Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants Exposed Prenatally to Dexamethasone Versus Betamethasone

Lee, Ho-Chang; Stoll, Barbara J.; McDonald, Scott A.; Higgins, Rosemary D.

doi:10.1542/peds.2007-1103

Cited by 81 publications

(53 citation statements)

References 32 publications

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“…In contrast, several human studies did not find significant effects on the neonatal ABR [4,5,19] or other hearing tests [38,56]. There are several possible explanations for these differences.…”

Section: Discussionmentioning

confidence: 91%

Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats

Church

Adams

Anumba

et al. 2012

Neurotoxicology and Teratology

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Antenatal corticosteroid (AC) treatment is given to pregnant women at risk for preterm birth to reduce infant morbidity and mortality by enhancing lung and brain maturation. However, there is no accepted regimen on how frequently AC treatments should be given and some studies found that repeated AC treatments can cause growth retardation and brain damage. Our goal was to assess the dose-dependent effects of repeated AC treatment and estimate the critical number of AC courses to cause harmful effects on the auditory brainstem response (ABR), a sensitive measure of brain development, neural transmission and hearing loss. We hypothesized that repeated AC treatment would have harmful effects on the offspring’s ABRs and growth only if more than 3 AC treatment courses were given. To test this hypothesis, pregnant Wistar rats were given either a high regimen of AC (HAC), a moderate regimen (MAC), a low regimen (LAC), or saline (SAL). An untreated control (CON) group was also used. Simulating the clinical condition, the HAC dams received 0.2 mg/kg Betamethasone (IM) twice daily for 6 days during gestation days (GD) 17-22. The MAC dams received 3 days of AC treatment followed by 3 days of saline treatment on GD 17-19 and GD 20-22, respectively. The LAC dams received 1 day of AC treatment followed by 5 days of saline treatment on GD 17 and GD 18-22, respectively. The SAL dams received 6 days of saline treatment from GD 17-22 (twice daily, isovolumetric to the HAC injections, IM). The offspring were ABR-tested on postnatal day 24. Results indicated that the ABR’s P4 latencies (neural transmission time) were significantly prolonged (worse) in the HAC pups and that ABR’s thresholds were significantly elevated (worse) in the HAC and MAC pups when compared to the CON pups. The HAC and MAC pups were also growth retarded and had higher postnatal mortality than the CON pups. The SAL and LAC pups showed little or no adverse effects. In conclusion, repeated AC treatment had harmful effects on the rat offspring’s ABRs, postnatal growth and survival. The prolonged ABR latencies reflect slowed neural transmission times along the auditory nerve and brainstem auditory pathway. The elevated ABR thresholds reflect hearing deficits. We concluded that repeated AC treatment can have harmful neurological, sensory and developmental effects on the rat offspring. These effects should be considered when weighing the benefits and risks of repeated AC treatment and when monitoring and managing the prenatally exposed child for possible adverse effects.

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Section: Discussionmentioning

confidence: 91%

Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats

Church

Adams

Anumba

et al. 2012

Neurotoxicology and Teratology

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“…These results implied MAPK signalling cascade in LA plays an important role in the adverse effect of neonatal DEX treatment on amygdala function. Previous studies demonstrated that dexamethasone treatment had long-term neurological effects, including an increased incidence of cerebral palsy and decreased cerebral volume (Lee et al, 2008;Wilson-Costello et al, 2009). In addition, results also suggest neonatal dexamethasone treatment impaired brain development and cognitive function (for review Barrington, 2001;Neal et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats

Hung

et al. 2014

Int. J. Neuropsychopharm.

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Synthetic glucocorticoid dexamethasone (DEX) is frequently used as a therapeutic agent to lessen the morbidity of chronic lung disease in premature infants. Previous studies suggested that neonatal DEX treatment altered brain development and cognitive function. It has been recognized that the amygdala is involved in emotional processes and also a critical site of neuronal plasticity for fear conditioning. Little is known about the possible long-term adverse effect of neonatal DEX treatment on amygdala function. The present study was aimed to evaluate the possible effect of neonatal DEX treatment on the synaptic function of amygdala in adult rats. Newborn Wistar rats were subjected to subcutaneous tapering-dose injections of DEX (0.5, 0.3 and 0.1 mg/kg) from post-natal day one to three, PN1-PN3. Animals were then subjected to a forced swimming test (FST) and electrophysiological recording aged eight weeks. The results of the FST showed neonatal DEX treatment increased depression-like behaviour in adulthood. After acute stress evoking, the percentage of time spent free floating is significantly increased in the DEX treated group compared with the control animals. Furthermore, neonatal DEX treatment elevated long-term potentiation (LTP) response and the phosphorylation level of MAPK in the lateral nucleus of amygdala (LA). Intracerebroventricular infusion of the MAPK inhibitor, PD98059, showed significant rescue effects including reduced depression-like behaviour and restoration of LTP to within normal range. In conclusion, our results suggested that MAPK signalling cascade in the LA plays an important role in the adverse effect of neonatal DEX treatment on amygdala function, which may result in adverse consequences in adult age, such as the enhancement of susceptibility for a depressive disorder in later life.

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“…9 Several large NRN observational studies suggested benefits on short and long term neonatal outcomes when mothers received betamethasone compared to dexamethasone. 10,11 …”

Section: Nrn Evaluation Of the Effects Of Obstetrical Perinatal Managmentioning

confidence: 99%

Perinatal management: What has been learned through the network?

Chawla

Foglia

Kapadia

et al. 2016

Seminars in Perinatology

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The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) has examined the effects of various obstetrical perinatal interventions and neonatal delivery room practices on the newborn with particular focus on those born preterm. Studies exploring the effects and safety of various antepartum maternal medications and the effects of the route and timing of delivery are examined. The NRN has contributed key studies to the evidence base for the International Liaison Committee on Resuscitation neonatal resuscitation guidelines. These studies are reviewed including research on timing of cord clamping, the importance of maintaining euthermia immediately after birth, delivery room ventilation strategies, outcomes following delivery room cardiopulmonary resuscitation and the effects of prolonged resuscitation efforts. In addition, the NRN’s detailed outcome data at the lowest gestational ages has greatly influenced how providers counsel families regarding the appropriateness of resuscitation efforts at the lowest gestational ages.

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Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants Exposed Prenatally to Dexamethasone Versus Betamethasone

Cited by 81 publications

References 32 publications

Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats

Repeated antenatal corticosteroid treatments adversely affect neural transmission time and auditory thresholds in laboratory rats

Neonatal glucocorticoid treatment increased depression-like behaviour in adult rats

Perinatal management: What has been learned through the network?

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