Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial

Schmitz, Thomas; Doret-Dion, Muriel; Sentilhes, Loïc; Parant, Olivier; Claris, Olivier; Renesme, Laurent; Abbal, Julie; Girault, A.; Torchin, Héloïse; Houllier, Marie; Saché, Nolwenn Le; Vivanti, Alexandre J.; Luca, Danièle De; Winer, Norbert; Flamant, Cyrille; Thuillier, Claire; Boileau, Pascal; Blanc, Julie; Brevaut, Véronique; Bouet, Pierre‐Emmanuel; Gascoin, Géraldine; Beucher, G.; Datin-Dorrière, Valérie; Bounan, Stéphane; Bolot, Pascal; Poncelet, C.; Alberti, Corinne; Ursino, Moreno; Aupiais, Camille; Baud, Olivier

doi:10.1016/s0140-6736(22)01535-5

Cited by 29 publications

(18 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current antenatal steroid dosage appears to be high, and the release of betamethasone acetate proceeds slowly for several days [33]. However, a recent RCT from France, in which a single betamethasone injection was compared to two injections 24 h apart ( normal care ), showed a 2.5 percent reduced need for surfactant in the full betamethasone arm but no between-group differences in rates of mortality, or other important outcomes [34]. Maternal BMI might be a confounder, and further studies are needed.…”

Section: Introductionmentioning

confidence: 99%

European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update

et al. 2023

View full text Add to dashboard Cite

Respiratory distress syndrome (RDS) care pathways evolve slowly as new evidence emerges. We report the sixth version of “European Guidelines for the Management of RDS” by a panel of experienced European neonatologists and an expert perinatal obstetrician based on available literature up to end of 2022. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, appropriate maternal transfer to a perinatal centre, and appropriate and timely use of antenatal steroids. Evidence-based lung-protective management includes initiation of non-invasive respiratory support from birth, judicious use of oxygen, early surfactant administration, caffeine therapy, and avoidance of intubation and mechanical ventilation where possible. Methods of ongoing non-invasive respiratory support have been further refined and may help reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation by targeted use of postnatal corticosteroids remains essential. The general care of infants with RDS is also reviewed, including emphasis on appropriate cardiovascular support and judicious use of antibiotics as being important determinants of best outcome. We would like to dedicate this guideline to the memory of Professor Henry Halliday who died on November 12<sup>,</sup> 2022.These updated guidelines contain evidence from recent Cochrane reviews and medical literature since 2019. Strength of evidence supporting recommendations has been evaluated using the GRADE system. There are changes to some of the previous recommendations as well as some changes to the strength of evidence supporting recommendations that have not changed. This guideline has been endorsed by the European Society for Paediatric Research (ESPR) and the Union of European Neonatal and Perinatal Societies (UENPS).

show abstract

Section: Introductionmentioning

confidence: 99%

European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update

et al. 2023

View full text Add to dashboard Cite

show abstract

“…This finding is consistent with the results of betamethasone (Beta) clinical trials for women at risk of preterm delivery given half-dose versus full dose. 32 This study showed that the neonatal outcomes related to fetal lung maturity in the half-dose group was similar to that of standarddose after 34 GW. However, around 28 GW, infants exposed to half-dose Beta had an increased risk of developing NRDS and requiring exogenous surfactant therapy.…”

Section: Discussionmentioning

confidence: 52%

“…However, around 28 GW, infants exposed to half-dose Beta had an increased risk of developing NRDS and requiring exogenous surfactant therapy. 32 Based on the above proof, we are undergoing another clinical trial involving the administration of half-dose DEX (2.5 mg Q12h for 4 times) to pregnant women after 34 GW, which aims to offer an 20,29 The white column is the simulated result, and the gray column is the observed value; data are presented as mean ± SD. optimal approach to enhance the effectiveness and safety of clinical DEX applications.…”

Section: Discussionmentioning

confidence: 99%

Systematic Quantitative Analysis of Fetal Dexamethasone Exposure and Fetal Lung Maturation in Pregnant Animals: Model Informed Dexamethasone Precision Dose Study

Song,

Wang

et al. 2024

ACS Pharmacol. Transl. Sci.

View full text Add to dashboard Cite

Dexamethasone (DEX) was applied in neonatal respiratory distress syndrome treatment of pregnant women. We established a pharmacokinetics (PK)/pharmacodynamics(PD)/end point model of pregnant animals based on published data and then extrapolated to simulate fetal exposure and lung maturation in pregnant women. We first established the PK/PD/end point model for DEX in pregnant sheep. We considered the competitive effect of cortisol (Cort) and DEX binding with glucocorticoid receptor and then used the indirect response model to describe disaturated-phosphatidylcholine (DSPC) dynamics. Based on that, we established a regression relationship between DSPC and fetal lung volume (V40). We then extrapolated the PD/end point model of pregnant sheep to pregnant monkeys by corrected stages of morphologic lung maturation in two species. Finally, we utilized the interspecies extrapolation strategy to simulate fetal exposure (AUC0–48h) and V40 relationship in pregnant women. The current model could well describe the maternal-fetal PK of DEX in pregnant animals. Simulated DEX AUC0–24h values of the umbilical venous to maternal plasma ratio in pregnant sheep and monkeys were 0.31 and 0.27, respectively. The simulated Cort curve and V40 in pregnant sheep closely matched the observed data within a 2-fold range. For pregnant monkeys, model-simulated V40 were well fitted with external verification data, which showed good interspecies extrapolation performance. Finally, we simulated fetal exposure–response relationship in pregnant women, which indicated that the fetal AUC0–48h of DEX should not be less than 300 and 100 ng/mL·hr at GW28 and GW34 to ensure fetal lung maturity. The current model preliminarily provided support for clinical DEX dose optimization.

show abstract

“…[44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] The reviewers were in agreement on 98% of the included and excluded articles. All the population based studies and all except two of the randomised controlled trials were from high income countries (Australia, Canada, Finland, France, New Zealand, and the US), [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] one randomised controlled trial was from a middle income country (Iran), 57 and one international randomised controlled trial was from low and middle income countries (Bangladesh, India, Kenya, Nigeria, and Pakistan). 55 Most of the study outcomes were at a low risk of bias but had low or very low levels of certainty based on GRADE.…”

Section: Patient and Public Involvementmentioning

confidence: 99%

The proportions of term or late preterm births after exposure to early antenatal corticosteroids, and outcomes: systematic review and meta-analysis of 1.6 million infants

Ninan,

Gojic,

Wang

et al. 2023

BMJ

View full text Add to dashboard Cite

Objective To systematically review the proportions of infants with early exposure to antenatal corticosteroids but born at term or late preterm, and short term and long term outcomes. Design Systematic review and meta-analyses. Data sources Eight databases searched from 1 January 2000 to 1 February 2023, reflecting recent perinatal care, and references of screened articles. Eligibility criteria for selecting studies Randomised controlled trials and population based cohort studies with data on infants with early exposure to antenatal corticosteroids (<34 weeks) but born at term (≥37 weeks), late preterm (34-36 weeks), or term/late preterm combined. Data extraction and synthesis Two reviewers independently screened titles, abstracts, and full text articles and assessed risk of bias (Cochrane risk of bias tool for randomised controlled trials and Newcastle-Ottawa scale for population based studies). Reviewers extracted data on populations, exposure to antenatal corticosteroids, and outcomes. The authors analysed randomised and cohort data separately, using random effects meta-analyses. Main outcome measures The primary outcome was the proportion of infants with early exposure to antenatal corticosteroids but born at term. Secondary outcomes included the proportions of infants born late preterm or term/late preterm combined after early exposure to antenatal corticosteroids and short term and long term outcomes versus non-exposure for the three gestational time points (term, late preterm, term/late preterm combined). Results Of 14 799 records, the reviewers screened 8815 non-duplicate titles and abstracts and assessed 713 full text articles. Seven randomised controlled trials and 10 population based cohort studies (1.6 million infants total) were included. In randomised controlled trials and population based data, ∼40% of infants with early exposure to antenatal corticosteroids were born at term (low or very low certainty). Among children born at term, early exposure to antenatal corticosteroids versus no exposure was associated with increased risks of admission to neonatal intensive care (adjusted odds ratio 1.49, 95% confidence interval 1.19 to 1.86, one study, 5330 infants, very low certainty; unadjusted relative risk 1.69, 95% confidence interval 1.51 to 1.89, three studies, 1 176 022 infants, I 2 =58%, τ 2 =0.01, low certainty), intubation (unadjusted relative risk 2.59, 1.39 to 4.81, absolute effect 7 more per 1000, 95% confidence interval from 2 more to 16 more, one study, 8076 infants, very low certainty, one study, 8076 infants, very low certainty), reduced head circumference (adjusted mean difference −0.21, 95% confidence interval −0.29 to −0.13, one study, 183 325 infants, low certainty), and any long term neurodevelopmental or behavioural disorder in population based studies (eg, any neurodevelopmental or behavioural disorder in children born at term, adjusted hazard ratio 1.47, 95% confidence interval 1.36 to 1.60, one study, 641 487 children, low certainty). Conclusions About 40% of infants exposed to early antenatal corticosteroids were born at term, with associated adverse short term and long term outcomes (low or very low certainty), highlighting the need for caution when considering antenatal corticosteroids. Systematic review registration PROSPERO CRD42022360079.

show abstract

Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial

Cited by 29 publications

References 30 publications

European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update

European Consensus Guidelines on the Management of Respiratory Distress Syndrome: 2022 Update

Systematic Quantitative Analysis of Fetal Dexamethasone Exposure and Fetal Lung Maturation in Pregnant Animals: Model Informed Dexamethasone Precision Dose Study

The proportions of term or late preterm births after exposure to early antenatal corticosteroids, and outcomes: systematic review and meta-analysis of 1.6 million infants

Contact Info

Product

Resources

About