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While the effect of antenatally administered corticosteroids on fetal heart rate (HR) and heart rate variability (HRV) is well established, little information is available on how these drugs affect maternal physiology. In this secondary analysis of a prospective, observational cohort study, we quantify how corticosteroids affect maternal HR and HRV, which serve as a proxy measure for autonomic regulation. Abdominal ECG measurements were recorded before and in the five days following the administration of betamethasone-a corticosteroid commonly used for fetal maturation-in 46 women with singleton pregnancies. Maternal HR and HRV were determined from these recordings and compared between these days. HRV was assessed with time- and frequency-domain features, as well as non-linear and complexity features. In the 24 h after betamethasone administration, maternal HR was significantly increased (p < 0.01) by approximately 10 beats per minute, while HRV features linked to parasympathetic activity and HR complexity were significantly decreased (p < 0.01 and p < 0.001, respectively). Within four days after the initial administration of betamethasone, HR decreases and HRV features increase again, indicating a diminishing effect of betamethasone a few days after administration. We conclude that betamethasone administration results in changes in maternal HR and HRV, despite the heterogeneity of the studied population. Therefore, its recent administration should be considered when evaluating these cardiovascular metrics.

Producción Científica, Herein, we report a computational investigation of the binding affinity of dexamethasone, betamethasone, chloroquine and hydroxychloroquine to SARS-CoV-2 main protease using molecular and quantum mechanics as well as molecular docking methodologies. We aim to provide information on the anti-COVID-19 mechanism of the abovementioned potential drugs against SARS-CoV-2 coronavirus. Hence, the 6w63 structure of the SARS-CoV-2 main protease was selected as potential target site for the docking analysis. The study includes an initial conformational analysis of dexamethasone, betamethasone, chloroquine and hydroxychloroquine. For the most stable conformers, a spectroscopic analysis has been carried out. In addition, global and local reactivity indexes have been calculated to predict the chemical reactivity of these molecules. The molecular docking results indicate that dexamethasone and betamethasone have a higher affinity than chloroquine and hydroxychloroquine for their theoretical 6w63 target. Additionally, dexamethasone and betamethasone show a hydrogen bond with the His41 residue of the 6w63 protein, while the interaction between chloroquine and hydroxychloroquine with this amino acid is weak. Thus, we confirm the importance of His41 amino acid as a target to inhibit the SARS-CoV-2 Mpro activity.

While maternally administered corticosteroids are vital for premature infants’ survival, the benefits for neonates born between 34 and 37 weeks of gestation, also coined the late preterm period, remain unclear. This period represents a vulnerable time in fetal brain development that is highly susceptible to fetal programming and represents the largest distribution of prenatal births, with the lowest neonatal mortality rates. Animal studies have shown that antenatal betamethasone (BTM) exposure disrupt neuroanatomy and functionality, specifically by interacting with the developing hypothalamic-pituitary-adrenal axis (HPA). Thus, the safety of antenatal corticosteroids administration during the late preterm period is currently being questioned. We hypothesized that mice exposed to betamethasone would show signs of impaired neurodevelopment defined as worsened or unfavorable behavioral scores and decreased total volumes in anatomical regions associated with stress response. We had 2 objectives: i) determine if late preterm administration of BTM induces a change in locomotor activity, exploratory behavior, short-term memory or social behavior, ii) determine whether BTM alters the anatomical size of brain structures related to stress. Furthermore, in comparison to humans, a newborn mouse born at full term, has a brain development like that of a human preterm infant. Thus, most of their neurodevelopment takes place during the postpartum period. Therefore, we also evaluated if the administration of BTM via maternal circulation influences murine neurodevelopment in order to mimic clinical protocols. We conducted a study in the form of a randomized, blinded, placebo-controlled trial in a mouse model. Ten CD-1 gravid mice were randomly assigned to 4 groups: Antenatal-intervention, Antenatal-control, Postnatal-intervention, or Postnatal-control. Timing and doses aimed to replicate human exposure at 24-26- and 34-36-weeks gestation respectively. Antenatal-intervention, Alors que les corticostéroïdes administrés via la mère demeurent vitaux pour la survie des prématurés, les avantages pour les nouveaux-nés nés entre 34 et 37 semaines de gestation, c’est- à-dire dans la période de prématurité tardive, restent peu clairs. Cette période en est une de vulnérabilité pour le développement du cerveau du foetus, est très propice à la programmation foetale et représente la plus grande distribution de naissances prénatales, mais avec les taux de mortalité néonatale les plus bas. Des études animales ont montré que l'exposition anténatale à la bétaméthasone (BTM) perturbe la neuroanatomie et aussi la fonction, spécifiquement en interagissant avec l'axe hypothalamo-hypophyso-surrénalien (HPA) en développement. Ainsi, la sécurité de l'administration anténatale de corticostéroïdes pendant la période de prématurité tardive est actuellement remise en question. Nous avons émis l’hypothèse que les souris exposées à la BTM présenteraient des signes d’un développement neurologique affecté sous la forme de score comportementaux défavorables ou faibles ainsi qu’une diminution du volume total des régions cérébrales associées aux réactions de stress. Nous avions deux objectifs : i) déterminer si l’administration de BTM lors de la prématurité tardive mène à un changement au niveau de l’activité locomotrice, des comportements d’exploration, de la mémoire à court terme ou du comportement social et ii) déterminer si la BTM influence la taille anatomique des structures cérébrales liées au stress. De plus, comparativement aux humains, un souriceau nouvellement né à terme a un développement cérébral comparable à celui d’un nouveau-né prématuré. Ainsi, la majorité de son neurodéveloppement a lieu durant la période postnatale. Nous avons donc évalué si l’administration de BTM via la circulation maternelle a une influence sur le neurodéveloppement murin afin d’émuler les protocoles cliniques. Nous avons mené une étude sous la forme d’un essai randomisé contrôlé à l’

The aim was to assess the association between fetal growth restriction (FGR) and fetal heart rate variability (FHRV) in relation to fetal movements. A prospective observational cohort study was performed. Non-invasive fetal electrocardiography (NI-FECG) allowed beat-to-beat assessments with <5% corrections of RR intervals. FHRV analyses included: Root mean square of successive RR interval differences (RMSSD), high frequency power (HF power), and low frequency power (LF power). Fetal movements were categorized by continuous ultrasound scanning. We enrolled 36 singleton pregnant women expecting a small fetus (< the 2.3 percentile of mean weight for gestational age) diagnosed by ultrasound, of whom 25 presented with a birthweight < the 2.3 percentile. Among these, 11 were excluded due to low quality NI-FECG recordings, leaving 14 women with 28 recordings eligible for inclusion in the analyses. The control group consisted of 22 healthy fetuses with birthweights between the 10th and the 90th percentile (average for gestational age [AGA]). In FGR fetuses the HRV response to respiratory activity was comparable to that of AGA fetuses. RMSSD (Ratio 1.54 [95% CI: 1.33; 1.79]) and HF power (Ratio 2.88 [95% CI: 2.12; 3.91]) increased, whereas LF/HF power (Ratio: 0.44 [95% CI: 0.31;0.63]) decreased. However, during fetal quiescence, FGR fetuses differed significantly from AGA fetuses. Compared to AGA fetuses, FGR fetuses displayed lower RMSSD (Ratio 0.77 (95% CI: 0.58; 1.02)) and HF power (Ratio 0.56 (95% CI:0.32; 0.98)). This reduction was associated with the severity of the FGR. In conclusion, FGR fetuses displayed a respiratory sinus arrhythmia (RSA) comparable to AGA fetuses; however, more important, parameters representing cardiac vagal activity were impaired in FGR fetuses during quiescence. RSA may constitute an intrinsic function of the cardiovascular system, which is unaffected by fetal compromise. However, the basic cardiac outflow assessed during fetal qui

The aim was to assess the association between fetal growth restriction (FGR) and fetal heart rate variability (FHRV) in relation to fetal movements. A prospective observational cohort study was performed. Non-invasive fetal electrocardiography (NI-FECG) allowed beat-to-beat assessments with <5% corrections of RR intervals. FHRV analyses included: Root mean square of successive RR interval differences (RMSSD), high frequency power (HF power), and low frequency power (LF power). Fetal movements were categorized by continuous ultrasound scanning. We enrolled 36 singleton pregnant women expecting a small fetus (< the 2.3 percentile of mean weight for gestational age) diagnosed by ultrasound, of whom 25 presented with a birthweight < the 2.3 percentile. Among these, 11 were excluded due to low quality NI-FECG recordings, leaving 14 women with 28 recordings eligible for inclusion in the analyses. The control group consisted of 22 healthy fetuses with birthweights between the 10th and the 90th percentile (average for gestational age [AGA]). In FGR fetuses the HRV response to respiratory activity was comparable to that of AGA fetuses. RMSSD (Ratio 1.54 [95% CI: 1.33; 1.79]) and HF power (Ratio 2.88 [95% CI: 2.12; 3.91]) increased, whereas LF/HF power (Ratio: 0.44 [95% CI: 0.31;0.63]) decreased. However, during fetal quiescence, FGR fetuses differed significantly from AGA fetuses. Compared to AGA fetuses, FGR fetuses displayed lower RMSSD (Ratio 0.77 (95% CI: 0.58; 1.02)) and HF power (Ratio 0.56 (95% CI:0.32; 0.98)). This reduction was associated with the severity of the FGR. In conclusion, FGR fetuses displayed a respiratory sinus arrhythmia (RSA) comparable to AGA fetuses; however, more important, parameters representing cardiac vagal activity were impaired in FGR fetuses during quiescence. RSA may constitute an intrinsic function of the cardiovascular system, which is unaffected by fetal compromise. However, the basic cardiac outflow assessed during fetal qui

Darier's disease is a dominantly inherited acantholytic dermatosis which typically occurs in childhood and adolescence in patients with a positive family history. Sporadic cases and late onset cases are rarely reported in the literature. We present the case of a 75-year-old female who presents with sporadic late onset Darier's Disease as well as a review of the literature. Histopathology showed hyperkeratosis, parakeratosis, papillomatosis and elongation of rete ridges in the epidermis, as well as suprabasal acantholysis. Dyskeratotic cells (corps ronds) were present in the upper malpighian layer, consistent with Darier's disease. The patient was treated effectively with acitretin 10 mg per day, topical betamethasone dipropionate 0.05% ointment, soap free wash and Sorbolene moisturiser. Our atypical case highlights the potential for Darier's Disease, a condition which most commonly presents in early life, to sporadically arise in the elderly. Dermatologists should consider Darier's Disease as a potential differential diagnosis in elderly patients with classical clinical signs.

Background: Lichen planus (LP) can affect all Fitzpatrick skin phototypes but its morphology can differ.1 The diagnosis of lichen planus in the skin of colour is challenging for clinicians because of this potential clinical variations and the overall lack of confidence in diagnosing and managing those with skin of colour.2,3,4,5 Objective: To add to the limited dermoscopic literature on LP in skin of colour and highlights the importance of comprehensive dermoscopic examination and precise history taking in the skin of colour population. Method(s): We present a case that demonstrates the importance of using dermoscopy to assess the extent of lichen planus in Fitzpatrick skin types 4-6. Result(s): The histological study has confirmed the diagnosis of lichen planus and lichen planopilaris. The patient was recalled 8-weeks post the initial visit to observe for the progress. There was ongoing pruritus present to surround the pigmented plaque despite prescribed topical Betamethasone dipropionate 0.1% cream. Dermoscopy was re-performed to study the plaque but this time also extended inferiorly to observe the enduring area of pruritus. The examined skin appeared normal macroscopically, but showed a subclinical extension of lichen planus. In the skin of colour, lichen planus does not necessarily demonstrate the classical features of lichen planus, such as erythema, in which clinicians can miss subclinical diagnosis or extension of the disease. Therefore, careful dermoscopy and comprehensive history taking including a specific questioning about pruritus are imperative to avoid overlooking subclinical lichen planus in individuals with a high suspicion of the condition despite normal-appearing skin.

Darier's disease is a dominantly inherited acantholytic dermatosis which typically occurs in childhood and adolescence in patients with a positive family history. Sporadic cases and late onset cases are rarely reported in the literature. We present the case of a 75-year-old female who presents with sporadic late onset Darier's Disease as well as a review of the literature. Histopathology showed hyperkeratosis, parakeratosis, papillomatosis and elongation of rete ridges in the epidermis, as well as suprabasal acantholysis. Dyskeratotic cells (corps ronds) were present in the upper malpighian layer, consistent with Darier's disease. The patient was treated effectively with acitretin 10 mg per day, topical betamethasone dipropionate 0.05% ointment, soap free wash and Sorbolene moisturiser. Our atypical case highlights the potential for Darier's Disease, a condition which most commonly presents in early life, to sporadically arise in the elderly. Dermatologists should consider Darier's Disease as a potential differential diagnosis in elderly patients with classical clinical signs.

Background: Lichen planus (LP) can affect all Fitzpatrick skin phototypes but its morphology can differ.1 The diagnosis of lichen planus in the skin of colour is challenging for clinicians because of this potential clinical variations and the overall lack of confidence in diagnosing and managing those with skin of colour.2,3,4,5 Objective: To add to the limited dermoscopic literature on LP in skin of colour and highlights the importance of comprehensive dermoscopic examination and precise history taking in the skin of colour population. Method(s): We present a case that demonstrates the importance of using dermoscopy to assess the extent of lichen planus in Fitzpatrick skin types 4-6. Result(s): The histological study has confirmed the diagnosis of lichen planus and lichen planopilaris. The patient was recalled 8-weeks post the initial visit to observe for the progress. There was ongoing pruritus present to surround the pigmented plaque despite prescribed topical Betamethasone dipropionate 0.1% cream. Dermoscopy was re-performed to study the plaque but this time also extended inferiorly to observe the enduring area of pruritus. The examined skin appeared normal macroscopically, but showed a subclinical extension of lichen planus. In the skin of colour, lichen planus does not necessarily demonstrate the classical features of lichen planus, such as erythema, in which clinicians can miss subclinical diagnosis or extension of the disease. Therefore, careful dermoscopy and comprehensive history taking including a specific questioning about pruritus are imperative to avoid overlooking subclinical lichen planus in individuals with a high suspicion of the condition despite normal-appearing skin.

Background: Glucocorticoids (GCs) play a pivotal role in fetal programming. Antenatal treatment with synthetic GCs (sGCs) in individuals in danger of preterm labor is common practice. Adverse short- and long-term effects of antenatal sGCs have been reported, but their effects on placental epigenetic characteristics have never been systematically studied in humans. Results: We tested the association between exposure to the sGC betamethasone (BET) and placental DNA methylation (DNAm) in 52 exposed cases and 84 gestational-age-matched controls. We fine-mapped associated loci using targeted bisulfite sequencing. The association of placental DNAm with gene expression and co-expression analysis on implicated genes was performed in an independent cohort including 494 placentas. Exposure to BET was significantly associated with lower placenta DNAm at an enhancer of FKBP5. FKBP5 (FK506-binding protein 51) is a co-chaperone that modulates glucocorticoid receptor activity. Lower DNAm at this enhancer site was associated with higher expression of FKBP5 and a co-expressed gene module. This module is enriched for genes associated with preeclampsia and involved in inflammation and immune response. Conclusions: Our findings suggest that BET exposure during pregnancy associates with few but lasting changes in placental DNAm and may promote a gene expression profile associated with placental dysfunction and increased inflammation. This may represent a pathway mediating GC-associated negative long-term consequences and health outcomes in offspring.

[Resumen] Introducción: Según la organización mundial de la salud (OMS), cada año nacen 15 millones de niños prematuros y 1 millón muere por complicaciones en el parto relacionadas con la prematuridad. La patología respiratoria es la primera causa de morbi-mortalidad y viene representada por el síndrome de distrés respiratorio (SDR) por déficit de surfactante pulmonar. Para inducir la maduración pulmonar se emplean corticosteroides entre la semana 24 y 34 de gestación, siendo la betametasona y la dexametasona los fármacos más empleados. Objetivo: El objetivo de este estudio es conocer si existen diferencias en la eficacia de tratamiento con dexametasona y betametasona para el desarrollo pulmonar ante la existencia de riesgo de parto prematuro. Metodología: Se llevó a cabo una revisión sistemática mediante la búsqueda de ensayos clínicos y estudios de cohortes en las bases de datos: PubMed, Cinahl, Web of Science (WOS) y Scopus. La estrategia de búsqueda se realizó sobre estudios realizados en humanos en los últimos 10 años en inglés, español o portugués. Finalmente, se seleccionaron 10 artículos que cumplían nuestros criterios de selección. Resultados: Tanto la dexametasona como la betametasona son efectivos para la reducción de las tasas de SDR y complicaciones respiratorias, excepto en partos pretérminos tardíos, y se recomiendan administrar en el período de 7 días antes del parto. Deben evitarse las dosis repetitivas y elevadas de betametasona ya que se relaciona con una disminución del peso corporal del niño. La dexametasona sería el fármaco de elección en países de bajos recursos ya que su coste es menor que el de la betametasona. Conclusiones: Ambos fármacos son efectivos para reducir el riesgo de SDR y así conseguir la maduración pulmonar. Serían necesarias más investigaciones para determinar si existen diferencias en cuanto a seguridad y eficacia entre estos corticosteroides, para maximizar así los beneficios y minimizar los posibles daños tanto a la madre c, [Resumo] Introdución: Según a organización mundial da saúde (OMS), cada ano nacen aproximadamente 15 millóns de nenos prematuros e 1 millón morre por complicacións no parto relacionadas coa prematuridad. A patoloxía respiratoria é a primeira causa de morbi-mortalidade e ven representada polo síndrome de distrés respiratorio (SDR) por déficit de surfactante pulmonar. Para inducir a maduración pulmonar empréganse corticosteroides entre a semana 24 e 34 de xestación, sendo a betametasona e a dexametasona os fármacos máis empregados. Obxectivo: O obxectivo deste estudo é coñecer se existen diferenzas na eficacia de tratamento con dexametasona e betametasona para o desenvolvemento pulmonar ante a existencia de risco de parto prematuro. Metodoloxía: Levouse a cabo unha revisión sistemática mediante a procura de ensaios clínicos e estudos de cohortes nas bases de datos: PubMed, Cinahl, Web of Science (WOS) e Scopus. A estratexia de procura realizouse sobre estudos realizados en humanos nos últimos 10 anos en inglés, español ou portugués. Finalmente, seleccionáronse 10 artigos que cumprían os nosos criterios de selección. Resultados: Tanto a dexametasona como a betametasona son efectivos para a redución das taxas de SDR e complicacións respiratorias, excepto en partos pretérminos tardíos, e recoméndanse administrar no período de 7 días antes do parto. Deben evitarse as doses repetitivas e elevadas de betametasona xa que se relaciona cunha diminución do peso corporal do neno. A dexametasona sería o fármaco de elección en países de baixos recursos xa que o seu custo é menor que o da betametasona. Conclusións: Ambos os fármacos son efectivos para reducir o risco de SDR e así conseguir a maduración pulmonar. Serían necesarias máis investigacións para determinar se existen diferenzas en canto a seguridade e eficacia entre estes corticosteroides, para maximizar así os beneficios e minimizar os posibles danos tanto á nai como ao feto., [Abstract] Introduction: According to the World Health Organisation (WHO), every year 15 million babies are born prematurely and 1 million die from birth complications related to prematurity. Respiratory pathology is the leading cause of morbidity and mortality and is represented by respiratory distress syndrome (RDS) due to pulmonary surfactant deficiency. Corticosteroids are used to induce lung maturation between 24 and 34 weeks of gestation, with betamethasone and dexamethasone being the most used drugs. Objective: The aim of this study is to determine whether there are differences in the efficacy of treatment with dexamethasone and betamethasone for lung development in the presence of risk of preterm birth. Methodology: A systematic review was conducted by searching for clinical trials and cohort studies in the following databases: PubMed, Cinahl, Web of Science (WOS) and Scopus. The search strategy was based on studies conducted in humans in the last 10 years in English, Spanish or Portuguese. Finally, 10 articles were selected that met our selection criteria. Results: Both dexamethasone and betamethasone are effective in reducing the rates of RDS and respiratory complications, except in late preterm deliveries, and are recommended to be administered in the 7-day antepartum period. High and repetitive doses of betamethasone should be avoided as it is associated with a decrease in infant body weight. Dexamethasone would be the drug of choice in resource-poor countries as it is cheaper than betamethasone. Conclusions: Both drugs are effective in reducing the risk of RDS to achieve lung maturation. Further research would be needed to determine if there are differences in safety and efficacy between these corticosteroids to maximize the benefits and minimize potential harm to both mother and fetus.

Topical treatment is the mainstay for mild or moderate psoriasis, but patients are generally little satisfied. Calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam has shown to improve signs and symptoms in plaque psoriasis patients. This study assessed patient's satisfaction with Cal/BD foam in a real-life Italian dermatological clinical practice. A multicenter, 4-week observational prospective cohort study enrolled, in 17 Italian dermatology clinics, adult patients with plaque psoriasis on the body and/or scalp. Treatment satisfaction was assessed by 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9), preference over previous treatments by Patient Preference Questionnaire (PPQ), and change in disease state by Psoriasis Area Severity Index (PASI). Overall 256 patients were eligible, with a mean (SD) age of 55.6 (15.4) years, 59.4% were males. Psoriasis severity was mild in 52.0% of patients, moderate in 43.3%, and severe in 4.7%. Scalp involvement was present in 36.7% of patients. Previous antipsoriatic treatments had been received by 80.5% of patients. TSQM-9 median (25th-75th percentile) scores were 83.3 (66.7-88.9) for effectiveness, 77.8 (66.7-88.9) for convenience, and 78.6 (64.3-92.9) for global satisfaction. Mean (SD) PASI value decreased from 7.3 (4.8) to 2.1 (2.7) after 4 weeks. More than 90% of patients previously treated for psoriasis evaluated the Cal/BD foam more effective, easier to use and better tolerated compared to previous topical treatments at PPQ. This observational study provides real-life evidence of a high level of satisfaction with effectiveness and convenience of the Cal/BD foam in a cohort of plaque psoriasis patients, with an objective improvement in PASI.

BackgroundPsoriasis is a disease that commonly manifests in adolescence. Up to half of adults with psoriasis develop it before the age of 20. Topical formulations containing corticosteroids and/or vitamin D3 analogs are recommended for treatment.ObjectiveThis phase II study aimed to evaluate the safety, including any potential effect on the hypothalamic-pituitary-adrenal axis and calcium metabolism, and efficacy of fixed-dose combination calcipotriene (0.005%) and betamethasone (0.064% as dipropionate) (Cal/BD) gel in adolescents with psoriasis.MethodsPatients aged 12 to <17 years, with at least mild psoriasis on the body and scalp, received topical Cal/BD gel once daily for ≤8 weeks. Safety response criteria included adverse drug reactions [ADRs; any adverse event (AE) possibly or probably related to treatment as determined by the investigator; a primary response criterion] and AEs (a secondary response criterion). Only treatment-emergent AEs (events that occurred after the first application of Cal/BD gel or events which started before this and increased in intensity after the first application of Cal/BD gel) are presented here. Efficacy response criteria included controlled disease, by physician's global assessment of disease severity (PGA), following Cal/BD gel treatment.ResultsA total of 107 patients (median age 14 years; range 12-16) were enrolled and treated. Eight ADRs were observed in 7 (7%) patients and 38 (36%) patients experienced ≥1 AE. The most common AEs were headache [6 (6%) patients], nasopharyngitis [6 (6%) patients] and blood parathyroid hormone increased [4 (4%) patients]. One severe AE was reported (attempted suicide) but was considered unrelated to treatment. At the end of treatment, 58% of patients had controlled disease on the body and 69% on the scalp according to PGA.ConclusionIn this uncontrolled phase II study, Cal/BD gel was well tolerated and effective for treating scalp and body psoriasis in adolescents.

Glucocorticoid (GC) signaling via the glucocorticoid receptor (GR) is essential for lung maturation in mammals. Previous studies using global or conditional mouse model knockouts of the GR gene have established that GR-mediated signaling in the interstitial mesenchyme of the fetal lung is critical for normal lung development. Screens for downstream GC-targets in conditional mesenchymal GR deficient mouse lung (GRmesKO) identified Versican (Vcan), an important extracellular matrix component and cell proliferation regulator, as a potential GR-regulated target. We show that, of the five major VCAN isoforms, the VCAN-V1 isoform containing the GAGbeta domain is the predominant VCAN isoform in the fetal mouse lung distal mesenchyme at both E16.5 and E18.5, whereas the GAGalpha-specific VCAN-V2 isoform was only localized to the smooth muscle surrounding proximal airways. Both Vcan-V1 mRNA and protein levels were strongly overexpressed in the GRmesKO lung at E18.5. Finally, we investigated the GC regulation of the ECM protease ADAMTS 12 and showed that Adamts 12 mRNA levels were markedly reduced at E18.5 in GRmesKO fetal mouse lung and were strongly induced by both cortisol and betamethasone in cultures of primary rat fetal lung fibroblasts. ADAMTS12 protein immunoreactivity was also strongly increased in the distal lung at E18.5, after dexamethasone treatment in utero. In summary, glucocorticoid signaling via GR represses GAGbeta domain-containing VCAN isoforms in distal lung mesenchyme in vivo by repressing Vcan gene expression and, in part, by inducing the ECM protease ADAMTS12, thereby contributing to the control of ECM remodelling and lung cell proliferation prior to birth.Copyright © 2020 Society for Endocrinology Published by Bioscientifica Ltd.

Glucocorticoid (GC) signaling via the glucocorticoid receptor (GR) is essential for lung maturation in mammals. Previous studies using global or conditional mouse model knockouts of the GR gene have established that GR-mediated signaling in the interstitial mesenchyme of the fetal lung is critical for normal lung development. Screens for downstream GC-targets in conditional mesenchymal GR deficient mouse lung (GRmesKO) identified Versican (Vcan), an important extracellular matrix component and cell proliferation regulator, as a potential GR-regulated target. We show that, of the five major VCAN isoforms, the VCAN-V1 isoform containing the GAGbeta domain is the predominant VCAN isoform in the fetal mouse lung distal mesenchyme at both E16.5 and E18.5, whereas the GAGalpha-specific VCAN-V2 isoform was only localized to the smooth muscle surrounding proximal airways. Both Vcan-V1 mRNA and protein levels were strongly overexpressed in the GRmesKO lung at E18.5. Finally, we investigated the GC regulation of the ECM protease ADAMTS 12 and showed that Adamts 12 mRNA levels were markedly reduced at E18.5 in GRmesKO fetal mouse lung and were strongly induced by both cortisol and betamethasone in cultures of primary rat fetal lung fibroblasts. ADAMTS12 protein immunoreactivity was also strongly increased in the distal lung at E18.5, after dexamethasone treatment in utero. In summary, glucocorticoid signaling via GR represses GAGbeta domain-containing VCAN isoforms in distal lung mesenchyme in vivo by repressing Vcan gene expression and, in part, by inducing the ECM protease ADAMTS12, thereby contributing to the control of ECM remodelling and lung cell proliferation prior to birth.Copyright © 2020 Society for Endocrinology Published by Bioscientifica Ltd.

BackgroundPsoriasis is a disease that commonly manifests in adolescence. Up to half of adults with psoriasis develop it before the age of 20. Topical formulations containing corticosteroids and/or vitamin D3 analogs are recommended for treatment.ObjectiveThis phase II study aimed to evaluate the safety, including any potential effect on the hypothalamic-pituitary-adrenal axis and calcium metabolism, and efficacy of fixed-dose combination calcipotriene (0.005%) and betamethasone (0.064% as dipropionate) (Cal/BD) gel in adolescents with psoriasis.MethodsPatients aged 12 to <17 years, with at least mild psoriasis on the body and scalp, received topical Cal/BD gel once daily for ≤8 weeks. Safety response criteria included adverse drug reactions [ADRs; any adverse event (AE) possibly or probably related to treatment as determined by the investigator; a primary response criterion] and AEs (a secondary response criterion). Only treatment-emergent AEs (events that occurred after the first application of Cal/BD gel or events which started before this and increased in intensity after the first application of Cal/BD gel) are presented here. Efficacy response criteria included controlled disease, by physician's global assessment of disease severity (PGA), following Cal/BD gel treatment.ResultsA total of 107 patients (median age 14 years; range 12-16) were enrolled and treated. Eight ADRs were observed in 7 (7%) patients and 38 (36%) patients experienced ≥1 AE. The most common AEs were headache [6 (6%) patients], nasopharyngitis [6 (6%) patients] and blood parathyroid hormone increased [4 (4%) patients]. One severe AE was reported (attempted suicide) but was considered unrelated to treatment. At the end of treatment, 58% of patients had controlled disease on the body and 69% on the scalp according to PGA.ConclusionIn this uncontrolled phase II study, Cal/BD gel was well tolerated and effective for treating scalp and body psoriasis in adolescents.

Background: Topical corticosteroids are available in many vehicles. However, patients' preference for vehicles are variable and could be tailored to maximize patient adherence. Spray vehicles may offer, convenience, and strong efficacy. Methods: A literature review was conducted using keywords: clobetasol, desoximetasone, betamethasone, triamcinolone, corticosteroid, topical, spray, vehicles, treatment, and clinical trial. Results: For moderate-to-severe plaque psoriasis, 87% of subjects achieved an Overall Disease Severity (ODS) Score ≤2 at week two and 78% achieved an ODS ≤1 after four weeks with clobetasol propionate (CP) 0.05% spray compared to 17% and 3% in the control group, respectively (P<0.001). For desoximetasone 0.25% spray, 31%-53% with moderate-to-severe psoriasis achieve Physician's Global Assessment (PGA) score ≤1 at day 28 versus 5%-18% in the vehicle spray group (P<0.01). For betamethasone dipropionate 0.05% spray, 19% with mild-to-moderate plaque psoriasis achieved an Investigator's Global Assessment (IGA) score ≤1 or a 2-grade reduction in IGA versus 2.3% in vehicle group (P≤0.001). For mild-to-severe steroid responsive inflammatory dermatoses, 64% using triamcinolone acetonide 0.2% spray achieved clear or almost clear skin at day 14 (no P value reported). Adverse events including burning, irritation, and dryness were similar across all corticosteroids.

Antenatal corticosteroids (ACS) are standard of care for women at risk of preterm delivery, although choice of drug, dose or route have not been systematically evaluated. Further, ACS are infrequently used in low resource environments where most of the mortality from prematurity occurs. We report proof of principle experiments to test betamethasone-phosphate (Beta-P) or dexamethasone-phosphate (Dex-P) given orally in comparison to the clinical treatment with the intramuscular combination drug beta-phosphate plus beta-acetate in a Rhesus Macaque model. First, we performed pharmacokinetic studies in non-pregnant monkeys to compare blood levels of the steroids using oral dosing with Beta-P, Dex-P and an effective maternal intramuscular dose of the beta-acetate component of the clinical treatment. We then evaluated maternal and fetal blood steroid levels with limited fetal sampling under ultrasound guidance in pregnant macaques. We found that oral Beta is more slowly cleared from plasma than oral Dex. The blood levels of both drugs were lower in maternal plasma of pregnant than in non-pregnant macaques. Using the pharmacokinetic data, we treated groups of 6-8 pregnant monkeys with oral Beta-P, oral Dex-P, or the maternal intramuscular clinical treatment and saline controls and measured pressure-volume curves to assess corticosteroid effects on lung maturation at 5d. Oral Beta-P improved the pressure-volume curves similarly to the clinical treatment. Oral Dex-P gave more variable and nonsignificant responses. We then compared gene expression in the fetal lung, liver and hippocampus between oral Beta-P and the clinical treatment by RNA-sequencing. The transcriptomes were largely similar with small gene expression differences in the lung and liver, and no differences in the hippocampus between the groups. As proof of principle, ACS therapy can be effective using inexpensive and widely available oral drugs. Clinical dosing strategies must carefully consider the pharmacokine

Background: Topical corticosteroids are available in many vehicles. However, patients' preference for vehicles are variable and could be tailored to maximize patient adherence. Spray vehicles may offer, convenience, and strong efficacy. Methods: A literature review was conducted using keywords: clobetasol, desoximetasone, betamethasone, triamcinolone, corticosteroid, topical, spray, vehicles, treatment, and clinical trial. Results: For moderate-to-severe plaque psoriasis, 87% of subjects achieved an Overall Disease Severity (ODS) Score ≤2 at week two and 78% achieved an ODS ≤1 after four weeks with clobetasol propionate (CP) 0.05% spray compared to 17% and 3% in the control group, respectively (P<0.001). For desoximetasone 0.25% spray, 31%-53% with moderate-to-severe psoriasis achieve Physician's Global Assessment (PGA) score ≤1 at day 28 versus 5%-18% in the vehicle spray group (P<0.01). For betamethasone dipropionate 0.05% spray, 19% with mild-to-moderate plaque psoriasis achieved an Investigator's Global Assessment (IGA) score ≤1 or a 2-grade reduction in IGA versus 2.3% in vehicle group (P≤0.001). For mild-to-severe steroid responsive inflammatory dermatoses, 64% using triamcinolone acetonide 0.2% spray achieved clear or almost clear skin at day 14 (no P value reported). Adverse events including burning, irritation, and dryness were similar across all corticosteroids.

Antenatal corticosteroids (ACS) are standard of care for women at risk of preterm delivery, although choice of drug, dose or route have not been systematically evaluated. Further, ACS are infrequently used in low resource environments where most of the mortality from prematurity occurs. We report proof of principle experiments to test betamethasone-phosphate (Beta-P) or dexamethasone-phosphate (Dex-P) given orally in comparison to the clinical treatment with the intramuscular combination drug beta-phosphate plus beta-acetate in a Rhesus Macaque model. First, we performed pharmacokinetic studies in non-pregnant monkeys to compare blood levels of the steroids using oral dosing with Beta-P, Dex-P and an effective maternal intramuscular dose of the beta-acetate component of the clinical treatment. We then evaluated maternal and fetal blood steroid levels with limited fetal sampling under ultrasound guidance in pregnant macaques. We found that oral Beta is more slowly cleared from plasma than oral Dex. The blood levels of both drugs were lower in maternal plasma of pregnant than in non-pregnant macaques. Using the pharmacokinetic data, we treated groups of 6-8 pregnant monkeys with oral Beta-P, oral Dex-P, or the maternal intramuscular clinical treatment and saline controls and measured pressure-volume curves to assess corticosteroid effects on lung maturation at 5d. Oral Beta-P improved the pressure-volume curves similarly to the clinical treatment. Oral Dex-P gave more variable and nonsignificant responses. We then compared gene expression in the fetal lung, liver and hippocampus between oral Beta-P and the clinical treatment by RNA-sequencing. The transcriptomes were largely similar with small gene expression differences in the lung and liver, and no differences in the hippocampus between the groups. As proof of principle, ACS therapy can be effective using inexpensive and widely available oral drugs. Clinical dosing strategies must carefully consider the pharmacokine

Preterm infants are often exposed to both antenatal and postnatal glucocorticoids (GCs). We tested the hypothesis that combined antenatal and postnatal GCs have long-lasting adverse effects on fetal and neonatal growth, growth factors, and neurological outcomes. Pregnant rats were administered a single IM dose of betamethasone (0.2 mg/Kg, AB), dexamethasone (0.2 mg/Kg, AD), or equivalent volumes of saline (AS) at 17 & 18 days gestation. Following delivery, pups from each treatment group were sacrificed at P0, and the remainder was treated with a single IM dose of either betamethasone (0.25 mg/Kg, PB), dexamethasone (0.25 mg/Kg, PD), or equivalent volumes of saline (PS) on P5, P6, and P7. Somatic growth, neurological status, and growth factors were determined at P14, P21, and P45. At birth, AD resulted in decreased somatic growth. AB advanced the hopping reflex associated with spinal rhythmic mechanisms. At P21, all GC groups were growth suppressed, but only the AS/PD group had deficits in brain weight and delayed plantar reflex associated with brainstem function. By P45, sustained reductions in body and brain weight occurred all combined antenatal and postnatal GC groups, as well as elevated ACTH and corticosterone. Retardation in plantar reflex occurred in all AD groups. IGF-I, GH and insulin levels were elevated at all ages with dexamethasone. Combined antenatal and postnatal GCs has persistent detrimental lasting effects on growth, growth factors, neurological outcomes, and HPA axis activity. Whether these effects persist in adult life and are risk factors for insulin resistance, remains to be elucidated.

Background: Betamethasone is widely used to enhance fetal lung maturation in case of threatened preterm birth. Antenatal corticosteroids are known to reduce fetal heart rate variability (fHRV) in the days following administration. Since decreased fHRV is a marker for fetal distress, this transient decrease of fHRV can cause unnecessary medical intervention. Aim: To describe the effect of betamethasone on fHRV, by applying spectral analysis on non-invasive fetal electrocardiogram (fECG) recordings. Study design: Secondary analysis of a prospective cohort study. Subjects: Women with a singleton pregnancy, at risk for preterm delivery and receiving betamethasone, admitted to the obstetric high care unit in the period from March 2013 until July 2016. Outcome measures: The primary outcome measure was fHRV in both time- and frequency-domain. Secondary outcome measures included basal fetal heart rate (fHR) and fHR variance. FHRV parameters were then calculated separately for the quiet and active state. Results: Following 68 inclusions, 22 patients remained with complete series of measurements and sufficient data quality. FHRV parameters and fHR showed a decrease on day 2 compared to day 1, significant for short-term variability and high-frequency power. Similar results were found when analyzing for separate behavioral states. The number of segments in quiet state increased during days 1 and 2. Normalized values showed no difference for all behavioral states. Conclusion: FHRV decreases on day 2 after betamethasone administration, while periods of fetal quiescence increase. No changes were found in the normalized values, indicating that the influence of autonomic modulation is minor. Clinical trial registration number NL43294.015.13

Background: Corticosteroids are widely prescribed drugs in dermatology. Rational prescribing of steroids is important for best therapeutic outcome at lowest possible dose. A study was carried out at a tertiary care teaching hospital in order to evaluate the use of corticosteroids which provided a picture of trends in the usage of corticosteroids in dermatology at that set-up. Materials and Methods: This prospective, observational study was carried out in department of dermatology for 1 year after ethical approval. Data was analysed for parameters related to corticosteroids, their potency, WHO drug prescribing indicators, effectiveness as well as effects of corticosteroids on quality of life of patients. Statistical analysis was done using Microsoft Excel Office 365. Results: In the 223 patients, 44.84% patients belonged to 21-40 years age group. Mostcommon indication was eczema in 29.15% cases. Topical betamethasone (25.11%) and oral prednisolone (20.17%) were most frequently prescribed. 95/140 topical steroids prescribed were super highly potent. Among concomitant drugs, a majority of 38% were antihistaminics. Degree of polypharmacy showed 04 drugs in a majority (43.15%) of prescriptions. Only 6.27% drugs were prescribed by generic name. Conclusion: Corticosteroids were beneficial to a large no. of patients. Initial usage of low potency steroids topically wherever possible can be emphasized. WHO drug prescribing indicators analysis indicated the need to adhere to WHO guidelines as well as prescribing drugs by generic name. To maintain a balance between judicious use and frequent abuse with corticosteroid is important along with physician’s vigilance and patient education.

Background: Corticosteroids are widely prescribed drugs in dermatology. Rational prescribing of steroids is important for best therapeutic outcome at lowest possible dose. A study was carried out at a tertiary care teaching hospital in order to evaluate the use of corticosteroids which provided a picture of trends in the usage of corticosteroids in dermatology at that set-up. Materials and Methods: This prospective, observational study was carried out in department of dermatology for 1 year after ethical approval. Data was analysed for parameters related to corticosteroids, their potency, WHO drug prescribing indicators, effectiveness as well as effects of corticosteroids on quality of life of patients. Statistical analysis was done using Microsoft Excel Office 365. Results: In the 223 patients, 44.84% patients belonged to 21-40 years age group. Mostcommon indication was eczema in 29.15% cases. Topical betamethasone (25.11%) and oral prednisolone (20.17%) were most frequently prescribed. 95/140 topical steroids prescribed were super highly potent. Among concomitant drugs, a majority of 38% were antihistaminics. Degree of polypharmacy showed 04 drugs in a majority (43.15%) of prescriptions. Only 6.27% drugs were prescribed by generic name. Conclusion: Corticosteroids were beneficial to a large no. of patients. Initial usage of low potency steroids topically wherever possible can be emphasized. WHO drug prescribing indicators analysis indicated the need to adhere to WHO guidelines as well as prescribing drugs by generic name. To maintain a balance between judicious use and frequent abuse with corticosteroid is important along with physician’s vigilance and patient education.

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth.

BackgroundAntenatal steroids are standard of care for women who are at risk of preterm delivery; however, antenatal steroid dosing and formulation have not been evaluated adequately. The standard clinical 2-dose treatment with betamethasone-acetate+betamethasone-phosphate is more effective than 2 doses of betamethasone-phosphate for the induction of lung maturation in preterm fetal sheep. We hypothesized that the slowly released betamethasone-acetate component induces similar lung maturation to betamethasone-phosphate+betamethasone-acetate with decreased dose and fetal exposure.ObjectiveThe purpose of this study was to investigate pharmacokinetics and fetal lung maturation of antenatal betamethasone-acetate in preterm fetal sheep.Study designGroups of 10 singleton-pregnant ewes received 1 or 2 intramuscular doses 24 hours apart of 0.25 mg/kg/dose of betamethasone-phosphate+betamethasone-acetate (the standard of care dose) or 1 intramuscular dose of 0.5 mg/kg, 0.25 mg/kg, or 0.125 mg/kg of betamethasone-acetate. Fetuses were delivered 48 hours after the first injection at 122 days of gestation (80% of term) and ventilated for 30 minutes, with ventilator settings, compliance, vital signs, and blood gas measurements recorded every 10 minutes. After ventilation, we measured static lung pressure-volume curves and sampled the lungs for messenger RNA measurements. Other groups of pregnant ewes and fetuses were catheterized and treated with intramuscular injections of betamethasone-phosphate 0.125 mg/kg, betamethasone-acetate 0.125 mg/kg, or betamethasone-acetate 0.5 mg/kg. Maternal and fetal betamethasone concentrations in plasma were measured for 24 hours.ResultsAll betamethasone-treated groups had increased messenger RNA expression of surfactant proteins A, B, and C, ATP-binding cassette subfamily A member 3, and aquaporin-5 compared with control animals. Treatment with 1 dose of intramuscular betamethasone-acetate 0.125mg/kg improved dynamic and static lung compliance

BackgroundAntenatal steroids are standard of care for women who are at risk of preterm delivery; however, antenatal steroid dosing and formulation have not been evaluated adequately. The standard clinical 2-dose treatment with betamethasone-acetate+betamethasone-phosphate is more effective than 2 doses of betamethasone-phosphate for the induction of lung maturation in preterm fetal sheep. We hypothesized that the slowly released betamethasone-acetate component induces similar lung maturation to betamethasone-phosphate+betamethasone-acetate with decreased dose and fetal exposure.ObjectiveThe purpose of this study was to investigate pharmacokinetics and fetal lung maturation of antenatal betamethasone-acetate in preterm fetal sheep.Study designGroups of 10 singleton-pregnant ewes received 1 or 2 intramuscular doses 24 hours apart of 0.25 mg/kg/dose of betamethasone-phosphate+betamethasone-acetate (the standard of care dose) or 1 intramuscular dose of 0.5 mg/kg, 0.25 mg/kg, or 0.125 mg/kg of betamethasone-acetate. Fetuses were delivered 48 hours after the first injection at 122 days of gestation (80% of term) and ventilated for 30 minutes, with ventilator settings, compliance, vital signs, and blood gas measurements recorded every 10 minutes. After ventilation, we measured static lung pressure-volume curves and sampled the lungs for messenger RNA measurements. Other groups of pregnant ewes and fetuses were catheterized and treated with intramuscular injections of betamethasone-phosphate 0.125 mg/kg, betamethasone-acetate 0.125 mg/kg, or betamethasone-acetate 0.5 mg/kg. Maternal and fetal betamethasone concentrations in plasma were measured for 24 hours.ResultsAll betamethasone-treated groups had increased messenger RNA expression of surfactant proteins A, B, and C, ATP-binding cassette subfamily A member 3, and aquaporin-5 compared with control animals. Treatment with 1 dose of intramuscular betamethasone-acetate 0.125mg/kg improved dynamic and static lung compliance

BackgroundAlthough studies involving preterm infants ≤34 weeks gestation report a decreased incidence of patent ductus arteriosus after antenatal betamethasone, studies involving younger gestation infants report conflicting results.MethodsWe used preterm baboons, mice, and humans (≤276/7 weeks gestation) to examine betamethasone's effects on ductus gene expression and constriction both in vitro and in vivo.ResultsIn mice, betamethasone increased the sensitivity of the premature ductus to the contractile effects of oxygen without altering the effects of other contractile or vasodilatory stimuli. Betamethasone's effects on oxygen sensitivity could be eliminated by inhibiting endogenous prostaglandin/nitric oxide signaling. In mice and baboons, betamethasone increased the expression of several developmentally regulated genes that mediate oxygen-induced constriction (K+ channels) and inhibit vasodilator signaling (phosphodiesterases). In human infants, betamethasone increased the rate of ductus constriction at all gestational ages. However, in infants born ≤256/7 weeks gestation, betamethasone's contractile effects were only apparent when prostaglandin signaling was inhibited, whereas at 26-27 weeks gestation, betamethasone's contractile effects were apparent even in the absence of prostaglandin inhibitors.ConclusionsWe speculate that betamethasone's contractile effects may be mediated through genes that are developmentally regulated. This could explain why betamethasone's effects vary according to the infant's developmental age at birth.

Objectives and methods: Topical therapy is the first-line treatment in mild and moderate psoriasis. We performed a real-life study on topical therapies in psoriasis and observed a variation in the amounts of ointment patients applied during the study. Results: A statistically significant correlation was found between gender and the total amount of ointment used: women used more than men (p = .020). Also, heavier patients tended to use less ointment (p = .038). Conclusions: We look forward to seeing whether the current pressure to improve psoriasis treatment leads to more patients receiving systemic therapies or to better adherence to, and persistence with, topical therapies.

Background: Betamethasone is widely used to enhance fetal lung maturation in case of threatened preterm labour. Fetal heart rate variability is one of the most important parameters to assess in fetal monitoring, since it is a reliable indicator for fetal distress. Aim: To describe the effect of betamethasone on fetal heart rate variability, by applying spectral analysis on non-invasive fetal electrocardiogram recordings. Study design: Prospective cohort study. Subjects: Patients that require betamethasone, with a gestational age from 24 weeks onwards. Outcome measures: Fetal heart rate variability parameters on day 1, 2, and 3 after betamethasone administration are compared to a reference measurement. Results: Following 68 inclusions, 12 patients remained with complete series of measurements and sufficient data quality. During day 1, an increase in absolute fetal heart rate variability values was seen. During day 2, a decrease in these values was seen. All trends indicate to return to pre-medication values on day 3. Normalised high- and low-frequency power show little changes during the study period. Conclusions: The changes in fetal heart rate variability following betamethasone administration show the same pattern when calculated by spectral analysis of the fetal electrocardiogram, as when calculated by cardiotocography. Since normalised spectral values show little changes, the influence of autonomic modulation seems minor.

OBJECTIVES: To investigate whether a treat-to-target strategy based on methotrexate (MTX) and intra-articular (IA) betamethasone suppresses magnetic resonance imaging (MRI)-determined measures of disease activity and reduces joint destruction in early rheumatoid arthritis (eRA) patients, and to investigate whether concomitant cyclosporin A (CyA) provides an additional effect.METHOD: In the 2-year randomized, double-blind, treat-to-target trial CIMESTRA, 160 patients with eRA (< 6 months) were randomized to MTX, intra-articular betamethasone and CyA, or placebo CyA. A total of 129 patients participated in the MRI substudy, and had contrast-enhanced MR images of the non-dominant hand at months 0, 6, 12, and 24. MR images were evaluated for osteitis, synovitis, tenosynovitis, bone erosion, and joint space narrowing (JSN), using validated scoring methods.RESULTS: Significant reductions were seen at 6 months in all inflammatory parameters [synovitis, mean change -1.6 (p < 0.001, Wilcoxon), tenosynovitis, -3.5 (p < 0.001), and osteitis, -1.3 (p < 0.05)] and at 12/24 months in synovitis and tenosynovitis [-1.6/-2.2 and -3.6/-3.8, respectively; all p < 0.001]. MRI signs of inflammation were not fully eliminated, and increases in erosion and JSN scores were observed at 6 months [0.4 (p < 0.01)/0.1 (p < 0.05)], 12 months [0.8 (p < 0.001)/0.3 (p < 0.01)], and 24 months [1.0 (p < 0.001)/0.4 (p < 0.001)]. Clinical measures decreased significantly (p < 0.001) at all time points. There were no consistent statistically significant differences between treatment groups.CONCLUSIONS: In this eRA treat-to-target trial, MTX and intra-articular glucocorticoids markedly reduced, but did not eliminate, MRI osteitis, synovitis, and tenosynovitis. Accordingly, minimal but statistically significant increases in bone erosion and JSN were observed. No additional effect of CyA was demonstrated.

Introduction: Glucocorticoids, widely used in the perinatal period, may be associated with adverse neurodevelopmental effects.Objectives: To analyze neurodevelopmental outcomes in a cohort of very low birth weight newborns treated with antenatal and/or postnatal corticosteroids.Materials and methods: This was a prospective cohort study in which we included all very low birth weight babies admitted to the neonatal intensive care unit of a tertiary hospital between 2008 and 2013. We compared the neurodevelopment among very low birth-weight newborns who did not receive prenatal corticosteroid therapy and those who received a complete course (two doses of 12 mg betamethasone) and an incomplete course (one dose), and between those who did not receive postnatal corticosteroid therapy and those who received it (systemic dexamethasone after the first week of life). Motor, neurosensory and cognitive functions, as well as behavior disorders during the first two years of age were evaluated.Results: A total of 225 very low birth weight newborns were analyzed; 83.6% received prenatal corticosteroid therapy (24% incomplete treatment schedule and 59.6% complete schedule). Only 13.3% received systemic dexamethasone during the postnatal period. Neurological monitoring was performed corticosteroid therapy and more neurological disorders, and no significant differences were found among those who received complete and incomplete courses of prenatal corticosteroid therapy.Conclusion: These results did not demonstrate an association between perinatal corticosteroid therapy and worse neurodevelopmental outcomes in very low birth weight newborns., Introducción. Los glucocorticoides, ampliamente utilizados en el periodo perinatal, pueden asociarse con efectos adversos en el neurodesarrollo.Objetivo. Analizar los resultados del tratamiento con corticoides en el periodo prenatal y en el posnatal en el neurodesarrollo de una cohorte de recién nacidos de muy bajo peso.Materiales y métodos. Se hizo un estudio prospectivo de cohortes en los recién nacidos de muy bajo peso hospitalizados en la unidad de cuidados intensivos neonatales de un hospital de tercer nivel entre el 2008 y el 2013. Se comparó el neurodesarrollo entre aquellos que no recibieron tratamiento prenatal con corticoides y quienes recibieron el esquema completo (dos dosis de 12 mg de betametasona) o el incompleto (una dosis). También, se compararon los resultados en el neurodesarrollo de los recién nacidos que no recibieron tratamiento posnatal y aquellos que sí (dexametasona sistémica a partir de la primera semana de vida). Se evaluó la función motora, la neurosensorial y la cognitiva, así como los trastornos de conducta durante los dos primeros años de vida.Resultados. Se analizaron 225 recién nacidos de muy bajo peso; 83,6 % de las madres había recibido tratamiento prenatal con corticoides (esquema incompleto: 24 %; esquema completo: 59,6 %). Durante el periodo posnatal solamente el 13,3 % había recibido dexametasona sistémica. El seguimiento neurológico se llevó a cabo en 194 neonatos. En el análisis de regresión logística no se detectó que el tratamiento prenatal no el posnatal se asociara con más trastornos neurológicos, ni hubo diferencias significativas entre quienes recibieron el esquema completo y los que recibieron el incompleto durante el periodo prenatal.Conclusión. Los resultados de este estudio no pudieron demostrar que el tratamiento perinatal con corticoides se asociara con peores resultados en el neurodesarrollo en recién nacidos de muy bajo peso.

Glucocorticoids are the most important and widely used treatment modality in dermatology. A large variety of topical as well as systemic preparations is available. Most patients treated with glucocorticoids respond quickly to the treatment, but some are considered insensitive or even resistant to glucocorticoid therapy. Currently, there is no known measurable variable, through which the response can be predicted. Glucocorticoids mediate their actions through glucocorticoid receptors (GR). Several isoforms of GR exist, but the α (GRα) and β (GRβ) isoforms are clinically the most important. Based on previous studies, it has been proposed that the abundance of GR isoforms or the GRβ: GRα –ratio could affect individual responsiveness to corticosteroid treatment. In particular, up-regulation of GRβ expression has been shown to be linked to resistance to corticosteroid treatment. This thesis comprises three sub-studies. Firstly, we wanted to determine whether GRα and GRβ are expressed in inflammatory skin diseases. Secondly, we examined if the expression is altered by corticosteroid treatment in eczema atopicum, bullous pemphigoid and psoriasis. Finally, we measured the effects of a topical vitamin D3 analogue (calcipotriol) combined with betamethasone compared with betamethasone monotherapy on inflammatory biomarkers of psoriasis. Our studies provide detailed novel data about the expression of GRα and GRβ. GRα and GRβ were shown to be expressed in the blood lymphocytes and lesional skin of patients with eczema atopicum, bullous pemphigoid and psoriasis, as well as in the skin of patients with eczema nummulare, lichen simplex chronicus and lichen ruber planus. Systemic corticosteroid treatment was shown to affect the expression of GRα and GRβ in eczema atopicum and bullous pemphigoid, but the inconsistent variation in their expression between patients prevented us from drawing firm conclusions. Neither GRα nor GRβ as a single marker were found to be a suitable pr, Tiivistelmä Glukokortikoideja (”kortisoni”) käytetään tulehduksellisten ihotautien hoidossa paikallisesti tai systeemisenä lääkkeenä. Suurin osa potilaista reagoi hoitoon nopeasti, mutta osalla hoitovaste on heikompi tai ilmenee hitaasti. Tällä hetkellä ei tunneta keinoja ennustaa luotettavasti kortisonihoidon vastetta. Glukokortikoidit vaikuttavat elimistössä glukokortikoidireseptorien (GR) kautta. Glukokortikoidireseptorista tunnetaan useita alatyyppejä, joista tärkeimmät ovat α (GRα) ja β (GRβ). Aiemman tiedon pohjalta on pidetty mahdollisena, että GR-alatyyppien suhteella tai määrällä on merkitystä kortisonivasteen syntymisessä. Erityisesti on arveltu, että ylimäärä GRβ:aa voisi estää kortisonihoidon vaikutusta. Tässä väitöskirjassa tavoitteena on ollut selvittää, tapahtuuko GR-alatyyppien ilmenemisessä muutoksia tulehduksellisia ihosairauksia sairastavilla potilailla sekä tutkia, miten kortisonihoito vaikuttaa GR-tasoihin atooppista ihottumaa, pemfigoidia ja psoriaasia sairastavilla potilailla. Lisäksi olemme verranneet paikallishoitoa pelkällä kortisonivoiteella D-vitamiinijohdos kalsipotriolin ja kortisonin yhdistelmähoitoon psoriaatikoilla. Tutkimus on antanut uutta yksityiskohtaista tietoa GRα:n ja GRβ:n esiintymisestä ihossa ja tulehdussoluissa ihosairauksia sairastavilla potilailla. Tutkimustulosten perusteella voidaan todeta, että GRα ja GRβ esiintyvät atooppista ihottumaa, pemfigoidia ja psoriaasia sairastavien potilaiden ihossa ja veren tulehdussoluissa sekä nummulaari-ihottumaa, neurodermatiittia ja punajäkälää sairastavien potilaiden ihossa. Suun kautta annettu kortisonihoito vaikuttaa GRα- ja GRβ–lähetti-RNA:n ilmenemiseen, mutta potilaskohtaiset erot ovat suuret, eikä kumpikaan, GRα tai GRβ, sovellu yksinään ennustamaan kortisonihoidon vastetta. Paikallisella kortisonihoidolla D-vitamiinijohdos kalsipotrioliin yhdistettynä on suotuisampi vaikutus psoriaasin tulehduksellisiin välittäjäaineisiin ja tulehdussoluihin kuin pelkällä paikallisella kortiso

Acute bacterial meningitis (ABM) is a highly lethal disease. Available data support the use of corticosteroids in high-income countries, but the effect on mortality is still controversial. The effects of corticosteroids on mortality and sequelae were evaluated in the national Swedish quality registry. In total, during 1995-2014 1746 adults with ABM were included, of whom 989 were treated with corticosteroids (betamethasone, n = 766; dexamethasone, n = 248; methylprednisolone, n = 2), 498 were not given corticosteroids and in 259 patients data for corticosteroids were missing. Fatal outcome was observed in 8.9% of the patients in the corticosteroid-treated group vs. 17.9% in the non-corticosteroid-treated group (p < 0.001), resulting in an odds ratio (OR) of 0.57 with a 95% confidence interval (CI) of 0.40-0.81 adjusted for age, sex, mental status, and door-to-antibiotic time. In patients with meningitis caused by S. pneumoniae, mortality was 10.2% in the corticosteroid-treated group and 21.3% in the noncorticosteroid-treated group (p < 0.001) with an adjusted OR of 0.50 (95% CI 0.31-0.80). In ABM patients with non-pneumococcal aetiology the adjusted OR was 0.71 (95% CI 0.40-1.26). Lower mortality was observed in the corticosteroid-treated group with impaired mental status, whereas no significant difference was found in patients with unaffected mental status. The adjusted ORs for betamethasone and dexamethasone were 0.49 (95% CI 0.28-0.84) and 0.61 (95% CI 0.37-1.01), respectively. Corticosteroid treatment decreases mortality in ABM and should be administered initially with antibiotics in adult ABM patients with impaired mental status regardless of presumed aetiology. Betamethasone seems to be at least as effective as dexamethasone.

BackgroundAn aerosol foam formulation of fixed combination calcipotriene 0.005% (as hydrate; Cal) plus betamethasone dipropionate 0.064% (BD) was developed to improve psoriasis treatment.ObjectivesTo compare the efficacy and safety of Cal/BD aerosol foam with Cal/BD ointment after 4 weeks.MethodsIn this Phase II, multicenter, investigator-blind, 4-week trial, adult patients with psoriasis vulgaris were randomized to Cal/BD aerosol foam, Cal/BD ointment, aerosol foam vehicle or ointment vehicle (3:3:1:1). The primary efficacy endpoint was the proportion of patients at week 4 who achieved treatment success (clear or almost clear with at least a two-step improvement) according to the physician's global assessment of disease severity.ResultsIn total, 376 patients were randomized. At week 4, significantly more patients using Cal/BD aerosol foam achieved treatment success (54.6% versus 43.0% [ointment]; p = 0.025); mean modified (excluding the head, which was not treated) psoriasis area and severity index score was significantly different between Cal/BD aerosol foam and Cal/BD ointment (mean difference -0.6; p = 0.005). Rapid, continuous itch relief occurred with both active treatments. One adverse drug reaction was reported with Cal/BD aerosol foam (application site itch).ConclusionsCal/BD aerosol foam demonstrates significantly greater efficacy and similar tolerability compared with Cal/BD ointment for psoriasis treatment.

Due to the rapid developmental changes that occur during the fetal period, prenatal influences can affect the developing central nervous system with lifelong consequences for physical and mental health. Glucocorticoids are one of the proposed mechanisms by which fetal programing occurs. Glucocorticoids pass through the blood-brain barrier and target receptors throughout the central nervous system. Unlike endogenous glucocorticoids, synthetic glucocorticoids readily pass through the placental barrier to reach the developing fetus. The synthetic glucocorticoid, betamethasone, is routinely given prenatally to mothers at risk for preterm delivery. Over 25% of the fetuses exposed to betamethasone will be born at term. Few studies have examined the lasting consequences of antenatal treatment of betamethasone on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study is to examine whether antenatal exposure to betamethasone alters circadian cortisol regulation in children who were born full term. School-aged children prenatally treated with betamethasone and born at term (n=19, mean (SD)=8.1 (1.2) years old) were compared to children not treated with antenatal glucocorticoids (n=61, mean (SD)=8.2 (1.4) years old). To measure the circadian release of cortisol, saliva samples were collected at awakening; 30, 45, and 60min after awakening; and in the evening. Comparison children showed a typical diurnal cortisol pattern that peaked in the morning (the cortisol awakening response) and gradually decreased throughout the day. In contrast, children exposed to antenatal betamethasone lacked a cortisol awakening response and had a flatter diurnal slope (p's<0.01). These data suggest that antenatal glucocorticoid treatment may disrupt the circadian regulation of the HPA axis among children born at term. Because disrupted circadian regulation of cortisol has been linked to mental and somatic health problems, future research is needed to determine

BackgroundAn aerosol foam formulation of fixed combination calcipotriene 0.005% (as hydrate; Cal) plus betamethasone dipropionate 0.064% (BD) was developed to improve psoriasis treatment.ObjectivesTo compare the efficacy and safety of Cal/BD aerosol foam with Cal/BD ointment after 4 weeks.MethodsIn this Phase II, multicenter, investigator-blind, 4-week trial, adult patients with psoriasis vulgaris were randomized to Cal/BD aerosol foam, Cal/BD ointment, aerosol foam vehicle or ointment vehicle (3:3:1:1). The primary efficacy endpoint was the proportion of patients at week 4 who achieved treatment success (clear or almost clear with at least a two-step improvement) according to the physician's global assessment of disease severity.ResultsIn total, 376 patients were randomized. At week 4, significantly more patients using Cal/BD aerosol foam achieved treatment success (54.6% versus 43.0% [ointment]; p = 0.025); mean modified (excluding the head, which was not treated) psoriasis area and severity index score was significantly different between Cal/BD aerosol foam and Cal/BD ointment (mean difference -0.6; p = 0.005). Rapid, continuous itch relief occurred with both active treatments. One adverse drug reaction was reported with Cal/BD aerosol foam (application site itch).ConclusionsCal/BD aerosol foam demonstrates significantly greater efficacy and similar tolerability compared with Cal/BD ointment for psoriasis treatment.

Due to the rapid developmental changes that occur during the fetal period, prenatal influences can affect the developing central nervous system with lifelong consequences for physical and mental health. Glucocorticoids are one of the proposed mechanisms by which fetal programing occurs. Glucocorticoids pass through the blood-brain barrier and target receptors throughout the central nervous system. Unlike endogenous glucocorticoids, synthetic glucocorticoids readily pass through the placental barrier to reach the developing fetus. The synthetic glucocorticoid, betamethasone, is routinely given prenatally to mothers at risk for preterm delivery. Over 25% of the fetuses exposed to betamethasone will be born at term. Few studies have examined the lasting consequences of antenatal treatment of betamethasone on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study is to examine whether antenatal exposure to betamethasone alters circadian cortisol regulation in children who were born full term. School-aged children prenatally treated with betamethasone and born at term (n=19, mean (SD)=8.1 (1.2) years old) were compared to children not treated with antenatal glucocorticoids (n=61, mean (SD)=8.2 (1.4) years old). To measure the circadian release of cortisol, saliva samples were collected at awakening; 30, 45, and 60min after awakening; and in the evening. Comparison children showed a typical diurnal cortisol pattern that peaked in the morning (the cortisol awakening response) and gradually decreased throughout the day. In contrast, children exposed to antenatal betamethasone lacked a cortisol awakening response and had a flatter diurnal slope (p's<0.01). These data suggest that antenatal glucocorticoid treatment may disrupt the circadian regulation of the HPA axis among children born at term. Because disrupted circadian regulation of cortisol has been linked to mental and somatic health problems, future research is needed to determine

ObjectiveTo examine the effects of antenatal steroids on severe intraventricular hemorrhage (IVH) in infants born during the IVH vulnerable period (<28 weeks gestational age) and to evaluate rates of IVH correlated with the time interval between treatment or retreatment and birth.Study designA total of 429 infants (<28 weeks gestation), who delivered ≥24 hours after the first betamethasone (BMZ) course (2 doses), were divided into groups based on the interval between the first course of BMZ and delivery: <10 days or ≥10 days. The primary outcome was severe IVH. Multiple regression analyses were performed to adjust for potential confounders.ResultsThree hundred ninety-two infants delivered after a single BMZ course (312 delivered <10 days; 80 ≥10 days). The incidence of severe IVH was 17% for infants delivered ≥10 days and 7% for those delivered <10 days after a single BMZ course (aOR 4.16; 95% CI 1.59-10.87, P = .004); 37 infants (born ≥10 days from the first BMZ course) received a second/rescue BMZ course. The incidence of severe IVH among infants receiving a second/rescue course was 8%, which was similar to the incidence among infants born <10 days (aOR 1.7; 95% CI 0.41-6.6, P = .48).ConclusionsIn infants born before 28 weeks gestation, delivery ≥10 days from the first BMZ course is associated with a higher incidence of severe IVH; a second/rescue course may reverse this effect.

Background: Postoperative nausea and vomiting (PONV) is common after general anaesthesia, and corticosteroids are used in many protocols for enhanced recovery after surgery (ERAS). However, surgical techniques are developing, and ERAS protocols need to be reevaluated from time to time. Patients and method: In this study, we compared the effects of oral vs. parenteral corticosteroid administration on postoperative nausea. Elective Roux-y-gastric bypass (RYGB) patients were randomly assigned to either 8 mg betamethasone orally (n = 50) or parentally (n = 25) or as controls (n = 25), in a double-blind design. PONV risk factors were noted. All patients had the same anaesthetic technique. Data were collected at baseline, on arrival to the recovery room (RR) and at five more time points during the first 24 h. Nausea and tiredness were patient assessed using visual analogue scales; rescue drug consumption was recorded. Results: Operation time was 30–40 min. Neither demographics nor risk factors for nausea differed between groups. Neither peak values for nor total amount of nausea differed between groups. The number of supplemental injections was the same for all groups. Comments: In a setting of modern laparoscopic RYGB, the value of betamethasone in preventing PONV seems to be limited. ERAS protocols may need re-evaluation.

[Background]Rats showing spontaneous atopic dermatitis (AD)-like skin lesions were observed in the Kyoto Fancy Rat Stock 4 (KFRS4) strain breeding colony. [Objective]To establish the KFRS4 rat as a model of AD. [Methods]The clinical symptoms of AD-like skin lesions were assessed by scoring the degree of dermatitis and examining scratching behavior. The transepidermal water loss was measured to evaluate skin barrier function. Cells infiltrating the skin lesions were identified using histological and immunohistological analyses. IgE and cytokine levels were measured to examine immune status. An ointment treatment experiment was carried out to characterize dermatitis in the KFRS4 rats. [Results]Dermatitis initially appeared around 4 months of age and rapidly worsened from 6 to 8 months of age. The skin lesions accompanied scratching behavior and were predominantly observed in females. The increased transepidermal water loss indicated skin barrier dysfunction. Extensive infiltration of eosinophils, mast cells and lymphocytes was observed in the skin lesions. The plasma IgE level increased in accord with increasing severity of dermatitis. The Th2 and Th17 cytokine mRNA levels were significantly higher in the skin-draining lymph nodes than those in the non-skin-draining lymph nodes. It was demonstrated that betamethasone improved the symptoms of dermatitis. These findings demonstrated that dermatitis in the KFRS4 rats closely resembled that seen in human AD. [Conclusion]Female KFRS4 rats have the potential to serve as an animal model of human AD.

The objective of this study was to assess the safety and efficacy of the fixed combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% topical suspension in adolescents with extensive scalp psoriasis. In this phase II, open-label, 8-week study, adolescents with psoriasis (ages 12-17 years) with 20% or more of the scalp area affected (at least moderate severity according to Investigator's Global Assessment [IGA]) were assigned to once-daily treatment with calcipotriene plus betamethasone dipropionate topical suspension. The primary endpoint was safety, focusing on calcium metabolism and hypothalamic-pituitary-adrenal axis function. Secondary efficacy endpoints were the proportion of patient's achieving treatment success (clear or almost clear disease according to the IGA and clear or very mild disease according to the Patient's Global Assessment [PaGA]) and percentage change in investigator-assessed Total Sign Score (TSS). Pruritus was also assessed. Overall, 31 patients received treatment. Sixteen patients (52%) experienced a total of 20 adverse events; 19 were considered unrelated to study treatment, 14 were mild, and none were serious or lesional or perilesional on the scalp. One patient showed signs of mild adrenal suppression at week 4; the patient discontinued treatment and had normal test results at follow-up 4 weeks later. No cases of hypercalcemia were reported. By treatment end, treatment success was reported for 17 patients (55%) according to the IGA and 18 (58%) according to the PGA. Mean TSS improved from 6.9 at baseline to 2.9 at treatment end (59% improvement). By week 8, 28 patients (90%) experienced mild or no itching, versus 20 (65%) at baseline. Once-daily calcipotriene plus betamethasone dipropionate topical suspension was well tolerated and efficacious for the treatment of scalp psoriasis in adolescents.

The objective of this study was to assess the safety and efficacy of the fixed combination calcipotriene 0.005% plus betamethasone dipropionate 0.064% topical suspension in adolescents with extensive scalp psoriasis. In this phase II, open-label, 8-week study, adolescents with psoriasis (ages 12-17 years) with 20% or more of the scalp area affected (at least moderate severity according to Investigator's Global Assessment [IGA]) were assigned to once-daily treatment with calcipotriene plus betamethasone dipropionate topical suspension. The primary endpoint was safety, focusing on calcium metabolism and hypothalamic-pituitary-adrenal axis function. Secondary efficacy endpoints were the proportion of patient's achieving treatment success (clear or almost clear disease according to the IGA and clear or very mild disease according to the Patient's Global Assessment [PaGA]) and percentage change in investigator-assessed Total Sign Score (TSS). Pruritus was also assessed. Overall, 31 patients received treatment. Sixteen patients (52%) experienced a total of 20 adverse events; 19 were considered unrelated to study treatment, 14 were mild, and none were serious or lesional or perilesional on the scalp. One patient showed signs of mild adrenal suppression at week 4; the patient discontinued treatment and had normal test results at follow-up 4 weeks later. No cases of hypercalcemia were reported. By treatment end, treatment success was reported for 17 patients (55%) according to the IGA and 18 (58%) according to the PGA. Mean TSS improved from 6.9 at baseline to 2.9 at treatment end (59% improvement). By week 8, 28 patients (90%) experienced mild or no itching, versus 20 (65%) at baseline. Once-daily calcipotriene plus betamethasone dipropionate topical suspension was well tolerated and efficacious for the treatment of scalp psoriasis in adolescents.

Background: Topical corticosteroids are the primary treatment for scalp psoriasis. Keratolytic agents are promoted as adjunctive treatments. However, complex treatment regimens may result in poor adherence and outcomes.Objective: To evaluate the evidence for the need for use of topical keratolytic agents as opposed to topical corticosteroid monotherapy in the treatment of scalp psoriasis.Methods: A review of the literature was performed seeking clinical trials using topical keratolytics, topical corticosteroids or the combination for treatment of scalp psoriasis.Results: Complete clearance of scalp psoriasis can be achieved in 10-78% of patients using topical corticosteroids alone, in 3% of patients using topical keratolytics alone, and in up to 84% using a combination of topical keratolytics and topical steroids. Clinical trials comparing the combination of keratolytics and topical corticosteroids versus topical corticosteroids alone found marginally more efficacy using combination regimens.Limitations: We could not find any long term study evaluating the efficacy of combination therapy in scalp psoriasis and its effect on the patients’ adherence.Conclusion: High potency topical corticosteroids are usually effective in treating scalp psoriasis in clinical trials. Poor efficacy in clinical practice may be owing to poor adherence to the treatment regimen. Using a keratolytic agent in conjunction with a topical corticosteroid may provide marginal additional benefit in clinical trials, but that benefit is likely outweighed by the downside of complicating treatment and reducing adherence in the clinical setting, unless a single product containing both medications were used.

Fetal lung arteries Doppler after to use of betamethasone for lung maturation. The objective of research was to determine Doppler modifications of fetal pulmonary arteries after use of betamethasone for lung maturation. An explicative, prospective and longitudinal research was done with a quasi-experimental design and an intentional non probabilistic sample of 106 patients who assisted to High Risk Antenatal Consult at Hospital Central “Dr. Urquinaona". Once patients were selected, two intramuscular injections of betamethasone (12 mg/day) were administered for two consecutive days. Measurements of pulsatility index, resistance index and systolic / diastolic ratio of fetal pulmonary arteries were done. There was observed a significant reduction of mean values of pulsatility index after second measurement compared with initial measurement (p < 0.05). However, mean value of third measurement did not show significant difference with initial value (p = ns). Resistance index decreased in second measurement and later increased in third measurement compared with initial measurements (p < 0.05 for both measurements). Mean value of systolic / diastolic ratio showed a significant reduction during second measurements and then presented a significant increase at the moment of third measurements (p < 0.05 for both measurements). It is concluded that the use of betamethasone for induction of lung maturation produces modifications in Doppler measurements of fetal pulmonary arteries., El objetivo de la investigación fue determinar las modificaciones del Doppler de las arterias pulmonares fetales posterior al uso de betametasona para la maduración pulmonar. Se realizó una investigación de tipo explicativa, prospectiva y longitudinal con un diseño cuasi-experimental y una muestra no probabilística intencional de 106 pacientes que acudieron a la consulta Pre-natal de Alto Riesgo del Hospital Central “Dr. Urquinaona". Una vez seleccionadas las pacientes se les administró inyecciones intramusculares de betametasona (12 mg/día) por dos días consecutivos. Se realizaron las mediciones de índice de pulsatilidad, índice de resistencia y relación sistólico / diastólica de las arterias pulmonares fetales. Se observó disminución significativa de los valores promedio del índice de pulsatilidad en la segunda medición comparado con la medición inicial (p < 0,05). Sin embargo, el promedio de la tercera medición no mostró diferencia significativas con los valores iniciales (p = ns). El índice de resistencia disminuyó en la segunda medición para luego aumentar en la tercera medición comparado con el valor inicial (p < 0,05 para las dos mediciones). El valor promedio de la relación sistólico / diastólica presentó disminución significativa durante la segunda medición para luego presentar un aumento significativo al momento de la tercera medición comparado con el valor inicial (p < 0,05 para las dos mediciones). Se concluye que el uso de betametasona para la inducción de la maduración pulmonar produce modificaciones en las mediciones Doppler de las arterias pulmonares fetales.

The objective of research was to determine modifications of obstetric Doppler after to fetal lung maturation. An explicative, prospective and longitudinal research was done with a quasi-experimental design and an intentional non probabilistic sample of 106 patients who assisted to High Risk Antenatal Consult at Hospital Central “Dr. Urquinaona". Once patients were selected, two intramuscular injections of betamethasone (12 mg/day) were administered for two consecutive days. Measurements of pulsatility and resistance index of uterine, umbilical and fetal middle artery were done. There were not found significant differences among measurements of pulsatility and resistance index of uterine arteries among 3 periods (p = ns). There were observed significant reduction in pulsatility and resistance index of umbilical artery in second and third measurements when compared to initial measurement (p < 0.05). There was found a significant reduction in pulsatility index of fetal middle cerebral artery in both studied period compares with initial values and only was observed a significant decreased in resistance index in second measurements (p < 0.05). It is concluded that use of betamethasone for fetal lung maturation produces modifications in Doppler evaluation of umbilical and fetal middle cerebral arteries., El objetivo de la investigación fue determinar las modificaciones del Doppler obstétrico posterior al uso de betametasona para la maduración pulmonar fetal. Se realizó una investigación de tipo explicativa, prospectiva y longitudinal con un diseño cuasi-experimental y una muestra no probabilística intencional de 106 pacientes que acudieron a la consulta Pre-natal de Alto Riesgo del Hospital Central “Dr. Urquinaona". Una vez seleccionadas las pacientes se les administró inyecciones intramusculares de betametasona (12 mg/día) por dos días consecutivos. Se realizaron las mediciones de índice de pulsatilidad e índice de resistencia en las arterias uterinas, umbilical y cerebral media fetal. No se encontraron diferencias estadísticamente significativas entre las determinaciones del índice de pulsatilidad y de resistencia de las arterias uterinas (p = ns). Se observaron disminuciones significativas en el índice de pulsatilidad y de resistencia de la arteria umbilical en la segunda y tercera medición al compararla con la medición inicial (p < 0,05). Se encontraron disminuciones en el índice de pulsatilidad de la arteria cerebral media fetal en ambos periodos de estudio comparado con los valores iniciales y solo se observó una disminución significativa del índice de resistencia en la segunda medición (p < 0,05). Se concluye que el uso de betametasona para la maduración pulmonar fetal produce modificaciones en la evaluación Doppler de las arterias umbilical y cerebral media fetal.