Enhanced nutrient supply and intestinal microbiota development in very low birth weight infants.

BACKGROUND: Promoting a healthy intestinal microbiota may have positive effects on short- and long-term outcomes in very low birth weight (VLBW; BW < 1500 g) infants. Nutrient supply influences the intestinal microbiota. METHODS: Fifty VLBW infants were randomized to an intervention group receiving enhanced nutrient supply or a control group. Fecal samples from 45 infants collected between birth and discharge were analyzed using 16S ribosomal RNA (rRNA) amplicon sequencing. RESULTS: There was considerable individual variation in microbiota development. Microbial richness decreased towards discharge in the controls compared to the intervention group. In the intervention group, there was a greater increase in diversity among moderately/very preterm (MVP, gestational age ≥ 28 weeks) infants and a steeper decrease in relative Staphylococcus abundance in extremely preterm (EP, gestational age < 28 weeks) infants as compared to controls. Relative Bifidobacterium abundance tended to increase more in MVP controls compared to the intervention group. Abundance of pathogens was not increased in the intervention group. Higher relative Bifidobacterium abundance was associated with improved weight gain. CONCLUSION: Nutrition may affect richness, diversity, and microbiota composition. There was no increase in relative abundance of pathogens among infants receiving enhanced nutrient supply. Favorable microbiota development was associated with improved weight gain.

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 · day (P < 0.001) and 4.0 (3.9-4.2) versus 3.2 (3.1-3.3) g · kg · day (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 · day in the intervention group and 13.8 (13.2-15.5) g · kg · day 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.

Survey of transfusion practices in preterm infants in Europe.

BACKGROUND: Preterm infants commonly receive red blood cell (RBC), platelet and fresh frozen plasma (FFP) transfusions. The aim of this Neonatal Transfusion Network survey was to describe current transfusion practices in Europe and to compare our findings to three recent randomised controlled trials to understand how clinical practice relates to the trial data. METHODS: From October to December 2020, we performed an online survey among 597 neonatal intensive care units (NICUs) caring for infants with a gestational age (GA) of <32 weeks in 18 European countries. RESULTS: Responses from 343 NICUs (response rate: 57%) are presented and showed substantial variation in clinical practice. For RBC transfusions, 70% of NICUs transfused at thresholds above the restrictive thresholds tested in the recent trials and 22% below the restrictive thresholds. For platelet transfusions, 57% of NICUs transfused at platelet count thresholds above 25×109/L in non-bleeding infants of GA of <28 weeks, while the 25×109/L threshold was associated with a lower risk of harm in a recent trial. FFP transfusions were administered for coagulopathy without active bleeding in 39% and for hypotension in 25% of NICUs. Transfusion volume, duration and rate varied by factors up to several folds between NICUs. CONCLUSIONS: Transfusion thresholds and aspects of administration vary widely across European NICUs. In general, transfusion thresholds used tend to be more liberal compared with data from recent trials supporting the use of more restrictive thresholds. Further research is needed to identify the barriers and enablers to incorporation of recent trial findings into neonatal transfusion practice.

Estimated daily intake of phthalates, parabens, and bisphenol A in hospitalised very low birth weight infants.

Very low birth weight infants (VLBW, birth weight (BW) < 1500 g) are exposed to phthalates, parabens and bisphenol A (BPA) early in life. We estimated daily intake (EDI) of these excipients in 40 VLBW infants the first and fifth week of life while hospitalised. Based on urinary samples collected in 2010, EDI was calculated and compared to the tolerable daily intake (TDI) with hazard quotients (HQs) evaluated. A HQ > 1 indicates that EDI exceeded TDI with increased risk of adverse health effects. EDI was higher in VLBW infants compared to term-born infants and older children. VLBW infants born at earlier gestational age (GA), or with lower BW, had higher EDI than infants born at later GA or with higher BW. First week median EDI for BPA was higher than TDI in 100% of infants, in 75% for di(2-ethylhexyl) phthalate (DEHP), 90% for the sum of butyl benzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), DEHP and di-iso-nonyl phthalate (DiNP) = ∑BBzP+DnBP+DEHP+DiNP, and in 50% of infants for propylparaben (PrPa), indicating increased risk of adverse effects. Fifth week EDI remained higher than TDI in all infants for BPA, in 75% for DEHP and ∑BBzP+DnBP+DEHP+DiNP, and 25% of infants for PrPa, indicating prolonged risk. Maximum EDI for di-iso-butyl phthalate was higher than TDI suggesting risk of adverse effects at maximum exposure. VLBW infants born earlier than 28 weeks GA had higher EDI, above TDI, for PrPa compared to infants born later than 28 weeks GA. Infants with late-onset septicaemia (LOS) had higher EDI for DEHP, ∑BBzP+DnBP+DEHP+DiNP and BPA, above TDI, compared to infants without LOS. More 75% of the infants' EDI for DEHP and ∑BBzP+DnBP+DEHP+DiNP, 25% for PrPa, and 100% of infants' EDI for BPA, were above TDI resulting in HQs > 1, indicating increased risk of adverse health effects.

Asymmetric dimethylarginine in the maternal and fetal circulation in preeclampsia.

Preeclampsia is a leading cause of intrauterine growth restriction and preterm birth. Endothelial dysfunction is the common final pathway leading to clinical signs of preeclampsia including hypertension and proteinuria. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NOS and induces endothelial dysfunction by reversibly inhibiting NO production from l-arginine. The purpose of this study was to investigate maternal and fetal concentrations of ADMA, l-arginine, and symmetric dimethylarginine (SDMA). Women with preeclampsia (n = 47) and controls (n = 51) who gave birth by cesarean section were included in the study. We analyzed the maternal plasma and umbilical vein and artery plasma. We found that not only maternal concentrations of ADMA and SDMA but also l-arginine were significantly higher in women with preeclampsia than in controls. In fetal samples, only SDMA concentrations were higher in the preeclampsia group than in controls. The median ADMA concentration was three times higher in the fetal circulation than in the maternal circulation, but there was no difference between the preeclampsia group and the control group, and the veno-arterious gradient indicated that the placenta was the source of ADMA.

Blood pressure augmentation and maternal circulating concentrations of angiogenic factors at delivery in preeclamptic and uncomplicated pregnancies.

OBJECTIVE: The objective of the study was to determine whether blood pressure increases are associated with maternal angiogenic factors in uncomplicated and preeclamptic pregnancies. STUDY DESIGN: Associations of blood pressure increases from mid- to late pregnancy with maternal serum concentrations of soluble fms-like tyrosine kinase receptor (sFlt1), soluble endoglin (sEng), and placental growth factor (PlGF) at delivery were analyzed in 43 uncomplicated and 44 preeclamptic pregnancies. RESULTS: In uncomplicated pregnancies, increases in diastolic and mean arterial pressure were inversely associated with PlGF at delivery and positively associated with sEng and sFlt1/PlGF ratio. There were no significant associations between blood pressure increases and angiogenic factor concentrations in preeclampsia. CONCLUSION: These data suggest that angiogenic factors are involved in blood pressure modulation in normotensive pregnancy and are consistent with the hypothesis that angiogenic balance plays a role in maternal breast cancer risk reduction associated with mid- to late blood pressure increases in uncomplicated pregnancies.

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 weight < 1500 g) 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.

Oxidative stress markers and antioxidant status after oral iron supplementation to very low birth weight infants.

OBJECTIVE: To evaluate whether our current practice of giving iron 18 mg daily to 6-week-old infants with very low birth weight (VLBW) was associated with increased oxidative stress markers or decreased antioxidant status. STUDY DESIGN: The study was a prospective observational study of 21 healthy VLBW infants (born at gestational age <32 weeks, birth weight <1500 g). Blood and urine were sampled twice before starting iron supplementation at 6 weeks postnatal age and after 1 week of iron supplementation at age 7 weeks. Urine 8-isoprostane was analyzed by gas chromatography-mass spectrometry and plasma total hydroperoxides were measured. Antioxidant status was assessed by ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), ferric-reducing ability of plasma, and plasma glutathione. RESULTS: After 1 week of iron supplementation, no significant changes in urine 8-isoprostane or plasma total hydroperoxides were seen, and plasma antioxidants were largely unchanged. CONCLUSIONS: Markers of oxidative stress in urine and plasma antioxidant status in healthy VLBW infants fed human milk remained unchanged after high-dose oral iron supplementation.

Circulating concentrations of soluble endoglin (CD105) in fetal and maternal serum and in amniotic fluid in preeclampsia.

OBJECTIVE: We explored whether concentrations of soluble endoglin in fetal serum and amniotic fluid and in maternal serum were elevated in preeclampsia. STUDY DESIGN: Umbilical vein serum, amniotic fluid, and maternal serum from 42 preeclamptic and 43 uncomplicated pregnancies that were delivered by cesarean section were analyzed by enzyme-linked immunosorbent assay for soluble endoglin. RESULTS: Median maternal serum and amniotic fluid soluble endoglin concentrations were elevated in preeclampsia, compared with control pregnancies (66.9 ng/mL vs 15.1 ng/mL; P < .001, and 1.9 ng/mL vs 0.6 ng/mL; P < .001). Low concentrations of soluble endoglin were found in fetal circulation, which did not differ between preeclampsia and control pregnancies (5.0 ng/mL vs 4.7 ng/mL; P = .2). Maternal serum soluble endoglin levels correlated with circulating soluble fms-like tyrosine kinase 1 concentrations. CONCLUSION: We confirmed elevated soluble endoglin in maternal circulation in preeclampsia, which correlated with soluble fms-like tyrosine kinase 1 concentrations and soluble fms-like tyrosine kinase 1/placental growth factor ratio. The fetus appears not to contribute to elevated circulating maternal soluble endoglin concentrations in preeclampsia.

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

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.

Enhanced nutrient supply to very low birth weight infants is associated with higher blood amino acid concentrations and improved growth.

BACKGROUND & AIMS: Customized nutrient supply is vital to ensure optimal growth among very low birth weight infants (birth weight < 1500 g). The supply of amino acids is especially important due to their impact on protein synthesis and growth. The objectives of this study were to evaluate the impact of enhanced nutrition on growth, blood concentrations of amino acids, and explore possible associations between amino acid concentrations and common neonatal morbidities. We hypothesized higher amino acids levels and growth velocity among infants on enhanced nutrient supply. METHODS: This randomized controlled trial was performed in three university neonatal intensive care units in Oslo, Norway. Fifty very low birth weight infants were randomized to a control or intervention group. Within 24 h after birth, infants in the intervention group received enhanced supply of energy, amino acids, lipids, long-chain polyunsaturated fatty acids and vitamin A, whereas the control group received a standard nutrient supply. The intervention continued until 52 weeks postmenstrual age or until a body weight of 5.5 kg was reached. Amino acid analyses were performed at birth, day 3, 5 weeks of age and 5 months corrected age. Detailed information about nutrient intake, morbidities, blood amino acid concentrations and growth velocity were collected from 44 infants (6 infants excluded). High-performance liquid chromatography was used for amino acid analysis. RESULTS: The intervention group (n = 23) received higher supply of proteins, with higher blood concentrations of amino acids measured at 5 weeks of age, and improved growth velocity (mean 17.4 vs 14.3 g/kg/day, p < 0.001) at 36 weeks postmenstrual age, compared to the control group (n = 21). The correlation between concentrations of branched chain amino acids (leucine, isoleucine and valine) and growth was stronger and more positive among infants: a) in the control group (correlation coefficient ≥ 0.68, p ≤ 0.004); b) born with birth weight appropriate for gestational age (correlation coefficient ≥ 0.53, p ≤ 0.009) and c) not diagnosed with septicemia (correlation coefficient ≥ 0.63, p ≤ 0.005). CONCLUSION: Enhanced nutrient supply to very low birth weight infants led to higher blood amino acid concentrations and improved growth. The correlations between amino acid concentrations and growth velocity were weaker in the intervention group as compared to the control group. This could reflect an upper threshold for protein synthesis and growth with our intervention, whereas a potential for further growth with increasing amino acid supply was possible for the control group. CLINICAL TRIAL REGISTRATION NO: NCT01103219.

Augmented oxidative stress as well as antioxidant capacity in maternal circulation in preeclampsia.

OBJECTIVES: Isoprostanes are stable markers of oxidative stress. We wanted to assess maternal circulating levels of total 8-isoprostane and indices of antioxidant capacity in preeclampsia compared to uneventful pregnancies. STUDY DESIGN: Total 8-isoprostane concentrations, FRAP (ferric reducing ability of plasma), Vitamin E and d-ROM (diacron reactive oxygen metabolites) were measured in maternal venous blood samples from preeclamptic (n=21) and uncomplicated (n=38) pregnancies at cesarean section. RESULTS: Median total 8-isoprostane concentration was elevated in preeclampsia compared to uncomplicated pregnancies (354 and 218 pg/mL, P=0.02). Median FRAP level was also elevated in preeclampsia compared to uncomplicated pregnancies, but to a lesser degree than 8-isoprostane. A positive correlation between 8-isoprostane and previously analyzed placenta-derived sFlt1 (soluble fms-like tyrosine kinase 1) levels in the maternal circulation was found in preeclampsia. CONCLUSION: We found a relative more increase for the oxidative stress marker (8-isoprostane) than for the antioxidant capacity (FRAP) in preeclampsia compared to uneventful pregnancies.

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.

Circulating concentrations of sFlt1 (soluble fms-like tyrosine kinase 1) in fetal and maternal serum during pre-eclampsia.

OBJECTIVE: We hypothesized that umbilical vein serum soluble fms-like tyrosine kinase 1 (sFlt1) concentration was augmented in pre-eclampsia. We also explored a possible association between fetal and maternal concentrations of sFlt1. STUDY DESIGN: At cesarean delivery, maternal serum samples from pre-eclamptic (n=38) and uncomplicated (n=32) pregnancies were obtained, as well as umbilical vein serum and amniotic fluid samples. ELISA for human sFlt1, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were performed. RESULTS: Median sFlt1 concentrations were elevated in pre-eclampsia compared to uncomplicated pregnancy, in umbilical venous serum (246 and 163 pg/mL, P=0.04), in maternal serum (9932 and 3417 pg/mL, P<0.001), as well as in amniotic fluid (51,040 and 33,490 pg/mL, P=0.03). A positive association between the fetal and maternal serum levels of sFlt1 was found in the pre-eclampsia group. Median PlGF concentration in the maternal serum was significantly lower in the pre-eclampsia group compared to the control group (82 pg/mL and 169 pg/mL, P<0.001). CONCLUSIONS: sFlt1 concentration is elevated in the fetal circulation in pre-eclampsia, but at a much lower level than in the maternal circulation. The results of our study do not support a substantial fetal contribution to the elevated circulating maternal sFlt1 protein concentration in pre-eclampsia.

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.151C > T (p.Arg51Cys) in MAB21L2.

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.

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 feeding in very-low-birth-weight infants may cause electrolyte disturbances and septicemia--a randomized, controlled trial.

BACKGROUND & AIMS: High 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. METHODS: Fifty very-low-birth-weight infants were randomized to either an enhanced or a standard feeding protocol within 24 h after birth. Chi-square and T-tests were applied. RESULTS: First week protein, fat and energy supply was significantly higher in the intervention group compared to the control group (all P < 0.001). After inclusion of 50 patients we observed a higher occurrence of septicemia in the intervention group, 63% vs. 29% (P = 0.02), 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 (1.23 (0.50) mmol/L) as compared to the infants without (1.61 (0.61) mmol/L) (P = 0.03). CONCLUSION: Our 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.

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

OBJECTIVE: We 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). STUDY DESIGN: Third 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. RESULTS: Median 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). CONCLUSION: Elevated 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.