Harry N Lafeber

Maturity of the adrenal cortex in very preterm infants is related to gestational age

To study the maturity of the adrenal cortex in preterms born before 33 wk of gestation, basal levels of cortisol and cortisone and the cortisol and 17-hydroxyprogesterone (17-OHP) response to 1 μg/kg adrenocorticotropic hormone stimulation were measured in 24 appropriate-for-gestational age preterm infants (26-33 wk; 690-1985 g). Gestational age influenced the response of cortisol, 17-OHP, and the ratio between cortisol/17-OHP in the studied infants. In preterms born <30 wk of gestation, levels of cortisol, and the ratio between cortisol/17-OHP were lower compared with preterms born between 30 and 33 wk. Levels of cortisone were higher in preterms born <30 wk, suggesting a lower activity of 11β-hydroxysteroid dehydrogenase that may be related to maturity as well. These findings indicate that the adrenal cortex function in preterm infants is closely related to the duration of gestation and may be important in neonatal morbidity.

Quantitation of oxidation of medium-chain triglycerides in preterm infants.

ABSTRACT: Medium-chain triglycerides, with a chain length of eight and 10 carbon atoms, form up to 50% of the total fat content in some preterm infant formulas. In 20 small preterm infants (birthwt: 1153 ± 227 g; mean ± SD) fed a special formula containing 40% MCT, a primed constant oral infusion study of l-13C-potassium octanoate was conducted to quantify the oxidation of MCT. A plateau in 13C enrichment in breath CO2 was reached in all patients within 1-3 h. Simultaneously, substrate utilization was measured using a closed system indirect calorimeter. No significant difference was found between appropriate for gestational age (»=8) and small for gestational age (»=12) infants in the percentage of the administered tracer that was oxidized (44.9 ± 9.1% versus 48.5 ± 11.0%). In all patients, the recovery was calculated to be 47.1 ± 10.2%, which is less than previously estimated and corresponds to a mean MCT oxidation of 1.26 ± 0.27 g/kg/d. With indirect calorimetry, a total fat oxidation of 1.42 ± 0.84 g/kg/d in appropriate for gestational age and 2.00 ± 0.85 g/kg/d in small for gestational age infants was found, indicating that MCT accounted for around 85% of the total fat oxidation in appropriate for gestational age versus 65% in small for gestational age infants

Comparison of Short Term Indirect Calorimetry and Doubly Labeled Water Method for the Assessment of Energy Expenditure in Preterm Infants

The accuracy of 8-hour indirect calorimetry (IDC) as an estimate of energy expenditure was investigated in 8 healthy preterm infants (birth weight 1,270 +/- 193 g, gestational age 32 +/- 3 weeks, mean +/- SD) in comparison with an analysis over 5 days using the doubly-labeled water (2H2(18)O) method (DLW). The infants that were fed continuously by nasogastric drip with 120 kcal/kg/day of special infant formula were measured twice under thermoneutral conditions in a closed system indirect calorimeter during 8 h with a 4-day interval; simultaneously isotope decay was measured by isotope ratio mass spectrometry in urine samples collected daily during 5 days from 6 h after an oral dose of 2H2(18)O on the first day of IDC, all during the 4th postnatal week. The mean differences between carbon dioxide production rate (rCO2) measured either by single 8-hour IDC or by duplicate 8-hour IDC and the 5-day DLW method, using the two-point analysis or the multipoint analysis were not significantly different from zero. The rCO2 calculated from the DLW method using the two-point analysis differed -1.4 +/- 1.7% from that measured by the multipoint analysis. The mean differences between the metabolic rate estimated from 8 h of IDC and from the 5-day DLW method based on a measured RQ of 0.90 was -6.7 +/- 6.2% and based on the RQ of the feeding -4.5 +/- 6.0%. These differences were not significantly different from zero. We conclude that IDC over 8 h and two-point DLW measurement over 5 days, both methods that can be applied with relative ease in practice, offer an adequate average estimate of energy expenditure in continuously fed preterm infants under thermoneutral conditions.

Starter formula enriched in prebiotics and probiotics ensures normal growth of infants and promotes gut health: a randomized clinical trial

Background:Prebiotics and probiotics exert beneficial effects by modulating gut microbiota and immune system. This study evaluates efficacy and safety of an infant formula containing bovine milk-derived oligosaccharides and Bifidobacterium animalis ssp lactis (B. lactis) (CNCM I-3446) on incidence of diarrhea and febrile infections during the first year of life (primary outcome).Methods:Full-term infants receiving Test or Control (without bovine milk-derived oligosaccharide and B. lactis) formulae were enrolled in a multicenter, randomized, controlled, and double-blind trial with a reference breastfeeding group. .Results:413 infants were assigned between Test (n = 206) and Control (n = 207) formula. There was no significant difference for diarrhea and febrile infections incidence between groups at 6 (odds ratio (95% confidence interval) = 0.56 (0.26–1.15), P = 0.096) and 12 mo (odds ratio = 0.66 (0.38–1.14), P = 0.119). Test formula was well tolerated, anthropometrics parameters were not significantly different between groups and aligned with WHO growth standards up to 12 mo. Data from test group showed that gut microbiota pattern, fecal IgA and stool pH were brought to be closer to those of breastfed infants.Conclusion:An infant formula enriched with bovine milk-derived oligosaccharide and B. lactis supports normal infant growth, is well tolerated and improves intestinal health markers. No differences in diarrhea and febrile infection incidence were found in the population studied.

Gentamicin Pharmacokinetics in Preterm Infants with a Patent Ductus Arteriosus (PDA) 353

Background and objective: Gentamicin is a widely used antibiotic drug in neonatal infections. In sick newborn infants who are ventilated because of respiratory distress a patent ductus arteriosus (PDA) may lead to a difference in renal function and hence to a difference in gentamicin kinetics. Patients and methods: Pharmacokinetics of gentamicin were therefore studied in two groups of preterm infants all treated with gentamicin based on an (suspected) infection. Group A: patients with a PDA (N=12; GA:25 to 33 wks; BW:590 to 2380 g) and group B: patients with a closed ductus arteriosus (CDA)(N=12; GA:28 to 37 wks; BW:915 to 2510 g). Gentamicin was administered intravenously 3 mg/kg.day in a single dose. Gentamicin serum concentrations were determined before and 1 hr after the 2nd dose by a fluorescence polarisation immunoassay. Individual gentamicin pharmacokinetic parameters(Volume of distribution (Vd); Elimination rate (Kel); Clearance (Cl)) were calculated using a one-compartment open model and related to patient parameters. Patent or closed ductus arteriosus were confirmed by ECHOcardiography. Results see table. Conclusion: No difference was found in Cl and Kel of gentamicin between patients with a PDA and CDA. Vd of gentamicin shows a significant but marginal increase in preterm infants with a PDA compared to those with a closed ductus. This implies that the same dose gentamicin can be practised in patients with a PDA.

Growth and Substrate Utilization in Preterm Infants Fed Formula with 100 kcal.kg-1.d-1 or 120 kcal.kg-1.d-1

Growth and Substrate Utilization in Preterm Infants Fed Formula with 100 kcal.kg -1 .d -1 or 120 kcal.kg -1 .d -1

Growth during the First Two Years of Life in Preterm Infants Who Developed Bronchopulmonary Dysplasia (BPD) and Received Initial Dexamethason (DXM) Therapy. † 1169

Growth during the First Two Years of Life in Preterm Infants Who Developed Bronchopulmonary Dysplasia (BPD) and Received Initial Dexamethason (DXM) Therapy. † 1169

The Use of Bioimpedance Analysis (BIA) as a Reflection of Bodycomposition Regarding Gentamicin (G) Kinetics in Neonates 356

Background and objective: Gentamicin (G) is often used in neonates suffering from sepsis. Sepsis in these infants may lead to renal impairment and aminoglycoside toxicity. For pharmacokinetic modeling of G in neonates, a parameter predicting G clearance is needed. In general, poor renal function can be accompanied by an increase in extracellular volume. The aim of this study was to investigate the relationship between G clearance and BIA(measured as resistance (R)) as a reflection of total body water. Patients and methods: Twenty three patients (GA 25 to 42 wks, BW 670 to 4185 g) were treated with G. G was administered intravenously 3 mg/kg.day in a single dose. G serum concentrations for therapeutic drug monitoring were measured before and 1 hr after the 2nd dose by a fluorescence polarisation immunoassay. On the day of bloodsampling a BIA was performed using a bodycomposition analyser (model BIA-101 RJL systems, Detroit). Individual G pharmacokinetic parameters (Volume (Vol); Volume of distribution (Vd); Elimination rate (Ke); Clearance (Cl) were calculated using a one-compartment open model and related to patient parameters. Results see table. Conclusion: Vol and Cl correlated best with the traditional parameters height (H) and body weight (BW). This implies that BIA as a reflection of bodycomposition (H2/R) has less predictive value for G kinetics in neonates compared to H and BW. Further studies are needed to evaluate if this method can be used in severe illness of the neonate when actual weight is not available.

202 ELEVATED PRECURSORS OF THE PRIMARY BILE ACIDS (PBA): CHOLIC-AND CHENODEOXYCHOLIC ACID (CA; CDCA) IN NEONATAL CHOLESTASIS (NC)

The bile acid concentrations in serum of 2 preterm infants (GA: 27 and 32 wk; BW: 900 and 1800 g) with NC were compared with the values of 7 preterm infants (mean GA 30 wk; mean BW 1345 g) without cholestasis (NonC) during the first 4 weeks after birth with a radio-immunoassay method (RIA) and a gas chromatography/mass spectrometry (GC/ MS) method. NC was diagnosed with “normal” liverfunction tests: direct acting bilirubin, SGOT, SGPT and γ-GT. There was no difference in feeding: parenteral, oral, frequency, formula or mothers own milk. The mean values of the conjugated CDCA and CA were the same in both groups with both procedures. The mean GC/MS values of hyocholic-, lithocholic-, 3-β-hydroxy-5-cholenoic- and deoxycholic acid were also the same during the study. The precursors of CDCA: 3α, 7α-dihydroxy-5β-cholestanoic acid (DHCA) and of CA: trihydroxycoprostanoic acid (THCA) measured with GC/MS were much higher in infants with NC at the end of the first week till the end of the investigation.In conclusion: serum PBA concentration in preterm infants is not conclusive to diagnose NC. In infants with NC, however the precursors of the PBA are elevated, probably as the result of a temporary deficiency of the enzymsystern or of the peroxisomal function.

GLUCOSE OXIDATION AND SUBSTRATE UTILIZATION IN VLBW INFANTS FED A FORMULA CONTAINING 5 OR 40 PERCENT OF FAT AS MEDIUM CHAIN TRIGLYCERIDES (MCT)

The fat composition of special formula milk for VLBW infants may include up to 50% MCT. During feeding with two formulas (Nutricia, Holland) containing per 100 ml: 80 kcal, 8.0 g carbohydr., 2.2 g protein and 4.4 g fat with 40% MCT (A) or 5% MCT (B), glucose oxidation was measured by primed constant oral infusion of U-13C glucose as 13CO2 recovery in breath and substrate utilization by indirect calorimetry. At week 4, 15 infants (birthw.1236±228 g, gest.age 32.0±2.2 wks) received 150 ml/kg/day of formula A and 10 infants (birthw.1304±165 g, gest.age.32.6±1.9wks) received B. Net fat oxid. was calculated as non-protein met.rate - net gluc.oxid. Results in g/kg/d or kcal/kg/d ±S.D.:Conclusions: 1. No differences were found in net.rate and substrate util of infants fed formula A or B. 2. However, increasing the % MCT causes a significant decrease in net glucose oxid as measured with stable isotopes. 3. Combining these methods we also conclude that net fat oxidation is higher in the high MCT group.