Shasha Bai

An Immunoassay to Rapidly Measure Acetaminophen Protein Adducts Accurately Identifies Patients With Acute Liver Injury or Failure

BACKGROUND & AIMS A rapid and reliable point‐of‐care assay to detect acetaminophen protein adducts in the serum of patients with acute liver injury could improve diagnosis and management. AcetaSTAT is a competitive immunoassay used to measure acetaminophen protein adducts formed by toxic metabolites in serum samples from patients. We compared the accuracy of AcetaSTAT vs high‐pressure liquid chromatography with electrochemical detection (HPLC‐EC; a sensitive and specific quantitative analytic assay) to detect acetaminophen protein adducts. METHODS We collected serum samples from 19 healthy individuals (no liver injury, no recent acetaminophen use), 29 patients without acetaminophen‐associated acute liver injury, and 33 patients with acetaminophen‐associated acute liver injury participating in the Acute Liver Failure Study Group registry. Each serum sample was analyzed by AcetaSTAT (reported as test band amplitude) and HPLC‐EC (the reference standard). We also collected data on patient age, sex, weight, level of alanine aminotransferase on test day and peak values, concentration of acetaminophen, diagnoses (by site investigator and causality review committee), and outcome after 21 days. Differences between groups were analyzed using the Fisher exact test for categoric variables and the Kruskal–Wallis test or rank‐sum test for continuous variables. RESULTS AcetaSTAT discriminated between patients with and without acetaminophen‐associated acute liver injury; the median AcetaSTAT test band amplitude for patients with acetaminophen‐associated acute liver injury was 584 (range, 222–1027) vs 3678 (range, 394–8289) for those without (P < .001). AcetaSTAT identified patients with acetaminophen‐associated acute liver injury with 100% sensitivity, 86.2% specificity, a positive predictive value of 89.2%, and a negative predictive value of 100%. Results from AcetaSTAT were positive in 4 subjects who received a causality review committee diagnosis of non–acetaminophen‐associated acute liver injury; HPLC‐EC and biochemical profiles were consistent with acetaminophen‐associated acute liver injury in 3 of these cases. CONCLUSIONS The competitive immunoassay AcetaSTAT shows a high degree of concordance with HPLC‐EC results in identifying patients with acetaminophen‐associated acute liver injury. This rapid and simple assay could increase early detection of this disorder and aid clinical management.

Erythropoietin and Brain Magnetic Resonance Imaging Findings in Hypoxic-Ischemic Encephalopathy: Volume of Acute Brain Injury and 1-Year Neurodevelopmental Outcome

&NA; In the Neonatal Erythropoietin and Therapeutic Hypothermia Outcomes study, 9/20 erythropoietin‐treated vs 12/24 placebo‐treated infants with hypoxic‐ischemic encephalopathy had acute brain injury. Among infants with acute brain injury, the injury volume was lower in the erythropoietin than the placebo group (P = .004). Higher injury volume correlated with lower 12‐month neurodevelopmental scores. Trial registration ClinicalTrials.gov: NCT01913340.

Newborn Plasma Glucose Concentration Nadirs by Gestational-Age Group.

Background: The glucose concentrations and times to nadir for newborns of all gestational ages when intrapartum glucose-containing solutions are not routinely provided are unknown. Objective: To characterize and compare patterns of initial glucose concentration nadirs by gestational-age groups. Methods: A cross-sectional cohort study of 1,366 newborns born in 1998 at the University of Arkansas for Medical Sciences, appropriate for gestational age, nonasphyxiated, nonpolycythemic, and not infants of diabetic mothers, were included. Initial plasma glucose concentrations, before intravenous fluids or feedings, were plotted against time after birth for 4 gestational-age groups (full term [FT], ≥37–42 weeks; late preterm [LPT], ≥34 and < 37 weeks; preterm [PT], ≥28 and < 34 weeks; and extremely low gestational age newborns [ELGAN], 23 and < 28 weeks of gestation). Results: ELGAN had the earliest nadir at 61 ± 4 min, followed by PT newborns (71 ± 2 min), and then LPT and FT newborns at 92–93 min. The time to nadir for ELGAN and PT newborns was significantly earlier than for FT newborns. Glucose nadir concentrations for ELGAN, PT, and LPT newborns were significantly lower than for FT newborns. LPT newborns’ pattern of glucose paralleled those of FT newborns, with values approximately 5–6 mg/dL lower during the first 3 h. Conclusion: Plasma glucose nadirs occurred at different times among gestational-age groups during the early postnatal period as follows: ELGAN < PT < LPT ≈ FT. In order to potentially prevent low glucose concentrations at the time of the nadir, exogenous glucose should be provided to all newborns as soon as possible after birth.

The Effect of Early Feeding on Initial Glucose Concentrations in Term Newborns

Objective To evaluate the influence of early feeding on initial glucose concentrations in healthy term newborns who were not at risk for hypoglycemia. Study design This retrospective observational study was conducted at the University of Arkansas for Medical Sciences where universal early glucose screening was standard of care for newborn infants. Plasma glucose concentrations were compared in term infants born in 2008 who were not at risk for neonatal hypoglycemia and who were fed before (early feeders) and after (late feeders) their initial glucose screens. Multiple linear regression models were built to determine whether glucose concentrations differed significantly between early vs late feeders. Results In the 315 early and 572 late feeders, the mean (SD) age of first feeding was 0.9 (0.6) and 3.8 (2.0) hours, respectively. The age at initial glucose specimen collection was 2.2 (1.1) and 1.8 (0.8) hours, respectively. The initial glucose concentration was not higher in early vs late feeders (51.8 ± 11.9 vs 55.5 ± 13.3 mg/dL; P < .001). In linear regression analyses of all infants, the mean initial glucose concentration was 3.61 (95% CI 1.75‐5.48) mg/dL lower in early vs late feeders. Conclusions Early feeding in otherwise healthy term newborns did not increase initial glucose concentrations compared with newborns who fed later (ie, fasted). Before direct evidence is available, these observations may be instructive for managing early asymptomatic hypoglycemia in at‐risk newborns.

Video intervention changes parent perception of all-terrain vehicle (ATV) safety for children

Background Children aged <16 years account for 25% of deaths on all-terrain vehicles (ATVs), despite public health and industry warning against paediatric use. Parents often underestimate instability and other risks associated with ATVs. Objective To determine if a brief intervention consisting of validated computer simulations of ATV performance with a child driver changes attitudes, beliefs and planned safety behaviours of parents of children who ride ATVs. Design/methods Participants were parents of children presenting to a childrens hospital emergency department. All participants had children who had ridden an ATV in the past year. Subjects viewed a video simulation of ATVs in scenarios featuring 6-year-old and 10-year-old biofidelic anthropomorphic test devices. Parents completed a survey both before and after viewing the video to report attitudes/beliefs on ATV safety for children, use of safety equipment and family ATV use, as well as risk and safety perception. Results Surveys were collected from 99 parents, mostly mothers (79%), Caucasian (61%) and had high school education or less (64%). The intervention shifted parents’ belief in overall ATV safety (48% unsafe pre-intervention, 73% unsafe post-intervention, p<0.001). After viewing the video simulation, parents were almost six times more likely to perceive ATVs as unsafe (OR 5.96, 95% CI 2.32 to 15.31, p<0.001) and many parents (71%) planned to change family ATV safety rules. Conclusion Video simulations of ATV performance with child riders changed short-term risk perception and planned safety behaviours of parents whose children ride ATVs. Similar educational interventions hold promise for larger-scale studies in at-risk populations.

Reply to the Letter to the Editor “The Postnatal Glucose Concentration Nadir Is Not Abnormal and Does Not Need to Be Treated”

Dear Editor, We appreciate and agree with the comments by Hay et al. [1] regarding our paper, “Newborn Plasma Glucose Concentration Nadirs by Gestational-Age Group” [2]. In this study, we showed for the first time that glucose concentration nadirs for extremely low gestational age newborns (ELGANs) as well as for preterm and late preterm newborns were lower than those for full term newborns and that the time to nadir for ELGAN and preterm newborns was significantly earlier than for full term newborns. The last sentence of the abstract was not supported by our study results, and we understand the concerns raised by Hay et al. [1] in the interpretation of the sentence: “In order to potentially prevent low glucose concentrations at the time of the nadir, exogenous glucose should be provided to all newborns as soon as possible after birth.” We would like to formally retract this sentence. Although not mentioned by Hay et al. [1], we would also like to amend the last sentence of the manuscript from “At the present time, we suggest providing exogenous glucose as soon as possible after birth and using the screening guidelines for timing and whom to screen based on AAP guidelines [29]” to the following: “At the present time, we suggest providing exogenous glucose to ELGAN and very preterm newborns as soon as possible after birth. For late preterm and term newborns, recommendations for timing and whom to screen should be based on AAP guidelines [29].”

The impact of prematurity and maternal socioeconomic status and education level on achievement-test scores up to 8th grade

Background The relative influence of prematurity vs. maternal social factors (socioeconomic status and education level) on academic performance has rarely been examined. Objective To examine the impact of prematurity and maternal social factors on academic performance from 3rd through 8th grade. Methods We conducted a retrospective cohort study of infants born in 1998 at the University of Arkansas for Medical Sciences. The study sample included 58 extremely low gestational age newborns (ELGANs, 23‒<28 weeks), 171 preterm (≥28‒<34 weeks), 228 late preterm (≥34‒<37 weeks), and 967 term ((≥37‒<42 weeks) infants. Neonatal and maternal variables were collected including maternal insurance status (proxy measure for socioeconomic status) and education level. The primary outcomes were literacy and mathematics achievement-test scores from 3rd through 8th grade. Linear mixed models were used to identify significant predictors of academic performance. All two-way interactions between grade level, gestational-age (GA) groups, and social factors were tested for statistical significance. Results Prematurity, social factors, gender, race, gravidity, and Apgar score at one minute were critical determinants of academic performance. Favorable social factors were associated with a significant increase in both literacy and mathematic scores, while prematurity was associated with a significant decrease in mathematic scores. Examination of GA categories and social factors interaction suggested that the impact of social factors on test scores was similar for all GA groups. Furthermore, the impact of social factors varied from grade to grade for literacy, while the influence of either GA groups or social factors was constant across grades for mathematics. For example, an ELGAN with favorable social factors had a predicted literacy score 104.1 (P <.001), 98.2 (P <.001), and 76.4 (P <.01) points higher than an otherwise similar disadvantaged term infant at grades 3, 5, and 8, respectively. The difference in their predicted mathematic scores was 33.4 points for all grades (P <.05). Conclusion While there were significant deficits in academic performance for ELGANs compared to PT, LPT, and term infants, the deficit could be offset by higher SES and better-educated mothers. These favorable social factors were critical to a child’s academic achievement. The role of socioeconomic factors should be incorporated in discussions on outcome with families of preterm infants.

PW 2388 Factors associated with safe sleep knowledge and intent among pregnant teens

Background Interventions to prevent sudden unexpected infant death (SUID) typically include education to increase knowledge, thereby improving parenting practice. However, health decision-making is based on a complex interplay of knowledge, attitudes, and beliefs related to intent to initiate behaviors. Further, based on the Health Belief Model, self-efficacy and locus of control are also linked to behavior change. Objective: This study examined the link between pregnant teens’ report on several safe sleep constructs thought to influence parent’s safe sleep behaviors and prenatal knowledge of safe sleep practices. Design/methods We recruited pregnant teens (13–19 years old) into a trial of an educational intervention for safe sleep during second trimester in a US state with high sleep-related SUID rates. A self-administered survey was completed before intervention. The survey included safe sleep constructs: attitudes (3 items), beliefs (4), self-efficacy (3), intentions (4), knowledge (3), and a standardized measure of knowledge of infant development (KIDI). Results 115 subjects completed baseline surveys, including 27 white (20%), 103 black (76%), and 5 other (4%) teens with median age 18 y±2. In regression analyses, the KIDI predicted safe sleep knowledge (R2=0.05, F(1, 112)=6.24, p<0.014). Controlling for KIDI, we regressed safe sleep factors on safe sleep knowledge (R2=0.26, F(1, 108)=7.41, p<0.000). Safe sleep knowledge was significantly correlated (p<0.01) with attitudes (r=0.28), intent to act (r=0.30), and safe sleep self-efficacy (r=0.37). Conclusions The prenatal period presents an important opportunity for educational intervention, as women develop knowledge and form beliefs that may shape early parenting behavior. The link between key safe sleep-related constructs may inform interventions before the birth. Our results suggest that safe sleep knowledge is associated with both key beliefs and with knowledge of general infant development. Interventions that target these beliefs may be more successful.

Searching for the Best Oral Treatment for Hypoglycemic Newborns

curred. A reliable NBS test offers a diagnosis that allows therapy to be instituted before the occurrence of irrevocable pathology. Prediction of prognosis and age of onset from enzyme or molecular data is difficult in many cases, necessitating ongoing monitoring by specialists. In 219 793 infants screened in Illinois for LSDs since November 2014, Burton et al identified 28 affected individuals with one of the LSDs. Molecular confirmation was complicated in some cases by variants of unknown significance in the affected gene. The authors conclude that the benefits of early diagnosis led to early treatment options in 3 of 28 cases: 1 patient with severe MPS I who had hematopoietic stem cell transplantation/ERT and 2 patients with infantile-onset Pompe disease who received ERT. The other 25 cases were asymptomatic and continue to be followed for early signs of disease before initiating therapy. A large number of pseudodeficiency cases were identified for Pompe (15), MPS I (30), and Fabry (16) disease. The Fabry cases were all carriers of p.A143T variant, for which clinical significance currently is unclear. The authors thoughtfully discuss the benefits of this NBS protocol and the potential for psychological damage. In addition, in cases of unknown penetrance and prognosis, the appropriateness of testing other at-risk family members is called into question. The difficulty and cost (financially and otherwise) of following asymptomatic patients over many years is difficult for all concerned. NBS relies on the logic that metabolic or molecular aberrations relative to normal can diagnose accurately affected individuals before symptoms appear. This logic does not apply equally to all diseases, as both NBS studies makes clear. Patients appear to fall along a spectrum of affectedness that cannot clearly be understood solely by enzyme levels and DNAbased studies. Advances that better allow prediction of likely symptomatic cases will enhance the NBS for these complex diseases and others. Until then, voices continue to call out for additional disease screening in the unaffected newborn. Advocates of whole-exome/genome screening in newborns, testing that is not far into the future, have much to learn from current NBS protocols. ■