Wendy Yee

Incidence and Timing of Presentation of Necrotizing Enterocolitis in Preterm Infants

OBJECTIVES: To examine the variation in the incidence and to identify the timing of the presentation of necrotizing enterocolitis (NEC) in a cohort of preterm infants within the Canadian Neonatal Network (CNN). METHODS: This was a population-based cohort of 16 669 infants with gestational age (GA) <33 weeks, admitted to 25 NICUs participating in the CNN between January 1, 2003, and December 31, 2008. Variations in NEC incidence among the participating NICUs for the study period were examined. We categorized early-onset NEC as occurring at <14 days of age and late-onset NEC occurring at ≥14 days. Multivariate logistic regression analysis was performed to identify risk factors for early-onset NEC. RESULTS: The overall incidence of NEC was 5.1%, with significant variation in the risk adjusted incidence among the participating NICUs in the CNN. Early-onset NEC occurred at a mean of 7 days compared with 32 days for late-onset NEC. Early-onset NEC infants had lower incidence of respiratory distress syndrome, patent ductus treated with indomethacin, less use of postnatal steroids, and shorter duration of ventilation days. Multivariate logistic regression analysis identified that greater GA and vaginal delivery were associated with increased risk of early-onset NEC. CONCLUSIONS: Among infants <33 weeks’ gestation, NEC appears to present at mean age of 7 days in more mature infants, whereas onset of NEC is delayed to 32 days of age in smaller, lower GA infants. Further studies are required to understand the etiology of this disease process.

Outcomes of preterm infants <29 weeks gestation over 10-year period in Canada: a cause for concern?

Objective:To compare risk-adjusted changes in outcomes of preterm infants <29 weeks gestation born in 1996 to 1997 with those born in 2006 to 2007.Study Design:Observational retrospective comparison of data from 15 units that participated in the Canadian Neonatal Network during 1996 to 1997 and 2006 to 2007 was performed. Rates of mortality and common neonatal morbidities were compared after adjustment for confounders.Result:Data on 1897 infants in 1996 to 1997 and 1866 infants in 2006 to 2007 were analyzed. A higher proportion of patients in the later cohort received antenatal steroids and had lower acuity of illness on admission. Unadjusted analyses revealed reduction in mortality (unadjusted odds ratio (UAOR): 0.83, 95% confidence interval (CI): 0.63, 0.98), severe retinopathy (UAOR: 0.68, 95% CI: 0.50 to 0.92), but increase in bronchopulmonary dysplasia (UAOR: 1.61, 95% CI: 1.39 to 1.86) and patent ductus arteriosus (UAOR: 1.22, 95% CI: 1.07 to 1.39). Adjusted analyses revealed increases in the later cohort for bronchopulmonary dysplasia (adjusted odds ratio (AOR): 1.88, 95% CI: 1.60 to 2.20) and severe neurological injury (AOR: 1.49, 95% CI: 1.22 to 1.80). However, the ascertainment methods for neurological findings and ductus arteriosus differed between the two time periods.Conclusion:Improvements in prenatal care has resulted in improvement in the quality of care, as reflected by reduced severity of illness and mortality. However, after adjustment of prenatal factors, no improvement in any of the outcomes was observed and on the contrary bronchopulmonary dysplasia increased. There is need for identification and application of postnatal strategies to improve outcomes of extreme preterm infants.

Elective cesarean delivery, neonatal intensive care unit admission, and neonatal respiratory distress.

OBJECTIVE: To evaluate the relationship among gestational age at elective cesarean delivery, neonatal intensive care unit (NICU) admission, and whether the presence of pre–cesarean delivery labor or ruptured membranes affected the incidence of neonatal respiratory distress. METHODS: A chart review was performed of all elective caesarean deliveries (documented planned in advance) during 1 year, 2004–2005, in the Calgary Health Region; resulting in liveborn infants at or after 36 weeks of gestation and birth weight equal to or greater than 2,500 g. The primary outcomes are relative risk of NICU admission or respiratory distress. RESULTS: A total of 1,193 paired maternal and infant charts were reviewed. Admission rate to the NICU was 156 of 1,195 (13.1%). The most common admitting diagnosis was respiratory distress, 126 of 156 (80%). Male gender was a significant risk factor for admission to the NICU or respiratory distress (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.27–2.60, and OR 1.98, 95% CI 1.33–2.95, respectively). Elective cesarean delivery beyond 270 days of gestational age (384/7 weeks) significantly reduced the risk for NICU admission or respiratory distress (OR 0.62, 95% CI 0.43–0.89, and OR 0.50, 95% CI 0.34–0.74, respectively). The presence of spontaneous contractions or rupture of membranes before elective cesarean delivery did not reduce the risk of NICU admission or respiratory distress (OR 1.05, 95% CI 0.69–1.62, and OR 0.96, 95% CI 0.60–1.55, respectively). CONCLUSION: Admission to NICU and development of respiratory distress were associated with gestational age at time of elective cesarean delivery and male gender. Awaiting the onset of labor or ruptured membranes did not appear to reduce the risk of NICU admission or neonatal respiratory distress. LEVEL OF EVIDENCE: II

Evaluation of the effectiveness of the standardized neonatal resuscitation program.

OBJECTIVE: To determine if health care personnel trained in the Neonatal Resuscitation Program (NRP) used the NRP guidelines in the resuscitation of newborn babies. To determine differences between self-reporting and documentation of resuscitation in medical records.STUDY DESIGN: Using a validated questionnaire, individuals participating in resuscitation of newborns voluntarily phoned and answered questions on an Interactive Voice Response (IVR) system. The study was undertaken in level II hospitals in Southern Alberta with 7500 deliveries per year.RESULTS: Of the 5155 babies delivered during the study, 16% required resuscitation (bag and mask ventilation 10.6%, intubation for meconium or intermittent positive pressure ventilation, IPPV, 3.6%, cardiac massage, CM, 0.3%, epinephrine 0.1%, naloxone 6.9%). Of babies whose interventions could be assessed, bag and mask was correct in 99%, endotracheal intubation for IPPV in 100%, and CM in 100%. Only 75% of babies had meconium managed correctly and 92% had naloxone administered according to guidelines. There were more instances where IVR (48) reported a procedure, which was not charted versus charted and not reported by IVR (21). Educational needs identified by IVR included skills of resuscitation and NRP indications for management.CONCLUSION: Bag and mask ventilation and intubation for neonatal resuscitation are more common than previously reported. Management of the meconium-stained baby and use of naloxone require further education. Compared to charts, use of IVR system allows more complete documentation with rationale of interventions and identification of continuing educational needs.

Venous Thromboembolism Prophylaxis in Patients Undergoing Cranial Neurosurgery: A Systematic Review and Meta-analysis

BACKGROUND:Randomized clinical trials (RCTs) have usually supported using heparin prophylaxis against venous thromboembolism (VTE) in patients undergoing cranial neurosurgery. The tradeoff between benefit and bleeding risk, however, has not been adequately characterized. OBJECTIVE:To conduct a systematic review and meta-analysis assessing the extent to which low-dose unfractionated heparin (LDUH) or low-molecular-weight heparin (LMWH) prophylaxis reduces the rate of VTE and increases the rate of intracerebral hemorrhage (ICH) and other bleeding in patients undergoing elective cranial neurosurgery. METHODS:We selected RCTs that evaluated LDUH or LMWH prophylaxis of VTE in patients undergoing elective cranial neurosurgery. A meta-analysis assessing heparins vs no heparin (either with or without mechanical methods) was performed. RESULTS:Eight RCTs were identified. Six RCTs involving 1170 patients evaluated LDUH or LMWH vs a control group. Five of 6 trials found a significant reduction in the risk of symptomatic and asymptomatic VTE with heparin prophylaxis. The pooled risk ratio was 0.58 (95% confidence interval, 0.45-0.75). ICH was more common in those receiving heparin, but not statistically significantly. For every 1000 patients who receive heparin prophylaxis, 91 VTE events will be prevented (approximately 35 of which are proximal deep vein thrombosis or pulmonary embolism and 9 to 18 of which are symptomatic), whereas 7 ICHs and 28 more minor bleeds will occur. CONCLUSION:Heparin prophylaxis for patients undergoing elective cranial neurosurgery reduces the risk of VTE but may also increase bleeding risks with a ratio of serious or symptomatic VTE relative to serious bleeding that is only slightly favorable.

Neonatal Outcomes of Small for Gestational Age Preterm Infants in Canada

To compare the effect of small for gestational age (SGA) on mortality, major morbidity and resource utilization among singleton very preterm infants (<33 weeks gestation) admitted to neonatal intensive care units (NICUs) across Canada. Infants admitted to participating NICUs from 2003 to 2008 were divided into SGA (defined as birth weight <10th percentile for gestational age and sex) and non-small gestational age (non-SGA) groups. The risk-adjusted effects of SGA on neonatal outcomes and resource utilization were examined using multivariable analyses. SGA infants (n = 1249 from a cohort of 11,909) had a higher odds of mortality (adjusted odds ratio [AOR] 2.46; 95% confidence interval [CI], 1.93-3.14), necrotizing enterocolitis (AOR 1.57; 95% CI, 1.22-2.03), bronchopulmonary dysplasia (AOR 1.78; 95% CI, 1.48-2.13), and severe retinopathy of prematurity (AOR 2.34; 95% CI, 1.71-3.19). These infants also had lower odds of survival free of major morbidity (AOR 0.50; 95% CI, 0.43-0.58) and respiratory distress syndrome (AOR 0.79; 95% CI, 0.68-0.93). In addition, SGA infants had a more prolonged stay in the NICU, and longer use of ventilation continuous positive airway pressure, and supplemental oxygen (p < 0.01 for all). SGA infants had a higher risk of mortality, major morbidities, and higher resource utilization compared with non-SGA infants.

Prediction of survival without morbidity for infants born at under 33 weeks gestational age: a user-friendly graphical tool

Objective To develop models and a graphical tool for predicting survival to discharge without major morbidity for infants with a gestational age (GA) at birth of 22–32 weeks using infant information at birth. Design Retrospective cohort study. Setting Canadian Neonatal Network data for 2003–2008 were utilised. Patients Neonates born between 22 and 32 weeks gestation admitted to neonatal intensive care units in Canada. Main outcome measure Survival to discharge without major morbidity defined as survival without severe neurological injury (intraventricular haemorrhage grade 3 or 4 or periventricular leukomalacia), severe retinopathy (stage 3 or higher), necrotising enterocolitis (stage 2 or 3) or chronic lung disease. Results Of the 17 148 neonates who met the eligibility criteria, 65% survived without major morbidity. Sex and GA at birth were significant predictors. Birth weight (BW) had a significant but non-linear effect on survival without major morbidity. Although maternal information characteristics such as steroid use, improved the prediction of survival without major morbidity, sex, GA at birth and BW for GA predicted survival without major morbidity almost as accurately (area under the curve: 0.84). The graphical tool based on the models showed how the GA and BW for GA interact, to enable prediction of outcomes especially for small and large for GA infants. Conclusion This graphical tool provides an improved and easily interpretable method to predict survival without major morbidity for very preterm infants at the time of birth. These curves are especially useful for small and large for GA infants.

Intrapartum magnesium sulfate and need for intensive delivery room resuscitation

Objective To evaluate the association of intrapartum magnesium sulfate for fetal neuroprotection (MgSO4-FN) with the delivery room resuscitation and neonatal outcomes of preterm infants in an era of minimisation of invasive mechanical ventilation. Design Retrospective cohort study. Setting Neonatal intensive care units in the Canadian Neonatal Network. Patients and intervention Preterm infants (230 to 316 weeks gestational age) born in 2011 or 2012. Resuscitation requirements and neonatal outcomes were compared between infants exposed and unexposed to intrapartum MgSO4-FN. Main outcome measures The primary outcome was a composite outcome of ‘intensive resuscitation’, defined as the need for intubation and ventilation or chest compressions or epinephrine administration in the delivery room. Secondary outcomes included mortality and major neonatal morbidities. Results Of 6015 eligible infants, 1387 (23.1%) were exposed to intrapartum MgSO4-FN. Significantly fewer MgSO4-FN infants (41.0% vs 44.6%, p=0.02) required intensive resuscitation. However, after adjustment for confounders, this difference was no longer significant (adjusted OR (AOR) 0.88; 95% CI 0.66 to 1.17). Infants exposed to MgSO4-FN had decreased odds of death (AOR 0.61; 95% CI 0.40 to 0.94), but there was no difference in neonatal morbidities compared with the unexposed infants. Conclusions Intrapartum MgSO4 for fetal neuroprotection was not associated with an increased need for intensive delivery room resuscitation in this cohort of preterm infants.

Coagulase-negative staphylococcus sepsis in preterm infants and long-term neurodevelopmental outcome

Objective:The objective of this study was to examine the impact of Coagulase-negative staphylococcus (CoNS) sepsis in preterm infants on the neurodevelopmental outcomes at 30 to 42 months corrected age (CA).Study Design:This is a retrospective cohort study. All preterm infants born at <29 weeks gestational age between 1995 and 2008 and had a neurodevelopmetnal assessment at 30 to 42 months CA were eligible. The neurodevelopmetnal outcomes of infants exposed to CoNS sepsis were compared with infants unexposed to any type of neonatal sepsis.Result:A total of 105 eligible infants who were exposed to CoNS sepsis were compared with 227 infants with no neonatal sepsis. In univariate analysis, infants with CoNS sepsis were more likely to have total major disability (odds ratio (OR)=1.9; 95% CI: 1.07 to 3.38) and cognitive delay (OR=2.53; 1.26 to 5.14).There was no significant difference in the incidence of cerebral palsy, blindness and deafness between the two groups. After correcting for potential confounders, CoNS sepsis was associated with increased risk of cognitive delay (adjusted odds ratio (aOR)= 2.23; 95% CI 1.01 to 4.9), but not with the total major disability (aOR=1.14; 95% CI: 0.55 to 2.34).Conclusion:Our study suggests that CoNS sepsis in preterm infants might be associated with increased risk for cognitive delay at 36 months CA.

Survey of noninvasive respiratory support practices in Canadian neonatal intensive care units

To evaluate practice variation with respect to noninvasive respiratory support (NRS) use across Canadian neonatal intensive care units (NICUs).