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Antenatal corticosteroids for impending late preterm (34-36+6 weeks) deliveries-A systematic review and meta-analysis of RCTs.

ABSTRACT:

Background

Administration of antenatal corticosteroids (ANC) for impending preterm delivery beyond 34 weeks of gestation continues to be a controversial issue despite various guidelines for obstetricians and gynaecologists.

Objective

To compare outcomes following exposure to ANC for infants born between 34-36+6 weeks' gestation.

Methods

A systematic review of randomised controlled trials (RCT) reporting neonatal outcomes after ANC exposure between 34-36+6 weeks' gestation using Cochrane methodology. Databases including PubMed, Embase, Emcare, Cochrane Central library and Google Scholar were searched in May 2020. Primary outcomes: (1) Need for respiratory support (Mechanical ventilation, CPAP, high flow) or oxygen (2) Hypoglycemia. Secondary outcomes included respiratory distress syndrome (RDS), transient tachypnoea of newborn (TTN), need for neonatal resuscitation at birth [only in the delivery room immediately after birth (not in neonatal intensive care unit (NICU)], admission to NICU, mortality and developmental follow up. Level of evidence (LOE) was summarised by GRADE guidelines.

Main results

Seven RCTs (N = 4144) with low to high risk of bias were included. Only one RCT was from high income countries, Meta-analysis (random-effects model) showed (1) reduced need for respiratory support [5 RCTs (N = 3844); RR = 0.68 (0.47-0.98), p = 0.04; I2 = 55%; LOE: Moderate] and (2) higher risk of neonatal hypoglycaemia [4 RCTs (N = 3604); RR = 1.61(1.38-1.87), p<0.00001; I2 = 0%; LOE: High] after ANC exposure. Neonates exposed to ANC had reduced need for resuscitation at birth. The incidence of RDS, TTN and surfactant therapy did not differ significantly. None of the included studies reported long-term developmental follow up.

Conclusions

Moderate quality evidence indicates that ANC exposure reduced need for respiratory support, and increased the risk of hypoglycaemia in late preterm neonates. Large definitive trials with adequate follow up for neurodevelopmental outcomes are required to assess benefits and risks of ANC in this population.

SUBMITTER: Deshmukh M

PROVIDER: S-EPMC7984612 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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.

Project description:ObjectiveThis study aimed to synthesise available evidence on the efficacy of antenatal corticosteroid (ACS) therapy among women at risk of imminent preterm birth with pregestational/gestational diabetes, chorioamnionitis or fetal growth restriction (FGR), or planned caesarean section (CS) in the late preterm period.MethodsA systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Library, Web of Science and Global Index Medicus was conducted for all comparative randomised or non-randomised interventional studies in the four subpopulations on 6 June 2021. Risk of Bias Assessment tool for Non-randomised Studies and the Cochrane Risk of Bias tool were used to assess the risk of bias. Grading of Recommendations Assessment, Development and Evaluations tool assessed the certainty of evidence.ResultsThirty-two studies involving 5018 pregnant women and 10 819 neonates were included. Data on women with diabetes were limited, and evidence on women undergoing planned CS was inconclusive. ACS use was associated with possibly reduced odds of neonatal death (pooled OR: 0.51; 95% CI: 0.31 to 0.85, low certainty), intraventricular haemorrhage (pooled OR: 0.41; 95% CI: 0.23 to 0.72, low certainty) and respiratory distress syndrome (pooled OR: 0.59; 95% CI: 0.45 to 0.77, low certainty) in women with chorioamnionitis. Among women with FGR, the rates of surfactant use (pooled OR: 0.38; 95% CI: 0.23 to 0.62, moderate certainty), mechanical ventilation (pooled OR: 0.42; 95% CI: 0.26 to 0.66, moderate certainty) and oxygen therapy (pooled OR: 0.48; 95% CI: 0.30 to 0.77, moderate certainty) were probably reduced; however, the rate of hypoglycaemia probably increased (pooled OR: 2.06; 95% CI: 1.27 to 3.32, moderate certainty).ConclusionsThere is a paucity of evidence on ACS for women who have diabetes. ACS therapy may have benefits in women with chorioamnionitis and is probably beneficial in FGR. There is limited direct trial evidence on ACS efficacy in women undergoing planned CS in the late preterm period, though the totality of evidence suggests it is probably beneficial.Prospero registration numberCRD42021267816.

Project description:BackgroundInfants who are born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse respiratory and other outcomes than those born at 37 weeks of gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases the risks of neonatal morbidities.MethodsWe conducted a multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery.ResultsThe primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001).ConclusionsAdministration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications. (Funded by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01222247.).