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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The effect of lung inflation on the control of respiratory frequency in the neonate.

1. We have measured the relationship between tidal volume (V(T)) and the duration of inspiration (T(i)) and expiration (T(e)) for individual breaths (30 in each steady state).2. Ten pre-term and ten term infants were studied during steady state while breathing 21% O(2), then 21% O(2) plus 2 and 4% CO(2).3. In all infants, the average T(i) at the various chemical drives was remarkably constant, and did not decrease as the tidal volume increased. However, at any given level of respiratory drive, there was a slightly positive correlation of V(T) with T(i) and T(e) in 95% of the cases.4. In four pre-term and two term infants, T(e) increased with increasing respiratory drive. In these infants, therefore, instantaneous respiratory frequency (1/(T(i) + T(e))) actually decreased as lung volume increased.5. We suggest that T(i) is independent of V(T) within the range of volumes studied (up to 2 times the resting V(T)) and that changes in instantaneous respiratory frequency (1/(T(i) + T(e))) result from changes in T(e).

The effect of gestational age on the effective elastance of the respiratory system in neonates.

We measured the effective elastance of the respiratory system (E'RS) in 38 "healthy" neonates, gestational ages ranging from 28-42 weeks. E'RS was calculated by dividing the inspiratory pressure generated after nasal occlusion by the tidal volume of the breath preceding occlusion (E'RS = P/VT). E'RS decreased from 790 +/- 0.070 cm H2O/liter at 30.4 +/- 0.4 weeks of gestation to 520 +/- 0.030 at 34.5 +/- 0.3 weeks (P less than 0.01); then to 340 +/- 0.020 at 40 +/- 0.2 weeks (P less than 0.01). E'RS corrected for lung volume ("specific" E'RS) were 32 +/- 2,32 +/- 4, and 28 +/- 2 cm H2O at the above gestational ages, respectively (P greater than 0.05). We suggest: (1) the increased E'RS observed in preterm infants is lung volume dependent. Changes in lung volume may alter the geometry of the thorax, and therefore, the force/length characteristics of the respiratory muscles; (2) this increased E'RS is not of much benefit to preterm infants who have little respiratory stability when E'RS is maximum; and (3) if E'RS is an index of mechanical stability, apnea in preterm infants is independent of the mechanical properties of the respiratory system.

The immediate ventilatory response to added inspiratory elastic and resistive loads in preterm infants.

We measured the changes in tidal volume, duration of the various phases of the respiratory cycle, and peak nasal pressure during elastic and resistive loading in preterm infants. Values were calculated during the first loaded breath, when chemical drive was unchanged. Tidal volume decreased by equivalent percentages with resistive loads of 400, 900, and 2,400 cm H2O/liter/sec, and elastic loads of 330, 1,000, and 3,000 cm H2O/liter. Infinite load was also applied (nasal occlusion). Inspiratory duration (ti) was prolonged during resistive loading, as compared with elastic loading (P less than 0.05). Changes in expiratory duration (Te) were not different with both loads (P greater than 0.05). Total duration of the respiratory cycle (T), however, tended to increase in relation to control, more so with resistive loads. Peak nasal pressure was greater with resistive than with elastic loads ( less than 0.025). We suggest that (1) preterm infants, like adult subjects and other animal species, increase inspiratory duration with resistive loads as compared with elastic loads; (2) T of the first loaded breath tends to increase with progressively larger loads and, consequently, instantaneous frequency tends to decrease; and (3) if peak nasal pressure reflects tension developed by the respiratory muscles, then the latter does not offer the inhibitory information needed to terminate inspiration.

Basal and post-ACTH cortisol levels in preterm infants following treatment with dexamethasone.

Dexamethasone (DEX) has been shown to decrease ventilator dependence in bronchopulmonary dysplasia (bronchopulmonary dysplasia). Abnormal metapyrone tests have been reported in 50% of infants who were weaned from a 45-day course of dexamethasone. We postulated that such infants would have adrenal suppression and would not respond to Cosyntropin (ACTH). We examined morning cortisol levels in 14 premature infants who had been treated with dexamethasone for 36 +/- 4 (mean +/- SEM) days, starting at 38 +/- 6 days of life, and performed ACTH stimulation tests in 12 of them. Morning cortisol levels were 87 +/- 36 nmol/L (range undetectable: 543; n = 14). Random basal cortisol levels were 109 +/- 42 nmol/L (range 34-540; n = 12). The mean cortisol level was 568 +/- 63 nmol/L (range 117-934) 60 min after adrenocorticotrophic hormone. In all cases, cortisol level increased three-fold after adrenocorticotrophic hormone. Low cortisol levels are almost universal in infants after treatment with dexamethasone, but the adrenal gland remains responsive to adrenocorticotrophic hormone stimulation. We speculate that dexamethasone causes secondary adrenal suppression at the hypothalamic-pituitary level. Normal adrenal function in the preterm infant needs to be defined.

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.

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

The differences in the immediate (30 sec or 1 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.