J.B. van Goudoever

Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infants own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable-growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.

Continuous stroke volume monitoring by modelling flow from non-invasive measurement of arterial pressure in humans under orthostatic stress

The relationship between aortic flow and pressure is described by a three-element model of the arterial input impedance, including continuous correction for variations in the diameter and the compliance of the aorta (Modelflow). We computed the aortic flow from arterial pressure by this model, and evaluated whether, under orthostatic stress, flow may be derived from both an invasive and a non-invasive determination of arterial pressure. In 10 young adults, Modelflow stroke volume (MFSV) was computed from both intra-brachial arterial pressure (IAP) and non-invasive finger pressure (FINAP) measurements. For comparison, a computer-controlled series of four thermodilution estimates (thermodilution-determined stroke volume; TDSV) were averaged for the following positions: supine, standing, head-down tilt at 20 degrees (HDT20) and head-up tilt at 30 degrees and 70 degrees (HUT30 and HUT70 respectively). Data from one subject were discarded due to malfunctioning thermodilution injections. A total of 155 recordings from 160 series were available for comparison. The supine TDSV of 113+/-13 ml (mean+/-S.D.) dropped by 40% to 68+/-14 ml during standing, by 24% to 86+/-12 ml during HUT30, and by 51% to 55+/-15 ml during HUT70. During HDT20, TDSV was 114+/-13 ml. MFSV for IAP underestimated TDSV during HDT20 (-6+/-6 ml; P<0.05), but that for FINAP did not (-4+/-7 ml; not significant). For HUT70 and standing, MFSV for IAP overestimated TDSV by 11+/-10 ml (HUT70; P<0.01) and 12+/-9 ml (standing; P<0.01). However, the offset of MFSV for FINAP was not significant for either HUT70 (3+/-8 ml) or standing (3+/-9 ml). In conclusion, due to orthostasis, changes in the aortic transmural pressure may lead to an offset in MFSV from IAP. However, Modelflow correctly calculated aortic flow from non-invasively determined finger pressure during orthostasis.

Functional outcomes and participation in young adulthood for very preterm and very low birth weight infants: the Dutch Project on Preterm and Small for Gestational Age Infants at 19 years of age.

OBJECTIVE. Young adults who were born very preterm or with a very low birth weight remain at risk for physical and neurodevelopmental problems and lower academic achievement scores. Data, however, are scarce, hospital based, mostly done in small populations, and need additional confirmation. METHODS. Infants who were born at <32 weeks of gestation and/or with a birth weight of <1500 g in the Netherlands in 1983 (Project on Preterm and Small for Gestational Age Infants) were reexamined at age 19. Outcomes were adjusted for nonrespondents using multiple imputation and categorized into none, mild, moderate, or severe problems. RESULTS. Of 959 surviving young adults, 74% were assessed and/or completed the questionnaires. Moderate or severe problems were present in 4.3% for cognition, 1.8% for hearing, 1.9% for vision, and 8.1% for neuromotor functioning. Using the Health Utility Index and the London Handicap Scale, we found 2.0% and 4.5%, respectively, of the young adults to have ≥3 affected areas in activities and participation. Special education or lesser level was completed by 24%, and 7.6% neither had a paid job nor followed any education. Overall, 31.7% had ≥1 moderate or severe problems in the assessed areas. CONCLUSIONS. A total of 12.6% of young adults who were born very preterm and/or with a very low birth weight had moderate or severe problems in cognitive or neurosensory functioning. Compared with the general Dutch population, twice as many young adults who were born very preterm and/or with a very low birth weight were poorly educated, and 3 times as many were neither employed nor in school at age 19.

Pulse contour cardiac output derived from non-invasive arterial pressure in cardiovascular disease

Pulse contour methods determine cardiac output semi‐invasively using standard arterial access. This study assessed whether cardiac output can be determined non‐invasively by replacing the intra‐arterial pressure input with a non‐invasive finger arterial pressure input in two methods, Nexfin CO‐trek® and Modelflow®, in 25 awake patients after coronary artery bypass surgery. Pulmonary artery thermodilution cardiac output served as a reference. In the supine position, the mean (SD) differences between thermodilution cardiac output and Nexfin CO‐trek were 0.22 (0.77) and 0.44 (0.81) l.min−1, for intra‐arterial and non‐invasive pressures, respectively. For Modelflow, these differences were 0.70 (1.08) and 1.80 (1.59) l.min−1, respectively. Similarly, in the sitting position, differences between thermodilution cardiac output and Nexfin CO‐trek were 0.16 (0.78) and 0.34 (0.83), for intra‐arterial and non‐invasive arterial pressure, respectively. For Modelflow, these differences were 0.58 (1.11) and 1.52 (1.54) l.min−1, respectively. Thus, Nexfin CO‐trek readings were not different from thermodilution cardiac output, for both invasive and non‐invasive inputs. However, Modelflow readings differed greatly from thermodilution when using non‐invasive arterial pressure input.

Intelligence of very preterm or very low birthweight infants in young adulthood

Objective: To examine the effect of intrauterine and neonatal growth, prematurity and personal and environmental risk factors on intelligence in adulthood in survivors of the early neonatal intensive care era. Methods: A large geographically based cohort comprised 94% of all babies born alive in the Netherlands in 1983 with a gestational age below 32 weeks and/or a birth weight >1500 g (POPS study). Intelligence was assessed in 596 participants at 19 years of age. Intrauterine and neonatal growth were assessed at birth and 3 months of corrected age. Environmental and personal risk factors were maternal age, education of the parent, sex and origin. Results: The mean (SD) IQ of the cohort was 97.8 (15.6). In multiple regression analysis, participants with highly educated parents had a 14.2-point higher IQ than those with less well-educated parents. A 1 SD increase in birth weight was associated with a 2.6-point higher IQ, and a 1-week increase in gestational age was associated with a 1.3-point higher IQ. Participants born to young mothers (<25 years) had a 2.7-point lower IQ, and men had a 2.1-point higher IQ than women. The effect on intelligence after early (symmetric) intrauterine growth retardation was more pronounced than after later (asymmetric) intrauterine or neonatal growth retardation. These differences in mean IQ remained when participants with overt handicaps were excluded. Conclusions: Prematurity as well as the timing of growth retardation are important for later intelligence. Parental education, however, best predicted later intelligence in very preterm or very low birthweight infants.

Risk factors for sensorineural hearing loss in NICU infants compared to normal hearing NICU controls

OBJECTIVES To evaluate independent etiologic factors associated with sensorineural hearing loss in infants who have been admitted to the neonatal intensive care unit compared to normal hearing controls. METHOD Between 2004 and 2009, 3366 infants were admitted to the neonatal intensive care unit of Sophia Childrens Hospital, of which 3316 were screened with AABR. A total of 103 infants were referred for auditory brainstem response analysis after failure on neonatal hearing screening. We included all infants diagnosed with sensorineural hearing loss. Each patient was matched with two normal hearing controls from the neonatal intensive care unit of the same gender and postconceptional age. The following risk factors were studied: birth weight, dysmorphic features, APGAR scores (at 1, 5 and 10 min), respiratory distress (IRDS), CMV infection, sepsis, meningitis, cerebral bleeding, cerebral infarction, hyperbilirubinemia requiring phototherapy, peak total bilirubin level, furosemide, dexamethason, vancomycin, gentamycin and tobramycin administration. RESULTS Fifty-eight infants were diagnosed with sensorineural hearing loss: 26 girls and 32 boys. The incidence of dysmorphic features (P=0.000), low APGAR score (1 min) (P=0.01), sepsis (P=0.003), meningitis (P=0.013), cerebral bleeding (P=0.016) and cerebral infarction (P=0.000) were significantly increased in infants with sensorineural hearing loss compared to normal hearing controls (n=116). CONCLUSION Dysmorphic features, low APGAR scores at 1 min, sepsis, meningitis, cerebral bleeding and cerebral infarction are associated with sensorineural hearing loss independent of neonatal intensive care unit admittance.

Growth and body composition in preterm infants with bronchopulmonary dysplasia

Objective: To compare growth and body composition in preterm infants with bronchopulmonary dysplasia (BPD) with normal healthy term infants during the first year of life. Design: Twenty nine preterm infants with BPD (mean (SD) gestational age 27.1 (1.6) weeks; birth weight 852 (173) g) were followed prospectively. Anthropometry and body composition determined by total body electrical conductivity were measured and compared with those of healthy term infants at the same post-term age. Results: In infants with BPD, the mean weight standard deviation scores (SD scores) 6 weeks after term were significantly lower (−1.44 and −2.68, boys and girls respectively) than in healthy term infants of the same age and did not improve during the first year. The mean length SD score was significantly lower in infants with BPD 6 weeks after term than in healthy term infants of the same age, and, although it improved significantly during the first year, the mean length SD score in girls with BPD was significantly below 0 12 months after term. In infants with BPD, the mean free fat mass (FFM) SD score and the mean total body fat (TBF) SD score at 6 weeks post-term age were significantly below 0. The mean FFM SD scores (−1.01 and −2.56, boys and girls respectively) and the mean TBF SD scores (−1.14 and −2.40, boys and girls respectively) 12 months after term were significantly lower than in healthy term infants of the same age. Conclusions: Preterm infants with BPD have impaired growth, with a deficit in TBF and FFM already 6 weeks after term; FFM and TBF remain low compared with healthy term infants during the first year of life. Nutritional intervention studies in infants with BPD are needed to evaluate if nutrition is the major determinant of growth and body composition or if this pattern of growth in preterm infants with BPD is the result of disturbed endocrine control.

Whole-body protein turnover in preterm appropriate for gestational age and small for gestational age infants: comparison of [15N]glycine and [1-(13)C]leucine administered simultaneously.

ABSTRACT: Measurements of whole-body protein turnover in preterm infants have been made using different stable isotope methods. Large variation in results has been found, which could be due to different clinical conditions and/or the use of different tracers. We studied 14 appropriate for gestational age and nine small for gestational age orally fed preterm infants using [15N]glycine and [1-13C]leucine simultaneously, which allowed us to make a comparison of commonly used methods to calculate whole-body protein turnover. Whole-body protein turnover was calculated from 15N enrichment in urinary ammonia and urea after [15N]-glycine administration and from the 13C enrichment in expired CO2 after administration of [1-13C]leucine. Enrichment of α-ketoisocaproic acid after [1-13C]leucine constant infusion was measured as a direct parameter of whole-body protein turnover. Group means for whole-body protein turnover using [15N]glycine or [1-13C]leucine ranged from 10 to 14 g.kg-1.d-1, except when using the end product method that assumes a correlation between leucine oxidation and total nitrogen excretion. We found very low 15N enrichment of urinary urea in the majority of small for gestational age infants. These infants also had a lower nitrogen excretion in urine and oxidized less leucine. Nitrogen balance was higher in small for gestational age infants (416 pm 25 mg±kg-1d-1) compared with appropriate for gestational age infants (374 pm 41 mg±kg-1d-1, p= 0.003). [15N]Glycine does not seem to exchange its label with the body nitrogen pool to a significant degree and is therefore not always suitable as a carrier for 15N in protein turnover studies in premature infants.

Glucose kinetics and glucoregulatory hormone levels in ventilated preterm infants on the first day of life.

ABSTRACT: Glucose production and oxidation were measured in ventilated preterm appropriate-for-gestational-age and small-for-gestational-age infants on the first day of life. Using a new technique of NaH13CO3 infusion followed by a [U-13C]glucose infusion, we measured glucose oxidation rates without measuring the CO2 production rate. Infants were studied at 18 ± 4 h (mean ± 1 SD) of life and received parenterally administered glucose only (4.2 ± 0.5 mg·kg−1 · min−1). In 13 of 16 patients, the glucose production rate exceeded 1.0 mg·kg−1·min−1. Infants born from mothers who had been receiving steroids antenatally had higher glucose production rates (2.3 ± 1.1 mg·kg−1·min−1) compared with infants from mothers who had not (1.1 ± 0.8 mg · kg−1 · min−1, p = 0.036). The glucose oxidized (2.9 ±1.0 mg · kg−1 · min−1) was lower than the amount of glucose infused (p = 0.005) and was not different for appropriate-for-gestational-age and small-for-gestational-age infants. Plasma levels of glucose, insulin, glucagon, and total IGF-I were not correlated with glucose metabolism on the first day of life. Total IGF-II levels were negatively correlated with the rate of glucose appearance. We conclude that preterm infants on the first day of life receiving a glucose infusion of 4.2 mg · kg−1 · min−1 continue to produce glucose. The glucose oxidation rate is lower than the glucose infusion rate and the contribution of glucose oxidation to the total energy expenditure is limited.

Lysine kinetics in preterm infants: the importance of enteral feeding

Introduction: Lysine is the first limiting essential amino acid in the diet of newborns. First pass metabolism by the intestine of dietary lysine has a direct effect on systemic availability. We investigated whether first pass lysine metabolism in the intestine is high in preterm infants, particularly at a low enteral intake. Patients and methods: Six preterm infants (birth weight 0.9 (0.1) kg) were studied during two different periods: period A (n = 6): 40% of intake administered enterally, 60% parenterally; lysine intake 92 (6) μmol/(kg×h); and period B (n = 4): 100% enteral feeding; lysine intake 100 (3) μmol/(kg×h). Dual stable isotope tracer techniques were used to assess splanchnic and whole body lysine kinetics. Results: Fractional first pass lysine uptake by the intestine was significantly higher during partial enteral feeding (period A 32 (10)% v period B 18 (7)%; p<0.05). Absolute uptake was not significantly different. Whole body lysine oxidation was significantly decreased during full enteral feeding (period A 44 (9) v period B 17 (3) μmol/(kg×h); p<0.05) so that whole body lysine balance was significantly higher during full enteral feeding (period A 52 (25) v period B 83 (3) μmol/(kg×h); p<0.05). Conclusions: Fractional first pass lysine uptake was much higher during partial enteral feeding. Preterm infants receiving full enteral feeding have lower whole body lysine oxidation, resulting in a higher net lysine balance, compared with preterm infants receiving partial enteral feeding. Hence parenterally administered lysine is not as effective as dietary lysine in promoting protein deposition in preterm infants.