Maissa Rayyan

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. Target lipid dosage was 1.0 g fat/kg body weight [BW]/d on days 1–3, 2 g/kg BW/d on day 4, 3 g/kg BW/d on day 5, and 3.5 g/kg BW/d on days 6–14. Results: Test emulsion vs control, mean ± SD: baseline triglyceride concentrations were 0.52 ± 0.16 vs 0.54 ± 0.19 mmol/L and increased similarly in both groups to 0.69 ± 0.38 vs 0.67 ± 0.36 on day 8 of treatment (P = .781 for change). A significantly higher decrease in total and direct bilirubin vs baseline was seen in the test group compared with the control group P < .05 between groups). In plasma and red blood cell phospholipids, eicosapentaenoic acid and docosahexaenoic acid were higher, and the n-6/n-3 fatty acid ratio was lower in the test group (P < .05 vs control). Conclusions: The lipid emulsion, based on a mixture of MCTs and soybean, olive, and fish oils, was safe and well tolerated by preterm infants while beneficially modulating the fatty acid profile.

Array comparative genomic hybridization as a diagnostic tool for syndromic heart defects.

OBJECTIVES To investigate different aspects of the introduction of array comparative genomic hybridization (aCGH) in clinical practice. STUDY DESIGN A total 150 patients with a syndromic congenital heart defect (CHD) of unknown cause were analyzed with aCGH at 1-Mb resolution. Twenty-nine of these patients, with normal results on 1Mb aCGH, underwent re-analysis with 244-K oligo-microarray. With a logistic regression model, we assessed the predictive value of patient characteristics for causal imbalance detection. On the basis of our earlier experience and the literature, we constructed an algorithm to evaluate the causality of copy number variants. RESULTS With 1-Mb aCGH, we detected 43 structural variants not listed as clinically neutral polymorphisms, 26 of which were considered to be causal. A systematic comparison of the clinical features of these 26 patients to the remaining 124 patients revealed dysmorphism as the only feature with a significant predictive value for reaching a diagnosis with 1-Mb aCGH. With higher resolution analysis in 29 patients, 75 variants not listed as clinically neutral polymorphisms were detected, 2 of which were considered to be causal. CONCLUSIONS Molecular karyotyping yields an etiological diagnosis in at least 18% of patients with a syndromic CHD. Higher resolution evaluation results in an increasing number of variants of unknown significance.

Hepatic tolerance of repeated intravenous paracetamol administration in neonates.

Introduction:  An intravenous (i.v.) formulation of paracetamol is available, but reports on its hepatic tolerance in neonates are limited. We therefore assessed hepatic tolerance of i.v. paracetamol in neonates.

DEVELOPMENTAL PHARMACOLOGY: NEONATES ARE NOT JUST SMALL ADULTS…

Abstract Neonatal drug dosing needs to be based on the physiological characteristics of the newborn and the pharmacokinetic parameters of the drug. Size-related changes can in part be modelled based on allometry and relates to the observation that metabolic rate relates to weight by a kg0.75 trend. Until adult metabolic activity has been reached, ontogeny, i.e. isoenzyme-specific maturation and maturation of renal clearance also contributes to drug metabolism, making isoenzyme-specific documentation of maturation necessary. Changes in body composition and ontogeny are most prominent in neonates. The body fat content (/kg) is markedly lower and the body water content (/kg) is markedly higher in neonates. These findings have an impact on the distribution volume of both lipophilic and hydrophilic drugs. Drugs are cleared either by metabolism or elimination. While the first is mainly hepatic, the second route is mainly renal. Both hepatic metabolism and renal clearance display maturation in early life although other covariables (e.g. polymorphisms, co-administration of drugs, first pass metabolism, disease characteristics) further contribute to the interindividual variability in drug disposition. Documentation of these maturational processes based on in vivo ‘case’ studies is of value since these drug-specific observations can subsequently be extrapolated to other drugs which are either already being prescribed or even considered for use in neonates by the introduction of these observations in ‘generic physiologically-based pharmacokinetic’ models.

Pasteurization of mother's own milk for preterm infants does not reduce the incidence of late-onset sepsis.

Background: Feeding preterm infants human milk has a beneficial effect on the risk of late-onset sepsis (LOS). Due to lack of microbiological standards, practices such as pasteurization of mother’s own milk differ widely among neonatal intensive care units worldwide. Objectives: To investigate whether pasteurization of mother’s own milk for very-low-birth-weight (VLBW) infants influences the incidence and severity of infection-related outcomes. Methods: In this randomized controlled trial, preterm infants (gestational age <32 weeks and/or birth weight <1,500 g) received either raw or pasteurized mother’s own milk during the first 8 weeks of life. The primary outcome was the incidence of proven LOS. A dose-response relation was verified, i.e. the dependence of the risk of sepsis on the actual and cumulative quantities of mother’s own milk. Results: This study included 303 VLBW infants (mean birth weight: 1,276 g; mean gestational age: 29 weeks) whose baseline and nutritional characteristics were similar. The incidence of laboratory-confirmed sepsis was not statistically different in infants fed raw milk compared to infants who received pasteurized milk: 22/151 (0.15, CI: 0.08–0.20) and 31/152 (0.20, CI: 0.14–0.27), respectively (RR: 0.71; 95% CI: 0.43–1.17). A significant dose-response relation was observed between the adjusted quantity of enteral feeding and the risk of LOS, regardless of the type of feeding. Conclusion: For preterm infants, pasteurization of mother’s own milk shows a trend towards an increase in infectious morbidity, although no statistical significance was reached. Practices should focus on collection, storage and labeling procedures to ensure the safety and quality of expressed milk.

Cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy

OBJECTIVE To study cefazolin pharmacokinetics in maternal plasma and amniotic fluid during pregnancy. STUDY DESIGN Newly collected time-concentrations profiles and reported studies investigating cefazolin disposition (plasma, amniotic fluid) were pooled. Nonlinear mixed effect modeling was applied. A 2-compartment linear disposition model was used to fit cefazolin plasma observations. A third compartment was used to model amniotic fluid concentration. RESULTS One hundred eighty-seven plasma and 96 amniotic fluid samples were collected in 82 pregnancies (17-40 weeks gestational age). Cefazolin clearance and distribution estimates were 7.44 L/h and 12.04 L without gestational age-dependent trends in maternal plasma. The equilibration half-life (T(eq)) between plasma and amniotic fluid at term gestational age was 4.4 hours, increased with decreasing gestational age, and was 9.09 times longer in patients with polyhydramnios. CONCLUSION Cefazolin clearance and distribution volume are increased during pregnancy. The cefazolin T(eq) depends on gestational age and polyhydramnios. On the basis of these observations, dosing regimes to attain higher amniotic fluid concentrations were formulated.

Characteristics of respiratory syncytial virus‐related apnoea in three infants

Apnoea is a common sign in respiratory syncytial virus (RSV) infections in young infants and can be the first presentation of an acquired RSV infection. We describe polysomnographic recordings of three infants revealing prolonged RSV‐related apnoea before RSV infection was diagnosed. The apnoeas were of central origin. The caregivers had not noted any apparent life‐threatening events (ALTE) prior to the polysomnography. Cardiorespiratory monitoring after the acute infection did not reveal any further apnoeas.

Urinary propofol metabolites in early life after single intravenous bolus

BACKGROUND /st> Propofol clearance is lower in neonates than in adults and displays extensive interindividual variability, in part explained by postmenstrual age (PMA) and postnatal age (PNA). Since propofol is almost exclusively cleared metabolically, urinary propofol metabolites were determined in early life and compared with similar observations reported in adults. METHODS /st> Twenty-four hours urine collections were sampled after a single i.v. bolus of propofol (3 mg kg(-1)) in neonates undergoing procedural sedation. Clinical characteristics (PMA, PNA, weight, and cardiopathy) were recorded. Urine metabolites [propofol glucuronide (PG), 1- and 4-quinol glucuronide (QG)] were quantified using high-pressure liquid chromatography. Urine recovery (% administered dose) and the contribution of PG and QG to urinary elimination were calculated. Data were reported by median and range, analysed by Mann-Whitney U or Spearmans rank. RESULTS /st> Eleven neonates (median PNA 11 days, PMA 38 weeks) were included. Median propofol metabolite recovery was 64% (range 34-98%). PG contributed 34% (range 8-67%) and QG 65% (range 33-92%). There was no significant correlation between either PMA, PNA, or cardiopathy and propofol metabolites. Compared with adults, the contribution of PG (34% vs 77%) was lower and the contribution of QG (65% vs 22%) was higher in neonates. CONCLUSIONS /st> Propofol metabolism in neonates differs from adults, reflecting the age-dependent limited glucuronidation capacity. Hydroxylation to quinol metabolites already contributes to propofol metabolism. These differences likely explain the PMA- and PNA-dependent reduced propofol clearance in neonates.

Does intravenous paracetamol administration affect body temperature in neonates

Introduction Intravenous paracetamol (actaminophen) has recently been registered for treatment of pain in neonates but the pharmacodynamics, including effects on body temperature, have not been reported. Methods A pooled analysis on body temperature recordings in neonates exposed to intravenous paracetamol was performed. Body temperature was recorded by skin probe and registered before and every 2 h following initiation of single or repeated intravenous paracetamol administration (up to 48 h). Repeated measures ANOVA and paired analysis were used to quantify differences following paracetamol exposure. Results The pooled analysis was based on 99 neonates (median weight 2.7 (range 0.5–5.4) kg, median postmenstrual age 37 (range 27–50) weeks). Based on observations in 93 normothermic (<37.8°C) neonates and six neonates with fever, it was documented that paracetamol administration does not affect body temperature in normothermic patients. In neonates with fever, the median decrease (−0.8°C) is most prominent in the first 2 h (p<0.01) following paracetamol administration with subsequent further normalisation. Conclusions Administration of intravenous paracetamol does not result in hypothermia in normothermic neonates. In those with fever, maximal temperature reduction is achieved within 2 h following paracetamol administration.

Long term respiratory outcomes of congenital diaphragmatic hernia, esophageal atresia, and cardiovascular anomalies

Intrathoracic congenital malformations may be associated with long-term pulmonary morbidity. This certainly is the case for congenital diaphragmatic hernia, esophageal atresia and cardiac and aortic arch abnormalities. These conditions have variable degrees of impaired development of both the airways and lung vasculature, with a postnatal impact on lung function and bronchial reactivity. Pulmonary complications are themselves frequently associated to non-pulmonary morbidities, including gastrointestinal and orthopaedic complications. These are best recognized in a structured multidisciplinary follow-up clinic so that they can be actively managed.