The association of cumulative vasoactive drugs and neurodevelopmental outcomes in preterm Infants <29 weeks gestation.

OBJECTIVE: To assess the effect of cardiovascular medications on the neurodevelopment of preterm infants, as measured by calculated cumulative time of vasoactive-inotropic score (VISct). METHODS: A retrospective study was conducted on preterm infants who developed significant hypotension defined as a mean BP more than 2SDs below the mean for GA and received treatment with duration > 6 hours for each hypotensive episode, we calculated the vasoactive inotropic score (VIS) and cumulative exposure to cardiovascular medications over time (VISct). The composite Bayley III was reported from the high-risk follow-up clinic for the surviving infants between 18 to 21 months corrected age. RESULTS: VISct was significantly higher in infants with abnormal neurodevelopment. Cognitive Bayley was the most affected component with median (IQR) VISct 882.5(249,2047) versus 309(143,471) (p-value 0.012), followed by language function with VISct 786(261,1563.5), versus 343(106.75,473.75) (p-value 0.016) when those with Bayley III <85 were compared with those with normal Bayley IIIs. CONCLUSION: High VISct scores may have negative effect on cognitive and language neurodevelopmental outcomes.

A vasoactive inotropic score predicts the severity of compromised systemic circulation and mortality in preterm infants.

OBJECTIVE: To validate the vasoactive inotropic score as a predictor of the severity of compromised systemic circulation and mortality in preterm infants. METHODS: A retrospective study was conducted on preterm infants with Compromised systemic circulation [hypotension±lactic acidosis±oliguria] who received a cardiovascular support, we calculated the vasoactive inotropic score (VIS) and cumulative exposure to cardiovascular medications over time (VISct). Receiver operator curve was constructed to predict the primary outcome which was death & refractory hypotension. RESULTS: VIS had an area under the curve of 0.73 (95% CI 0.85-0.98, p < 0.001). A VIS cut off of 25 has sensitivity and specificity of 66% and 92%, and positive and negative predictive values of 78.5% and 83%, respectively. CONCLUSION: High VIS predicts the severity of Compromised systemic circulation and mortality rate in preterm infants.

Surfactant utilization and short-term outcomes in an era of non-invasive respiratory support in Canadian neonatal intensive care units.

OBJECTIVE: Increased use of non-invasive respiratory support (NRS) in the delivery room management of preterm neonates has resulted in delayed surfactant treatment, yet the short-term effects of this change are unknown. The aim of this study was to comparatively evaluate the use of surfactant and the short-term outcomes prior to and after the implementation of early routine use of NRS. STUDY DESIGN: Eligible infants of <29 weeks gestational age (GA) admitted to a Canadian tertiary neonatal center during two time periods (2005 to 2008 and 2010 to 2013) were included in this retrospective cohort study. Timing of surfactant (prophylactic vs therapeutic) and short-term outcomes were compared between the two groups. Univariate and multivariate regression analysis was performed to determine the adjusted odds ratio (AOR) along with 95% confidence interval (CI) of receiving exogenous surfactant and developing bronchopulmonary dysplasia (BPD) using the later cohort as the reference group. Subgroup analyses were also performed for infants <26 and 26 to 286/7 weeks GA, respectively. RESULTS: A total of 3980 and 5137 infants were included in the first and second time periods, respectively. There was no significant difference in overall surfactant utilization between the two time periods (AOR 1.00, 95% CI 0.89, 1.13). However, between 2005 and 2008, a lower proportion of neonates received therapeutic surfactant compared with the later cohort (47.1% vs 56.9%, P<0.01) but were more likely to receive prophylactic surfactant (52.9% vs 43.1%, P<0.01). BPD overall was significantly higher in the earlier cohort (AOR 1.19, 95% CI 1.07, 1.33), particularly among the <26 weeks gestation subgroup (AOR 1.34, 95% CI 1.08, 1.66). CONCLUSION: Early routine use of NRS did not impact overall surfactant utilization rate, although therapeutic surfactant administration rates were higher with a concomitant decrease in BPD rates.

The impact of integrated evaluation of hemodynamics using targeted neonatal echocardiography with indices of tissue oxygenation: a new approach.

OBJECTIVE: To study the impact of integrated evaluation of hemodynamics (IEH) using targeted neonatal echocardiography, together with regional tissue oxygenation, fractional oxygen extraction using near-infrared spectroscopy on the management of infants with compromised hemodynamics. STUDY DESIGN: Retrospective cohort comparison of two groups of infants with compromised hemodynamics. EPOCH 1: did not undergo IEH (January 2012 to March 2014); EPOCH 2: underwent IEH (April 2014 to December 2015). The primary outcome was the time to recovery. RESULTS: In all, 340 infants were included; 158 underwent IEH with a median (IQR) of 2 (1 to 3) evaluations per infant. Reasons for assessment included PDA (60%), compromised systemic circulation (14%) and clinically suspected pulmonary hypertension (22%). The time to recovery was shorter in IEH group in patients with compromised systemic circulation median (IQR), 32 h (24 to 63) compared with none IEH group 71 h (36 to 96), pulmonary hypertension 63 h (14.2 to 102) in IEH group compared with 68 h (24 to 240) in none IEH group, there were fewer PDA-related complications in preterm infants with PDA in IEH group. CONCLUSION: IEH was associated with shorter time to clinical recovery in infants with compromised hemodynamics.

Intestinal perforation in very preterm neonates: risk factors and outcomes.

OBJECTIVE: To compare neonatal outcomes of preterm infants (born at <32 weeks' gestation) with focal/spontaneous intestinal perforation (SIP), necrotizing enterocolitis (NEC)-related perforation, NEC without perforation or no NEC/perforation. STUDY DESIGN: Retrospective cohort study of 17,426 infants admitted to Canadian neonatal intensive care units during 2010 to 2013. The primary outcome was a composite of mortality or morbidity (bronchopulmonary dysplasia, severe retinopathy, periventricular leukomalacia or nosocomial infection). Association of intestinal perforation with neonatal outcome was evaluated using multivariate logistic regression. RESULT: SIP was present in 178 (1.0%) infants, NEC-related perforation in 246 (1.4%) and NEC without perforation in 538 (3.1%). Any intestinal perforation was associated with higher odds of the composite outcome (adjusted odds ratio (AOR): 8.21, 95% confidence interval (95% CI) 6.26 to 10.8); however, the odds were significantly lower for focal/SIP compared with NEC-related perforation (AOR: 0.29, 95% CI 0.17 to 0.51). CONCLUSION: Of the two types of intestinal perforation, NEC-related perforation was associated with the highest risk of an adverse neonatal outcome.

Post transfusion lung injury in the neonatal population.

OBJECTIVE: The objective of this study was to examine the changes in level of respiratory support following transfusion in neonates who require intermediate or intensive care. STUDY DESIGN: Data on respiratory support were collected retrospectively from the medical record before, during and after transfusion. Neonatal post transfusion lung injury (NPTLI) was defined as an increase in the highest mean airway pressure (MAP) of ≥2 cm H(2)O or FiO(2) >0.15 in the 6-h after transfusion that persisted from 6 to 18 h post transfusion. RESULT: A total of 373 (330 packed red blood cell) transfusions were given to 108 infants. NPTLI occurred following 31 (8.3%) transfusions in 23 patients. During the first 6 h after transfusion, FiO2 or MAP was increased in 47 transfusions (12.6%) and the changes persisted in 31 transfusions (7.8%). Infants who developed NPTLI were less mature (27.1±0.7 vs 31.0±0.5 weeks; P=0.005) and of lower birth weight (1001±110 vs1692±104 g; P=0.001). Infants who developed NPTLI were more likely to develop necrotizing enterocolitis (6/24 vs 4/85; P=0.002) and die within 24 h of transfusion (5/22 vs 3/85; P=0.003). CONCLUSION: In neonates receiving intensive or intermediate care, blood transfusion was associated with need for increased respiratory support in a significant number of cases. Development of NPTLI was associated with poorer outcomes.

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.

Effective delivery of neonatal stabilization education using videoconferencing in Manitoba.

We compared face-to-face and videoconference delivery of an education programme for health professionals on the subject of neonatal stabilization skills. A pre-test/post-test control group design was used to compare knowledge acquisition and satisfaction between the two modalities. There were no statistically significant differences between delivery modalities for knowledge acquisition. Both groups showed significant gains in knowledge when pre- and post-test scores were compared. Responses to most of the items in a survey of satisfaction with the course did not differ significantly between the two groups. Face-to-face participants expressed higher levels of comfort in interacting with the presenter, and those in the videoconference group were more willing to receive the course via videoconference in the future. Videoconferencing provided an effective and acceptable way of delivering neonatal stabilization skills.

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.

Percent body fat and bone mass in healthy Canadian females 10 to 19 years of age.

The primary aim of the investigation was to assess the relationship between whole-body fat expressed as a percentage of body weight with whole-body bone mineral content relative to age and anthropometry. Sixty females between 10 and 19 years of age were recruited to this cross-sectional study, which included measurements of weight and height and whole-body fat and bone mineral content using dual-energy X-ray absorptiometry. To assess bone mineral content, data were expressed as a weight or standard deviation scores using age and bone area. Relationships between outcome variables were determined using multiple correlation analysis followed by multiple linear regression with age, weight, height, and fat as predictor variables for outcomes of bone mineral content and density. Correlation analysis indicated that whole-body fat expressed as a percent was significantly related to weight (p < 0.01), but was not related to age or bone mineral content or density unless bone mineral content was corrected to age or bone area using standard deviation scores. In addition, body fat was associated with bone area for age and height (p < 0.01). However, multiple linear regression yielded opposite results. When included in regression, body fat had a negative impact on bone mineral content (p = 0.003), mineral content corrected to bone area (p = 0.02), and bone density (p = 0.003), while age, weight, and height had positive impacts on these outcome measurements. The data suggest that for younger children, the relative influence of percent body fat will be greater and could be linked with suboptimal attainment of peak bone mass. The females in this study appeared to be within reference limits for percent body fat. However, greater amounts of body fat relative to weight could be a marker for lifestyles that do not support attainment of optimal peak bone mass.

Observer variability in interpretation of abdominal radiographs of infants with suspected necrotizing enterocolitis.

We examined (1) the observer variability (both interobserver and intraobserver) in interpretation of abdominal radiographs of infants with suspected necrotizing enterocolitis (NEC), (2) the interobserver variability for individual radiologic signs used to diagnose NEC, and (3) the influence of experience in determining the extent of observer variability. Our hypotheses were (1) there would be considerable observer variability in interpretation of abdominal radiographs of infants with suspected NEC; (2) the extent of observer variability would differ for individual radiologic signs of NEC; and (3) the extent of observer variability would be determined by the observer's experience. The participants included 12 observers: two pediatric radiologists, four attending neonatologists, three neonatal fellows, and three pediatric residents. The participating observers under similar interpretation conditions, twice independently, interpreted the same 40 pairs of abdominal radiographs from infants with suspected NEC. The interval between the two interpretations was 3 to 6 months. Intraobserver and interobserver variability was assessed by applying the Kappa statistic to the radiologic signs of NEC for the two separate interpretations. The observers were blinded to patient's identity and the clinical course. Each observer recorded the absence, suspicion, or presence of (1) intestinal distention, (2) air fluid levels, (3) bowel wall thickening, (4) pneumatosis intestinalis, (5) portal venous gas, (6) pneumoperitoneum, and (7) NEC. We found low intraobserver and interobserver agreements. There was considerable variation in observer variability for individual radiologic signs. Trained observers performed better than intraining observers. We conclude that the radiologic signs in isolation should not be considered reliable. We recommend studies to formulate more objective criteria for many of the radiographic features of NEC. Standardization and periodic enforcement of these criteria among observers could reduce observer variability. We suggest that, to decrease both false-negative and false-positive interpretation, an experienced observer should always review the radiographs of infants with suspected NEC.

Neonatal withdrawal from maternal volatile substance abuse.

AIM: To determine whether neonates born to mothers who are volatile substance abusers are at risk for an abstinence syndrome. METHODS: A consecutive sample of infants born to volatile substance abusing mothers was studied over four years, in a university affiliated medical centre with a variable mix of primary, secondary, and tertiary care patients. Infants were clinically scored with the Finnegan Neonatal Abstinence Scoring System. Those who fulfilled a priori scoring criteria were treated with phenobarbital and scoring was continued. RESULTS: There were 48 babies of whom 32 fulfilled the criteria for pharmacotherapy. All eight babies with the characteristic odour, and 15 of the 21 born to mothers with that odour, fulfilled these criteria. The typical symptoms were excessive and high pitched cry, sleeplessness, hyperactive Moro reflex, tremor, hypotonia, and poor feeding. Mean age of onset of treatment was 27.1 hours and mean duration was 5.8 days. Treatment was judged effective in 17 of 27, while benefit was borderline in three and absent in seven. CONCLUSIONS: It is suggested that there is an identifiable neonatal volatile substance abuse abstinence syndrome. The characteristic chemical odour in the neonate or mother is a marker for its occurrence, and phenobarbital treatment seems to be effective. The Finnegan Scoring System seems to be useful for grading its severity.

Neurodevelopmental outcome of infants exposed to indomethacin antenatally.

The use of indomethacin as a tocolytic agent has been limited because of potential fetal and neonatal complications. We investigated the neonatal and neurodevelopmental outcome of preterm infants exposed antenatally to this drug. The records of 779 women admitted in premature labor during a five year period were reviewed. Nineteen women who received indomethacin (initial dose of 50-100 mg followed by 50-100 mg/day) and their 25 infants were identified. Delivery was delayed for a week or longer in 86.6% of the mothers. There were two deaths: a stillborn with multiple congenital anomalies and a neonate with congenital listeriosis. Seven infants were born at term without complications. Fifteen infants born prematurely were compared to 15 control infants not exposed to indomethacin antenatally. There were no statistically significant differences between the two groups in the prevalence or severity of thrombocytopenia, hyperbilirubinemia, intraventricular hemorrhages, patent ductus arteriosus, persistent pulmonary hypertension, bronchopulmonary dysplasia, and necrotizing enterocolitis. Mean BUN, creatine, and urine output for the first three days of life were similar in the two groups. No differences were found at the 6-12 month neurodevelopment assessment. We found no neonatal complications attributable to the antenatal use of indomethacin.

Fetofetal transfusion in triplets.

A case of fetofetal transfusion syndrome (FFTS) in a monochorionic triplet pregnancy, in which all three fetuses shared a common circulation, is reported. All babies were born alive, although two died within two days of delivery. This case highlights the problem of FFTS with accompanying high perinatal morbidity and mortality in naturally occurring monochorionic triplet gestations.

Intravenous pentazocine and methylphenidate abuse during pregnancy. Maternal lifestyle and infant outcome.

OBJECTIVE: To report the effects of intravenous abuse of pentazocine hydrochloride and methylphenidate hydrochloride during pregnancy. DESIGN: Retrospective chart review. PATIENTS: All pregnant women and their offspring, whose hospital records indicated prenatal abuse of pentazocine and methylphenidate during the 2-year study period. RESULTS: The median for maternal age was 22 years and the median number of prenatal visits was two. Twenty mothers had sexually transmitted diseases, 27 abused alcohol, 10 abused other drugs, and all smoked cigarettes. Eight infants were premature, and 12 were growth retarded. Four infants had congenital anomalies: fetal alcohol syndrome (two [twins]), structural heart defect (one), and polydactyly (one). Eleven infants were treated for neonatal abstinence syndrome. Seventeen infants had normal developmental quotients, and four had low-normal developmental quotients. CONCLUSIONS: Intrauterine exposure to pentazocine and methylphenidate appears to be associated with prematurity, growth retardation, and signs of neonatal withdrawal, but not with any particular teratogenic anomaly or severe developmental delay.

Earlier discharge with community-based intervention for low birth weight infants: a randomized trial.

BACKGROUND: Prolonged hospitalization of low birth weight infants increases the risk of medical and psychosocial complications. The feasibility of earlier discharge with community-based follow-up of infants of < or = 2000 g birth weight, without the use of home apnea monitors, was investigated. METHODS: One hundred infants of < or = 2000 g birth weight were randomized to either an intervention or control group. Intervention infants were discharged when readiness criteria were met. Based on assessed need, intervention group families received public health nursing and homemaker services for up to 8 weeks. Control infants were discharged to their homes at the discretion of the attending physician. All infants were assessed blindly at age 1 year with the Bayley and Home Observation for Measurement of the Environment (HOME) scales. RESULTS: There were no group differences in baseline infants' characteristics or in neonatal complications. Infants in the intervention group were discharged from the hospital at an earlier postconceptional age (mean +/- SD 36.6 +/- 1.5 weeks vs 37.3 +/- 1.6 weeks; P < .04). Median length of hospital stay (23 days vs 31.5 days) and mean weight at the time of discharge (2200 +/- 288 g vs 2275 +/- 301 g) were lower, but not significantly, for infants in the intervention group. A secondary analysis by birth weight strata (< or = 1500 g and 1501 through 2000 g) revealed that the most significant reductions in hospital stay and weight at discharge were realized in infants of 1501 through 2000 g birth weight. The persistence of apneic episodes and need for electronic monitoring prevented earlier discharge of infants of < or = 1500 g birth weight. Postdischarge services to the intervention group included 185 public health nurse home visits (3.8 +/- 0.91), 410 phone contacts (8.4 +/- 5), and 2298 homemaker hours (46 +/- 78) of service. At 1 year, there were no deaths and no group differences in rehospitalization rates, use of ambulatory services, or Bayley scores. Intervention families had significantly higher 1-year HOME scores. Minimum cost of hospital care was $873 per day, while the total cost of community-based services averaged $626 per infant. CONCLUSIONS: A significant reduction in average length of hospital stay was achieved for infants of 1501 through 2000 g birth weight. Earlier discharge of infants weighing < or = 1500 g at birth was hampered by persistent apneic episodes and feeding difficulties. A community-based program designed to provide individualized support and education for families of low birth weight infants was cost-effective and had a positive influence on the home environment.