Gentamicin Dosing in Neonates with Normal Renal Function: Trough and Peak Levels.

BACKGROUND AND OBJECTIVE: Gentamicin is commonly used in neonates, and it requires drug concentration monitoring. The objective of this study was to determine the extent of high trough (≥ 2 mg/l) and therapeutic peak serum gentamicin concentrations (5-12 mg/l) using our current gentamicin regimen and to adjust the dosing regimen accordingly and reassess. METHODS: This was a prospective cohort study of neonates, with normal renal function, who were prescribed gentamicin. Group 1: March 2014-July 2017-gentamicin intravenous (IV) 2.5 mg/kg given every 36 h if < 30 weeks gestational age (GA) and every 24 h if ≥ 30 weeks GA; Group 2: August 2019-February 2020-gentamicin IV 3.5 mg/kg given every 36 h if < 30 weeks GA and every 24 h if ≥ 30 weeks GA. We assessed the number of neonates with aberrant trough and peak serum gentamicin concentrations. RESULTS: Forty-eight neonates < 30 weeks GA and 34 ≥ 30 weeks GA were given 2.5 mg/kg gentamicin. Eleven (23%) neonates < 30 weeks GA and four (13%) ≥ 30 weeks GA had subtherapeutic peak concentrations (< 5 mg/l); none had supratherapeutic (> 12 mg/l) or toxic trough concentrations (≥ 2 mg/l). Forty-four neonates < 30 weeks GA and 54 ≥ 30 weeks GA were given 3.5 mg/kg gentamicin. Eighty-four (86%) had non-toxic trough concentrations (< 2 mg/l). One (1%) < 30 weeks GA neonate had subtherapeutic (< 5 mg/l) and one (1%) neonate ≥ 30 weeks GA had supratherapeutic (> 12 mg/l) peak concentrations. CONCLUSIONS: Gentamicin regimen of 2.5 mg/kg given every 36 h for neonates < 30 weeks GA and every 24 h for neonates ≥ 30 weeks GA was suboptimal at achieving therapeutic gentamicin peak. Increasing the dosage to 3.5 mg/kg achieved therapeutic peak concentrations in 98% and non-toxic trough concentrations in 86% of all neonates (prior to dose interval adjustment).

Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants.

BACKGROUND: Treatment with nasal high-flow therapy has efficacy similar to that of nasal continuous positive airway pressure (CPAP) when used as postextubation support in neonates. The efficacy of high-flow therapy as the primary means of respiratory support for preterm infants with respiratory distress has not been proved. METHODS: In this international, multicenter, randomized, noninferiority trial, we assigned 564 preterm infants (gestational age, ≥28 weeks 0 days) with early respiratory distress who had not received surfactant replacement to treatment with either nasal high-flow therapy or nasal CPAP. The primary outcome was treatment failure within 72 hours after randomization. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the chosen margin of noninferiority was 10 percentage points. Infants in whom high-flow therapy failed could receive rescue CPAP; infants in whom CPAP failed were intubated and mechanically ventilated. RESULTS: Trial recruitment stopped early at the recommendation of the independent data and safety monitoring committee because of a significant difference in the primary outcome between treatment groups. Treatment failure occurred in 71 of 278 infants (25.5%) in the high-flow group and in 38 of 286 infants (13.3%) in the CPAP group (risk difference, 12.3 percentage points; 95% confidence interval [CI], 5.8 to 18.7; P<0.001). The rate of intubation within 72 hours did not differ significantly between the high-flow and CPAP groups (15.5% and 11.5%, respectively; risk difference, 3.9 percentage points; 95% CI, -1.7 to 9.6; P=0.17), nor did the rate of adverse events. CONCLUSIONS: When used as primary support for preterm infants with respiratory distress, high-flow therapy resulted in a significantly higher rate of treatment failure than did CPAP. (Funded by the National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12613000303741 .).

Subgaleal haemorrhage in the newborn: A call for early diagnosis and aggressive management.

Subgaleal haemorrhage (SGH) is an important cause of preventable morbidity and mortality in the neonate. Its increased prevalence in recent years has coincided with the rise in the number of births assisted by vacuum extraction. Three deaths in Australia within the last 7 years have been the subject of two coronial inquests. Subsequent coronial reports have highlighted that neonatal death from SGH can be prevented if appropriate attention is paid to identification of risk factors, early diagnosis, close observation and aggressive treatment. To prevent unnecessary deaths, all involved in the care of the baby after birth need to be aware of the importance of prompt diagnosis, monitoring and early treatment of SGH.

Prevalence and outcomes of laser treatment of aggressive posterior retinopathy of prematurity.

BACKGROUND: To describe outcomes in a cohort of extremely premature infants treated for aggressive posterior retinopathy of prematurity by diode laser panretinal photocoagulation. DESIGN: Retrospective study. PARTICIPANTS: Fifteen eyes in eight infants. METHODS: A review was carried out on infants between 23 and 25.6 weeks gestational age admitted to The Royal Brisbane and Women's Hospital neonatal intensive care unit between 1992 and 2009. MAIN OUTCOME MEASURES: Success of treatment, visual and refractive outcomes. RESULTS: Five hundred fifty-four infants were admitted to neonatal intensive care unit, 373 survived till screening, and 304 had retinopathy of prematurity. Sixty-six infants required treatment, and eight of these had aggressive posterior retinopathy of prematurity (2.5% of all infants with retinopathy of prematurity). Mean gestational age was 24.2 weeks, mean birthweight was 634 g, and treatment occurred at mean 34.1 weeks post-menstrual age. The mean total number of burns per eye was 2967. Five of 15 treated eyes required retreatment. Two patients subsequently died of unrelated causes. Regression occurred in 9 of 11 remaining eyes; one eye progressed to stage 4b and another to stage 5 retinopathy of prematurity. Vitrectomy was performed in two eyes. Five eyes had 6/12 vision, one had 3/60, and three had no perception of light. Of the remaining two eyes, one had good fixation and the other had poor fixation. CONCLUSIONS: Despite good structural outcomes, visual outcomes for conventional laser treatment of aggressive posterior retinopathy of prematurity are poor.

Determination of umbilical venous catheter tip position with radiograph.

OBJECTIVES: To compare the cardiac silhouette method with the vertebral body method in predicting the umbilical venous catheter tip position on ultrasound; to measure the length of the target zone for the umbilical venous catheter tip; and to determine the time taken for a neonatologist to ascertain position of the umbilical venous catheter tip with ultrasound. DESIGN: Prospective cohort study. SETTING: Neonatal ICU. PATIENTS: Newborn infants with an umbilical venous catheter. INTERVENTIONS: Ultrasound scans to determine the umbilical venous catheter tip position were performed within an hour of corresponding anteroposterior chest-abdominal radiograph. MEASUREMENTS AND MAIN RESULTS: Two hundred paired radiograph and ultrasound scans in 82 newborn infants were analyzed. Each radiograph was reviewed independently by an experienced neonatologist who recorded the position of the umbilical venous catheter tip by vertebral level and by the cardiac silhouette method. For each method, the sensitivity, specificity, and positive and negative predictive values were calculated for the prediction of the true position of the catheter tip on ultrasound. The umbilical venous catheter tip was well positioned in just 28 of 200 scans. The cardiac silhouette method was superior to the vertebral level method for all test variables, with a sensitivity and specificity of 86% and 94% compared with 61% and 74%. The length of the target zone approximates to a single T8 vertebral body height on radiograph. CONCLUSIONS: For radiograph and ultrasound scans performed within an hour of each other, the cardiac silhouette method more accurately predicts umbilical venous catheter tip than vertebral body level and methods described in previous studies. Catheters are frequently malpositioned. The length of the target zone for optimal umbilical venous catheter tip position is short. Ultrasound assessment of umbilical venous catheter tip position is quick.

High-flow nasal cannulae in very preterm infants after extubation.

BACKGROUND: The use of high-flow nasal cannulae is an increasingly popular alternative to nasal continuous positive airway pressure (CPAP) for noninvasive respiratory support of very preterm infants (gestational age, <32 weeks) after extubation. However, data on the efficacy or safety of such cannulae in this population are lacking. METHODS: In this multicenter, randomized, noninferiority trial, we assigned 303 very preterm infants to receive treatment with either high-flow nasal cannulae (5 to 6 liters per minute) or nasal CPAP (7 cm of water) after extubation. The primary outcome was treatment failure within 7 days. Noninferiority was determined by calculating the absolute difference in the risk of the primary outcome; the margin of noninferiority was 20 percentage points. Infants in whom treatment with high-flow nasal cannulae failed could be treated with nasal CPAP; infants in whom nasal CPAP failed were reintubated. RESULTS: The use of high-flow nasal cannulae was noninferior to the use of nasal CPAP, with treatment failure occurring in 52 of 152 infants (34.2%) in the nasal-cannulae group and in 39 of 151 infants (25.8%) in the CPAP group (risk difference, 8.4 percentage points; 95% confidence interval, -1.9 to 18.7). Almost half the infants in whom treatment with high-flow nasal cannulae failed were successfully treated with CPAP without reintubation. The incidence of nasal trauma was significantly lower in the nasal-cannulae group than in the CPAP group (P=0.01), but there were no significant differences in rates of serious adverse events or other complications. CONCLUSIONS: Although the result for the primary outcome was close to the margin of noninferiority, the efficacy of high-flow nasal cannulae was similar to that of CPAP as respiratory support for very preterm infants after extubation. (Funded by the National Health and Medical Research Council; Australian New Zealand Clinical Trials Network number, ACTRN12610000166077.).

Treatment of retinopathy of prematurity in extremely premature infants over an 18-year period.

BACKGROUND: To report the efficacy of laser diode therapy in the treatment of retinopathy of prematurity (ROP) in extremely premature (EP) infants over an 18-year period. DESIGN: Retrospective study. PARTICIPANTS: One hundred twenty-eight eyes in 66 infants treated between 23 and 25.6 weeks. METHODS: Five hundred fifty-four infants between 23 and 25.6 weeks gestational age (GA) were admitted to The Royal Brisbane and Women's Hospital Neonatal Intensive Care Unit (NICU) between 1992 and 2009. Three hundred seventy-three patients survived to undergo screening, 304 were diagnosed with ROP, and 66 infants required diode laser therapy. MAIN OUTCOME MEASURES: Success of treatment, visual and refractive outcomes. RESULTS: One hundred twenty-eight eyes from 66 infants (18.8% of those screened) underwent laser treatment with a mean GA of 24.3 weeks and mean birth weight of 711.4g. Fifty-six eyes were treated at pre-threshold disease, and 72 eyes at threshold disease. Over the study period, the number of laser spots and regression rate of ROP increased, while the frequency of re-treatment decreased. At 40 weeks, 119 eyes had regressed ROP (93%), two advanced to stage 4a, three to stage 4b and four to stage 5. Aggressive posterior ROP (AP-ROP) occurred in 15 eyes (11.7% of those treated). Forty-three patients (65%) were followed up for a mean of 56.5 months. The number of laser spots correlated well with subsequent refractive error but poorly with corrected visual acuity. CONCLUSIONS: In EP infants, laser diode therapy is an effective technique to halt the progression of ROP in most cases. AP-ROP is uncommon, even in this subgroup of extremely premature infants.

Incidence of retinopathy of prematurity in extremely premature infants over an 18-year period.

BACKGROUND: To report the incidence of retinopathy of prematurity (ROP) in a subgroup of extremely premature infants admitted to an Australian tertiary centre over an 18-year period. DESIGN: Retrospective study. Royal Brisbane and Women's Hospital Neonatal Intensive Care Unit. PARTICIPANTS: Five hundred and fifty-four infants admitted between 23 and 25.6 weeks gestational age (GA). METHODS: The 18-year study was divided into three 6-year periods for analysis: period 1 (1992-1997), period 2 (1998-2003) and period 3 (2004-2009). Infants were compared based on their week of GA and by the study period in which they were born. MAIN OUTCOME MEASURES: GA, birthweight, incidence and severity of ROP. RESULTS: Three hundred seventy-three (67.3%) infants survived until ROP screening, and 351 (63.4%) survived until discharge. ROP incidence increased from 78.2% in period 1 to 86.1% in period 3. Over the entire study, 90.5% of 23-week GA infants had ROP compared with 89.7% of 24-week GA infants and 76.1% of 25-week GA infants. Mean birthweight was significantly lower in infants with any ROP (725.1 g) and ROP of at least stage 3 (720.8 g) compared with infants without ROP (806.5 g) (P < 0.0001). Twenty-three-week GA infants had more severe ROP (28.6%) than 24 weeks (18.3%) and 25 weeks GA (11.9%). CONCLUSIONS: There has been increased survival and incidence of ROP in extremely premature infants over the past 20 years. Lower birthweight and GA are both associated with higher incidence and more severe ROP.

Gastroschisis: ward reduction compared with traditional reduction under general anesthesia.

BACKGROUND/PURPOSE: In gastroschisis it is proposed that gut reduction may be achieved without intubation or general anesthesia (GA) through ward reduction. The authors aimed to determine if ward reduction decreased morbidity and duration of treatment. METHODS: Infants born from January 1, 1995, to December 31, 2001, with gastroschisis were managed with either reduction under GA in the operating theatre (OT group)--up to September 1999, or ward reduction (when eligible) in the neonatal unit without GA/ventilation (ward reduction [WR] group)--from September 1999. RESULTS: Of the 37 infants, 31 were eligible for ward reduction-15 from the OT group, 16 from the WR group. All infants in the OT group had at least 1 episode of ventilation and 1 GA: 62% of infants in the WR group avoided ventilation (P = .0002) and 81% avoided GA (P < .0001). Infants who had ward reduction had significantly shorter durations of ventilation and oxygen therapy. Septicemia occurred in 31% of the WR group and 7% of the OT group (P = .17). Infants who had ward reduction left intensive care 16 days earlier (P = .02) and tended to reach full enteral feeds 8 days sooner (P = .06) and be discharged from hospital 15 days earlier (P = .05). CONCLUSIONS: Infants who had ward reduction do better in terms of avoiding GA/ventilation, establishing feeds, and going home earlier. A randomized, controlled trial comparing the 2 approaches is feasible, safe, and worthwhile.

Preterm birth a long distance from home and its significant social and financial stress.

The present paper reports a retrospective cohort of preterm infants admitted to our hospital who delivered outside the normal geographical catchment area of the mother's local level three neonatal nursery. Nineteen mothers had 21 preterm infants (23.1-34.9 weeks, 500-2330 g born) where 14 infants required ventilation (median 57 h, range 3-428). Eighteen survivors had a median length of stay of 41 days (range 3-91). Twelve of 19 mothers were interviewed: all described isolation, loneliness, poor social support and significant financial hardship related to getting their infants back to a local hospital or home. To avoid these problems, we recommend confining travel to within a short distance from home or local maternity unit after 22 weeks.