The effect of single or multiple courses of antenatal corticosteroid therapy on neonatal respiratory distress syndrome in singleton versus twin pregnancies

Background: Antenatal corticosteroid (ACS) treatment is widely used for the prevention of respiratory distress syndrome (RDS) in preterm infants. However, the efficacy and safety of ACS treatment remains controversial in twin pregnancies.
Aims: To investigate the effect of ACS therapy, single or multiple courses, on the incidence of neonatal RDS in singleton and twin pregnancies.
Methods: We retrospectively evaluated the pregnancy and neonatal outcomes of 450 singleton and 117 twin pregnancies delivered at 24–34 weeks of gestation due to preterm labour or preterm premature rupture of membranes. The subjects were categorised into four groups according to ACS exposure: 0, 1, 2 and ≥ 3 courses.
Results: Overall, RDS occurred more frequently in twins compared to singletons (41.0% vs 25.3%, P  < 0.001). In singleton pregnancy, the incidence of RDS was significantly lower in the ACS user groups than in the non-user group, with the lowest incidence in the multiple course groups. An increase in the number of courses of ACS was associated with a reduction in the incidence of RDS (odds ratio 0.349, 95% confidence interval 0.226, 0.537, P  < 0.001) independent of confounding variables. In twin pregnancies, however, the incidence of RDS was not significantly different in comparisons among the four groups.
Conclusion: Multiple courses of ACS were associated with a significantly decreased risk of RDS in singleton pregnancies. However, the current standard dose or interval for ACS administration in singleton pregnancy, as either a single or multiple courses, did not reduce RDS in twins.     

Multiple Courses of Antenatal Corticosteroids for Preterm Birth

a single course of antenatal corticosteroids (ACS) reduces the risks of neonatal death, respiratory distress syndrome (RDS) and possibly intraventricular haemorrhage (IVH) in preterm infants. Because the maximum benefit of therapy appears to occur between 24 hours and seven days following the initial treatment, some physicians have suggested that repeated courses of ACS be administered at weekly intervals to women who remain at increased risk of preterm delivery. In some centres, this approach has become routine, despite the fact that repeated courses of ACS have not been evaluated in a randomized fashion. There are limited numbers of small human studies which have reported that multiple courses of ACS are associated with a decreased risk of RDS. They also have reported a slightly higher risk of necrotizing enterocolitis (NEC) and neonatal mortality, and a reduction in birth head circumference and birthweight. In animals, multiple courses of ACS have been associated with a progressive improvement in post-natal lung function. However, infant growth restriction and alteration of central nervous system myelination have also been shown as adverse effects. The Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study (MACS) has been proposed as a multicentre, double-blind, randomized controlled trial of multiple courses versus a single course of ACS for women at increased risk of preterm birth. Centres in Canada, the USA and Israel have been invited to participate. Prior to MACS, a pilot study will be undertaken at Sunnybrook and Women’s College Health Science Centre and Mount Sinai Hospital in Toronto, to determine the feasibility of MACS.     

Multiple Versus Single Courses of Antenatal Corticosteroids for Preterm Birth: A Pilot Study

Objectives: (1) To determine the feasibility of a multicentre, randomized, double-masked, placebo-controlled trial to investigate the effects of multiple courses of antenatal corticosteroids (ACS) more than 7 days following the initial course of ACS therapy, on perinatal or neonatal mortality or neonatal morbidity. (2) To determine the risk of complications that would require discontinuation of ACS therapy. (3) To determine if multiple courses of ACS have an effect on the concentrations of plasma cortisol and adrenocorticotropin hormone (ACTH) in cord blood and in maternal blood immediately following delivery, compared to a single course of ACS.Methods: Women at 24 to 30 weeks' gestation, at continued increased risk of preterm birth 7 or more days following a single course of ACS were randomized to receive weekly courses of betamethasone or placebo until 33 weeks' gestation or delivery.Results: Women were recruited at two hospitals in Toronto from 01 September 1999 to 31 August 2000. Of the 78 women who were approached and were eligible for the study, 12 (15%) were recruited and 66 (85%) refused to participate. Of the 66 refusals, 38 (58%) did not feel their physicians were supportive of the study, 10 (15%) did not want to be randomized, and 4 (6%) had other personal reasons for refusing to enter the trial. Fourteen women (21%) had physicians who did not allow them to join the study. The lack of physician support was due to concerns related to the potential adverse effects of multiple courses of ACS. There were no complications requiring discontinuation of ACS. Plasma cortisol and ACTH concentrations in cord and maternal blood taken after delivery were not significantly different between ACS and placebo groups.Conclusion: A multicentre randomized controlled trial is required to determine the benefits and risks of multiple versus a single course of ACS. If the study Protocols are supported by physicians and their patients, a multicentre randomized controlled trial is feasible.     

Patterns of antenatal corticosteroid prescribing 1998-2004

BACKGROUND: The administration of antenatal corticosteroids to women at risk of preterm birth is an important component of care for such women. However, inevitably, attempts to maximise the number of women who receive corticosteroids ahead of preterm birth will also expose women perceived at risk who subsequently deliver at term. These women have not been previously quantified. AIMS: To describe antenatal corticosteroid prescribing practices at a single institution over a seven-year period. METHODS: Interrogation of an electronic birthing outcome system supplemented by hand-searching of medical records, recording all women birthing before 34 weeks and all women with a hospital admission before 34 weeks but birthing after 34 weeks. The number of women receiving antenatal corticosteroids in each of these groups was recorded, and trends between groups and over time were analysed using logistic regression. RESULTS: While the total number of women receiving antenatal corticosteroids in our institution has risen over the last seven years, the proportion of women receiving antenatal corticosteroids who deliver between 24 and 35 weeks has increased inconsistently and modestly (average increase 12% per year (95% CI: 6-19%, P < 0.001). In contrast, the number of women receiving antenatal corticosteroids who subsequently deliver after 34 weeks has increased consistently, with an average increase rate of 21% per year (95% CI: 16-25%, P < 0.001). CONCLUSIONS: Increasing numbers of women birthing after 34 weeks in our hospital are receiving antenatal corticosteroids before 34 weeks. The long-term implications of this are not currently clear.     

Maternal ethnicity influences on neonatal respiratory outcomes after antenatal corticosteroid use for anticipated preterm delivery

Objective.?To explore the influence of maternal ethnicity on neonatal outcomes after antenatal corticosteroid administration.

Methods.?A retrospective review of ethnicity, maternal factors, and neonatal birth outcomes was performed for preterm births at a single institution. Cases were limited to women who received antenatal corticosteroids. The impact of ethnicity on specific neonatal respiratory outcomes and mortality was analyzed by bivariate comparisons and by logistic regression analysis.

Results.?Complete ethnicity data were obtained for 548 women. Controlling for gestational age at delivery, diabetes, whether the subject completed a course of steroids, and the dosing of the steroids, logistic regression demonstrated that ethnicity was independently associated with respiratory distress syndrome (compared to Caucasians: African-Americans OR 0.49 (95% CI 0.29–0.85); Filipinos OR 0.45 (95% CI 0.21–0.96).

Conclusions.?Ethnicity is independently associated with neonatal respiratory outcomes after antenatal corticosteroid use. Perhaps individualized dosing of antenatal corticosteroids is needed to further improve neonatal outcomes.     

Antenatal corticosteroids at the beginning of the 21st century

Corticosteroids administered to women in preterm labor are the standard of care for reducing neonatal morbidity and mortality associated with prematurity. These agents promote lung development and reduce the incidence of neonatal intraventricular hemorrhage. Several studies have investigated the method by which fetal lung fluid is cleared after birth. This exploration resulted in the elucidation of the Starling equation or the hypothesis that fluid filtration through capillary membranes is dependent on the balance between the pressure blood places on the capillary membranes and the osmotic pressure of the membranes. The clinical observation that a neonate experiences a vaginal squeeze during a vaginal birth may be important, but it can account for only a small percentage of the lung fluid absorbed. Perhaps more importantly, amiloride-sensitive sodium transport channels (ENaCs) have emerged as key factors in the movement of alveolar fluid from the lung into the vascular system. Several potential clinical applications have been developed from this new knowledge about the physiology of lung fluid clearance at birth. Neonates born late preterm or at term by elective cesarean before the onset of labor are more likely to develop respiratory distress than those born vaginally. Based on the mechanism of action of antenatal corticosteroids, these drugs may be beneficial in the clearance of fetal lung fluid in this population. This article reviews how fetal lung fluid is cleared; the pharmacologic effects of corticosteroids on the fetus; and the risks, benefits, and controversies associated with corticosteroid use.     

Use of Antenatal Corticosteroid Therapy: A Descriptive Study of Clinical Practice Trends

Objectives

Antenatal corticosteroids (ACS) received within 7 days of delivery reduce perinatal morbidity and mortality associated with preterm birth. We aimed to describe the trends of ACS administration over the last decade.

Antenatal therapy with corticosteroids and postpartum complications

In a group of patients receiving dexamethasone antenataly, there was no difference in incidence of postpartum complications when compared to a group treated with a placebo. It is concluded that, from the maternal point of view, selected pregnant patients may safely receive corticosteroids to minimize the incidence of respiratory distress syndrome.     

Antenatal corticosteroid therapy in premature infants

Objective The objective was to examine the effect of antenatal corticosteroid treatment on premature infants, with special attention to any possible adverse effects on neonatal outcome.Methods A retrospective chart review of all singleton and multiple pregnancies delivered in our perinatal center between 1991 and 1999, who had a birth weight of 1,500 g and who were subsequently admitted to our neonatal intensive care unit. Three hundred and sixty-five infants were included in the study and divided into two groups. One group had a gestational age below 28 weeks (196 days) and one group was 28 weeks (>196 days) onward.Results Antenatal corticosteroid therapy reduced the duration of mechanical ventilation, the need for supplementary oxygen, and the need for exogenous surfactant in neonates born at >196 dayss gestation (p<0.05). Corticosteroid treatment seemed to benefit the respiratory distress syndrome (RDS; p=0.051) in this group. There were less cases of necrotizing enterocolitis and neonatal death in the group with corticosteroid treatment (p<0.05). Before 28 weeks gestation, all parameters that were examined (e.g., duration of mechanical ventilation, need for supplemental oxygen, need for exogenous surfactant, RDS) showed no significant differences between those pregnancies pre-treated with corticosteroids or those not treated with corticosteroids. There was no adverse effect of corticosteroids on chorioamnionitis and early onset sepsis in pregnancies with a premature rupture of the membranes. Repeated corticosteroid treatment had no effect on birth weight, but did not improve neonatal outcome either. The interval between last corticosteroid treatment and delivery had no influence on RDS. There was no effect of corticosteroids on periventricular leukomalacia and intraventricular hemorrhage. Regression analysis showed a higher risk of severe RDS in multiple gestations.Conclusion Antenatal betamethasone treatment reduces perinatal morbidity and mortality after 28 weeks gestation. We found no adverse effects and also no benefit of repetitive corticosteroid treatment. The interval between last corticosteroid treatment and delivery did not influence the incidence of RDS. Dose, timing, and rate of antenatal corticosteroids should be reconsidered in multiple gestations.     

早产的诊治现状和面临的问题

近20年来,我国为降低早产发病率,改善早产儿结局不懈努力,取得了令人瞩目的成就,但由于中国人口基数庞大,早产的数量仍不容小觑。加之早产和分娩启动的机制至今仍未完全阐明,区域内早产诊疗水平和早产儿救治水平存在较大差异,在一定程度上制约了早产诊治水平的提高。对我国围产医学工作者而言,进一步降低早产率,改善早产儿远、近期结局,依旧任重而道远。     

产前皮质激素促胎肺成熟研究进展

早产是造成新生儿死亡和患病的最主要因素。产前皮质激素(ACS)促胎肺成熟治疗能显著降低早产儿病死率、新生儿呼吸窘迫综合征及脑室内出血的发生率。目前推荐对妊娠24～34周可能早产的妇女给予单疗程倍他米松或地塞米松治疗。另一种多疗程ACS的治疗方法,在远期安全性研究方面尚缺乏肯定依据,不推荐常规采用。对1周内估计将早产的妊娠妇女可考虑给予一次抢救性的重复ACS,即重复给予1疗程糖皮质激素常规治疗方案。对于妊娠不足39周的择期剖宫产者术前给予ACS的远期安全性尚存争议。就ACS两种给药方法进行综述,评估临床疗效。     

Antenatal Corticosteroid Prophylaxis at Late Preterm Gestation: Clinical Guidelines Versus Clinical Practice

ObjectiveWe investigated how the Antenatal Late Preterm Steroids (ALPS) trial findings have been translated into clinical practice in Canada and the United States (U.S.).MethodsThe study included all live births in Nova Scotia, Canada, and the U.S. from 2007 to 2020. Antenatal corticosteroids (ACS) administration within specific categories of gestational age was assessed by calculating rates per 100 live births, and temporal changes were quantified using odds ratio (OR) and 95% confidence intervals (CI). Temporal trends in optimal and suboptimal ACS use were also assessed.ResultsIn Nova Scotia, the rate of any ACS administration increased significantly among women delivering at 35⁰ to 36⁶ weeks, from 15.2% in 2007–2016 to 19.6% in 2017–2020 (OR 1.36, 95% CI 1.14–1.62). Overall, the U.S. rates were lower than the rates in Nova Scotia. In the U.S., rates of any ACS administration increased significantly across all gestational age categories: among live births at 35⁰ to 36⁶ weeks gestation, any ACS use increased from 4.1% in 2007–2016 to 18.5% in 2017–2020 (OR 5.33, 95% CI 5.28–5.38). Among infants between 24⁰ and 34⁶ weeks gestation in Nova Scotia, 32% received optimally timed ACS, while 47% received ACS with suboptimal timing. Of the women who received ACS in 2020, 34% in Canada and 20% in the U.S. delivered at ≥37 weeks.ConclusionPublication of the ALPS trial resulted in increased ACS administration at late preterm gestation in Nova Scotia, Canada, and the U.S. However, a significant fraction of women receiving ACS prophylaxis delivered at term gestation.     

Use of tocolytics: what is the benefit of gaining 48 hours for the fetus?

Preterm birth remains one of the serious problems in perinatal medicine and is associated with an increased risk of neonatal complications and long-term morbidity. Although each day that delivery is delayed between 22 and 28 weeks of gestation increases survival by 3%, since most spontaneous preterm labour occurs between 28 and 34 weeks of gestation, this is of secondary concern; the primary goal of delay is to improve the function of certain systems in the fetus and to balance the risks of a hostile intrauterine environment with the complications of extrauterine preterm life. Although there is a lack of definitive evidence that tocolytic drugs improve outcome following spontaneous preterm labour and preterm birth, there is ample evidence that tocolysis delays delivery for long enough to permit administration of a complete course of antepartum glucocorticoids and to facilitate in utero transfer to a tertiary care unit where neonatal care will be optimal. Both these measures have been associated with improved outcomes; antepartum glucocorticoids reduce the incidence of respiratory distress syndrome, intraventricular haemorrhage, periventricular leucomalacia and necrotising enterocolitis, and in utero transfer is associated with decreased morbidity and mortality and less hospital-based intervention compared with postnatal transportation. Consequently, women who are more likely to benefit from tocolysis are those at early gestational ages, those needing transfer to a hospital that can provide neonatal intensive care and those who have not yet received a full course of antepartum glucocorticosteroids. In these cases, delaying labour for at least 48 hours with drugs such as atosiban should be considered, since it offers clear advantages for the fetus.     

Surfactant therapy for neonatal respiratory distress syndrome in 2013

Abstract

Surfactant whether given prophylactically in the delivery room or to babies with established respiratory distress syndrome (RDS) reduces the severity of RDS, incidence of air leaks and pneumothorax and, most importantly, neonatal death. Despite being the most intensively studied intervention in neonatal medicine, there is still debate among neonatologists regarding the best preparations, the optimal dose and mode of administration and when best to intervene with surfactant. European Consensus Guidelines on the management of RDS have been developed and updated twice since 2007 reflecting changes in practice as new evidence emerges and in this article we summarize current opinion regarding optimal surfactant use in the present era of non-invasive respiratory support.     

Antenatal corticosteroid treatment: factors other than lung maturation

Antenatal corticosteroid (CS) therapy improves both fetal lung mechanism and gas exchange due to accelerated morphologic development of type one and two pneumocytes. This therapy also enhances the production of surfactant binding proteins and fetal lung antioxidant enzymes. In women with threatening preterm delivery, a single course is advocated between 24 and 34 weeks’ gestation with either betamethasone (two doses of 12?mg 24?h apart) or dexamethasone (four doses of 6?mg at 12-h intervals). Such treatment reduces the rate of respiratory distress syndrome, comorbidity, and mortality in neonates in the first 48?h of life. The optimal time interval between CS administration and delivery is reported to be 1–7 days. Weekly repeat courses reduce the occurrences and severity of respiratory diseases but are associated with reduce fetal growth. Multiple courses should be avoided. However, a repeat course should be considered in women at risk of preterm birth 7 or more days after an initial course in women who remain at risk of preterm birth <34 weeks’ gestation. CS may be harmful in growth restricted fetuses associated with an absent or reversed end-diastolic UA flow since they are at increased risk of acidosis and perinatal death. The purpose of this publication is to update and highlight antenatal CS therapy.     

Obstetrical attitudes to glucocorticoid treatment for fetal lung maturation: time for a change?

A questionnaire survey was conducted among 1004 specialist and trainee obstetricians in the Netherlands and northern Belgium (i.e., Flanders). Glucocorticoids would be used by 85% in Belgium and 74% in the Netherlands, while 59% in both countries would combine them with betamimetic drugs in preterm labor. The more frequently respondents relied on glucocorticoids, the more likely they were to use them at more advanced gestational ages, to combine them with betamimetic drugs and to use that combination beyond 34 wk. Of those using glucocorticoids, only 11% would not do so after 32 wk, while 37% would use them after 34 wk and 5% even beyond 36 wk of gestation. Gestational age limits did not differ for glucocorticoids with or without betamimetic drugs. The findings indicate that the encouraging results of the early trials have lead to widespread inappropriate use of prenatal glucocorticoid therapy. Substantial overuse was more frequent than rejection of its use.     

Respiratory distress syndrome after elective caesarean section in near term infants: a 5-year cohort study

Objective: to assess the incidence of respiratory distress syndrome (RDS) in late preterm (34^0/7–36^6/7) and just term (37^0/7–37^6/7) infants born via elective caesarean section (CS) in a tertiary care maternity facility.

Methods: retrospective cohort study between 2005 and 2009. Hundred and eighty-eight near term infants, divided in two groups: group A: 125 late preterm (34^0/7–36^6/7) and group B: 63 just term (37^0/7–37^6/7), from elective CS (except CS after pre-mature rupture of membranes and foetuses presenting congenital malformation) were included.

Results: In group A the overall incidence of RDS (RDS at or shortly after birth, requiring respiratory support or oxygen therapy) was 44% (n = 55) vs. 15.9% (n = 10) in group B (p < 0.01). The incidence of SRDS (requiring admission in the neonatal intensive care unit (NICU)) in group A was 13.6% (n = 17) and 3.2% (n = 2) group B (p < 0.01). The risk decreased significantly as gestational age (GA) increased: for RDS, 50.9% at 34 weeks of gestation (WG), 52.5% at 35 WG, 21.5% at 36 WG, and 15.9% at 37 WG; for admission, 30.2% at 34 WG, 25% at 35 WG, 9.4% at 36 WG, and 6.3% at 37 WG. Among late preterm infants with RDS, 30.9% (n = 17) developed severe RDS (SRDS).

Conclusions: Late preterm infants born via elective CS are at high risk for RDS and NICU admission. The risk is influenced by each additional week spent in utero. As the incidence of CS is increasing within this population, new preventative strategies must be sought.