Robert G. Dillard

Randomized Placebo-controlled Trial of a 42-Day Tapering Course of Dexamethasone to Reduce the Duration of Ventilator Dependency in Very Low Birth Weight Infants: Outcome of Study Participants at 1-Year Adjusted Age

Objective. Ventilator-dependent preterm infants are often treated with a prolonged tapering course of dexamethasone to decrease the risk and severity of chronic lung disease. The objective of this study was to assess the effect of this therapy on developmental outcome at 1 year of age. Methods. Study participants were 118 very low birth weight infants who, at 15 to 25 days of life, were not weaning from assisted ventilation and were then enrolled in a randomized, placebo-controlled, double-blind trial of a 42-day tapering course of dexamethasone. Infants were examined at 1 year of age, adjusted for prematurity, by a pediatrician and a child psychologist. A physical and neurologic examination was performed, and the Bayley Scales of Infant Development were administered. All examiners were blind to treatment group. Results. Groups were similar in terms of birth weight, gestational age, gender, and race. A higher percentage of dexamethasone recipients had major intracranial abnormalities diagnosed by ultrasonography (21% vs 11%). Group differences were not found for Bayley Mental Development Index (median [range] for dexamethasone-treated group, 94 [50–123]; for placebo group, 90 [28–117]) or Psychomotor Development Index Index (median [range]) for dexamethasone-treated group, 78 (50–109); for placebo-treated group, 81 [28–117]). More dexamethasone-treated infants had cerebral palsy (25% vs 7%) and abnormal neurologic examination findings (45% vs 16%). In stratified analyses, adjusted for major cranial ultrasound abnormalities, these associations persisted (OR values for cerebral palsy, 5.3; 95% CI: 1.3–21.4; OR values for neurologic abnormality 3.6; 95% CI: 1.2–11.0). Conclusions. A 42-day tapering course of dexamethasone was associated with an increased risk of cerebral palsy. Possible explanations include an adverse effect of this therapy on brain development and/or improved survival of infants who either already have neurologic injury or who are at increased risk for such injury.

Early human milk feeding is associated with a lower risk of necrotizing enterocolitis in very low birth weight infants

Background:Necrotizing enterocolitis (NEC) is a frequent cause of mortality and morbidity in very low birth weight (VLBW) infants. Human milk (HM) feeding has been associated with lower risk of NEC. However, mothers of VLBW infants often experience insufficient milk production, resulting in mixed feedings of HM and formula. Moreover, medical complications often limit the volume of feeding they can be given.Objective:To determine if high proportions of (50% or greater) HM enteral feeding within the first 14 days of life are protective against NEC.Method:This was a prospective cohort study of VLBW infants who were grouped according to the HM proportion of enteral feeding in the first 14 days: <50% (low human milk, LHM, n=46) and ⩾50% (high human milk, HHM, n=156). The outcome of interest was development of NEC (Bell stage 2 or 3). Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) and to assess potential confounding due to perinatal risk factors.Result:Two hundred and two infants were studied. Confirmed NEC occurred in 5/46 (10.6%) of the LHM group, as compared with 5/156 (3.2%) of the HHM. Gestational age was the only perinatal factor associated with risk of NEC. After adjustment for gestational age, HHM was associated with a lower risk of NEC ((OR=0.17, 95% CI: 0.04 to 0.68), P=0.01).Conclusion:Enteral feeding containing at least 50% HM in the first 14 days of life was associated with a sixfold decrease in the odds of NEC.

Are Outcomes of Extremely Preterm Infants Improving? Impact of Bayley Assessment on Outcomes

OBJECTIVES To compare 18- to 22-month cognitive scores and neurodevelopmental impairment (NDI) in 2 time periods using the National Institute of Child Health and Human Developments Neonatal Research Network assessment of extremely low birth weight infants with the Bayley Scales of Infant Development, Second Edition (Bayley II) in 2006-2007 (period 1) and using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), with separate cognitive and language scores, in 2008-2011 (period 2). STUDY DESIGN Scores were compared with bivariate analysis, and regression analyses were run to identify differences in NDI rates. RESULTS Mean Bayley III cognitive scores were 11 points higher than mean Bayley II cognitive scores. The NDI rate was reduced by 70% (from 43% in period 1 to 13% in period 2; P < .0001). Multivariate analyses revealed that Bayley III contributed to a decreased risk of NDI by 5 definitions: cognitive score <70 and <85, cognitive or language score <70; cognitive or motor score <70, and cognitive, language, or motor score <70 (P < .001). CONCLUSION Whether the Bayley III is overestimating cognitive performance or whether it is a more valid assessment of emerging cognitive skills than the Bayley II is uncertain. Because the Bayley III identifies significantly fewer children with disability, it is recommended that all extremely low birth weight infants be offered early intervention services at the time of discharge from the neonatal intensive care unit, and that Bayley scores be interpreted with caution.

Trends in Mortality and Cerebral Palsy in a Geographically Based Cohort of Very Low Birth Weight Neonates Born Between 1982 to 1994

Objective. To analyze whether the increasing survival of very low birth weight infants during the 1980s and 1990s has increased the risk of cerebral palsy among survivors. Methods. The study cohort consisted of 2076 consecutively born infants, with birth weights of 500 to 1500 g and no major anomaly, born July 1, 1982, through June 30, 1994, to residents of a 17-county region in North Carolina. These infants had a mean birth weight of 1096 g (standard deviation, 251 g) and a mean gestational age of 29 weeks (standard deviation, 3 weeks). One thousand five hundred sixty-eight infants (76%) survived to 1 year adjusted age, at which point 1282 infants (82%) were examined at our medical center. The diagnosis of cerebral palsy was made only if the examining pediatrician and a pediatric physical therapist agreed on the diagnosis. To analyze trends across time, the Cochran-Armitage χ2 test and logistic regression were applied to data for infants categorized into six 2-year epochs according to year of birth. Results. Mortality did not change significantly through 1990, and then began to decrease in 1990 to 1994. During the study period, mortality decreased from 36.8% between 1982 and 1984, to 13.8% between 1992 and 1994. The prevalence of cerebral palsy among survivors was constant from 1982 to 1988 (11.3%), decreased slightly from 1988 to 1990 (9.2%), and was lowest in 1990 to 1994 (5.2%). These secular trends in mortality and cerebral palsy risk remained significant when adjusted for gestational age, gender, and race. When adjusted for surfactant use, the trend in mortality was no longer significant, whereas the trend in cerebral palsy risk persisted. Conclusions. The increasing survival of very low birth weight infants in the 1980s and 1990s has not resulted in an increased prevalence of cerebral palsy among survivors.

Outbreak of Candida bloodstream infections associated with retrograde medication administration in a neonatal intensive care unit

An outbreak of candidemia involving five infants receiving total parenteral nutrition in the neonatal intensive care unit was investigated. Cultures of the intravenous fluids demonstrated that the retrograde medication syringe fluids were significantly more likely to be contaminated with Candida than were other fluids being administered to the infants (p less than 0.001). Candidemia was significantly associated with total parenteral nutrition (p = 0.04) and retrograde medication administration (p = 0.02). A survey of nursing practice found that reuse of the retrograde syringes was the most likely cause of contamination. Molecular typing showed that the strains of Candida albicans that were isolated from the bloodstream were also found in the retrograde syringes and that at least three strains of C. albicans and one strain each of Candida tropicalis and Candida parapsilosis were involved. In vitro growth curves demonstrated that Candida species had a selective growth advantage versus bacteria in the total parenteral nutrition fluid. An in vitro simulation of the retrograde medication administration system suggested that the outbreak probably developed after the frequency of changing intravenous tubing was decreased from every 24 hours to every 72 hours. The outbreak was terminated by using syringes only once and resuming intravenous tubing changes every 24 hours. Retrograde medication administration in association with total parenteral nutrition may increase the risk of Candida line infection.

Randomized Placebo-controlled Trial of a 42-Day Tapering Course of Dexamethasone to Reduce the Duration of Ventilator Dependency in Very Low Birth Weight Infants

Objective. To assess the effect on duration of ventilator dependency of a 42-day tapering course of dexamethasone in very low birth weight neonates. Methods. Infants (N = 118) were assigned randomly, within birth weight/gender strata, to treatment with either a 42-day tapering course of dexamethasone or an equal volume of saline as placebo. Entry criteria were 1) birth weight <1501 g; 2) age between 15 and 25 days; 3) <10% decrease in ventilator settings for 24 hours and Fio 2 ≥0.3; 4) absence of patent ductus arteriosus, sepsis, major congenital malformation, congenital heart disease; and 5) no evidence of maternal HIV or hepatitis B infection. The dosage schedule was 0.25 mg/kg bid for 3 days, then 0.15 mg/kg bid for 3 days, then a 10% reduction in the dose every 3 days until a dose of 0.1 mg/kg had been given for 3 days, from which time a dose of 0.1 mg/kg qod was continued until 42 days after entry. The primary endpoint was the number of days on assisted ventilation after study entry. Secondary outcomes of interest included days on supplemental oxygen, days of hospitalization, and potential adverse effects, such as infection, gastrointestinal bleeding, left ventricular hypertrophy, and severe retinopathy of prematurity. Results. Infants in the dexamethasone- and placebo-treated groups were similar in terms of baseline attributes, including birth weight, gestational age, gender, race, and ventilator settings at entry. Infants treated with dexamethasone were on assisted ventilation and supplemental oxygen for fewer days after study entry (median days on ventilator, 5th and 95th percentiles, 13 [1–64] vs 25 [6–104]; days on oxygen, 59 [6–247] vs 100 [11–346]). No differences were found in risk of death, infection, or severe retinopathy. In subgroup analyses, the association of dexamethasone with more rapid weaning from the ventilator was weaker among infants enrolled before the 16th day of life, infants with chest radiographs showing cystic changes and/or hyperinflation, and infants requiring an Fio 2 ≥0.7 or a peak inspiratory pressure ≥19 at study entry. Conclusions. A 42-day tapering course of dexamethasone decreases the duration of ventilator and oxygen dependency in very low birth weight infants and is not associated with an increased risk of short-term adverse effects.

Human Milk Consumption and Full Enteral Feeding Among Infants Who Weigh ≤1250 Grams

OBJECTIVE. Establishing enteral feeding is an important goal in the care of very low birth weight infants. In such infants, receipt of ≥50 mL/kg per day human milk during hospitalization has been associated with shorter time to full enteral feeding. The objective of this study was to determine whether high proportions (≥50%) of human milk during feeding advancement are associated with shorter time to full enteral feeding and improved feeding tolerance. METHODS. This was a prospective cohort study of very low birth weight infants (n = 127) who were grouped into low (<50%; n = 34) and high (≥50%; n = 93) human milk consumption groups according to their human milk proportion of enteral feeding during the time of feeding advancement. The primary outcomes of interest were ages at which 100 and 150 mL/kg per day enteral feedings were achieved. RESULTS. The high human milk group reached 100 mL/kg per day enteral feeding 4.5 days faster than the low human milk group. The high human milk group reached 150 mL/kg per day enteral feeding 5 days faster than the low human milk group. After adjustment for gestational age, gender, and respiratory distress syndrome, times to reach 100 and 150 mL/kg per day were significantly shorter for those in the high human milk group. Infants in the high human milk group had a greater number of stools per day; other indicators of feeding tolerance were not statistically different. CONCLUSION. In infants who weighed ≤1250 g, enteral feeding that contained at least 50% maternal human milk was associated with fewer days to full enteral feedings.

The psychological impact of false positive elevations of maternal serum α-fetoprotein☆

Abstract The purpose of this study was to assess the psychological impact of maternal serum α-fetoprotein screening on pregnant women with false positive elevations of maternal serum α-fetoprotein and on their male partners. Subjects with maternal serum α-fetoprotein elevations and their partners exhibited significantly heightened anxiety as measured by the State-Trait Anxiety Inventory following notification of the elevation, and this anxiety persisted until normal results were obtained by further testing. Heightened anxiety was not alleviated by counseling prior to definitive testing. Once normal results were obtained, anxiety returned to control levels and heightened anxiety was not observed throughout the remainder of pregnancy. Maternal serum α-fetoprotein elevations had little effect on maternal attitudes toward pregnancy as measured by the Maternal Attitudes to Pregnancy Inventory. Similarly, no differences were observed between subjects with normal and elevated maternal serum α-fetoprotein levels with regard to depression, marital discord, work attendance, or work productivity.

Video and CD-ROM as a Training Tool for Performing Neurologic Examinations of 1-Year-Old Children in a Multicenter Epidemiologic Study

In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions. In the first interobserver variability evaluation, 89% (531 of 594) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the two items that had a 60% correct rate, the correct response rate rose to 93% (114 of 123). In the second interobserver variability evaluation, 88% (493 of 560) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the four items that had a 70% correct rate, the correct response rate rose to 96% (104 of 108). Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children. It provides an effective means to evaluate interobserver variability, offers a route for feedback, and creates an opportunity to reevaluate variability, both immediately and at periodic intervals. (J Child Neurol 2005;20:829—831).

Antibody response to oral polio vaccine in premature infants.

APPROXIMATELY 50% OF TERM INFANTS will obtain protection to all three Serotypes of orally administered polio vaccine after a single dose at 2 months of age; multiple vaccine doses will increase the protection to 83% to 96% of children, v9 However, the optimal time to administer OPV to a child born prematurely has not been determined. The American Academy of Pediatrics recommends giving the first dose of OPV to a premature infant at 2 months of chronologic age if the child has been discharged from the hospital and is otherwise healthyJ ~ The Academy notes, however, that this recommendation is not based on adequate data. This study was undertaken to determine whether the antibody response in preterm infants to OPV given at 2 and 4 months of age is comparable to that in term infants.