Course Of Antenatal Glucocorticoids Research Articles

Real-life experience with antenatal glucocorticoid administration in premature pregnancies complicated by diabetes mellitus

Background: Diabetes mellitus (DM) in pregnancy is associated with an increased risk of premature birth, which therefore increases the risk of acute respiratory distress syndrome (ARDS) of the neonate and is associated with high morbidity and mortality of the newborn. The administration of glucocorticoids to the mother before premature birth decreases the risk of neonatal complications. However, the data regarding the administration of this therapy to mothers with DM is limited. Clinical guidelines recommend treating them in the same manner as the non-DM women, even if there is no recent data to support the benefit in this subpopulation. The aim of this study is to evaluate the real-life effects of glucocorticoid administration on the maternal and fetal prognosis of pregnancies complicated with DM. Material and methods: A retrospective study was conducted on 67 pregnant females who were admitted to the Obstetrics & Gynecology Department of The Emergency University Hospital of Bucharest between December 2016–March 2021, and who received corticosteroid before prematurely giving birth to 70 newborns. There was a group of 33 mothers with DM and a second group with 34 non-DM pregnant women selected for control of glucocorticoids’ real-life administration in the high risk for premature birth population. Results: The administration of glucocorticoids was not restricted by the presence of DM; 78% of the mothers with DM and 79.41% of the mothers without DM received one course of antenatal glucocorticoids for fetal lung maturation (p = 0.6). The incidence of ARDS differs between groups was statistically insignificant: 35.29% in the DM group versus 30.55% in the control group (p = 0.8). There were similar cases of maternal complications such as pregnancy-induced hypertension (PIH), or preeclampsia in the two groups. These findings suggest that glucocorticoid therapy is effective for premature newborns from pregnancies with DM and does not negatively impact the complication rate of the mothers, sustaining their administration in these cases. Conclusions: The administration of antenatal glucocorticoids before premature birth is not influenced by the presence of DM regarding Apgar score at 1 and 5 minutes, the incidence of ARDS, but there were differences such as more large for gestational age (LGA) newborns and neonatal hypoglycemia in the DM group. Considering the low number of patients enrolled from a single-center, future multicentric studies are needed. It is important to emphasize that this study’s findings reflect the local practice and cannot be generalized.

Repeat doses of antenatal betamethasone and risk factors for cardiometabolic disease at early school age.

Commentary on: McKinlay CJ, Cutfield WS, Battin MR, Dalziel SR, Crowther CA, Harding JE, ACTORDS Study Group. Cardiovascular risk factors in children after repeat doses of antenatal glucocorticoids: an RCT. Pediatrics 2015; 135: e405–15. McKinlay et al. 1 provides new evidence regarding some aspects of long-term safety with the use of repeated courses of antenatal corticosteroids. The original aim of the ACTORDS study was to evaluate short-term outcomes, and it has shown reduced neonatal morbidity after repeated courses of antenatal corticosteroids without an associated increase in neurologic disability at two years of corrected age or at mid-childhood 2. In the context of cardiometabolic health, the associations between preterm birth and later hypertension, diabetes, stroke and even death from cardiovascular disease 3 – boosted by animal data – have generated worries about glucocorticoid exposure in foetal life, especially if repeated. The central worry is that this glucocorticoid exposure might be in the causal pathway towards cardiometabolic disease in adult life. Previously, there had been some conflicting observational data 4-9. The long-term evaluation by McKinlay et al. carries an important message; that is, there were no adverse cardiovascular and metabolic outcomes in children exposed to repeat dose(s) of antenatal betamethasone. Although reassuring, there are some, as always, remaining questions and limitations. First, extremely preterm infants were few in the ACTORDS study. The average gestational age at study entry was >28 weeks. It cannot be excluded that extremely low gestational age at exposure may exert long-standing effects on glucose metabolism. Secondly, although six to eight years of follow-up most be considered as long term from a neonatologist's perspective, it may be too short for the outcomes addressed. Finally, the authors state that they will report other outcomes separately. These include neurologic function, lung function, general intellectual ability, specific cognitive skills, behaviour, general health and health-related quality of life. I look forward to coming reports. So what should the attending obstetrician and neonatologist recommend? The latest Cochrane review of 10 randomised trials comparing single and repeat courses of antenatal glucocorticoids for neonatal morbidity favours repeat courses. And although repeated courses have been associated with lower birthweight and small reductions in head circumference, data on long-term safety outcomes are so far generally reassuring 2. According to ACOG present guidelines, a single rescue course of antenatal corticosteroids may be considered if the antecedent treatment was given more than two weeks prior, the gestational age is less than 32 weeks and the women are judged by the clinician to be likely to give birth within the next week. The ACTORDS follow-up studies – the one reviewed herein and others 2 – add further support for such recommendation. https://ebneo.org/2015/05/repeat-doses-of-antenatal-betamethasone-and-risk-factors-for-cardio-metabolic-disease-at-early-school-age/ None. None.

Antenatal glucocorticoids and neonatal inflammation-associated proteins

BackgroundTo date, studies of the relationship between antenatal glucocorticoids (AGC) and neonatal inflammation in preterm newborns have been largely limited to umbilical cord blood specimens. AimTo explore the association between exposure to antenatal glucocorticoids and concentrations of inflammation-related proteins in whole blood collected from very preterm newborns at multiple times during the first postnatal month. MethodsWe measured the protein concentrations on postnatal day 1 (N=1118), day 7 (N=1138), day 14 (N=1030), day 21 (N=936) and day 28 (N=877) from infants born before the 28th week of gestation and explored the relationship between antenatal steroid receipt and protein concentrations in the highest and lowest quartiles. The creation of multinomial logistic regression models (adjusted for potential confounders) allowed us calculate odds ratios and 95% confidence intervals. ResultsTwenty of 420 assessments [21 (proteins)×2 (exposure levels: partial and full)×2 (quartile levels: top and bottom)×5 (days)] were statistically significant without any cohesive pattern. ConclusionAmong infants born before 28 weeks of gestational age, neither full, nor partial courses of antenatal glucocorticoids have a sustained anti-inflammatory effect.

Antenatal corticosteroids alter insulin signaling pathways in fetal baboon skeletal muscle.

We hypothesize that prenatal exposure to glucocorticoids (GCs) negatively alters the insulin signal transduction pathway and has differing effects on the fetus according to gestational age (GA) at exposure. Twenty-three fetal baboons were delivered from 23 healthy, nondiabetic mothers. Twelve preterm (0.67 GA) and 11 near-term (0.95 GA) baboons were killed immediately after delivery. Half of the pregnant baboons at each gestation received two doses of i.m. betamethasone 24 h apart (170 μg/kg) before delivery, while the other half received no intervention. Vastus lateralis muscle was obtained from postnatal animals to measure the protein content and gene expression of insulin receptor β (IRβ; INSR), IRβ Tyr 1361 phosphorylation (pIRβ), IR substrate 1 (IRS1), IRS1 tyrosine phosphorylation (pIRS1), p85 subunit of PI3-kinase, AKT (protein kinase B), phospho-AKT Ser473 (pAKT), AKT1, AKT2, and glucose transporters (GLUT1 and GLUT4). Skeletal muscle from preterm baboons exposed to GCs had markedly reduced protein content of AKT and AKT1 (respectively, 73 and 72% from 0.67 GA control, P<0.001); IRβ and pIRβ were also decreased (respectively, 94 and 85%, P<0.01) in the muscle of premature GC-exposed fetuses but not in term fetuses. GLUT1 and GLUT4 tended to increase with GC exposure in preterm animals (P=0.09), while GLUT4 increased sixfold in term animals after exposure to GC (P<0.05). In conclusion, exposure to a single course of antenatal GCs during fetal life alters the insulin signaling pathway in fetal muscle in a manner dependent on the stage of gestation.

Exposure to repeat doses of antenatal glucocorticoids is associated with altered cardiovascular status after birth

Objective: To determine if exposure to more than one course of antenatal glucocorticoids is associated with changes in infant blood pressure and myocardial wall thickness in the first month after...

Antenatal Glucocorticoids Increase Early Total Thyroxine Levels in Premature Infants

Background: Hypothyroxinemia is associated with adverse neonatal outcomes including white matter damage, cerebral palsy, poor neurodevelopment and death. It has become increasingly important to understand the natural history and modifiers of thyroid function in the premature infant. It is standard obstetrical practice to offer antenatal glucocorticoids to pregnant women with threatened preterm delivery. Few studies have investigated the effect of antenatal glucocorticoids on neonatal thyroid function. Objective: To examine the association between antenatal exposure to glucocorticoids and early total thyroxine (T4) levels among extremely premature infants. Methods: We studied 521 infants born at 4 medical centers. Entry criteria included a gestational age of 23–28 weeks and a serum thyroxine level obtained in the first postnatal week. Receipt of antenatal glucocorticoids was recorded as none, partial, or complete. A complete course consisted of two doses of betamethasone or four doses of dexamethasone within a 48-hour period between 2 and 7 days of delivery. Early total T4 levels were obtained from state-mandated newborn screening programs. Results: Controlling for potential maternal, perinatal and neonatal confounding variables, infants exposed to a complete course of antenatal glucocorticoids had total T4 levels 0.8 µg/dl higher than their peers who were not exposed to a complete course of antenatal glucocorticoids (p = 0.03). Conclusions: Extremely premature infants who received a complete course of antenatal glucocorticoids had significantly higher total thyroxine levels in the first postnatal week. Maternal, perinatal, and early neonatal variables did not completely explain this association. We speculate that antenatal glucocorticoids influence early neonatal thyroid function.

Brain injury in preterm infants—what can the obstetrician do?

Mothers at increased risk of preterm birth often receive glucocorticoids (GC), antibiotics and tocolytics by the obstetrician but the question is whether such interventions affect the risk of brain injury and neurological outcome. We suggest that one single course of antenatal GC is the most important treatment that can be offered to patients at risk of preterm birth at 24–34 weeks of gestation to prevent brain injury. Betamethasone seems advantageous to dexamethasone and repeated courses of GC should probably be avoided. Antibiotics given to patients with preterm premature rupture of membranes reduce neonatal morbidity and decrease the risk of sonographic cerebral abnormalities even though the effect on long-term neurological outcome is uncertain. From the perspective of the immature CNS, there is no evidence for treatment with tocolytics even though it allows transfer of the patient to a tertiary center and increases the likelihood of administration of a complete course of corticosteroids which may affect outcome.

Perinatal glucocorticoid therapy and neurodevelopmental outcome: an epidemiologic perspective

A relatively brief course of antenatal glucocorticoids (ACS), given to reduce the severity of respiratory distress syndrome in preterm infants, improves survival and appears to protect against brain damage. In clinical trials as well as observational studies, ACS have been associated with a decreased risk of intraventricular haemorrhage and cerebral palsy. In observational studies a decreased risk of white-matter damage, identified with cranial ultrasound, has been observed. There is some evidence, from observational studies, that repeated courses of ACS (typically given at weekly intervals) can reduce the rate of fetal head growth, and experiments in animals provide further support for this possibility. In contrast to the effects of a brief course of ACS, postnatal glucocorticoids (PCS), given to preterm infants to reduce the severity of chronic lung disease have been associated with an increased risk of neurologic impairment. Available evidence suggests that PCS does not improve survival. Further study is needed of the neurodevelopmental consequences of both multiple courses of ACS, as well as PCS.

Lung maturation therapy with glucocorticoids in threatened premature labor. Considerations of risk-benefit in evidence-based medicine

Prematurity is a major cause of perinatal morbidity and mortality. Antenatal administration of glucocorticoids improves the neonatal outcome of preterm born infants. 1994 the NIH published recommendations for the use of glucocorticoids for women at risk of preterm delivery. A recent evaluation by the Cochrane Collaboration in 1999 showed that antenatal administration of glucocorticoids significantly reduced the rate of RDS and IVH in the gestational age between 24 and 34 weeks. Consequences of repeated courses of antenatal glucocorticoids are not sufficiently studied. The effectivity and safety regarding birth weights, infectious diseases, and the best timing remains unknown. Administration of glucocorticoids lowers fetal activity and heart rate variability. Effects on fetal growth, maternal and fetal immunosystem, and the development of atopic diseases are controversely discussed. Thus preterm labour not leading to a cervical ripening is not necessarily a reason for antenatal glucocorticoids. Antenatal glucocorticoids with PROM do not lower the rate of RDS but of IVH. No prospective randomized trial evaluated the effectivity of antenatal glucocorticoids in diabetes mellitus and IUGR. In preeclampsia beta-methason could improve the rate of RDS and the neonatal outcome. Still our knowledge of antenatal glucocorticoid administration is not sufficient. But despite possible (longtime-) risks for mother and child the administration of glucocorticoids according to the guidelines of the NIH is a major part in the treatment of prematurity and improves the outcome of premature infants. The indication for multiple courses of glucocorticoids should be considered carefully.

Effects of Single and Multiple Courses of Antenatal Glucocorticoids in Preterm Newborns Less Than 30 Weeks??? Gestation

Background: We compared outcomes between neonates receiving either single course, multiple courses, or no antenatal glucocorticoid exposure.Methods: We retrospectively identified neonates whose mothers received a single course (SIN) of dexamethasone, multiple (2-3) weekly courses (MULT), or no (NO) glucocorticoids. Multiple gestations and infants with chromosomal abnormalities or not receiving a full course of antenatal dexamethasone were excluded from the study. The incidences of the following outcomes were examined: respiratory distress syndrome (RDS), Grades III or IV intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, and in-hospital death. Means were compared with analysis of variance and outcome variable frequencies with chi-square test.Results: A total of 147 infants were included in the analysis. There were no differences in the gestational age or growth parameters among the groups. As anticipated, infants ...

Effects of single and multiple courses of antenatal glucocorticoids in preterm newborns less than 30 weeks' gestation.

We compared outcomes between neonates receiving either single course, multiple courses, or no antenatal glucocorticoid exposure. We retrospectively identified neonates whose mothers received a single course (SIN) of dexamethasone, multiple (2-3) weekly courses (MULT), or no (NO) glucocorticoids. Multiple gestations and infants with chromosomal abnormalities or not receiving a full course of antenatal dexamethasone were excluded from the study. The incidences of the following outcomes were examined: respiratory distress syndrome (RDS), Grades III or IV intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, and in-hospital death. Means were compared with analysis of variance and outcome variable frequencies with chi-square test. A total of 147 infants were included in the analysis. There were no differences in the gestational age or growth parameters among the groups. As anticipated, infants exposed to antenatal glucocorticoids had a significantly lower incidence of morbidities (BPD, NEC, and IVH) than the unexposed infants. There were no differences in the incidence of RDS, IVH, BPD, NEC, ROP, PDA, sepsis, or death between the SIN and MULT groups. A single course of antenatal glucocorticoid therapy is associated with improved neonatal outcomes in infants less than 30 weeks' gestation. Multiple courses were not shown to confer additional benefits, but further investigation is required to definitively address the need for weekly treatment.

Effects of single and multiple courses of antenatal glucocorticoids in preterm newborns less than 30 weeks' gestation

Background We compared outcomes between neonates receiving either single course, multiple courses, or no antenatal glucocorticoid exposure. Methods We retrospectively identified neonates whose mothers received a single course (SIN) of dexamethasone, multiple (2–3) weekly courses (MULT), or no (NO) glucocorticoids. Multiple gestations and infants with chromosomal abnormalities or not receiving a full course of antenatal dexamethasone were excluded from the study. The incidences of the following outcomes were examined: respiratory distress syndrome (RDS), Grades III or IV intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), sepsis, and in-hospital death. Means were compared with analysis of variance and outcome variable frequencies with chi-square test. Results A total of 147 infants were included in the analysis. There were no differences in the gestational age or growth parameters among the groups. As anticipated, infants exposed to antenatal glucocorticoids had a significantly lower incidence of morbidities (BPD, NEC, and IVH) than the unexposed infants. There were no differences in the incidence of RDS, IVH, BPD, NEC, ROP, PDA, sepsis, or death between the SIN and MULT groups. Conclusion A single course of antenatal glucocorticoid therapy is associated with improved neonatal outcomes in infants less than 30 weeks' gestation. Multiple courses were not shown to confer additional benefits, but further investigation is required to definitively address the need for weekly treatment. J. Matern.-Fetal Med. 2000; 9:131–135. © 2000 Wiley-Liss, Inc.

Effects of Single and Multiple Courses of Antenatal Glucocorticoids in Preterm Newborns Less Than 30 Weeks' Gestation

Effects of Single and Multiple Courses of Antenatal Glucocorticoids in Preterm Newborns Less Than 30 Weeks' Gestation

Fetal Versus Maternal and Gestational Age Effects of Repetitive Antenatal Glucocorticoids

Background. Although single courses of antenatal glucocorticoids decrease respiratory distress syndrome and mortality, repetitive courses of antenatal glucocorticoids are being given to women at risk of preterm delivery without evidence of benefit or appreciation of potential risks. Objectives. To evaluate the effects of single and repetitive antenatal glucocorticoid exposures on fetal growth and postnatal lung function in sheep. Methods. Pregnant ewes were randomized to three protocols that included one or three doses (at 7-day intervals) of 0.5 mg/kg of betamethasone (β) given to the ewe or fetus beginning at gestations ranging from 104 to 128 days9 gestation with delivery at 125, 135, and 146 days9 gestation. Postnatal assessments included measurements of gas exchange, compliance, ventilation efficiency, static lung volume, and lung tissue and alveolar wash saturated phosphatidylcholine. Results. Single or repetitive maternal β but not fetal β caused fetal growth retardation at delivery at 125, 135, and 146 days9 gestation. Single-dose fetal β had no effect on postnatal lung function whereas single-dose maternal β significantly increased compliance, lung volume, and tissue and alveolar surfactant after preterm delivery. Although three-dose fetal β improved all indicators of postnatal lung function, three-dose maternal β resulted in larger responses. The added benefits of repetitive β relative to a single-dose β on postnatal lung function after preterm delivery were not as great when therapy was begun later in gestation. Postnatal lung function after delivery at 146 days9 gestation (term is 150 days) was improved after repetitive maternal β at early gestational age. Conclusions. In sheep, single or repetitive maternal β causes growth retardation from 104 to 121 days9 gestation and the growth retardation persists to term. In contrast, single or repetitive fetal β does not cause fetal growth retardation and is less potent at improving postnatal lung function and increasing surfactant pools. There are potential benefits as well as risks for the use of repetitive antenatal glucocorticoids. Randomized, controlled trials in humans are essential given the widespread use of repetitive courses of antenatal glucocorticoids in women at risk of preterm delivery. respiratory distress syndrome, maturation, prematurity, growth retardation, surfactant.

Fetal versus maternal and gestational age effects of repetitive antenatal glucocorticoids.

Although single courses of antenatal glucocorticoids decrease respiratory distress syndrome and mortality, repetitive courses of antenatal glucocorticoids are being given to women at risk of preterm delivery without evidence of benefit or appreciation of potential risks. To evaluate the effects of single and repetitive antenatal glucocorticoid exposures on fetal growth and postnatal lung function in sheep. Pregnant ewes were randomized to three protocols that included one or three doses (at 7-day intervals) of 0.5 mg/kg of betamethasone (beta) given to the ewe or fetus beginning at gestations ranging from 104 to 128 days' gestation with delivery at 125, 135, and 146 days' gestation. Postnatal assessments included measurements of gas exchange, compliance, ventilation efficiency, static lung volume, and lung tissue and alveolar wash saturated phosphatidylcholine. Single or repetitive maternal beta but not fetal beta caused fetal growth retardation at delivery at 125, 135, and 146 days' gestation. Single-dose fetal beta had no effect on postnatal lung function whereas single-dose maternal beta significantly increased compliance, lung volume, and tissue and alveolar surfactant after preterm delivery. Although three-dose fetal beta improved all indicators of postnatal lung function, three-dose maternal beta resulted in larger responses. The added benefits of repetitive beta relative to a single-dose beta on postnatal lung function after preterm delivery were not as great when therapy was begun later in gestation. Postnatal lung function after delivery at 146 days' gestation (term is 150 days) was improved after repetitive maternal beta at early gestational age. In sheep, single or repetitive maternal beta causes growth retardation from 104 to 121 days' gestation and the growth retardation persists to term. In contrast, single or repetitive fetal beta does not cause fetal growth retardation and is less potent at improving postnatal lung function and increasing surfactant pools. There are potential benefits as well as risks for the use of repetitive antenatal glucocorticoids. Randomized, controlled trials in humans are essential given the widespread use of repetitive courses of antenatal glucocorticoids in women at risk of preterm delivery. respiratory distress syndrome, maturation, prematurity, growth retardation, surfactant.

Maternal Glucocorticoid Therapy and Reduced Risk of Bronchopulmonary Dysplasia

Because of substantial clinical and laboratory evidence of the efficacy of glucocorticoids in the treatment of acute pulmonary surfactant deficiency in preterm newborns, we explored the hypothesis that maternal antenatal glucocorticoid receipt is followed by reduced risk of bronchopulmonary dysplasia (BPD). A sample of 223 intubated infants weighing less than 1751 g birth weight provided 76 infants with BPD (defined by both oxygen requirement and compatible chest radiograph) and 147 who had neither BPD characteristic by day 28 of life. When compared to babies who received a complete and timely course of antenatal glucocorticoids, those whose mothers received no glucocorticoids were at prominently increased risk of BPD (odds ratio = 3.0; 95% confidence interval = 1.1, 8.2). Babies whose mothers received a partial course of glucocorticoids were not at increased risk of BPD (odds ratio = 1.3; 95% confidence interval = 0.4, 4.3). Stratification by gender and birth weight at 1 kg showed a benefit of therapy in all strata except that of extremely low birth weight male infants. These data support the hypothesis that maternal antenatal glucocorticoid therapy offers very low birth weight infants protection against BPD.