Neonatal end of life care in a tertiary care centre in Canada: a brief report.

OBJECTIVE: To describe the processes followed by a neonatal team engaging parents with respect to end of life care of babies in whom long term survival was negligible or impossible; and to describe feedback from these parents after death of their child. METHODS: A retrospective review was conducted of health records of neonates who had died receiving palliative care over a period of 5 years at a tertiary neonatal centre. Specific inclusion criteria were determined in advance that identified care given by a dedicated group of caregivers. RESULTS: Thirty infants met eligibility criteria. After excluding one outlier an average of 4 discussions occurred with families before an end of life decision was arrived at. Switching from aggressive care to comfort care was a more common decision-making route than having palliative care from the outset. Ninety per cent of families indicated satisfaction with the decision making process at follow-up and more than half of them returned later to meet with the NICU team. Some concerns were expressed about the availability of neonatologists at weekends. CONCLUSIONS: A compassionate and humane approach to the family with honesty and empathy creates a positive environment for decision-making. An available, experienced team willing to engage families repeatedly is beneficial. Initiating intensive care with subsequent palliative care is acceptable to families and caregivers.

Effects of nosocomial infection trends on neonatal outcomes in preterm infants <33 weeks of gestational age in Canadian NICUs.

OBJECTIVE: To characterize recent trends of nosocomial infection (NI) among preterm infants admitted to Canadian Level 3 NICUs during 2008-2012, and its association with neonatal outcomes. METHODS: A retrospective observational cohort study was performed including infants born <33 weeks gestational age and admitted to 24 NICU sites participating in the Canadian Neonatal NetworkTM during 2008-2012. NICU sites were classified into three groups according to their baseline NI rates in 2008 [Low NI group (≤14%), Medium NI group (14.1%-19%) and High NI group (>19%)], and NICU sites were also classified according to their NI trend during 2008-2012 (decreased, null and increased). Trends in NI were further examined for each baseline-NI group. Trends for a composite outcome indicating mortality or severe morbidities (intraventricular hemorrhage grades≥3 or periventricular leukomalacia, retinopathy of prematurity stages≥3, bronchopulmonary dysplasia or necrotizing enterocolitis stages≥2) were examined for each baseline-NI and trend-NI NICU site groups using multivariable logistic regression analyses adjusted for potential confounders. RESULTS: Baseline high NI group showed significantly decreased trends in NI rates, while for with medium or low baseline NI groups showed no significant trends in NI rates. The composite outcome (mortality during NICU stay or any severe neonatal morbidity such as intraventricular hemorrhage grades 3-4, periventricular leukomalacia, retinopathy of prematurity stages 3-5, bronchopulmonary dysplasia and necrotizing enterocolitis stages 2-3) decreased significantly for sites with decreased (OR=0.89, 95% CI=0.85-0.93) or null (OR=0.94, 95% CI=0.90-0.98) NI trends, but no significant trends in the composite outcome were detected for sites with increased NI rates. CONCLUSIONS: The neonatal outcome is possibly influenced by NI rates and trend. The trend in the mortality and the risk of bronchopulmonary dysplasia, retinopathy of prematurity stage≥3 and intraventricular hemorrhage>2 were significantly decreased for sites with decreased NI trend, suggesting that these improved outcomes may be associated with effort to decrease NI rate.

Reduction in developmental coordination disorder with neonatal caffeine therapy.

OBJECTIVE: To determine the effect of neonatal caffeine treatment on rates of developmental coordination disorder (DCD). STUDY DESIGN: Children in the Caffeine for Apnea of Prematurity trial were assessed for motor performance (Movement Assessment Battery for Children [MABC]), clinical signs of cerebral palsy, and Full-Scale IQ at 5 years of age by staff who were unaware of the children's treatment group. DCD was defined as MABC<5th percentile in children with a Full-Scale IQ>69 who did not have a diagnosis of cerebral palsy. RESULTS: There were 1433 children with known MABC corrected-age percentile as well as known Full-Scale IQ at 5 years and cerebral palsy status, of whom 735 had been randomly assigned to caffeine and 698 to placebo therapy. The rate of DCD was lower in those treated with caffeine (11.3%) than in the placebo group (15.2%) (OR adjusted for center and baseline covariates, 0.71, 95% CI, 0.52-0.97; P=.032). CONCLUSIONS: Neonatal caffeine therapy for apnea of prematurity reduces the rate of DCD at 5 years of age. As more children have DCD than have cerebral palsy, this is an important additional benefit from neonatal caffeine treatment.

Children hospitalized with respiratory syncytial virus infection in Saskatchewan pediatric tertiary care centers, 2002-2005.

OBJECTIVE: To describe the epidemiology and severity of illness of children hospitalized with respiratory syncytial virus (RSV) infection, including those who received palivizumab prophylaxis, at Royal University Hospital (RUH), Saskatoon and Regina General Hospital (RGH) from July 2002 to June 2005. METHODS: Children hospitalized for ≥ 24 hours with laboratory-confirmed RSV infection were enrolled, and their health records were retrospectively reviewed for patient demographics and referral patterns, use of palivizumab prophylaxis, severity of infection (length of hospitalization, need for and duration of pediatric intensive care and mechanical ventilation) and outcome of infection. RESULTS: A total of 590 children (324 males) were hospitalized over the three years. The median chronological age at admission was 5.3 months, and median hospital stay was 4.0 days. Gestational age at birth was ≥ 36 weeks in 82.4% of patients. RSV disease severity was mild to moderate in 478 patients (81.0%) and severe in 110 (18.6%). Thirty-nine patients (6.6%) required pediatric intensive care unit admission, for a median of 5.0 days. Twenty-two of these patients (56%) were mechanically ventilated for a median of 6.0 days. Two children died, not attributed to RSV infection. Twenty-two patients had received palivizumab prophylaxis before hospital admission, with 18 completing at least 2 of the monthly doses. Most of these children (17/22) had mild to moderate illness. CONCLUSIONS: RSV causes significant morbidity in Saskatchewan, affecting predominantly term infants. The majority of illness is mild to moderate. Some patients who have received palivizumab may still develop significant RSV disease.

Prevention of respiratory syncytial viral infections in late preterm infants.

RSV prophylaxis is not routine in infant born 33 to 35 weeks gestation. Risk scoring tool can be utilized to identify infants that have significant chance for hospitalization. Premature birth is a leading cause of infant mortality and chronic pulmonary morbidity, therefore prevention of RSV hospitalization though immune prophylaxis in late preterm infants appears attractive.

Influence of nutrition provision during the first two weeks of life in premature infants on adolescent body composition and blood pressure.

OBJECTIVE: Adequate nutrition is paramount for premature infants. Longitudinal information is scant on the effects of early nutrition and later growth. The purpose of this study was to determine the influence of early energy and protein provision in premature infants on adolescent body composition and blood pressure. METHODS: In 2007-2008 we obtained data from 36 male (12.3±1.7 years) and 25 female (11.5±1.8 years) adolescents born preterm at <34 weeks gestation (range 23-34 weeks) between October 1st 1989 and December 31st 1995 (birth weight <1850 g). The adolescents were divided into groups depending on infant intake mode (enteral vs parenteral), energy provision (<70 kcal/kg/d and ≥70 kcal/kg/d) and protein provision (>2.5 g/kg/d for ≥5 days and >2.5 g/kg/d for <5 days) during the first 14 days of life. RESULTS: After controlling for birth weight and biological maturity, adolescents who received ≥70 kcal/kg/d during infancy were significantly taller (163±11 cm vs. 156±11 cm) and heavier (58±16 kg vs. 49±16 kg) than adolescents who received <70 kcal/kg/d. There were no significant differences in systolic and diastolic BP and total percent body fat between the two groups. CONCLUSIONS: Our data suggests that higher infant energy provision appears to be related to adolescent size, it does not appear to contribute to adverse risk factors such as higher systolic BP or increased body fat.

Treatment of patent ductus arteriosus and neonatal mortality/morbidities: adjustment for treatment selection bias.

OBJECTIVE: To examine the association between treatment for patent ductus arteriosus (PDA) and neonatal outcomes in preterm infants, after adjustment for treatment selection bias. STUDY DESIGN: Secondary analyses were conducted using data collected by the Canadian Neonatal Network for neonates born at a gestational age ≤ 32 weeks and admitted to neonatal intensive care units in Canada between 2004 and 2008. Infants who had PDA and survived beyond 72 hours were included in multivariable logistic regression analyses that compared mortality or any severe neonatal morbidity (intraventricular hemorrhage grades ≥ 3, retinopathy of prematurity stages ≥ 3, bronchopulmonary dysplasia, or necrotizing enterocolitis stages ≥ 2) between treatment groups (conservative management, indomethacin only, surgical ligation only, or both indomethacin and ligation). Propensity scores (PS) were estimated for each pair of treatment comparisons, and used in PS-adjusted and PS-matched analyses. RESULTS: Among 3556 eligible infants with a diagnosis of PDA, 577 (16%) were conservatively managed, 2026 (57%) received indomethacin only, 327 (9%) underwent ligation only, and 626 (18%) were treated with both indomethacin and ligation. All multivariable and PS-based analyses detected significantly higher mortality/morbidities for surgically ligated infants, irrespective of prior indomethacin treatment (OR ranged from 1.25-2.35) compared with infants managed conservatively or those who received only indomethacin. No significant differences were detected between infants treated with only indomethacin and those managed conservatively. CONCLUSIONS: Surgical ligation of PDA in preterm neonates was associated with increased neonatal mortality/morbidity in all analyses adjusted for measured confounders that attempt to account for treatment selection bias.

Effect of fresh red blood cell transfusions on clinical outcomes in premature, very low-birth-weight infants: the ARIPI randomized trial.

CONTEXT: Even though red blood cells (RBCs) are lifesaving in neonatal intensive care, transfusing older RBCs may result in higher rates of organ dysfunction, nosocomial infection, and length of hospital stay. OBJECTIVE: To determine if RBCs stored for 7 days or less compared with usual standards decreased rates of major nosocomial infection and organ dysfunction in neonatal intensive care unit patients requiring at least 1 RBC transfusion. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized controlled trial in 377 premature infants with birth weights less than 1250 g admitted to 6 Canadian tertiary neonatal intensive care units between May 2006 and June 2011. INTERVENTION: Patients were randomly assigned to receive transfusion of RBCs stored 7 days or less (n = 188) vs standard-issue RBCs in accordance with standard blood bank practice (n = 189). MAIN OUTCOME MEASURES: The primary outcome was a composite measure of major neonatal morbidities, including necrotizing enterocolitis, retinopathy of prematurity, bronchopulmonary dysplasia, and intraventricular hemorrhage, as well as death. The primary outcome was measured within the entire period of neonatal intensive care unit stay up to 90 days after randomization. The rate of nosocomial infection was a secondary outcome. RESULTS: The mean age of transfused blood was 5.1 (SD, 2.0) days in the fresh RBC group and 14.6 (SD, 8.3) days in the standard group. Among neonates in the fresh RBC group, 99 (52.7%) had the primary outcome compared with 100 (52.9%) in the standard RBC group (relative risk, 1.00; 95% CI, 0.82-1.21). The rate of clinically suspected infection in the fresh RBC group was 77.7% (n = 146) compared with 77.2% (n = 146) in the standard RBC group (relative risk, 1.01; 95% CI, 0.90-1.12), and the rate of positive cultures was 67.5% (n = 127) in the fresh RBC group compared with 64.0% (n = 121) in the standard RBC group (relative risk, 1.06; 95% CI, 0.91-1.22). CONCLUSION: In this trial, the use of fresh RBCs compared with standard blood bank practice did not improve outcomes in premature, very low-birth-weight infants requiring a transfusion. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00326924; Current Controlled Trials Identifier: ISRCTN65939658.

Noninvasive respiratory support in neonates: a brief review.

In the era of gentle ventilation and open lung strategy noninvasive ventilatory support in neonates has gained momentum and its use in nurseries around the world is also increased. This paper reviews various modalities of non-invasive respiratory support in some details and its relevance in the recent evidence based use. Continuous positive airway pressure (CPAP) is a mode of ventilatory assistance in which positive pressure is delivered to the airway throughout the respiratory cycle. It is also referred to as continuous distending pressure (CDP) or positive end expiratory pressure (PEEP) when applied through a ventilator along with intermittent mandatory ventilation (IMV). It has been proven over the years to be an effective mode of ventilatory support and as such has gained widespread use in the management of a variety of neonatal respiratory diseases. It is relatively cheap and easy to apply and certainly feasible for routine use in underdeveloped world. Besides improving oxygenation CPAP often functions as an airway stabilizer of the trachea thus helping to decrease the frequency of neonatal apneas, particularly the obstructive variety. There is good to fair quality supportive evidence from several studies that the use of primary CPAP can reduce the need for intubation and mechanical ventilation in infants less than 32 weeks gestation. In this review, we will attempt to describe different delivery devices and pressure generating systems and discuss different ways in which CPAP can be applied. Although it is unclear that primary use of CPAP can reduce overall neonatal mortality and morbidity it is becoming increasingly clear that early CPAP use is less invasive, baby friendly and decreases the need and frequency of the use of surfactants. Besides, clinical indications for CPAP, its advantages and limitations will also be explored. CPAP adjuncts such as nasal intermittent positive pressure ventilation (NIPPV) and infant flow driver will also be discussed.

[Vitamin D intake in young children with acute lower respiratory infection].

OBJECTIVE: To determine if vitamin D intake is associated with acute lower respiratory infections (ALRI) in children. METHODS: The vitamin D intakes of children younger than 5 years of age admitted to hospital with either bronchiolitis or pneumonia were compared to an unmatched control group of the same age without respiratory infection. Caregivers of 197 children completed a questionnaire collecting information on demographic variables, ALRI risk factors and diet. Associations of ALRI with vitamin D intake and other ALRI risk factors were determined. RESULTS: The mean vitamin D intake of children with ALRI was 48 IU/kg/d compared to 60 IU/kg/d in the control group. When controlling for age, ethnicity, socio-economic status, northern residence, breastfeeding, immunizations and smoking contact, children with a vitamin D intake of less than 80 IU/kg/d were greater than 4 times more likely to have ALRI compared to children with a vitamin D intake exceeding 80 IU/kg/d (OR=4.9; 95%CI: 1.5-16.4). CONCLUSIONS: A higher vitamin D intake than currently recommended might be needed to offer protection against diseases such as ALRI. Increased vitamin D supplementation could have important public health consequences, as bronchiolitis and pneumonia are the most common reasons for hospitalization in young children. (Full English version will be available online at www.amepc.org/tp.).

Preterm birth and adolescent bone mineral content.

The purpose of this study was to determine the influence of preterm low birth weight on bone mineral content in adolescence. In 2007 to 2008, data on adolescents were obtained for study, including 16 females and 25 males who were born preterm (≤37 weeks' gestation) between October 1, 1989, and December 31, 1995, with a birth weight of less than 1850 g. Preterm low-birth-weight individuals were age- and sex-matched to full-term (>37 weeks) normal-birth-weight (>2500 g) controls. Total body, hip, and spine bone mineral content (BMC) was assessed using dual energy X-ray absorptiometry. Male preterm individuals had less BMC at the proximal femur in adolescence compared with controls ( p < 0.05). However, once adjusted for age, maturity, height, weight, physical activity, and diet, there were no differences between groups ( p < 0.05) in any bone parameters. These findings suggest that preterm birth and low birth weight did not influence bone accrual in these individuals at adolescence.

Neonatal seizures: diagnosis and management.

The recognition of epileptic seizures in newborns is challenging as neonates exhibit a variety of paroxysmal motor phenomena, some epileptic but others not. The distinction, frequently requiring video-EEG monitoring, is crucial for management. Causes are often multi-factorial, specific to country/region, and change over time. Hypoxia-ischemia and infection are still common in both developed and developing countries. Venous and arterial strokes are being increasingly recognized. Treatable conditions, including inborn errors of metabolism, must be anticipated and considered early in the course. Etiology is the principal determinant of outcome. Management is based on uncontrolled studies and expert opinions. Information on neonatal seizures is reviewed, and suggestions for management provided. Phenobarbital remains the first anti-epileptic drug of choice, worldwide. Pharmacogenetic information and hepatic or renal dysfunction will influence doses of all drugs. The toxicity of excipients present in intravenous medicines should be kept in mind, especially when infusions are given to critically ill neonates. Therapeutic trials with pyridoxine or ideally pyridoxal phosphate, folinic acid and biotin should be considered early, if seizures are intractable. The management of electrographic seizures without clinical seizures needs critical study. When anti-epileptic drug treatment is required, maintenance should be for a short duration if seizures are of an acute symptomatic nature.

Improving the quality of care for infants: a cluster randomized controlled trial.

BACKGROUND: We developed and tested a new method, called the Evidence-based Practice for Improving Quality method, for continuous quality improvement. METHODS: We used cluster randomization to assign 6 neonatal intensive care units (ICUs) to reduce nosocomial infection (infection group) and 6 ICUs to reduce bronchopulmonary dysplasia (pulmonary group). We included all infants born at 32 or fewer weeks gestation. We collected baseline data for 1 year. Practice change interventions were implemented using rapid-change cycles for 2 years. RESULTS: The difference in incidence trends (slopes of trend lines) between the ICUs in the infection and pulmonary groups was - 0.0020 (95% confidence interval [CI] - 0.0007 to 0.0004) for nosocomial infection and - 0.0006 (95% CI - 0.0011 to - 0.0001) for bronchopulmonary dysplasia. INTERPRETATION: The results suggest that the Evidence-based Practice for Improving Quality method reduced bronchopulmonary dysplasia in the neonatal ICU and that it may reduce nosocomial infection.

Capillary blood sampling as an alternative to venipuncture in the assessment of serum 25 hydroxyvitamin D levels.

This study compared 25-hydroxyvitamin D [25(OH)D] measurements in capillary and venous blood samples collected, respectively by fingerprick and venipuncture. Capillary blood for measuring 25(OH)D has potential advantages by reducing blood volume required (2mL versus 0.3mL for venipuncture and capillary sampling, respectively), facilitating blood collection for those populations in whom venipuncture is difficult (e.g. infants and children), improving patient convenience and reducing costs associated with phlebotomy. The results demonstrated a highly significant relationship between 25(OH)D levels in serum derived from venous and capillary blood samples (r(2)=0.901). Despite statistically higher 25(OH)D levels in fingerprick samples (108+/-9nmol/L) compared with venipuncture samples (90+/-7nmol/L), the correlation between venous and capillary samples provides support for this approach as a practical alternative to venipuncture for vitamin D determination. However, clinical application may require the incorporation of a correction factor for the assessment of insufficiency, and research studies should avoid using the two methods interchangeably. Studying vitamin D's role in health and disease requires collection techniques and measurement methods that are reliable, reproducible, easily accessible, inexpensive and minimally burdensome to the patient. The option to collect patient samples by fingerprick may facilitate the collection process.

Cue-based feeding for preterm infants: a prospective trial.

We set out to test whether premature infants were able to be fed orally on feeding cues and be discharged home earlier than infants fed by traditional feeding regimens. Attainment of adequate growth, adverse events, and nursing time to provide care were also assessed. After screening, the recruited premature infants (< 36 wks post-conceptual age [PCA]) were divided into two feeding regimens. A control group of 40 infants was fed using an initial combination of scheduled gavage and bottle feeding and then graduating to demand feeds. The intervention group comprised 39 neonates who had gavage feeds discontinued at study entrance and fed orally on cues. Outcomes measured were: weight gain in grams/kg/day, length of stay (in days) after enrollment, PCA on entrance and at discharge, adverse events during feeding, number of cues per feed in the intervention group, and resource utilization using nurse/patient ratios. Differences between groups were evaluated using Mann-Whitney U test, Fisher's exact test, and regression analysis. Two-tailed P values of < 0.05 were considered significant. There was no difference between groups in the mean weight gain; in the control group mean weight gain was 12.5 gm/kg/day and in the intervention group 12.1 gm/kg/day ( P = 0.83). The average length of stay in the control group of 14.5 days was significantly longer than the 10.0 days in the intervention group ( P = 0.009). This difference remained significant after adjusting for gestational age at birth in regression analysis. The average total number of adverse events in the control group (12.5 events) was significantly greater than in the intervention group (3.5 events; P = 0.007). The mean PCA on study entry was 34.4 wks in both groups and on exit 36.5 wks in the control group and 35.8 wks in the intervention group, a significant difference ( P = 0.02), The intervention group elicited 2.8 cues/feed. The nurse to patient ratios was equal in both groups throughout the study period. Cue-based feeding was possible for premature infants with similar weight gain as traditional feeding without affecting workload. Hospitalization and adverse events were decreased.

Nonepileptic motor phenomena in the neonate.

The newborn infant is prone to clinical motor phenomena that are not epileptic in nature. These include tremors, jitteriness, various forms of myoclonus and brainstem release phenomena. They are frequently misdiagnosed as seizures, resulting in unnecessary investigations and treatment with anticonvulsants, which have potentially harmful side effects. Unfortunately, there is a paucity of literature about many of these phenomena in the newborn, and some of the major textbooks refer to these events as nonepileptic seizures, leading to further confusion for the practitioner. The present paper aims to review these phenomena with special emphasis on differentiating them from epileptic seizures, and offers information on treatment and prognosis wherever possible.

Association of a novel single nucleotide polymorphism, G(-248)A, in the 5'-UTR of BAX gene in chronic lymphocytic leukemia with disease progression and treatment resistance.

In B-cell chronic lymphocytic leukemia (CLL) a high Bcl-2/Bax ratio contributes to death defiance. We sought to identify any genetic changes in the BAX as a possible mechanism for its altered expression in CLL. The BAX gene from the RL cell line and B-cells from 34 CLL patients and 25 controls were sequenced. A novel heterozygous G(-248)A polymorphism in the 5'-UTR was present in 69% of stage I-IV patients and 5.5% of stage 0 patients, and in 4.0% of controls. It was associated with reduced protein expression (P=0.049), progression beyond Rai stage 0 (P=0.00018) and failure to achieve complete response (P=0.038).