Differences in Copy Number Variation between Discordant Monozygotic Twins as a Model for Exploring Chromosomal Mosaicism in Congenital Heart Defects.

Studies addressing the role of somatic copy number variation (CNV) in the genesis of congenital heart defects (CHDs) are scarce, as cardiac tissue is difficult to obtain, especially in non-affected individuals. We explored the occurrence of copy number differences in monozygotic (MZ) twins discordant for the presence of a CHD, as an illustrative model for chromosomal mosaicism in CHDs. Array comparative genomic hybridization was performed on peripheral blood-derived DNA obtained from 6 discordant MZ twin pairs and on sex-matched reference samples.

Drug disposition and clinical practice in neonates: cross talk between developmental physiology and pharmacology.

Drug dosing in infants should be based on their physiological characteristics and the pharmacokinetic and -dynamic profile of the compound. Since maturational physiological changes are most prominent in infancy, variability is the key feature of clinical pharmacology in infancy: developmental physiology drives developmental pharmacology. This is illustrated by the link between renal physiology and renal drug clearance and between hepatic physiology and hepatic drug elimination for some specific compounds.

Neonatal pharmacology: extensive interindividual variability despite limited size.

Providing safe and effective drug therapy to neonates requires knowledge of the impact of development on the pharmacokinetics and pharmacodynamics of drugs. Although maturational changes are observed throughout childhood, they are most prominent during the first year of life. Several of these processes overlap, making development an extremely dynamic system in the newborn compared with that in infants, children, or adults.

Pharmacokinetics of Drugs in Neonates: Pattern Recognition Beyond Compound Specific Observations.

Although the principles of drug disposition also apply in neonates, their specific characteristics warrant focussed assessment. Children display maturation in drug disposition, but this is most prominent in the first year of life. Besides maturational aspects of drug absorption and distribution, maturation mainly relates to (renal) elimination and (hepatic) metabolic clearance.

Pharmacokinetics of Aminoglycosides in the Newborn.

Aminoglycosides have played a major role in antimicrobial therapy since their discovery in the 1940s. Their bactericidal efficacy in gram-negative infections, synergism with beta-lactam antibiotics, limited bacterial resistance, and low cost have given these agents a firm place in antimicrobial treatment. After penicillins, aminoglycosides are the most commonly used drugs in the neonatal intensive care unit.

Pharmacokinetics of a loading dose of intravenous paracetamol post caesarean delivery.

Background: The postpartum period affects drug disposition, but data of intravenous paracetamol loading dose pharmacokinetics immediately following caesarean delivery have not yet been reported.

Methods: Immediately following caesarean delivery, women received a 2-g loading dose of intravenous paracetamol. Plasma samples were collected at 1, 2, 4 and 6 h.

Congenital heart defects in a novel recurrent 22q11.2 deletion harboring the genes CRKL and MAPK1.

The proximal region of the long arm of chromosome 22 is rich in low copy repeats (LCR). Non-allelic homologous recombination (NAHR) between these substrates explains the high prevalence of recurrent rearrangements within this region. We have performed array comparative genomic hybridization in a normally developing girl with growth delay, microcephaly, and truncus arteriosus, and have identified a novel recurrent 22q11 deletion that spans LCR22-4 and partially affects the common 22q11.

A bodyweight-dependent allometric exponent for scaling clearance across the human life-span.

Purpose: To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug.

Methods: Data from seven previously published propofol studies ((pre)term neonates, infants, toddlers, children, adolescents and adults) were analysed using NONMEM VI. To scale clearance, a bodyweight-based exponential equation with four different structures for the exponent was used: (I) 3/4 allometric scaling model; (II) mixture model; (III) bodyweight-cut-point separated model; (IV) bodyweight-dependent exponent model.

Creatinine reference values in ELBW infants: impact of quantification by Jaffe or enzymatic method.

Objective: Serum creatinine (Scr) reflects to a certain extent glomerular filtration rate in neonates, but postnatal observations also depends on the technique used to quantify Scr (Jaffe colorimetry or enzymatic quantification).

Methods: In an attempt to quantify differences between these techniques, we compared postnatal Scr trends in two consecutive cohorts of extremely low birth-weight (ELBW) neonates before and following a switch from uncompensated Jaffe to enzymatic Scr quantification. Postnatal Scr (Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 14, 21, 28, and 42) in 151 ELBW neonates (uncompensated Jaffe) was compared to 116 more recently admitted ELBW neonates (enzymatic).

Short-term use of parenteral nutrition with a lipid emulsion containing a mixture of soybean oil, olive oil, medium-chain triglycerides, and fish oil: a randomized double-blind study in preterm infants.

Background: For premature neonates needing parenteral nutrition (PN), a balanced lipid supply is crucial. The authors hypothesized that a lipid emulsion containing medium-chain triglycerides (MCTs) and soybean, olive, and fish oils would be as safe and well tolerated as a soybean emulsion while beneficially influencing the fatty acid profile.

Methods: Double-blind, controlled study in 53 neonates (<34 weeks' gestation) randomized to receive at least 7 days of PN containing either an emulsion of MCTs and soybean, olive, and fish oils or a soybean oil emulsion.

Maturation of the glomerular filtration rate in neonates, as reflected by amikacin clearance.

Background And Objectives: During the newborn period and early infancy, renal function matures, resulting in changes in the glomerular filtration rate (GFR). This study was performed to quantify developmental changes in the GFR in (pre)term neonates by use of amikacin clearance as proof of concept. The model was used to derive a rational dosing regimen in comparison with currently used dosing regimens for amikacin.

Pharmacokinetics and pharmacodynamics of intravenous acetaminophen in neonates.

Effective analgesia in neonates is still hampered owing to a lack of data on pharmacokinetics and pharmacodynamics of analgesics. In this article, the consecutive steps taken to document aspects of disposition (pharmacokinetics and metabolism) and safety (hepatic tolerance, hemodynamic stability and effects on body temperature) during exposure to intravenous acetaminophen in neonates are summarized. Based on these data, dosing suggestions were formulated.

The clinical pharmacology of short acting analgo-sedatives in neonates.

Effective pain management remains an important indicator of the quality of care provided to neonates, not only from an ethical, but also from a clinical outcome perspective. Significant progresses in non-pharmacological therapies have been made. However - in the meanwhile - neonatal practice also evolved.

Educational paper: Retinopathy of prematurity.

Unlabelled: Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease affecting the premature infant with an incompletely vascularized retina. The spectrum of ophthalmological findings in ROP exists from minimal sequelae, which do not affect vision, to bilateral retinal detachment and total blindness. With the increased survival of very small infants, retinopathy of prematurity has become one of the leading causes of childhood blindness.

Continuous glucose monitoring and retinopathy of prematurity.

Purpose: To use the continuous glucose monitoring system (CGMS) in very low birthweight (VLBW) infants to further explore the association between elevated glucose levels and retinopathy of prematurity (ROP) and to find new preventive strategies for ROP.

Methods: A secondary analysis of risk factors for ROP in VLBW infants was performed in the neonatal intensive care units of University Hospital Leuven and ZOL Genk, Belgium. The subjects were part of the NIRTURE trial (ISRCTN78428828).

Outcome of fetuses with congenital diaphragmatic hernia and associated intrafetal fluid effusions managed in the era of fetal surgery.

Objective: Fetuses with congenital diaphragmatic hernia (CDH) and for whom additional ultrasound findings are abnormal typically are considered to have a dismal prognosis. Our aim was to assess the outcome of fetuses with CDH and associated intrafetal fluid effusions.

Methods: This was a retrospective bicentric cohort study on the perinatal management of fetuses with CDH and intrafetal fluid effusions.

Results of fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia and the set up of the randomized controlled TOTAL trial.

In isolated congenital diaphragmatic hernia, lung size and/or the position of the liver are predictive of neonatal outcome. Percutaneous Fetal Endoscopic Tracheal Occlusion (FETO) by a balloon can be undertaken to prompt lung growth in the worst cases. The feasibility and safety of FETO is no longer at stake, and it is associated with an apparent increase in neonatal survival.

Creatinaemia at birth is equal to maternal creatinaemia at delivery: does this paradigm still hold?

Objective: The paradigm that creatinaemia at birth is equal to maternal creatinaemia may also depend upon the quantification technique applied. Paired maternal-neonatal creatinaemia samples in whom Jaffe in both or compensated Jaffe (maternal) and enzymatic quantification (neonate) were applied.

Methods: Extreme low birth weight infants in two time intervals were included when paired maternal-neonatal creatinaemia samples were available.

Quantification of amikacin in bronchial epithelial lining fluid in neonates.

Amikacin efficacy is based on peak concentrations and the possibility of reaching therapeutic levels at the infection site. This study aimed to describe amikacin concentrations in the epithelial lining fluid (ELF) through bronchoalveolar lavage (BAL) in newborns. BAL fluid was collected in ventilated neonates treated with intravenous (i.

Perinatal pharmacology: applications for neonatal neurology.

The principles of clinical pharmacology also apply to neonates, but their characteristics warrant a tailored approach. We focus on aspects of both developmental pharmacokinetics (concentration/time relationship) and developmental pharmacodynamics (concentration/effect relationship) in neonates. We hereby aimed to link concepts used in clinical pharmacology with compound-specific observations (anti-epileptics, analgosedatives) in the field of neonatal neurology.

Postnatal trends in creatinemia and its covariates in extremely low birth weight (ELBW) neonates.

To document trends and covariates of creatinemia (Scr) in extremely low birth weight (ELBW, < 1,000 g) neonates, maternal characteristics [betamethasone, premature preterm rupture of membranes (PPROM), pre-eclampsia, maternal Scr], characteristics at delivery [gestational age (GA), birth weight (BW), small for GA (SGA), Apgar, intubation] and during neonatal stay [ventilation, oxygen, parenteral nutrition, ibuprofen, steroids, intraventricular hemorrhage, retinopathy of prematurity (ROP), phototherapy] were linked with Scr observations. Data were reported by median and range or incidence. Characteristics in ELBW neonates with raised peak Scr (>P75) were compared to controls ( View Article and Find Full Text PDF

Mechanism based medicine in infancy: complex interplay between developmental pharmacology and pharmacogenetics.

Introduction of the available knowledge on pharmacogenetics very likely is one of the tools to close the gap between 'population' focused evidence based and 'individual' mechanism based medicine. However, besides pharmacogenetics, other covariates like age, renal function and/or co-medication should also be considered simultaneously when aiming for a 'tailored' pharmacotherapy. To illustrate this, we further extended the tramadol example used by Wilffert et al.