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Effect of dexamethasone exposure on the neonatal unit on the school age lung function of children born very prematurely.

ABSTRACT: The objective of this study was to determine the impact of postnatal dexamethasone treatment on the neonatal unit on the school age lung function of very prematurely born children. Children born prior to 29 weeks of gestational age had been entered into a randomised trial of two methods of neonatal ventilation (United Kingdom Oscillation Study). They had comprehensive lung function measurements at 11 to 14 years of age. One hundred and seventy-nine children born at a mean gestational age of 26.9 (range 23-28) weeks were assessed at 11 to 14 years; 50 had received postnatal dexamethasone. Forced expiratory flow at 75% (FEF75), 50%, 25% and 25-75% of the expired vital capacity, forced expiratory volume in one second, peak expiratory flow and forced vital capacity and lung volumes including total lung capacity and residual volume were assessed. Lung function outcomes were compared between children who had and had not been exposed to dexamethasone after adjustment for neonatal factors using linear mixed effects regression. After adjustment for confounders all the mean spirometry results were between 0.38 and 0.87 standard deviations lower in those exposed to dexamethasone compared to the unexposed. For example, the mean FEF75 z-score was 0.53 lower (95% CI 0.21 to 0.85). The mean lung function was lower as the number of courses of dexamethasone increased. In conclusion, postnatal dexamethasone exposure was associated with lower mean lung function at school age in children born extremely prematurely. Our results suggest the larger the cumulative dose the greater the adverse effect on lung function at follow-up.

SUBMITTER: Harris C

PROVIDER: S-EPMC6037362 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Effect of dexamethasone exposure on the neonatal unit on the school age lung function of children born very prematurely.

Harris Christopher C Crichton Siobhan S Zivanovic Sanja S Lunt Alan A Calvert Sandy S Marlow Neil N Peacock Janet L JL Greenough Anne A

PloS one 20180709 7

The objective of this study was to determine the impact of postnatal dexamethasone treatment on the neonatal unit on the school age lung function of very prematurely born children. Children born prior to 29 weeks of gestational age had been entered into a randomised trial of two methods of neonatal ventilation (United Kingdom Oscillation Study). They had comprehensive lung function measurements at 11 to 14 years of age. One hundred and seventy-nine children born at a mean gestational age of 26.9 ...[more]

PMID: 29985964

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Project description:Prematurity, size at birth, and postnatal growth are important factors that determine cardiometabolic and neurodevelopmental outcomes later in life. In the present study, we aimed to investigate the associations between the size at birth and growth velocity after birth with cardiometabolic and neurodevelopmental outcomes in preterm infants. Fifty-six preterm infants born at < 32 weeks of gestation or having a birth weight of < 1500 g were enrolled and categorized into small for gestational age (SGA) and appropriate for gestational age (AGA) groups. Anthropometric and cardiometabolic parameters were assessed at school-age, and the Korean Wechsler Intelligence Scale for Children, fourth edition (K-WISC-IV) was used for assessing the intellectual abilities. The growth velocity was calculated by changes in the weight z-score at each time period. Multivariate analysis was conducted to investigate the associations of growth velocity at different periods with cardiometabolic and neurodevelopmental outcomes. Forty-two (75%) were classified as AGA and 25% as SGA. At school-age, despite the SGA children showing significantly lower body weight, lean mass index, and body mass index, there were no differences in the cardiometabolic parameters between SGA and AGA groups. After adjusting for gestational age, birth weight z-score, weight z-score change from birth to discharge and sex, change in weight z-score beyond 12 months were associated with a higher systolic blood pressure, waist circumference, and insulin resistance. Full-scale intelligent quotient (β = 0.314, p = 0.036) and perceptional reasoning index (β = 0.456, p = 0.003) of K-WISC-IV were positively correlated with postnatal weight gain in the neonatal intensive care unit. Although cardiometabolic outcomes were comparable in preterm SGA and AGA infants, the growth velocity at different time periods resulted in different cardiometabolic and neurocognitive outcomes. Thus, ensuring an optimal growth velocity at early neonatal period could promote good neurocognitive outcomes, while adequate growth after 1 year could prevent adverse cardiometabolic outcomes in preterm infants.

Project description:Exposure to pain-related stress from frequent invasive procedures in the neonatal intensive care unit (NICU) has been associated with altered physiological stress regulation, neurodevelopment, and behavior in children born very preterm (≤32 weeks gestation). Previously, in a cohort born 2003-2006 (Cohort 1), we found that, at 18 months corrected age (CA), children born extremely low gestational age (ELGA; 24-28 weeks) and very low gestational age (VLGA; 29-32 weeks), had higher pre-test cortisol levels and a different pattern of cortisol output across a developmental assessment involving cognitive challenge compared to children born full-term (FT; 39-41 weeks). Also, greater neonatal pain-related stress exposure among the preterm children was related to higher pre-test cortisol levels. Given the adverse long-term effects of neonatal pain in preterm infants and the ensuing rise in clinical concerns to appropriately manage pain in the NICU in recent years, we aimed to examine whether our findings from Cohort 1 would still be evident in an independent cohort (Cohort 2) born 2006-2011 and recruited from the same tertiary NICU in Vancouver, Canada. We also compared the cortisol patterns, clinical and socio-demographic factors, and their interrelationships between the two cohorts. In Cohort 2, our findings using multi-level modeling support and extend our earlier findings in Cohort 1, demonstrating that children born ELGA display higher pre-test cortisol levels than FT. As well, greater cortisol output across assessment was related to more anxiety/depressive behaviors in children born VLGA. Importantly, children born ELGA were exposed to less neonatal pain/stress, mechanical ventilation, and morphine in Cohort 2 than Cohort 1. In both cohorts, however, cortisol levels and patterns were related to neonatal pain/stress and clinical factors (days on mechanical ventilation, overall morphine exposure). Despite less exposure to pain/stress and adverse clinical factors in Cohort 2 compared to Cohort 1, cortisol levels and patterns across cognitive challenge in preterm children at 18-month CA were consistent across the two independent cohorts. These findings highlight that, despite improvements to neonatal care, children born extremely preterm continue to display altered HPA axis activity, which is associated with their poorer neurodevelopmental and behavioral outcomes.

Project description:Preterm birth (gestational age?<?37 weeks) with very low birth weight (VLBW, birth weight???1500?g) is associated with lifelong cognitive deficits, including in executive function, and persistent alterations in cortical and subcortical structures. However, it remains unclear whether "catch-up" growth is possible in the preterm/VLBW brain. Longitudinal structural MRI was conducted with children born preterm with VLBW (n?=?41) and term-born peers participating in the Norwegian Mother and Child Cohort Study (MoBa) (n?=?128) at two timepoints in early school age (mean ages 8.0 and 9.3 years). Images were analyzed with the FreeSurfer 5.3.0 longitudinal stream to assess differences in development of cortical thickness, surface area, and brain structure volumes, as well as associations with executive function development (NEPSY Statue and WMS-III Spatial Span scores) and perinatal health markers. No longitudinal group?×?time effects in cortical thickness, surface area, or subcortical volumes were seen, indicating similar brain growth trajectories in the groups over an approximately 16-month period in middle childhood. Higher IQ scores within the VLBW group were associated with greater surface area in left parieto-occipital and inferior temporal regions. Among VLBW preterm-born children, cortical surface area was smaller across the cortical mantle, and cortical thickness was thicker occipitally and frontally and thinner in lateral parietal and posterior temporal areas. Smaller volumes of corpus callosum, right globus pallidus, and right thalamus persisted in the VLBW group from timepoint 1 to 2. VLBW children had on average IQ 1?SD below term-born MoBa peers and significantly worse scores on WMS-III Spatial Span. Executive function scores did not show differential associations with morphometry between groups cross-sectionally or longitudinally. This study investigated divergent or "catch-up" growth in terms of cortical thickness, surface area, and volumes of subcortical gray matter structures and corpus callosum in children born preterm/VLBW and did not find group?×?time interactions. Greater surface area at mean age 9.3 in left parieto-occipital and inferior temporal cortex was associated with higher IQ in the VLBW group. These results suggest that preterm VLBW children may have altered cognitive networks, yet have structural growth trajectories that appear generally similar to their term-born peers in this early school age window.

Project description:ImportanceSurvivors of preterm birth often present with medical morbidities; however, variation in their long-term educational performance has not been well described.ObjectiveTo estimate the association between gestational age and 4 outcomes in school-aged children: readiness to enter kindergarten, scores on standardized tests in elementary and middle school, gifted status, and low performance.Design, setting, and participantsIn a retrospective cohort study, children born in Florida between 1992 and 2002 at 23 to 41 weeks' gestation who entered Florida's public schools between 1995 and 2012 were assessed for kindergarten readiness and tested in mathematics and reading in grades 3 through 8. Data analysis was performed from January 12, 2016, to March 1, 2017.ExposuresGestational age at birth.Main outcomes and measuresKindergarten readiness, scores on the Florida Comprehensive Achievement Test (FCAT), classified as gifted, and classified as low performance.ResultsA total of 1?527?113 singleton infants with gestational ages of 23 to 41 weeks born between 1992 and 2002 were matched to Florida public school records. Of these, 1?301?497 children were included in the analysis; 641?479 (49.3%) were girls. A total of 301 (65.0%) Florida children born at 23 to 24 weeks' gestation were designated as ready to start kindergarten. When the FCAT test scores were adjusted for potentially confounding maternal and infant variables, children born at 23 to 24 weeks' gestation performed 0.66 SD (95% CI, -0.73 to -0.59) lower compared with those born at full term. A total of 123?554 (9.5%) of all Florida-born public school students were considered gifted, including 17 (1.8%) of those born at 23 to 24 weeks' gestation. In comparison, 75?458 (5.8%) of all Florida-born public school students were low performing; 310 (33.5%) of these children had been born at 23 to 24 weeks' gestation. Kindergarten readiness, FCAT scores, and gifted status were positively related to gestational age, whereas low performance was inversely related to gestational age.Conclusions and relevanceAlthough gestational age has long been associated with poor educational performance, a sufficient proportion of children born near the limits of viability performed within expected school norms, warranting further investigation into how and why certain children are able to overcome the educational burdens that may follow preterm birth.

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Effect of dexamethasone exposure on the neonatal unit on the school age lung function of children born very prematurely.

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Effect of dexamethasone exposure on the neonatal unit on the school age lung function of children born very prematurely.

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