Population pharmacokinetics of levetiracetam in neonates with seizures.

WHAT IS KNOWN AND OBJECTIVE: This study developed a population pharmacokinetic (PK) model of levetiracetam (LEV) for treating neonatal seizures (NS) and determined the influence of clinically relevant covariates to explain the interindividual variability and residual error. METHODS: Twenty newborns admitted to the Neonatal Intensive Care Unit at the Hospital Central "Dr. Ignacio Morones Prieto" were included. LEV doses were administered by intermittent infusion. Blood samples were drawn 3 times post-infusion. Levetiracetam was quantified by a chromatographic technique. NONMEM software was used to determine the population PK model of LEV in neonates and the influence of clinical covariates on drug disposition. RESULTS AND DISCUSSION: The LEV PK in neonates is described by a one-compartment open model with first-order elimination. The influence of creatinine clearance (CRCL) and body weight (BW) on clearance (CL[L/h] = 0.47*CRCL), as well as the volume of the distribution (Vd[L] = 0.65*BW) of LEV, were confirmed, considering interindividual variabilities of 36% and 22%, respectively, and a residual error of 13%. WHAT IS NEW AND CONCLUSION: Based on the PK of LEV in neonates and the influence of the final PK model, a priori dosing guidelines are proposed considering CRCL, BW and LEV plasma concentrations between 6 and 20 mg/L for NS treatment.

Differential expression profiles of circulating microRNAs in newborns associated to maternal pregestational overweight and obesity.

BACKGROUND: The perinatal environment has a role in the establishment of altered metabolic and inflammatory responses, and could be modulated by microRNAs regulating immune and metabolic processes. OBJECTIVE: To analyze the expression profile of four circulating microRNAs and cytokine serum concentrations in neonates born to overweight and obese women. METHODS: Pregnant women were included and grouped by pregestational body mass index (21 with normal weight, 10 overweight and 10 obese women). A peripheral blood sample was obtained from newborn infants and used to determine circulating miRNAs expression and cytokine serum concentrations. RESULTS: There were significant differences in the expression of three microRNAs between newborns of pregestational obese women and newborns from pregestational normal weight women: miR-155 (p = 0.03), miR-181a (p = 0.02) and miR-221 (p = 0.04). A significant reduction in IL-1ß (p = 0.005) expression was also found in newborns of overweight women; although this cytokine was also diminished in newborns of obese women, this was not statistically significant. An association between IL-1ß concentrations and miR-146a and miR-221 expression was also observed. CONCLUSIONS: Expression of miR-155, miR-181a and miR-221 differs in infants born to obese women compared with infants born to normal weight women. Changes in microRNA expression could participate in the epigenetic foetal programming of metabolic disorders in children born to obese women.

Population pharmacokinetics of cefepime in neonates with severe nosocomial infections.

OBJECTIVE: To define the pharmacokinetic behaviour of cefepime in neonates with severe nosocomial infections using a mixed effects model. PATIENTS AND METHODS: Thirty-one newborn infants were included in the study; 10 additional infants participated in the validation of the pharmacokinetic model. Cefepime CL and V were determined using an open monocompartmental model with first-order elimination. The influence of demographic and clinical characteristics on the model was evaluated. The non-linear mixed effect model (nonmem) program was used to determine the pharmacokinetic population model. RESULTS: The mean corrected gestational age for infants participating in the construction and validation of the model were 35 and 33 weeks, respectively. Factors included in the final pharmacokinetic model were body surface area (BSA) and calculated CL(CR). The final population model was CL (L/h) = 0.457 BSA (m(2)) + 0.243 CL(CR) (L/h) and V(L) = 4.12 BSA (m(2)). This model explains 33.3% of the interindividual variability for CL and 12.8% for V. This model was validated in ten neonates with nosocomial infections by assessing the predictive capacity of plasma cefepime concentrations using a priori and Bayesian strategies. CONCLUSIONS: The predictive performance of this population model for cefepime plasma concentrations was adequate for clinical purposes and can be used for individualizing cefepime therapy in newborn infants with severe infections. Cefepime plasma concentrations can be predicted based on BSA and calculated CL(CR). Cefepime therapy using a 250 mg/m(2) dose administered every 12 h is adequate to achieve plasma concentrations greater than 8 mug/mL during more than 60% of the dosing interval and is expected to be effective in the treatment of bloodstream infections caused by most gram negative organisms in newborn infants. A dose of 550 mg/m(2) would be required for the treatment of infections caused by Pseudomonas sp.

[Efficacy of early erythropoietin use in critically ill, very-low-birthweight premature newborn infants: controlled clinical trial]. / Eficacia del uso precoz de eritropoyetina en recién nacidos pretérmino de muy bajo peso, críticamente enfermos: ensayo clínico controlado.

OBJECTIVE: To determine the efficacy of erythropoietin in very low birth weight (VLBW) newborns less than 72 h of age. PATIENTS AND METHODS: We randomly assigned 40 critically ill newborn VLBW infants to receive either recombinant human erythropoietin (EPO) 150 units/kg per day (21 patients) or placebo (19 patients) during their first six weeks of life. The observers were unaware of the treatment assignments. Frequency of erythrocyte transfusion, adverse effects and haematologic measures were evaluated and compared. RESULTS: Before treatment gestational age, weight, haemoglobin, and pathology were similar in both groups. During the subsequent 6 weeks, haemoglobin and haematocrit of the placebo group fell significantly below those of the EPO recipients. More transfusions were received by the placebo recipients (7/21) than by the EPO recipients (2/21; p = 0.04). No adverse effects of EPO were observed. CONCLUSIONS: We recommend the administration of recombinant human erythropoietin since the first 72 h of age, because of the high frequency of anaemia, the efficacy of EPO and lack of side effects.

[Cardiac tamponade in newborn infants with central venous catheter receiving parenteral nutrition]. / Taponamiento cardiaco en neonatos con catéter venoso central y alimentación parenteral.

OBJECTIVE: To alert about an unusual and poorly informed entity, with high mortality. That should be considered in critically ill neonates with central venous catheter and parenteral nutrition, in order to establish early diagnosis and treatment. CASE REPORT: Two neonates, one born at term and the other premature, with central venous catheter and parenteral nutrition. They had sudden unexplained hypotension and signs of decompensation and death secondary to cardiac tamponade. DISCUSSION: Cardiac tamponade secondary to central venous catheter is an unusual entity seldom discussed in the literature. The estimated incidence is 0.3 to 2% with a 74 to 100% mortality. It must be suspected and diagnosed early in order to decrease the mortality.

[Neonatal cardiac rhabdomyoma: case report and clinico-epidemiologic considerations]. / Rabdomioma cardiaco neonatal: informe de un caso y consideraciones clínico-epidemiológicas.

Primary cardiac tumors are very infrequent at all ages; the most frequent in the pediatric age is rhabdomyoma. This tumor is associated with tuberous sclerosis in 37 to 80%, with a frequency of 1 for each 40,000 live newborns. This case is about a newborn, who in the immediate postnatal period presented pansystolic murmur, grade IV cardiomegaly, electrocardiographic changes of biventricular hypertrophy and heart failure. Echocardiogram and magnetic resonance images showed several tumors in the septum and in ventricular walls; histopathology study of the heart, confirmed the diagnosis. The diagnosis of tuberous sclerosis was made clinically (seizures, hypomelanotic macules) and with the image of parenchymal hypodense areas. In our country there is little information about both diseases, that's why we made a review of the incidence, diagnosis, prognosis and treatment.