Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants.

BACKGROUND: Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia. METHODS: We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity. RESULTS: A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P = 0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively. CONCLUSIONS: In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).

Initial and delayed thyroid-stimulating hormone elevation in extremely low-birth-weight infants.

BACKGROUND: To determine the incidence, etiology, and outcomes of thyroid-stimulating hormone (TSH) elevation in extremely low-birth-weight infants (ELBWIs). METHODS: Newborn thyroid screening data of 584 ELBWIs (birth weight, < 1000 g; gestational age, ≥ 23 weeks) were retrospectively analyzed to identify initial (≤ 2 postnatal weeks) and delayed (> 2 weeks) TSH elevations. Growth and neurodevelopmental outcomes at 2 years' corrected age (CA) were assessed according to levothyroxine replacement. RESULTS: Initial and delayed TSH elevations were detected at CAs of 27 and 30 weeks, respectively, with incidence rates of 0.9 and 7.2%, respectively. All infants with initial TSH elevations had perinatal asphyxia, and 95% of those with delayed TSH elevation were exposed to various stressors, including respiratory support, drugs, and surgery within 2 weeks before diagnosis of TSH elevation. Free thyroxine (T4) levels were simultaneously reduced in 80 and 57% of infants with initial and delayed TSH elevations, respectively. Both initial and delayed TSH elevations were transient, regardless of levothyroxine replacement. Infants receiving levothyroxine replacement therapy had significantly higher TSH elevations, significantly lower free T4 levels, and significantly reduced mortality, compared to untreated infants. However, levothyroxine replacement had no significant effect on long-term growth and neurodevelopmental outcomes. CONCLUSIONS: The timing of insult superimposition on hypothalamic-pituitary-thyroid axis maturation is a major determinant of initial or delayed TSH elevation in ELBWIs. Levothyroxine replacement did not affect growth or neurodevelopmental outcomes in this population.

The level of extracellular superoxide dismutase in the first week of life in very and extremely low birth weight infants and the risk of developing bronchopulmonary dysplasia.

Background Antioxidant enzymes may play a significant role in the development of bronchopulmonary dysplasia (BPD). The aim of the study was to assess the relationship between the level of extracellular superoxide dismutase (SOD3) in the serum at days 1 and 7 of life and the risk of developing BPD. Methods The study comprised 103 neonates born before 32 weeks' gestation with a birth weight of ≤1500 g. Results In the investigated group, the median serum SOD3 level at day 1 of life was 4.01 ng/mL [interquartile range (IQR) 2.59-5.09 ng/mL] and at day 7 of life 3.13 ng/mL (IQR 2.49-4.34 ng/mL). A statistically significant decrease in the serum SOD3 level was found in the first week of life, P < 0.0001. No correlation was found between the serum SOD3 level at day 1 of life and gestational age R = 0.07, P = 0.4543 and birth weight R = 0.10, P = 0.3083. No statistically significant correlation was found between the dynamics of change in the SOD3 level in serum at days 1 and 7 of life and the risk of BPD development for the definition of BPD at day 28 of life, P = 0.8764 nor at 36 weeks' postmenstrual age, P = 0.6598. Conclusion The study revealed a statistically significant decrease in the serum SOD3 level in the first week of life in very and extremely low birth weight infants born before 32 weeks of gestation. In the clinical setting, no relationship was observed between the level of SOD3 in serum and the risk of developing BPD.

Pharmacometabolomics of Respiratory Phenotypic Response to Dexamethasone in Preterm Infants at Risk for Bronchopulmonary Dysplasia.

A prospective cohort study was performed in preterm infants less than 32 weeks gestation at birth who were treated with dexamethasone for developing or established bronchopulmonary dysplasia (BPD). Respiratory phenotype (Respiratory Severity Score (RSS)), serum, and urine metabolomics were assessed before and after treatment. Ten infants provided nine matched serum and nine matched urine samples. There was a significant decrease in RSS with steroid treatment. Serum gluconic acid had the largest median fold change (140 times decreased, P = 0.008). In metabolite set enrichment analysis, in both serum and urine, the urea cycle, ammonia recycling, and malate-aspartate shuttle pathways were most significantly enriched when comparing pretreatment and post-treatment (P value < 0.05). In regression analyses, 6 serum and 28 urine metabolites were significantly associated with change in RSS. Urine gluconic acid lactone was the most significantly correlated with clinical response (correlational coefficient 0.915). Pharmacometabolomic discovery of drug response biomarkers in preterm infants may allow precision therapeutics in BPD treatment.

Dysnatremia in extremely low birth weight infants is associated with multiple adverse outcomes.

OBJECTIVE: The objective of this study is to discern patterns of serum sodium in a broad cohort of extremely low birth weight (ELBW) infants and associate those patterns with hospital outcomes. STUDY DESIGN: Retrospective cohort study of ELBW infants from 323 neonatal intensive care units (NICUs) discharged from 2004 to 2014. We included patients who survived at least 7 days and had daily sodium levels available, and categorized infants by their minimum and maximum sodium levels. RESULTS: We identified 26,871 infants of whom 12,428 met inclusion criteria. Only 1964 (15.8%) maintained eunatremia for the first week. We found most dysnatremias to be associated with increased overall mortality compared with eunatremic patients including moderate hyponatremia (12.9% vs. 8.6%, p < 0.05) and severe hypernatremia (34.8% vs. 8.6%, p < 0.001). Most of these associations were maintained after regression modeling for mortality. CONCLUSION: Sodium fluctuations occurring within the first week of life are associated with increased mortality.

Use of whole exome sequencing in the NICU: Case of an extremely low birth weight infant with syndromic features.

Single gene (Mendelian) disorders are one of the leading causes of neonatal morbidity and mortality. However, in the setting of preterm birth phenotypic features of genetic diseases are often undifferentiated and are clinically very difficult to interpret based on the wide range of differential diagnoses. We report an extremely low birth weight infant (ELBW) born prematurely at 23 + 0 gestational weeks after twin pregnancy with a novel clinical manifestation with persistent hyperglycaemia as well as the known manifestations of disease-associated hypokinesia, renal salt wasting, and multifocal atrial tachycardia. The patient died of heart failure on the 72nd day of life. Whole exome sequencing (WES) revealed a previously well established, disease-causing heterozygous likely pathogenic variant in the Harvey rat sarcoma viral oncogene homolog (HRAS)-gene (c.35G > C, p. G12A, rs104894230), which implied the clinical diagnosis of Costello syndrome (CS; OMIM#190020.0004). The twin brother merely had complications related to preterm birth and did not show any CS symptoms. In conclusion, our case illustrated that CS should be considered in ELBW infants showing a life-threatening combination of complex cardiac arrhythmia and hypokinesia. If a syndromic disorder is suspected in the neonatal intensive care unit (NICU) setting, rapid WES is a useful, non-invasive diagnostic tool in critically ill ELBW infants.

Hypophosphatemia is Prevalent among Preterm Infants Less than 1,500 Grams.

OBJECTIVE: This article identifies the prevalence and associated factors of hypophosphatemia (HP) in very low birth weight (VLBW) infants in the first week of life. STUDY DESIGN: Prospective exploratory cohort study of 106 consecutive VLBW infants admitted to neonatal intensive care at Foothills Hospital, Calgary, Canada. HP was defined as at least one measurement of serum phosphate < 1.5 mmol/L (4.5 mg/dL). RESULTS: Seventy-seven percent (82/106) of the VLBW infants had HP, with significantly higher prevalence in infants < 1,000 g (94%) compared to infants ≥ 1,000 g (61%) (p < 0.001). Hypophosphatemic infants had lower birth weight (p < 0.001), gestational age (p < 0.001), and their increase in phosphate intake was slower (p = 0.003). Respiratory distress syndrome (RDS) (p = 0.002), intraventricular hemorrhage (IVH) ≥ grade III (p = 0.020), and hyperglycemia (p = 0.013) were more frequent among hypophosphatemic infants, especially among those < 1,000 g. Mortality, seizures, arrhythmias, and need for transfusion were not different between groups. Birth weight modified the association between RDS, IVH, hyperglycemia, and HP. CONCLUSION: HP was ubiquitous among infants < 1,000 g and highly prevalent among those weighing 1,000 to 1,500 g. While the direction of effect was not clear, RDS, IVH, and hyperglycemia were associated with HP. Prevention of HP in these physiologically immature neonates might improve neonatal outcomes.

Evaluation of dynamic thiol-disulfide homeostasis in very low-birth-weighted preterms.

BACKGROUND: Thiols are organic compounds containing sulfhydryl groups which exert antioxidant effects via dynamic thiol-disulfide homeostasis. The shift towards disulfides indicates the presence of oxidative environment. Thiol-disulfide homeostasis has not been evaluated in neonates. We aimed to evaluate dynamic thiol-disulfide homeostasis in preterm infants. METHODS: Preterm infants with birth weight less than 1500 g (25-32 weeks of gestation) were included. Infants with major congenital anomaly, perinatal asphyxia, twin to twin transfusion and infants who were mechanically ventilated and nil by mouth for more than 3 days or fed with formula, had intraventricular hemorrhage ≥ grade 2 or sepsis, received blood/blood product transfusion or inotrope treatment and developed bronchopulmonary dysplasia or retinopathy of prematurity (≥ stage 3), and died were excluded thereafter. Serum thiol-disulfide homeostasis was evaluated for three times: (Baseline, first week, third week). Serum native thiol, total thiol and disulfide were measured (µmol/Lt), disulfide:native thiol, disulfide:total thiol, and native thiol:total thiol ratios were calculated. Wilcoxon's test was used to analyze the significance of change in measurements. Baseline results were analyzed for gender and mode of delivery. RESULTS: Eighty preterm infants [1255 (1080-1415) grams] were included. Baseline values were native thiol: 209.54 ± 41.83 µmol/L; total thiol: 251.70 ± 45.82 µmol/L; disulfide: 21.08 ± 7.43 µmol/Lt; disulfide:native thiol: 10.49 ± 4.62; disulfide:total thiol: 8.45 ± 2.93; native thiol:total thiol: 83.10 ± 5.87. Thiol levels increased in each measurement, disulfide and disulfide/thiol ratios increased in the first week, decreased in the third week, ratio of native/total thiol decreased in the first week, increased in the third week. No effect of gender or mode of delivery on baseline thiol-disulfide homeostasis was detected. CONCLUSIONS: The shift in the thiol-disulfide equilibrium towards disulfides in the first week can be attributed to subjection of infants to many oxidative insults. Furthermore, the thiol predominance in the third week could be explained by the decrease in oxidative events and increase in feeding as a supply of antioxidants. This study, displaying the levels of the dynamic thiol-disulfide homeostasis in preterm infants without obvious risks for increased oxidative stress, may provide acceptable range for thiol-disulfide homeostasis in recovering preterm infants.

Lead and Mercury Levels in Preterm Infants Before and After Blood Transfusions.

Very low birth weight (VLBW) infants usually receive packed red blood cell unit (pRBC) transfusions. Heavy metal transfer via pRBCs is not widely discussed before. This study aimed to determine pre-/post-transfusion erythrocyte lead and mercury levels in infants and to correlate these levels to heavy metal concentrations in pRBCs. VLBW infants (n = 80), needing pRBC transfusion for the first time, were enrolled. Erythrocyte heavy metal levels were determined in pre-/post-transfusion blood samples and also in pRBC units. Mean lead and mercury levels in the pRBCs were found to be 16.3 ± 10.8 and 3.75 ± 3.23 µg/L, respectively. Of the infants, 69.7% received lead above reference dose. Erythrocyte lead levels increased significantly after transfusions (10.6 ± 10.3 vs. 13 ± 8.5, p < 0.05) with significant correlated to amount of lead within pRBCs (r = 0.28). Mean pre-/post-transfusion erythrocyte mercury levels were 3.28 ± 3.08 and 3.5 ± 2.83 µg/L, respectively (p > 0.05). There was a significant correlation between mean difference of mercury levels after transfusion and amount of mercury delivered by pRBCs (r = 0.28). Infants can be subject to high levels of lead and mercury through pRBC transfusions.

Vitamin D and associated perinatal-neonatal outcomes among extremely low-birth-weight infants.

OBJECTIVE: To evaluate vitamin D inadequacy among extremely low-birth-weight (ELBW, <1000 g) infants and the association between circulating vitamin D concentrations and perinatal-neonatal outcomes. STUDY DESIGN: Prospective cohort study of ELBW infants in the neonatal ICU. Blood was collected within the first 3 days after birth after obtaining informed consent. Circulating 25-hydroxyvitamin D concentrations (25(OH)D) were quantified using liquid chromatography-tandem mass spectroscopy and classified as vitamin D deficient, insufficient, or adequate ( < 20, 20-30, or > 30 ng/mL, respectively). Associations between 25(OH)D and perinatal-neonatal outcomes were determined by multivariable regression, adjusted for covariates that differ in the bivariate analysis. RESULTS: Of the 60 ELBW infants enrolled, 13 (22%) were vitamin D deficient, 15 (25%) were insufficient, and 32 (53%) were adequate. 25(OH)D levels were positively associated with fetal growth restriction and prolonged rupture of the membranes. CONCLUSIONS: Vitamin D inadequacy was frequent among ELBW infants. Circulating vitamin D concentrations were significantly associated with perinatal outcomes in this contemporary cohort.

Effect of fluctuation of oxygenation and time spent in the target range on retinopathy of prematurity in extremely low birth weight infants.

BACKGROUND: The association between saturation of peripheral oxygenation (SpO2) fluctuation and severity of retinopathy of prematurity (ROP) is well elucidated in extremely low birth weight (ELBW) infants. Time spent in the Target range of SpO2 is also associated with the severity of ROP. METHODS: In a prospective observational study, the SpO2 of all ELBW infants admitted to our unit were monitored for the first four weeks of life, and averaged every minute for analysis. The percent time spent at SpO2 <90%, 90-95%, and >95% and weekly SpO2 fluctuations [as SpO2 coefficient of variation (CoV)] were calculated. RESULTS: During the study period 21 infants had moderate to severe ROP and 35 infants served as controls. Infants with moderate to severe ROP were smaller and younger than their controls [676±124 grams vs. 796±148 grams (p < 0.001); and 24.0±1.0 weeks vs. 25.0±1.7 weeks (p < 0.001) respectively]. There were no significant differences in time spent in the 90-95% range between groups (p = 0.66). However there was a significant increase in weekly SpO2 CoV in infants with moderate to severe ROP vs. controls (p = 0.007). CONCLUSION: In ELBW infants, there was an association between SpO2 fluctuation during the first four weeks of life and severity of ROP, although, no association was established with time spent in the target range of SpO2.

Can Sequential Coagulation Monitoring Predict Major Haemorrhage in Extremely Low Birth Weight Infants?

INTRODUCTION: Bleeds such as intra-ventricular (IVH) and pulmonary haemorrhage (PH) are life-threatening events in extremely low birth weight (ELBW) infants. Serial coagulation monitoring by measuring the international normalized ratio (INR) with small volume samples might facilitate early diagnosis and possibly prevent major bleeds. MATERIALS AND METHODS: This was a prospective longitudinal study performed in ELBW infants, who received serial INR monitoring by point of care testing during their first 30 days of life. The primary objective was to explore whether INR monitoring could predict major bleeding events (IVH, PH). Secondary objectives were mortality and feasibility in this patient population. RESULTS: A total of 127 ELBW infants were stratified into a bleeding and a non-bleeding group. Bleeding events occurred in 31% (39/127) of the infants, whereupon 24% developed IVH and 9% PH. Infants in the bleeding group were 4 days younger at birth (p = 0.05) and had a substantially higher mortality rate of 26% versus 5% in controls (p = 0.005). Median INR during the first 3 days before a bleeding event was 1.55 (95% confidence interval [CI]: 1.39-1.74) compared with the control group with 1.45 (95% CI: 1.44-1.58; p = 0.81). Platelet counts were significantly lower in the bleeding group on the 3rd day and during the 2nd to 4th week of life. DISCUSSION: Serial coagulation monitoring by an INR point of care testing is feasible in ELBW infants but could not predict bleeding events. Further studies with daily monitoring of INR and platelet counts during the first days of life might be able to more precisely detect a risk of major haemorrhage in ELBW infants.

Serum glutathione S-transferase Pi as predictor of the outcome and acute kidney injury in premature newborns.

BACKGROUND: The incidence of acute kidney injury (AKI) among the neonates treated at the Neonatal Intensive Care Unit is high with high mortality rates. Glutathione S-transferase (GST) class Pi plays an important role in the protection of cells from cytotoxic and oncogenic agents. The aim of the study was to examine whether the levels of serum glutathione S-transferase Pi (GST Pi) determined after birth have any predictive value for the outcome and development of AKI in premature neonates. METHODS: The prospective study included 36 premature neonates. The data about morbidity was gathered for all the neonates included in the study. The blood samples were taken in the first 6 h of life and GST Pi levels were measured. RESULTS: The mean values and standard deviations of GST Pi among the neonates who died and who survived were 1.904 ± 0.4535 vs 1.434 ± 0.444 ng/ml (p = 0.0128). Logistic regression revealed a statistically significant, positive correlation between GST Pi levels and death (p = 0.0180, OR7.5954; CI 1.4148-40.7748).The mean value of GST Pi levels in the neonates with AKI was higher than in neonates without AKI (p = 0.011). CONCLUSIONS: The conclusion of our study is that high levels of serum GST Pi in the first 6 h after birth are associated with an increased mortality and development of AKI in prematurely born neonates.

Association of unit-wide oxygen saturation target on incidence of pulmonary hypertension in very low birthweight premature infants.

OBJECTIVE: Assess the effect of increasing pulse oximetry targets on incidence of pulmonary hypertension in very low birthweight premature infants. STUDY DESIGN: Retrospective cohort study comparing pulmonary hypertension incidence among three cohorts of premature infants exposed to varying oxygen saturation targets (Cohort 1: n=459, 1 May 2009 to 30 April 2011, 85-94%; Cohort 2: n=474, 1 May 2011 to 31 May 2013, 88-94%; Cohort 3: n=387, 1 June 2013 to 31 May 2015, 90-95%). Subjects had birth weight <1500 g and gestational age 23-32 weeks. Chi-square, Kruskall-Wallis and Anderson-Darling tests were used, as well as multivariable logistic regression. RESULTS: Incidence of pulmonary hypertension declined with higher oxygen saturation targets (19.0% Cohort 1, 7.9% Cohort 2, 9.6% Cohort 3, P<0.001). Other parameters were largely not different between cohorts though rates of chorioamnionitis and prenatal steroids increased and oxygen use, inhaled nitric oxide use, necrotizing enterocolitis and patent ductus arteriosus ligation decreased over time. CONCLUSION: Higher oxygen saturation targets for very low-birthweight premature infants were associated with reduced rates of pulmonary hypertension in this retrospective cohort study.

Bone fracture in severe small-for-gestational-age, extremely low birth weight infants: A single-center analysis.

INTRODUCTION: Bone fracture is a complication of extremely low birth weight infants (ELBWIs). This study aimed to analyze risk factors for bone fracture in a population of severe small-for-gestational-age (SGA) ELBWIs. METHODS: We retrospectively studied data from ELBWIs with a birth weight <1000g and <-2 standard deviations (SDs) born at the National Center for Child Health and Development, Japan, from 2013 to 2015. Infants were divided into fracture and control groups. Serum calcium (Ca) and phosphorus (P) levels, perinatal factors, and previously reported risk factors were analyzed. RESULTS: Of 25 cases of severe SGA ELBWIs, 5 cases of bone fracture were identified. Gestational age was 27.7±2.2, 29.1±2.6weeks (mean difference [MD] -1.4, 95% confidence interval [CI]: -4.0, -1.2, p=0.280), birth weight (BW) 448±105, 673±216g (MD -225, 95% CI: -433, -17, p=0.036) and BW-SD -4.1±0.1, -3.4±0.8 (MD -0.8, 95% CI: -1.5, -0.02, p=0.045) in the fracture and control groups, respectively. Minimums of serum Ca and P were 6.6±1.4, 8.1±0.8mg/dl (MD -1.5, 95% CI: -2.5, -0.6), p=0.003) and 2.3±0.6, 3.5±1.1mg/dl (MD -1.2, 95% CI: -2.2, -0.1, p=0.027) in the fracture and control groups, respectively. CONCLUSION: Lower BW and BW-SD were possible risk factors for bone fracture. Hypocalcemia and hypophosphatemia may also contribute to the condition.

Reference values for nucleated red blood cells and serum lactate in very and extremely low birth weight infants in the first week of life.

STUDY PURPOSE: To provide reference values for nucleated red blood cells and serum lactate concentrations in very and extremely low birth weight (VLBW/ELBW) infants in the first week of life. PATIENTS AND METHODS: Retrospective data analysis of serial, daily measurements of NRBC counts and serum lactate during the first 6days of life in VLBW and ELBW infants. RESULTS: In total, 250 infants<1500g were included in this study. Intrauterine growth retardation (IUGR) was seen in 87 (34.8%) patients. Gestational age (GA) ranged from 23 to 35weeks (mean 29.0weeks) and birth weight (BW) was 320-1499g (mean 1047.9g). During hospital stay, 55 (22%) patients developed IVH and 55 children (22%) BPD. PVL was seen in 12 (4.8%) cases, ROP in 93 (37.2%) and NEC in only 1 (0.4%) patient. NRBC counts as well as serum lactate concentrations depended significantly on birth weight (p<0.01) and presence respectively absence of IUGR (p<0.01). Both NRBC counts and serum lactate concentrations declined constantly during the 6-day period (p<0.01), and both were highly inter-correlated (p<0.01). CONCLUSIONS: This is one of only a very few studies that systematically and serially evaluated both NRBC counts and serum lactate concentration in VLBW and ELBW infants in the first 6days of life. Both parameters were significantly dependent on birth weight and the presence of IUGR. Moreover, a significant correlation between NRBC counts and serum lactate concentrations in this early period of life could be demonstrated. In future studies, the role of these readily available biomarkers in predicting important neonatal outcome parameters needs to be evaluated in a prospective manner.

Serum α-fetoprotein concentration in extremely low-birthweight infants.

BACKGROUND: Extremely low-birthweight infants (ELBWI) are at greater risk of developing hepatoblastoma than are normal-weight infants. Serum α-fetoprotein (AFP) plays an important role as a tumor marker in the diagnosis of hepatoblastoma, therefore the aim of this study was to determine the changes in serum AFP concentration after birth in ELBWI. METHODS: Data were obtained for infants born between January 2005 and March 2008 with birthweight <1000 g who were followed up at Gunma Children's Medical Center with clinical examinations, including monitoring of the development of hepatoblastoma. The relationship between serum AFP concentration and age was analyzed up to 730 days after birth. RESULTS: Overall, 95 serum AFP measurements were obtained from 23 infants 30-730 days of age, with gestational age 24-32 weeks, and birthweight 498-982 g. Log10 (AFP [ng/mL]) was significantly correlated with log10 (age [days]) (r = -0.961, P = 0.000, n = 95), with the following regression formula: log10 (AFP [ng/mL]) = 11.063 - 3.752 log10 (age [days]) (adjusted R2  = 0.923, n = 95). The standard error of the estimate, mean log10 (age [days]), and the sum of squares for log10 (age [days]) were 0.363, 2.503, and 10.579, respectively. CONCLUSIONS: A correlation was found between serum AFP concentration and age in ELBWI, and the 95%CI of serum AFP concentration was determined for ELBWI up to 2 years after birth.

Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants.

Objective To determine whether reduced growth velocity (GV) in extremely low birth weight infants is preceded by elevated inflammatory cytokines. Study Design GV was determined at 36 weeks' postmenstrual age (PMA) in 768 infants 401 to 1,000 g birth weight (BW). Association between blood cytokines measured through day of life 21 and GV was explored using linear regression models that adjusted for late-onset sepsis (LOS), BW, small for gestational age (SGA), gender, race, energy intake, and center. Results Serum interleukin-6 (IL-6) was increased at days 14 and 21 in LOS infants. LOS was associated with reduced energy intake and GV for weight (weight-GV) at 36 weeks' PMA. Linear regression analysis controlling for LOS and energy intake showed significant relationships between increased IL-6 at days 14 and 21 with reduced weight-GV at 36 weeks' PMA (p < 0.0001). The relationship between day 21 IL-6 and weight-GV was not associated with LOS (p = 0.12) when controlling for BW and energy intake. Both BW (p = 0.02) and energy intake (p = 0.003) influenced the relationship between day 14 IL-6 and weight-GV. Conclusion IL-6 elevation during the first month of life is associated with lower weight-GV at 36 weeks' PMA and may have a direct effect upon energy balance and postnatal growth.

Bone Mineral Density According to Dual Energy X-ray Absorptiometry is Associated with Serial Serum Alkaline Phosphatase Level in Extremely Low Birth Weight Infants at Discharge.

BACKGROUND: To examine bone mineral density in extremely low birth weight infants at discharge and investigate whether serial measurements of serum alkaline phosphatase (ALP) and phosphate can predict bone mineralization. METHODS: The individuals were 70 preterm infants. Serum calcium, phosphate, and ALP were measured at weekly intervals during admission in extremely low birth weight infants (mean gestational age, 25.3±2.1 weeks; birth weight, 812.8±141.1 g). Bone mineral apparent density (BMAD) of the lumbar spine was prospectively evaluated by dual energy X-ray absorptiometry at discharge (n=70). RESULTS: BMAD was classified as poor (< 25th percentile) at < 0.014 g/cm3, fair (25th-75th percentile) at < 0.014-0.021 g/cm3, and good (> 75th percentile) at > 0.021 g/cm3, based on the distribution of BMAD values in infants with noncomplicated courses of prematurity (n=43). In a further multivariate analysis, the number of total parenteral nutrition days, phosphate at 2 postnatal weeks and 3 postnatal weeks, and ALP at 4 postnatal weeks and 5 postnatal weeks had an impact on bone mineral density at the lumbar spine, independent of gestational age and body weight. Peak ALP activities exceeding 650 IU/L revealed low bone mineral density with 80% sensitivity and 64% specificity (AUC, 0.70; p=0.005). CONCLUSION: Serial measurements of serum ALP and phosphate are associated with decreased bone mineralization by dual energy X-ray absorptiometry at discharge in extremely low birth weight infants.

Risk factors vary early preterm birth and perinatal complications after assisted reproductive technology.

We conducted a study of markers of endothelial dysfunction and angiogenesis regulation, as well as the identification of the main lymphocyte populations, activated CD3 + CD95+-cells and cytokine-producing CD4 + IFN-γ+-, CD4 + IL-4+ -lymphocytes in the 1st trimester of gestation in women with ART-induced pregnancy and spontaneous pregnancy. We used the same indicators to assess the immune status of ELBW infants at birth and at the post-conceptual age of 38-40 weeks. It was determined that the risk factors of very early preterm delivery are: threatened miscarriage, chronic placental insufficiency, endothelial dysfunction, increased spontaneous production of intracellular cytokines. Adverse perinatal outcomes in ELBW infants from ART-induced pregnancy are associated with lower anthropometric measures, low Apgar scores high level of inflammatory infections (pneumonia), grade II intraventricular hemorrhage, movement disorders in the form of lower paraparesis. Immune status of those infants is characterized by the increase in the number of CD8+- and CD3-CD16 + CD56+ -lymphocytes, the expression level of Fas-receptor by T-cells, and the increased production of intracellular and serum IFNγ against the decrease in the number of CD4+-cells, which indicates enhancing of cytotoxic effector potential and proinflammatory orientation of cell responses.