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Pediatric Research 10/2011; 70(4):424-5. · 2.70 Impact Factor
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ABSTRACT: The population pharmacokinetic (PK) profile of oral clonidine was characterized in newborns with neonatal abstinence syndrome, and significant covariates affecting its PK parameters were identified. Plasma clonidine concentration data were obtained from a clinical trial in which 36 newborns, aged 1 to 25 days (postnatal age, PNA) and weighing 2.1 to 3.9 kg, were enrolled to take multiple oral doses of clonidine. The population PK model of clonidine was developed by NONMEM, and significant covariates were identified, followed by nonparametric bootstraps (2000 replicates) and simulation experiments. A 1-compartment open linear PK model was chosen to describe plasma concentrations of clonidine, and body weight and PNA were significant covariates for apparent clearance (CL/F) as follows: CL/F (L/h) = 15.2 × [body weight (kg)/70](0.75) × [PNA (day)(0.441)/(4.06(0.441) + PNA (day)(0.441))]. Furthermore, CL/F of clonidine increased rapidly with PNA during the first month of life after body weight was adjusted. Any optimal dosage regimen for clonidine in term neonates should be based on infant's age and body weight, and 1.5 µg/kg every 4 hours is proposed starting the second week of life based on the simulation results.
The Journal of Clinical Pharmacology 04/2011; 51(4):502-11. · 2.91 Impact Factor
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ABSTRACT: The study objective was to determine whether Ureaplasma respiratory tract colonization of preterm infants <33 wk gestation is associated with an increased risk for necrotizing enterocolitis (NEC). One or more tracheal or nasopharyngeal aspirates for Ureaplasma culture and PCR were obtained during the first week of life from 368 infants <33 wk gestation enrolled from 1999 to 2003 or from 2007 to 2009. NEC Bell stage ≥ 2 was confirmed by radiological criteria, and pathology, if available. Cord serum samples were analyzed for IL-6 and IL-1β concentrations, and placentas were reviewed for histological chorioamnionitis in the first cohort. NEC was confirmed in 29 of 368 (7.9%) of the combined cohorts. The incidence of NEC was 2.2-fold higher in Ureaplasma-positive (12.3%) than Ureaplasma-negative (5.5%) infants <33 wk (OR, 2.43; 95% CI, 1.13-5.2; p = 0.023) and 3.3-fold higher in Ureaplasma-positive (14.6%) than Ureaplasma-negative (4.4%) infants ≤ 28 wk (OR, 3.67; 95% CI, 1.36-9.93; p = 0.01). Age of onset, hematologic parameters at onset, and NEC severity were similar between Ureaplasma-positive and negative infants. Cord serum IL-6 and IL-1β concentrations were significantly higher in Ureaplasma-positive than in Ureaplasma-negative NEC-affected infants. Ureaplasma may be a factor in NEC pathogenesis in preterm infants by contributing to intestinal mucosal injury and/or altering systemic or local immune responses.
Pediatric Research 01/2011; 69(5 Pt 1):442-7. · 2.70 Impact Factor
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ABSTRACT: To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome.
Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of > or =9) were enrolled at 2 hospitals during 2002-2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 microg/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation.
The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8-15 days]) than in the placebo group (15 days [95% confidence interval: 12-17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age.
In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.
PEDIATRICS 05/2009; 123(5):e849-56. · 4.47 Impact Factor
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ABSTRACT: Retinopathy of prematurity (ROP) remains a leading cause of morbidity in the very low-birth-weight (VLBW) infant. This study investigates a possible association between serum/blood glucose and the development of ROP.
A retrospective case-control study of all infants born between 1992 and 1997 at the Johns Hopkins Hospital with birth weights less than 1000 g who developed Stage 3 or 4 ROP was conducted. Controls either had Stage 1 ROP or no eye disease and were matched 2:1 with ROP patients for gestational age, birth weight and year of birth. Odds ratios (ORs) of ROP were calculated for multiple exposures over the first month after birth, including oxygen concentration (FiO(2)), blood glucose levels, vitamin E, mean airway pressure and mean blood pressure.
In a simple logistic regression analysis, we found an increased ROP risk for: (1) each 10 mg/dl increase of mean glucose (OR 1.96; 95% CI 1.13 to 3.42), (2) each 1% increase of mean FiO(2) (OR 1.06; 95% CI 1.004 to 1.13), (3) history of dopamine infusion (OR 5.4; 95% CI 1.16 to 25.2) and (4) intraventricular hemorrhage Grade 3 or 4 (OR 7.3; 95% CI 1.53 to 34.7). Using a multiple regression model, we found an increased ROP risk for each 10 mg/dl increase of mean glucose (OR 2.7; 95% CI 1.003 to 7.27). Each IU/kg/day of vitamin E supplementation reduced ROP risk (OR 0.37; 95% CI 0.16-0.86).
In this study, we could demonstrate that glucose levels in the first month of life are associated with the development of ROP. Further studies have to determine if this association is causal or if hyperglycemia is just an expression of severity of illness.
Journal of Perinatology 23(3):186-94. · 1.80 Impact Factor
