Impact of maternal medication for opioid use disorder on neurodevelopmental outcomes of infants treated for neonatal opioid withdrawal syndrome.

BACKGROUND: Increasing rates of maternal opioid use disorder has led to greater number of opioid exposed newborns (OENs). Maternal enrollment in medication for opioid use disorder (MOUD) program improves short term neonatal outcomes. This study aimed at assessing neurobehavioral outcomes for OENs. METHODS: Retrospective observational cohort study of OENs between Jul 2006 and Dec 2018. Two study groups were identified as initiation of medication for opioid use disorder (MOUD) prior to diagnoses of pregnancy or after. Primary outcome variables were enrollment in and duration of EI services. Secondary outcome variable was diagnoses of a behavioral and/or developmental disorder (BDD) during the study period. RESULTS: Of 242 infants, 113 were enrolled in EI and BDD diagnoses data was available for all infants [age range 6 to 12 years], 82% infants had exposure to maternal MOUD, while 18% were exposed to either maternal prescription non-MOUD opioids or illicit opioids. Maternal MOUD initiation prior to pregnancy was associated with improved short term outcomes for OENs. Almost a third of infants were diagnosed with a BDD with no differences between the two study groups. CONCLUSION: Early initiation of maternal MOUD improved short term outcomes and discharge disposition for OENs. Prolonged in-utero exposure to opioids presents a potential for negative impact on neurodevelopmental and behavioral outcomes. These risks must be considered to increase access and adherence to EI services, as well as to focus on non-opioid based maternal MOUD. Longitudinal studies assessing the safety of MOUD on short and long-term child health outcomes are needed.

Efficacy of clonidine versus phenobarbital in reducing neonatal morphine sulfate therapy days for neonatal abstinence syndrome. A prospective randomized clinical trial.

OBJECTIVE: To compare the efficacy of clonidine versus phenobarbital in reducing morphine sulfate treatment days for neonatal abstinence syndrome (NAS). STUDY DESIGN: Prospective, non-blinded, block randomized trial at a single level III NICU (Neonatal Intensive Care Unit). Eligible infants were treated with a combination of medications as per protocol. Primary outcome was treatment days with morphine sulfate. Secondary outcomes were the mean total morphine sulfate dose, outpatient phenobarbital days, adverse events and treatment failures. RESULTS: A total of 82 infants were eligible, of which 68 were randomized with 34 infants in each study group. Adjusting for covariates phenobarbital as compared with clonidine had shorter morphine sulfate treatment days (-4.6, 95% confidence interval (CI): -0.3, -8.9; P=0.037) with no difference in average morphine sulfate total dose (1.1 mg kg(-1), 95% CI: -0.1, 2.4; P=0.069). Post-discharge phenobarbital was continued for an average of 3.8 months (range 1 to 8 months). No other significant differences were noted. CONCLUSION: Phenobarbital as adjunct had clinically nonsignificant shorter inpatient but significant overall longer therapy time as compared with clonidine.

Use of fraction flow reserve to predict changes over time in management of superficial femoral artery.

BACKGROUND: Peripheral arterial disease is a condition characterized by progressive arterial narrowing, which affects patients' quality of life. The purposes of this study were to (1) establish the feasibility of obtaining peripheral fractional flow reserve (pFFR) in the peripheral vascular circulation, (2) demonstrate an association between baseline pFFR and peak systolic velocity (PSV) measured by duplex ultrasound, and (3) correlate postintervention pFFR with future restenosis using the change in PSV over time as a surrogate. METHODS: Twenty patients underwent baseline ankle brachial index (ABI) and PSV testing. Pre- and postintervention pFFR was performed. Patients were followed with three ABI and PSV recordings during the 1 year follow-up period. The association between baseline PSV, ABI, and pFFR with changes in PSV over time were explored. Predictors of postprocedural PSV over time were determined. RESULTS: The baseline translesional-resting ratio was significantly different from the pFFR using adenosine (0.79 ± 0.08 vs. 0.71 ± 0.09, P = 0.01). Baseline PSV was significantly associated with preintervention pFFR (-0.77, P < 0.001). Compared to patients with a postprocedure pFFR > 0.95, patients with a postprocedure pFFR < 0.95 had a significantly more rapid rise in PSV over time (P = 0.009). CONCLUSION: This is the first study to demonstrate that the peripheral vascular bed does respond to vasodilatation thereby supporting the use of pFFR for this procedure. In our study, postintervention pFFR < 0.95 predicted a more rapid increase in PSV over time, which is a reasonably accepted surrogate for restenosis.

Association of necrotizing enterocolitis with anemia and packed red blood cell transfusions in preterm infants.

OBJECTIVE: To determine association of anemia and red blood cell (RBC) transfusions with necrotizing enterocolitis (NEC) in preterm infants. STUDY DESIGN: A total of 111 preterm infants with NEC ≥ stage 2a were compared with 222 matched controls. In all, 28 clinical variables, including hematocrit (Hct) and RBC transfusions were recorded. Propensity scores and multivariate logistic regression models were created to examine effects on the risk of NEC. RESULT: Controlling for other factors, lower Hct was associated with increased odds of NEC (odds ratio (OR)=1.10, P=0.01). RBC transfusion has a temporal relationship with NEC onset. Transfusion within 24 h (OR=7.60, P=0.001) and 48 h (OR=5.55, P=0.001) has a higher odds of developing NEC but this association is not significant by 96 h (OR=2.13, P=0.07), post-transfusion. CONCLUSION: Anemia may increase the risk of developing NEC in preterm infants. RBC transfusions are temporally related to NEC. Prospective studies are needed to better evaluate the potential influence of transfusions on the development of NEC.

NICU lactation consultant increases percentage of outborn versus inborn babies receiving human milk.

OBJECTIVE: To determine the effect of a dedicated lactation consultant (LC) on the percentage of neonates receiving any human milk in the neonatal intensive care unit (NICU) and at discharge over time. STUDY DESIGN: Retrospective chart review of three time periods of 3 months each; Time period 1 (before LC hire), Time period 2 (T2; after LC arrival) and Time period 3 (subsequent period after T2). RESULT: Percentage of infants receiving any HM during hospital stay and at discharge increased significantly over time after LC hire and with LC experience. Outborn (OB) infants receiving any HM in the NICU and at discharge increased over time, but there was no significant change for inborn infants, as the proportion receiving any HM remained consistently high over time. CONCLUSION: Addition of a dedicated LC to the NICU increased the percentage of neonates receiving any HM, specifically in the OB population.

Cerebrovascular disease among patients from the Indian subcontinent.

In this study, the authors document the characteristics of South Asian (SA) cerebrovascular patients. A retrospective medical record review comparing SA (n = 99) and European-American (n = 106) patients was performed. SA patients were younger and had a greater prevalence of diabetes, but lower prevalences of hyperlipidemia and tobacco use. SA patients experienced a 75% lower risk of cardiogenic infarctions, but a threefold increased risk of intracranial atherothrombosis. Risk factor modifications and secondary prevention strategies may differ for SA patients.

X-irradiation of the contusion site improves locomotor and histological outcomes in spinal cord-injured rats.

We have determined whether X-irradiation of the injury site can oppose tissue loss and improve recovery of locomotor function following contusion injury of the spinal cord. Contusion injury was produced in rats at the level of T10 with a weight drop device. Localized X-irradiation (20 Gy) of the injury site was performed at 20 min and 1, 2, 4, 7, and 17 days postinjury. Locomotor recovery was then determined with the 21-point Basso, Beattie, and Bresnahan (BBB) scale. X-irradiation enhanced recovery of locomotor function during a subsequent 6-week observation period when administered 20 min and 1 or 2 days following contusion injury (final BBB score approximately 7-8). X-irradiation at 4-17 days postinjury did not significantly affect final locomotor scores compared with unirradiated rats (final BBB score approximately 2), in marked contrast to previous studies where X-irradiation applied only at 17-18 days benefitted transection injury. The extent of recovery was directly related to measurements of sparing of spinal cord tissue at the contusion center. Because the treatment time window occurred earlier in contusion than reported for transection injury, the results suggest that contusion injury rapidly initiates underlying radiation-sensitive processes that occur only following a delay of several weeks after transection injury. Further optimization of X-ray treatment may lead to a useful therapeutic modality for use in spinal cord contusion injury.

Reference values of amniotic fluid neuron-specific enolase.

OBJECTIVE: Enolase is a dimeric cytoplasmic enzyme whose double gamma isoenzyme, neuron-specific enolase, is predominantly found in neuronal and neuroendocrine tissues. Cell injury causes its release into the blood and cerebrospinal fluid (CSF). Neuron-specific enolase has been measured in the serum and CSF of adults and full-term asphyxiated neonates as a marker of neurological injury. We recently observed an elevation of neuron-specific enolase in the amniotic fluid of women whose neonates subsequently developed intraventricular hemorrhage or periventricular leukomalacia. The purpose of our study was to establish reference values of neuron-specific enolase in the amniotic fluid as a function of gestational age. METHODS: A total of 110 amniotic fluid samples, obtained primarily for genetic studies (16-20 weeks, n = 22), for evaluation of preterm labor (21-35 weeks, n = 66) and for fetal lung maturity studies (36-40 weeks, n = 22), were analyzed for neuron-specific enolase. Samples were from women who subsequently delivered term neonates with normal neurological examinations or who delivered preterm neonates with normal neurosonograms up to the 7th day of life. Descriptive statistics and non-parametric correlations were used for analysis. RESULTS: There was no correlation between gestational age and concentration of neuron-specific enolase (Spearman's r = 0.059, p = 0.63). The overall mean neuron-specific enolase value was 2.5 +/- 1.39 microg/l. The highest value obtained was 6 microgl. Of the 110 women, 105 (95.5%) had neuron-specific enolase values of less than 5 microg/l, while five (4.5%) had values ranging from 5 to 6 microg/l. CONCLUSIONS: The amniotic fluid level of neuron-specific enolase does not change as a function of gestational age. These stable levels may have utility in the evaluation of cases with fetal neurological injury.

Intravenous anesthesia with propofol for painful procedures in children with cancer.

OBJECTIVE: To study the safety and efficacy of propofol-based intravenous anesthesia in children with cancer undergoing painful procedures. METHODS: This study is a retrospective analysis of data collected from 52 consecutive children who underwent 335 procedures using propofol anesthesia. These data were routinely collected in all patients: time to induction, duration of the procedure, time to recover, and the doses of the drugs used. Monitoring with electrocardiography and pulse oximetry was continuous during the procedure; blood pressures were recorded before and after the procedure and every 5 to 10 minutes during the procedure. The patients received one of these four propofol-based intravenous regimens according to the anesthesiologist's preference: propofol only; propofol plus fentanyl; propofol plus midazolam; or propofol, fentanyl, and midazolam. The efficacy of sedation was rated by this scoring system: 3 = no movement during procedure; 2 = minimal movement that did not interfere with the procedure; 1 = moderate movement requiring physical restraint to complete the procedure. RESULTS: There were six episodes of mild hypoxia (oxygen saturation 85%-94%) and one episode of laryngospasm. None required intubation. Two patients had agitation and one patient had emesis during the postrecovery phase. There was no difference in the efficacy of sedation between the four regimens. Patients receiving the combination of propofol, fentanyl, and midazolam received the least amount of propofol and required the least time to recover. There were no life-threatening complications. CONCLUSIONS: Propofol-based anesthesia, when administered by an anesthesiologist in a controlled setting, is safe and effective for performing painful procedures in children with cancer.

Antenatal steroids and neonatal periventricular leukomalacia.

OBJECTIVE: To evaluate the effect of antenatal steroid treatment on the development of neonatal periventricular leukomalacia. METHODS: This retrospective cohort study included 1161 neonates with gestational ages of 24-34 weeks and birth weights of 500-1750 g, divided into two groups on the basis of antenatal steroid treatment. Neonatal neurosonograms were done on days 3 and 7 of life and labeled normal or abnormal. The abnormal outcomes evaluated were periventricular leukomalacia or intraventricular hemorrhage, periventricular leukomalacia with intraventricular hemorrhage, and isolated periventricular leukomalacia. The group treated with antenatal steroids was compared with the untreated group for these outcomes. RESULTS: Antenatal steroids were associated with significantly less periventricular leukomalacia or intraventricular hemorrhage (23% versus 31%, P =.005), periventricular leukomalacia with intraventricular hemorrhage (5% versus 11%, P =.001), and isolated periventricular leukomalacia (3% versus 7%, P =.009). Logistic regression analysis of antenatal steroid treatment, controlling for confounding maternal and neonatal characteristics, indicated that neonates treated with antenatal steroids had a 56% lower likelihood of periventricular leukomalacia with intraventricular hemorrhage (adjusted odds ratio [OR] 0.44, 95% confidence interval [CI] 0.25, 0.77) and a 58% lower likelihood of isolated periventricular leukomalacia (adjusted OR 0.42, 95% CI 0.20, 0.88). CONCLUSION: Antenatal steroid treatment was associated with over 50% reduction in the incidence of periventricular leukomalacia in preterm neonates. Increased use of antenatal steroid therapy might improve long-term neonatal neurologic outcomes.

Survey of the extent and nature of care for adults and older adults by allergy/immunology practitioners.

BACKGROUND: The proportion of older adults in the US population will increase dramatically in the near future, yet the frequency and nature of care furnished to older adults by Allergy/Immunology practitioners has not been described. OBJECTIVE: To determine the extent and nature of care being provided to adults and older adults by Allergy/Immunology practitioners. METHODS: ACAAI members and fellows were surveyed to obtain information regarding certification and training as well as their practice patterns. RESULTS: The distribution of diagnoses among patients aged 40 to 54 years were very similar to distributions found among adults age 55 to 69 years and > or = 70 years of age. Virtually all respondents indicated they provide inhalant allergen immunotherapy for patients age 40 to 54 years with asthma and/or allergic rhinitis; administration of inhalant allergen immunotherapy for asthma and allergic rhinitis was also frequently reported for adults > or = 55 years. The proportions of respondents providing venom immunotherapy for adults aged 40 to 54, 55 to 69, and > or = 70 years were 82%, 70%, and 39%, respectively. CONCLUSION: ACAAI members and fellows commonly provide care to older adults. Our survey findings highlight the need to develop strategies for successful management of Allergy/Immunology conditions specifically pertaining to older adults, including studies to determine the therapeutic utility of inhalant allergen and venom immunotherapy in this age group.

Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes.

OBJECTIVE: To determine the perinatal effects of histologic chorioamnionitis on preterm neonates and the effectiveness of antenatal steroids in the presence of histologic chorioamnionitis. METHODS: We studied neonates at our institution who weighed 1750 g or less at birth from January 1990 through December 1997. The population was stratified primarily by presence of histologic chorioamnionitis and secondarily by exposure to antenatal steroids. Subgroups were compared by various perinatal outcomes and confounding variables. Student t test, chi(2), Fisher exact test, and logistic regression were used for analysis. RESULTS: Among 1260 neonates entered, the placentas of 527 had evidence of histologic chorioamnionitis and 733 did not. Those with histologic chorioamnionitis had a lower mean gestational age, lower birth weight, and higher rate of major neonatal morbidities than those without it. After adjusting for confounding variables, histologic chorioamnionitis independently associated with lower gestational age, lower birth weight, and neonatal death. Among neonates exposed to antenatal steroids who had histologic chorioamnionitis, there was a significantly lower incidence of low Apgar scores (18% compared with 33.5%, P <.001), respiratory distress syndrome (RDS) (39.6% compared with 55.9%, P <.001), intraventricular hemorrhage and periventricular leukomalacia (21.9% compared with 36.9%, P <.001), major brain lesions (7.7% compared with 18.4%, P <.001), patent ductus arteriosus (14.8% compared with 23.7%, P =.018), and neonatal death (8.3% compared with 16.2%, P =.02), with no increase in rate of proven neonatal sepsis (18.3% compared with 14%, P =.24). CONCLUSION: Histologic chorioamnionitis increases major perinatal morbidity through its association with preterm birth and is independently associated with neonatal death. In the presence of histologic chorioamnionitis, antenatal steroids significantly decreased the incidence of RDS, intraventricular hemorrhage and periventricular leukomalacia, major brain lesions, and neonatal mortality, without increasing neonatal sepsis.

Open-ring imaging sign: highly specific for atypical brain demyelination.

OBJECTIVE: To test the specificity for demyelination of a new neuroimaging sign: contrast enhancement shaped as an open ring or a crescent circumscribed to the white matter. BACKGROUND: Brain demyelination can cause ring enhancement mimicking neoplasm or infection on CT or MRI. METHODS: A MEDLINE search of pathology-proved demyelination yielded 32 illustrated cases of ring-enhancing lesions published between 1981 and 1995. Controls consisted of the same number of published images of neoplasms and infections, pathology proved, and matched by year of publication, and age and gender of the patient. Two neuroradiologists read the images twice independently 1 year apart. RESULTS: Interrater agreement was good (kappa = 0.64 and 0.66 for either reading). Test-retest reliability was high (kappa = 0.75 and 0.74 for either rater). The open-ring sign clearly distinguished demyelinating lesions from neoplasms and infections. For demyelination versus neoplasm or infection, the specificity of the reading by the first neuroradiologist was 93.8 (95% CI, 86 to 98), and that of the second was 84.4 (95% CI, 74 to 92). The likelihood ratio of demyelination versus neoplasm averaged 5.2, and versus infection, 17.2. That is, if the lesions had the same incidence in the population, in the presence of an open-ring sign demyelination would be five times more likely than neoplasm and 17 times more likely than infection. However, given the much higher incidence of neoplasms and infections, these lesions are still frequently responsible for open-ring enhancement. CONCLUSIONS: The open-ring sign is often present in large, contrast-enhancing demyelinating lesions and helps to differentiate them from neoplasms and infections.

Reduced risk of low weight births among indigent women receiving care from nurse-midwives.

STUDY OBJECTIVE: To examine the effect of a comprehensive prenatal and delivery programme administered by nurse-midwives on the risk of low weight births among indigent women. STUDY DESIGN: Historical prospective study. Birth outcomes among the cohort were compared with all county births during the same period, adjusting for maternal age and race. Results are expressed as relative risks with 95% confidence intervals. SETTING: An enhanced Medicaid funded pre-natal programme administered by nurse-midwives from 1992 to 1994 in Westchester County, New York. PARTICIPANTS: Indigent mothers (n = 1443), between the ages of 15 and 44, who were residents of Westchester County and indicated having Medicaid or no health care coverage. RESULTS: There were 1474 live births among cohort mothers. Mean (SD) gestational age was 39.4 (1.9) weeks. Less than 6% of births occurred before 37 weeks gestation. The mean birth weight of cohort infants was 3365.6 (518.6) g. Only 4.1% of the cohort births were less than 2500 g. Compared with all county births, the cohort showed a 41% reduction in the risk of low weight births (RRlbw = 0.59, 95% CI: 0.46 to 0.73, p < .001) and a 56% reduction when compared with county Medicaid births only (RR = 0.44, 95% CI: 0.34 to 0.57, p < .005) adjusting for maternal age and race. Larger reductions were found for very low weight births. CONCLUSIONS: Mothers need not be considered at high risk for adverse pregnancy outcomes based on their socioeconomic status alone. Moreover, a comprehensive prenatal programme administered by nurse-midwives may promote a reduction in adverse pregnancy outcomes among indigent mothers.

Effectiveness of multidose antenatal steroids.

OBJECTIVE: To compare effectiveness between single and multiple courses of antenatal steroids in preterm births and determine adverse effects attributable to multiple courses. METHODS: We studied retrospectively the neonatal outcomes of infants who weighed 1750 g or less at birth between January 1990 and December 1997. Infants exposed to a single course were compared with those exposed to two or more courses of antenatal steroids, with respect to various perinatal outcome variables. RESULTS: Ninety-three neonates were exposed to two or more courses of antenatal steroids and 261 neonates had been given single courses. The mean (+/- standard deviation) gestational age (29.6 +/- 2.8 weeks compared with 28.7 +/- 2.7 weeks; P = .007) and birth weight (1252 +/- 321 g compared with 1159 +/- 339 g; P = .013) were significantly higher among neonates exposed to multiple courses. There were no significant differences between groups in perinatal outcomes; however, those exposed to multiple courses had a significantly lower rate of respiratory distress syndrome (RDS) (17 [18%] compared with 107 [41%]; P < or = .001) and surfactant use (40 [43%] compared with 149 [57%]; P = .02). Adjusting for confounding variables, multiple courses of steroids were significantly associated with a 65% reduction in the incidence of RDS (odds ratio 0.35; 95% confidence interval = 0.18, 0.70; P = .003). CONCLUSION: Compared with single courses, multiple courses of antenatal steroids reduced significantly the incidence of RDS with no apparent increase in neonatal sepsis or disturbances in fetal growth.

Corticosteroid prophylaxis for neurologic complications of intravenous immunoglobulin G therapy in childhood immune thrombocytopenic purpura.

To assess in a retrospective analysis if there is evidence suggesting corticosteroids can prevent the neurologic complications of intravenous immunoglobulin (IVIG) therapy in children with immune thrombocytopenic purpura (ITP). From March 1985 to September 1997, 112 children received IVIG (1 g/kg/day for one or two dosages) for the treatment of ITP. During the years 1990 to 1997, 23 children nonrandomly received a short course of prednisone (2 mg/kg/day during and for 3 days after the completion of IVIG therapy) as a prophylaxis against the neurologic complications of IVIG therapy. The authors analyzed the data of all 112 children and compared the incidence of neurologic complications in those who received prednisone prophylaxis with those who did not. The severity of the complications was assessed as follows: grade 1, headache only; grade 2, headache plus vomiting; grade 3, headache, vomiting, and fever; grade 4, headache, vomiting, fever, and meningeal signs (aseptic meningitis). Of the 23 children who received prednisone prophylaxis, 2 (8.7%) experienced headache and vomiting after the completion of prednisone prophylaxis. Of the 89 children without prednisone prophylaxis, 27 (30.3%) experienced neurologic symptoms of varying severity, including one patient with aseptic meningitis proven by examination of the spinal fluid. Twelve of these patients needed additional hospital care for the complications. Children receiving prednisone had a 78% lower risk of neurologic complications (OR = 0.22; CI = 0.05-0.90; P = 0.036). This retrospective study shows a short course of prednisone therapy, given during and until 3 days after the completion of IVIG infusion, is likely to decrease the incidence and severity of neurologic complications of IVIG in children with ITP.

Aniseikonia in relation to strabismus, anisometropia and amblyopia.

PURPOSE: To study the interrelationships among these four entities which are critical to binocular vision and its precision. SUBJECTS AND METHODS: 102 selected patients (for their ability to have stereoscopic depth perception, a requisite for space eikonometry) were evaluated. Patient testing included stereoscopic testing, Essilor Projection Space Eikonometry, ultrasonic echographic axial length measurements and orthoptic evaluation. Aniseikonia was measured on the Essilor Projection Space Eikonometer. RESULTS: 1. Anisometropia alone was correlated with a marked increase in amblyopia, a moderate increase in aniseikonia and no noteworthy increase in strabismus. Statistical analysis (chi square ratio) showed that persons with elevated anisometropic values had a 4.4 fold increased risk of aniseikonia (p=.003). 2. Aniseikonia alone was not responsible for marked variations in strabismus. 3. Amblyopia was correlated with increases in anisometropia and aniseikonia. 4. Adding aniseikonia to anisometropia produced a possible increase in strabismus and a great increase in amblyopia (using Fisher's Exact Test, 2-tailed). 5. Spearman correlations of the "absolute values" (the mean of the mathematical difference between the two eyes of anisometropia and amblyopia) were as follows: anisometropia (abs) vs. aniseikonia r=.294, p=.006; anisometropia (abs) vs. amblyopia (abs) 4=.555, p=<.001; amblyopia (abs) vs. aniseikonia r=.234, p=.02. CONCLUSIONS: Aniseikonia per se does not appear to have a major causal role in amblyopia or strabismus, but anisometropia does for amblyopia. This role is greatly augmented by aniseikonia and this combination may then produce strabismus.