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In this paper, we review the management of neonatal opioid withdrawal syndrome (NOWS) and clinical pharmacology of primary treatment agents in NOWS, including morphine, methadone, buprenorphine, clonidine, and phenobarbital. Pharmacologic treatment strategies in NOWS have been mostly empirical, and heterogeneity in dosing regimens adds to the difficulty of extrapolating study results to broader patient populations. As population pharmacokinetics (PKs) of pharmacologic agents in NOWS become more well‐defined and knowledge of patient‐specific factors affecting treatment outcomes continue to accumulate, PK/pharmacodynamic modeling and simulation will be powerful tools to aid the design of optimal dosing regimens at the patient level. Although there is an increasing number of clinical trials on the comparative efficacy of treatment agents in NOWS, here, we also draw attention to the importance of optimizing the dosing regimen, which can be arguably equally important at identifying the optimal treatment agent.

This study examined acute findings and long-term outcome trajectories between birth and adolescence in children with prenatal opiate exposure. Ninety children (45 opiate-exposed, 45 non-exposed) completed assessments between 1 month and 15 years of age. Outcome variables (medical, anthropomorphic, developmental, and behavioral) were analyzed at individual time points and using longitudinal statistical modeling. Opiate-exposed infants displayed transient neurologic findings, but no substantial signs or symptoms long term. There were no group differences in growth, cognitive functioning, or behavior at individual time periods; however, the trajectories of outcomes using longitudinal analyses adjusting for variables known to impact outcome demonstrated increased deficits among opiate-exposed children over time with regards to weight, head circumference, cognitive functioning, and behavior. Findings support concerns that maternal opiate use during pregnancy may negatively impact a child’s developmental trajectory, which in turn may impose concerns to society (e.g., increased need for social, medical, and/or educational services).

Objective The objective of the study was to determine the clinical utility of brain natriuretic peptide (NT-proBNP) for prediction of moderate to severe bronchopulmonary dysplasia (BPD). We hypothesized that elevated NT-proBNP levels at 4 weeks of postnatal age may predict the severity of BPD in preterm infants. Study design The study design was a prospective observational study. The research team enrolled and followed a cohort of 70 infants with gestational age less than or equal to 30 weeks. The plasma NT-proBNP levels were measured at the postnatal day 28th. We further followed and categorized infants into two groups. Infants with no or mild BPD (Group 1) and infants with moderate or severe BPD (Group 2). We compared plasma NT-proBNP levels at 28th day of postnatal life between Groups 1 and 2. The difference in NT-proBNP levels on day 28th between groups was used to predict the severity of BPD. Results Plasma NT-proBNP was significantly elevated in Group 2 compared with Group 1, median (IQR) of 845 pg/mL (553, 1632) compared with 726 pg/mL (391, 923), P = 0.02. NT-proBNP had a fair predictive accuracy (C statistics of 0.68) to determine moderate to severe BPD. Conclusion NT-proBNP may be a useful biomarker in conjunction with clinical factors as a predictor of severe BPD. For future directions, the trend of NT-proBNP in infants with BPD may have clinical significance in monitoring of the disease.

BACKGROUND An increasing number of clinical practice guidelines recommend screening children with obesity for non-alcoholic fatty liver disease (NAFLD). However, there is limited evidence regarding what parameters should be used to initiate the screening. OBJECTIVE The objective of this study was to determine whether obesity class rather than age group can identify a higher percent of children at risk of NAFLD as assessed by abnormal alanine aminotransferase (ALT). METHODS This is a cross-sectional study in a regional referral clinic for evaluation of obesity. Children were stratified by age group or by obesity class, and data obtained at first visit were analysed. RESULTS Of the 784 children, 482 were ≥10, 209 were 6 to 9 and 93 were 2 to 5 years of age. Abnormal ALT was observed in 32.1%, 46.9% and 61.0% of children with class I, II or III obesity, respectively (p

Continuous and longitudinal imaging of cerebral blood flow (CBF) variations provide vital information to investigate pathophysiology and interventions for a variety of neurological and cerebral diseases. An innovative noncontact speckle contrast diffuse correlation tomography (scDCT) system was downscaled and adapted for noninvasive imaging of CBF distributions in rat brain through intact scalp and skull. Algorithms for 2D mapping and 3D image reconstruction of CBF distributions were developed and optimized. The continuous imaging capability of the system was shown by imaging global CBF increases during CO2 inhalations and regional CBF decreases across two hemispheres during sequential unilateral and bilateral common carotid artery ligations. The longitudinal imaging capability was demonstrated by imaging CBF variations over a long recovery period of 14 days after an acute stroke. Compared to the 2D mapping method, the 3D imaging method reduces partial volume effects, but needs more computation time for image reconstruction. Results from this study generally agree with those reported in the literature using similar protocols to induce CBF changes in rats. The scDCT enables a relatively large penetration depth (up to ∼10 mm), which is sufficient for transcranial brain measurements in small animals and human neonates. Ultimately, we expect to provide a noninvasive noncontact cerebral imager for basic neuroscience research in small animal models and clinical applications in human neonates.

We present an innovative, wearable, fiber-free, near-infrared diffuse speckle contrast flowmetry (DSCF) probe that is fixed on the skull for continuous monitoring of cerebral blood flow (CBF) variations in mice during anesthesia, awake, and freely behaving. Results show a small surge when the animal waked up, a mild decrease after the isoflurane washed off, a 37 ± 9% increase during 10%CO2 inhalation (n = 3), and mild elevations during grooming and walking. These CBF variations are consistent with clinical observations when recovery from anesthesia and impacts by isoflurane, hypercapnia (CO2), and activity-induced cortical excitations.

Significance: There is an essential need to develop wearable multimodality technologies that can continuously measure both blood flow and oxygenation in deep tissues to investigate and manage various vascular/cellular diseases. Aim: To develop a wearable dual-wavelength diffuse speckle contrast flow oximetry (DSCFO) for simultaneous measurements of blood flow and oxygenation variations in deep tissues. Approach: A wearable fiber-free DSCFO probe was fabricated using 3D printing to confine two small near-infrared laser diodes and a tiny CMOS camera in positions for DSCFO measurements. The spatial diffuse speckle contrast and light intensity measurements at the two different wavelengths enable quantification of tissue blood flow and oxygenation, respectively. The DSCFO was first calibrated using tissue phantoms and then tested in adult forearms during artery cuff occlusion. Results: Phantom tests determined the largest effective source–detector distance (15 mm) and optimal camera exposure time (10 ms) and verified the accuracy of DSCFO in measuring absorption coefficient variations. The DSCFO detected substantial changes in forearm blood flow and oxygenation resulting from the artery occlusion, which meet physiological expectations and are consistent with previous study results. Conclusions: The wearable DSCFO may be used for continuous and simultaneous monitoring of blood flow and oxygenation variations in freely behaving subjects.

BACKGROUND Bronchodilator responses among preterm infants are heterogeneous. Bedside measurements may identify responders. STUDY DESIGN Respiratory measurements (Resistance, Compliance, FiO2) and pulse oximetry (SpO2) patterns were downloaded from infants

Objective A major consequence of prematurity is intermittent hypoxemia (IH). Data from both adult studies and neonatal animal models suggest that IH is proinflammatory; however, there is limited data in preterm infants. Here, we assess the relationship between IH and systemic inflammation, namely, serum C-reactive protein (CRP) in preterm infants.Study Design Serum CRP was measured at 30 days of life, at the time of peak IH frequency. IH measures (e.g., per cent time in hypoxemia, frequency, duration) were calculated the week prior to CRP collection. Statistical analyses were based on Spearman's correlation.Results A total of 26 infants were included. Median gestational age and birth weight were 274/7 weeks and 980 g, respectively. There were positive correlations between primary IH measures and CRP levels, especially for events longer than 1-minute duration (r range: 0.56–0.74, all p Conclusion We demonstrate that IH is associated with increased CRP for the first time in preterm infants. Our findings are consistent with studies from adults and neonatal animal models suggesting that IH is a proinflammatory process.Key Points

Background Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with an increase in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH. Study design and methods We prospectively enrolled infants less than 30 weeks' gestation age. PI and oxygen saturation (SpO2 ) were monitored with high-resolution pulse oximeters 24 hours before and after RBC transfusion. Data were analyzed at three postnatal periods: Epoch 1, first week of life (1 to 7 days of life); Epoch 2, 2 to 4 weeks of life (8 to 28 days of life); and Epoch 3, 4 to 8 weeks of life. Results A total of 118 transfusions were analyzed. IH measures significantly decreased after transfusion in Epochs 2 and 3. PI significantly increased after transfusion, but it did not correlate with the decrease in IH measures. Mechanical ventilation, fraction of inspired oxygen (FiO2 ), and IH measures influenced the effects on oxygenation. Conclusions RBC transfusion improved IH after the first week of life. The benefit in IH did not correlate with PI increase after transfusion. Pretransfusion respiratory support and IH measures predicted the effect of transfusion on oxygenation.

Continuous and longitudinal monitoring of cerebral blood flow (CBF) in animal models provides information for studying the mechanisms and interventions of various cerebral diseases. Since anesthesia may affect brain hemodynamics, researchers have been seeking wearable devices for use in conscious animals. We present a wearable diffuse speckle contrast flowmeter (DSCF) probe for monitoring CBF variations in mice. The DSCF probe consists of a small low-power near-infrared laser diode as a point source and an ultrasmall low-power CMOS camera as a two-dimensional detector array, which can be affixed on a mouse head. The movement of red blood cells in brain cortex (i.e., CBF) produces spatial fluctuations of laser speckles, which are captured by the camera. The DSCF system was calibrated using tissue phantoms and validated in a human forearm and mouse brains for continuous monitoring of blood flow increases and decreases against the established technologies. Significant correlations were observed among these measurements ( $\text{R}^{2}\geq \,{\text{0.80}}$ , $\text{p} ). This small fiberless probe has the potential to be worn by a freely moving conscious mouse. Moreover, the flexible source–detector configuration allows for varied probing depths up to ${\sim\text{8 mm}}$ , which is sufficient for transcranially detecting CBF in the cortices of rodents and newborn infants.

There is a gap in knowledge about the postnatal growth of thyroid gland in preterm infants. To determine postnatal growth of thyroid gland in preterm infants. Thyroid gland volume was calculated in 57 prospectively enrolled preterm infants by measuring serial longitudinal, antero-posterior, and transverse dimensions of thyroid gland with ultrasound. Data were analyzed by using the Wilcoxon and independent t test. There was a significant correlation between thyroid volume (TV) and birthweight (BW) (p = 0.01), and between TV and gestational age (p = 0.02). However, unexpectedly, 12 infants had a decrease in TV between the first and second ultrasounds. Infants with late onset bacterial sepsis had lower TVs on their second ultrasounds than infants without sepsis. Thyroid ultrasound in preterm infants provides noninvasive and quick approach to determine TV and morphology. TV in preterm infants correlates positively with BW and gestational age. However, postnatal growth of thyroid gland is variable and may seemingly be affected by postnatal factors.

Perfusion index (PI) is a noninvasive measure of perfusion. ΔPI (difference between pre- and postductal PI) may identify hemodynamically significant PDA. However, studies are limited to brief and intermittent ΔPI sampling. Our objective is to assess the value of continuous high resolution ΔPI monitoring in the diagnosis of PDA. Continuous ΔPI monitoring in preterm infants was prospectively performed using two high-resolution pulse oximeters. Perfusion Index measures (ΔPI mean and variability, pre- and postductal PI) were analyzed over a 4-h period prior to echocardiography. A cardiologist blinded to the results evaluated for PDA on echocardiography. Linear mixed regression models were utilized for analyses. We obtained 31 echocardiography observations. Mean ΔPI (−0.23 vs. 0.16; P < 0.05), mean pre-PI (0.86 vs. 1.26; P < 0.05), and ΔPI variability (0.39 vs. 0.61; P = 0.05) were lower in infants with PDA compared to infants without PDA at the time of echocardiography. Mean ΔPI, ΔPI variability, and mean pre-PI measured 4 h prior to echocardiography detect PDA in preterm infants. PI is dynamic and should be assessed continuously. Perfusion index is a promising bedside measurement to identify PDA in preterm infants.

This study examined infants' early visual attention (at 1 month of age) and social engagement (4 months) as predictors of their later joint attention (12 and 18 months). The sample (n = 325), drawn from the Maternal Lifestyle Study, a longitudinal multicenter project conducted at 4 centers of the National Institute of Child Health and Human Development Neonatal Research Network, included high-risk (cocaine-exposed) and matched noncocaine-exposed infants. Hierarchical regressions revealed that infants' attention orienting at 1 month significantly predicted more frequent initiating joint attention at 12 (but not 18) months of age. Social engagement at 4 months predicted initiating joint attention at 18 months. Results provide the first empirical evidence for the role of visual attention and social engagement behaviors as developmental precursors for later joint attention outcome. (PsycINFO Database Record

This study examined acute findings and long-term outcome trajectories between birth and adolescence in children with prenatal opiate exposure.Ninety children (45 opiate-exposed, 45 non-exposed) completed assessments between 1 month and 15 years of age. Outcome variables (medical, anthropomorphic, developmental, and behavioral) were analyzed at individual time points and using longitudinal statistical modeling.Opiate-exposed infants displayed transient neurologic findings, but no substantial signs or symptoms long term. There were no group differences in growth, cognitive functioning, or behavior at individual time periods; however, the trajectories of outcomes using longitudinal analyses adjusting for variables known to impact outcome demonstrated increased deficits among opiate-exposed children over time with regards to weight, head circumference, cognitive functioning, and behavior.Findings support concerns that maternal opiate use during pregnancy may negatively impact a child's developmental trajectory, which in turn may impose concerns to society (e.g., increased need for social, medical, and/or educational services).

The developmental impact of opioid use during pregnancy is a subject of ongoing debate. Short-term neonatal outcomes, such as lower birth weight and neonatal abstinence syndrome, are the most well-recognized outcomes. However, knowledge gaps exist regarding longer-term neurocognitive and mental health outcomes. In this article, we summarize an expert panel discussion that was held in April 2018 by the Substance Abuse and Mental Health Services Administration and attended by national experts in the field of perinatal opioid exposure and its impact on child development. Despite the challenges with research in this area, there is emerging literature revealing an association between neonates exposed to opioids in utero and longer-term adverse neurocognitive, behavioral, and developmental outcomes. Although adverse sequalae may not be apparent in the neonatal period, they may become more salient as children develop and reach preschool and school age. Multiple variables (genetic, environmental, and biological) result in a highly complex picture. The next steps and strategies to support families impacted by opioid use disorder are explored. Model programs are also considered, including integrated care for the child and mother, parenting supports, and augmentations to home visiting.

Neonatal abstinence syndrome (NAS) refers to a constellation of signs occurring in newborn infants who were exposed to opioids or opiates in utero. These manifestations include poor feeding, gastrointestinal disorders, abnormal sleep patterns, and neurological signs such as jitteriness, tremors, and seizures (1, 2). Myoclonus, jitteriness, and tremors often may be interpreted as seizures and therefore treated as epileptic seizures. Objective: To determine whether seizure like activity observed in infants with NAS correlate with electroencephalogram (EEG) findings. Design/ Method: We reviewed the standard EEG or video electroencephalogram (VEEG) of infants with NAS who were admitted because of seizure-like clinical activity. The exclusion criteria were major neurological anomalies, hypoxic ischemic encephalopathy, metabolic disorders, or with clinical diagnosis other than NAS. Results: Forty neonates met study criteria; 28 had standard EEG recordings and 18 had VEEG. Mean gestational age was 38.5 weeks. The onset of seizure-like clinical activity was as early as day 1 and as late as day 16 of life. The clinical seizure-like activity described at the referring hospital were jerking, rhythmic movement of the extremities, or tremors. Only three (7.5%) neonates had epileptic seizures. There were increased sharp transients in frontal, central, temporal, and or occipital regions. VEEG showed disturbed non-rapid eye movement (REM) sleep with frequent arousal, jittery movements, or sleep myoclonus. Conclusion: Clinical seizure-like activity correlates poorly with epileptic seizures in infants with NAS. In neonates with NAS, a VEEG would be useful to determine if the clinical seizure-like activity is of epileptic origin or not, prior to initiation of anti-seizure medications.

Objectives: To compare the Shennan's and the consensus definition of Bronchopulmonary Dysplasia (BPD) from the National Institutes of Health (NIH) workshop and analyze specific risk factors associated with each definition. Study design: Retrospective analysis of records of 274 infants admitted to a level IV intensive care unit. Infants were classified as having BPD or no BPD by both definitions. Differences in incidence and risk factors were analyzed. Statistical methods included descriptive statistics, comparative tests, and marginal logistic regression modeling. Results: The estimated difference in prevalence was 32% [95% CI: (26%, 37%), (p < 0.0001)] between both criteria. The prevalence of BPD was 80% higher based on the NIH criteria [RR = 1.80; 95% CI: (1.58, 2.06)]. Infants with no BPD by the Shennan definition were breathing room air with or without positive or continuous pressure support and were most likely to be discharged home on oxygen [OR = 4.47, 95% CI: (1.20, 16.61), p = 0.03]. Gestational age, birth weight, and 1-min Apgar score predicted BPD by both definitions. Chorioamnionitis increased the risk of BPD by the Shennan definition but was associated with lower risk by the NIH criteria. IUGR was associated with BPD by the Shennan definition and with severe BPD by the NIH criteria. Conclusion: Compared to the Shennan's definition, the NIH consensus identified 80% more infants with BPD and is a better predictor of oxygen requirement at discharge. Until a new better criteria is develop, the NIH consensus definition should be used across centers.

We modified and adapted a novel noncontact speckle contrast diffuse correlation tomography (scDCT) system, developed in our laboratory, for noninvasive 3D imaging of blood flow distributions in small animals and large human tissue volumes. The new system has the flexibility of selecting small and large regions of interest (ROIs) with different imaging depths for the use in both the small mouse head and large human mastectomy skin flaps. The capability of the upgraded scDCT system was demonstrated by continuous imaging of cerebral blood flow (CBF) changes in a small mouse head during sequential common carotid artery ligations and blood flow distributions in human mastectomy skin flaps during surgery. As expected, arterial occlusions resulted in substantial CBF decreases in deep brain tissues of the mouse. Spatial heterogeneity existed, and lower blood flow values were observed around the incision area of mastectomy skin flaps. The noncontact scDCT system with flexible ROIs and imaging depths has the potential to be used in many preclinical and clinical settings for noninvasive assessment of tissue hemodynamics and viability.

Extremely preterm infants’ hemodynamic instability places them at high risk of brain injury. Currently there is no reliable bedside method to continuously monitor cerebral hemodynamics in the neonatal intensive care unit (NICU). This paper reports a feasibility study to adapt and test an innovative speckle contrast diffuse correlation tomography (scDCT) device for noncontact, high-density, 3D imaging of cerebral blood flow (CBF) in preterm infants. The scDCT scans a focused point near-infrared illumination to multiple source positions for deep tissue penetration, and controls an electron multiplying charge-coupled-device camera with thousands of pixels to achieve a high-density sampling. The optimized scDCT for use in preterm infants was first evaluated against an established diffuse correlation spectroscopy in an infant-head-simulating phantom with known properties. The observed significant correlation between the two measurements verified the capability of scDCT for transcranial brain imaging. The insignificant influence of transparent incubator wall on scDCT measurements was then confirmed by comparing adult forearm blood flow responses to artery cuff occlusions measured inside and outside the incubator. Finally, the scDCT device was moved to the NICU to image CBF variations in two preterm infants. Infant #1 with no major organ deficits showed little CBF fluctuation over the first 3 weeks of life. Infant #2 showed a significant CBF increase after the 2 h pharmacotherapy for patent ductus arteriosus closure. While these CBF variations meet physiological expectations, the fact that no significant changes are noted with peripheral monitoring of blood oxygen saturation suggests necessity of direct cerebral monitoring. This feasibility study with timely technology development is an important and necessary step towards larger clinical studies with more subjects to further validate it for continuous monitoring and instant management of cerebral pathologies and interventions in the NICU.

Emerging data suggest intraventricular hemorrhage (IVH) of the preterm neonate is a complex disorder with contributions from both the environment and the genome. Environmental analyses suggest factors mediating both cerebral blood flow and angiogenesis contribute to IVH, while candidate gene studies report variants in angiogenesis, inflammation, and vascular pathways. Gene-by-environment interactions demonstrate the interaction between the environment and the genome, and a non-replicated genome-wide association study suggests that both environmental and genetic factors contribute to the risk for severe IVH in very low-birth weight preterm neonates.

Key Points Question Can a simplified Finnegan Neonatal Abstinence Scoring Tool (FNAST), composed only of dichotomized items that are independently associated with the decision to initiate pharmacologic therapy, discriminate between infants who did and did not receive therapy as effectively as the original FNAST? Findings In this cohort study of 424 neonates with opioid exposure, the simplified FNAST discriminated between neonates who did and did not receive pharmacologic treatment nearly as well as the original FNAST. Meaning Use of a simplified FNAST may provide an accurate means of identifying neonatal abstinence syndrome and may enhance the clinical utility of the tool., This cohort study identifies items on the Finnegan Neonatal Abstinence Scoring Tool (FNAST) that are independently associated with the decision to use pharmacologic therapy and simplifies the tool while minimizing loss of information for the treatment decision., Importance Observer-rated scales, such as the Finnegan Neonatal Abstinence Scoring Tool (FNAST), are used to quantify the severity of neonatal abstinence syndrome (NAS) and guide pharmacologic therapy. The FNAST, a comprehensive 21-item assessment tool, was developed for research and subsequently integrated into clinical practice; a simpler tool, designed to account for clinically meaningful outcomes, is urgently needed to standardize assessment. Objectives To identify FNAST items independently associated with the decision to use pharmacologic therapy and to simplify the FNAST while minimizing loss of information for the treatment decision. Design, Setting, and Participants This multisite cohort study included 424 neonates with opioid exposure who had a gestational age of at least 36 weeks with follow-up from birth to hospital discharge in the derivation cohort and 109 neonates with opioid exposure from the Maternal Opioid Treatment: Human Experimental Research Study in the validation cohort. Neonates in the derivation cohort were included in a medical record review at the Universities of Louisville and Kentucky or in a randomized clinical trial and observational study conducted at Tufts University (2014-2018); the Maternal Opioid Treatment: Human Experimental Research was conducted from 2005 to 2008. Data analysis was conducted from May 2017 to August 2019. Exposures Prenatal opioid exposure. Main Outcomes and Measures All FNAST items were dichotomized as present or not present, and logistic regression was used to identify binary items independently associated with pharmacologic treatment. The final model was validated with an independent cohort of neonates with opioid exposure. Results Among 424 neonates (gestational age, ≥36 weeks; 217 [51%] female infants), convulsions were not observed, and high-pitched cry and hyperactive Moro reflex had extremely different frequencies across cohorts. Therefore, these 3 FNAST items were removed from further analysis. The 2 tremor items were combined, and 8 of the remaining 17 items were independently associated with pharmacologic treatment, with an area under the curve of 0.86 (95% CI, 0.82-0.89) compared with 0.90 (95% CI, 0.87-0.94) for the 21-item FNAST. External validation of the 8 items resulted in an area under the curve of 0.86 (95% CI, 0.79-0.93). Thresholds of 4 and 5 on the simplified scale yielded the closest agreement with FNAST thresholds of 8 and 12 (weighted κ = 0.55; 95% CI, 0.48-0.61). Conclusions and Relevance The findings of this study suggest that 8 signs of NAS may be sufficient to assess whether a neonate meets criteria for pharmacologic therapy. A focus on these signs could simplify the FNAST tool and may enhance its clinical utility.

BACKGROUND: Red blood cell (RBC) transfusion decreases intermittent hypoxemia (IH) events beyond the first week of life. This benefit may be related to improved perfusion to the respiratory control network. Perfusion index (PI) is a perfusion measure provided by the pulse oximeter. We hypothesized that the benefit in IH after RBC transfusion is associated with a rise in PI. In addition, we assessed the value of PI and clinical measures in predicting the effect of RBC transfusion on IH. STUDY DESIGN AND METHODS: We prospectively enrolled infants less than 30 weeks gestational age. PI and oxygen saturation (SpO(2)) were monitored with high-resolution pulse oximeters 24 hours pre and post RBC transfusion. Data was analyzed at three postnatal periods, epoch 1: first week of life (1 to 7 days of life), epoch 2: 2 to 4 weeks of life (8 to 28 days of life), and epoch 3: 4 to 8 weeks of life. RESULTS: One hundred eighteen transfusions were analyzed. IH measures significantly decreased post transfusion in epochs 2 and 3. PI significantly increased after transfusion, but it did not correlate with the decrease in IH measures. Mechanical ventilation, fraction of inspired oxygen (FiO(2)), and IH measures influenced the effects on oxygenation. CONCLUSIONS: RBC transfusion improved IH after the first week of life. The benefit in IH did not correlate with PI increase after transfusion. Pre transfusion respiratory support and IH measures predicted the effect of transfusion on oxygenation.

We reported a novel, low-cost, compact, fiberless, diffuse speckle contrast flowmeter consisting of a laser diode and a bare CCD/CMOS chip for tissue blood flow measurement. We validated the system in tissue phantoms and explored its applications in human tissues.

Background: BPD is associated with significant morbidity and mortality in extremely premature infants. Incidence of BPD is used in neonatal centers as an index of quality of care. NICHD has adapted the criteria for BPD as need of oxygen support (>21%) at 36 weeks of postmenstrual age (PMA) in infants born 28 days but 32 weeks. It was further categorized by severity based on …

Objective Vitamin E deficiency in premature infants has been associated with hemolytic anemia. Its incidence decreased after the supplementation of preterm formulas and parenteral nutrition with vitamin E. Despite this, some infants still develop hemolytic anemia and receive vitamin E. Study Design Retrospective analysis of 70 infants admitted to a level IV intensive care unit and who developed hemolytic anemia and were treated with vitamin E. Infants were classified into two groups based on whether or not they responded to vitamin E therapy. Statistical methods included the use of descriptive statistics and marginal logistic regression models. Results Low hematocrit and reticulocytosis before vitamin E administration were associated with adequate response to treatment. Thrombocytosis, iron treatment (duration and dose), gestational age, birth weight, and type of feedings were not. Infants who received a short duration of parenteral nutrition and were on oxygen responded to vitamin E therapy. Infants with a hematocrit ≤ 26% and reticulocyte of 36.1% were more likely to respond to vitamin E. Conclusion Although formulas and parenteral nutrition are supplemented with vitamin E; some preterm infants may still develop hemolytic anemia. Those with anemia, reticulocytosis, and oxygen requirement may benefit from additional vitamin E.

IntroductionIntermittent hypoxemia (IH) is defined as episodic drops in oxygen saturation (SpO2). Preterm infants are at increased risk for IH due to their immature respiratory control/apnea of prematurity. The clinical relevance of IH is a relatively new observation with rising evidence linking IH to neonatal morbidities and long-term impairment. Hence, assessing factors that influence IH in preterm infants is imperative. Given the epidemic of opioid misuse in the USA, there is an urgent need to understand the impact of prenatal opioid exposure on neonatal outcomes. Hence, we wanted to assess the relationship between isolated prenatal opioid exposure and IH in preterm infants.MethodsIn order to accurately calculate IH, SpO2 data were prospectively collected using high-resolution pulse oximeters during the first 8 weeks of life in preterm infants less than 30 weeks gestational age. Data related to prenatal opioid misuse were retrospectively collected from medical charts. Infants with tobacco or poly-drug exposure were excluded. The primary outcome measure is percent time spent with SpO2 below 80% (%time-SpO2

Opiate addiction is now a major public health problem. Perinatal insults and exposure to opiates such as morphine in utero are well known to affect development of the hypothalamic-pituitary-adrenal (HPA)-axis of the offspring adversely and are associated with a higher risk of developing neurobehavioral problems. Oxycodone is now one of the most frequently abused pain killers during pregnancy, however limited data are available regarding whether and how perinatal oxycodone exposure (POE) alters neurobehavioral outcomes of the offspring. We demonstrated that exposure to 0.5 mg/kg/day oxycodone in utero was associated with hyperactivity in adult rats in an open field. No significant effects of POE were detected on isolation induced ultrasonic vocalizations in the early postnatal period or on learning and memory in the water maze in adult offspring. Our findings are consistent with hyperactivity problems identified in children exposed to opiates in utero.

Physiological correlates of behavioral and emotional problems, substance use onset and initiation of risky sexual behavior have not been studied in adolescents with prenatal drug exposure. We studied the concordance between baseline respiratory sinus arrhythmia (RSA) at age 3 and baseline cortisol levels at age 11. We hypothesized that children who showed concordance between RSA and cortisol would have lower neurobehavioral disinhibition scores which would in turn predict age of substance use onset and first sexual intercourse. The sample included 860 children aged 16 years participating in the Maternal Lifestyle Study, a multisite longitudinal study of children with prenatal exposure to cocaine and other substances. Structural equation modeling was used to test pathways between prenatal substance exposure, early adversity, baseline RSA, baseline cortisol, neurobehavioral disinhibition, drug use, and sexual behavior outcomes. Concordance was studied by examining separate male and female models in which there were statistically significant interactions between baseline RSA and cortisol. Prenatal substance exposure was operationalized as the number of substances to which the child was exposed. An adversity score was computed based on caregiver postnatal substance use, depression and psychological distress, number of caregiver changes, socioeconomic and poverty status, quality of the home environment, and child history of protective service involvement, abuse and neglect. RSA and cortisol were measured during a baseline period prior to the beginning of a task. Neurobehavioral disinhibition, based on composite scores of behavioral dysregulation and executive dysfunction, substance use and sexual behavior were derived from questionnaires and cognitive tests administered to the child. Findings were sex specific. In females, those with discordance between RSA and cortisol (high RSA and low cortisol or low RSA and high cortisol) had the most executive dysfunction which, in turn, predicted earlier initiation of alcohol by age 16. Among boys, there also existed a significant baseline RSA by baseline cortisol interaction. Boys with low baseline RSA and high baseline cortisol had the highest levels of behavioral dysregulation. This increase in behavioral dysregulation was in turn related to initiation of alcohol use by age 16 and lower age of first sexual intercourse. We found sex-specific pathways to the initiation of alcohol use and risky sexual behavior through the combined activity of parasympathetic and neuroendocrine functioning. The study of multiple physiological systems may suggest new pathways to the study of age of onset of substance use and engagement in risky sexual behavior in adolescents.

To evaluate factors that can influence the Finnegan Neonatal Abstinence Score (FNAS). Retrospective analysis of 367 patients admitted to two level IV neonatal intensive care units. Linear mixed effects models were developed to evaluate daily census, time of the day, and day of the week as fixed effect predictors. The degree of influence that nurses had on FNAS variability was also estimated. Bivariate analyses showed that daily census and the time of day have significant influence on the FNAS in institution 1, with minimal clinical significance. The proportion of variation in the FNAS attributable to differences in nurses was of 9.8% and 5.1% for institutions 1 and 2, respectively (P

A high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of morphine, morphine's major metabolites morphine-3-glucuronide and morphine-6-glucuronide, and clonidine, to support the pharmacokinetic analysis of an ongoing double-blinded randomized clinical trial that compares the use of morphine and clonidine in infants diagnosed with neonatal abstinence syndrome. Plasma samples were processed by solid-phase extraction and separated on an Inertsil ODS-3 (4 μm) column using an 0.1% formic acid in water-0.1% formic acid in methanol gradient. Detection of the analytes was conducted in the positive multiple reaction monitoring mode. The range of quantitation was 1-1000 ng/mL for morphine, morphine-3-glucuronide and morphine-6-glucuronide, and 0.25-100 ng/mL for clonidine. Intra-day and inter-day accuracy and precision were ≤15% for all analytes across the quantitation range. Extraction recovery rates were ≥94% for morphine, ≥90% for M3G, ≥87% for M6G and ≥ 79% for clonidine. Matrix effect ranged from 85-94% for clonidine to 101-106% for M3G. The method fulfilled all predetermined acceptance criteria and required only 100 μL of starting plasma volume. Furthermore, it was successfully applied to 30 clinical trial plasma samples.

Objectives At some institutions all infants requiring RBC transfusions in neonatal intensive care units (NICUs) receive only group O RBCs. Although transfused group O plasma is minimized in packed RBCs, small amounts of residual anti-A, anti-B, and anti-A,B in group O packed RBCs may bind to the corresponding A and B antigens of non–group O RBCs, possibly hemolyzing their native RBCs and thereby releasing free hemoglobin, theoretically resulting in hypercoagulability and promoting bacterial growth from free iron. Methods Premature infants in the University of Kentucky Children’s Hospital NICU database who were transfused (all received group O transfusions) were compared for a number of severity markers to determine if non–group O patients had worse outcomes than group O patients. Results In this NICU sample, 724 neonates received at least 1 blood component. No significant differences were found between group O and non–group O infants with regard to final disposition or complications. Conclusions This reassuring finding validates the longstanding neonatal transfusion practice of using group O packed RBCs for infants of all blood groups in the NICU. However, a recent study shows increased mortality from necrotizing enterocolitis in group AB neonates at a facility transfusing only group O RBCs to neonates of all blood groups and suggests a change in neonatal transfusion practice to ABO group–specific RBCs; therefore more studies may be warranted.

BACKGROUND: We determined the role of risk and protective factors on the trajectories of behavior problems associated with high prenatal cocaine exposure (PCE)/polydrug exposure. METHODS: The Maternal Lifestyle Study enrolled 1388 children with or without PCE, assessed through age 15 years. Because most women using cocaine during pregnancy also used other substances, we analyzed for the effects of 4 categories of prenatal drug exposure: high PCE/other drugs (OD), some PCE/OD, OD/no PCE, and no PCE/no OD. Risks and protective factors at individual, family, and community levels that may be associated with behavior outcomes were entered stepwise into latent growth curve models, then replaced by cumulative risk and protective indexes, and finally by a combination of levels of risk and protective indexes. Main outcome measures were the trajectories of externalizing, internalizing, total behavior, and attention problems scores from the Child Behavior Checklist (parent). RESULTS: A total of 1022 (73.6%) children had known outcomes. High PCE/OD significantly predicted externalizing, total, and attention problems when considering the balance between risk and protective indexes. Some PCE/OD predicted externalizing and attention problems. OD/no PCE also predicted behavior outcomes except for internalizing behavior. High level of protective factors was associated with declining trajectories of problem behavior scores over time, independent of drug exposure and risk index scores. CONCLUSIONS: High PCE/OD is a significant risk for behavior problems in adolescence; protective factors may attenuate its detrimental effects. Clinical practice and public health policies should consider enhancing protective factors while minimizing risks to improve outcomes of drug-exposed children.

Using existing longitudinal data from 570 infants in the Maternal Lifestyle Study, we explored the predictive value of maternal and infant affect and maternal vocalizations during 2 minutes of face-to-face interactions at 4 months on IQ scores at 4.5 and 7 years. After controlling for demographic factors, maternal depression, and prenatal drug exposure, maternal positive affect and maternal positive vocalizations emerged as predictors of both verbal and performance IQ at 4.5 and 7 years. Although infant positive affect during the interaction with the mother was not predictive of these outcome measures, infant positive affect towards an examiner predicted verbal but not performance IQ at 4.5 years. These results suggest that maternal positive affect may index emotional engagement in interaction that facilitates both verbal and nonverbal cognitive development, while infant social positive affect is specifically related to the acquisition of verbal reasoning abilities. These findings are significant because they are based on a discrete snapshot of observable behavior in infancy (just 2 minutes of interaction), because they extend the range of maternal behaviors and characteristics known to support positive developmental outcomes, and because they are derived from high-risk infants where prevention efforts may be beneficial. Potential mechanisms for these associations are discussed, as are the clinical implications for identifying dyads most in need of targeted interventions.

Patent ductus arteriosus (PDA) is common in preterm infants and is associated with significant morbidities. B type natriuretic peptide (BNP) is synthesized in the ventricles secondary to volume overload and excreted as urinary N-terminal pro-brain natriuretic peptide (NT-proBNP). We report an observational prospective study of 64 preterm infants with birth weight ⩽1000 g. Echocardiographic parameters were obtained from clinical echocardiograms performed in the first week of life. Urinary NT-proBNP/creatinine ratios (pg mg−1) were measured on the same day of the echocardiograms. Infants with medium to large PDA (n=39) had significantly higher NT-proBNP/creatinine levels compared with infants with small PDA (n=10) (median (IQ range): 2333 (792–6166) vs 714 (271–1632) pg mg−1, P=0.01) and compared with infants with no PDA (n=15) (2333 (792–6166) vs 390 (134–1085) pg mg−1, P=0.0003). Urinary NT-proBNP/creatinine ratios were significantly lower post treatment if PDA closed (n=17), P=0.001 or if PDA became smaller after treatment (n=9), P=0.004. Urinary NT-proBNP/creatinine levels correlated with ductal diameter (P⩽0.0001), but not with LA/Ao ratio (P=0.69) or blood flow velocity through the ductus (P=0.06). Our findings indicate that there is a positive correlation between ductal diameter and urinary NT-proBNP in preterm infants.