Objective Assessment of Physiologic Alterations Associated with Hemodynamically Significant Patent Ductus Arteriosus in Extremely Premature Neonates

Delay in closure of ductus arteriosus in postnatal life may lead to serious consequences and complications in an extremely premature neonate secondary to hemodynamic alterations in regional blood flow pattern in various organs. Despite the widespread recognition amongst neonatologists to identify a hemodynamically significant patent ductus arteriosus (hsPDA) early in the postnatal course, there is lack of consensus in its definition and thus the threshold to initiate treatment. Echocardiographic assessment of PDA shunt size and volume combined with neonatologists\u27 impression of clinical significance is most frequently used to determine the need for treatment of PDA. Common clinical signs of hsPDA utilized as surrogate for decreased tissue perfusion may lag behind early echocardiographic signs. Although echocardiogram allows direct assessment of PDA shunt and hemodynamic alterations in the heart, it is limited by dependence on pediatric cardiologist availability, interobserver variation and isolated time point assessment. Electrical cardiometry (EC) is a non-invasive continuous real time measurement of cardiac output by applying changes in thoracic electrical impedance. EC has been validated in preterm newborns by concomitant transthoracic echocardiogram assessments and may be beneficial in studying changes in cardiac output in premature newborns with hsPDA. Alterations in perfusion index derived from continuous pulse oximetry monitoring has been used to study changes in cardiac performance and tissue perfusion in infants with PDA. Near infrared spectroscopy (NIRS) has been used to objectively and continuously assess variations in renal, mesenteric, and cerebral oxygen saturation and thus perfusion changes due to diastolic vascular steal from hsPDA in preterm neonates. Doppler ultrasound studies measuring resistive indices in cerebral circulation indicate disturbance in cerebral perfusion secondary to ductal steal. With recent trends of change in practice toward less intervention in care of preterm newborn, treatment strategy needs to be targeted for select preterm population most vulnerable to adverse hemodynamic effects of PDA. Integration of these novel ways of hemodynamic and tissue perfusion assessment in routine clinical care may help mitigate the challenges in defining and targeting treatment of hsPDA thereby improving outcomes in extremely premature neonates

Clinical Pharmacology and Dosing Regimen Optimization of Neonatal Opioid Withdrawal Syndrome Treatments

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

EEG Findings in Infants With Neonatal Abstinence Syndrome Presenting With Clinical Seizures

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

Bronchopulmonary Dysplasia: Comparison Between the Two Most Used Diagnostic Criteria

Objectives: To compare the Shennan\u27s 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 \u3c 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\u27s 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

Effects of Perinatal Oxycodone Exposure on the Cardiovascular Response to Acute Stress in Male Rats at Weaning and in Young Adulthood

Oxycodone (OXY) is one of the most commonly abused opiates during pregnancy. Perinatal opiate exposure (POE) is associated with neurobehavioral and hormone changes. Little is known about the effects of perinatal OXY on the cardiovascular (CV) responses to stress. Objectives: to determine the effects of POE on: (1) CV responses to acute stress and ability to discriminate using a classical conditioning paradigm; (2) changes in CV response to the paradigm and retention of the ability to discriminate from postnatal day (PD) 40 to young adulthood. Methods: Pregnant rats were given i.v. OXY or vehicle (CON) daily. OXY and CON males were fitted with BP telemetry units. Offspring were classically conditioned by following a pulsed tone (CS+) with tail shock. A steady tone (CS-) was not followed by shock. BP and HR were recorded during resting periods and conditioning. Changes in BP, HR from composite analysis were compared. The paradigm was repeated on PD 75. Results: At PD 40, OXY rats had a lower baseline mean BP (OXY: 114.8 ± 1.0 vs. CON: 118.3 ± 1.0 mm Hg; mean ± SEM) but larger amplitude of the conditional BP increase during the stress response (OXY: +3.9 ± 0.4 vs. CON: +1.7 ± 0.4 mm Hg). Both OXY and CON rats were able to discriminate between CS+ and CS-. At PD 75, the effects of OXY on the increased amplitude of the conditional BP had dissipated (CON: +3.4 ± 2.3 vs. OXY: +4.5 ± 1.4 mm Hg). BP responses to the stress and non-stress stimuli did not differ in the OXY group, suggesting that OXY may have decreased the ability of the offspring to discriminate (OXY: CS+: 147.1 ± 1.6, CS-: 145.9 ± 1.6 mm Hg vs. CON: CS+: 155.4 ± 2.7, CS-: 147.8 ± 2.7 mm Hg). Conclusion: POE is associated with subtle alterations in stress CV responses in weanling rats which dissipate when the conditioning is repeated at an early adult age. Although POE effect on the ability to discriminate at weanling age could not be detected, POE may impair retention of this ability in adulthood

Enhancement of PCA-based fault detection system through utilising dissimilarity matrix for continuous-based process

This research is about enhancement of PCA-based fault detection system through utilizing dissimilarity matrix. Nowadays, the chemical process industry is highly based on the non-linear relationships between measured variables. However, the conventional PCA-based MSPC is no longer effective because it only valid for the linear relationships between measured variables. Due in order to solve this problem, the technique of dissimilarity matrix is used in multivariate statistical process control as alternative technique which models the non-linear process and can improve the process monitoring performance. The conventional PCA system was run and the dissimilarity system was developed and lastly the monitoring performance in each technique were compared and analysed to achieve aims of this research. This research is to be done by using Matlab software. The findings of this study are illustrated in the form of Hotelling’s T2 and Squared Prediction Errors (SPE) monitoring statistics to be analysed. As a conclusion, the dissimilarity system is comparable to the conventional method. Thus can be the other alternative ways in the process monitoring performance. Finally, it is recommended to use data from other chemical processing systems for more concrete justification of the new technique

The Effects of Perinatal Oxycodone Exposure on Behavioral Outcome in a Rodent Model

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 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

Plasma Brain-Derived Neurotrophic Factor Levels in Newborn Infants with Neonatal Abstinence Syndrome

Background: Brain-derived neurotrophic factor (BDNF) is a type of growth factor that promotes growth and survival of neurons. Fetal exposure to opiates can lead to postnatal withdrawal syndrome, which is referred as neonatal abstinence syndrome (NAS). Preclinical and clinical studies have shown an association between opiates exposure and alteration in BDNF expression in the brain and serum levels in adult. However, to date, there are no data available on the effects of opiate exposure on BDNF levels in infant who are exposed to opiates in utero and whether BDNF level may correlate with the severity of NAS. Objective: To compare plasma BDNF levels among NAS and non-NAS infants and to determine the correlation of BDNF levels and the severity of NAS. Methods: This is a prospective cohort study with no intervention involved. Infants ≥35 weeks of gestation were enrolled. BDNF level was measured using enzyme-linked immunosorbent assay technique from blood samples drawn within 48 h of life. The severity of NAS was determined by the length of hospital stay, number of medications required to treat NAS. Results: 67 infants were enrolled, 34 NAS and 33 non-NAS. Mean gestational age did not differ between the two groups. Mean birth weight of NAS infants was significantly lower than the non-NAS infants (3,070 ± 523 vs. 3,340 ± 459 g, p = 0.028). Mean BDNF level in NAS group was 252.2 ± 91.6 ng/ml, significantly higher than 211.3 ± 66.3 ng/ml in the non-NAS group (p = 0.04). There were no differences in BDNF levels between NAS infants that required one medication vs. more than one medication (254 ± 91 vs. 218 ± 106 ng/ml, p = 0.47). There was no correlation between the BDNF levels and length of hospital stay (p = 0.68) among NAS infants. Overall, there were no significant correlations between BDNF levels and NAS scores except at around 15 h after admission (correlation 0.35, p = 0.045). Conclusion: Plasma BDNF level was significantly increased in NAS infants during the first 48 h when compared to non-NAS infants. The correlations between plasma BDNF levels and the severity of NAS warrant further study. These results suggest that BDNF may play a neuromodulatory role during withdrawal after in utero opiate exposure

Simplification of the Finnegan Neonatal Abstinence Scoring System: Retrospective Study of Two Institutions in the USA

Objective To develop a simplified Finnegan Neonatal Abstinence Scoring System (sFNAS) that will highly correlate with scores ≥ 8 and ≥12 in infants being assessed with the FNAS. Design, setting and participants This is a retrospective analysis involving 367 patients admitted to two level IV neonatal intensive care units with a total of 40 294 observations. Inclusion criteria included neonates with gestational age ≥ 37 0/7 weeks, who are being assessed for neonatal abstinence syndrome (NAS) using the FNAS. Infants with a gestational age \u3c 37 weeks were excluded. Methods A linear regression model based on the original FNAS data from one institution was developed to determine optimal values for each item in the sFNAS. A backward elimination approach was used, removing the items that contributed least to the Pearson’s correlation. The sFNAS was then cross-validated with data from a second institution. Results Pearson’s correlation between the proposed sFNAS and the FNAS was 0.914. The optimal treatment cut-off values for the sFNAS were 6 and 10 to predict FNAS scores ≥ 8 and ≥ 12, respectively. The sensitivity and specificity of these cut-off values to detect FNAS scores ≥ 8 and ≥ 12 were 0.888 and 0.883 for a cut-off of 6, and 0.637 and 0.992 for a cut-off of 10, respectively. The sFNAS cross-validation resulted in a Pearson’s correlation of 0.908, sensitivity and specificity of 0.860 and 0.873 for a cut-off of 6, and 0.525 and 0.986 for a cut-off of 10, respectively. Conclusion The sFNAS has a high statistical correlation with the FNAS, and it is cross-validated for the assessment of infants with NAS. It has excellent specificity and negative predictive value for identifying infants with FNAS scores ≥ 8 and ≥ 12

Bronchopulmonary Dysplasia: Comparison Between the Two Most Used Diagnostic Criteria

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