for the adoption of standardized, AAP-aligned policies across all NICUs in the US. Continued research is vital to monitor the progress of this crucial practice and address any underlying barriers to implementation.

Evaluation of Autism Spectrum Disorder Risk in Infants With Intraventricular Hemorrhage.

Background This study evaluates the long-term risk of autism spectrum disorder (ASD) in infants with intraventricular hemorrhage (IVH) using the Modified Checklist for Autism in Toddlers-Revised with Follow-Up (M-CHAT-R/F) screening tool. Methods This retrospective cohort study compared IVH (exposed) infants across all gestational age groups with no-IVH (non-exposed) infants admitted to level IV neonatal intensive care unit (NICU). The M-CHAT-R/F screening tool was used to assess the ASD risk at 16-30 months of age. Discharge cranial ultrasound (CUS) findings also determined the ASD risk. Descriptive statistics comprised median and interquartile range for skewed continuous data and frequencies and percentages for categorical variables. Comparisons for non-ordinal categorical measures in bivariate analysis were carried out using the χ2 test or Fisher exact test. Results Of the 334 infants, 167 had IVH, and 167 had no IVH. High ASD risk (43% vs. 20%, p = 0.044) and cerebral palsy (19% vs. 5%, p = 0.004) were significantly associated with severe IVH. Infants with CUS findings of periventricular leukomalacia had 3.24 odds of developing high ASD risk (odds ratios/OR: 3.24, 95% confidence interval/CI: 0.73-14.34), and those with hydrocephalus needing ventriculoperitoneal (VP) shunt had 4.75 odds of developing high ASD risk (OR: 4.75, 95% CI: 0.73-30.69). Conclusion Severe IVH, but not mild IVH, increased the risk of ASD and cerebral palsy. This study demonstrates the need for timely screening for ASD in high-risk infants. Prompt detection leads to earlier treatment and better outcomes.

Successful Weaning From Veno-Venous Extracorporeal Membrane Oxygenation (VV-ECMO) After Initiation of Inhaled Epoprostenol in a Neonate With Refractory Persistent Pulmonary Hypertension of the Newborn (PPHN).

Despite improvements in the medical management of persistent pulmonary hypertension of the newborn (PPHN), a significant number of patients persist with inadequate gas exchange and are treated with extracorporeal membrane oxygenation (ECMO). Prolonged time to weaning ECMO can increase mortality risk. Therefore, multiple therapies are utilized for pulmonary hypertension treatment, including pharmacotherapy with pulmonary vasodilators, to improve the prognosis of these critical patients. We report a case of a 37 2/7-week neonate with severe PPHN refractory to triple pulmonary vasodilator therapy (inhaled nitric oxide (iNO), sildenafil, and milrinone) and required veno-venous (VV)-ECMO support to improve oxygenation. Our patient was successfully weaned from ECMO after the addition of inhaled epoprostenol (iEPO) therapy. This report indicates that inhaled prostacyclin therapy effectively helps refractory PPHN patients off extracorporeal life support (ECLS) and should be considered a valuable treatment.

Comparison of clinical outcomes and biochemical markers in normal and preeclamptic pregnancies: a prospective cohort study.

Background: Preeclampsia (PreE), the de novo onset of hypertension and proteinuria at 20 weeks of gestation, is a leading cause of maternal and fetal morbidity and mortality. This study compared inflammatory biomarkers in PreE and normal pregnancies using paired samples of mothers and neonates. Methods: Twenty normal pregnant and 27 PreE patients were monitored for biomarkers, neonatal outcomes, and placental morphologies. Fetal and maternal serum levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF), soluble endoglin (sENG), and soluble fms-like tyrosine kinase-1 (sFLT-1) were measured by enzyme-linked immunosorbent assay. Results: Placental thickness was 25 mm in early PreE subjects compared to 32 mm in late PreE subjects (P < 0.05). Placental volume was 296 cm3 in early PreE compared to 393 cm3 in late PreE (P < 0.05). The average hospital stay for PreE babies was longer (20 ± 5 days) compared to babies from normal pregnancies (2 ± 1 days; P < 0.05). PreE babies had a lower Ponderal index (2.28 ± 0.3) than those from normal pregnancies (2.95 ± 0.2; P < 0.05). sENG and sFLT-1 had cord values like the maternal values, while VEGF and PlGF did not. Conclusion: PreE alters the intrauterine environment by activating chemical mediators that result in maternal and fetal complications.

The role of supervised school therapy in poorly controlled asthma in children.

Background: In children, nonadherence to inhaled corticosteroid (ICS) therapy leads to poor asthma control and complications. Methods: We evaluated the benefit from initiation of ICS administration once daily at school. We retrospectively chose patients from our pediatric pulmonary clinic who had poorly controlled asthma and prescribed ICS daily. For the study period, we examined the number of corticosteroid courses, emergency room visits, hospital admissions, symptom history, and pulmonary function tests. Results: Thirty-four patients who satisfied the inclusion criteria began the intervention. Preintervention, there were a mean number of 2.6 oral corticosteroid courses compared to 2 courses in the year following intervention (P = 0.8). Postintervention emergency department visits decreased from a mean of 1.4 to 1.0 (P = 0.71), and hospital admissions decreased from 1.23 to 0.57 (P = 0.04). There was also a significant increase in forced expiratory volume in 1 second (1.69 vs 1.4 L/sec, P = 0.02), a decrease in systemic steroid-free days in a year (96 vs 141 days, P = 0.03), and an increase in symptom-free days postintervention (28 vs 26 days, P = 0.325). Conclusion: These findings suggest that ICS administration in schools may help reduce hospital admissions and improve lung function in patients with poorly controlled asthma.

The Perfect Storm: A Case of Rapid-Onset Obesity With Hypoventilation, Hypothalamic, Autonomic Dysregulation, Neuroendocrine Tumor (ROHHADNET) With Heart Failure, Narcolepsy, and a Rare Location of a Pelvic Neuroendocrine Tumor.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare disease of concurrent respiratory dysfunction and autonomic dysregulation with endocrine abnormalities. ROHHADNET includes ROHHAD plus coexisting neuroendocrine tumors (NETs). We describe an eight-year-old boy, who originally presented at four years of age with rapid weight gain and hyperhidrosis and who developed mild obstructive sleep apnea (OSA). His clinical course was eventually complicated by hypoxic respiratory failure requiring admission to the pediatric intensive care unit (PICU). Echocardiogram at that time demonstrated dilated cardiomyopathy left ventricular ejection fraction (LVEF) of 28% at time of admission. His respiratory failure persisted despite average volume-assured pressure support (AVAPS) around the clock leading to tracheostomy placement for cardiopulmonary support. He also demonstrated autonomic instability with multiple pituitary hormone deficiencies. Computed tomography (CT) imaging of the abdomen and pelvis demonstrated a presacral soft tissue mass consistent with a tumor of neural crest origin. Daytime somnolence and confusion progressed and a low cerebrospinal fluid hypocretin level revealed a diagnosis of narcolepsy type 1.

Maternal preeclampsia as a risk factor for developing bronchopulmonary dysplasia in neonates.

OBJECTIVE: To determine the effect of preeclampsia on the development of bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Retrospective cohort study of infants' ≤32 weeks' gestation admitted to a level-IV single center neonatal intensive care unit from 2014 to 2016. Infants with major congenital anomalies, death or transfer before 28 days were excluded. Infants were stratified by maternal preeclampsia status. Demographic, clinical, and laboratory data were reviewed. Logistic regression was used to examine predictors for BPD. MAIN OUTCOME MEASURE: The primary outcome was BPD incidence. RESULTS: 432 infants met inclusion criteria; 22% developed BPD, of which, 16% had severe BPD. Thirty-eight percent of infants were born to preeclamptic mothers, with 23% of those infants developing BPD. Infants born to preeclamptic mothers were delivered by cesarean section (88% vs. 60%; p<0.0001) more often and had lower birthweight (Median=1265g, IQR 910-1555 vs. Median=1388g, IQR 959-1752; p=0.008) compared to infants born to non-preeclamptic mothers. Higher incidence of intrauterine growth restriction was noted in pre-eclampsia group,24% vs 8%, p=0.0001). Gestational age, length of stay and days on ventilator were all associated with the development of BPD. In multivariable logistic regression, preeclampsia was not a risk factor for development of BPD (OR 1.12 [0.68, 1.83]). CONCLUSIONS: Preeclampsia was not a significant risk factor for development of BPD nor the severity of BPD in infants' ≤32 weeks' gestation. IUGR infants with or without preeclampsia mothers were at higher risk for BPD.

Infant nutrition (donor human milk vs. maternal milk) and long-term neurodevelopmental and growth outcomes in very low birth weight infants.

BACKGROUND: Human milk, the ultimate source of nutrition for premature infants, enhances host defense mechanism, gastrointestinal maturation, lowers infection rate, improves neurodevelopmental outcomes, and reduces long-term cardiovascular and metabolic disease. Recently, there has been an increase in donor breast milk (DBM) use for premature infants; however, data are limited on the long-term effects of DBM on the infant's growth and neurodevelopmental outcomes. OBJECTIVE: To determine if there is an association between type of infant nutrition (maternal breast milk (MBM) or DBM) and neurodevelopmental and growth outcomes in very low birth weight (VLBW) infants. DESIGN/METHODS: Retrospective cohort study of VLBW (<1500 g) infants admitted to the Baylor Scott & White Memorial Hospital Neonatal Intensive Care Unit from January 2014 to December 2016. Infants with major congenital anomalies, born at an outside hospital, who were nil per os (NPO) for >15 days, or who died before NICU discharge were excluded. Infants were stratified into two groups (MBM or DBM) based on predominant nutrition (>50%) received in the first month of life. Primary outcomes of neurodevelopmental delay(s) between 2 and 4 years of age identified via ICD 9/10 codes. Growth data (weight, length, and head circumference) were obtained from well-check visits at 12-, 18-, 24-, 36-, and 48-months. Severity of illness was determined using the Clinical Risk Index in Babies-II (CRIB-II) score. Generalized linear models were used to assess the relationship between nutrition and neurodevelopmental delay and trends in growth over time. RESULTS: Two hundred and nine infants were included: 146 MBM; 63 DBM. Median gestational age was 28 weeks (range, 23-35) and median birthweight was 1050 g (range, 410-1470). There were no significant differences in birthweight, gestational age, CRIB-II score, or length of stay between the groups. Infants fed DBM had a significantly larger weight z-score (p=.005), length z-score (p=.01), and head circumference z-score (p=.04), on average from birth to 48 months compared to MBM infants, while controlling for NICU length of stay and number of follow-up months; however, this only equated to DBM infants being 0.5 in taller and 0.9 lbs heavier at 48 months. There were no statistically significant differences among type of infant nutrition and long-term neurodevelopmental outcomes, while controlling for CRIB-II score. CONCLUSIONS: Infants fed DBM have a slightly greater propensity for growth over time compared to infants fed MBM. Longer follow-up is needed to further determine the effect, infant nutrition has on neurodevelopmental outcomes.

25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized patients.

OBJECTIVES: Studies investigating the association between vitamin D and severity of COVID-19 have mixed results perhaps due to immunoassay assessment of total 25-hydroxyvitamin D (tD) (the sum of 25-hydroxyvitamin-D2 [25-OH-D2] and 25-hydroxyvitamin-D3 [25-OH-D3]). Liquid chromatography tandem mass spectrometry (LC-MS/MS) has high analytical specificity and sensitivity for 25-OH-D2 and 25-OH-D3, and thus enables a more accurate assessment of impact on COVID-19 outcomes. METHODS: We established reference intervals for 25-OH-D3 and tD using LC-MS/MS. 25-OH-D2, 25-OH-D3 and tD were quantitated for 88 COVID-19 positive and 122 COVID-19 negative specimens. Chi-square or Fisher's exact tests were used to test associations in binary variables. T-Tests or Wilcoxon rank sum tests were used for continuous variables. Cox proportional hazards were used to test associations between 25-OH-D3 or tD levels and length of stay (LOS). For mortality and ventilation, logistic regression models were used. RESULTS: COVID-19 patients with deficient (<20 ng/mL) levels of 25-OH-D3 had significantly longer LOS by 15.3 days. COVID-19 P patients with deficient (<20 ng/mL) and insufficient (<30 ng/mL) of tD had significantly longer LOS by 12.1 and 8.2 days, respectively. Patients with insufficient levels of tD had significantly longer LOS by 13.7 days. COVID-19 patients with deficient serum 25-OH-D3 levels had significantly increased risk-adjusted odds of in-hospital mortality (OR [95% CI]: 5.29 [1.53-18.24]); those with insufficient 25-OH-D3 had significantly increased risk for requiring ventilation during hospitalization was found at LCMS insufficient cutoff (OR [95% CI]: 2.75 [1.10-6.90]). CONCLUSIONS: There is an inverse relationship of 25-hydroxyvitamin D levels and hospital LOS for COVID-19 patients. Vitamin D status is a predictor for severity of outcomes. LCMS results are useful for assessing the odds of mortality and the need for ventilation during hospitalization.

Short-Term Complications Associated with Surgical Ligation of Patent Ductus Arteriosus in ELBW Infants: A 25-Year Cohort Study.

OBJECTIVE: This article aims to determine the incidence of short-term complications of surgical patent ductus arteriosus (PDA) ligations, the factors associated with those complications, and whether complications are associated with poor long-term outcomes. STUDY DESIGN: Retrospective cohort study of all extremely low birth weight (ELBW, < 1,000 g) infants who underwent surgical PDA ligation at a single-center neonatal intensive care unit from 1989 to 2015. Demographic, clinical, and laboratory data were reviewed. The primary outcome was development of a short-term (< 2 weeks from ligation) surgical complication. Secondary outcomes include bronchopulmonary dysplasia (BPD), length of stay, and mortality. RESULTS: A total of 180 ELBW infants were included; median gestational age and birth weight was 24 weeks and 683 g, respectively, and 44% of infants had at least one short-term complication. Need for vasopressors (33%) was the most common medical complication and vocal cord paralysis (9%) was the most common surgical complication. Younger corrected gestational age at time of repair was associated with increased risk for complications. Mortality, length of stay, and BPD rates were similar between infants with and without complications. CONCLUSION: Serious complications were seen in a minority of infants. Additional research is needed to determine if short-term complications are associated with long-term adverse outcomes.

In utero ultrafine particulate matter exposure causes offspring pulmonary immunosuppression.

Early life exposure to fine particulate matter (PM) in air is associated with infant respiratory disease and childhood asthma, but limited epidemiological data exist concerning the impacts of ultrafine particles (UFPs) on the etiology of childhood respiratory disease. Specifically, the role of UFPs in amplifying Th2- and/or Th17-driven inflammation (asthma promotion) or suppressing effector T cells (increased susceptibility to respiratory infection) remains unclear. Using a mouse model of in utero UFP exposure, we determined early immunological responses to house dust mite (HDM) allergen in offspring challenged from 0 to 4 wk of age. Two mice strains were exposed throughout gestation: C57BL/6 (sensitive to oxidative stress) and BALB/C (sensitive to allergen exposure). Offspring exposed to UFPs in utero exhibited reduced inflammatory response to HDM. Compared with filtered air (FA)-exposed/HDM-challenged mice, UFP-exposed offspring had lower white blood cell counts in bronchoalveolar lavage fluid and less pronounced peribronchiolar inflammation in both strains, albeit more apparent in C57BL/6 mice. In the C57BL/6 strain, offspring exposed in utero to FA and challenged with HDM exhibited a robust response in inflammatory cytokines IL-13 and Il-17. In contrast, this response was lost in offspring exposed in utero to UFPs. Circulating IL-10 was significantly up-regulated in C57BL/6 offspring exposed to UFPs, suggesting increased regulatory T cell expression and suppressed Th2/Th17 response. Our results reveal that in utero UFP exposure at a level close to the WHO recommended PM guideline suppresses an early immune response to HDM allergen, likely predisposing neonates to respiratory infection and altering long-term pulmonary health.