A clinical study on plasma biomarkers for deciding the use of adjuvant corticosteroid therapy in bronchopulmonary dysplasia of premature infants.

Objective: The study was designed to investigate some plasma markers which help us to decide the use of adjuvant corticosteroid therapy in bronchopulmonary dysplasia (BPD) of premature infants. Methods: Thirty BPD infants were treated by dexamethasone. Among these cases, dexamethasone was significant effective in 10 cases, and no significant effective in 20 cases. These patients were divided into two groups as the significant effect (SE) group (n=10) and the non-significant effect (NE) group (n=20) according to the curative effect of dexamethasone. Fifteen non-BPD infants with gestational age and gender matching were selected as the control group. Plasma samples before and after dexamethasone treatment were collected from three infants chosen randomly from SEG for the data-independent acquisition (DIA) analysis. ELISA was further used to detect the levels of differential proteins LRP1 and S100A8 in all individuals, including SE, NE and control groups. Results: DIA analysis results showed that after dexamethasone treatment, there were a total of 52 plasma proteins that showed significant differences, of which 43 proteins were down-regulated and 9 proteins were up-regulated. LRP1 and S100A8 were two plasma proteins that were significantly changed after dexamethasone treatment. Compared with the control group, plasma LRP1 was significantly increased in BPD. Interestingly, the plasma concentration of LRP1 in the NE group was significantly higher than that in the SE group. S100A8, as an indicator of plasma inflammation, was significantly higher in BPD than the control group. Unlike LRP1, there was no significantly difference between the SE and NE group (P=0.279) before dexamethasone treatment. Conclusion: Elevated plasma LRP1 and S100A8 in BPD infants are two indicators that correlated with the efficacy of dexamethasone, and might be used as biomarkers for deciding the use of adjuvant corticosteroids therapy in the BPD.

Rate of rise of total serum bilirubin in very low birth weight preterm infants.

BACKGROUND: To assess the postnatal rate of rise (ROR) of total serum bilirubin (TSB) in very low birth weight (VLBW) preterm infants, to determine risk factors associated with a rapid rise (>90th percentile), and to compare ROR and hour-specific TSB at postnatal 12-48 h with data of term infants retrieved from the literature. METHODS: Retrospective analysis of 2430 routine TSB concentrations obtained between birth and initiation of phototherapy in 483 VLBW infants. RESULTS: TSB increased by a median (interquartile range) ROR of 0.15 (0.11-0.19) mg/dL/h. The 50th percentile of TSB was below the 40th percentile of (near-)term counterparts at 12-48 h. TSB ROR correlated with the age at initiation (RS = -0.687; p < 0.001) and the duration (RS = 0.444; p < 0.001) of phototherapy. ROR >90th percentile (>0.25 mg/dL/h) was associated with lower gestational ages [27.2 (25.4-29.3) vs. 28.4 (26.4-30.4) weeks], lower birth weights [978 (665-1120) vs. 1045 (814-1300) g], and lower 5-min Apgar scores [7 (7-8) vs. 8 (7-9)]. CONCLUSION: ROR of TSB is an indicator for early and prolonged phototherapy. While hour-specific TSB and ROR at 12-48 h are lower than those reported for (near-)term infants, TSB appears to rise more rapidly in infants with low gestational age, low birth weight, and low 5-min Apgar score.

Plasma unbound free fatty acid profiles in premature infants before and after intralipid infusion.

Background: Unbound free fatty acids (FFAu) are the bioactive fraction of plasma free fatty acids (FFA). Most plasma FFA are bound to albumin. Only when FFA dissociate from albumin, do they become biologically active.Objective: To measure the first FFAu profiles in human infants and to measure these profiles before and during intravenous administration of the soybean lipid, intralipid (IL).Study design: The study population was 16 premature infants, from a parent study of 130 infants with birth weights 500-2000 g and gestational age 23-34 weeks. The infants chosen had plasma samples of ≥120 µL (volume needed for each FFAu profile measurement) in the first day of life. Infants received IL infusions starting in the second day of life at 1 g/kg/day, increasing by 1-g/kg/day daily up to 3 g/kg/day. FFAu profiles were determined during IL infusion when plasma was available. Profiles are the concentrations of the nine most abundant long-chain FFAu and were determined using novel fluorescent probes.Results: Before intralipid infusion unbound myristic acid was the dominant FFAu, as high as 78% of the total FFAu (sum of the 9 FFAu). In contrast, unbound linoleic acid was 0% in all infants. With increasing infusion of IL to 3 g/kg/day, unbound linoleic increased to 26% of the total FFAu, with unbound oleic, myristic, and linolenic acid the second, third and fourth most abundant. The average total FFAu concentration also increased from 4 nM before intralipid to 53 nM at 3 g/kg/day. During IL infusion the FFAu profiles approached the fatty acid composition of intralipid at 3 g/kg/day.Conclusions: This first study of FFAu profiles in neonates revealed that before IL infusion unbound linoleic acid was zero in all 16 infants and levels of myristic acid were exceptionally large, as much as 78% of the total FFAu profile. These results suggest important and previously unrecognized roles of lipid metabolism in early development. Zero unbound linoleic acid before IL infusion may help promote closure of the ductus arteriosus but after IL infusion, synthesis of arachidonic from linoleic acid may tend to promote patency. The high levels of unbound myristate may be needed for immediate neonatal energy needs.

First-year growth of 834 preterm infants in a Chinese population: a single-center study.

BACKGROUND: The aim of this study was to follow the growth and hematological indicators of preterm infants during their first year. METHODS: Neonates below 37 gestational weeks had routine follow-ups up through 1 year from January 2012 to December 2015 at West China 2nd University Hospital, Sichuan University. Weight, length and head circumference (HC) were measured monthly during the first 6 months, followed by monitoring every second month until 12 months. The catch-up growth defined as a gain of Z-score > 0.67 according to previous study. All preterm infants were prescribed iron prophylaxis based on national guideline. The hemoglobin concentration was examined at 6 and 12 months. RESULTS: Altogether, 132 very-low-birth-weight (VLBW), 504 low-birth-weight (LBW) and 198 normal-birth-weight (NBW) infants were followed. The rates of catch-up growth for weight, length and HC 12 months of corrected age (CA) were 22.6, 29.1 and 14.6%, respectively. SGA and VLBW infants showed higher catch-up growth rates. The overall prevalence of anemia was 6.8% at 6 months and 7.8% at 12 months. The Z-scores for weight-for-length, length and HC were lower in the VLBW and SGA preterm infant groups than in the other preterm groups throughout the first year of life. The incidences of stunting, microcephaly and wasting changed from 5, 1.3 and 3.7% to 2, 1.1, 0.9 and 2.4%, respectively, during the first year. However, the incidences of wasting and stunting were higher for the VLBW infants than for the LBW and NBW infants at 12 months (9.3% vs. 1.4%, p < 0.01; 9.3% vs. 1%, p < 0.01,respectively; 4.7% vs. 0.8%, p < 0.01, 4.7% vs. 0%, p < 0.01,respectively). Similar results were observed between SGA and AGA infants (8.7% vs. 1.5%, p < 0.01; 5.8% vs. 0.4%, p < 0.01). Logistic regression revealed SGA and VLBW as risk factors for poor growth (WLZ < -2SD) at 12 months (OR = 5.5, 95% CI: 2.1-14.8, p < 0.01: OR = 4.8, 95% CI: 1.8-12.8, p < 0.01, respectively). CONCLUSION: The VLBW and SGA preterm infants showed significant catch-up growth during their first year of life. However, SGA and VLBW were risk factors for poor growth during the preterm infants' first year of life. Prophylactic iron supplementation in preterm infants appears to reduce the prevalence of anemia.

Performance of LC/MS/MS in Analyzing Multiple Amino Acids and Acylcarnitines in Dried Blood Spot of Very Low Birth Weight, Low Birth Weight, and Normal Weight Neonates.

BACKGROUND: Amino acid (AA) and acylcarnitine (AC) are important biomarkers of protein and fatty acid metabolism. Examining their levels in newborns may reveal multiple inherited metabolic diseases. However, they have rarely been assessed in very low birth weight (VLBW) neonates, low birth weight (LBW) neonates and rarely been compared with normal weight (NW) neonates. The aim of the study was to identify the AA and AC profiles in dried blood spot (DBS) specimens of LBW and VLBW neonates, then compare with NW neonates, and make a contribution to the determination of cutoff values of VLBW and LBW neonates. METHODS: Liquid Chromatography tandem mass spectrometry (LC/MS/MS) is an excellent tool for quantitatively detecting AA and AC profiles. This article verified the precision, accuracy, and linearity of the LC/MS/MS method in AA and AC detection, then analyzed AA and AC profiles in DBS of VLBW, LBW and NW neonates, and compared the difference of AA and AC in the three groups. RESULTS: The results showed that the LC/MS/MS method had wide linear range, satisfied precision and reproducibility in detecting AA and AC in DBS specimens; most AA and AC concentrations significantly correlated with birth weight in DBS samples (p < 0.05). CONCLUSIONS: The results suggested that VLBW and LBW neonates have different metabolic or nutritional status with NW neonates and different AA and AC cutoffs should be defined for them to reduce the risk of false-positive cases.

Effects of Chromium on Glucose Tolerance in Infants Receiving Parenteral Nutrition Therapy.

OBJECTIVES: Early hyperglycemia is prevalent in preterm infants receiving parenteral nutrition (PN) therapy. Chromium improves glucose tolerance by potentiating the action of insulin. Therefore, we hypothesized that supplementing PN with chromium would improve glucose tolerance and PN calorie delivery in infants during the first week of life. METHODS: We collected data on neonates receiving PN initiated at birth with chromium (0.2 mcg/kg/d) started either on days 5-7 (group A) vs day 1 (group B) on PN and compared glucose tolerance and PN calorie administration over the first week of life. RESULTS: For similar mean serum glucose concentrations between group A (n = 348) and B (n = 358) (107 ± 48 vs 111 ± 52 mg/dL, P = .3), infants in group B tolerated higher glucose infusion rates and received more PN calories during the first week of life: 8.4 ± 2 vs 8 ± 2 mg/kg/min (P < .001) and 74.8 ± 23 vs 71.5 ± 12 kcal/kg/d (P = .017), respectively. The difference in calories delivered was more pronounced among very low birth weight (VLBW) infants compared with infants >1500 g: 76.5 ± 14 vs 72.4 ± 11 kcal/kg/d (P = .009) and 73.8 ± 27 vs 70.3 ± 12 kcal/kg/d (P = .079), respectively. CONCLUSIONS: PN chromium supplementation resulted in better glucose tolerance and calorie delivery during the first week of life, especially in VLBW infants. This supports chromium's essential role in enhancing glucose tolerance during PN therapy in VLBW infants at risk for early hyperglycemia.

Half-life of plasma phytosterols in very low birth weight preterm infants on routine parenteral nutrition with vegetable oil-based lipid emulsions.

BACKGROUND: Phytosterols in vegetable oil (VO)-based lipid emulsions (LE) likely contribute to parenteral nutrition-associated cholestasis (PNAC) in preterm infants. No characterization of plasma phytosterol half-lives has been done in very low birth weight (VLBW) preterm infants receiving parenteral nutrition (PN) with LE. METHODS: In a prospective cohort study, 45 VLBW preterm infants who received PN underwent serial blood sample measurements of sitosterol (SITO), campesterol (CAMP), and stigmasterol (STIGM). Plasma phytosterol half-lives were calculated from the phytosterol concentrations-decay curves by using a single-compartment model. RESULTS: After the stop of the intravenous LE, study infants had significantly lower plasma total CAMP, STIGM and SITO concentrations. The decay of plasma phytosterol concentrations was monoexponential. Half-life of plasma total CAMP, STIGM and SITO was 13.5 ± 6.9, 10.3 ± 4.5 and 10.3 ± 4.0 days, respectively. Plasma phytosterol half-lives did not correlate with gestational age, birth weight, cumulative phytosterol intakes and plasma conjugated bilirubin. CONCLUSION: VLBW preterm infants on PN with LE had rather long plasma phytosterol half-lives similar to hypercholesterolemic adults and phytosterolemic homozygotes patients. We speculate that the accumulation of phytosterols could contribute to their vulnerability to PNAC. CLINICAL TRIAL REGISTRY: The Ethics Committee of Marche-Italy (DG/469); www.clinicaltrials.gov (identification number NCT02758834).

Serum 25 Hydroxy Vitamin D Levels in Very Low Birth Weight Infants Receiving Oral Vitamin D Supplementation.

BACKGROUND AND OBJECTIVE: Vitamin D supplementation in preterm infants has been recommended by American Academy of Pediatrics (AAP); however, its efficacy and safety has not been well studied. To study 25-hydroxy vitamin D (25OHD) levels as a marker of vitamin D status of very low birth weight infants while on vitamin D supplementation during neonatal intensive care unit hospitalization. METHODS: Retrospective study of preterm infants with birth weight <1500 g admitted to our unit from January 2013 to December 2015 who were on oral vitamin D3 400 IU supplementation. Serum 25OHD level were checked at 4, 8, and 12 weeks of age or before discharge and the levels were stratified as deficient <20 ng/mL, insufficient 20 to 29 ng/mL, normal 30 to 60 ng/mL, high 61 to 100 ng/mL and very high >100 ng/mL. RESULTS: A total of 301 infants were enrolled, 186 very low birth weight (VLBW; 1000-1499 g) infants and 115 extremely low birth weight (ELBW; <1000 g) infants. Approximately 80% of both VLBWs and ELBWs had deficient or insufficient 25OHD levels at 4 weeks of age. On oral vitamin D supplementation, VLBW infants increased their 25OHD levels significantly by 8 and 12 weeks of age, whereas ELBW infants lagged behind at 8 weeks and increased their 25OHD levels by 12 weeks of age. CONCLUSIONS: Eighty percent of ELBW and VLBW infants have either deficient or insufficient vitamin D status at 4 weeks of age. Vitamin D supplementation helps in improving the vitamin D levels, VLBW infants significantly more than ELBW infants. AAP recommendation appears to be safe; however, if using higher supplement dosing, 25OHD level should be monitored to avoid high and very high vitamin D levels.

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.

Risk Factors for the Development of Refeeding Syndrome-Like Hypophosphatemia in Very Low Birth Weight Infants.

BACKGROUND: Refeeding syndrome is characterized by metabolic disturbance including hypophosphatemia and hypokalemia upon reinstitution of nutrition in severely malnourished patients. OBJECTIVE: The present study sought to identify the risk factors for the development of refeeding syndrome-like metabolic disturbance in very low birth weight infants. METHODS: The correlations of severe hypophosphatemia with the serum levels of potassium and ionized calcium, daily calorie and phosphate intake, and umbilical cord blood flow on ultrasonography were analyzed in 49 very low birth weight infants. RESULTS: Fifteen infants (36%) presented with hypophosphatemia during the first postnatal week. Hypophosphatemia was significantly associated with birth weight z score (odds ratio, 1.60; 95% confidence interval, 1.04-2.47; p = 0.034) and umbilical artery resistance index (odds ratio, 7.72E-04; 95% confidence interval, 1.14E-06-0.523; p = 0.031). Multiple regression analysis revealed that umbilical artery resistance index was independently associated with hypophosphatemia. CONCLUSIONS: Umbilical artery resistance index may serve as a useful marker for future development of refeeding syndrome-like hypophosphatemia in very low birth weight infants. Close monitoring of serum phosphorus and potassium levels and early intervention are important for the management of very low birth weight infants with intrauterine growth restriction due to placental dysfunction.

Postnatal RBC arachidonic and docosahexaenoic acids deficiencies are associated with higher risk of neonatal morbidities and mortality in preterm infants.

Arachidonic (AA) and docosahexaenoic (DHA) acids are essential for the health and development of the neonate. Red blood cell (RBC) fatty acids were analyzed in 583 very low birth weight (VLBW) infants and 274 term infants using capillary gas chromatography. VLBW infants exhibited significantly lower RBC AA (13.0 ± 0.89 vs. 13.5 ± 0.98) and DHA (3.77 ± 0.60 vs. 3.80 ± 0.62), but higher n6:n3 ratio (3.97 ± 0.46 vs. 3.63 ± 0.37) than term infants. In VLBW infants, DHA was lower in those born with small for gestational age (3.69 ± 0.57 vs. 3.86 ± 0.58) and those who suffered from neonatal sepsis (3.73 ± 0.60 vs. 3.86 ± 0.55). Both AA and DHA were significantly lower in infants who developed respiratory distress syndrome or intraventricular hemorrhage, and those who died during the hospital stay. VLBW infants had lower postnatal RBC AA and DHA levels than term infants did. These deficits are associated with higher risk of neonatal morbidities and mortality.

Trace elements, oxidative status and antioxidant capacity as biomarkers in very low birth weight infants.

Reference data on trace elements, oxidative status and antioxidants in very low birth weight infants (VLBW) are limited and need to be updated for use in clinical settings. Serum and urine of 30 VLBW infants (mean weight, 1167g) at mean age of 23.8 (t0) and 37.8 (t1) days were analyzed. Cadmium (Cd), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), selenium (Se) and zinc (Zn), nitrate/nitrite (NOx), catalase (CAT), CuZnFeMn-superoxide dismutases (CuZnFeMn-SODs), total antioxidant capacity (SAC: sum of thiols, proteins, bilirubin, uric acid, ß-beta-carotene, ascorbic acid, vitamin E) and total oxidative status (SOS: sum of lipo- and hydroperoxides) were determined. A higher urinary excretion of Cu and Zn was observed at t0 than at t1; while an increase in urine Cd was found at t1 respect to t0. A deficiency in serum levels of Cu and Zn was also found. A lower CAT activity, a higher total oxidants level (SOS) and a reduction of total antioxidant barriers (SAC) were observed in some infants. No Fe and Mn deficiency or Hg overload was found; also CuZnFeMn-SODs and NOx levels did not change. The findings showed that losses of trace elements and incomplete mineral body stores were more pronounced in the earlier life stage (at 23.8th day) than later on; moreover, antioxidant defenses were poor and lipo- and hydroperoxides were higher still at 5 weeks of infants' life.

Impact of l-carnitine supplementation on metabolic profiles in premature infants.

OBJECTIVE: To describe the influence that of l-carnitine supplementation on acylcarnitine (AC) profiles and hospital outcomes in premature infants. STUDY DESIGN: This study is a secondary analysis of previously reported work. Metabolic profiles were obtained using standard newborn techniques on infants born between 23 and 31 completed weeks of gestation. The profiles were drawn within the first 24 h after birth and on approximately days 7, 28 and 42 of life, or at the time of discharge. A single, central, contract laboratory analyzed and managed the samples. RESULTS: We studied 995 patients; none was subsequently diagnosed with an inborn error of metabolism. l-Carnitine was added to parenteral nutrition in 390 (39%) study subjects; 592 (60%) did not receive supplementation. Non-supplemented infants were more likely to develop low levels of free carnitine (FC; <7 µm) on day 28; (41% vs 5%, P<0.01); and FC values were lower on day 7. Despite higher levels of FC and fewer patients with significant carnitine deficiencies, we found no evidence that l-carnitine supplementation was associated with improved short-term hospital outcomes. CONCLUSION: l-Carnitine supplementation is common in prematurely born neonates and is associated with higher carnitine levels, but is not associated with improved short-term hospital outcomes.

An Elevation of Serum Ferritin Level Might Increase Clinical Risk for the Persistence of Patent Ductus Arteriosus, Sepsis and Bronchopulmonary Dysplasia in Erythropoietin-Treated Very-Low-Birth-Weight Infants.

BACKGROUND: The substantial risk of iron overload is not routinely monitored in most of the neonatal intensive care units (NICUs) in Japan; however, blood transfusion is an essential strategy for successfully treating preterm low-birth-weight infants. OBJECTIVE: The aim of this study was to investigate the iron status and clinical features of infants with a birth weight of <1,500 g, i.e. very-low-birth-weight infants (VLBWIs). METHODS: This prospective observational study enrolled 176 (82.6%) patients from a total of 213 VLBWIs admitted to our NICU from 2009 to 2014. Clinical information was collected including maternal records and infant morbidity and treatment. Management strategies including enteral iron supplementation, erythropoietin administration and blood transfusion were allowed according to the consensus in Japan. The hematological status was surveyed from birth to 12 postnatal weeks of age. The iron status was determined according to serum iron, unbound iron-binding capacity and serum ferritin. The definition of hyperferritinemia was set as a value of ≥500 ng/ml. RESULTS: Twenty-four (13.6%) infants displayed hyperferritinemia. A multiple logistic analysis selected 3 associated factors of hyperferritinemia: surgical ligation for patent ductus arteriosus, sepsis and moderate or severe states of bronchopulmonary dysplasia. We also verified that the value of ferritin was significantly correlated with those of aspartate transaminase, creatine kinase and C-reactive protein according to a multilinear regression analysis. After excluding the ferritin data of these outliers, we did not observe any factors associated with hyperferritinemia. CONCLUSIONS: Hyperferritinemia might be associated with oxygen radical diseases and susceptibility to infection.

Vitamin D and bronchopulmonary dysplasia in preterm infants.

OBJECTIVE: Vitamin D deficiency is associated with asthma and reactive airway disease in childhood but its potential contribution to bronchopulmonary dysplasia (BPD) in preterm infants is unknown. Preterm infants have lower levels of 25-hydroxyvitamin D (25(OH)D) at birth and are at risk for nutritional deficiencies after birth. The objective of the study was to evaluate the association of 25(OH)D concentrations at birth and at 36 weeks' corrected gestational age with BPD in preterm infants born before 29 completed weeks of gestation. STUDY DESIGN: We collected umbilical cord blood samples from 44 preterm infants (gestational age <29 weeks) delivered at Brigham and Women's Hospital in Boston. In addition, with parental consent we collected venous samples at 36 weeks' corrected age from 20 preterm infants born before 29 weeks' gestation (including 6 infants with previously collected cord blood). Samples were frozen at -80 °C until subsequent measurement of 25(OH)D levels by chemiluminescence. We used multivariable logistic models to adjust for gestational age and considered other confounding variables, including maternal race, age, mode of delivery and infant sex. RESULTS: Among 44 infants, 41 (93.2%) survived and 3 (6.8%) died before 36 weeks' corrected age. Median 25(OH)D levels at birth were 30.4 ng ml(-1) in preterm infants who subsequently died or developed BPD and 33.8 ng ml(-1) in infants who survived without BPD (P=0.6). Median 25(OH)D levels at corrected age of 36 weeks were 59.0 ng ml(-1) among survivors without BPD and 64.2 ng ml(-1) among survivors with BPD (P=0.9). Neither cord blood nor 36 weeks' corrected 25(OH)D levels were associated with odds of death or BPD (adjusted odds ratio (OR) 1.00, 95% confidence interval (CI): 0.73 to 1.37; and OR 0.93, 95% CI: 0.61 to 1.43, respectively). CONCLUSIONS: Among this population of extremely preterm infants neither cord blood nor the 36 weeks' corrected age 25(OH)D levels were associated with development of BPD. Notably, at the current level of supplementation, all extremely preterm infants in our cohort had achieved 25(OH)D levels >30 ng ml(-1) by 36 weeks' corrected age, which is thought to represent sufficiency in adult and pediatric populations.

Clinical utility of transcutaneous bilirubinometer (TcB) in very low birth weight (VLBW) infants.

OBJECTIVE: This is a comprehensive study designed to evaluate the clinical usefulness of transcutaneous bilirubinometry (TcB) in very low birth weight (VLBW) newborns of African American (AA) descent. METHODS: TcB was conducted at the anterior superior iliac spine (ASIS), temporal region and sternum within 2 h of total serum bilirubin (TSB) measurements in newborns born at ≤32 weeks' gestation prospectively. Average (AVG) TcB levels were also calculated. The relationships between TSB and TcB levels were analyzed using non-parametric Spearman bivariate correlations, a Bland-Altman plot procedure and a decision tree (DT) analysis. RESULTS: One hundred newborns and 555 TSB data points were available. Eighty-nine percent of the newborns were AA. A significant correlation (P<0.0001) was observed between TSB and TcB values obtained at the ASIS (r=0.73), sternum (0.73), temporal region (0.61) and AVG (0.77). The Bland-Altman plot revealed a good agreement between AVG TcB values and TSB values. A DT analysis indicated that AVG TcB was also found to be the most significant predictor of TSB values in both the no phototherapy (PT) and biliblanket subgroups. CONCLUSION: TcB can be used reliably in VLBW AA newborns in the absence of overhead PT. The use of TcB in monitoring jaundice in VLBW newborns would help decrease the number of blood draws and cost of care.

Neonatal Serum Phosphorus Levels and Enamel Defects in Very Low Birth Weight Infants.

BACKGROUND: Very low birth weight (VLBW) infants miss out on the period of greatest mineral accretion that occurs during the last trimester of pregnancy and are at higher risk of enamel defects. No studies have well described the relationship between neonatal nutrition and dental outcomes in preterm, VLBW infants. The objective of this study was to assess the differences in nutrition biomarkers, feeding intake, and comorbidities among VLBW infants with and without enamel defects. METHODS: A retrospective chart review of VLBW infants recruited for an ongoing longitudinal dental study between 2007 and 2010 was done. Participants were classified as cases and controls according to the presence/absence of developmental defects of enamel at 8 and/or 18-20 and/or 36 months. Demographics and medical and nutrition data were abstracted from 76 subjects' medical charts. RESULTS: Of the 76 VLBW subjects, 62% had enamel defects (hypoplasia and/or opacity). The only significant variable in the logistic regression analysis was that infants with a 1-mg/dL increase in serum phosphorus levels had a 68% reduction in the odds of having enamel hypoplasia (odds ratio, 0.322; P = .024). CONCLUSION: Neonatal lower serum phosphorus levels are significantly associated with enamel hypoplasia in VLBW infants younger than 3 years.

Albumin synthesis in very low birth weight infants is enhanced by early parenteral lipid and high-dose amino acid administration.

BACKGROUND & AIMS: Albumin is one of the most important plasma proteins and plays a key role in many physiologic processes, such as preserving colloid osmotic pressure, scavenging radicals, and binding and transporting bilirubin, hormones, and drugs. However, albumin concentrations are often low in preterm infants during the first days of life. We hypothesized that early parenteral lipid and high-dose amino acid (AA) administration to very low birth weight (VLBW) infants from birth onwards increases hepatic albumin synthesis rates. METHODS: Inborn VLBW infants were randomized to receive from birth onwards either 2.4 g amino acids/(kg(·)d) (control group), 2.4 g amino acids/(kg(·)d) plus 2 g lipids/(kg(·)d) (AA + lipid group), or 3.6 g amino acids/(kg(·)d) plus 2 g lipids/(kg(·)d) (high AA + lipid group). On postnatal day 2, infants received a primed continuous infusion of [U-(13)C6,(15)N]leucine. Mass spectrometry was used to determine the fractional and absolute albumin synthesis rates (FSR and ASR, respectively). RESULTS: In total, 28 infants (median gestational age 27 weeks (IQR 25-28), median birth weight 810 g (IQR 679-998) were studied. The median FSR was 6.5%/d in the control group, 10.6%/d in the AA group, and 12.3%/d in the high AA + lipid group, while the median was 84 mg/(kg(·)d) in the control group, 138 mg/(kg(·)d) in the AA group, and 160 mg/(kg(·)d) in the high AA + lipid group. CONCLUSION: A group of VLBW infants given parenteral nutrition containing lipids and high-dose amino acids showed a higher rate of albumin synthesis compared to infants receiving no lipids and standard amounts of amino acids during the first two days of life.

Maternal/neonatal vitamin D deficiency: a risk factor for bronchopulmonary dysplasia in preterms?

OBJECTIVE: The objective of this study was to investigate the possible association between maternal/neonatal 25-hydroxy vitamin D (25-OHD) levels and development of bronchopulmonary dysplasia. STUDY DESIGN: One hundred and thirty-two preterm infants ⩽32 weeks of gestation who were diagnosed with respiratory distress syndrome were enrolled. 25-OHD levels were determined in maternal/neonatal blood samples that were obtained at the time of admission to the neonatal intensive care unit. RESULT: A total of 100 infants were included and 31 (31%) developed bronchopulmonary dysplasia (BPD). Both maternal and neonatal 25-OHD levels in the BPD group were significantly lower compared with those in the no-BPD group (P=0.0001). A positive correlation was detected between maternal and neonatal 25-OHD levels. All of the infants with BPD had a 25-OHD level <10 ng ml(-1), which represented severe deficiency. Univariate logistic regression analysis revealed that maternal/neonatal vitamin D levels were a significant predictor of BPD (odds ratio (OR): 0.76 and 0.61, respectively, P<0.001). CONCLUSION: We demonstrated for the first time that lower maternal and neonatal vitamin 25-OHD levels were associated with BPD development in preterm infants. However, further studies with larger sample sizes are needed to delineate the possible link between vitamin D deficiency and BPD.

[Study on levels of serum phosphorus, bone alkaline phosphatase and 25-hydroxyvitamin D in preterm infants with very low birth weight].

OBJECTIVE: To compare the levels of serum phosphorus, bone alkaline phosphatase and 25-hydroxyvitamin D3 in preterm infants with very low birth weight, and provide evidence for early screening, prevention of metabolic bone disease in preterm infants. METHODS: A total of 110 newborns who met the inclusion criteria were selected in pediatric ward in our hospital. The case group included 60 preterm infants with very low birth weight and control group included 50 full term infants. Fasting blood were taken from the subjects at week 1, 4, and 12 respectively, and ELISA was conducted to quantitatively detect the serum levels of phosphorus, bone alkaline phosphatase and 25-hydroxyvitamin D. RESULTS: The increase of serum 25-hydroxyvitamin D3in case group was smaller than that in control group; the levels of serum phosphorus had no significant difference between two groups. In case group, the level of bone alkaline phosphatase increased at week 1, 4, and 12, and the 25-hydroxyvitamin D3level had significant difference at week 12 (P<0.05). The abnormal rate of 25-hydroxyvitamin D3 level was 26.7% for case group and 0% for control group. CONCLUSION: There were significant differences between case group and control group in levels of bone alkaline phosphatase and 25-hydroxyvitamin D3, suggesting that detecting the serum levels of bone alkaline phosphatase and 25-hydroxyvitamin D3 would facilitate the early diagnosis of metabolic bone disease in preterm infants.