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.

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 kg 0.75 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.

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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.

This retrospective study on hepatic tolerance provides evidence on safety aspects of i.v. paracetamol in neonates. Future studies should focus on dose-findings and pharmacodynamics of this formulation in 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 (P75 (112.3 μmol/l), Scr remained elevated until day 28. Mothers of cases received less betamethasone, neonates had a lower GA, lower BW, lower Apgar, and needed more often intubation. Postnatal ventilation, oxygen, parenteral nutrition, ibuprofen, steroids, ROP, and intraventricular hemorrhage were different. GA and ventilation or Apgar were independent factors for raised peak Scr. ELBW neonates display trends similar to heavier neonates, but peak Scr is higher, and the subsequent decrease slower. Raised creatinemia in ELBW neonates reflects immaturity (GA) and morbidity (ventilation, Apgar).

AimTo investigate growth patterns and anthropometrics in former extremely low birth weight (ELBW, <1000 g) children and link these outcomes to neurocognition and body composition in childhood.MethodsELBW children were examined at birth (n = 140), at 9 and 24 months (n≥96) and at approximately 11 years within the framework of the PREMATCH (PREMATurity as predictor children’s of Cardiovascular and renal Health) case–control (n = 93–87) study. Regional growth charts were used to convert anthropometrics into Z–scores. Catch–up growth in the first two years of life was qualified as present if ΔZ–score >0.67 SDS. At 11 years, anthropometrics, neurocognitive performance, body composition, grip strength and puberty scores were assessed.ResultsELBW neonates displayed extra–uterine growth restriction with mean Z–scores for height, weight and head circumference of –0.77, –0.93 and –0.46 at birth, –1.61, –1.67 and –0.72 at 9 months, –1.22, –1.61 and –0.84 at 24 months, and –0.42, –0.49 and –1.09 at 11 years. ELBW children performed consistently worse on neurocognitive testing with an average intelligence quotient equivalent at 11 years of 92.5 (SD 13.1). Catch–up growth was not associated with neurocognitive performance. Compared to controls, ELBW cases had lower grip strength (13.6 vs. 15.9 kg) and percentage lean body weight (75.1 vs. 80.5%), but higher body fat (24.6 vs. 19.2%) and advanced puberty scores at 11 years (all P≤0.025). Catch–up growth for weight and height in the first two years of life in cases was associated with a lower percentage body fat compared to cases without catch–up growth (16.8% catch-up growth for weight vs. 25.7%, P<0.001; 20.9% catch-up for height vs. 25.8%, P = 0.049).ConclusionsIn young adolescence, former ELBW children still have difficulties to reach their target height. Compared to normal birth weight controls, ELBW adolescents show lower neurocognitive performance and grip strength and a higher percentage body fat, a potential risk factor for adverse health outcomes in adulthood. Our key finding is that catch–up growth in ELBW children in the first two years of life is associated with a lower percentage body fat and is therefore likely to be beneficial.

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