What we have learned about antenatal corticosteroid regimens.
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ABSTRACT:
SUBMITTER: Wapner RJ
PROVIDER: S-EPMC6335646 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
Publications
What we have learned about antenatal corticosteroid regimens.
Wapner Ronald J RJ Gyamfi-Bannerman Cynthia C Thom Elizabeth A EA
Seminars in perinatology 20160425 5
Administration of antenatal corticosteroids has been standard of care for women between 24 and 34 weeks of gestation who are at risk for preterm delivery for more than 20 years longer in other parts of the world. Although the benefit of steroids in this population has been confirmed, there remain many questions including the frequency of dosing and whether it is possible to expand the gestational age criteria to women likely to deliver before 24 weeks or after 34 weeks. The MFMU Network has play ...[more]
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Project description:Respiratory complicˆations are the major cause of morbidity and mortality among preterm infants, which is partially prevented by the administration of antenatal corticosteroids (ACS). Most very preterm infants are exposed to chorioamnionitis, but short- and long-term effects of ACS treatment in this setting are not well defined. In low-resource settings, ACS increased neonatal mortality by perhaps increasing infection. We report that treatment with low-dose ACS in the setting of inflammation induced by intraamniotic lipopolysaccharide (LPS) in rhesus macaques improves lung compliance and increases surfactant production relative to either exposure alone. RNA sequencing shows that these changes are mediated by suppression of proliferation and induction of mesenchymal cellular death via TP53. The combined exposure results in a mature-like transcriptomic profile with inhibition of extracellular matrix development by suppression of collagen genes COL1A1, COL1A2, and COL3A1 and regulators of lung development FGF9 and FGF10. ACS and inflammation also suppressed signature genes associated with proliferative mesenchymal progenitors similar to the term gestation lung. Treatment with ACS in the setting of inflammation may result in early respiratory advantage to preterm infants, but this advantage may come at a risk of abnormal extracellular matrix development, which may be associated with increased risk of chronic lung disease.
| S-EPMC7819743 | biostudies-literature
Project description:OBJECTIVE:To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment. STUDY DESIGN:A multicenter cohort study of 4858 infants 22-26 weeks of gestation born 2006-2011 at 24 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, with follow-up through 2013. Survival and neurodevelopmental outcomes were available at 18-22 months of corrected age for 4576 (94.2%) infants. We described antenatal interventions, resuscitation, and infant outcomes. We modeled the effect on infant outcomes of each hospital increasing antenatal corticosteroid exposure for resuscitated infants born at 22-24 weeks of gestation to rates observed at 25-26 weeks of gestation. RESULTS:Discordant antenatal corticosteroid use and resuscitation, where one and not the other occurred, were more frequent for births at 22 and 23 but not 24 weeks (rate ratio [95% CI] at 22 weeks: 1.7 [1.3-2.2]; 23 weeks: 2.6 [2.2-3.2]; 24 weeks: 1.0 [0.8-1.2]) when compared with 25-26 weeks. Among infants resuscitated at 23 weeks, adjusting each hospital's rate of antenatal corticosteroid use to the average at 25-26 weeks (89.2%) was projected to increase infant survival by 7.1% (95% CI 5.4-8.8%) and survival without severe impairment by 6.4% (95% CI 4.7-8.1%). No significant change in outcomes was projected for infants resuscitated at 22 weeks, where few (n = 22) resuscitated infants received antenatal corticosteroids. CONCLUSIONS:Infants born at 23 weeks were more frequently resuscitated without antenatal corticosteroids than other extremely preterm infants. When resuscitation is intended, consistent provision of antenatal corticosteroids may increase infant survival and survival without impairment. TRIAL REGISTRATION:ClinicalTrials.govNCT00063063 (Generic Database) and NCT00009633 (Follow-Up Study).
| S-EPMC6486854 | biostudies-literature
Project description:Examination of regional care patterns in antenatal corticosteroid use (ACU) rates may be salient for the development of targeted interventions. Our objective was to assess network-level variation using California perinatal care regions as a proxy. We hypothesized that (1) significant variation in ACU exists within and between California perinatal care regions, and (2) lower performing regions exhibit greater NICU-level variability in ACU than higher performing regions.We undertook cross-sectional analysis of 33,610 very low birth weight infants cared for at 120 hospitals in 11 California perinatal care regions from 2005 to 2011. We computed risk-adjusted median ACU rates and interquartile ranges (IQR) for each perinatal care region. The degree of variation was assessed using hierarchical multivariate regression analysis with NICU as a random effect and region as a fixed effect.From 2005 to 2011, mean ACU rates across California increased from 82% to 87.9%. Regional median (IQR) ACU rates ranged from 68.4% (24.3) to 92.9% (4.8). We found significant variation in ACU rates among regions (P < .0001). Compared with Level IV NICUs, care in a lower level of care was a strongly significant predictor of lower odds of receiving antenatal corticosteroids in a multilevel model (Level III, 0.65 [0.45-0.95]; Level II, 0.39 [0.24-0.64]; P < .001). Regions with lower performance in ACU exhibited greater variability in performance.We found significant variation in ACU rates among California perinatal regions. Regional quality improvement approaches may offer a new avenue to spread best practice.
| S-EPMC4306799 | biostudies-other
Project description: Not available
| S-EPMC7387231 | biostudies-literature
Project description:Importance:Maternal antenatal corticosteroid treatment is standard care to accelerate fetal maturation when birth before 34 weeks is imminent. Recently, expansion of the indications beyond 34 gestational weeks has been debated. However, data about long-term outcomes remain limited, especially among infants who after treatment exposure are born at term. Objective:To study if antenatal corticosteroid treatment is associated with mental and behavioral disorders in children born at term (?37 weeks 0 days' gestation) and preterm (<37 weeks 0 days' gestation) and if unmeasured familial confounding explains these associations. Design, Setting, and Participants:Population-based retrospective cohort study using nationwide registries of all singleton live births in Finland surviving until 1 year and a within-sibpair comparison among term siblings. Children were born between January 1, 2006, and December 31, 2017, and followed up until December 31, 2017. Exposures:Maternal antenatal corticosteroid treatment. Main Outcomes and Measures:Primary outcome was any childhood mental and behavioral disorder diagnosed in public specialized medical care settings. Results:Of the 674?877 singleton children born in Finland during the study period, 670?097 were eligible for analysis. The median length of follow-up was 5.8 (interquartile-range, 3.1-8.7) years. Of the 14?868 (2.22%; 46.1% female) corticosteroid treatment-exposed children, 6730 (45.27%) were born at term and 8138 (54.74%) were born preterm; of the 655?229 (97.78%; 48.9% female) nonexposed children, 634?757 (96.88%) were born at term and 20?472 (3.12%) were born preterm. Among the 241?621 eligible term-born maternal sibpairs nested within this population, 4128 (1.71%) pairs were discordant for treatment exposure. Treatment exposure, compared with nonexposure, was significantly associated with higher risk of any mental and behavioral disorder in the entire cohort of children (12.01% vs 6.45%; absolute difference, 5.56% [95% CI, 5.04%-6.19%]; adjusted hazard ratio [HR], 1.33 [95% CI, 1.26-1.41]), in term-born children (8.89% vs 6.31%; absolute difference, 2.58% [95% CI, 1.92%-3.29%]; HR, 1.47 [95% CI, 1.36-1.69]), and when sibpairs discordant for treatment exposure were compared with sibpairs concordant for nonexposure (6.56% vs 4.17% for within-sibpair differences; absolute difference, 2.40% [95% CI, 1.67%-3.21%]; HR, 1.38 [95% CI, 1.21-1.58]). In preterm-born children, the cumulative incidence rate of any mental and behavioral disorder was also significantly higher for the treatment-exposed compared with the nonexposed children, but the HR was not significant (14.59% vs 10.71%; absolute difference, 3.38% [95% CI, 2.95%-4.87%]; HR, 1.00 [95% CI, 0.92-1.09]). Conclusions and Relevance:In this population-based cohort study, exposure to maternal antenatal corticosteroid treatment was significantly associated with mental and behavioral disorders in children. These findings may help inform decisions about maternal antenatal corticosteroid treatment.
| S-EPMC7237984 | biostudies-literature
Project description:ObjectiveTo determine the impact of maternal and fetal single nucleotide polymorphisms in key betamethasone pathways on neonatal outcomes.Study designDNA was obtained from women given betamethasone and their infants. Samples were genotyped for 73 exploratory drug metabolism and glucocorticoid pathway single nucleotide polymorphisms. Clinical variables and neonatal outcomes were obtained. Logistic regression analysis using relevant clinical variables and genotypes to model for associations with neonatal respiratory distress syndrome was performed.ResultsOne hundred nine women delivering 117 infants were analyzed. Sixty-four infants (49%) developed respiratory distress syndrome. Multivariable analysis revealed that respiratory distress syndrome was associated with maternal single nucleotide polymorphisms in CYP3A5 (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.30) and the glucocorticoid resistance (OR, 0.28; 95% CI, 0.08-0.95) and fetal single nucleotide polymorphisms in ADCY9 (OR, 0.17; 95% CI, 0.03-0.80) and CYP3A7*1E (rs28451617; OR, 23.68; 95% CI, 1.33-420.6).ConclusionMaternal and fetal genotypes are independently associated with neonatal respiratory distress syndrome after treatment with betamethasone for preterm labor.
| S-EPMC3340461 | biostudies-literature
Project description:Purpose: Evaluate fetal lung maturation and transcriptome after clinical treatment with antenatal corticosteroids compared to an alternative treatment with a slow release low-dose formulation. Methods: Lung mRNA profiles of rhesus macaques were generated by RNA sequencing. Reads that met quality thresholds were aligned to the rhesus macaque genome and number of reads per gene was counted. RNA-sequencing of the hippocampus was done. Differential expression analysis was done using read counts. Results: A relatively low dose of Beta-Ac increased lung compliance, surfactant concentration and relative airspace of the fetal lung equivalent to the clinical drug. By transcriptome analyses, the early suppression of genes associated with immune responses and the downregulation of genes associated with developmental pathways were less changed by Beta-Ac than the clinical drug. There were no significant differences between Beta-Ac and control while the clinical drug suppressed maturational pathways including genes involved in neurogenesis, neuronal differentiation and stem cell fate commitment. Conclusions: We report that low-dose betamethasone-acetate has decreased impact on lung transcriptome compared to the clinical treatment.
2019-06-21 | GSE118438 | GEO
Project description:Antenatal corticosteroid (AC) treatment is given to pregnant women at risk for preterm birth to reduce infant morbidity and mortality by enhancing lung and brain maturation. However, there is no accepted regimen on how frequently AC treatments should be given and some studies found that repeated AC treatments can cause growth retardation and brain damage. Our goal was to assess the dose-dependent effects of repeated AC treatment and estimate the critical number of AC courses to cause harmful effects on the auditory brainstem response (ABR), a sensitive measure of brain development, neural transmission and hearing loss. We hypothesized that repeated AC treatment would have harmful effects on the offspring's ABRs and growth only if more than 3 AC treatment courses were given. To test this hypothesis, pregnant Wistar rats were given either a high regimen of AC (HAC), a moderate regimen (MAC), a low regimen (LAC), or saline (SAL). An untreated control (CON) group was also used. Simulating the clinical condition, the HAC dams received 0.2mg/kg Betamethasone (IM) twice daily for 6 days during gestation days (GD) 17-22. The MAC dams received 3 days of AC treatment followed by 3 days of saline treatment on GD 17-19 and GD 20-22, respectively. The LAC dams received 1 day of AC treatment followed by 5 days of saline treatment on GD 17 and GD 18-22, respectively. The SAL dams received 6 days of saline treatment from GD 17 to 22 (twice daily, isovolumetric to the HAC injections, IM). The offspring were ABR-tested on postnatal day 24. Results indicated that the ABR's P4 latencies (neural transmission time) were significantly prolonged (worse) in the HAC pups and that ABR's thresholds were significantly elevated (worse) in the HAC and MAC pups when compared to the CON pups. The HAC and MAC pups were also growth retarded and had higher postnatal mortality than the CON pups. The SAL and LAC pups showed little or no adverse effects. In conclusion, repeated AC treatment had harmful effects on the rat offspring's ABRs, postnatal growth and survival. The prolonged ABR latencies reflect slowed neural transmission times along the auditory nerve and brainstem auditory pathway. The elevated ABR thresholds reflect hearing deficits. We concluded that repeated AC treatment can have harmful neurological, sensory and developmental effects on the rat offspring. These effects should be considered when weighing the benefits and risks of repeated AC treatment and when monitoring and managing the prenatally exposed child for possible adverse effects.
| S-EPMC3268869 | biostudies-other
Project description:ObjectivesThe primary aims of this study were to investigate if exposure to antenatal corticosteroids (ACS) was associated with lower rates of perinatal mortality (primary outcome) and other adverse perinatal outcomes (i.e., stillbirth, early neonatal mortality, APGAR score of < 7 at 5 mins, neonatal sepsis and respiratory distress syndrome) in preterm infants in hospitals in Tanzania. We also examine factors associated with administration of ACS among women at risk of preterm delivery.MethodsA hospital-based prospective chart review study was undertaken in four hospitals located in Nyamagana and Sengerema districts, Tanzania. The study population included all stillborn and live born preterm infants delivered between 24 to 34 weeks of gestation between July 2019 to February 2020. A total 1125 preterm infants were delivered by 1008 women (895 singletons, 230 multiple). Sociodemographic and medical data were recorded from participants' medical records.ResultsThree hundred and fifty-six (35.3%) women were administered at least one dose of ACS between 24 to 34 weeks' gestation and 385 (34.2%) infants were exposed to ACS. Infants exposed to ACS had a lower rate of perinatal mortality (13.77%) compared to those who were not exposed (28.38%). Multivariate analysis indicated that infants exposed to ACS were less likely to die during perinatal period, aRR 0.34 (95%CI 0.26-0.44). Only one-third of the sample was provided with ACS. Administration of ACS was associated with maternal education, attending antenatal care more than 3 times, method used to assess gestational age, maternal infection, exposure to maternal antibiotics, delivery mode and level of health facility.ConclusionACS significantly reduced the risk in perinatal mortality among infants born preterm in a limited resource setting. However, only about one-third of eligible women were provided with ACS, indicating low usage of ACS. Numerous factors were associated with low usage of ACS in this setting.
| S-EPMC8297919 | biostudies-literature
Project description:The intent of this National Institutes of Health-sponsored study was to compare a belatacept-based immunosuppressive regimen with a maintenance regimen of tacrolimus and mycophenolate. Nineteen primary, Epstein-Barr virus-immune renal transplant recipients with a negative cross-match were randomized to one of three groups. All patient groups received perioperative steroids and maintenance mycophenolate mofetil. Patients in groups 1 and 2 were induced with alemtuzumab and maintained on tacrolimus or belatacept, respectively. Patients in group 3 were induced with basiliximab, received 3 mo of tacrolimus, and maintained on belatacept. There was one death with a functioning allograft due to endocarditis (group 1). There were three graft losses due to vascular thrombosis (all group 2) and one graft loss due to glomerular disease (group 1). Biopsy-proven acute cellular rejection was more frequent in the belatacept-treated groups, with 10 treated episodes in seven participants compared with one episode in group 1; however, estimated GFR was similar between groups at week 52. There were no episodes of posttransplant lymphoproliferative disorder or opportunistic infections in any group. Protocol enrollment was halted prematurely because of a high rate of serious adverse events. Such negative outcomes pose challenges to clinical investigators, who ultimately must weigh the risks and benefits in randomized trials.
| S-EPMC5623170 | biostudies-literature