Multiple Courses Of Steroids Research Articles

Maternal Steroids in High-Risk Congenital Lung Malformations

IntroductionThe purpose of the present study is to evaluate our institutional management of high-risk congenital lung malformations (CLM) with particular consideration of the use of multiple maternal steroid courses and maternal steroids in CLMs with pathologies other than congenital pulmonary airway malformation (CPAM). MethodsA single-center retrospective review was performed for all fetuses evaluated for CLM who received maternal steroids and/or had a CLM volume ratio (CVR) ≥ 1.6 (2015-2020). Fetuses were categorized as receiving no steroids, single steroid, or multiple steroid courses. Outcomes evaluated included CVR growth rate, resolution of early hydrops, and resolution of hydrops. Results are reported with a descriptive analysis. ResultsNineteen patients were identified who had CVR ≥ 1.6 (single steroid course 9/19, multiple steroid courses 6/19, and no steroids 4/19). A majority (n = 13, 68%) of all lesions had a reduction or no change in CVR between initial and final measurements (single steroid course 7/9, 78%; multiple steroid courses 4/6, 67%). When evaluating by pathology, ≥ 50% of each classification had reduction or no growth of CVR (CPAM 7/11, bronchial atresia 2/4, sequestration 3/3, congenital lobar emphysema 1/1). Seventy five percent (3/4) of lesions with early hydrops had resolution following steroid treatment (single steroid course 1, multiple steroid courses 2). Of the four lesions that had hydrops, only one had resolution after receiving multiple steroid courses. ConclusionsOur institutional experience reports the majority of CLM (including pathologies other than CPAM) who received steroids had reduction or no change in CVR. Given the low risk-benefit ratio of maternal steroids, physicians could consider use of multiple steroid courses for CLM refractory to a single course.

An unusual case of breathlessness.

We present the case of an asthmatic patient who continued to present with breathlessness and received multiple courses of steroids for her presumed asthma exacerbations. After multiple investigations, we made the diagnosis of TBM secondary to relapsing polychondritis. https://bit.ly/3b8Uw1O

A233 VEDOLIZUMAB FOR STEROID & INFLIXIMAB-REFRACTORY ICI-COLITIS

Abstract Background Immune checkpoint inhibitors (ICI), such as anti-PD1, improve survival in melanoma, renal carcinoma and prostate cancer. However, by disinhibiting the immune system, these treatments cause significant immune-related adverse events (irAE), including colitis. For ICI-colitis, guidelines suggest escalating from observation to steroids to infliximab, without strong evidence for additional options should these fail. Vedolizumab has been used in a small number of cases for steroid-refractory or dependent ICI-colitis; only 9 cases have been reported in patients who failed infliximab therapy with a response rate of 67%. Aims To discuss a case of ICI-colitis that failed multiple steroid courses and infliximab infusions, but achieved remission with vedolizumab. Methods A 65-year-old male with malignant melanoma was randomized to adjuvant nivolumab +/- ipilimumab and developed non-bloody diarrhea. Despite loperamide, diarrhea worsened to 4–5 bowel movements daily. Stool cultures and C. diff were negative and 85mg of daily prednisone was started, while the ICI was held for 8 weeks. After a 2nd steroid taper, diarrhea recurred and the patient received 2 infliximab infusions 18 days apart. Despite initial improvement, biopsies demonstrated colitis and he underwent a 3rd infusion with little response. Clinical and biopsy-confirmed remission was only achieved once 2 vedolizumab infusions were given. Results Colitis is the most common ICI irAE, ranging in severity from mild to perforation and death. The incidence of grade 3 and 4 colitis, which require ICI discontinuation, is 1.3% for anti-PD1 and 13.6% in combination therapy. The severity of irAE is positively correlated with malignancy response and stopping ICI risks recurrence. Those that fail irAE medical management may require surgery. Thus, there is an impetus to continue the ICI and provide effective medical management for irAE. ICI-colitis guidelines are based on the CTCAE diarrhea classification and suggest supportive management and ICI continuation for grade 1. For grade 2, the ICI is held and steroids are started; infliximab is added for grades 3 and 4. However, 33–66% of patients are steroid-refractory or dependent; and patients may be infliximab non-responders, or unable to tolerate systemic side effects. Vedolizumab, an anti-α4β7-integrin, acts locally to inhibit T cells in the bowel wall, reducing inflammation in IBD. Recent reports, including ours, suggest usefulness in steroid and infliximab-refractory ICI colitis after only 2–4 infusions. When the inflammatory burden is high, the response rate is >80% and given its gut-specificity, side effects are minimal compared to infliximab. Although further evaluation is required, using vedolizumab as second-line therapy is reasonable. Conclusions Given vedolizumab’s safety and gut-specificity, it should readily be considered in the treatment of ICI irAE. Funding Agencies None

A CASE OF ADULT-ONSET, STEROID-RESISTANT ASTHMA DIAGNOSED AS BRONCHOCENTRIC GRANULOMATOSIS RESPONSIVE TO MEPOLIZUMAB

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: Several asthma related diagnoses that involve granulomatous inflammation have been described in the literature. Bronchocentric granulomatosis (BG) is a histopathological finding characterized by the granulomatous necrotizing reaction centered in the airways. Asthmatic granulomatosis (AG) has features of autoimmunity, non-necrotizing granulomas, and physiologic features of asthma. CASE PRESENTATION: A 48-year-old man with adult onset asthma, GERD, allergic rhinitis, and atopic dermatitis, presented with chronic cough for 10 months. His cough began during a trip to Puerto Vallarta, Mexico, where he suffered from pneumonia requiring mechanical ventilation. Over the next year, he continued to suffer from recurrent pneumonia and chronic cough. He was treated with multiple courses of steroids without much relief of symptoms. He demonstrated persistently elevated CRP, serum eosinophils, and IgE levels. CT Chest showed pre-tracheal lymphadenopathy, ground glass opacities, and tree-in-bud nodules. Workup was negative for any fungal or rheumatologic serologies. Eventually, VATS wedge biopsy was performed and read as BG. The pathology was sent for and confirmed by a second opinion. Patient was started on mepolizumab and corticosteroids with full resolution of his cough. DISCUSSION: BG is an older entity first described in 1973 and was initially related to asthmatic patients with ABPA and to non-asthmatic patients with no identified etiologic agent. Current etiologies for non-asthmatic patients have been related to many diseases such as infectious etiologies (mycobacteria, pulmonary echinococcosis, Influenza A) and other diseases such as RA, CGD, and GPA. While his IgE and eosinophil count were elevated, our patient had neither IgE nor serum percipitins against Aspergillus or other mycoses ruling out ABPA. Our patient did demonstrate histopathologic findings of BG, however, was unresponsive to multiple courses of oral glucocorticoids. BG is rarely refractory to glucocorticoids, and there are no case reports demonstrating response to mepolizumab, which is used to treat severe eosinophilic asthma. This case shares features of both BG and AG in regards to its clinical presentation, histopathologic findings, and response to treatment. Our patient did not meet criteria for severe asthma and could not be appropriately categorized as BG related to asthma and ABPA. CONCLUSIONS: This case highlights overlap of BG, AG and other granulomatous lung diseases that comprise a heterogeneous group of disorders that have a wide spectrum of pathologies with variable clinical manifestations and outcomes. We can conclude that our case is a unique presentation of idiopathic glucocorticoid-refractory-BG with shared features of AG, responsive to newer immunotherapy. As far as we can tell this is the first report of glucocorticoid-refractory BG responsive to mepolizumab. Reference #1: Liebow AA. Pulmonary angiitis and granulomatosis. Am Rev Respir Dis 1973;108:1-18. Reference #2: Wenzel SE, Vitari CA, Shende M, Strollo DC, Larkin A, Yousem SA. Am J Respir Crit Care Med. 2012 Sep 15;186(6):501-7. Reference #3: J.L. Myers, Bronchocentric granulomatosis. Disease or diagnosis? Chest 96 (1989) 3e4. DISCLOSURES: No relevant relationships by Bhavik Gupta, source=Web Response No relevant relationships by Brian Stephenson, source=Web Response No relevant relationships by Ajeet Vinayak, source=Web Response

Vedolizumab Achieved Clinical and Histologic Remission in a Patient with Lung Cancer Who Had a Steroid-Refractory Upper Gastrointestinal Injury Due to Nivolumab Treatment

Abstract Immune checkpoint inhibitors (ICIs) have emerged as a novel therapeutic class for various malignancies. Their immune upregulation promotes significant anti-tumor effect, but simultaneously, can also result in treatment-limiting immune-related adverse events (irAEs). The data on upper gastrointestinal (GI) tract irAEs are sparse. We herein describe a case of steroid-dependent upper GI toxicity with nivolumab (an anti-programmed death [PD] protein-1) that achieved clinical and histological remission with vedolizumab treatment (a GI tract targeted anti-integrin antibody). A 65-year-old male patient with progressive lung cancer was treated with nivolumab and following 16 cycles, developed severe nausea, vomiting, and epigastric abdominal cramps requiring five hospitalizations. His initial esophagogastroduodenoscopy (EGD) showed active inflammation in both the stomach and duodenum. Nivolumab was discontinued, but despite treatment with multiple steroid courses, his symptoms always recurred during prednisone taper. Clinical remission was ultimately achieved with vedolizumab. His last EGD after five infusions of vedolizumab demonstrated resolution of inflammation. His lung cancer has since relapsed and the treatment plan was to resume nivolumab concurrently with vedolizumab. In conclusion, ICIs, such as nivolumab, have emerged as therapy for various malignancies. Their use can be associated with various irAEs including the upper GI adverse events which is uncommon. This case scenario showed that vedolizumab can provide a steroid-sparing therapeutic effect to achieve remission of upper GI irAEs even in cases where multiple steroid courses have failed.

693: Tocolysis the setting of preterm premature rupture of membranes

Tocolysis after PPROM is controversial, and evidence to guide management is limited. We sought to determine if tocolysis after PPROM is associated with adverse neonatal outcomes. This is a secondary analysis of a randomized trial of magnesium for neuroprotection. Women at 24-32 weeks with singleton gestations and PPROM were eligible. We excluded women tocolyzed prior to randomization, fetuses with chromosomal or single gene abnormalities, and those with incomplete outcome data. The primary exposure was post randomization tocolysis. The primary neonatal outcome was culture proven sepsis, and the primary childhood outcome was a composite of death or Bayley scores 2 standard deviations below the mean at age 2 (score <70). Death is included as a competing outcome. Patient characteristics were compared by exposure. We fit logistic regression models to adjust for factors that influence odds of the outcomes including exposure to magnesium, race, education level, gestational age at birth, maternal BMI and smoking status. Of 1667 patients, 38 (2.3%) received tocolysis while 1629 (97.7%) did not. The most common tocolytic agent was magnesium (42.1%). Maternal age, race and BMI were similar among groups. Women in the tocolysis group were more educated, more likely to have multiple courses of steroids, and less likely to smoke. Neonates of tocolyzed women were larger (1687g v 1439g, p=0.01) and delivered at a later gestational age (31+1 v 29+6 weeks, p=0.01). Rates of neonatal sepsis were similar in tocolyzed versus non-tocolyzed groups (6 (15%) v 260 (16%), p=0.9). In the adjusted model the odds for sepsis and abnormal psychomotor developmental index (PDI) or death were elevated with tocolysis, although this finding did not reach statistical significance. There was no difference in abnormal mental developmental index (MDI) or death. Although the neonates of mothers given tocolysis prolonged gestation and achieved higher birth weights, tocolysis after PPROM may be harmful given possible increase risks for sepsis and low Bayley PDI/death. Further data are needed to verify findings and guide practice.

Natural History of Ulcerative Colitis in Patients With Concomitant Primary Sclerosing Cholangitis

Introduction: The natural history of Ulcerative Colitis (UC) in patients with concomitant primary sclerosing cholangitis (PSC) is poorly defined. We aimed to examine whether concurrent PSC and UC status was associated with increased risk of colectomy and requirement for multiple courses of corticosteroids (CS). Methods: We conducted a retrospective study among a cohort of nation-wide VA patients with UC. We first performed univariate comparison between UC patients with and without PSC. We then conducted two case-control analyses to determine the association between PSC status and outcomes related to UC disease course: colectomy for UC disease and receipt of two or more courses of CS after UC diagnosis. The exposure was presence or absence of PSC. Multivariable logistic regression analysis was conducted to estimate odds ratios (OR) and associated 95% confidence intervals (CIs) in each case-control analysis. We examined the following covariates in the multivariable model: duration of follow-up after UC diagnosis, sex, age at UC diagnosis, race, severity of UC, and extent of UC. Results: The analysis included 836 UC patients without PSC and 103 UC patients with PSC. In univariate comparisons, the PSC patients were more likely to have more extensive UC than those without PSC. However, the PSC patients were slightly less likely to have severe UC than non-PSC patients. The PSC patients were younger at diagnosis of UC and had longer period of follow-up after UC diagnosis. In multivaribale logistic regression analysis adjusting for duration of follow-up after UC diagnosis, sex, age at UC diagnosis, race, severity of UC, and extent of UC, PSC status was not associated with the risk of colectomy for UC (AOR 1.18, 95% CI: 0.49-2.84). Furthermore, PSC was not associated with a significantly increased risk of receiving two or more courses of steroids after adjusting for duration of follow-up after UC diagnosis, sex, age at UC diagnosis, race, severity of UC, and extent of UC (AOR 1.37, 95% CI: 0.85-2.22). However, without adjusting for UC extent and severity, PSC was associated with a modestly increased risk for the need for two or more courses of CS (AOR 1.58, 95% CI: 1.01-2.49); without adjusting for disease extent, the AOR was 1.72, 95% CI: 1.09-2.74.Table: Table. Comparison of PSC and non-PSC UC patientsConclusion: UC patients with PSC do not have a more benign disease course than UC patients without PSC. UC patients with PSC may have a modestly increased risk for multiple courses of steroids, and the risk increase appears to be mediated by more extensive UC involvement.

Recent Update in The Management of Childhood Nephrotic Syndrome

Nephrotic Syndrome (NS) is a common renal disease seen in children. Children who go into complete remission following treatment with corticosteroids are classified as having steroid sensitive NS. In developed countries over 80% of children with idiopathic NS have steroid sensitive disease. The exact pathogenesis of this condition remains elusive. Podocyte injury and proteinuria are the two main issues in the pathogenesis. Recent studies suggest release of cytokines by T-cells as well as a strong contribution of Bcell immunity. Genetic studies have reported human leucocyte antigen (HLA) class II antigens DR and DQ associations linked to steroid sensitive NS. Most children with steroid sensitive NS have multiple relapses and a significant percentage also develop steroid dependent NS. Diuretic- resistant edema also a clinical problem to manage these patients. These children receive multiple courses of steroids and are at high risk of developing steroid toxicity. Patient with frequent relapses who develop steroid dependency thus require alternative treatment. Steroid resistant NS considers when failure to response within 8 weeks of steroid therapy. Steroids sparing agents used include levamisole, cyclophosphamide, mycophenolate mofetil (MMF), calcineurin inhibitors (cyclosporine and tacrolimus), rituximab and vincristine; these agents have greatly reduced the adverse effects seen with long-term use of steroids; so therapy needs to be individualized to achieve optimal care of each child.J Bangladesh Coll Phys Surg 2016; 34(1): 26-32

Effect of single and multiple courses of maternal betamethasone on prenatal congenital lung lesion growth and fetal survival

PurposeAdministration of maternal betamethasone (BMZ) is a therapeutic option for fetuses with large microcystic congenital lung lesions at risk for, or causing, hydrops. Not all fetuses respond to a single course of BMZ. We review our experience with the use of single and multiple courses of maternal BMZ for the management of these patients. MethodsA retrospective review of fetuses with congenital lung lesions managed with maternal BMZ from 2003 to 2014 was performed. ResultsForty-three patients were managed with prenatal steroids (28 single course, 15 multiple courses). Single course recipients demonstrated a reduction in lesion size and resolution of hydrops in 82% and 88% of patients respectively compared to 47% and 56% in recipients of multiple steroid courses. Survival of multiple course patients (86%) was comparable to that of single course patients (93%) and improved compared to non-treated historical controls. Multiple course recipients demonstrated an increased need for open fetal surgery and postnatal surgery at a younger age. ConclusionFetuses who fail to respond to a single course of BMZ may benefit, as indicated by hydrops resolution and improved survival, from additional courses. However, failure to respond is indicative of a lesion which may require fetal or immediate neonatal resection.

Cytogenetic and Molecular Characterization of Sweet's Syndrome in Patients with Acute Myeloid Leukemia.

AbstractAbstract 2587▪▪This icon denotes a clinically relevant abstract Background:Sweet's syndrome (SS), also known as acute febrile dermatosis, has been associated with hematologic malignancies including acute myeloid leukemia (AML). We sought to identify the disease characteristics of AML patients (pts) who develop SS, and to report the cytogenetic (CG) and molecular genetic (MG) abnormalities observed. Methods:We conducted a retrospective review of charts of newly diagnosed AML pts that underwent induction chemotherapy and had follow up at our institution. Pts with SS were identified if both the clinical signs and symptoms and a biopsy of the skin lesion were consistent with SS. CG and MG abnormalities are reported here as part of our descriptive analysis. Results:Between years 2000 to 2011, we identified a total of 2178 newly diagnosed AML pts that underwent induction chemotherapy and had follow-up at our institution. During this time, 697 pts (32%) underwent skin biopsies in the course of their AML treatment and follow-up. 21 pts (1% of all pts and 3% of all who underwent skin biopsy) demonstrated signs and symptoms and had skin biopsy consistent with SS. Table 1 summarizes the baseline characteristics of pts with AML at the time of dx of SS, including the CG and MG abnormalities observed. Myelodysplastic syndrome (MDS) prior to diagnosis of AML and SS was present in 9 pts (43%). CG analysis revealed diploid karyotype in 7 pts (33%), deletion 5p in 8 pts (38%; 4 pts had del5p as sole abnormality, and 4 pts with del5p as part of other accompanying/complex CG) and 4 patients had complex CG (19%). Most common MG abnormality was seen in the FLT3 gene, found in 7 out of 18 pts (39%) tested (FLT3 –ITD present in 4 pts while mutation of FLT3 codon 835 occurred in 3 pts). In addition, two out of 7 (28%) pts tested, had NPM1 gene mutation (one pt had concomitant FLT3 gene mutation). Other CG and MG abnormalities are summarized in Table 1. Eight pts (38%) with SS received systemic steroids for treatment, 1 pt (5%) received topical steroids while 19 (90%) received antibiotics and supportive care. The treatment for SS was effective in 16 out of 16 pts (100%) for whom follow-up information was available. Three pts required multiple courses of steroids while 5 pts required one course of steroids. The median time to improvement reported in the signs and symptoms of SS was 14 days (range 4–153). The median overall survival of AML pts who developed SS during course of their management was 14 months (95% confidence interval 12.6 – 15.4 months). Conclusions:SS is a frequent occurrence among AML pts as compared to its incidence in the general population. It can occur in AML pts during all phases of the disease. In this retrospective review, we found that SS frequently occurs in AML that has developed in the setting of prior MDS and where leukemic cells carry CG and MG abnormalities of del5p and FLT3 gene respectively.Table 1:SS in AML ptsNPercentage/RangeTotal AML pts2178Total pts undergoing skin biopsies during treatment of AML69732Pts diagnosed with SS211% of all pts 3% of all pts biopsiedAgeAt dx of AML5527-87At dx of SS5627-83GenderFemale1466Laboratory values at dx of AMLMedian AML Blast %4314-92Median absolute neutrophil count (ANC; 109/L)1.60.1-45Median hemoglobin (Hb; g/dl)97.3-11Median platelets (109/L)528-156SS dx before allogeneic HSCT5/683Status of AML at time of SS dxSS dx before AML dx15SS dx at the time of AML dx733SS dx during primary induction therapy629SS dx during treatment for relapsed AML733Symptoms at presentation of SSFever with skin rash1466Tenderness in the skin rash10/2148History of filgrastim (G-CSF) use210Location of skin rashHead and Neck943Upper extremity1048Trunk and back838Lower extremity1048Laboratory values at dx of SSMedian AML Blast%250-92Neutrophilia (ANC ≥6 × 109/L)15Neutropenia (ANC ≤1.5× 109/L)1466Anemia (Hb <10g/dl)1990Thrombocytopenia (≤100 × 109/L)21100Kidney Dysfunction (GFR<60 ml/min)210CG analysisDel5p (as sole abnormality, n=4, as part of complex CG, n=4)838––Diploid733Complex CG (≥ 3 chromosomal abnormalities)419Del7p210t(6;9)210Trisomy 815t(11;17)15t(15;17)15t(3;3)15MG analysisFLT3 (total tested =18)––Internal Tandem Duplication422D835317NPM1 (total tested=7)228RAS (total tested=13)00C-Kit (total tested=5)00CEBPA (total tested=3)00 Disclosures:No relevant conflicts of interest to declare.

An unusual exacerbation of chronic obstructive pulmonary disease (COPD) with herpes simplex tracheitis: case report

Chronic obstructive pulmonary disease (COPD) is a common cause of morbidity in the UK and is increasingly seen in elderly patients, often requiring multiple courses of steroids. We present a case of a 72 year old lady with repeated exacerbations of COPD which did not respond to conventional treatment. Herpes simplex virus (HSV1) tracheobronchitis was diagnosed following a rigid bronchoscopy and her symptoms improved with intravenous acyclovir. This is the first published case of HSV tracheitis in a non immunosuppressed individual with chronic lung disease.

Rituximab in Children with Autoimmune Thrombocytopenia Complicating Underlying Congenital or Acquired Immunodeficiency State.

Rituximab (chimeric anti-CD20 monoclonal antibody) has been reported to be effective in various autoimmune conditions, especially in autoimmune cytopenias, but there are few reports of its use in paediatric population with underlying immunodeficiency states. We report three cases of autoimmune cytopenias (Evan's syndrome in DiGeorge syndrome, autoimmune thrombocytopenia in a HIV positive patient and lastly autoimmune thrombocytopenia in a post liver transplant patient) where rituximab was effective in reversing the cytopenias. First patient (11yrs) had DiGeorge syndrome which was complicated by Evan's syndrome. It was treated with multiple courses of steroids and immunosuppressive agents, with resultant recurrent systemic bacterial and fungal infections. She had rituximab as a last resort, which resulted in sustained improvements in her Haemoglobin and platelet count. Second patient (12yrs) was diagnosed with HIV in 1993. She had sudden onset Intra-cranial bleed as a result of immune thrombocytopenia. She was treated with Intravenous immunoglobulin (IVIg) and subsequently with prednisolone with no response. She however responded to rituximab and then went on to have rituximab for a further 2 courses, each 12 months apart. The third patient (14yrs) had auxiliary liver transplant in 2002. He developed immune thrombocytopenia and neutropenia in which remission was sustained only for a maximum of 6 weeks following IVIg. As he was already on immunosuppression, he was given rituximab to which he has had a sustained remission. Side effects: The patient with DiGeorge syndrome had recurrent chest infection which was thought to be due to aspiration as a result of her hiatus hernia. The other patients did not have major side-effects. Immunoglobulin levels in all three patients were in normal range. Thus, in our experience rituximab is a useful adjunct in management of autoimmune cytopenias with an underlying immunodeficiency state and should be considered early in steroid refractory cases, as it leads to sustained remissions in the blood counts. It is well tolerated without major infections in patients who are already immunosuppressed due to their immunodeficiency state and the fear of immuneparesis is not seen.

Antenatal corticosteroids: the controversy continues

Purpose of review Maternal administration of glucocorticoids remains the mainstay of perinatal medicine for the fetus at risk of premature delivery. The reductions of severity of respiratory distress syndrome, incidence of intraventricular hemorrhage, and neonatal death have all been well documented. Findings from both experimental studies in animals as well as clinical investigation in humans have raised issues of concern and controversy. These include the use of repetitive courses of corticosteroids. Questions have been raised regarding the postnatal neurobehavioral and prenatal cardiovascular responses to corticosteroids. The purpose of this review is to address the current data pertaining to these controversies. Recent findings Animal studies reflect the concerns of the use of multiple courses of steroids with alterations of brain growth and histology. Human data suggest that multiple courses of corticosteroids might reduce the risk of respiratory distress syndrome, but at the expense of alterations of lung architecture. There are concerns about decreased somatic and head size. Neurobehavioral abnormalities are more frequently seen in children exposed to multiple courses. In growth-restricted fetuses with evidence of placental dysfunction, there may be a risk of sudden in-utero decompensation. Summary Repetitive courses of corticosteroids have deleterious effects with little improvement in neonatal outcome. A ‘rescue dose’ given to a fetus previously yet remotely treated may be of some benefit. Animal studies suggest acute vascular changes with maternal steroids. This has not been consistently borne out with the indirect assessment using Doppler in the human. A select group of severely growth restricted fetuses with umbilical artery absent end diastolic flow may actually deteriorate with maternal corticosteroids.

Effect of single and multiple courses of prenatal corticosteroids on 17-hydroxyprogesterone levels: implication for neonatal screening of congenital adrenal hyperplasia.

Measurement of 17-hydroxyprogesterone (17-OHP) from filter-paper blood is widely used to screen for congenital adrenal hyperplasia (CAH). However, in pregnancies with an expected preterm delivery, prenatal treatment with steroids to induce pulmonary maturation could suppress the fetal adrenals and interfere with this screening. In 160 infants who were born between 25 and 35 wk of gestation, we measured 17-OHP in filter-paper blood at 72-96 h and compared the values between those who had not received antenatal steroids (n=50) and those who had (n=110). A single course of steroids was two 12-mg injections of betamethasone given within a 24-h interval: 30 infants received a half single course, 45 received a full single course, and 35 received multiple courses. Results are expressed as medians (25th percentile; 75th percentile). Blood 17-OHP differed significantly among groups: 23.7 (14.2; 30.7) nmol/L, 26.1 (15.0; 50.1) nmol/L, 20.1 (13.8; 29.1) nmol/L, and 14.9 (9.5; 26.2) nmol/L (for, respectively, no steroid, half a single course, a full single course, and multiple courses; p <0.05, multiple comparisons with the Kruskal-Wallis test). However, only infants who were treated with multiple antenatal courses of steroids had lower blood 17-OHP than those who were untreated (p <0.05 with the Mann-Whitney U test). In multiple regression analysis, steroid treatment and intrauterine growth retardation were significant negative predictors of blood 17-OHP, whereas respiratory distress syndrome was a significant positive predictor (multiple R=0.50, p <0.001). Multiple courses of steroids in preterm infants decrease 17-OHP values by approximately 30% in filter-paper blood, thus raising the risk of false-negative results in screening programs for CAH.

Preemies on steroids: a new iatrogenic disaster?

Preemies on steroids: a new iatrogenic disaster?

The effect of multiple courses of antenatal steroids on neonatal infection

Objective: The objective of this study was to determine if multiple courses of antenatal steroids in women with preterm premature rupture of membranes (PPROM) are associated with an increased incidence of neonatal sepsis.Methods: 206 women with PPROM between 22–34 weeks of gestation inclusive who did not deliver within 24 hours of admission were followed prospectively. Management included intravenous antibiotics, weekly betamethasone, daily fetal nonstress testing and twice weekly biophysical profiles. Neonatal complications including sepsis were extracted from the medical record at discharge. Fisher’s exact test was used to compare the incidence of neonatal sepsis among patients with single versus multiple courses of steroids. Significance was defined as P <0.05.Results: Ten (4.8%) neonates had the diagnosis of sepsis. The median number of steroid courses was 2 (range 1–11). No significant difference was noted between the incidence of sepsis when one course of steroids was compared with two or multiple courses.Conclusion: In our population, multiple courses of steroids do not increase the incidence of neonatal sepsis in patients with PPROM. Steroid Courses12345≥6Neonatal sepsis, n (%)6 (7.1)2 (2.7)2 (6.9)000Total (N = 206)8573291072

Effectiveness of multidose antenatal steroids

Objective: To compare effectiveness between single and multiple courses of antenatal steroids in preterm births and determine adverse effects attributable to multiple courses. Methods: We studied retrospectively the neonatal outcomes of infants who weighed 1750 g or less at birth between January 1990 and December 1997. Infants exposed to a single course were compared with those exposed to two or more courses of antenatal steroids, with respect to various perinatal outcome variables. Results: Ninety-three neonates were exposed to two or more courses of antenatal steroids and 261 neonates had been given single courses. The mean (± standard deviation) gestational age (29.6 ± 2.8 weeks compared with 28.7 ± 2.7 weeks; P = .007) and birth weight (1252 ± 321 g compared with 1159 ± 339 g; P = .013) were significantly higher among neonates exposed to multiple courses. There were no significant differences between groups in perinatal outcomes; however, those exposed to multiple courses had a significantly lower rate of respiratory distress syndrome (RDS) (17 [18%] compared with 107 [41%]; P ≤ .001) and surfactant use (40 [43%] compared with 149 [57%]; P = .02). Adjusting for confounding variables, multiple courses of steroids were significantly associated with a 65% reduction in the incidence of RDS (odds ratio 0.35; 95% confidence interval = 0.18, 0.70; P = .003). Conclusion: Compared with single courses, multiple courses of antenatal steroids reduced significantly the incidence of RDS with no apparent increase in neonatal sepsis or disturbances in fetal growth.

Repeated Courses of Steroids in Preterm Membrane Rupture Do Not Increase the Risk of Histologic Chorioamnionitis

Antenatal administration of steroids (betamethasone 12 mg i.m. twice q 24 hr) enhances fetal lung maturation and reduces neonatal morbidity in preterm prelabor rupture of membranes (PROM). However, the risks of repeated administration of steroids 7 days after the initial course are unknown. We evaluated the prevalence of histologic evidence of chorioamnionitis in patients receiving single versus multiple courses of steroids for fetal lung maturation. We performed a retrospective analysis of consecutive cases of preterm PROM at or = 2 courses of steroids (n = 89). Placental pathology examination was performed after delivery, and histologic evidence of acute placental inflammation was determined and scored semiquantitatively on a scale of 0-4, as previously described. Potential confounding variables considered were: presence of oligohydramnios (vertical pocket of amniotic fluid < or = 1 cm at ultrasound), onset of labor prior to delivery, gestational age at delivery, and mode of delivery. The three groups were comparable for gestational age at membrane rupture and at delivery, rate of oligohydramnios, labor prior to delivery, and mode of delivery. Administration of multiple courses of steroids was associated with a decrease in the rate of clinical chorioamnionitis (p < 0.0001) and severity of histologic acute placental inflammation (mean +/- SD total score of acute inflammation: 10.7 +/- 7.2 vs. 7.3 +/- 6.0 vs. 6.9 +/- 6.0, p = 0.005) compared with the groups receiving no steroids or administration of a single course of steroids. In preterm PROM at < 32 weeks, repeated administration of courses of steroids is not associated with an increase in the prevalence of clinical or histologic evidence of infectious outcome. These findings may reflect a greater likelihood for noninfected patients to remain quiescent and thus receive repeated courses of steroids.

Single VS multiple courses of steroids for fetal maturation: Is more better?

Single VS multiple courses of steroids for fetal maturation: Is more better?