Lisa K. Washburn

Follow-up of a Randomized, Placebo-Controlled Trial of Dexamethasone to Decrease the Duration of Ventilator Dependency in Very Low Birth Weight Infants: Neurodevelopmental Outcomes at 4 to 11 Years of Age

OBJECTIVE. High doses of dexamethasone reduce the risk of chronic lung disease among premature infants but may increase the risk of developmental impairments. The objective of this study was to compare developmental outcomes beyond infancy for children who, as neonates, participated in a randomized trial of dexamethasone. PATIENTS AND METHODS. One hundred eighteen children with birth weights <1500 g were randomly assigned at 15 to 25 days of life to a 42-day tapering course of dexamethasone or placebo. All 95 survivors were assessed by using standardized measures of developmental outcome at least once at or beyond 1 year of age, and 84 were examined at 4 to 11 years. For this follow-up study, the outcome of primary interest was death or major neurodevelopmental impairment, which was defined as cerebral palsy, cognitive impairment, or blindness. RESULTS. On the basis of each childs most recent follow-up, the rates of major neurodevelopmental impairments were 40% for the dexamethasone group and 20% for the placebo group. The higher impairment rate for the dexamethasone group was mainly attributed to a higher prevalence of cerebral palsy. Rates of the composite outcome of death or major neurodevelopmental impairment were 47% and 41%, respectively. CONCLUSION. A 42-day tapering course of dexamethasone, which was shown previously to decrease the risk of chronic lung disease in very low birth weight infants, does not increase the risk of the composite outcome of death or major neurodevelopmental impairment.

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).

Response to Haemophilus influenzae type bconjugate vaccine in chronically ill premature infants

Twenty-two premature infants with chronic lung disease (median gestational age 28 weeks) received polyribosylribitol phosphate-outer membrane protein conjugate Haemophilus vaccine at 2 and 4 months of chronologic age. The proportions with antibodies to polyribosylribitol phosphate at levels > 1 microgram/ml after doses 1 and 2 were 27% and 55%; geometric mean titers were 0.43 and 0.73 microgram/ml, significantly lower than values for term infants.

Survival and major neurodevelopmental impairment in extremely low gestational age newborns born 1990–2000: a retrospective cohort study

BackgroundIt is important to determine if rates of survival and major neurodevelopmental impairment in extremely low gestational age newborns (ELGANs; infants born at 23–27 weeks gestation) are changing over time.MethodsStudy infants were born at 23 to 27 weeks of gestation without congenital anomalies at a tertiary medical center between July 1, 1990 and June 30, 2000, to mothers residing in a thirteen-county region in North Carolina. Outcomes at one year adjusted age were compared for two epochs of birth: epoch 1, July 1, 1990 to June 30, 1995; epoch 2, July 1, 1995 to June 30, 2000. Major neurodevelopmental impairment was defined as cerebral palsy, Bayley Scales of Infant Development Mental Developmental Index more than two standard deviations below the mean, or blindness.ResultsSurvival of ELGANs, as a percentage of live births, was 67% [95% confidence interval: (61, 72)] in epoch 1 and 71% (65, 75) in epoch 2. Major neurodevelopmental impairment was present in 20% (15, 27) of survivors in epoch 1 and 14% (10, 20) in epoch 2. When adjusted for gestational age, survival increased [odds ratio 1.5 (1.0, 2.2), p = .03] and major neurodevelopmental impairment decreased [odds ratio 0.54 (0.31, 0.93), p = .02] from epoch 1 to epoch 2.ConclusionThe probability of survival increased while that of major neurodevelopmental impairment decreased during the 1990s in this regionally based sample of ELGANs.

Adiposity in Adolescent Offspring Born Prematurely to Mothers with Preeclampsia

OBJECTIVE To evaluate the relationship between maternal preeclampsia resulting in premature delivery and adiposity in the offspring during adolescence. STUDY DESIGN The 172 study participants were 14 years old and had very low birth weight. We compared height, weight, body mass index (BMI), percent fat, waist circumference, and triceps and subscapular skin fold thicknesses between those born prematurely secondary to preeclampsia (n = 51; 22 male) and those born prematurely after normotensive pregnancies (n = 121; 55 male). Multiple linear regression analysis was used to adjust for potential confounders (maternal BMI, antenatal steroid exposure, and race) and to evaluate potential explanatory variables (fetal, infancy, and childhood weight gain, and caloric intake, level of fitness, and physical activity at 14 years). RESULTS When adjusted for potential prenatal confounders (antenatal steroid exposure and race), adolescent male offspring of preeclamptic pregnancies had higher BMI (4.0 kg/m(2) [1.5, 6.6]) (mean difference [95% CI]), waist circumference (11.8 cm [3.8, 19.7]), triceps (4.6 mm [0.6, 8.6]) and subscapular skinfold thicknesses (6.2 mm [1.5, 10.9]), and percent body fat (4.1% [-0.1, 8.3]). Adjusting for infancy and childhood weight gain attenuated these group differences. There were no group differences among females. CONCLUSION Male adolescent offspring born prematurely of women with preeclampsia have higher measures of adiposity than those born prematurely of normotensive pregnancies.

Follow-up of a Randomized, Placebo-Controlled Trial of Postnatal Dexamethasone: Blood Pressure and Anthropometric Measurements at School Age

OBJECTIVE. The purpose of this work was to evaluate the effects of a 42-day tapering course of dexamethasone on blood pressure and anthropometric measurements in school-age children who were born with very low birth weight. METHODS. Sixty-eight children, who as neonates participated in a randomized placebo-controlled trial of a 42-day tapering course of dexamethasone (n = 38, dexamethasone; n = 30, placebo) to facilitate weaning from the ventilator, were seen at a median of 9 years of age. Participants underwent measurements of systolic blood pressure, diastolic blood pressure, mid-arm circumference, triceps skinfold thickness, height, and weight. Mann-Whitney U tests were used to compare groups, and Spearman coefficients were used to examine correlations between variables. RESULTS. Comparing dexamethasone- and placebo-treated children, we found no differences in systolic blood pressure, mid-arm circumference, triceps skinfold thickness, height, weight, or body mass index. Twenty-nine percent of all subjects had systolic blood pressure and/or diastolic blood pressure ≥90th percentile for age and gender. Thirty percent of all subjects had body mass index ≥85th percentile for age and gender. CONCLUSIONS. In a group of preterm very low birth-weight infants at high risk for chronic lung disease, we found no effects of dexamethasone on blood pressure or anthropometric measurements at 8 to 11 years of age. Of concern is that a high proportion in this sample had blood pressure ≥90th percentile and/or body mass index ≥85th percentile.

The renin–angiotensin–aldosterone system in adolescent offspring born prematurely to mothers with preeclampsia

Hypothesis/introduction: Preeclampsia is associated with alterations in the maternal renin–angiotensin–aldosterone system (RAAS), increased blood pressure (BP), and cardiovascular risk in the offspring. We hypothesized that preeclampsia is associated with alterations in the RAAS in the offspring that persist into adolescence. Materials and methods: We compared components of the circulating (n = 111) and renal (n = 160) RAAS in adolescents born prematurely with very low birth weight (VLBW) of preeclamptic (PreE) and normotensive (NoHTN) pregnancies. Multivariable linear regression was used to evaluate potential confounding and intermediate variables. Analyses were stratified by sex. Results: Adjusting for race and antenatal steroid exposure, male offspring of PreE mothers had higher circulating aldosterone than those of NoHTN mothers (adjusted mean difference = 109; 95% confidence limits: −9, 227 pmol/L). Further adjustment for current BMI attenuated this difference (adjusted mean difference: 93; 95% confidence limits: −30, 215 pmol/L). Conclusion: Among male preterm VLBW infants, maternal preeclampsia is associated with increased circulating aldosterone level in adolescence, which appears to be mediated in part by higher BMI.

Hemodynamic and hormonal responses to atrial distension in the ovine fetus

OBJECTIVE Our purpose was to evaluate the hemodynamic and endocrine responses to elevations of atrial pressure in fetal sheep. STUDY DESIGN By use of a randomized block design, 10 ovine fetuses underwent pulmonary artery constriction proximal to the ductus arteriosus with and without propranolol pretreatment. RESULTS Atrial pressure doubled (p < 0.05), whereas mean arterial pressure remained unchanged (p > 0.05), in response to pulmonary artery constriction in both groups. Atrial natriuretic peptide tripled (p < 0.01), arginine vasopressin tripled (p < 0.05), and plasma renin activity doubled (p < 0.05) in both the constriction and constriction plus propranolol groups. No changes in fetal hematocrit values were demonstrated in any group. CONCLUSIONS The fetal sheep responds to increased atrial pressure with not only increased levels of atrial natriuretic peptide but also with arginine vasopressin and plasma renin activity over time. These changes occur in spite of increases in both atrial pressure and atrial natriuretic peptide. We speculate that the fetal heart may participate in redistribution of cardiac output by releasing atrial natriuretic peptide and augmenting secretion of arginine vasopressin and plasma renin activity.

Antenatal steroid exposure and heart rate variability in adolescents born with very low birth weight.

Background:Reduced heart rate variability (HRV) suggests autonomic imbalance in the control of heart rate and is associated with unfavorable cardiometabolic outcomes. We examined whether antenatal corticosteroid (ANCS) exposure had long-term programming effects on HRV in adolescents born with very low birth weight (VLBW).Methods:Follow-up study of a cohort of VLBW 14-y olds born between 1992 and 1996 with 50% exposed to ANCS. HRV in both the time and frequency domains using Nevrokard Software was determined from a 5-min electrocardiogram tracing.Results:HRV data from 89 (35 male, 53 non-black) exposed (ANCS+) and 77 (28 male, 29 non-black) unexposed (ANCS-) adolescents were analyzed. HRV did not differ between ANCS+ and ANCS- black participants. However, in non-black participants, a significant interaction between ANCS and sex was observed, with ANCS- females having significantly greater HRV than ANCS+ females and males, and ANCS- males for both time and frequency domain variables.Conclusion:Among non-black adolescents born with VLBW, ANCS exposure is associated with reduced HRV with apparent sex-specificity. Reduced HRV has been associated with development of adverse cardiometabolic outcomes, thus supporting the need to monitor these outcomes in VLBW adolescents as they mature.

Aerobic Fitness and Physical Activity Levels of Children Born Prematurely following Randomization to Postnatal Dexamethasone

OBJECTIVE To investigate the effects of postnatal dexamethasone treatment on aerobic fitness and physical activity levels in school-aged children born with very low birth weight (VLBW). STUDY DESIGN This was a follow-up study of 65 VLBW infants who participated in a randomized controlled trial of dexamethasone (DEX) to reduce ventilator dependency. Aerobic fitness was determined from peak oxygen uptake (VO(2peak)) with a cycle ergometer. Habitual physical activity was assessed by questionnaire. RESULTS A trend for a treatment with an interaction between treatment and of diagnosis of chronic lung disease (CLD) was found, with the children in the placebo group with CLD having the lowest VO(2peak) (P = .09). Reduced fitness was seen in 53% of the group treated with DEX and 48% of the group given placebo. No between-group differences in physical activity were seen. Parental reports suggested that nearly two-thirds of the children participated in < 1 hour per week of vigorous physical activity, which was explained in part by decreased large airway function (r = 0.30; P = .03). CONCLUSIONS We found no adverse effect of postnatal DEX on aerobic fitness or habitual physical activity at school age. However, the reduced fitness and physical activity levels emphasize the need for closer follow-up and early interventions promoting physical activity to reduce the risk of chronic disease in this at-risk population.