Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia.

BACKGROUND: Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment. METHODS: In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter [2.0 mmol per liter]) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter [2.6 mmol per liter]) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 [mean {±SD}, 100±15]), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group. RESULTS: Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores [±SE], 102.9±0.7 [cognitive] and 104.6±0.7 [motor] in the lower-threshold group and 102.2±0.7 [cognitive] and 104.9±0.7 [motor] in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death. CONCLUSIONS: In otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months. (Funded by the Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768.).

Hospitalization for respiratory syncytial virus infection in young children: development of a clinical prediction rule.

BACKGROUND: Because passive immunization against respiratory syncytial virus (RSV) is costly, its use should be restricted to well-defined groups of high risk children. We aimed to develop a clinical prediction rule that estimates the individual monthly risk of hospitalization for RSV infection in young children. METHODS: A retrospective cohort study was conducted in the southwestern part of The Netherlands. We included children born between January 1, 1996 and December 31, 1998. Children hospitalized for proven RSV infection were compared with children not hospitalized for RSV infection. The monthly risk was estimated with a logistic regression model including 5 clinical predictors (gender, gestational age, birth weight, presence of bronchopulmonary dysplasia and age) and the mean seasonal monthly pattern of RSV infections. We compared the predictive performance of the prediction rule with the guidelines of the American Academy of Pediatrics (AAP). FINDINGS: Information was collected on 2469 hospitalized children and 140,661 children who were 1,181,790 months at risk. All predictors were statistically significant, with age and the seasonal monthly RSV pattern having the strongest effects. The clinical prediction rule that included these predictors could better discriminate between high and low risk children than the AAP guidelines and would potentially reduce the number of immunizations by 20%. INTERPRETATION: The prediction rule reliably estimates individual monthly risks of hospitalization for RSV infection in the population studied. It provides an improved index for passive immunization but further validation in other populations is required.

A randomized, placebo-controlled GH trial in very preterm infants who were at risk for bronchopulmonary dysplasia and were treated with dexamethasone.

Very preterm infants who develop bronchopulmonary dysplasia are often treated with dexamethasone (DEXA) to wean them from the ventilator. As DEXA has growth-suppressive and catabolic effects, which might have long-term consequences on growth and organ development, we investigated whether high-dose GH treatment could overcome these effects. In a randomized, double-blind, placebo-controlled trial, 30 ventilated very low birth weight infants were assigned to receive either GH or placebo treatment after start of DEXA. DEXA was given for 24 d (starting dose 0.5 mg . kg(-1) . d(-1), tapering off every third day). Simultaneously, high-dose GH (0.3 mg . kg(-1) . d(-1)) or placebo was administered during 6 wk. During high-dose DEXA treatment (dose 0.5-0.3 mg . kg(-1) . d(-1)), no gain in head circumference, weight, crown-heel length, and knee-heel length occurred in the GH and placebo groups. Growth during the 6-wk study period was not different between the GH and the placebo groups. Two patients in the placebo group died, but the number and the severity of adverse effects was not statistically different between the GH and placebo groups. In conclusion, high-dose GH treatment did not improve growth in DEXA-treated very preterm infants and thus cannot be recommended to prevent growth failure in these infants. During high-dose DEXA, a complete growth arrest occurred, including stunting of head growth. Growth in head circumference and weight with lower dose DEXA was comparable to growth after discontinuation of DEXA.

Effect of dexamethasone treatment on serum GH, IGF-I, and the binding proteins IGFBP-1 and -3 in ventilated very preterm infants.

Very preterm infants developing bronchopulmonary dysplasia frequently show a compromised growth in the neonatal period especially when steroids are given to facilitate weaning from the ventilator. The aim of this study was to evaluate the short-term effect of dexamethasone (DEXA) on the GH-IGF axis in ventilated very preterm infants developing bronchopulmonary dysplasia. We studied 10 very preterm artificially ventilated infants with bronchopulmonary dysplasia [median (range) gestational age 27.5 wk (25.9-32.0 wk), median (range) birth weight 970 g (610-2150 g)] immediately before and 2 d after the start of DEXA treatment. On both days of study, serum GH profiles were obtained, and serum IGF-I and IGF binding protein (IGFBP) -1 and -3 levels were measured. The ventilation score and the nutritional intake were calculated. Before the start of DEXA treatment, the median serum mean GH level was 12.0 microg/L (6-28.4 microg/L), whereas 2 d after the start of DEXA treatment the median serum mean GH level declined significantly to a value of 4.4 microg/L (1.7-11.9 microg/L). During DEXA treatment, mean, baseline, and maximal GH levels (Pulsar analysis) were significantly lower compared with pretreatment levels (p < 0.01, p < 0.01, and p < 0.05, respectively). Serum IGF-I and IGFBP-3 levels did not decline during DEXA. Serum IGFBP-1 levels were significantly lower compared with pretreatment levels (p < 0.01). Serum GH levels during DEXA treatment were correlated with neither the time interval between the administration of DEXA and the second GH profile nor the cumulative DEXA dose administered. Ventilation score and nutritional intake did not significantly correlate with serum GH, IGF-I, or IGFBP-1 or -3 levels, either before or after the start of DEXA. Two days of DEXA treatment in very preterm ventilated infants has a suppressive effect on serum GH levels, without an acute decline in serum IGF-I levels. A concomitant decrease in serum IGFBP-1 levels was found.

Worsening of V'maxFRC in infants with chronic lung disease in the first year of life: a more favorable outcome after high-frequency oscillation ventilation.

Little is known about the development of maximal flow at functional residual capacity, a measure of airway patency, in infants with chronic lung disease (CLD). In a follow-up study, we evaluated V'maxFRC in very low birth weight infants with CLD, treated with high-frequency oscillation ventilation (HFOV) or conventional mechanical ventilation. In 36 infants with CLD, V'maxFRC was evaluated at 6 and/or 12 months corrected age, and the relationship between perinatal factors and lung function was studied. Mean (SD) birth weight and gestational age were 837 (152) g and 26.8 (1.7) weeks, respectively. At 6 and 12 months, mean V'maxFRC was significantly below normal. Between 6 and 12 months, there was a mean (95% confidence interval) reduction in V'maxFRC (Z score) of 0.5 (0.2-0.7) (p < 0.001). At 12 months, the mean V'maxFRC (Z score) was higher for children initially treated with HFOV (n = 15), as compared with children treated with conventional mechanical ventilation (n = 16): mean (95% confidence interval) difference was 0.6 (0.2-1.0) (p = 0.008). We conclude that very low birth weight infants with CLD have decreased V'maxFRC that worsen during the first year of life. Initial treatment with HFOV was associated with a more favorable outcome of V'maxFRC at 12 months corrected age.