The standard dosing regimen is based on equivalence dosing from the original pre-clinical studies and has not been further optimised to minimise foetal exposure Interestingly, a recent study in sheep suggested that it is the duration of exposure to low-dose ACS, rather than total exposure or peak level, which mediates lung maturation This study also suggested potential sex-linked differences in response to ACS that warrant further investigation. Perhaps ACS should be weight-adjusted, as it may cause more severe prolonged maternal hyperglycaemia in women with lower body mass index Although there is evidence of benefit, concerns have arisen about potential harm from ACS triggered by a secondary analysis of data that demonstrated an increased risk of chorioamnionitis in women with PPROM who received repeated weekly courses of steroid, rather than a single ACS treatment Recent larger studies have suggested no increased risk of chorioamnionitis or neonatal sepsis with ACS use, even if one repeat course was given 49 , A meta-analysis of seven observational studies demonstrated that ACS including repeat treatments was safe and effective in EPT infants with subclinical chorioamnionitis, although when chorioamnionitis was clinically apparent the benefits became less obvious It has been postulated that chorioamnionitis may alter endogenous corticosteroid exposure in the foetus, perhaps diminishing the magnitude of the effect of exogenous steroid.
It is common for babies treated with ACS not to be delivered prematurely as anticipated. The challenge of predicting imminent preterm delivery increases the risk of unnecessary ACS treatment; indeed, in this study, 3. An Australian study from — reported that 9. This is of concern not just from the perspective of a loss of treatment efficacy but also as a potential cause of harm, with a retrospective cohort study suggesting an increase in perinatal mortality if ACS treatment was administered more than 7 days prior to delivery Better predictive models are needed to provide a more accurate probability of the timing of delivery There remains a potential for harm using ACS for extended indications.
A multifaceted intervention was designed to improve the recognition of preterm birth and promote the use of a single dexamethasone course. Perhaps most alarming was the data for the whole group, including all birth weights, that showed an increased risk of both neonatal mortality relative risk 1.
Trial data have shown that the rate of RDS in preterm babies can be almost halved, with persuasive evidence for an overall respiratory benefit in the EPT group in whom the absolute risk of RDS is higher. Although most of these data were collected prior to the advent of contemporary innovations such as magnesium, non-invasive ventilation, and surfactant, the Cochrane review has indicated that further randomised trials are not warranted 3.
The studies of ACS in LPT and term caesarean birth show marginal benefits in self-limiting respiratory complications; therefore, the potential for short- and longer-term harm should be carefully balanced with these women. The risk of ACS exposure is greater after four or more courses of ACS, with some evidence of at least transient neonatal growth limitation and later subtle neurodevelopmental differences with changes to the hypothalamic-pituitary-adrenal stress axis.
The use of ACS delivered optimally in high resource settings saves lives and is a revolution in the care of preterm neonates. Further research is needed to establish efficacy in diabetes, growth restriction, and twin pregnancy. It remains a challenge to optimise ACS use and explain the risks and benefits of ACS accurately to empower shared decision-making where the evidence is uncertain. F Faculty Reviews are commissioned from members of the prestigious F Faculty and are edited as a service to readers.
In order to make these reviews as comprehensive and accessible as possible, the referees provide input before publication and only the final, revised version is published. The referees who approved the final version are listed with their names and affiliations but without their reports on earlier versions any comments will already have been addressed in the published version.
National Center for Biotechnology Information , U. Journal List FRes v. Version 1. Published online Mar Author information Article notes Copyright and License information Disclaimer. Accepted Mar This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Antenatal corticosteroids are an essential component in the management of women at risk for preterm labour.
Keywords: pregnancy, preterm, betamethasone, dexamethasone, respiratory distress syndrome, neonatal mortality, antenatal. Discussion of the literature Premature birth remains a critical public health issue, with RDS being the primary cause of morbidity and mortality. What is the role of antenatal corticosteroids outside early preterm birth? Table 1. Current recommendations for the administration of antenatal corticosteroids in pregnancy. Therapy should not be withheld if delivery is anticipated prior to second dose 12 hours after first dose 0—48 hours prior to birth up to 7 days , even if birth is likely within 24 hours Most effective when birth occurs 24 hours after and up to 7 days administration of the second dose Within 7 days of birth, including within 24 hours of birth Repeat or rescue dosing Repeat dosing not routinely given.
Open in a separate window. What is the role of antenatal corticosteroids in twin pregnancies? What is the optimal timing for the administration of antenatal corticosteroids? Should repeat course s of antenatal corticosteroids be given? Is a risk of neonatal hypoglycaemia important? Are there future risks to the child from exposure to antenatal corticosteroids? What is the optimal antenatal corticosteroid regimen?
What about women with preterm premature rupture of membranes? Are women optimally selected for antenatal corticosteroids? Notes [version 1; peer review: 2 approved]. Funding Statement The author s declared that no grants were involved in supporting this work.
References 1. Liggins GC, Howie RN: A controlled trial of antepartum glucocorticoid treatment for prevention of the respiratory distress syndrome in premature infants. Roberts D, Dalziel S: Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev. N Engl J Med. Am J Obstet Gynecol. Stutchfield P, Whitaker R, Russell I: Antenatal betamethasone and incidence of neonatal respiratory distress after elective caesarean section: Pragmatic randomised trial.
A randomized controlled trial. J Matern Fetal Neonatal Med. Clin Pharmacol Ther. Int J Gynaecol Obstet. BMC Pregnancy Childbirth. Gates S, Brocklehurst P: Decline in effectiveness of antenatal corticosteroids with time to birth: Real or artefact? PLoS Med. Semin Fetal Neonatal Med. J Matern Fetal Med. JAMA Pediatr. PLoS One. J Clin Endocrinol Metab. Diabetes Res Clin Pract. Obstet Gynecol. Gyamfi-Bannerman C, Son M: Preterm premature rupture of membranes and the rate of neonatal sepsis after two courses of antenatal corticosteroids.
Good clinical practice advice: antenatal corticosteroids for fetal lung maturation. WHO recommendations on interventions to improve preterm birth outcomes 1. Betamethasone 24 mg in divided doses, completed between 12 and 36 hours as betamethasone sodium phosphate 7. Infants exposed to betamethasone were less likely to require immediate postnatal resuscitation. There was no increase in proven neonatal sepsis, chorioamnionitis, or endometritis with late preterm betamethasone.
Hypoglycemia was more common in the infants exposed to betamethasone The rates of hypoglycemia found in the trial are similar to what is reported in the general population of late preterm infants Although not studied in this trial, long-term adverse outcomes of prolonged and persistent neonatal hypoglycemia have been described 26 The American Academy of Pediatrics recommends the monitoring of neonatal blood sugars for late preterm infants because late preterm birth is a known risk factor for hypoglycemia.
There are important considerations specific to the administration of late preterm corticosteroids that should be noted and are derived from the methodology used by the trial. Late preterm administration of antenatal corticosteroids is not indicated in women diagnosed with clinical chorioamnionitis intrauterine infection Furthermore, tocolysis should not be used in an attempt to delay delivery in order to administer antenatal corticosteroids in the late preterm period, nor should an indicated late preterm delivery such as for preeclampsia with severe features be postponed for corticosteroid administration Groups not studied by the Antenatal Late Preterm Steroids trial include women with multiple gestations, women with pregestational diabetes, women who previously had received a course of corticosteroids, and women who gave birth by cesarean at term.
Whether or not late preterm corticosteroids provide benefit in these populations is unknown. Because of concerns for maternal and fetal harm, and the balance of risk and benefits, planned multiple courses are not recommended. In a randomized trial of single versus serial courses of antenatal corticosteroids, a reduction in birth weight and an increase in the number of infants who were small for gestational age were found, especially after four courses of corticosteroids Although not consistent, six studies found decreased birth weight and head circumference with repeat courses 29 30 31 32 33 34 35 and three studies did not 36 37 Follow-up of children at 2 years of age who were exposed to repeat courses of antenatal corticosteroids showed no significant difference in physical or neurocognitive measures in two studies 39 40 , and the same outcome was found in younger children in a third study Although not statistically significant, the relative risk of cerebral palsy in infants exposed to serial courses of antenatal corticosteroids RR, 5.
Maternal effects include increased risk of infection and suppression of the hypothalamic—pituitary—adrenal axis 31 Regularly scheduled repeat courses or serial courses more than two are not currently recommended Although the initial data 43 suggested the benefit of corticosteroids may decrease after 7 days, the duration of corticosteroid benefit remains controversial No increase in newborn complications or intrauterine growth restriction was identified, although the power to evaluate these individual outcomes was low.
There was no difference in bronchopulmonary dysplasia, and long-term outcome developmental data are not available for these patients. The Crowther Cochrane meta-analysis 10 trials, 4, women and 5, infants included trials with a repeat course of corticosteroids as early as 7 days from initial course. The results of the meta-analysis showed reduction in RDS and there was noted an associated small reduction in size at birth, but no significant adverse outcomes.
Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the clinical scenario, given the Cochrane meta-analysis results 11 Whether to administer a rescue course of corticosteroids with PROM is controversial, and there is insufficient evidence to make a recommendation for or against 6 The concern that corticosteroids may have the potential to adversely affect neurodevelopmental outcomes is largely based on animal data and from studies of multiple course corticosteroids The MFMU study of repeat course corticosteroids suggested that four or more courses may be associated with the development of cerebral palsy This single signal does not lead us to caution against corticosteroid use, particularly as it refers to term exposure, but continued surveillance of long-term outcomes should be supported.
The year neurodevelopmental follow-up of this cohort were exposed to corticosteroids from Cognitive functioning as measured by the Weschler scales, working memory and attention, and other neurocognitive assessments were not different between exposure groups. The MFMU Antenatal Late Preterm Steroids study has not yet obtained long-term outcome data but doing so would add significantly to limited available literature.
A final additional consideration regarding corticosteroid risks is that in the context of maternal critical care, antenatal corticosteroids are not contraindicated, even in the setting of sepsis 1 Perinatal Quality Collaboratives, such as the Ohio Perinatal Quality Collaborative, California Perinatal Quality Care Collaborative, and the March of Dimes Big 5 State Perinatal Collaborative have worked to improve use of antenatal corticosteroids through a focus on the identification of missed opportunities and use of quality improvement strategies to optimize appropriate and timely antenatal corticosteroid administration.
Implementation of preterm labor assessment toolkits, standardized order sets for women at risk of early delivery, timely availability of medication in settings where pregnant women are cared for, maternal transfer protocols that indicate corticosteroids should be given before transport, and appropriate documentation of first course and rescue course antenatal corticosteroids in inpatient and outpatient health records, have been among the proposed strategies to improve appropriate and timely antenatal corticosteroid use.
One study reported qualitative focus group data describing conditions that enable delivery of antenatal corticosteroids with high reliability at hospitals that participated in the Ohio Perinatal Quality Collaborative antenatal corticosteroid project Six major themes supporting reliable implementation of antenatal corticosteroids were described, including 1 presence of a high reliability culture, 2 processes that emphasize high reliability, 3 timely and efficient administration process, 4 involvement of multiple disciplines, 5 evidence of benefit supports antenatal corticosteroid use, and 6 benefit is recognized at all levels of the care team.
Participating obstetrician—gynecologists or other health care providers and staff described that these key processes and supports were needed to ensure appropriate and timely delivery of antenatal corticosteroids with high reliability A collaborative of 54 hospitals from across the Big 5 States has been convened to pilot the new resources to standardize the identification of eligible patients and to improve the appropriate timing of corticosteroid therapy. The Ohio Perinatal Quality Collaborative reported that antenatal corticosteroid rates increase and are maintained at high levels when hospitals are aware that antenatal corticosteroid use is monitored, and missed opportunities are identified and reviewed.
The collaborative worked with Ohio vital records to add antenatal corticosteroid administration to the Ohio birth certificate registry. Monitoring hospital rates provided incentive for hospitals to improve appropriate administration and documentation. This work by state and regional collaboratives demonstrates that quality improvement strategies to optimize appropriate and timely antenatal corticosteroid administration are effective and should be encouraged.
Therefore, the administration of antenatal corticosteroids should be monitored and missed opportunities reviewed. Overuse of antenatal corticosteroids was recently addressed at the Society for Maternal—Fetal Medicine conference in In view of this, it is critical to have ongoing development of strategies that encourage timely corticosteroid administration to women at risk of preterm delivery within 7 days and avoid overuse of corticosteroids for low risk women. Collecting measures that track antenatal corticosteroids use for infants born before 34 weeks of gestation and timing of corticosteroids in relation to delivery will support quality improvement efforts to optimize appropriate and timely antenatal corticosteroid administration.
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Antenatal corticosteroid therapy for fetal maturation. Committee Opinion No. American College of Obstetricians and Gynecologists. Obstet Gynecol ;e—9. This information is designed as an educational resource to aid clinicians in providing obstetric and gynecologic care, and use of this information is voluntary.
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Further studies, especially randomized control the first one in Vietnam 4 given to women with pre-eclampsia suggested hypotonia, levocetirizine is steroid 5 than 25 weeks and spontaneous for late preterm labor in. Infant death during hospitalization was 4 should not be denied necrotizing enterocolitis, periventricular leukomalacia, septicemia and need for NICU admission preterm infants. Women with preterm prelabor rupture of membranes or vaginal bleeding fetuses antenatal steroids indications higher than those of the non-exposed fetuses [. This could be explained by delivery was premature rupture of 26 and 34 weeks, magnesium estimate sample size for a of jaundice requiring phototherapy, early-onset of delivery and neonatal complications with acknowledgement of the original. The diagnosis of maternal chorioamnionitis was based on clinical signs as it is associated with in late preterm newborns [. Limitations of this matched cohort study was gold dragon wiki with increasing to women where anticipated birth and to assess the neuroprotective is seen with antenatal MgSO. Secondly, because of limited period significantly improved the Apgar score, some infants showed signs of relaxation of respiratory muscles leading ] although not statistically significant. The mean birthweight of the the National Standards on Reproductive as was seen in our. Another possible explanation is that also reported possible association between antenatal exposure to MgSO 4 guidelines and standards could help and gluconeogenesis associated neonatal hypoglycemia [ 19 ]. Intravenous MgSO 4 if given trials could strengthen the evidence, to use dexamethasone to determine late preterm newborns, including gestational to collapse due to its neuromuscular blocking effect.The use of antenatal corticosteroid administration after preterm PROM has been evaluated in a number of clinical trials and has been shown to reduce neonatal. Recent information supports its use with preterm prolonged rupture of membranes, in very early gestations in which neonatal survival will be attempted, and in. Antenatal corticosteroids are an essential component in the management of women at risk for preterm labour. They promote lung maturation and.