Machine learning approaches to evaluate infants' general movements in the writhing stage-a pilot study.

The goals of this study are to describe machine learning techniques employing computer-vision movement algorithms to automatically evaluate infants' general movements (GMs) in the writhing stage. This is a retrospective study of infants admitted 07/2019 to 11/2021 to a level IV neonatal intensive care unit (NICU). Infant GMs, classified by certified expert, were analyzed in two-steps (1) determination of anatomic key point location using a NICU-trained pose estimation model [accuracy determined using object key point similarity (OKS)]; (2) development of a preliminary movement model to distinguish normal versus cramped-synchronized (CS) GMs using cosine similarity and autocorrelation of major joints. GMs were analyzed using 85 videos from 74 infants; gestational age at birth 28.9 ± 4.1 weeks and postmenstrual age (PMA) at time of video 35.9 ± 4.6 weeks The NICU-trained pose estimation model was more accurate (0.91 ± 0.008 OKS) than a generic model (0.83 ± 0.032 OKS, p < 0.001). Autocorrelation values in the lower limbs were significantly different between normal (5 videos) and CS GMs (5 videos, p < 0.05). These data indicate that automated pose estimation of anatomical key points is feasible in NICU patients and that a NICU-trained model can distinguish between normal and CS GMs. These preliminary data indicate that machine learning techniques may represent a promising tool for earlier CP risk assessment in the writhing stage and prior to hospital discharge.

Single-center Experience with Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy in Infants with <36 Weeks' Gestation.

OBJECTIVE: Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in neonates. Therapeutic hypothermia (TH) has improved outcomes and mortality in infants with >36 weeks' gestational age (GA) with moderate-to-severe HIE. There are limited data on the safety and efficacy of TH in preterm infants with HIE. This study describes our experience and examines the safety of TH in neonates with <36 weeks' GA. STUDY DESIGN: A single-center, retrospective study of preterm neonates born at <36 weeks' GA with moderate-to-severe HIE and treated with TH, compared to a cohort of term neonates with HIE (≥37 weeks' GA), was conducted. The term cohort was matched for degree of background abnormality on electroencephalogram, sex, inborn versus outborn status, and birth year. Medical records were reviewed for pregnancy and delivery complications, need for transfusion, sedation and antiseizure medications, electroencephalography and imaging findings, and in-hospital mortality. RESULTS: Forty-two neonates born at <36 weeks' GA with HIE received TH between 2005 and 2022. Data from 42 term neonates were analyzed for comparison. The average GA of the preterm cohort was 34.6 weeks and 39.3 weeks for the term cohort. Apgar scores, degree of acidosis, and need for blood product transfusions were similar between groups. Preterm infants were more likely to require inotropic support (55 vs. 29%, p = 0.026) and hydrocortisone (36 vs. 12%, p = 0.019) for hypotension. The proportion of infants without evidence of injury on magnetic resonance imaging was similar in both groups: 43 versus 50% in preterm and term infants, respectively. No significant difference was found in mortality between groups. CONCLUSION: In this single-center cohort, TH in preterm infants appears to be as safe as in term infants, with no significant increase in intracranial bleeds or mortality. Preterm infants more frequently required inotropes and steroids for hypotension. Further research is needed to determine efficacy of TH in preterm infants. KEY POINTS: · TH is used off-protocol in preterm infants.. · Preterm and term infants have similar mortality.. · Preterm cohort required more inotropic support..

Dexmedetomidine During Therapeutic Hypothermia: A Multicenter Quality Initiative.

OBJECTIVES: Sedation is typically used during neonatal therapeutic hypothermia (TH). This report describes a quality improvement (QI) initiative with the aim of decreasing opioid exposure during TH by implementing dexmedetomidine as the primary sedative agent. METHODS: This dual-center QI initiative used a multidisciplinary team to create a sedation algorithm for safe implementation of dexmedetomidine as first-line therapy during TH. The primary measure in this initiative was cumulative opioid exposure during TH; balancing measures included safety parameters, primarily the rate of dexmedetomidine discontinuation because of bradycardia. Baseline demographic and clinical data were collected retrospectively for the period before implementation and prospectively during the QI period. Data were analyzed using statistical process control charts to identify change over time. RESULTS: One-hundred and fifty-four neonates in the 2-year pre-QI period were compared with 135 neonates in the 2 years after guideline implementation. Guideline compliance with dexmedetomidine initiation was 99% and compliance with initial dosing increased from 70% to 91% during the QI period. The cumulative dose of opioid during TH decreased by >90% by the end of the QI period. Dexmedetomidine was discontinued for transient bradycardia in 9.6% of the study population. No other adverse effects were observed. CONCLUSIONS: Dexmedetomidine may be used as the primary sedative during neonatal TH with a low incidence of adverse effects. Clinical trials evaluating the impact of sedation during TH on neurologic outcomes are needed.

Changes in Cerebral Regional Oxygen Saturation Variability in Neonates Undergoing Cardiac Surgery: A Prospective Cohort Study.

Near-infrared spectroscopy is routinely used in the monitoring of cerebral regional oxygen saturation (crSO2) in neonates following congenital heart surgery. Decreased postoperative crSO2 variability in these patients is associated with worse clinical outcomes, including neurodevelopmental outcomes. We sought to explore changes in crSO2 variability between the preoperative and postoperative periods and associations with short-term clinical outcomes in neonates undergoing cardiac surgery. We performed a prospective cohort study of neonates undergoing cardiac surgery with cardiopulmonary bypass between November 2019 and May 2021. We calculated crSO2 variability using averaged 1 min of crSO2 values for a minimum of 12 h before, and the first 48 h following surgery. 37 neonates (median age at start of monitoring 4 days (interquartile range 2-5 days)) were included in our study. We observed a 30% decrease in crSO2 variability between the preoperative and postoperative monitoring periods (p < 0.001). Preoperative crSO2 variability increased by 9% (p = 0.009) for each additional postnatal day. There were no associations between the degree of decrease in crSO2 variability postoperatively and class of cardiac lesion (e.g., aortic arch obstruction, single ventricle physiology) or short-term postoperative clinical outcomes. There was a significant decrease in postoperative crSO2 variability following neonatal cardiac surgery as compared to the preoperative period, likely influenced by several factors. The impact of interventions on crSO2 variability and resultant influence on long-term outcomes, such as neurodevelopmental outcomes, requires further exploration.

Early Vital Sign Differences in Very Low Birth Weight Infants with Severe Intraventricular Hemorrhage.

OBJECTIVE: Severe intraventricular hemorrhage (sIVH, grades 3 and 4) is a serious complication for very low birth weight (VLBW) infants and is often clinically silent requiring screening cranial ultrasound (cUS) for detection. Abnormal vital sign (VS) patterns might serve as biomarkers to identify risk or occurrence of sIVH. STUDY DESIGN: This retrospective study was conducted in VLBW infants admitted to two level-IV neonatal intensive care units (NICUs) between January 2009 and December 2018. Inclusion criteria were: birth weight <1.5 kg and gestational age (GA) <32 weeks, at least 12 hours of systemic oxygen saturation from pulse oximetry (SpO2) data over the first 24 hours and cUS imaging. Infants were categorized as early sIVH (sIVH identified in the first 48 hours), late sIVH (sIVH identified after 48 hours and normal imaging in the first 48 hours), and no IVH. Infants with grades 1 and 2 or unknown timing IVH were excluded. Mean heart rate (HR), SpO2, mean arterial blood pressure (MABP), number of episodes of bradycardia (HR < 100 bpm), and desaturation (SpO2 < 80%) were compared. RESULTS: A total of 639 infants (mean: 27 weeks' gestation) were included (567 no IVH, 34 early sIVH, and 37 late sIVH). In the first 48 hours, those with sIVH had significantly higher HR compared with those with no IVH. Infants with sIVH also had lower mean SpO2 and MABP and more desaturations <80%. No significant differences in VS patterns were identified in early versus late sIVH. Logistic regression identified higher HR and greater number of desaturations <80% as independently associated with sIVH. CONCLUSION: VLBW infants who develop sIVH demonstrate VS differences with significantly lower SpO2 and higher mean HR over the first 48 hours after birth compared with VLBW infants with no IVH. Abnormalities in early VS patterns may be a useful biomarker for sIVH. Whether VS abnormalities predict or simply reflect sIVH remains to be determined. KEY POINTS: · A higher HR in the first 48 hours is seen in infants with severe IVH.. · Infants with sIVH have lower blood pressure in the first 48 hours.. · Infants with sIVH have more oxygen desaturations in the first 48 hours..

A phase-II clinical trial of targeted cerebral near infrared spectroscopy using standardized treatment guidelines to improve brain oxygenation in preterm infants (BOx-II): A study protocol.

BACKGROUND: Mortality and brain injury are common adverse outcomes in infants born <28 weeks. Conventional pulse oximetry may not detect subclinical changes prior to deterioration and fails to detect changes within the brain. Increasing evidence supports the use of cerebral near-infrared spectroscopy (NIRS) in the early care of preterm infants, yet the impact of specific interventions on cerebral oxygenation and the relationship between cerebral hypoxia and brain injury on MRI remain to be determined. METHODS/DESIGN: 100 infants <28 completed weeks of gestation will be recruited for a prospective, multicenter intervention trial. After informed consent, infants will undergo cerebral NIRS monitoring starting within 6 h of birth and continuing through 72 h. Infants with persistent cerebral desaturation will receive interventions following a standard treatment algorithm selected by the provider based on the patient's clinical condition. Providers will record the timing and choice of intervention(s) and term equivalent brain MRI will be performed for survivors. There are three objectives of this study: 1) to identify the relationship between cerebral hypoxia burden and brain injury on term-equivalent MRI. 2) to identify most common interventions after cerebral hypoxia, and 3) to quantify frequency of occult cerebral hypoxia events. DISCUSSION: There is increasing evidence for the role of early cerebral NIRS monitoring in the neuroprotective care of preterm infants. This phase-II trial will provide essential data to improve the intervention approach, model the effect size of interventions on a wider extent of brain injury, and quantify the discrepancy between measurements of systemic and cerebral hypoxia.

A feasibility randomized controlled trial of a NICU rehabilitation program for very low birth weight infants.

Motor disability is common in children born preterm. Interventions focusing on environmental enrichment and emotional connection can positively impact outcomes. The NICU-based rehabilitation (NeoRehab) program consists of evidence-based interventions provided by a parent in addition to usual care. The program combines positive sensory experiences (vocal soothing, scent exchange, comforting touch, skin-to-skin care) as well as motor training (massage and physical therapy) in a gestational age (GA) appropriate fashion. To investigate the acceptability, feasibility and fidelity of the NeoRehab program in very low birthweight (VLBW) infants. All interventions were provided by parents in addition to usual care. Infants (≤ 32 weeks' GA and/or ≤ 1500 g birthweight) were enrolled in a randomized controlled trial comparing NeoRehab to usual care (03/2019-10/2020). The a priori dosing goal was for interventions to be performed 5 days/week. The primary outcomes were the acceptability, feasibility and fidelity of the NeoRehab program. 36 participants were randomized to the intervention group and 34 allocated to usual care. The recruitment rate was 71% and retention rate 98%. None of the interventions met the 5 days per week pre-established goal. 97% of participants documented performing a combination of interventions at least 3 times per week. The NeoRehab program was well received and acceptable to parents of VLBW infants. Programs that place a high demand on parents (5 days per week) are not feasible and goals of intervention at least 3 times per week appear to be feasible in the context of the United States. Parent-provided motor interventions were most challenging to parents and alternative strategies should be considered in future studies. Further studies are needed to evaluate the relationship between intervention dosing on long term motor outcomes.

Low Variability of Blood Pressure Predicts Abnormal Electroencephalogram in Infants with Hypoxic Ischemic Encephalopathy.

OBJECTIVE: This study aimed to evaluate the role of an objective physiologic biomarker, arterial blood pressure variability, for the early identification of adverse short-term electroencephalogram (EEG) outcomes in infants with hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: In this multicenter observational study, we analyzed blood pressure of infants meeting these criteria: (1) neonatal encephalopathy determined by modified Sarnat exam, (2) continuous mean arterial blood pressure (MABP) data between 18 and 27 hours after birth, and (3) continuous EEG performed for at least 48 hours. Adverse outcome was defined as moderate-severe grade EEG at 48 hours. Standardized signal preprocessing was used; the power spectral density was computed without interpolation. Multivariate binary logistic regression was used to identify which MABP time and frequency domain metrics provided improved predictive power for adverse outcomes compared with standard clinical predictors (5-minute Apgar score and cord pH) using receiver operator characteristic analysis. RESULTS: Ninety-one infants met inclusion criteria. The mean gestational age was 38.4 ± 1.8 weeks, the mean birth weight was 3,260 ± 591 g, 52/91 (57%) of infants were males, the mean cord pH was 6.95 ± 0.21, and 10/91 (11%) of infants died. At 48 hours, 58% of infants had normal or mildly abnormal EEG background and 42% had moderate or severe EEG backgrounds. Clinical predictor variables (10-minute Apgar score, Sarnat stage, and cord pH) were modestly predictive of 48 hours EEG outcome with area under curve (AUC) of 0.66 to 0.68. A composite model of clinical and optimal time- and frequency-domain blood pressure variability had a substantially improved AUC of 0.86. CONCLUSION: Time- and frequency-domain blood pressure variability biomarkers offer a substantial improvement in prediction of later adverse EEG outcomes over perinatal clinical variables in a two-center cohort of infants with HIE. KEY POINTS: · Early outcome prediction in HIE is suboptimal.. · Patterns in blood pressure physiology may be predictive of short-term outcomes.. · Early time- and frequency-domain measures of blood pressure variability predict short-term EEG outcomes in HIE infants better than perinatal factors alone..

High Prevalence of Abnormal General Movements in Hospitalized Very Low Birth Weight Infants.

OBJECTIVE: Abnormal general movements (GMs) are predictive of later risk of motor impairments in preterm infants. The goals of this study are to (1) describe the implementation of the GM assessment (GMA) in a neonatal intensive care unit (NICU) and (2) investigate the prevalence and evolution of abnormal GMs in very low birth weight (VLBW) infants. STUDY DESIGN: Observational study of GMs in VLBW infants (gestational age [GA] <32 weeks and/or birth weight [BW] <1,500 g) following GMA implementation in a level-IV NICU. All VLBW infants admitted between November 2017 and April 2019 were eligible for the GMA. Infants were excluded if they required high-frequency ventilation or if they could not be unbundled for video acquisition. GMAs were scored weekly by at least 2 GMA-certified providers. RESULTS: The GMA was performed in 121 VLBW infants with a mean (standard deviation [SD]) GA of 28.3 (2.6) and BW of 1,113 (400 g). Only 28% of infants had normal GMs on initial assessment (32.9 ± 2.7 weeks' GA), while 61 and 11% had poor repertoire and cramped-synchronized GMs, respectively. At NICU discharge (37.6 ± 3.4 weeks corrected GA), 45 and 21% of infants were classified as having poor repertoire and cramped-synchronized GMs, respectively. Most infants with cramped-synchronized GMs on initial assessment had persistent abnormal GMs at discharge. In contrast, only one infant with normal GMs on first assessment developed cramped-synchronized GMs. CONCLUSION: Abnormal GMs are common in VLBW infants, including a high prevalence of the more concerning cramped-synchronized movement pattern. The GMA can be successfully performed in VLBW infants. The GMA may be helpful in identifying infants at increased risk of later motor impairments, as well as assisting clinicians, in the stratification of infants who may benefit from additional brain imaging and/or an intensive hospital-based interventions. KEY POINTS: · Abnormal GMs are common in VLBW infants.. · Poor repertoire in the most prevalent pattern observed.. · Infants at risk for abnormal motor outcomes can be identified in the NICU..

A Maternal-Administered Multimodal Neonatal Bundle in Hospitalized Very Preterm Infants: A Pilot Study.

BACKGROUND: Premature infants are at an increased risk for developing cerebral palsy (CP). Evidence-based strategies designed to promote healthy brain development and facilitate adaptation after brain injury in infants still admitted to the neonatal intensive care unit (NICU) represent a novel approach that may lead to improved long-term outcomes. PURPOSE: To investigate the feasibility of a maternal-administered early intervention bundle in very preterm infants prior to NICU discharge. METHODS: A pilot trial evaluating a maternal-administered NICU-based bundle of interventions in preterm infants (≤32 weeks' gestational age and/or ≤1500 g birth weight). The impact of the bundle on short-term developmental outcomes of infants, as well as maternal stress, anxiety, and depression, is evaluated. RESULTS: The intervention bundle was implemented in 11 mother-infant dyads (including 1 set of twins) for a median of 8 weeks and was overall well received. Vocal soothing, scent exchange, and comforting touch were feasible, performed at or above the predetermined goal of 71% of the time (5/7 days), while kangaroo care and infant massage were not. Maternal stress, anxiety, and depression were decreased during the study time. IMPLICATIONS TO PRACTICE: A neonatal multimodal intervention bundle provided by mothers is feasible. IMPLICATIONS TO RESEARCH: Additional randomized controlled studies are needed to determine whether this type of bundled interventions can (1) improve the neurodevelopmental outcomes of participating infants and (2) improve long-term parental outcomes, including decreased burden of anxiety and depression, as well as improved attachment and optimal patterns of social interaction.

Blood Pressure Profiles in Infants With Hypoxic Ischemic Encephalopathy (HIE), Response to Dopamine, and Association With Brain Injury.

Objective: To describe mean arterial blood pressure (MABP), responsiveness to dopamine, and relationship to brain injury in infants with moderate/severe hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). We hypothesized that, when utilized, dopamine would rapidly and effectively increase MABP in treated patients. Methods: Continuous arterial blood pressure measurements were prospectively recorded from infants with moderate/severe HIE undergoing TH in a multi-institutional cohort from 2010 to 2018. Treatment with dopamine was at the discretion of the medical team for hypotension/hypoperfusion. MABP values of treated infants were compared to those obtained at an equivalent time period in control infants receiving TH but not dopamine (24 h after birth). MRI was obtained per unit protocols and included T1/T2/DWI sequences. Injury was classified as no injury/mild injury or moderate/severe injury using a standardized scoring system. Seizures were confirmed with conventional EEG. Results: Eighteen infants were treated with dopamine and were similar to untreated controls (n = 36) with the exception of lower cord gas pH (6.92 ± 0.2 vs. 7.07 ± 0.2, p < 0.05). Dopamine was initiated at a mean of 24 h after birth. MABP was significantly lower in the dopamine group at the start of therapy (39.9 ± 2.0 vs. 49.1 ± 1.3, p < 0.01) and 1 h later (44.3 ± 2.0 vs. 49.8 ± 1.1, p < 0.05). However, after 9 h of treatment, dopamine increased the MABP by an average of 9 mmHg and MABP values were similar to untreated controls for the remainder of the observation period. There were no significant differences in rates of seizures, brain injury, or death. Conclusion: Neonates with moderate/severe HIE treated with dopamine during TH had MABP significantly lower than controls. The majority of infants responded to dopamine monotherapy following adequate volume resuscitation. An association between requirement for dopamine and severity of brain injury was not detected.

Gabapentin for pain, movement disorders, and irritability in neonates and infants.

We aimed to report our institution's experience with gabapentin therapy to manage agitation and pain in the neonatal intensive care unit (NICU) setting. This was a retrospective, single-center study of NICU patients admitted between January 2015 and December 2017, who received gabapentin. Data on neonatal agitation, pain, Neonatal Pain, Agitation and Sedation Scale (N-PASS) scores, neurosedative medications, and adverse events were collected. Gabapentin was initiated in 16 patients at a corrected gestational age of 44 weeks (range 36.2-75wks) for agitation (n=9), pain (n=6), and movement disorders (n=1). A neurological diagnosis was present in 13 patients. Neonatal agitation, pain, and N-PASS scores and the need for other neurosedatives were significantly decreased 14 days after treatment initiation. Gabapentin is well tolerated in neonates and infants; it is associated with decreased pain scores and decreased need for multiple neurosedative medications 2 weeks after initiation. WHAT THIS PAPER ADDS: Gabapentin is well tolerated in neonates and infants. Gabapentin decreases pain scores and the need for other neurosedative medications in neonates and infants.

Blood pressure extremes and severe IVH in preterm infants.

BACKGROUND: The optimal upper and lower limits of blood pressure in preterm infants are not known. Exceeding these thresholds may contribute to intraventricular hemorrhage (IVH). METHODS: Preterm infants born ≤30 weeks GA were identified. Infants had continuous measurement of mean arterial blood pressure (MABP) for 7 days and cranial ultrasound imaging. IVH was classified as severe IVH (grade 3/4), no severe IVH (no IVH; grade 1/2), or no IVH. Mean ± SEM MABP values from hours 1-168 were calculated and sorted into bins 2 mm Hg wide. The normalized proportion of each recording spent in each bin was then calculated. Candidate limits were identified by comparison of MABP distribution in those with severe IVH vs. those without severe IVH. RESULTS: Eighty-five million measurements were made from 157 infants. Mean EGA was 25.2 weeks; mean BW was 749 g; 65/157 female; inotrope use in 59/157; grade 3/4 IVH in 29/157. Infants with severe IVH spent significantly more time with extreme MABP measurements (<23 mm Hg or >46 mm Hg) compared to those without severe IVH (12% vs. 8% of recording, p = 0.02). CONCLUSIONS: Infants who developed severe IVH had substantially more unstable MABP and spent a significantly greater period of time with MABP outside of the optimal range.

The Role of Kainate Receptors in the Pathophysiology of Hypoxia-Induced Seizures in the Neonatal Mouse.

Kainate receptors (KARs) are glutamate receptors with peak expression during late embryonic and early postnatal periods. Altered KAR-mediated neurotransmission and subunit expression are observed in several brain disorders, including epilepsy. Here, we examined the role of KARs in regulating seizures in neonatal C57BL/6 mice exposed to a hypoxic insult. We found that knockout of the GluK2 subunit, or blockade of KARs by UBP310 reduced seizure susceptibility during the period of reoxygenation. Following the hypoxic insult, we observed an increase in excitatory neurotransmission in hippocampal CA3 pyramidal cells, which was blocked by treatment with UBP310 prior to hypoxia. Similarly, we observed increased excitatory neurotransmission in CA3 pyramidal cells in an in vitro hippocampal slice model of hypoxic-ischemia. This increase was absent in slices from GluK2-/- mice and in slices treated with UBP310, suggesting that KARs regulate, at least in part, excitatory synaptic neurotransmission following in vivo hypoxia in neonatal mice. Data from these hypoxia models demonstrate that KARs, specifically those containing the GluK2 subunit, contribute to alterations in excitatory neurotransmission and seizure susceptibility, particularly during the reoxygenation period, in neonatal mice. Therapies targeting KARs may prove successful in treatment of neonates affected by hypoxic seizures.

Short children born small for gestational age outcomes in the era of growth hormone therapy.

Small-for-gestational age (SGA) infants are at risk for short and long term medical and metabolic complications. Most SGA infants (85-90%) demonstrate spontaneous catch-up growth, typically in the first year after birth. Although catch-up growth (CUG) is a desired goal, it is important to note if CUG is too rapid the infants are at increased risk for insulin resistance and type 2 diabetes mellitus as they become adults. On the flip side, infants who do not exhibit CUG are also at increased risk of adverse adult outcomes including those for cardiovascular disease, insulin resistance and type 2 diabetes mellitus, neurodevelopmental and cognitive impairments, in addition to adult short stature. Treatment with growth hormone is safe and effective not only in increasing adult height, but also in improving body composition and decreasing metabolic complications. The aims of this review are to summarize the current knowledge on what constitutes "healthy" catch-up growth in children born SGA as well as provide an update on the role of growth hormone treatment for short children born SGA.

Impact of Caffeine Boluses and Caffeine Discontinuation on Apnea and Hypoxemia in Preterm Infants.

Background: Apnea of prematurity often occurs during and following caffeine therapy. We hypothesized that number of apnea events would be impacted by adjustments in caffeine therapy. Materials and Methods: An automated algorithm was used in all infants ≤32 weeks gestation admitted to a level IV Neonatal Intensive Care Unit from 2009 to 2014 to analyze chest impedance, electrocardiogram, and oxygen saturation data around the time of serum caffeine levels, caffeine boluses while on maintenance therapy, and caffeine discontinuation. Episodes of central apnea/bradycardia/desaturation (ABDs), and percent time with SpO2 <88% and <75% were measured. Results: ABDs were analyzed in 302 preterm infants (mean gestational age 27.6 weeks) around the time of 485 serum caffeine levels, 90 caffeine boluses, and 273 episodes of caffeine discontinuation. Higher serum caffeine levels were not associated with fewer ABDs or higher heart rate. For caffeine boluses given due to clinically recognized spells, hypoxemia and algorithm-detected ABDs decreased day 1-2 after the bolus compared to the day before and day of the bolus (mean 4.4 events/day after vs. 6.6 before, p = 0.004). After caffeine discontinuation, there was no change in hypoxemia and a small increase in ABDs (2 events/day 3-5 days after discontinuation vs. 1 event/day before and >5 days after, p < 0.01). This increase in ABDs occurred irrespective of gestational age, respiratory support, or postmenstrual age at the time caffeine was stopped. Conclusions: In this retrospective analysis, caffeine boluses and caffeine discontinuation were associated with a small change in the number of ABD events in preterm infants.

Neonatal therapeutic hypothermia outside of standard guidelines: a survey of U.S. neonatologists.

AIM: Therapeutic hypothermia is standard of care in term infants with moderate-to-severe hypoxic-ischaemic encephalopathy (HIE). The goal of this survey was to explore the attitudes of U.S. neonatologists caring for infants with HIE who fall outside of current guidelines. METHODS: Case-based survey administered to members of the Section on Neonatal-Perinatal Medicine of the American Academy of Pediatrics. RESULTS: A total of 447 responses were analysed, a response rate of 19%. We found significant variability amongst U.S. neonatologists with regard to the use of therapeutic hypothermia for infants with HIE who fall outside standard inclusion criteria. Scenarios with the most variability included HIE in a late preterm infant and HIE following a postnatal code. Provision of therapeutic hypothermia outside of standard guidelines was not influenced by number of years in practice, neonatal intensive care type (NICU) or NICU size. CONCLUSION: Significant variability in practice exists when caring for infants with HIE who do not meet standard inclusion criteria, emphasizing the need for continued and rigorous research in this area.

Congenital Cutaneous Candidiasis: Prompt Systemic Treatment Is Associated With Improved Outcomes in Neonates.

BACKGROUND: Congenital cutaneous candidiasis (CCC) is a challenging diagnosis due to various rash presentations. Inadequate early treatment is associated with high rates of dissemination and death. The effects of early diagnosis, dermatologic presentation, and antifungal treatment on outcomes are lacking. METHODS: CCC cases were reviewed from 2 academic neonatal intensive care units (NICUs) from 2004 to 2015. We defined CCC as a diffuse rash involving the body, extremities, face or scalp, and/or funisitis, presenting in the first week (≤7 days), with identification of Candida species from skin or mucous membrane cultures, and/or by culture or staining of the placenta or umbilical cord. RESULTS: CCC occurred in 0.1% of all NICU admissions (21 of 19 303) and 0.6% of infants <1000 grams birth weight. Median gestational age of CCC infants was 26 3/7 (range, 23 0/7-40 4/7) weeks. Skin findings were commonly present on the day of birth [median (range): 0 (0-6) days], appearing most frequently as a desquamating, maculopapular, papulopustular, and/or erythematous diffuse rash. When systemic antifungal therapy was started empirically at the time of rash presentation and continued for a median (interquartile range) of 14 (14-15) days, all patients survived and none developed dissemination. Delaying systemic treatment, exclusive use of nystatin, and treating for <10 days was associated with Candida bloodstream dissemination. CONCLUSIONS: CCC is an invasive infection that presents as a diffuse rash in preterm and term infants. Prompt systemic antifungal treatment at the time of skin presentation for ≥14 days prevents dissemination and Candida-related mortality.

Time outside targeted oxygen saturation range and retinopathy of prematurity.

OBJECTIVE: To better understand the impact of hypoxia and hyperoxia on neonatal morbidity and mortality, we examined the number of hypoxia and hyperoxia events as well as percentage of time spent outside oxygen saturation targets in relationship to threshold retinopathy of prematurity (tROP) and mortality in preterm infants. STUDY DESIGN: Saturation data in 2-second sampling from pulse oximeters was prospectively collected in a single NICU. Average SaO2, low and high saturation events, duration of events, and percentage of time infants spent outside of oxygen saturation range were collected and analyzed continuously during the hospitalization. RESULTS: 102 infants <1500g or <32 weeks gestation were enrolled. There were 125, 112, and 43 hypoxia events/day and 106, 80, and 34 hyperoxia events/day for tROP (N=8), non-survivor (N=16) and non-tROP patients (N=78), respectively. Infants were outside saturation targets for 2:35, 1:38, and 1:03 (hypoxia) and 2:02, 1:25, and 0:38 hours/day (hyperoxia) for tROP, non-survivor and non-tROP, respectively. Time spent outside saturation range (hypoxia, hyperoxia and total time) for the hospital course was higher in tROP (P≤0.006) and non-survivor (P≤0.005) compared with non-tROP patients. The three groups defined themselves in the first 10 days after birth, with regard to duration of hypoxia (P=0.0003), hyperoxia (P=0.0004) and total time outside the targeted saturation range (P=0.0006). CONCLUSIONS: Information such as the duration and number of hypoxia and hyperoxia events, as well as total time outside the targeted saturation range, could be factored into assessing clinical interventions and research studies in the prevention, treatment and evaluation of neonatal outcomes.