Kristin Brække

Enhanced feeding in very-low-birth-weight infants may cause electrolyte disturbances and septicemia – A randomized, controlled trial

BACKGROUND & AIMSnHigh supply of protein and energy has been introduced to very-low-birth-weight infants to improve growth and cognitive development. The aim of this study was to compare two different feeding strategies on postnatal growth and clinical outcome during neonatal hospitalization.nnnMETHODSnFifty very-low-birth-weight infants were randomized to either an enhanced or a standard feeding protocol within 24xa0h after birth. Chi-square and T-tests were applied.nnnRESULTSnFirst week protein, fat and energy supply was significantly higher in the intervention group compared to the control group (all Pxa0<xa00.001). After inclusion of 50 patients we observed a higher occurrence of septicemia in the intervention group, 63% vs. 29% (Pxa0=xa00.02), and no more patients were included. The infants in the intervention group demonstrated improved postnatal growth, but they also disclosed significant electrolyte deviations during the first week of life with hypophosphatemia, hypokalemia and hypercalcemia. First week phosphate nadir was lower in the infants experiencing septicemia (1.23xa0(0.50)xa0mmol/L) as compared to the infants without (1.61xa0(0.61)xa0mmol/L) (Pxa0=xa00.03).nnnCONCLUSIONnOur study implies that enhanced feeding may induce electrolyte imbalances in VLBW infants, and that deleterious side effects similar to those seen in refeeding syndrome may occur. ClinicalTrials.gov, number NCT01103219 and the EudraCT number is 2010-020464-38.

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 (nu200a=u200a24) or a control (nu200a=u200a26) 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 (Pu200a=u200a0.03) and a higher proportion of infants small-for-gestational age (Pu200a=u200a0.04) 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 (Pu200a<u200a0.001) and 4.0 (3.9–4.2) versus 3.2 (3.1–3.3) g · kg−1 · day−1 (Pu200a<u200a0.001). The infants in the intervention group regained birth weight faster (Pu200a=u200a0.001) and maintained their z scores for weight and head circumference from birth to 36 weeks’ postmenstrual age (both Pu200a<u200a0.001). 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 (Pu200a<u200a0.001). 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 (Pu200a=u200a0.04). 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.

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.

Neonatal Morbidity and 1-Year Survival of Extremely Preterm Infants.

This is a prospective, population-based cohort study comparing survival and neonatal morbidity in infants born at 22 to 26 weeks’ gestation in Norway in 2013–2014. OBJECTIVE: To determine 1-year survival and major neonatal morbidities (intracranial hemorrhage grade >2, cystic periventricular leukomalacia, retinopathy of prematurity grade >2, necrotizing enterocolitis, severe bronchopulmonary dysplasia) among extremely preterm infants in Norway in 2013–2014, and to compare the results to the first Norwegian Extreme Prematurity Study 1999–2000 and similar contemporary European population-based studies. METHODS: Population-based study of all infants born at 22 through 26 weeks’ gestation in Norway in 2013–2014. Prospectively collected data were obtained by linking data in the Norwegian Neonatal Network to the Medical Birth Registry of Norway. RESULTS: Of 420 infants (incidence 3.5 per 1000 births), 145 were stillborn (34.5%), 275 were live-born (82.3% of the 334 fetuses alive at admission for obstetrical care), and 251 (91.3% of live-born infants) were admitted to a neonatal unit. The survival among live-born infants was 18% at 22 weeks, 29% at 23 weeks, 56% at 24 weeks, 84% at 25 weeks and 90% at 26 weeks (for each week increment in gestational age: odds ratio 3.3; 95% confidence interval, 2.4–4.4). Among infants surviving to 1 year of age, major neonatal morbidity was diagnosed in 55%. Decreasing gestational age was moderately associated with rates of major morbidity (odds ratio 1.6; 95% confidence interval, 1.2–2.2). CONCLUSIONS: Compared to the previous 1999–2000 cohort, the rate of stillbirth before admission to an obstetrical unit increased, whereas the survival rate among live born infants was similar in our 2013–2014 cohort. Neonatal morbidity rates remain high among extremely preterm infants.

Improved Visual Perception in Very Low Birth Weight Infants on Enhanced Nutrient Supply

Background: Optimal nutrient supply to very low birth weight (VLBW: BW <1,500 g) infants is important for growth and neurodevelopment. Growth restriction is common among these infants and may be associated with neurocognitive impairments. Objectives: To compare an enhanced nutrient supply to a routine supply given to VLBW infants and to evaluate the effects on visual perception of global form and motion measured by visual event-related potentials (VERP). Methods: A total of 50 VLBW infants were randomized to an intervention group that received an increased supply of energy, protein, fat, essential fatty acids, and vitamin A or a control group that received standard nutritional care. At 5 months corrected age the infants were examined using VERP to investigate the responses to global form and motion. VERP were analysed at the first (f1) and third (f3) harmonics of the stimulus frequency. Results: Data from 31 subjects were eligible for analysis. The motion VERP responses for the f1 and f3 components were stronger in the area near the posterior midline region in the intervention group compared to the controls in the group analyses (p = 0.02 and p = 0.001, respectively). Conclusion: The results showed a more consistent response to global motion among infants receiving enhanced nutrition. The intervention may have improved visual perception of global motion.

Intestinal microbiota development and gestational age in preterm neonates

The intestinal microbiota is an important contributor to the health of preterm infants, and may be destabilized by a number of environmental factors and treatment modalities. How to promote the development of a healthy microbiota in preterm infants is largely unknown. We collected fecal samples from 45 breastfed preterm very low birth weight (birth weightu2009<u20091500u2009g) infants from birth until 60 days postnatal age to characterize the intestinal microbiota development during the first weeks of life in preterm infants. Fecal microbiota composition was determined by 16S rRNA amplicon sequencing. The main driver of microbiota development was gestational age; antibiotic use had strong but temporary effects and birth mode had little influence. Microbiota development proceeded in four phases indicated by the dominance of Staphylococcus, Enterococcus, Enterobacter, and finally Bifidobacterium. The Enterococcus phase was only observed among the extremely premature infants and appeared to delay the microbiota succession. The results indicate that hospitalized preterm infants receiving breast milk may develop a normal microbiota resembling that of term infants.

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.

A Novel Oculo-Skeletal syndrome with intellectual disability caused by a particular MAB21L2 mutation.

We describe a novel recognizable phenotype characterized by anophthalmia, a distinctive skeletal dysplasia and intellectual disability. Radiographic anomalies include severe rhizomelic shortness of the limbs and abnormal joint formation. Recent exome studies showed that these characteristics are part of the phenotypic spectrum of MAB21L2 gene mutations which cause a range of structural eye malformations such as microphthalmia/anophthalmia and ocular coloboma. The two unrelated individuals described here in detail are heterozygous carriers of the same de novo missense mutation c.151Cxa0>xa0T (p.Arg51Cys) in MAB21L2.

Plasma calprotectin as inflammation marker in pregnancies complicated by diabetes mellitus and superimposed preeclampsia

OBJECTIVEnWe hypothesized that pregnancies complicated by diabetes mellitus with or without preeclampsia show an elevated systemic inflammatory response evaluated by the inflammation markers calprotectin and high-sensitivity C-reactive protein (hsCRP).nnnSTUDY DESIGNnThird trimester EDTA plasma and serum from 138 women with diabetes mellitus (type 1, n=53; type 2, n=11; gestational diabetes mellitus (GDM), n=63; diabetes mellitus with preeclampsia, n=11) were analyzed for calprotectin and hsCRP and compared to previously published results from 37 healthy and 27 preeclamptic pregnancies.nnnRESULTSnMedian plasma calprotectin concentration was intermediate in women with GDM as compared to healthy and preeclamptic pregnancies (729 vs 552 and 1081μg/L, P=.006 and P=.001, respectively). In diabetic pregnancies with preeclampsia, median plasma calprotectin concentration was elevated as compared to controls, but not different from women with preeclampsia alone (969 vs 552 and 1081μg/L, P=.01 and P=.1, respectively). hsCRP was only elevated in type 2 diabetic pregnancies as compared to healthy pregnancies (6.6 vs 3.8mg/L, P=.02).nnnCONCLUSIONnElevated plasma calprotectin concentrations in GDM may reflect an accentuated inflammatory process, possibly contributing to the augmented preeclampsia risk. Increased plasma calprotectin in diabetic pregnancies with preeclampsia may originate from the excess systemic inflammatory response associated with preeclampsia.

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