Mary Seshia

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.

Perinatal group B streptococcal colonization and infection

Of 2,169 patients screened in labor for vaginal group B streptococcal colonization, 164 (7.6%) had positive results. Five hundred twenty-four of the patients were screened in the antenatal period, and 57 patients with positive tests for group B streptococcus were treated in labor with intravenous ampicillin. Four of the treatment group gave birth to colonized infants but none became infected. Of the 136 untreated mother-infant pairs with positive tests, 62 neonates were colonized, nine became infected, and three died. In the presence of an attack rate of 6.6% among infants born to colonized mothers, antenatal screening and treatment in labor of mothers colonized with group B streptococcus will reduce neonatal colonization and infection.

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.

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.

Growth and bone mineralization of young adults weighing less than 1500 g at birth

BACKGROUND Preterm infants are at risk for suboptimal growth and bone mineralization compared to infants born at term but long-term outcomes into early adulthood are unclear. AIMS To determine (1) if growth and nutrition in the first year of life significantly predict the outcomes measured at adulthood and (2) whole body and regional bone mineral content (BMC) of young adults who were born preterm and weighing <1500 g. STUDY DESIGN AND SUBJECTS In this descriptive follow-up study, subjects were born preterm and weighing <1500 g (n=25, 17.2+/-1.2 years of age) and originally participated in a 1-year follow-up study of infant growth or subjects born at term (n=25, 17.3+/-1.4 years of age). OUTCOME MEASURES In the preterm group, relationships of growth and nutrition in the first year of life with adult anthropometry and BMC were identified using correlation and regression analysis. Birth groups were compared for measurements of anthropometry and whole body and regional BMC obtained at adulthood using t-tests. RESULTS After correcting for the effects of bone area using regression, rate of weight gain had a positive relationship and days to regain birth weight a negative relationship to adult BMC. Young adults, born preterm, were significantly shorter with lower whole body BMC than of those born at term, but BMC was appropriate for size. CONCLUSIONS Growth early in life predicts subsequent attainment of growth and bone mass. Premature birth results in lower attainment of height achieved by young adult age but bone mass is appropriate for body size.

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.

Alveolar capillary dysplasia. Report of a case of prolonged life without extracorporeal membrane oxygenation (ECMO) and review of the literature

We describe an unusual infant with the diagnosis of alveolar capillary dysplasia who had a relatively prolonged life without extracorporeal membrane oxygenation (ECMO). We have used this case as a springboard for a thorough review of the literature. This was a full-term female infant who presented with a picture of persistent pulmonary hypertension of the newborn. She was treated as such, with various ventilatory modes, alkalinizing agents, surfactant therapy, tolazoline, prostacyclin and nitric oxide. Because of the prolonged clinical course the possibility of alveolar capillary dysplasia was raised. The parents refused ECMO. Despite all efforts she progressively deteriorated and died at 22 days of age. Macro- and microscopic examination of the lung at autopsy were diagnostic of alveolar capillary dysplasia. A detailed review of 39 cases published in the literature with comments regarding incidence, etiology, pathophysiology, clinical picture, diagnosis and treatment is presented.

Immediate and late ventillatory response to high and low O2 in preterm infants and adult subjects.

Summary: The differences in the immediate (30 sec or l min) and late (5 min) ventilatory response to high and low O2 have not been quantitated in preterm infants and adult subjects using the same methods. It was thought that these differences might explain the paradoxical ventilatory response to CO2 at various O2 concentrations in preterm infants (12). Thus, 9 preterm infants and 10 adult subjects were given 21% O2 to breathe and then 100 or 15% O2 for 5 min each. Adults also breathed 15% O2 before 100% O2 or 12% O2 in order to make their resting arterial PO2 more comparable to those of infants breathing 21% O2. The ventilatory response to 100% O2 was the same in preterm infants and adult subjects, but the late response to 15% O2 remained paradoxical, ventilation decreasing at 5 min by 18% in infants and increasing by 19% in adults. The authors conclude: 1) the traditional concept of the ventilatory response to 100% O2 being different in infants and adult subjects is false; 2) the notion that the response to low O2 is paradoxical in infants is correct; and 3) the data do not explain why the response to CO2 under various background concentrations of O2 in infants is the reverse of that in adult subjects, but the depressed ventilatory response to hypoxia in infants may justify, at least in part, their flatter response to CO2 during low O2 breathing.Speculation: The findings suggest that the response of preterm infants to high and low O2 per se is not the cause of the paradoxical response to CO2 under various background concentrations of O2. If it were, it would be expected that the response to low and high O2 would differ in infants and adults. This was true for hypoxia only, the response to hyperoxia being the same in infants and adults. The speculation, therefore, is that differences in cerebral blood flow caused by CO2 and O2 interaction may be responsible for the paradoxical response to CO2.

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.

Association of a quality improvement program with neonatal outcomes in extremely preterm infants: a prospective cohort study

Background: We previously demonstrated improvement in bronchopulmonary dysplasia and nosocomial infection among preterm infants at 12 neonatal units using the Evidence-based Practice for Improving Quality (EPIQ). In the current study, we assessed the association of Canada-wide implementation of EPIQ with mortality and morbidity among preterm infants less than 29 weeks gestational age. Methods: This prospective cohort study included 6026 infants admitted to 25 Canadian units between 2008 and 2012 (baseline year, n = 1422; year 1, n = 1611; year 2, n = 1508; year 3, n = 1485). Following a 1-year baseline period and 6 months of training and planning, EPIQ was implemented over 3 years. Our primary outcome was a composite of neonatal mortality and any of bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity, necrotizing enterocolitis and nosocomial infection. We compared outcomes for baseline and year 3 using multivariable analyses. Results: In adjusted analyses comparing baseline with year 3, the composite outcome (70% v. 65%; adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.51 to 0.79), severe retinopathy (17% v. 13%; OR 0.60, 95% CI 0.45 to 0.79), necrotizing enterocolitis (10% v. 8%; OR 0.73, 95% CI 0.52 to 0.98) and nosocomial infections (32% v. 24%; OR 0.63, 95% CI 0.48 to 0.82) were significantly reduced. The composite outcome was lower among infants born at 26 to 28 weeks gestation (62% v. 52%; OR 0.62, 95% CI 0.49 to 0.78) but not among infants born at less than 26 weeks gestational age (90% v. 88%; OR 0.73, 95% CI 0.44 to 1.20). Interpretation: EPIQ methodology was generalizable within Canada and was associated with significantly lower likelihood of the composite outcome, severe retinopathy, necrotizing enterocolitis and nosocomial infections. Infants born at 26 to 28 weeks gestational age benefited the most.