Marta Thio

Early Insulin Therapy in Very-Low-Birth-Weight Infants

BACKGROUND Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates. METHODS In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm. RESULTS As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04). CONCLUSIONS Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)

Prevalence and Determinants of Hyperglycemia in Very Low Birth Weight Infants: Cohort Analyses of the NIRTURE Study

OBJECTIVES To investigate the prevalence and determinants of hyperglycemia in the preterm population, as part of the Neonatal Insulin Therapy in Europe (NIRTURE) Trial. STUDY DESIGN We conducted prospective cohort analyses of continuous glucose monitoring data from control infants participating in an international randomized controlled trial. Data were collected from 188 very low birth weight infants (<1500 g). RESULTS In the first week of life, 80% of infants had evidence of glucose levels >8 mmol/L, and 32% had glucose levels >10 mmol/L >10% of the time. Independent risk factors for hyperglycemia included increasing prematurity, small size at birth, use of inotropes, lipid infusions, and sepsis. There was a lack of association between rate of dextrose infused and risk of hyperglycemia. CONCLUSION The prevalence of hyperglycemia in the very low birth weight infant is high, with marked variability in prevalence between infants, not simply related to rates of glucose infused, but to other potentially modifiable risk factors.

A survey of neonatal resuscitation in Spain: gaps between guidelines and practice.

Objectives: To audit the knowledge and application of internationally recommended newborn resuscitation (NR) guidelines among delivery room (DR) caregivers of Spanish hospitals.

A randomised controlled trial of early insulin therapy in very low birth weight infants, "NIRTURE" (neonatal insulin replacement therapy in Europe)

BackgroundStudies in adult intensive care have highlighted the importance of insulin and improved glucose control on survival, with 32% reduction in mortality, 22% reduction in intensive care stay and halving of the incidence of bacteraemia. Very low birth weight infants requiring intensive care also have relative insulin deficiency often leading to hyperglycaemia during the first week of life. The physiological influences on insulin secretion and sensitivity, and the potential importance of glucose control at this time are not well established. However there is increasing evidence that the early postnatal period is critical for pancreatic development. At this time a complex set of signals appears to influence pancreatic development and β cell survival. This has implications both in terms of acute glucose control but also relative insulin deficiency is likely to play a role in poor postnatal growth, which has been associated with later motor and cognitive impairment, and fewer β cells are linked to risk of type 2 diabetes later in life.MethodsA multi-centre, randomised controlled trial of early insulin replacement in very low birth weight babies (VLBW, birth weight < 1500 g). 500 infants will be recruited from 10 centres in the UK and Europe. Babies will be randomised to receive a continuous insulin infusion (0.05 units/kg/h) or to receive standard neonatal care from the first day of life and for the next 7 days. If blood glucose (BG) levels fall infants will receive 20% dextrose titrated to maintain normoglycaemia (4–8 mmol/l). If BG is consistently above 10 mmol/l babies will receive standard treatment with additional insulin infusion. The primary end point will be mortality on or before expected date of delivery, secondary end points will be markers of morbidity and include episodes of sepsis, severity of retinopathy, chronic lung disease and growth.Trial RegistrationCurrent Controlled Trials ISRCTN78428828. EUDRACT Number 2004-002170-34

Comparison of heart rate and oxygen saturation measurements from Masimo and Nellcor pulse oximeters in newly born term infants.

To compare heart rate (HR) measurements from Masimo and Nellcor pulse oximeters (POs) against HR measured via a three lead electrocardiograph (ECG) (HRECG). We also compared peripheral oxygen saturation (SpO2) measurements between Nellcor and Masimo oximeters.

The risk for hyperoxaemia after apnoea, bradycardia and hypoxaemia in preterm infants

Objective To investigate the occurrence and duration of oxygen saturation (SpO2) ≥95%, after extra oxygen for apnoea, bradycardia, cyanosis (ABC), and the relation with the duration of bradycardia and/or SpO2 ≤80%. Methods All preterm infants <32 weeks’ gestation supported with nasal continuous positive airway pressure (nCPAP) admitted to our centre were eligible for the study. We retrospectively identified all episodes of ABCs. In ABCs where oxygen supply was increased, duration and severity of bradycardia (<80 bpm), SpO2 ≤80%, SpO2 ≥95% and their correlation were investigated. Results In 56 infants, 257 ABCs occurred where oxygen supply was increased. SpO2 ≥95% occurred after 79% (202/257) of the ABCs, duration of extra oxygen supply was longer in ABCs with SpO2 ≥95% than without SpO2 ≥95% (median (IQR) 20 (8–80) vs 2 (2–3) min; p<0.001)). The duration of SpO2 ≥95% was longer than bradycardia and SpO2 ≤80% (median (IQR) 13 (4–30) vs 1 (1–1) vs 2 (1–2) min; p<0.001). SpO2 ≥95% lasted longer when infants were in ambient air than when oxygen was given before the ABC occurred (median (IQR)15 (5–38) min vs 6 (3–24) min; p<0.01). Conclusions In preterm infants supported with nCPAP in the neonatal intensive care unit (NICU), SpO2 ≥95% frequently occurred when oxygen was increased for ABCs and lasted longer than the bradycardia and SpO2 ≤80%.

Validation of the continuous glucose monitoring sensor in preterm infants

Objective Recent studies have highlighted the need for improved methods of monitoring glucose control in intensive care to reduce hyperglycaemia, without increasing the risk of hypoglycaemia. Continuous glucose monitoring is increasingly used in children with diabetes, but there are little data regarding its use in the preterm infant, particularly at extremes of glucose levels and over prolonged periods. This study aimed to assess the accuracy of the continuous glucose monitoring sensor (CGMS) across the glucose profile, and to determine whether there was any deterioration over a 7 day period. Design Prospectively collected CGMS data from the NIRTURE Trial was compared with the data obtained simultaneously using point of care glucose monitors. Setting An international multicentre randomised controlled trial. Patients One hundred and eighty-eight very low birth weight control infants. Outcome measures Optimal accuracy, performance goals (American Diabetes Association consensus), Bland Altman, Error Grid analyses and accuracy. Results The mean (SD) duration of CGMS recordings was 156.18 (29) h (6.5 days), with a total of 5207 paired glucose levels. CGMS data correlated well with point of care devices (r=0.94), with minimal bias. It met the Clarke Error Grid and Consensus Grid criteria for clinical significance. Accuracy of single readings to detect set thresholds of hypoglycaemia, or hyperglycaemia was poor. There was no deterioration over time from insertion. Conclusions CGMS can provide information on trends in glucose control, and guidance on the need for blood glucose assessment. This highlights the potential use of CGMS in optimising glucose control in preterm infants.

Docosahexaenoic Acid and Bronchopulmonary Dysplasia in Preterm Infants

BACKGROUND Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n‐3 long‐chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking. METHODS We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen‐saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first. RESULTS A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06). CONCLUSIONS Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.)

Determining the best method of Nellcor pulse oximeter sensor application in neonates

Aim:  To identify the optimal sensor application method that gave the quickest display of accurate heart rate (HR) data using the Nellcor OxiMax N‐600x pulse oximeter (PO).

How ABBA may help improve neonatal resuscitation training: auditory prompts to enable coordination of manual inflations and chest compressions.

Resuscitation guidelines recommend 90 chest compressions (CCs) and 30 inflations (INFs) per minute for neonatal cardiopulmonary resuscitation (nCPR). We hypothesised that auditory prompts would help coordinate these actions. Our aim was to investigate the effect of musical prompts during nCPR training on adherence to recommended CC and INF rates and on the quality of delivered INFs.