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In the Netherlands, neonatal intensive care is provided in 10 neonatal intensive care centres. Although antenatal transport is preferred, each year more than 1000 newborns are transported to the centres, in the majority of cases by ambulance. Transport by helicopter became available in 1987. From June 1987 till December 1993, 583 infants were transported by helicopter (median gestational age 32 weeks, range 24– 43). Forty-four per cent had a gestational age of less than 32 weeks. Four hundred and forty-six infants were mechanically ventilated. No baby died in transfer. After admission, 101 infants died (18.4). There were no accidents during transport. Ten per cent of the requested flights was cancelled because of weather conditions. The mean transport time of the babies was 36 min (range 10– 145), and the mean transport time of the transport teams was 128 min (range 20– 345). The transports carried out from 1987 to 1989 were recalculated with regard to duration and cost, assuming they were carried out by ambulance instead of by helicopter for the babies, the mean transport time by helicopter was 75 less than the calculated mean transport time by ambulance. However, the financial costs per transport were on average Dutch florins (DEL) 3000 higher by helicopter than by ambulance. In the Netherlands, the use of a helicopter for neonatal transport reduces the transport time, but doubles the costs.

ABSTRACT: Several formulas for preterm infants contain medium-chain triglycerides (MCT) to enhance fat absorption. Although fat absorption with MCT was slightly higher in several studies in preterm infants, a beneficial effect on growth has only been reported in one publication. We hypothesized that when part of the fat blend of preterm formula is substituted by MCT oil, this might lead to a different metabolic pattern in which, due to the preferential oxidation of MCT, an increase in lipogenesis from glucose could lead to an increase in metabolic rate. To study the impact of MCT on glucose metabolism, 18 preterm infants were randomized to receive either an MCT or an LCT formula containing 38- and 6%-by-weight medium-chain fatty acids, respectively, in their fat blend. At 4 wk of age, the metabolic rate, substrate utilization, glucose kinetics, and oxidation were measured by indirect respiratory calorimetry in combination with a constant-rate oral infusion of [U-13C]glucose. The “true” rate of appearance of glucose (Ra “true”) was measured from the dilution of the uniformly labeled (m + 6) species of infused tracer, whereas “apparent” rate of appearance of glucose (Ra “apparent”) was measured from the dilution of infused tracer C (carbon). The latter was measured by an on-line combustion method using a gas chromatograph-isotope ratio mass spectrometer. At a carbohydrate intake of 8.4 mg·kg-1·min-1, total utilization of carbohydrate was equal in both groups at 7.6 mg·kg-1·-min-1. However, glucose oxidation, as measured by the appearance of 13C in breath CO2was significantly lower in the MCT group (4.5 ± 0.83 versus 5.7 ± 0.67 mg·kg-1· min-1, MCT versus LCT). Therefore, it can be assumed that a larger proportion of the glucose intake in the MCT group was used in the nonoxidative pathway, e.g. synthesis of fat as compared with the LCT group. There was no difference in the rate of endogenous glucose production and glucose C recycling between the two groups. In addition, the metabolic rate calculated from the rate of oxygen consumption was also similar (59 ± 5 versus 62 ± 4 kcal·kg-1·d-1MCT versus LCT). We conclude that, in preterm infants fed a formula containing 38% MCT in their fat blend, glucose oxidation is significantly decreased whereas lipogenesis is probably increased. These findings may provide a mechanism for the so-called metabolic inefficiency of MCT.

Abstract

Medium-chain triglycerides (MCTs) are included in the fat blend of several preterm formulas because of their complete absorption and rapid oxidation. The effects of two different fat blend compositions on calcium (Ca), phosphorus (P), and magnesium (Mg) balances and plasma levels and on plasma levels of parathyroid hormone (PTH), alkaline phosphatase (AP), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] were investigated in 28 healthy very-low-birth weight infants at 4 weeks of age. A preterm formula with a traditional corn oil/MCT blend containing 38% MCTs (MCT group) was compared to a new fat blend, designed to resemble human milk more, containing 6% MCTs (LCT group). There was a higher absorption of Ca in the MCT group (73% vs. 60%. p< 0.005), and an equal absorption of P (both 92%). The excretion of Ca correlated with the excretion of fat (p< 0.00005). The LCT group showed a higher median PTH level (MCT: 2.1 pmol/L, LCT: 4.7 pmol/L, p< 0.01) and a higher urinary P excretion (p< 0.001). Mg absorption was also lower with LCT, but retention of Mg exceeded intrauterine values in both groups. Mineral plasma levels were in the normal range in both groups. AP was not different between groups and in the upper part of the reference range, whereas 1,25-(OH)2D levels were above the normal range and also not different between groups. We conclude that with the LCT formula, Ca absorption is slightly lower than with the MCT formula, whereas P absorption is unaffected. The resulting imbalance in absorption is compensated for by an increased urinary excretion of P. We conclude that current recommendations for the maximum Ca/P ratio in preterm formulas (2:1) might be too low in formulas containing only LCT.

Several formulas for preterm infants contain medium-chain triglycerides (MCT) to enhance fat absorption. Although fat absorption with MCT was slightly higher in several studies in preterm infants, a beneficial effect on growth has only been reported in one publication. We hypothesized that when part of the fat blend of preterm formula is substituted by MCT oil, this might lead to a different metabolic pattern in which, due to the preferential oxidation of MCT, an increase in lipogenesis from glucose could lead to an increase in metabolic rate. To study the impact of MCT on glucose metabolism, 18 preterm infants were randomized to receive either an MCT or an LCT formula containing 38- and 6-by-weight medium-chain fatty acids, respectively, in their fat blend. At 4 wk of age, the metabolic rate, substrate utilization, glucose kinetics, and oxidation were measured by indirect respiratory calorimetry in combination with a constant-rate oral infusion of [U-13C]glucose. The “true” rate of appearance of glucose (Ra “true”) was measured from the dilution of the uniformly labeled (m 6) species of infused tracer, whereas “apparent” rate of appearance of glucose (Ra “apparent”) was measured from the dilution of infused tracer C (carbon). The latter was measured by an on-line combustion method using a gas chromatograph-isotope ratio mass spectrometer. At a carbohydrate intake of 8.4 mg·kg−1·min−1, total utilization of carbohydrate was equal in both groups at 7.6 mg·kg−1·-min−1. However, glucose oxidation, as measured by the appearance of 13C in breath CO2was significantly lower in the MCT group (4.5 ± 0.83 versus5.7 ± 0.67 mg·kg−1· min−1, MCT versusLCT). Therefore, it can be assumed that a larger proportion of the glucose intake in the MCT group was used in the nonoxidative pathway, e.g.synthesis of fat as compared with the LCT group. There was no difference in the rate of endogenous glucose production and glucose C recycling between the two groups. In addition, the metabolic rate calculated from the rate of oxygen consumption was also similar (59 ± 5 versus62 ± 4 kcal·kg−1·d−1MCT versusLCT). We conclude that, in preterm infants fed a formula containing 38 MCT in their fat blend, glucose oxidation is significantly decreased whereas lipogenesis is probably increased. These findings may provide a mechanism for the so-called metabolic inefficiency of MCT.

Mean arterial pressure (MAP) is the area under the pressure wave averaged over the cardiac cycle, and therefore depends on pressure wave contour. A generally used rule of thumb to estimate MAP of peripheral arteries in adults is adding one-third of the arterial pulse pressure (PP) to diastolic arterial pressure (DAP). As peripheral pressure wave forms in neonates do not resemble adult peripheral wave forms, it may be expected that this rule of thumb does not hold for neonates. Previously, we found that MAP can be calculated by adding 50% PP to DAP in radial artery waves in neonates. In the present study, we investigated in neonates how MAP in the posterior tibial artery depends on systolic and diastolic pressure and we compared these findings to those found in the radial artery. Forty infants admitted for intensive care were studied. We analyzed 5000 invasively and accurately obtained blood pressure waves in the posterior tibial artery of 20 neonates and another 5000 waves similarly obtained from the radial artery in another group of 20 neonates. We found that MAP in posterior tibial artery waves is well approximated by adding 41.5±2.0% of PP to DAP, whereas MAP in radial artery waves can be calculated by adding 46.7±1.7% of PP to DAP. These values are significantly different (p<0.0001). In conclusion, the rule of thumb as used in the adult to find MAP, where 33% PP is added to DAP, does not hold for the newborn. We recommend to calculate MAP in the tibial artery by adding 40% of PP to DAP and in the radial artery by adding 50% of PP to DAP.

Mean arterial pressure (MAP) is the area under the pressure wave form averaged over the cardiac cycle. A widely used rule of thumb to estimate MAP of peripheral arterial pressure waves in adults is adding one-third of the pulse pressure (PP) to diastolic arterial pressure (DAP). However, radial artery pressure waves in newborns differ from those in adults and resemble proximal aortic pressure waves, so that the above-mentioned calculation of MAP may not be correct. The present study was set up to obtain an arithmetical approximation to derive MAP from blood pressure waves measured in the radial artery of the neonate. We accurately recorded about 300 invasively obtained blood pressure curves in the radial artery of 10 neonates admitted for intensive care. We found that MAP in the radial artery in these neonates can be well approximated by adding 46.6% PP to DAP (range 43.0–50.1%). We suggest that the rule of thumb to derive MAP from radial artery waves in the neonate to be approximately the average of systolic and diastolic pressure, as opposed to adding one-third of the pulse pressure to the diastolic value in the adult.

Medium-chain triglycerides (MCTs) are included in the fat blend of several preterm formulas because of their complete absorption and rapid oxidation. The effects of two different fat blend compositions on calcium (Ca), phosphorus (P), and magnesium (Mg) balances and plasma levels and on plasma levels of parathyroid hormone (PTH), alkaline phosphatase (AP), and 1,25-dihydroxyvitamin D [1,25-(OH)2D] were investigated in 28 healthy very-low-birth weight infants at 4 weeks of age. A preterm formula with a traditional corn oil/MCT blend containing 38 MCTs (MCT group) was compared to a new fat blend, designed to resemble human milk more, containing 6 MCTs (LCT group). There was a higher absorption of Ca in the MCT group (73 vs. 60. p< 0.005), and an equal absorption of P (both 92). The excretion of Ca correlated with the excretion of fat (p< 0.00005). The LCT group showed a higher median PTH level (MCT: 2.1 pmol/L, LCT: 4.7 pmol/L, p< 0.01) and a higher urinary P excretion (p< 0.001). Mg absorption was also lower with LCT, but retention of Mg exceeded intrauterine values in both groups. Mineral plasma levels were in the normal range in both groups. AP was not different between groups and in the upper part of the reference range, whereas 1,25-(OH)2D levels were above the normal range and also not different between groups. We conclude that with the LCT formula, Ca absorption is slightly lower than with the MCT formula, whereas P absorption is unaffected. The resulting imbalance in absorption is compensated for by an increased urinary excretion of P. We conclude that current recommendations for the maximum Ca/P ratio in preterm formulas (2:1) might be too low in formulas containing only LCT.

Background and aims: We aimed to determine the effects of enteral supplementation of a prebiotic mixture of neutral and acidic oligosaccharides (SCGOS/LCFOS/AOS), who are supposed to improve the development of the immune system and therefore improve the immune response to DTaP-Hib vaccinations in preterm infants.Methods: In a RCT, preterm infants with a gestational age < 32weeks and/or birth weight < 1500g received enteral supplementation of SCGOS/LCFOS/AOS or a placebo (maltodextrin) between days 3-30 of life. Serum samples were taken at 5 and 12 months of age, after the 3thand 4thvaccination respectively. Samples were analyzed by multiplex immune assay (MIA, Luminex).Results: In total, 89 preterm infants at 5 months and 85 infants at 12 months were included. Baseline patient and nutritional characteristics were not different between both groups. Results are shown in table 1. No significant differences were shown (all p>0.05).Conclusions : Enteral supplementation with the prebiotic mixture of neutral and acidic oligosaccharides did not influence the immune response on vaccinations against DTaP-Hib in preterm infants.

Aim: Enteral administration of a prebiotic mixture of neutral and acidic oligosaccharides during the neonatal period in preterm infants may positively affect the Th2 response. Aim was to determine the effect of enteral supplementation of neutral and acidic (scGOS/lcFOS/AOS) oligosaccharides during neonatal period in preterm infants on the incidence of allergic diseases during the first year of life.Methods: In a RCT, preterm infants (GA< 32wks and/or BW< 1500g) were allocated to receive enteral scGOS/lcFOS/AOS supplementation or placebo (maltodextrin) between day 3 and 30 of life. Incidence of allergic disease (atopic dermatitis, bronchial hyperreactivity) was assessed by validated questionnaire. Data were analysed by logistic regression analysis.Results: In total, 113 preterm infants were enrolled in the initial study. Of these 113, 99 were eligible for follow-up (11 died, 3 were excluded). To date, 75 infants participated in our follow-up study. Incidence of atopic dermatitis was not different in scGOS/ lcFOS/AOS- and placebogroup (5/37 (14%)) versus (4/38 (11%)) respectively (p= 0.69, OR 1.33 95%CI 0.33-5.39). Incidence of bronchial hyperreactivity was not different between scGOS/lcFOS/AOS- or placebogroup (10/37 (27%) versus 12/38 (32%)) respectively (p= 0.67, OR 0.80 95%CI 0.30-2.18).Adjustments for confounding factors (maternal education, parental history of atopy, smoking, and presence of pets at home) did not change the results of the primary analysis.Conclusion: Enteral administration of a prebiotic mixture of acidic and neutral oligosaccharides during the neonatal period in preterm infants does not decrease the risk of atopic dermatitis or bronchial hyperreactivity during the first year of life.

Objectives: To investigate protein metabolism and urea production in preterm small for gestational age (SGA) neonates fed a preterm formula (PF) or fortified human milk (FHM).Methods: Ten preterm SGA neonates were fed either their own mothers milk, fortified with a powdered protein mineral supplement or a special preterm formula. Protein metabolism was determined using constant steady-state infusion of L-[ring-2H5]phenylalanine and L-[1–13C]valine. Urea production was determined from steady-state [13C]urea kinetics.Results: Protein intakes were 24% higher in the PF group than in the FHM group. Both kinetic methods showed no difference in protein turnover, synthesis and breakdown between the two groups, but protein accretion was 71–79% higher in the PF group than the FHM group (significance at p<0,05). Urea production rates were not different between the two groups. There was a strong negative correlation between urea production and protein accretion calculated from phenylalanine kinetics but not when calculated from valine kinetics.Conclusions: Both PF and FHM appear equally well tolerated by preterm SGA neonates, but protein accretion is higher in the PF group. It is speculated that even SGA preterm infants tolerate higher protein intakes that may improve their early postnatal growth. Protein intake from human milk source will vary but in practice it seems that even SGA preterm infants would benefit from human milk feeding fortified with a higher amount of protein than 0.7 g. per 100ml. In preterm SGA infants, both phenylalanine and valine kinetic methods can be used to accurately determine protein metabolism.

Objective: Insulin-like growth factor I (IGF-I) is necessary for normal growth and development in infants. Recent research suggested that IGF-I deficiency is associated with the development of oxygen-induced retinopathy of prematurity (1). We hypothesized that low IGF-I levels might be a risk factor for oxygen-induced pulmonary damage in preterm infants, which leads to chronic lung disease (CLD) of prematurity.Methods: We measured growth hormone (GH) secretory patterns and levels of IGF-I and IGF binding protein 3 (IGFBP-3) in 34 preterm infants (gestational age(GA): 25–32 weeks, weights 526-1985 grams) at risk to develop chronic lung disease. Measurements were performed in clinically stable infants, requiring respiratory support. Between the 4th and 12th day of life, 6 h (with hourly intervals) and 24 h (with 6 h intervals) blood samples were taken for the determination of GH. In addition, IGF-I and IGFBP-3 levels were measured in the first blood sample. Results were adjusted for GA and birth weight SD score (BWSDS).Results: No significant differences in GH concentration were found between the different time points studied either in the 6 h or 24 h profiles; GH concentration between infants who developed CLD vs no CLD was not different (mean GH respectively 77±11 vs 79±8 mg/l, p=0.86, adjusted p= 0.56). IGF-I levels were significantly lower in CLD vs no CLD infants even adjusted for GA and BWSDS (respectively 1.3±0.1 vs 1.9±0.2 nmol/l, p=0.02, adjusted p=0.04). IGFBP-3 levels were not different between both groups (CLD 0.60±0.04 mg/l vs no CLD 0.71±0.05 mg/l, p=0.11, adjusted p=0.94).Conclusion: Our results support the hypothesis that IGF-1 deficiency may increase the risk to develop CLD. Since GH levels do not differ between infants who develop CLD and those who do not, differences in IGF-I levels may be explained by a relative GH resistance. Alternatively, levels of IGF-I may be lower due to a decreased production in preterm infants. With respect to the relationship between IGF-I and the development of serious sequelae associated with prematurity (1) our findings are comparable with observations by others). We therefore suggest that IGF-I may play an important role in the development of chronic lung disease of prematurity.

Objective: Insulin-like growth factor I (IGF-I) is necessary for normal growth and development in infants. Recent research suggested that deficiency of IGF-I is associated with the development of oxygen-induced retinopathy of prematurity (1). We hypothesized that low IGF-I levels in might be a risk factor for oxygen-induced pulmonary damage in preterm infants, which causes chronic lung disease (CLD) of prematurity.Methods: We measured growth hormone (GH) secretory patterns and levels of IFG-I and IFG binding protein 3 (IGFBP-3) in 34 preterm infants (gestational ages: 25–32 weeks, weights 526-1985 grams) at risk of developing chronic lung disease. Measurements were performed in clinically stable infants, requiring respiratory support. Between the 4th and 12th day of life, 6 h (with hourly intervals) and 24 h (with 6 h intervals) growth hormone samples were taken. In addition, IGF-I and IGFBP-3 levels were measured in the first blood sample. Results were adjusted for gestational age and birth weight SD score.Results: No significant differences in GH concentration were found between the different time points studied in the 6 h or the 24 h profiles or in infants who developed CLD vs no CLD (mean GH respectively 77±11 vs 79±8 mg/l, p=0.86, adjusted p= 0.56). IGF-I levels were significantly lower in CLD vs no CLD even adjusted for gestational age and birth weight SD score (respectively 1.3±0.1 vs 1.9±0.2 nmol/l, p=0.02, adjusted p=0.04). IGFBP-3 levels were not significantly different between both groups (CLD 0.60±0.04 mg/l vs no CLD 0.71±0.05 mg/l, p=0.11, adjusted p=0.94).Conclusion: Our results support the hypothesis that IGF-1 deficiency may increase the risk of development of CLD. Since GH levels did not differ between infants who did developed CLD and those who did, differences in IGF-I levels may be explained by relative growth hormone resistance. Alternatively, levels may be lower by a decreased production of IGF-I in preterm infants. Our findings are comparable to those find by others with respect to the relationship between IGF-I and the development of retinopathy of prematurity. IGF-I may play an important role in the development of serious squelae associated with prematurity, which requires further investigation.

Objectives: To determine with a systematic review (SR) if Vitamin D, compared to placebo or no treatment, reduces rickets in healthy, full term infants.Methods: Types of studies: Randomized controlled trials (RCT) or quasi-randomized controlled trials assessing the efficacy of vitamin D in reducing rickets in newborn infants. Types of participants: Infants born at term (>=37 weeks gestational age). Types of interventions: Vitamin D given orally or i.m. given at least for 4 weeks versus placebo or no intervention. Types of outcome measures: Primary outcome measures include clinical sign of rickets; secondary outcome measures include any of the following: bone mineralization, linear growth, radiological signs of rickets. Search strategy: A search was done on MEDLINE using the highly sensitive strategy of Dickersin, modified to exclude studies on preterm and low birth weight newborn infants. Methods of the systematic review: Standard Cochrane systematic review methods were planned. A subgroup analysis was planned to evaluate effects in formula- and breast-fed infants.Results and conclusions: Only two RCT fulfilling the inclusion criteria were retrived. One study was excluded because comparison was made between different doses of vitamin D. No meta-analysis was therefore performed. The single RCT enrolled 18 healthy, full term, breast-fed infants (9 placebo, 9 vitamin D at 400 U/die); 13 infants were followed up to 52 weeks (7 placebo, 6 vitamin D). Bone mineral content was higher in supplemented infants at 12 weeks, but the difference was no longer significant at 26 and 52 weeks. No infant was reported to have rickets. Based on the results of this review it is concluded that current practice and guidelines are not based on data coming from consistent, well conducted RCTs, but from data coming from observational studies.

Glucose utilisation and oxidation were measured at day 8 in 19 stable VLBW infants (b.w. 1389±300g, g.a. 32±2wks) receiving cont. TPN of 76±4 kcal/kg/d. Glucose utilisation was measured by ind. calorimetry during 8 hrs and glucose oxidation by measurement of 13CO2/CO2ratio in breath by IRMS during primed constant infusion of U-13C glucose (2.7 μmol/kg/h). Results ± S.D.:In 5 patients the rate of glucose appearance (Ra) in plasma was quantified from the enrichment of 13C glucose (m+6) by GCMS analysis. The Ra was 10.8±9.6% above glucose intake representing endog. gluc.prod. and recycling. Therefore the max. plasma glucose oxidation is 5.85±1.42 mg/kg/min. We conclude that during this feeding regimen: 1) 66±13% of the Ra is directly oxidized representing 75±18% of the glucose intake; 2) endogenous glucose production and glucose recycling is low; 3) glucose utilisation is close to glucose oxidation indicating limited lipogenesis.

Formulas specially designed for preterm infants contain up to 50% MCT. The effects of MCT(C8 and C10) on growth and composition of weight gain were studied in infants receiving formula (Nutricia, Holland) with 5% or 40% of fat as MCT, providing 12 g carbohydrates-, 3.3 g protein and 6.8 g fat per kg·day. 72 hr balance studies were performed at 4 weeks of age. Simultaneously, 6 hr periods of indirect calorimetry were performed to measure substrate oxidation. Nitrogen and fat deposition was calculated from intake, losses and oxidation. As mean ± 1sd:Conclusions: 1 In stable, growing preterm infants fed 120 kcal/kg·d, addition of MCT to the feeding results in slightly better fat absorption. 2 However, this does not promote weight gain or nitrogen retention but only increases fat deposition.

Formulas specially designed for preterm infants contain up to 50% MCT because of their almost complete absorption. The effects of MCT(C8 and C10) on mineral absorption were studied in infants receiving formula (Nutricia, Holland) with 5%(LCT group) or 40%(MCT group) of fat as MCT, providing 80 mg P-, 152 mg Ca- and 120 kcal/kg·d,+ 600 IU/day vit D. 72 hr balance studies were performed at 4 weeks of age. Values:mean ± 1sd or median with interquartile range. Plasma levels (MCT vs LCT) of Ca(2.4±0.1 vs 2.4±0.1 mmol/L), P(2.2±0.3 vs 2.3±0.2 mmol/L) and Alkaline Phosphatase (273±74 vs 295±43 IU/L) were in the normal range.Conclusions: 1 Both formulas show satisfactory calcium and phosphate retention, with normal plasma levels. 2 Calcium absorption, but not phosphate absorption was lower with the LCT formula. 3 The elevation of PTH and of urinary P excretion suggest that in preterm LCT formula, Ca/P ratio should be slightly higher than 2:1.