Association of antenatal corticosteroids with morbidity and mortality among preterm multiple gestations: meta-analysis of observational studies.
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ABSTRACT: Objective
This meta-analysis aimed to assess the efficacy of antenatal corticosteroids (ACS) on morbidity and mortality among preterm multiple pregnancies.Methods
The PubMed, Embase, Web of Science and Cochrane Library databases were searched for studies investigating the outcomes among preterm multiple gestations following to ACS, from their inception to 1 November 2020. Two authors independently performed the study selection, risk of bias assessment and data extraction. The primary outcomes were respiratory distress syndrome (RDS) and mortality and secondary outcomes included intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), necrotising enterocolitis, retinopathy of prematurity and bronchopulmonary dysplasia. Pooled ORs were obtained using random effects models. Subgroup analyses were performed to explain heterogeneity by ACS completeness, administration-to-delivery intervals (≤7 days) and single or multicentre.Results
A total of 16 observational studies with 36 973 newborns were included in the meta-analysis. ACS treatment was associated with a reduction in RDS (OR 0.66; 95% CI 0.54 to 0.82; I2=91.4%; p<0.001), mortality (OR 0.64; 95% CI 0.50 to 0.81; I2=85.9%; p<0.001), IVH (OR 0.67; 95% CI 0.54 to 0.83; I2=77.4%; p<0.001) and PVL (OR 0.65; 95% CI 0.47 to 0.92; I2=75.5%; p<0.001). Subgroup analyses showed ACS completeness, administration-to-delivery interval and multicentre study affected these associations.Discussion
ACS may be beneficial for reducing the risks of RDS, mortality, IVH and PVL among preterm multiple gestations. The efficacy of ACS could be affected by ACS completeness and administration-to-delivery. More robust evidence on the efficacy of ACS treatment among multiple gestations is warranted.
SUBMITTER: Lin D
PROVIDER: S-EPMC8477320 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceLittle is known about the effects of antenatal corticosteroids (ANS) on extremely preterm multiples.ObjectiveTo examine if use of ANS is associated with improvement in major outcomes in extremely preterm multiples.Design, setting, and participantsInfants with a gestational age between 22 and 28 weeks born at a National Institute of Child Health and Human Development Neonatal Research Network center were studied between January 1998 and December 2013. Generalized estimating equation models were used to generate adjusted relative risks (aRR) controlling for important maternal and neonatal variables.ExposureAntenatal corticosteroids.Main outcomes and measuresIn-hospital mortality and the composite outcome of neurodevelopmental impairment at 18 to 22 months' corrected age or death before assessment.ResultsA total of 6925 multiple-birth infants were studied; 5775 of 6925 (83.4%) were twins, and 4276 (61.7%) were white. Of the total study population, 6094 (88%) were born to women who received ANS. In-hospital mortality was lower among infants with exposure to ANS vs no exposure (aRR = 0.87; 95% CI, 0.78-0.96). Neurodevelopmental impairment or death was not significantly lower among those exposed to ANS vs no exposure (aRR = 0.93; 95% CI, 0.84-1.03). Other adverse outcomes that occurred less frequently among infants of women receiving ANS included severe intraventricular hemorrhage (aRR = 0.68; 95% CI, 0.58-0.78) and the combined outcomes of necrotizing enterocolitis or death and severe intraventricular hemorrhage or death. Subgroup analyses indicated that exposure to ANS was associated with a lower risk of mortality and a lower composite of neurodevelopmental impairment or mortality among nonsmall for gestational age multiples (aRR = 0.82; 95% CI, 0.74-0.92; and aRR = 0.89; 95% CI, 0.80-0.98, respectively) and a higher risk among small for gestational age multiples (aRR = 1.40; 95% CI, 1.02-1.93; and aRR = 1.62; 95% CI, 1.22-2.16, respectively). Antenatal corticosteroids were associated with higher neurodevelopmental impairment or mortality among multiple-birth infants of mothers with diabetes (aRR = 1.55; 95% CI, 1.00-2.38) but not among infants of mothers without diabetes (aRR = 0.91; 95% CI, 0.83-1.01).Conclusions and relevanceCompared with no exposure, exposure to ANS was associated with a lower risk of mortality in extremely preterm multiples, with no significant differences in the composite of neurodevelopmental impairment or death. Future research should investigate the increased risks of mortality and the composite of neurodevelopmental impairment or death associated with exposure to corticosteroids among small for gestational age multiples.
| S-EPMC5270648 | biostudies-literature
Project description:BackgroundIn 2016, the American College of Obstetricians and Gynecologists recommended antenatal corticosteroids in the late preterm period for women at risk for preterm delivery. Limited real-world evidence exists on neonatal outcomes, particularly for twin gestations, following the guideline change. The study objective is to determine the association of antenatal corticosteroids in late preterm singleton and twin pregnancies with respiratory complications and hypoglycemia in a real-world clinical setting.MethodsThis is a retrospective cohort study comprising late preterm deliveries (4,341 mother-child pairs) within the Mount Sinai Health System, 2012-2018. The exposure of interest is antenatal corticosteroid administration of betamethasone during pregnancy between 34 0/7 and 36 6/7 weeks. Our primary outcomes are neonatal respiratory complications and hypoglycemia. Multivariable logistic regression was used to estimate the association between antenatal corticosteroid exposure and these two outcomes. We stratified the study population by singleton gestations and twins to minimize the potential confounding from different obstetric management between the two groups.ResultsAmong a total of 4,341 mother-child pairs (3,309 singleton and 1,032 twin mother-child pairs), 745 mothers received betamethasone, of which 40.94% (305/745) received the full course. Relative to no treatment, a full course of betamethasone was associated with reduced odds of respiratory complications (OR = 0.53, 95% CI:[0.31-0.85], p < 0.01) and increased odds of hypoglycemia (OR = 1.86, 95%CI:[1.34-2.56], p < 0.01) in singletons; however, the association with respiratory complications was not significant in twins (OR = 0.42, 95% CI:[0.11-1.23], p = 0.16), but was associated with increased odds of hypoglycemia (OR = 2.18, 95% CI:[1.12-4.10], p = 0.02). A partial course of betamethasone (relative to no treatment) was not significantly associated with any of the outcomes, other than respiratory complications in twins (OR = 0.34, 95% CI:[0.12-0.82], p = 0.02).ConclusionsExposure to antenatal corticosteroids in singletons and twins is associated with increased odds of hypoglycemia. Among singletons, exposure to the full dosage (i.e. two doses) was associated with decreased odds of respiratory complications but this was only the case for partial dose among twins. Twin gestations were not studied by the Antenatal Late Preterm Steroids trial. Therefore, our study findings will contribute to the paucity of evidence on the benefit of antenatal corticosteroids in this group. Health systems should systematically monitor guideline implementations to improve patient outcomes.
| S-EPMC9721054 | biostudies-literature
Project description:ObjectiveThe objective of this study was to determine whether antenatal corticosteroid exposure has a differential association with preterm neonatal morbidity among women with and without diabetes.Study designSecondary analysis of an observational cohort of 115,502 women and their neonates born in 25 U.S. hospitals (2008-2011). Women who delivered at 230/7 to 336/7 weeks' gestation and received antenatal corticosteroids were compared with those who did not receive antenatal corticosteroids. Women with a stillbirth and women who delivered a neonate that was not resuscitated were excluded. The primary outcome was neonatal respiratory distress syndrome or death within 48 hours. Secondary outcomes included composite neonatal morbidity (respiratory distress syndrome, necrotizing enterocolitis, grades 3-4 intraventricular hemorrhage, sepsis, or death) and mechanical ventilation. Multivariable modified Poisson regression was used to estimate the association between antenatal corticosteroid exposure and neonatal outcomes. Maternal diabetes (pregestational and gestational) was evaluated as a potential effect modifier, and sensitivity analyses were conducted to evaluate whether receipt of a partial, single, or multiple course(s) of antenatal corticosteroids influenced results.ResultsA total of 4,429 women with 5,259 neonates met inclusion criteria: 3,716 (83.9%) women received antenatal corticosteroids and 713 (16.1%) did not. Of the 510 diabetic women (181 pregestational and 329 gestational), 439 (86.1%) received antenatal corticosteroids. Of the 3,919 nondiabetic women, 3,277 (83.6%) received antenatal corticosteroids. Antenatal corticosteroid exposure was not associated with respiratory distress syndrome or early death (adjusted relative risk [aRR] = 0.94, 95% confidence interval [CI]: 0.85-1.04), composite neonatal morbidity (aRR = 0.98, 95% CI: 0.89-1.07), or mechanical ventilation (aRR = 0.95, 95% CI: 0.86-1.05). There was no significant effect modification of maternal diabetes on the relationship between antenatal corticosteroids and neonatal outcomes (p > 0.05), and outcomes were similar in sensitivity analyses of partial, single, or multiple courses of corticosteroids.DiscussionAntenatal corticosteroid administered to reduce preterm neonatal morbidity does not appear to have a differential association among women with diabetes compared with those without.Key points· Antenatal corticosteroids are used ubiquitously in women with and without diabetes.. · Maternal diabetes does not appear to modify the neonatal effect of antenatal corticosteroids.. · Larger studies of antenatal corticosteroids are needed to confirm our findings in diabetic women..
| S-EPMC7854806 | biostudies-literature
Project description:BACKGROUND:Antenatal corticosteroids are given primarily to induce fetal lung maturation but results from meta-analyses of randomized controlled trials have not shown mortality or pulmonary benefits for extremely preterm infants although these are the infants most at risk of mortality and pulmonary disease. OBJECTIVE:We sought to determine if exposure to antenatal corticosteroids is associated with a lower rate of death and pulmonary morbidities by 36 weeks' postmenstrual age. STUDY DESIGN:Prospectively collected data on 11,022 infants 22 0/7 to 28 6/7 weeks' gestational age with a birthweight of ?401 g born from Jan. 1, 2006, through Dec. 31, 2014, were analyzed. The rate of death and the rate of physiologic bronchopulmonary dysplasia by 36 weeks' postmenstrual age were analyzed by level of exposure to antenatal corticosteroids using models adjusted for maternal variables, infant variables, center, and epoch. RESULTS:Infants exposed to any antenatal corticosteroids had a lower rate of death (2193/9670 [22.7%]) compared to infants without exposure (540/1302 [41.5%]) (adjusted relative risk, 0.71; 95% confidence interval, 0.65-0.76; P < .0001). Infants exposed to a partial course of antenatal corticosteroids also had a lower rate of death (654/2520 [26.0%]) compared to infants without exposure (540/1302 [41.5%]); (adjusted relative risk, 0.77; 95% confidence interval, 0.70-0.85; P < .0001). In an analysis by each week of gestation, infants exposed to a complete course of antenatal corticosteroids had lower mortality before discharge compared to infants without exposure at each week from 23-27 weeks' gestation and infants exposed to a partial course of antenatal corticosteroids had lower mortality at 23, 24, and 26 weeks' gestation. Rates of bronchopulmonary dysplasia in survivors did not differ by antenatal corticosteroid exposure. The rate of death due to respiratory distress syndrome, the rate of surfactant use, and the rate of mechanical ventilation were lower in infants exposed to any antenatal corticosteroids compared to infants without exposure. CONCLUSION:Among infants 22-28 weeks' gestational age, any or partial antenatal exposure to corticosteroids compared to no exposure is associated with a lower rate of death while the rate of bronchopulmonary dysplasia in survivors did not differ.
| S-EPMC5842434 | biostudies-literature
Project description:ObjectivesTo examine the association between antenatal corticosteroids (ACS) use and perinatal mortality in singletons and twins delivered before 35 weeks of gestation.DesignSecondary analysis of data from an observational prospective chart review study that investigated if exposure to ACS was associated with lower rates of perinatal mortality in preterm infants.SettingThis study was conducted in four hospitals located in Mwanza region, Tanzania.ParticipantsThe study population included all preterm singletons and twins delivered at these hospitals between 24 weeks 0 days and 34 weeks 6 days of gestation from July 2019 to February 2020.Outcome measuresThe primary outcome was perinatal mortality; the secondary outcome was respiratory distress syndrome (RDS).ResultsThe study included 844 singletons and 210 twin infants. Three hundred and fourteen singletons (37.2%) and 52 twins (24.8%) were exposed to at least one dose of ACS. Adjusted multivariate analyses revealed that among singletons' exposure to ACS was significantly associated with a lower likelihood of perinatal mortality, adjusted relative risk (aRR) 0.30 (95% CI 0.22 to 0.40) and RDS, aRR 0.92 (95% CI 0.87 to 0.97). In twin infants, exposure to ACS was associated with a reduced risk of RDS only, aRR 0.87 (95% CI 0.78 to 0.98).ConclusionThe use of ACS between 24 weeks 0 days and 34 weeks 6 days of gestation in both singletons and twins in low-resource settings is associated with positive infant outcomes. No adverse effects were noted. Further research that examines the benefits of ACS for twin infants is needed.
| S-EPMC8991063 | biostudies-literature
Project description:BackgroundPreterm neonatal mortality (NM) has remained high and unchanged for many years in Tanzania, a resource-limited country. Major causes of mortality include birth asphyxia, respiratory insufficiency and infections. Antenatal corticosteroids (ACS) have been shown to significantly reduce mortality in developed countries. There is inconsistent use of ACS in Tanzania.ObjectiveTo determine whether implementation of a care bundle that includes ACS, maternal antibiotics (MA), neonatal antibiotics (NA) and avoidance of moderate hypothermia (temperature < 36°C) targeting infants of estimated gestational age (EGA) 28 to 34 6/7 weeks would reduce NM (< 7 days) by 35%.MethodsA Pre (September 2014 to May 2015) and Post (June 2015 to June 2017) Implementation strategy was used and introduced at three University-affiliated and one District Hospital. Dexamethasone, as the ACS, was added to the national formulary in May 2015, facilitating its free use down to the district level.FindingsNM was reduced 26% from 166 to 122/1000 livebirths (P = 0.005) and fresh stillbirths (FSB) 33% from 162/1000 to 111/1000 (p = 0.0002) Pre versus Post Implementation. Medications including combinations increased significantly at all sites (p<0.0001). By logistic regression, combinations of ACS, maternal and NA (odds ratio (OR) 0.33), ACS and NA (OR 0.30) versus no treatment were significantly associated with reduced NM. NM significantly decreased per 250g birthweight increase (OR 0.59), and per one week increase in EGA (OR 0.87). Moderate hypothermia declined pre versus post implementation (p<0.0001) and was two-fold more common in infants who died versus survivors.InterpretationA low-cost care bundle, ~$6 per patient, was associated with a significant reduction in NM and FSB rates. The former presumably by reducing respiratory morbidity with ACS and minimizing infections with antibiotics. If these findings can be replicated in other resource-limited settings, the potential for further reduction of <5 year mortality rates becomes enormous.
| S-EPMC5841752 | biostudies-literature
Project description:ObjectiveThis study aimed to estimate the effect of antenatal corticosteroid administration on neonatal mortality and morbidity in preterm small-for-gestational age infants through a systematic review and meta-analysis.Data sourcesA predefined, systematic search was conducted through Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trial Registry Platform, and ClinicalTrials.gov yielding 5324 articles from 1970 to 2019.Study eligibility criteriaEligible studies compared neonatal morbidity and mortality among small-for-gestational age infants delivered preterm who received antenatal corticosteroids with those who did not.MethodsThe primary outcome was neonatal mortality. Secondary outcomes were respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage and periventricular leukomalacia, bronchopulmonary dysplasia or chronic lung disease of prematurity, or neonatal sepsis. We assessed heterogeneity by means of Higgins I2 statistic and Cochran's Q test and calculated pooled odds ratios with 95% confidence intervals using random effects models.ResultsA total of 16 observational cohort and case-control studies published from 1995 to 2018 met the selection criteria for the systematic review and included 8989 preterm small-for-gestational age infants. Antenatal corticosteroid administration was explicitly reported among 8376 small-for-gestational age infants; 4631 (55.3%) received antenatal corticosteroids and 3741 (44.7%) did not. Of note, 13 studies including 6387 preterm small-for-gestational age infants were then included in the meta-analysis. Neonatal mortality was significantly lower among infants who received antenatal corticosteroids than those who did not (12 studies: 12.8% vs 15.1%; pooled odds ratio, 0.63; 95% confidence interval, 0.46-0.86), with significant heterogeneity between studies (I2=55.1%; P=.011). There was no significant difference in respiratory distress syndrome (12 studies: odds ratio, 0.89; 95% confidence interval, 0.69-1.15), necrotizing enterocolitis (7 studies: odds ratio, 0.93; 95% confidence interval, 0.70-1.22), intraventricular hemorrhage and periventricular leukomalacia (10 studies: odds ratio, 0.82; 95% confidence interval, 0.56-1.20), bronchopulmonary dysplasia or chronic lung disease of prematurity (8 studies: odds ratio, 1.11; 95% confidence interval, 0.88-1.41), or neonatal sepsis (6 studies: odds ratio, 1.13; 95% confidence interval, 0.86-1.49).ConclusionThese data indicate that antenatal corticosteroid administration reduces neonatal mortality in small-for-gestational age infants delivered preterm, with no apparent effect on neonatal morbidity. This supports the use of antenatal corticosteroids to reduce neonatal mortality in pregnancies with small-for-gestational age infants at risk of preterm birth.
| S-EPMC8237697 | biostudies-literature
Project description:BackgroundThe Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) showed no benefit in the reduction of major neonatal mortality/morbidity or neurodevelopment at 2 and 5 years of age. Using the data from the randomized controlled trial and its follow-up, the aim of this study was to evaluate the association between gestational ages at birth in children exposed to single versus multiple courses of antenatal corticosteroid (ACS) therapy in utero and outcomes at 5 years of age.MethodA total of 1719 children, with the breakdown into groupings of <30, 30-36, and ≥ 37 weeks gestation at birth, contributed to the primary outcome: death or survival with a disability in one of the following domains: neuromotor, neurosensory, and neurobehavioral/emotional disability and were included in this analysis.ResultsGestational age at birth was strongly associated with the primary outcome, p < 0.001. Overall, the interaction between ACS groups and gestational age at birth was not significant, p = 0.064. Specifically, in the 2 preterm categories, there was no difference in the primary outcome between single vs. multiple ACS therapy. However, for infants born ≥37 weeks gestation, there was a statistically significant increase in the risk of the primary outcome in multiple ACS therapy, 48/213 (22.5%) compared to 38/249 (15.3%) in the single ACS therapy; OR = 1.69 [95% CI: 1.04, 2.77]; p = 0.037.ConclusionPreterm birth (<37 weeks gestation) remained the primary factor contributing to an adverse outcome regardless of the number of courses of ACS therapy. Children born ≥ 37 weeks and exposed to multiple ACS therapy may have an increased risk of neurodevelopmental/neurosensory impairment by 5 years of age. To optimize outcomes for infants/children, efforts in reducing the incidence of preterm birth should remain the primary focus in perinatal research.Trial registrationThis study has been registered at (identifier NCT00187382).
| S-EPMC4261573 | biostudies-literature
Project description:BackgroundAntenatal corticosteroids have been proven to prevent adverse outcomes including respiratory morbidities in preterm neonates before 34 weeks of gestation. Recently, it has been suggested that antenatal corticosteroids may also be effective in singleton late preterm pregnancies, and guidelines recommend the use of corticosteroids in singleton pregnant women who are at risk for late preterm birth. On the contrary, there is a paucity of information regarding the effectiveness of corticosteroids in twin neonates with late preterm birth. This study aims to determine the effectiveness of antenatal corticosteroids in late preterm twin neonates.MethodsIn this multicentre randomized controlled trial, women who are at risk for late preterm birth will be enrolled at 34 0/7 to 36 5/7 weeks of gestation. The participants will be randomly assigned to receive antenatal corticosteroids (betamethasone 12 mg, 3 mL intramuscularly [IM]) or placebo (normal saline 3 mL IM). The perinatal outcomes will be compared between the two groups of cases. The primary outcome is severe respiratory complications (the use of continuous positive airway pressure or high-flow nasal cannula for at least 12 h, supplemental oxygen administration with a fraction of oxygen 0.3 or more for at least 24 h, mechanical ventilation, or extracorporeal membranes oxygenation) or perinatal death within the first 72 h of delivery. The secondary outcomes are neonatal mortality and/or other neonatal morbidities.DiscussionThis study will be the first randomized controlled trial that evaluates the effectiveness of antenatal corticosteroids in late preterm twin neonates.Trial registrationNCT03547791 (ClinicalTrials.gov), first submitted date: March 29, 2018, first posted date: June 6, 2018 (retrospectively registered).
| S-EPMC6446272 | biostudies-literature
Project description:This systematic review was to identify available evidence on the effectiveness of tocolysis in inhibiting preterm delivery for women with threatened extremely preterm birth, multiple gestations, and growth-restricted babies, and their infants' outcomes. A comprehensive search using MEDLINE, Embase, the Cochrane Library, CINAHL, POPLINE and the WHO Global Health Library databases was conducted on 14 February 2014. For selection criteria, randomized controlled trials and non-randomized studies that compared tocolysis treatment to placebo or no treatment were considered. Selection of eligible studies, critical appraisal of the included studies, data collection, meta-analyses, and assessment of evidence quality were performed in accordance with the Cochrane Collaboration's guidance and validated assessment criteria. The search identified seven studies for extremely preterm birth, in which three were randomized controlled trials (RCTs) and four were non-randomized studies (non-RCTs). There were no eligible studies identified for women with multiple pregnancy and growth-restricted fetuses. Meta-analyses indicated no significant difference was found for the relative effectiveness of tocolytics versus placebo for prolonging pregnancy in women with extremely preterm birth (RR 1.04, 95% CI 0.83 to 1.31) or reducing the rate of perinatal deaths (RR 2.22, 95% CI 0.26 to 19.24). In summary, there is no evidence to draw conclusions on the effectiveness of tocolytic therapy for women with threatened extremely preterm birth, multiple gestations, and growth-restricted babies.
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