David S. C. Lee

Variations in incidence of necrotizing enterocolitis in Canadian neonatal intensive care units.

Objectives: Necrotizing enterocolitis (NEC) is the most common acquired intestinal disease of neonates. Previous reports on incidence have generally examined small cohorts of extremely low–birth-weight infants and have not examined risk-adjusted variations among neonatal intensive care units (NICUs). The authors examined risk-adjusted variations in the incidence of NEC in a large group of Canadian NICUs and explored possible therapy-related risks. Methods: The authors obtained data on 18,234 infants admitted to 17 tertiary level Canadian NICUs from January 1996 to October 1997. They used multivariate logistic regression analysis to examine the inter-NICU variation in incidence of NEC, with adjustment for population risk factors and admission illness severity, and explored therapy-related variables. Results: The incidence of NEC was 6.6% (n = 238) among 3,628 infants with birth weight ≤1,500 g (VLBW), and 0.7% (n = 98) among 14,606 infants with birth weight >1,500 g (HBW). Multivariate logistic regression analysis showed that for VLBW infants, NEC was associated with lower gestational age and treatment for hypotension and patent ductus arteriosus. Among HBW infants, NEC was associated with lower gestational age, presence of congenital anomalies (cardiovascular, digestive, musculoskeletal, multiple systems) and need for assisted ventilation. There was no significant variation in the risk-adjusted incidence of NEC among NICUs, with the exception of one NICU reporting no cases of NEC. Conclusions: Risk factors for NEC were different in VLBW and HBW infants. There was no significant variation in the risk-adjusted incidence of NEC among Canadian NICUs, with one possible exception.

Enoxaparin for neonatal thrombosis: A call for a higher dose for neonates

INTRODUCTION Enoxaparin is the current anticoagulant of choice for neonatal thrombosis. Present neonatal treatment guidelines of 1.5 mg/kg every 12 hours (q12 h) are extrapolated primarily from an earlier study with 9 infants less than 2 months of age. More recent studies indicate an increased dose requirement for neonates. MATERIALS AND METHODS Relevant data from articles and abstracts were identified by searching MEDLINE and pediatric and hematology conference proceedings. RESULTS Publications between 1996 and 2007 included 8 papers, 4 abstracts and 1 review article with primary research documenting enoxaparin use in 240 neonates. The mean maintenance dose of enoxaparin ranged from 1.48 to 2.27 mg/kg q12 h for all infants, but was higher for preterm neonates at 1.9-2.27 mg/kg q12 h. The efficacy of enoxaparin, causing either complete or partial resolution was between 59 and 100%. Minor side effects were common and adverse events (major bleeding) occurred in 12 patients (0-19%). CONCLUSIONS Increased experience with enoxaparin use in neonates in the past decade has indicated higher doses to achieve accepted target anti-factor Xa values. The long-term use of indwelling catheters (Insuflon catheter) for enoxaparin administration may need to be reevaluated in ELBW infants. Suggested starting doses of enoxaparin are 1.7 mg/kg q12 h for term neonates and 2.0 mg/kg q12 h for preterm neonates if there is no considerable bleeding risk. However, further prospective studies are needed to validate an increased initial dose of enoxaparin.

Enoxaparin use in the neonatal intensive care unit: experience over 8 years.

Study Objective. To evaluate the effectiveness and safety of enoxaparin therapy in a neonatal intensive care unit (NICU).

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.

A Developmental Study on Types and Frequency Distribution of Short Apneas (3 to 15 Seconds) in Term and Preterm Infants

ABSTRACT: We measured the frequency distribution and the ventilatory correlates of the various types of apneas 3 to 15 s long during sleep in eight term infants (birth weight 3.65 ± 0.16 kg; gestational age 39.5 ± 0.3 wk) and eight preterm infants (birth weight 2.07 ± 0.18 kg; gestational age 34.3 ± 0.4 wk). Each infant was studied on five to seven occasions from birth to 56 wk of postconceptual age using a modified flow-through system. Sixty-six paired epochs of quiet sleep (1163 min) and rapid eye movement sleep (829 min) were analyzed in term infants and 85 paired epochs of quiet sleep (1553 min) and rapid eye movement sleep (1328 min) in preterm infants. Of the 783 apneas recorded in term infants 82% were central, 1.5% obstructive, 0.5% mixed, and 16% were of the breath-holding type; the corresponding figures for the 4086 apneas recorded in preterm infants were 93, 0.5, 1.0, and 5.5%. This distribution was similar in the two sleep states but term infants had a higher percentage of breath-holding apneas than preterm infants (p < 0.01). In preterm infants the rate of central apneas decreased with postnatal age (p < 0.01); in term infants the rate did not change significantly. The duration of apneas showed a modal distribution for central apneas at about 8 s for both groups during the 1st month of life (p < 0.05). The findings suggest: 1) apneas in the newborn and early infancy are primarily central and are more frequent in preterm than in term infants; 2) the higher rate of apnea in healthy preterm infants is accounted for almost entirely by the higher rate of central apneas; 3) a significant decrease in the rate of apnea occurs during the first 4 months after birth; and 4) preterm infants show longer respiratory pauses in both quiet sleep and rapid eye movement sleep when compared to term infants, and a maturation pattern can be discerned by 3 months of age.

Determinants of developmental outcomes in a very preterm Canadian cohort

Objectives Identify determinants of neurodevelopmental outcome in preterm children. Methods Prospective national cohort study of children born between 2009 and 2011 at <29 weeks gestational age, admitted to one of 28 Canadian neonatal intensive care units and assessed at a Canadian Neonatal Follow-up Network site at 21 months corrected age for cerebral palsy (CP), visual, hearing and developmental status using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Stepwise regression analyses evaluated the effect of (1) prenatal and neonatal characteristics, (2) admission severity of illness, (3) major neonatal morbidities, (4) neonatal neuroimaging abnormalities, and (5) site on neurodevelopmental impairment (NDI) (Bayley-III score < 85, any CP, visual or hearing impairment), significant neurodevelopmental impairment (sNDI) (Bayley-III < 70, severe CP, blind or hearing aided and sNDI or death. Results Of the 3700 admissions without severe congenital anomalies, 84% survived to discharge and of the 2340 admissions, 46% (IQR site variation 38%–51%) had a NDI, 17% (11%–23%) had a sNDI, 6.4% (3.1%–8.6%) had CP, 2.6% (2.5%–13.3%) had hearing aids or cochlear implants and 1.6% (0%–3.1%) had a bilateral visual impairment. Bayley-III composite scores of <70 for cognitive, language and motor domains were 3.3%, 10.9% and 6.7%, respectively. Gestational age, sex, outborn, illness severity, bronchopulmonary dysplasia, necrotising enterocolitis, late-onset sepsis, retinopathy of prematurity, abnormal neuroimaging and site were significantly associated with NDI or sNDI. Site variation ORs for NDI, sNDI and sNDI/death ranged from 0.3–4.3, 0.04–3.5 and 0.12–1.96, respectively. Conclusion Most preterm survivors are free of sNDI. The risk factors, including site, associated with neurodevelopmental status suggest opportunities for improving outcomes.

Early differences in production of mRNAs for phenylalanine ammonia-lyase and chalcone synthase in resistant and susceptible cultivars of soybean inoculated with Phytophthora megasperma f. sp. glycinea☆

Abstract The production of mRNAs for phenylalanine ammonia-lyase and chalcone synthase was determined in the first 5 h following infection of intact etiolated soybean hypocotyls with zoospores of Phytophthora megasperma f. sp. glycinea . mRNA was extracted from tissue excised from inoculated sites and mRNAs for the two enzymes detected by dot hybridization using corresponding cDNA probes. A major increase in mRNAs for both enzymes was detected by 3 h following inoculation in an incompatible interaction but not in a compatible interaction. The results are consistent with the development of early differences in glyceollin biosynthesis in the two types of interaction.

Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates

Importance Several definitions of bronchopulmonary dysplasia are clinically used; however, their validity remains uncertain considering ongoing changes in the panoply of respiratory support treatment strategies used within neonatal units. Objective To identify the optimal definition of bronchopulmonary dysplasia that best predicts respiratory and neurodevelopmental outcomes in preterm infants. Design, Setting, and Participants Retrospective cohort study at tertiary neonatal intensive care units. Preterm infants born at less than 29 weeks’ gestation between 2010 and 2011 who were admitted to neonatal intensive care units participating in the Canadian Neonatal Network and completed follow-up assessments in a Canadian Neonatal Follow-Up Network clinic at 18 to 21 months. Exposures Various traditional bronchopulmonary dysplasia criteria based on respiratory status at different postmenstrual ages. Main Outcomes and Measures Serious respiratory morbidity, neurosensory impairment at 18 to 21 months of age, and a composite outcome of respiratory or neurosensory morbidity or death after discharge. Adjusted odds ratios (AORs) and 95% CIs were calculated. Results Of 1914 eligible survivors, 1503 were assessed (mean gestational age was 26.3 weeks; 68% were white, 9% were black, and 23% were other race/ethnicity), 88 had serious respiratory morbidity, 257 infants had neurosensory impairment, and 12 infants died after discharge. Definitions using oxygen requirement alone as the criterion at various postmenstrual ages were less predictive compared with those using the criterion of oxygen/respiratory support (RS) (receiving supplemental oxygen and/or positive-pressure RS); among those, oxygen/RS at 36 weeks had the highest AOR and area under the curve (AUC) for all outcomes. Further analyses of oxygen/RS at each week between 34 and 44 weeks’ postmenstrual age indicated that the predictive ability for serious respiratory morbidity increased from 34 weeks (AOR, 1.8; 95% CI, 0.9-3.4, AUC, 0.721) to 40 weeks (AOR, 6.1; 95% CI, 3.4-11.0; AUC, 0.799). For serious neurosensory impairment, the AOR and AUC at 40 weeks’ PMA (AOR, 1.5, 95% CI, 1.0-2.1; AUC, 0.740) were only marginally below their peak values at 37 weeks’ PMA (AOR, 1.8; 95% CI, 1.3-2.6; AUC, 0.743). Conclusions and Relevance Defining bronchopulmonary dysplasia by the use of oxygen alone is inadequate because oxygen/RS is a better indicator of chronic respiratory insufficiency. In particular, oxygen/RS at 40 weeks’ PMA was identified as the best predictor for serious respiratory morbidity, while it also displayed a good ability to predict neurosensory morbidity at 18 to 21 months.

Using near-infrared spectroscopy to measure cerebral metabolic rate of oxygen under multiple levels of arterial oxygenation in piglets

Improving neurological care of neonates has been impeded by the absence of suitable techniques for measuring cerebral hemodynamics and energy metabolism at the bedside. Currently, near-infrared spectroscopy (NIRS) appears to be the technology best suited to fill this gap, and techniques have been proposed to measure both cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2). We have developed a fast and reliable bolus-tracking method of determining CMRO2 that combines measurements of CBF and cerebral venous oxygenation [venous oxygen saturation (CSvO2)]. However, this method has never been validated at different levels of arterial oxygenation [arterial oxygen saturation (SaO2)], which can be highly variable in the clinical setting. In this study, NIRS measurements of CBF, CSvO2, and CMRO2 were obtained over a range of SaO2 in newborn piglets (n=12); CSvO2 values measured directly from sagittal sinus blood samples were collected for validation. Two alternative NIRS methods that measure CSvO2 by manipulating venous oxygenation (i.e., head tilt and partial venous occlusion methods) were also employed for comparison. Statistically significant correlations were found between each NIRS technique and sagittal sinus blood oxygenation (P<0.05). Correlation slopes were 1.03 (r=0.91), 0.73 (r=0.73), and 0.73 (r=0.81) for the bolus-tracking, head tilt, and partial venous occlusion methods, respectively. The bolus-tracking technique displayed the best correlation under hyperoxic (SaO2=99.9±0.03%) and normoxic (SaO2=86.9±6.6%) conditions and was comparable to the other techniques under hypoxic conditions (SaO2=40.7±9.9%). The reduced precision of the bolus-tracking method under hypoxia was attributed to errors in CSvO2 measurement that were magnified at low SaO2 levels. In conclusion, the bolus-tracking technique of measuring CSvO2, and therefore CMRO2, is accurate and robust for an SaO2>50% but provides reduced accuracy under more severe hypoxic levels.

Development and Evaluation of an Instrument to Measure Parental Satisfaction With Quality of Care in Neonatal Follow-Up

Objective: The goal of this study was to develop and subsequently evaluate the psychometric properties of a new discriminative instrument to measure parental satisfaction with the quality of care provided in neonatal follow-up (NFU) programs. Method: The methodological framework for developing and evaluating measurement scales described by Streiner and Norman (Health Measurement Scales: A Practical Guide to Their Development and Use. 3rd ed. New York: Oxford University Press; 2003) was used for the study. Informing the phases of the research was a sample of 24 health care professionals and 381 parents who use NFU services. Results: A comprehensive list of items representing the construct, parental satisfaction with quality of care, was generated from published reliable and valid instruments, research studies, focus groups with health care experts, and focus groups with parents. Using a clinimetric approach, the 62 items generated were reduced to 39 items based on parents’ ratings of importance and refinement of the items by the research team. After content validation and pretesting, the instrument was tested with parents and underwent item-analysis. The resulting 16-item instrument was composed of 2 subscales, Process and Outcomes. Evaluation of the instrument’s psychometric properties indicated adequate test–retest reliability (intraclass correlation coefficient = 0.72) and internal consistency (Process subscale, &agr; = 0.77; Outcomes subscale, &agr; = 0.90; overall instrument, &agr; = 0.90), as well as good content and construct validity. A confirmatory factor analysis supported the multidimensionality of the construct. Conclusion: This new instrument provides clinicians and policy-makers with a tool to assess parental satisfaction with the quality of care in NFU, so areas of dissatisfaction can be identified and changes implemented to optimize service provision.