Astrid N. Almaas

Enhanced Feeding and Diminished Postnatal Growth Failure in Very-Low-Birth-Weight Infants

Objective: The aim of the present study was to determine whether an increased supply of energy, protein, essential fatty acids, and vitamin A reduces postnatal growth failure in very-low-birth-weight infants. Methods: Fifty infants with birth weight <1500 g were randomized to an intervention (n = 24) or a control (n = 26) feeding protocol within 24 hours after birth. Forty-four infants were included in the final analysis. This study was discontinued because of an increased occurrence of septicemia in the intervention group. Results: The intervention group had a lower mean birth weight (P = 0.03) and a higher proportion of infants small-for-gestational age (P = 0.04) than the control group. Other baseline characteristics were similar. The median (interquartile range) energy and protein supplies during the first 4 weeks of life were higher in the intervention group: 139 (128–145) versus 126 (121–128) kcal · kg−1 · day−1 (P < 0.001) and 4.0 (3.9–4.2) versus 3.2 (3.1–3.3) g · kg−1 · day−1 (P < 0.001). The infants in the intervention group regained birth weight faster (P = 0.001) and maintained their z scores for weight and head circumference from birth to 36 weeks’ postmenstrual age (both P < 0.001). The median (interquartile range) growth velocity was 17.4 (16.3–18.6) g · kg−1 · day−1 in the intervention group and 13.8 (13.2–15.5) g · kg−1 · day−1 in the control group (P < 0.001). In line with the improved growth in the intervention group, the proportion of growth-restricted infants was 11 of 23 both at birth and at 36 weeks’ postmenstrual age, whereas this proportion increased among the controls from 4 of 21 to 13 of 21 (P = 0.04). Conclusions: Enhanced supply of energy, protein, essential fatty acids, and vitamin A caused postnatal growth along the birth percentiles for both weight and head circumference.

Long-Chain Polyunsaturated Fatty Acids and Cognition in VLBW Infants at 8 years: an RCT

OBJECTIVE: To test the hypothesis that supplementation with the long chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and arachidonic acid (AA) to very low birth weight (VLBW) infants would improve long-term cognitive functions and influence neuroanatomical volumes and cerebral cortex measured by MRI. METHODS: The current study is a follow-up of a randomized, double-blinded, placebo-controlled study of supplementation with high-dose DHA (0.86%) and AA (0.91%) to 129 VLBW infants fed human milk. Ninety-eight children participated at 8 years follow-up and completed a broad battery of cognitive tests. Eighty-one children had cerebral MRI scans of acceptable quality. RESULTS: There were no significant differences between the intervention group and the control group on any of the cognitive measures. Equally, MRI data on segmental brain volumes and cerebral cortex volume, area, and thickness suggested no overall group effect. CONCLUSIONS: This study is the first long-term follow-up of a randomized controlled trial with supplementation of DHA and AA to human milk fed VLBW infants investigating both cognitive functions and brain macrostructure measured by MRI. No cognitive or neuroanatomical effects of the supplementation were detected at 8 years of age.

Urinary Metabolite Profiles in Premature Infants Show Early Postnatal Metabolic Adaptation and Maturation

Objectives: Early nutrition influences metabolic programming and long-term health. We explored the urinary metabolite profiles of 48 premature infants (birth weight < 1500 g) randomized to an enhanced or a standard diet during neonatal hospitalization. Methods: Metabolomics using nuclear magnetic resonance spectroscopy (NMR) was conducted on urine samples obtained during the first week of life and thereafter fortnightly. Results: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group. Enhanced nutrition did not appear to affect the urine profiles to an extent exceeding individual variation. However, in all infants the glucogenic amino acids glycine, threonine, hydroxyproline and tyrosine increased substantially during the early postnatal period, along with metabolites of the tricarboxylic acid cycle (succinate, oxoglutarate, fumarate and citrate). The metabolite changes correlated with postmenstrual age. Moreover, we observed elevated threonine and glycine levels in first-week urine samples of the small for gestational age (SGA; birth weight < 10th percentile for gestational age) as compared to the appropriate for gestational age infants. Conclusion: This first nutri-metabolomics study in premature infants demonstrates that the physiological adaptation during the fetal-postnatal transition as well as maturation influences metabolism during the breastfeeding period. Elevated glycine and threonine levels were found in the first week urine samples of the SGA infants and emerged as potential biomarkers of an altered metabolic phenotype.

Enhanced Nutrient Supply to Very Low Birth Weight Infants is Associated with Improved White Matter Maturation and Head Growth

Background: Extrauterine growth restriction is common among very low birth weight infants (VLBW, BW <1,500 g). Optimal postnatal nutrient supply is essential to limit growth restriction and ensure adequate growth and neurodevelopment. Objectives: We compared an enhanced postnatal nutrient supply to a standard supply and evaluated the effects on growth velocity, head circumference growth and cerebral maturation - the latter by magnetic resonance diffusion tensor imaging (DTI). We hypothesized increased growth velocity, head circumference growth and decreased mean diffusivity (MD) in cerebral white matter (WM) areas, suggesting improved cerebral maturation among infants on the enhanced nutrient supply. Methods: In this randomized controlled trial, infants on the enhanced nutrient supply received increased amounts of energy, protein, fat, essential fatty acids and vitamin A until discharge. DTI was performed close to term equivalent age. Outcomes were growth velocity, head circumference growth and WM mean diffusivity. Results: Among the 50 included infants, 14 in the intervention group and 11 controls underwent a successful DTI. Infants on the enhanced diet achieved improved growth velocity (16.5 vs. 13.8 g/kg/day, p = 0.01) and increased head circumference (Δz score: 0.24 vs. -0.12, p = 0.15). A significantly lower MD was seen in a large WM area such as the superior longitudinal fasciculi (1.19 × 10-3 vs. 1.24 × 10-3 mm2/s, p = 0.04, adjusted for age when scanned). Conclusions: Enhanced nutrient supply to VLBW infants is associated with improved growth velocity, increased head circumference growth and decreased regional WM mean diffusivity, suggesting improved maturation of cerebral connective tracts.

Diffusion tensor imaging and behavior in premature infants at 8 years of age, a randomized controlled trial with long-chain polyunsaturated fatty acids

BACKGROUND Very low birth weight (VLBW, birth weight<1500 g) children have increased risk of behavioral problems. Diffusion tensor imaging (DTI) of the brain shows reduced white matter maturation. Long-chain polyunsaturated fatty acids are hypothesized to improve both myelination and behavioral outcome. AIMS To test the hypothesis that postnatal supplementation with docosahexaenoic acid (DHA) and arachidonic acid (AA) to very low birth weight infants would influence cerebral white matter measured by DTI and improve behavioral outcome at 8 years of age. STUDY DESIGN Eight-year follow-up of a randomized, double-blinded, placebo-controlled study of postnatal supplementation with DHA and AA to 129 VLBW infants fed human milk. SUBJECTS Ninety-eight children (76%) met for follow-up at 8 years. OUTCOME MEASURES Cerebral white matter measured by DTI. Behavioral outcome measured by Strengths and Difficulties questionnaire and selected scales from the Child Behavior Checklist. RESULTS No significant differences between the intervention group and the control group were found on white matter microstructure or behavioral data. A non-significant finding of higher fractional anisotropy (FA) in a cluster in the corpus callosum of the intervention group is discussed. CONCLUSIONS The present study is the first long-term follow-up of a randomized controlled trial with DHA and AA to human milk fed VLBW infants exploring cerebral white matter microstructure measured by DTI and parent-reported behavioral problems. No effects on white matter microstructure or behavioral outcome were observed at 8 years of age.

Increased levels of phthalates in very low birth weight infants with septicemia and bronchopulmonary dysplasia.

Very low birth weight infants (VLBW; birth weight<1500g) are exposed to potentially harmful phthalates from medical devices during their hospital stay. We measured urinary phthalate concentrations among hospitalized VLBW infants participating in a nutritional study. Possible associations between different phthalates and birth weight (BW), septicemia and bronchopulmonary dysplasia (BPD) were evaluated. Forty-six VLBW infants were enrolled in this randomized controlled nutritional study. The intervention group (n=24) received increased quantities of energy, protein, fat, essential fatty acids and vitamin A, as compared to the control group (n=22). The concentrations of 12 urinary phthalate metabolites were measured, using high-performance liquid chromatography coupled to tandem mass spectrometry, at 3 time points during the first 5weeks of life. During this study, the levels of di (2-ethylhexyl) phthalate (DEHP) metabolites decreased, whereas an increasing trend was seen regarding metabolites of di-iso-nonyl phthalate (DiNP). Significantly higher levels of phthalate metabolites were seen in infants with lower BW and those diagnosed with late onset septicemia or BPD. A significant positive correlation between the duration of respiratory support and DEHP metabolites was observed (p≤0.01) at 2.9weeks of age. Birth weight was negatively associated with urinary phthalate metabolite concentrations. Infants with lower BW and those diagnosed with septicemia or BPD experienced prolonged exposure from medical equipment containing phthalates, with subsequent higher levels of phthalate metabolites detected. Clinical Trial Registration no.: NCT01103219.

Enhanced nutrition improves growth and increases blood adiponectin concentrations in very low birth weight infants

Background Adequate nutrient supply is essential for optimal postnatal growth in very low birth weight (VLBW, birth weight<1,500 g) infants. Early growth may influence the risk of metabolic syndrome later in life. Objective To evaluate growth and blood metabolic markers (adiponectin, leptin, and insulin-like growth factor-1 (IGF-1)) in VLBW infants participating in a randomized nutritional intervention study. Design Fifty VLBW infants were randomized to an enhanced nutrient supply or a standard nutrient supply. Thirty-seven infants were evaluated with growth measurements until 2 years corrected age (CA). Metabolic markers were measured at birth and 5 months CA. Results Weight gain and head growth were different in the two groups from birth to 2 years CA (weight gain: pinteraction=0.006; head growth: pinteraction=0.002). The intervention group improved their growth z-scores after birth, whereas the control group had a pronounced decline, followed by an increase and caught up with the intervention group after discharge. At 5 months CA, adiponectin concentrations were higher in the intervention group and correlated with weight gain before term (r=0.35) and nutrient supply (0.35≤r≤0.45). Leptin concentrations correlated with weight gain after term and IGF-1 concentrations with length growth before and after term and head growth after term (0.36≤r≤0.53). Conclusion Enhanced nutrient supply improved early postnatal growth and may have prevented rapid catch-up growth later in infancy. Adiponectin concentration at 5 months CA was higher in the intervention group and correlated positively with early weight gain and nutrient supply. Early nutrition and growth may affect metabolic markers in infancy. Clinical Trial Registration (ClinicalTrials.gov) no.: NCT01103219