GLYCEMIC VARIABILITY IS ASSOCIATED WITH TREATMENT REQUIRING RETINOPATHY OF PREMATURITY: A Case-Control Study.

PURPOSE: To assess the association between glycemic variability (GV) and Type 1 retinopathy of prematurity (ROP) in infants with birth weights of less than 1,251 g. METHODS: A case-control study of infants with birth weights of less than 1,251 g who developed Type 1 ROP (n = 20) was conducted. Controls had a less severe ROP or no eye disease and were individually matched for gestational age and birth weight (n = 40). Odds ratios of ROP were calculated based on multiple factors including oxygen exposure, respiratory support, incidence of hyperglycemia, and GV. For glucose measurements, a continuous glucose monitoring system was used. RESULTS: There were no significant differences in gender, antenatal steroid administration, severity of illness, and Apgar score. Univariate analyses suggest increased risk for the development of Type 1 ROP based on incidence of intraventricular hemorrhage Grade 3 or 4 (P = 0.048), duration of oxygen exposure (P = 0.003), incidence of hyperglycemia over 150 mg/dL (P = 0.01), and GV according to significantly higher SD (P = 0.002), coefficient of variation (P = 0.001), and mean amplitude of glucose excursion (P = 0.008). Using a multiple regression model, increased risk of Type 1 ROP was only found to be associated with duration of oxygen exposure and higher GV. CONCLUSION: Our study demonstrates a relationship between GV and the development of severe ROP.

Glycemic variability in continuous glucose monitoring negatively correlates with gestational age in very low birth weight infants.

Introduction: High glycemic variability is commonly observed in intensive care patients, both in pediatrics and adults. The aim of the study was to evaluate the correlation between gestational age and glycemic variability in cohort of very low birth infants.Patients and methods: A prospective, single-center, open cohort study enrolled 74 very low birth weight infants with a mean birth weight of 1066 g. Continuous glucose monitoring system (Guardian Real-Time CGM®, Medtronic, Northridge, CA, USA) was used to measure glucose levels. Spearman's rank correlation coefficients were calculated for glycemic variability indices and gestational age. Multiple linear regression analyses were used to assess the adjusted effect of multiple glycemic variability variables.Results: The correlations between all calculated glycemic variability indices and gestational age were negative. In multiple regression analysis, all glycemic variability indices negatively correlated with gestational age and positively correlated with mean interstitial fluid glucose concentration.Conclusions: Glycemic variability in very low birth weight infants correlates with gestational age and mean glucose concentrations.

Extremely Low Birth Weight Predisposes to Impaired Renal Health: A Pooled Analysis.

BACKGROUND: A number of studies examined the association between preterm delivery and kidney size and function later in life. However, the number of cases in published cohort studies is low. This study was aimed at performing a multicenter collaboration to pool data to obtain more accurate results to quantify the extent of renal impairment in former extremely low birth weight (ELBW; <1,000 g) children. METHODOLOGY: We performed a subject-level meta-analysis to pool data from Cracow (64 cases/34 controls) and Leuven (93 cases/87 controls). We assessed and analyzed cystatin C, estimated glomerular filtration rate (eGFR), ultrasound kidney length, and blood pressure (BP) in 11-year-old ELBW children compared with controls born at term. The prevalence of hypertension (HT) and prehypertension (preHT) in both groups was also analyzed. RESULTS: The study group comprised 157 former ELBW children (gestational age 23-33 weeks and birth weight 430-1,000 g) and 123 children born at term. Former ELBW children had lower mean eGFR (100.62 ± 16.53 vs. 111.89 ± 15.26 mL/min/1.73 m2; p < 0.001), smaller absolute kidney length (8.56 ± 0.78 vs. 9.008 ± 0.73 cm; <0.001), and higher systolic (111.8 ± 9.8 vs. 107.2 ± 9.07 mm Hg; p = 0.01) and diastolic (68.6 ± 6.8 vs. 66.3 ± 7.7 mm Hg; p = 0.03) BP. Smaller renal size in former ELBW children was positively associated with lower birth weight, shorter gestational age, and severity of perinatal complications (intraventricular hemorrhage, length of stay, mechanical ventilation, and oxygen therapy). CONCLUSION: ELBW is associated with lower eGFR and a high frequency of preHT and HT.

Lung ultrasound in the diagnosis of neonatal respiratory failure prior to patient transport.

PURPOSE: Lung ultrasound (LUS) at the point-of-care is a new method that is increasingly used in neonatology. The aim of this study was to determine the utility of the addition of LUS prior to the interhospital transport of neonates with respiratory failure. METHODS: LUS was performed on 50 newborns with respiratory failure prior to transport to a tertiary neonatal intensive care unit. We analyzed the performance of LUS for diagnosing the cause of respiratory failure, the concordance between LUS, chest X-ray (CXR) and final clinical diagnosis, and the impact of LUS on clinical decision making before transport. RESULTS: LUS sensitivity for the diagnosis of respiratory distress syndrome was 91.3% (95%CI: 70.5-98.5%), and specificity was 92.6% (95%CI: 74.2-98.7%), whereas sensitivity and specificity of CXR were 69.6% (95%CI: 47.0-85.9%) and 81.5% (95%CI: 61.2-92.9%), respectively. For the recognition of pneumothorax (PTX) LUS had a sensitivity of 83.3% (95%CI: 36.5-99.1%) and a specificity of 100% (95%CI: 89.9-100%). For CXR, sensitivity was 16.7% (95%CI: 0.01-63.5%) and specificity was 97.7% (95%CI: 86.4-99.9%). The agreement between LUS and CXR in diagnosing the cause of respiratory failure was substantial (κ of 0.57 [95%CI: 0.40-0.74]) and the agreement between LUS and the final clinical diagnosis was very good (κ of 0.86 [95%CI: 0.74-0.98]). In 42% of the patients, a LUS examination prior to transport indicated the need for endotracheal tube repositioning or PTX decompression. CONCLUSION: LUS may be a reliable imaging technique for differentiating the causes of respiratory failure before neonatal transport. Use of LUS may optimize the care of infants during transport.

Impact of early glycemic variability on mortality and neurologic outcome of very low birth weight infants: Data from a continuous glucose monitoring system.

OBJECTIVE: Background: Glycemic variability (GV) has been a matter of interest in recent years. However, glycemic variability in preterm infants has not been adequately investigated. Objectives: To evaluate the impact of glycemic variability obtained from continuous glucose monitoring on mortality and neurologic outcomes: grade 3 or 4 intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and retinopathy of prematurity (ROP) requiring treatment among very low birth weight infants. PATIENTS AND METHODS: Material and methods:A prospective, single-center, open cohort study enrolled 74 very low birth weight infants with a mean birthweight of 1066 g (+/-267). A continuous glucose monitoring system (CGM) was used to measure glucose during the first week of life. The impact of glycemic variability (standard deviation SD; coefficient of variation CV; and mean amplitude of glucose excursion MAGE) on mortality and neurologic outcomes of infants was evaluated. RESULTS: Results: Univariate analysis revealed that glycemic variability occurring during the first week of life was not be associated with mortality before term-equivalent age and PVL. Higher GV was associated with grade 3 or 4 IVH (CV p=0.025; MAGE p=0.032) and ROP requiring treatment (SD p=0.019; CV p=0.026; MAGE=0.029). However, logistic regression models did not show a significant association between GV occurring during the first week of life and grade 3 or 4 IVH (MAGE OR 2.64; 95% CI 0.71-9.92) or ROP requiring treatment (MAGE OR 1.74; 95% CI 0.57-5.32). CONCLUSION: Conclusions: Further prospective studies are needed to fully investigate the impact of GV on mortality and morbidity in premature infants. The potential benefits of reducing glucose blood fluctuations in VLBW infants need to be addressed.

Defining Glycemic Variability in Very Low-Birthweight Infants: Data from a Continuous Glucose Monitoring System.

BACKGROUND: Glucose variability (GV) is a matter of interest for researches in recent years. It is connected with oxidative stress, which is crucial in the development of multiple complication of prematurity. However, glycemic variability in preterm infants was poorly investigated. This study aims to investigate glycemic variability obtained from a continuous glucose monitoring (CGM) system in a cohort of very low-birthweight (VLBW) infants. METHODS: A prospective, single-center, open cohort study enrolled 74 VLBW infants with a mean birthweight of 1066 g and median gestational age of 28 weeks. A CGM system (Guardian Real-Time CGM®, Medtronic, Northridge, CA) was used to measure interstitial glucose concentration. The glycemic variability was calculated using EasyGV. RESULTS: Most glycemic variability indices in VLBW infants showed log-normal distribution and for these, geometric mean ÷/ × geometric standard deviation (GSD) was calculated: M-value 2.28 (÷/ × 1.82), mean amplitude of glycemic excursions (MAGE) 1.89 (÷/ × 1.34), average daily risk ratio (ADRR) 2.22 (÷/ × 2.56), lability index 0.46 (÷/ × 1.71), J-index 0.46 (÷/ × 1.71), low blood glucose index 2.05 (÷/ × 1.66), high blood glucose index 1.11 (÷/ × 2.44), continuous overlapping net glycemic action (CONGA) 5.54 (÷/ × 1.16), mean of daily differences (MODD) 1.23 (÷/ × 1.38), and coefficient of variation 1.15 (÷/ × 1.31). Only SD of glucose concentration showed a normal distribution: arithmetic mean 1.24 (+/-0.37). ADRR, J-index, MODD, CONGA, and MAGE are moderately to strongly correlated with SD. CONCLUSIONS: In our cohort of VLBW infants, almost all glycemic variability indices showed skewed positive distribution. The natural central tendency measure for the log-normally distributed data is the geometric mean and for statistical variation is the GSD.

Preterm Glycosuria - New Data from a Continuous Glucose Monitoring System.

BACKGROUND: Careful control of glucose homeostasis is essential for infants with very low birth weight (VLBW). In clinical practice, blood and urine glucose levels are monitored; however, their correlation has not been fully investigated in VLBW infants. OBJECTIVES: To evaluate the correlation between interstitial fluid glucose concentration (ISFG), glycosuria, and urine output among VLBW infants through continuous glucose monitoring (CGM). METHODS: A prospective, single-center, open cohort study enrolled 74 VLBW infants with a mean birth weight of 1,066 g. CGM (Guardian Real-Time CGM®; Medtronic, Northridge, CA, USA) was used to measure glucose. The urine output was calculated using 4-hour intervals. Reagent strips were used for semiquantitative measurement of glycosuria. RESULTS: The CGM delivered 102,334 glucose measurements. 2,684 urine samples were checked for glycosuria, of which 92.06% remained negative. Corresponding glycemia in samples without glycosuria remained normoglycemic (median 103 mg/dL; 10-90th percentile 80-144 mg/dL). The median glucose concentrations for samples in ascending glycosuria categories 1+, 2+, 3+, and 4+ were 152, 181, 214, and 222 mg/dL, respectively. A moderate correlation between ISFG and urine output was found for categories ≥1+ (rs = 0.56; 95% confidence interval 0.42-0.68; p < 0.001). The urine output was significantly lower when glycosuria was absent (p < 0.05). Polyuria was observed only in glycosuria 4+ (median urine output 9.9; interquartile range 7.4-12.2 mL/kg/h). CONCLUSIONS: The renal glucose threshold in VLBW infants is between 150 and 180 mg/dL. A negative result for glycosuria is a reliable screening test to exclude hyperglycemia. Occurrence of glycosuria ≥1+ is an indication to test blood glucose.

Longitudinal assessment of renal size and function in extremely low birth weight children at 7 and 11 years of age.

BACKGROUND: There are a lack of studies describing a longitudinal association between preterm delivery and renal complications later in life. We assessed renal size and function in preterm infants born with extremely low birth weight (ELBW) during 4 years of follow-up, comparing these parameters to age-matched children born full term (term controls). METHODS: The results of selected renal laboratory tests [levels of cystatin C, creatinine, blood urea nitrogen (BUN)] and of renal ultrasound evaluations were compared between the ELBW group and the term control group at age 7 and 11 years. RESULTS: The study population consisted of 64 children born with ELBW (ELBW children) who had been recruited at birth and 36 children born at term (term children) who took part in both follow-up assessments. Renal ultrasound examination revealed a significantly smaller renal volume in the 7- and 11-year-old ELBW children compared to the term controls [right kidney volume: 50.8 vs. 61.2 ml/m(2), respectively, at 7 years (p <0.01) and 51.4 vs. 58.2 ml/m(2), respectively, at 11 years (p <0.01); left kidney volume: 51.4 vs. 60.3 ml/m(2), respectively, at 7 years (p <0.01) and 55.2 vs. 60.7 ml/m(2), respectively, at 11 years (p = 0.02)]. Renal function in ELBW children was also affected. Serum cystatin C levels were significantly higher in ELBW children than in the controls at 7 years of age, and this difference remained statistically significant at 11 years of age [0.63 vs. 0.59 mg/l, respectively, at 7 years (p = 0.02) and 0.72 vs. 0.61 mg/l, respectively, at 11 years (p = 0.01)]. Six ELBW children also had elevated cystatin C levels (0.97-1.11 mg/l) at 11 years of age. Cystatin C levels were within normal range in the ELBW children at age 7 years and in term children in both follow-up studies. BUN levels were higher in ELBW children at the age of 11 years (4.49 vs. 4.15 mmol/l; p = 0.028). CONCLUSION: Continued follow-up of these patients will reveal whether the observed worsening in renal function will persist into adulthood.

THE INCIDENCE OF HYPERGLYCAEMIA IN VERY LOW BIRTH WEIGHT PRETERM NEWBORNS. RESULTS OF A CONTINUOUS GLUCOSE MONITORING STUDY--PRELIMINARY REPORT.

AIM: To determine the incidence of hyperglycaemia in very low birth weight preterm newborns. To assess risk factors in hyperglycemia and outcome in groups of children with and without clinically significant hyperglycaemia. MATERIAL AND METHODS: The prospective study included newborns with very low birth weight in whom the continuous glucose monitoring system was used for glucose measurements. A standardized hyperglycaemia treatment schedule was implemented and a uniform nutrition strategy introduced. The patients were divided into groups: group A--patients with under 5% of the readings over 150 mg/dL of glucose (control group), group B--patients with more than 5% of the readings over 150 mg/dL of glucose and under 5% of the readings over 180 mg/dL of glucose (mild hyperglycaemia), and group C--patients with over 5% of the readings > 180 mg/dL or on insulin treatment (moderate or severe hyperglycaemia). RESULTS: 63 patients were included in the study. Their mean gestational age was 27.7 weeks (SD:2.4), the mean birth weight was 1059g (SD: 262 g). Hyperglycaemia was detected in 27 (42.9%), including mild hyperglycaemia in 19 (30.2%), and moderate or severe hyperglycaemia in 8 (12.7%) neonates. Lower gestational age (p = 0.02) and higher CRIB IIscore (p < 0.01) were positively associated with hyperglycaemia. Early-onset sepsis (p < 0.01) was associated with higher glucose levels as well. A significantly higher mortality rate on the 28th day of life (p = 0.02), depending on the severity of hyperglycemia, was noted. No adverse effects related to the continuous glucose monitoring system were observed. CONCLUSIONS: The study confirmed the usefulness and safety of the continuous glucose monitoring system in VLBW neonates. A continuous glucose monitoring system should be used in neonatal intensive care units as a standard method.