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OBJECTIVE: To assess for possible missed hypothyroidism in infants of very low birth weight (VLBW) whose initial newborn screening (NBS) was within normal reference range. STUDY DESIGN: We analyzed serum thyroid-stimulating hormone (TSH) obtained at 36 weeks of corrected gestational age or at hospital discharge if earlier (retest TSH) in infants with VLBW in the neonatal intensive care unit to determine the prevalence and factors associated with retest TSH ≥5 mU/L, a concentration requiring close follow-up for hypothyroidism. Utility of alternative cut-offs for NBS TSH also was assessed. RESULTS: A total of 398 infants, median gestational age 29 (range 22-36) weeks, birth weight 1138 (470-1498) g, were included in this study. Retest TSH was obtained at 49.5 (12-137) days after birth. Median retest TSH was 3.1 (0.5-27.9) mU/L. Seventy-three (18.3%) of the cohort had retest TSH ≥5 mU/L. Adjusting NBS cut-off to ≥15 or ≥10 mU/L identified <50% of infants with TSH ≥5 mU/L, resulting in 6% false positives and >70% false negatives. Multiple regression modeling indicated that 35% of variance in retest TSH value was explained by NBS TSH concentration, birth weight, and gestational age, all P < .01. CONCLUSIONS: Retesting for hypothyroidism at 36 weeks of corrected gestational age in infants with VLBL and normal NBS could identify infants who require ongoing surveillance until thyroid function has been definitively ascertained. Adjusting NBS TSH cutoffs is not a valid option for identifying potential hypothyroidism in infants with VLBW because of lack of sensitivity and unacceptable false-positive and false-negative rates.

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OBJECTIVES: To compare the duration of opioid treatment and length of stay among infants treated for neonatal abstinence syndrome (NAS) by using a pilot buprenorphine vs conventional methadone treatment protocol. STUDY DESIGN: This retrospective cohort analysis evaluated infants who received pharmacotherapy for NAS at 6 hospitals in Southwest Ohio from January 2012 through August 2014. A single neonatology provider group used a standardized methadone protocol across all 6 hospitals. However, at one of the sites, infants were managed with a buprenorphine protocol unless they had experienced chronic in utero exposure to methadone. Linear mixed models were used to calculate adjusted mean duration of opioid treatment and length of inpatient hospitalization with 95% CIs in infants treated with oral methadone compared with sublingual buprenorphine. The use of adjunct therapy was examined as a secondary outcome. RESULTS: A total of 201 infants with NAS were treated with either buprenorphine (n = 38) or methadone (n = 163) after intrauterine exposure to short-acting opioids or buprenorphine. Buprenorphine therapy was associated with a shorter course of opioid treatment of 9.4 (CI 7.1-11.7) vs 14.0 (12.6-15.4) days (P < .001) and decreased hospital stay of 16.3 (13.7-18.9) vs 20.7 (19.1-22.2) days (P < .001) compared with methadone therapy. No difference was detected in the use of adjunct therapy (23.7% vs 25.8%, P = .79) between treatment groups. CONCLUSION: The choice of pharmacotherapeutic agent is an important determinant of hospital outcomes in infants with NAS. Sublingual buprenorphine may be superior to methadone for management of NAS in infants with select intrauterine opioid exposures.

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OBJECTIVE: To characterize the population pharmacokinetics of oral methadone in neonates requiring pharmacologic treatment of neonatal abstinence syndrome and to develop a pharmacokinetic (PK) model toward an evidence-based treatment protocol. STUDY DESIGN: Based on a methadone dosing protocol, serum concentrations of methadone and its metabolites were assessed by high performance liquid chromatography-tandem mass spectrometry from dried blood spots. Population PK analysis was performed to determine the volume of distribution and clearance of oral methadone. Methadone plasma concentration-time profiles were simulated from the deduced PK model to optimize the dosing regimen. RESULTS: There was substantial interindividual variability in methadone concentrations. Blood concentrations of methadone were best described by a 1-compartment model with first-order absorption. The population mean estimates (coefficient of variation percentage) for oral clearance and volume of distribution were 8.94 (103%) L/h/70 kg and 177 (133%) L/70 kg, respectively. Optimized dosing strategies were developed based on the simulated PK profiles. We suggest a starting dose of 0.1 mg/kg per dose every 6 hours for most patients requiring pharmacologic treatment of neonatal abstinence syndrome followed by an expedited weaning phase. CONCLUSIONS: The proposed dosing regimen may reduce the cumulative dose of opioid and shorten the length of hospitalization. Future studies should aim to validate the simulated dosing schemes with clinical data and expand our understanding of the between-patient PK variability. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01754324.

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OBJECTIVE: To assess the utility of hepcidin, a potent regulator of host defense and inflammation, in the diagnosis of late-onset sepsis in very low birth weight infants. STUDY DESIGN: We compared the diagnostic performance of hepcidin with C-reactive protein from the serum concentrations in acute and convalescent blood specimens obtained from 44 infants suspected of late-onset sepsis. The predictive accuracies were assessed from the areas under receiver operating characteristic curves and the cutoffs that differentiated infants with and without sepsis were identified using classification and regression tree analysis. RESULTS: Seventeen of the enrolled infants in this study were bacteremic and/or received antibiotics for neonatal sepsis for ≥ 5 days (infants with sepsis). The concentrations of hepcidin were increased 4-fold in infants with compared with infants without sepsis (P < .0001) and returned to similar levels following therapy. The areas under receiver operating characteristic curves of hepcidin was 0.93 compared with 0.83 for C-reactive protein, P = .06. Hepcidin concentration >92.2 ng/mL correctly classified 91% of all infants (positive predictive value: 100%, negative predictive value: 87%, specificity: 100%, and sensitivity: 76%). CONCLUSION: Serum hepcidin concentration may be a useful adjunct test, in addition to blood culture and other markers of infection, in the evaluation of late-onset sepsis in very low birth weight infants.

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OBJECTIVES: To compare the spectrum, concentration, and activity of host defense proteins (HDPs) on the skin surface of newborns and adults, to assess variation in HDP concentrations in different anatomic regions in newborns, and to examine alteration in HDP concentrations with care practices. STUDY DESIGN: Proteins recovered from tape discs applied to stratum corneum of 25 term newborns (forehead and posterior trunk) and 20 adults (forehead) were analyzed by Western analysis for 5 HDPs and for muramidase activity. Protein concentrations were compared in samples obtained after delivery, after the first bath, and at 24 hours of age. RESULTS: Total protein was 2.8-fold higher in adults compared with newborns. Lysozyme and lactoferrin were detected in all samples. In contrast to total protein, lysozyme concentrations and muramidase activity were 5-fold higher in newborns relative to adults and were not altered after bathing. Lysozyme concentrations were significantly higher over the trunk compared with the forehead in newborns. CONCLUSIONS: The newborn skin surface is replete with prototypical HDPs, lysozyme, and lactoferrin. Bathing does not significantly diminish concentrations. These factors are likely to contribute importantly to the newborn infants' defense against invasive bacterial infections.

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