Postnatal Dexamethasone Research Articles

Disrupted postnatal lung development in heme oxygenase-1 deficient mice

BackgroundHeme oxygenase (HO) degrades cellular heme to carbon monoxide, iron and biliverdin. The HO-1 isoform is both inducible and cyto-protective during oxidative stress, inflammation and lung injury. However, little is known about its precise role and function in lung development. We hypothesized that HO-1 is required for mouse postnatal lung alveolar development and that vascular expression of HO-1 is essential and protective during postnatal alveolar development.MethodsNeonatal lung development in wildtype and HO-1 mutant mice was evaluated by histological and molecular methods. Furthermore, these newborn mice were treated with postnatal dexamethasone (Dex) till postnatal 14 days, and evaluated for lung development.ResultsCompared to wildtype littermates, HO-1 mutant mice exhibited disrupted lung alveolar structure including simplification, disorganization and reduced secondary crest formation. These defects in alveolar development were more pronounced when these mice were challenged with Dex treatment. Expression levels of both vascular endothelial and alveolar epithelial markers were also further decreased in HO-1 mutants after Dex treatment.ConclusionsThese experiments demonstrate that HO-1 is required in normal lung development and that HO-1 disruption and dexamethasone exposure are additive in the disruption of postnatal lung growth. We speculate that HO-1 is involved in postnatal lung development through modulation of pulmonary vascular development.

Early corticosteroid treatment does not affect severity of unconjugated hyperbilirubinemia in extreme low birth weight preterm infants

To determine the relationship between early postnatal dexamethasone (DXM) treatment and the severity of hyperbilirubinemia in extreme low birth weight (ELBW) preterm infants. In 54 ELBW preterm infants, total serum bilirubin concentrations (TSB) and phototherapy (PT) data during the first 10 days were evaluated retrospectively. ELBW infants had participated in a randomized controlled trial of early DXM treatment which aimed to assess effects on chronic lung disease. Infants had been treated with DXM (0.25 mg/kg twice daily at postnatal day 1 and 2) or with placebo (normal saline). Analysis was performed on an intention to treat basis. Twenty-five Infants had been randomized into the DXM group; 29 into the placebo group. Mean (±SD) TSB [120 (±19) μmol/L vs. 123 (±28) μmol/L, DXM versus placebo, respectively] and maximum TSB [178 (±23) μmol/L vs. 176 (±48), DXM versus placebo, respectively] concentrations were similar. TSB concentrations peaked 30 h earlier in the DXM group (p ≤ 0.05). The need for PT as well as the duration of PT was similar in both groups. Early DXM treatment does not affect the severity of neonatal hyperbilirubinemia in ELBW preterm infants. Our results seem compatible with the concept that factors other than bilirubin conjugation capacity are important for the pathophysiology of neonatal jaundice in ELBW preterm infants.

Open-Label Glucocorticoids Modulate Dexamethasone Trial Results in Preterm Infants

Open-label glucocorticoids (OLGs) were often used in trials that investigated postnatal dexamethasone treatment in ventilated preterm infants. To determine if OLG use modulates the dexamethasone treatment effect on mortality, bronchopulmonary dysplasia (BPD), and neurodevelopmental outcome. Electronic databases, abstracts from the Pediatric Academic Societies, and results of manual reference searches were used as data sources. Fifteen randomized controlled trials comparing dexamethasone with placebo in 721 ventilated preterm infants older than 7 days were identified. The interaction between dexamethasone treatment effect and OLG use was assessed by meta-regression analysis and subgroup meta-analysis according to the percentage of OLG use in the placebo group. Trials with a moderately early (7- to 14-day) or delayed (>3-week) treatment onset were analyzed separately. Moderately early, but not delayed, dexamethasone treatment significantly reduced mortality rates in trials with OLG use at <30% in the placebo arm. Meta-regression analysis revealed that this reduction was inversely related to OLG use. Increasing OLG use strengthened the positive effect of dexamethasone on BPD in the moderately early trials but attenuated the effect in the delayed-treatment trials. In trials with <30% OLG use, dexamethasone increased the risk for cerebral palsy in the delayed, but not the moderately early, treatment trials. When OLG use is taken into account moderately early dexamethasone treatment reduced mortality rates and the combined outcome mortality and BPD without increasing the risk of adverse neurodevelopmental outcome in ventilated preterm infants. A large randomized controlled trial is needed to confirm or refute these findings.

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

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). 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. 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). 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.

Growth-restricted preterm newborns are predisposed to functional adrenal hyperandrogenism in adult life

The long-term effects of perinatal growth and corticosteroid exposure on adrenal steroid concentrations in adults born very preterm are uncertain. To examine the effect of birth weight, early postnatal growth, and pre- and postnatal corticosteroid administration on serum adrenal steroids in 19-year-old subjects born very preterm. Subjects born before 32 weeks of gestation in The Netherlands participating in the Project on Preterm and Small for Gestational Age Infants (POPS) were investigated at 19 years of age. Serum cortisol, DHEA sulfate (DHEAS), and androstenedione (Adione) concentrations were measured in 393 out of 676 eligible subjects, compared with controls, and associated with perinatal growth and pre- and postnatal corticosteroids administration using multiple linear regression analyses. Serum DHEAS and Adione in men and women were higher than in controls. In the multiple regression analyses, birth weight SDS showed a statistically significant negative association with serum DHEAS concentrations in women (β: -0.865, 95% confidence interval (CI): -1.254 to -0.476) and in men (β: -0.758, 95% CI: -1.247 to -0.268) and with serum Adione concentrations in women (β: -0.337, 95% CI: -0.593 to -0.082). Early postnatal weight gain showed no association with any of measured adrenal markers. In women, serum Adione was associated with postnatal dexamethasone exposure (β: 0.932, 95% CI: 0.022 - 1.843). Young adults born very preterm show elevated adrenal androgens, particularly when born small for gestational age. Postnatal corticosteroid administration is positively associated with serum Adione in young women.

The Effect of Hydrocortisone on Neurodevelopmental Outcome in Premature Infants Less than 29 Weeks’ Gestation

The use of postnatal dexamethasone in premature newborns can be associated with a deleterious neurodevelopmental outcome. The effect of hydrocortisone on developmental outcome in these patients is less clear. We therefore sought to examine the effect of hydrocortisone on early developmental outcome in premature newborns. We retrospectively examined the effect of hydrocortisone on developmental outcome during the first 2 years of life in premature infants <29 weeks' gestation at birth. Even though hydrocortisone was used in infants with a greater risk for poor outcome, its use, unless prolonged >7 days, was generally not associated with a worse developmental outcome or higher rate of referral for early intervention. A short course of hydrocortisone in sick premature newborns does not appear to have a deleterious effect on developmental outcome.

Postnatal dexamethasone treatment delays the onset of puberty and attenuates the regulation of Kiss-1 mRNA expression by allopregnanolone in pubertal female mice

eurosteroid allopregnanolone (3 ,5 -tetrahydroprogesterone; THP), a otent modulator of GABAA receptors and kisspeptin have been shown to egulate theonset of puberty.Whether exposure topostnatal stress effects on HP regulated expression of kisspeptin and thereby delayed pubertal onset, emain unknown. Therefore, in this study, femalemicewere subcutaneously njected with synthetic glucocorticoid, dexamethasone (DEX) (1.0mg/kg) rom postnatal day (PN) 1–4 and intraperitoneally with THP (10mg/kg) for 3 aysduringpuberty (PN45). PostnatalDEX treatedmicehaddelayedonset of uberty by 1 week and irregular estrous cycle patterns compared to control ice of the same age. Normal cycling pubertal femalemice injectedwith THP howed a significant increase in Kiss1 mRNA expression in the anterovenral periventricular nucleus (AVPV) and no change in Kiss1mRNA expression evels in the arcuate nucleus (Arc). Postnatal DEX treatment inhibited the pregulation of Kiss1 mRNA expression by THP in the AVPV during puberty ut had no effect on Kiss1 mRNA expression levels in the Arc. These results emonstrate that exposure to DEX during early development disrupts the isspeptin–GABAA system in the AVPV resulting in irregular estrus cycle and elayed the onset of puberty.

Antenatal and postnatal corticosteroid and resuscitation induced lung injury in preterm sheep

BackgroundInitiation of ventilation using high tidal volumes in preterm lambs causes lung injury and inflammation. Antenatal corticosteroids mature the lungs of preterm infants and postnatal corticosteroids are used to treat bronchopulmonary dysplasia.ObjectiveTo test if antenatal or postnatal corticosteroids would decrease resuscitation induced lung injury.Methods129 d gestational age lambs (n = 5-8/gp; term = 150 d) were operatively delivered and ventilated after exposure to either 1) no medication, 2) antenatal maternal IM Betamethasone 0.5 mg/kg 24 h prior to delivery, 3) 0.5 mg/kg Dexamethasone IV at delivery or 4) Cortisol 2 mg/kg IV at delivery. Lambs then were ventilated with no PEEP and escalating tidal volumes (VT) to 15 mL/kg for 15 min and then given surfactant. The lambs were ventilated with VT 8 mL/kg and PEEP 5 cmH20 for 2 h 45 min.ResultsHigh VT ventilation caused a deterioration of lung physiology, lung inflammation and injury. Antenatal betamethasone improved ventilation, decreased inflammatory cytokine mRNA expression and alveolar protein leak, but did not prevent neutrophil influx. Postnatal dexamethasone decreased pro-inflammatory cytokine expression, but had no beneficial effect on ventilation, and postnatal cortisol had no effect. Ventilation increased liver serum amyloid mRNA expression, which was unaffected by corticosteroids.ConclusionsAntenatal betamethasone decreased lung injury without decreasing lung inflammatory cells or systemic acute phase responses. Postnatal dexamethasone or cortisol, at the doses tested, did not have important effects on lung function or injury, suggesting that corticosteroids given at birth will not decrease resuscitation mediated injury.

Impact of postnatal dexamethasone on psychotomimetic effects of MK-801 measured on adult rats

The present study investigates the impact of dexamethasone (DEX) given in tapering doses in the postnatal period on MK-801-induced locomotor activity and MK-801-evoked deficits of sensorimotor gating of adult rats (60 days old). It has been found that DEX given on postnatal day 1 (0.5μg/g), day 2 (0.3μg/g) and day 3 (0.1μg/g) has no effects on spontaneous locomotor activity and does not influence locomotion observed after MK-801 given in a dose of 0.2 and 0.4mg/kg. Postnatal DEX treatment did not alter the efficacy of sensorimotor gating and its deficits evoked by MK-801 at a dose of 0.2 and 0.4mg/kg. However, a slight increase in the amplitude of startle reaction has been noted in DEX-treated animals. In conclusion, the results of the present study indicate that DEX given postnatally in tapering doses, although pharmacologically effective (decrease in a gain of body and brain weight), has no potential pro-psychotic effects and does not influence pharmacologically induced psychoses by MK-801. The above data indicate that apart from other side effects, the therapeutic application of DEX in the postnatal period is possibly safe in terms of the risk for developing schizophrenia.

Corticothérapie postnatale chez le prématuré : étude des pratiques des centres français de néonatologie en 2006

In 1999, 80% of French neonatal centers used corticosteroids, mainly betamethasone (BMT), to prevent or treat bronchopulmonary dysplasia (BPD) [Lee SK, McMillan DD, Ohlson A, et al. Variations in practice and outcomes in the canadian NICU Network 1996-1997. Pediatrics 2000;106:1070-9]. As many data suggested a low risk-benefit ratio, an updated assessment of this use was necessary [Desnoulez L, Empana J, Anceschi M, et al. Prise en charge de l'immaturité pulmonaire en néonatologie : enquête sur les pratiques européennes. Arch Pediatr 2005;12:4-9; Halliday HL, Ehrenkranz RA, Doyle LW. Early postnatal (less than 96h) corticosteroids for preventing chronic lung disease in preterm infants. Cochrane Database Syst Rev 2003:CD001146; Yeh TF, Lin YJ, Lin HC, et al. Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N Engl J Med 2004;350:1304-13; Lin YJ, LKin CH, Wu JM, et al. The effects of early postnatal dexamethasone therapy on pulmonary outcome in premature infants with respiratory distress syndrome: a 2-year follow-up study. Acta Paediatr 2005;94:310-16]. Questionnaires addressing the use of and indications for corticosteroids were sent to all French neonatal centers. The study was conducted over 5 months (July to November 2006). Of 202 questionnaires sent out, 186 (92%) were completed. Of these 186 centers, 147 (79%) had a standard protocol for corticosteroid use, covering systemic and inhaled steroids (76 units), only systemic steroid therapy (30 units) and only inhaled steroids (41 units). Systemic corticosteroids were used in 106 centers for hemodynamic purposes in 42 cases (40%), prevention of BPD in 1 case (1%), early treatment of BPD (day 4 to day 21) in 23 cases (22%) and late treatment of BPD (after day 21) in 74 cases (70%). Hemisuccinate hydrocortisone (HSHC) was the only corticoid used for hemodynamic failure. The steroid used for early treatment of BPD was BMT (21 out of 23). The duration of treatment was less than 4 days in 10 centers (43%). The steroid most often used for late treatment was BMT (67 out of 74). The duration of treatment was less than 4 days in 29 centers, between 4 and 8 days in 22 centers, and longer than 8 days in 26 centers. Among 117 centers administering corticosteroids by inhalation, 74% used budesonide. Use of corticosteroids was higher in teaching hospitals (86%) than in others (49%), likely due to the immaturity of the neonates hospitalized in these centers. We showed a still frequent use of corticosteroids in preterm infants in France but only after the fourth day of life to treat BPD and not as a prevention therapy. We also found a marginal use of DXM in accordance with both short-term and long-term adverse side effects, suggesting an unbalanced risk-benefit ratio even though it has a beneficial effect on respiratory status. Our findings indicate the need for national recommendations and trials to assess oral BMT treatment in premature neonates with BPD.

Finding the Optimal Postnatal Dexamethasone Regimen for Preterm Infants at Risk of Bronchopulmonary Dysplasia: A Systematic Review of Placebo-Controlled Trials

Postnatal dexamethasone therapy reduces the incidence of bronchopulmonary dysplasia in preterm infants but may be associated with an increased risk for adverse neurodevelopmental outcome. Our goal was to determine if the effects of dexamethasone on mortality and pulmonary and neurodevelopmental sequelae in preterm infants are modified by the cumulative dose given. Randomized, controlled trials comparing dexamethasone with placebo in ventilated preterm infants >7 days old were identified by searching the electronic databases and the abstracts from the Pediatric Academic societies and by performing manual reference searches. Two reviewers independently assessed eligibility and quality of trials and extracted data on study design, patient characteristics, and relevant outcomes. Original trialists were asked to provide additional data. Sixteen trials including 1136 patients were analyzed by using meta-analysis and metaregression. Additional data were provided by 12 original trialists. Trials with a moderately early (7- to 14-day) or delayed (>3-week) postnatal treatment onset were analyzed separately. Higher dexamethasone doses reduced the relative risk for the combined outcome, mortality or bronchopulmonary dysplasia, with the largest effect in trials that used a cumulative dose of >4 mg/kg. No effect was found of doses on the risk of neurodevelopmental sequelae in the delayed treatment studies, but in the moderately-early-treatment studies the risk of mortality or cerebral palsy decreased by 6.2%, and the risk of a Mental Developmental Index below -2 SDs decreased by 6.6% for each incremental mg/kg cumulative dexamethasone dose. Higher cumulative dexamethasone doses administered after the first week of life may decrease the risk for bronchopulmonary dysplasia without increasing the risk for neurodevelopmental sequelae in ventilated preterm infants. A large randomized trial is needed to confirm or refute these findings.

Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Follow-up Study of a Randomized Controlled Trial of Postnatal Dexamethasone Therapy in Very Low Birth Weight Infants: Effects on Pulmonary Outcomes at Age 8 to 11 Years

Impact of perinatal corticosteroids on neuromotor development and outcome: Review of the literature and new meta-analysis

Perinatal corticosteroids are like a double-edged sword. On the one hand, they reduce risk for major morbidity and even mortality; on the other hand, they modify growth and development of body systems, with short- and long-term consequences. The relationship between corticosteroids and neurodevelopmental outcome has been extensively studied in randomized controlled trials, cohort and case-control studies and meta-analyses. In this article we attempt accurately to reflect current clinical equipoise on this issue by reviewing the most recent literature and adding a new meta-analysis on the relationship between postnatal dexamethasone and cerebral palsy and neurodevelopmental impairment.

Postnatal betamethasone vs dexamethasone in premature infants with bronchopulmonary dysplasia: a pilot study

As effects of glucocorticoids differ with respect to preparation, dose and duration, we hypothesized that a postnatal regimen of a low-dose, short-course betamethasone treatment had comparable efficacy and a better safety profile compared to the conventional high-dose, dexamethasone. To test our hypothesis, we selected premature neonates with a birth weight <or=1000 g and a gestational age <or=29 weeks who were ventilated >10 postnatal days with an FiO(2)>0.4 and no ability to wean mechanical support for >or=3 consecutive days. These neonates either received twice daily dexamethasone 0.25 mg kg(-1) per dose intravenously for 3 days tapered to 0.125 mg kg(-1) per dose for 4 days (June 1999 to December 2000) or betamethasone 0.125 mg kg(-1) per day intramuscularly once per day for 3 days (January 2001 to December 2002). We found a significant reduction in FiO(2) after 3 days in both glucocorticoid treatment groups. There were no significant differences between the two treatment groups in the clinical parameters including decrease in FiO(2), oxygenation index, mean airway pressure and percent extubation. Duration of ventilation, number of oxygen days and length of hospital stay were comparable in the two groups. Of particular interest, the betamethasone group showed fewer adverse effects, such as poor weight gain and high blood glucose, than the dexamethasone group. A short course of low-dose betamethasone has comparable efficacy and seemingly a better short-term safety profile compared to conventional dexamethasone treatment.

Blood Pressure, Anti-Hypotensive Therapy, and Neurodevelopment in Extremely Preterm Infants

To compare neurodevelopment (ND) in 3 cohorts of extremely preterm infants: untreated with normal blood pressure (BP), untreated with low BP, and treated with low BP. We conducted a retrospective study of infants 23 to 25 weeks gestation. Low BP was defined as >or=3 mean arterial pressures <or=25 mm Hg in the first 72 hours of life. Treatment included fluids, inotropes, and corticosteroids. We examined 67 infants with normal BP, 31 infants with untreated low BP, and 70 infants with treated low BP. A total of 75% survived to be discharged from the hospital, and 95% of survivors had ND assessment. Perinatal variables differed between treated infants with low BP and the other groups. Untreated infants with low BP had similar survival rates, but more cerebral palsy, deafness, or any ND impairment when compared with infants with normal BP. Treated infants with low BP had more mortality, worse ND, and less survival without ND impairment compared with infants who had normal BP. Results were unchanged after logistic regression adjusting for prenatal steroids, maternal education, race, sex, bronchopulmonary dysplasia, and postnatal dexamethasone exposure. Infants with low BP-regardless of treatment-had worse ND than infants with normal BP. Early low BP may be independently associated with a poor outcome.

Postnatal Administration of Dexamethasone for Weaning off the Ventilator Affects Thyroid Function

Background: Very preterm neonates are at risk of hypothyroxinemia because of prematurity as well as because of neonatal disease. Hypothyroxinemia is associated with impaired developmental outcome. Preterm infants who cannot be weaned from the ventilator can be treated with dexamethasone. Glucocorticoid administration has been found to alter thyroid hormone parameters. Therefore, dexamethasone treatment in these infants might additionally impair their thyroid function, which could have consequences for developmental outcome. Objective: To assess what changes in thyroid function occur in the first hours after initiating dexamethasone treatment in ventilated preterm infants. Methods: Preterm infants, in whom the decision was taken to start dexamethasone treatment, were included. Thyroxine (T₄), 3,5,3′-triiodothyronine (T₃), reverse T₃ (rT₃), thyroid-stimulating hormone (TSH) and cortisol were determined before and 6–9 h after administration of the first dose of a postnatal dexamethasone course. Details of clinical condition were recorded at both time points. Results: Sixteen very preterm infants were included at a median age of 20 days. While clinical condition was stable between start of dexamethasone and 6–9 h thereafter, TSH and T₃ levels decreased significantly. rT₃ levels significantly increased, resulting in a decrease in the T₃/rT₃ ratio. There was no statistically significant effect on the levels of T₄. Conclusion: Postnatal dexamethasone administration negatively affects thyroid functionin the preterm infant with severe chronic lung disease.

Effects of Higher Versus Lower Dexamethasone Doses on Pulmonary and Neurodevelopmental Sequelae in Preterm Infants at Risk for Chronic Lung Disease: A Meta-analysis

Systemic postnatal dexamethasone treatment reduces the risk of chronic lung disease in preterm infants but also may be associated with increased risk of neurodevelopmental impairment. Because it is not known whether these effects are modulated by the cumulative dexamethasone dose, we systematically reviewed the available randomized evidence on the effects of lower versus higher cumulative dexamethasone doses, in terms of death, pulmonary morbidity, and neurodevelopmental outcomes, in preterm infants. Randomized, controlled trials comparing higher- versus lower-dosage dexamethasone regimens in ventilated preterm infants were identified by searching the main electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research (from 1990 onward). Eligibility and quality of trials were assessed, and data on study design, patient characteristics, and relevant outcomes were extracted. Six studies that enrolled a total of 209 participants were included; 2 studies contrasted cumulative dexamethasone doses in the higher ranges (>2.7 mg/kg in the higher-dosage regimen) and 4 in the lower ranges (<or=2.7 mg/kg in the higher-dosage regimen). Meta-analysis revealed no effect of dexamethasone dose on rates of death and neurodevelopmental sequelae in these 2 subgroups. Subgroup analysis of the studies contrasting dexamethasone doses in the higher ranges showed that the higher dose of dexamethasone was more effective in reducing the occurrence of chronic lung disease than was the lower dose. Interpretation of these data was hampered by the small samples of randomly assigned children, heterogeneity of study populations and designs, use of late rescue glucocorticoids, and lack of long-term neurodevelopmental data in some studies. Recommendations for optimal dexamethasone doses for preterm infants at risk for chronic lung disease cannot be based on current evidence. A well-designed, large, randomized, controlled trial is urgently needed to establish the optimal dexamethasone dosage regimen.

Effects of Postnatal Dexamethasone Exposure on the Developmental Outcome of Premature Infants

Extremely low birth weight premature infants are at risk for poor neurodevelopmental outcome. Postnatal dexamethasone has often been used in premature infants to prevent or treat bronchopulmonary dysplasia, and this drug is thought by some to affect neurodevelopmental outcome. We retrospectively examined the effect of this steroid on early neurodevelopment. Dexamethasone exposure was associated with an adverse outcome and was a stronger predictor of outcome than other accepted risk factors. If used, dexamethasone should be used in these high-risk infants for as short a period as possible.

Development of glucocorticoid receptor regulation in the rat forebrain: Implications for adverse effects of glucocorticoids in preterm infants

Glucocorticoids are the consensus treatment to avoid respiratory distress in preterm infants but there is accumulating evidence that these agents evoke long-term neurobehavioral deficits. Earlier, we showed that the developing rat forebrain is far more sensitive to glucocorticoid-induced disruption in the fetus than in the neonate. Feedback regulation of glucocorticoid receptors (GRs) is an essential homeostatic mechanism and we therefore examined the development of GR downregulation in the perinatal period. Pregnant rats or newborn pups were given dexamethasone daily (gestational days 17–19, postnatal days 1–3, or postnatal days 7–9), ranging from doses below that recommended for use in preterm infants (0.05 mg/kg) to therapeutic doses (0.2 or 0.8 mg/kg). Twenty-four hours after the last injection, we determined forebrain GR protein by Western blotting. Although postnatal dexamethasone treatment downregulated GRs at all doses, the fetal forebrain failed to show any decrement and instead exhibited slight GR upregulation. In controls, forebrain GR levels also showed a large increment over the course from late gestation through the second postnatal week, despite the fact that circulating glucocorticoid levels increase substantially during this period. Our results suggest that GR homeostasis develops primarily postnatally and that fetal inability to downregulate GRs in the face of exogenous glucocorticoid administration plays a role in the vulnerability of key neural circuits to developmental disruption. Since this developmental phase in the rat corresponds to the critical period in which glucocorticoids are used in preterm infants, adverse effects on brain development may be inescapable.

Below median birth weight in appropriate-for-gestational-age preterm infants as a risk factor for bronchopulmonary dysplasia

To assess the presence of chorioamnionitis and intrauterine growth as prenatal risk factors for broncho pulmonary dysplasia (BPD) in appropriate-for-gestational-age (AGA) infants of <28 weeks' gestation. Gender, race, birth weight, gestational age, histology of the placenta, diagnosis of BPD at 36 weeks' gestation, postnatal dexamethasone treatment, and death were recorded in 150 preterm infants born at <28 weeks' gestation, and admitted between 1996 and 2001. In 122 AGA infants (mean gestational age: 26.18 weeks, mean birth weight: 837 g), BPD was associated with gestational age-related birth weights below the 50(th) centile. Intrauterine growth deceleration started between 25 and 26 weeks' gestation. Chorioamnionitis was not related to BPD. AGA infants of 26-28 weeks' gestation with birth weights below the median showed an increased risk of developing BPD.