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.

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.

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.

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.

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.

Serum cytokines in a clinical trial of hypothermia for neonatal hypoxic-ischemic encephalopathy.

Inflammatory cytokines may mediate hypoxic-ischemic (HI) injury and offer insights into the severity of injury and the timing of recovery. In our randomized, multicenter trial of hypothermia, we analyzed the temporal relationship of serum cytokine levels in neonates with hypoxic-ischemic encephalopathy (HIE) with neurodevelopmental outcome at 12 months. Serum cytokines were measured every 12 hours for 4 days in 28 hypothermic (H) and 22 normothermic (N) neonates with HIE. Monocyte chemotactic protein-1 (MCP-1) and interleukins (IL)-6, IL-8, and IL-10 were significantly higher in the H group. Elevated IL-6 and MCP-1 within 9 hours after birth and low macrophage inflammatory protein 1a (MIP-1a) at 60 to 70 hours of age were associated with death or severely abnormal neurodevelopment at 12 months of age. However, IL-6, IL-8, and MCP-1 showed a biphasic pattern in the H group, with early and delayed peaks. In H neonates with better outcomes, uniform down modulation of IL-6, IL-8, and IL-10 from their peak levels at 24 hours to their nadir at 36 hours was observed. Modulation of serum cytokines after HI injury may be another mechanism of improved outcomes in neonates treated with induced hypothermia.

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.

[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.).

Cystic fibrosis: an unusual neonatal presentation.

In mechanically ventilated neonates it is not uncommon to observe obstructive atelectasis from various causes. However it is extremely rare to see mucous plugging and massive pulmonary atelectasis in the absence of infection, aspiration, and respiratory distress syndrome in the first couple of days of life. In this report we describe a neonate born with cystic fibrosis (CF) who presented to us with hypoxic respiratory failure, pulmonary hypertension, and hypercarbia without lactic acedemia from sticky mucous plugging and massive lung collapse. Neonatal respiratory distress and wide spread pulmonary atelectasis has not been reported in infants born with CF.

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/day (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.

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.

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.

Vitamin D deficiency in young children with severe acute lower respiratory infection.

RATIONALE: Acute lower respiratory infection (ALRI) is one of the most common reasons for hospitalization and intensive care unit admission among children. Season related decreases in the immunomodulatory molecule, vitamin D, remain an unexplored factor that might contribute to the increased occurrence of ALRI in children. OBJECTIVE: To investigate a possible association between vitamin D deficiency and respiratory infection by comparing serum 25 hydroxyvitamin D [25(OH)D] levels in a group of young children with ALRI to an age-matched group without respiratory infection. PATIENTS AND METHODS: Participants with a diagnosis of bronchiolitis or pneumonia (n = 55 or 50, respectively), as well as control subjects without respiratory symptoms (n = 92), were recruited at the Royal University Hospital, Saskatoon, Saskatchewan, Canada from November 2007 to May 2008. 25(OH)D levels were measured in patient serum using a competitive enzyme linked immunoassay. RESULTS: The mean vitamin D level for the entire ALRI group was not significantly different from the control group (81 +/- 40 vs. 83 +/- 30 nmol/L, respectively). The mean vitamin D level for the ALRI subjects admitted to the pediatric intensive care unit (49 +/- 24 nmol/L) was significantly lower than that observed for both control (83 +/- 30 nmol/L) and ALRI subjects admitted to the general pediatrics ward (87 +/- 39 nmol/L). Vitamin D deficiency remained statistically related to pediatric intensive care unit admission in the multivariate analysis. CONCLUSION: No difference was observed in vitamin D levels between the entire ALRI group and control groups; however, significantly more children admitted to the pediatric intensive care unit with ALRI were vitamin D deficient. These findings suggest that the immunomodulatory properties of vitamin D might influence ALRI disease severity.