Controversy: antenatal steroids

There is no controversy that women at risk of preterm delivery before 32 to 34 weeks' gestational age should be treated with antenatal steroids. Three recent meta-analyses by the Cochrane Collaboration on the benefits of antenatal steroids, the choice of steroid and dosing, and repeat doses of corticosteroids comprehensively summarize the available clinical information to about 2007. However, there are many unanswered questions about which steroid and dose to use and about their use in selected populations. This review focuses on those areas of uncertainty.     

The effect of multidose antenatal betamethasone on maternal and infant outcomes

OBJECTIVE: This study was undertaken to determine whether prolonged betamethasone therapy is, as has been suggested, associated with adverse maternal or neonatal outcomes. STUDY DESIGN: A secondary multivariate analysis of a randomized controlled trial was performed to determine whether duration of betamethasone therapy was associated with adverse maternal or neonatal outcomes. RESULTS: There were 414 fetuses whose mothers were randomly assigned to trial groups. Final models included only valid cases without missing or averaged data (N = 367 to N = 412, depending on the model). Three or more sets of weekly betamethasone injections were given in 21.3% of cases and > or =4 sets were given in 12.3% of cases. Prolonged antenatal betamethasone therapy was not associated with increases in incidences of antenatal fever, chorioamnionitis, reduced birth weight, suppressed neonatal adrenal function, neonatal sepsis, or neonatal death. It was associated with larger birth weights (P <.05). CONCLUSION: Prolonged antenatal betamethasone therapy was not associated with higher risks of antenatal maternal fever, chorioamnionitis, reduced birth weight, neonatal adrenal suppression, neonatal sepsis, and neonatal death.     

Effectiveness and efficacy of antenatal care

Antenatal care is recommended to pregnant women to improve the outcomes of childbirth. A common pattern of provision is seen in those parts of the industrialised world which have been influenced by British settlers. This paper presents the evolution of the current patterns of care, and the effectiveness and efficacy of the present system are discussed.     

Multiple courses of antenatal steroids: risks and benefits

OBJECTIVE: To review the existing literature regarding the effect of multiple courses of antenatal corticosteroids in reducing the occurrence of complications arising because of lung immaturity. DATA SOURCES: A systematic review of the English-language literature was conducted using a computerized database. We searched the English-language human and animal literature in MEDLINE and PubMed (National Library of Medicine, Bethesda, MD), as well as abstracts from recent meetings of the Society for Gynecologic Investigation and the Society for Maternal-Fetal Medicine. The search terms used were antenatal steroids, prenatal steroids, and respiratory distress syndrome. STUDY SELECTION: We screened 2472 abstracts and found 280 relevant articles, which we independently reviewed. Only prospective well-designed animal studies were included. In humans, no well-designed randomized controlled trials (RCTs) were identified. Data that specifically addressed the issue of beneficial and adverse outcome of multiple courses of antenatal corticosteroids were included. TABULATION, INTEGRATION, AND RESULTS: Twelve studies and three abstracts concerning animal models were included. These suggest multiple adverse consequences including decrease in birth and lung weights and brain growth restriction. In humans, 14 publications and five abstracts, mostly in the form of retrospective studies, although methodologically lacking, were included. Possible beneficial effects include lower rates of respiratory distress syndrome and a decrease in oxygen use, whereas adverse outcomes embody reduction in birth head circumference, birth weights, and increased neonatal and maternal infection rates. CONCLUSION: To date, there are no well-designed RCTs in humans that support the advantages of multiple courses over a single course of antenatal corticosteroids. An increasing body of evidence raises the concern of adverse consequences from the use of repeated courses. While awaiting results from RCTs in progress, we recommend that a single course of antenatal corticosteroids be given to all women at risk for preterm birth at 24-34 weeks' gestation.     

Histologic chorioamnionitis, antenatal steroids, and perinatal outcomes

OBJECTIVE: To determine the perinatal effects of histologic chorioamnionitis on preterm neonates and the effectiveness of antenatal steroids in the presence of histologic chorioamnionitis. METHODS: We studied neonates at our institution who weighed 1750 g or less at birth from January 1990 through December 1997. The population was stratified primarily by presence of histologic chorioamnionitis and secondarily by exposure to antenatal steroids. Subgroups were compared by various perinatal outcomes and confounding variables. Student t test, chi(2), Fisher exact test, and logistic regression were used for analysis. RESULTS: Among 1260 neonates entered, the placentas of 527 had evidence of histologic chorioamnionitis and 733 did not. Those with histologic chorioamnionitis had a lower mean gestational age, lower birth weight, and higher rate of major neonatal morbidities than those without it. After adjusting for confounding variables, histologic chorioamnionitis independently associated with lower gestational age, lower birth weight, and neonatal death. Among neonates exposed to antenatal steroids who had histologic chorioamnionitis, there was a significantly lower incidence of low Apgar scores (18% compared with 33.5%, P <.001), respiratory distress syndrome (RDS) (39.6% compared with 55.9%, P <.001), intraventricular hemorrhage and periventricular leukomalacia (21.9% compared with 36.9%, P <.001), major brain lesions (7.7% compared with 18.4%, P <.001), patent ductus arteriosus (14.8% compared with 23.7%, P =.018), and neonatal death (8.3% compared with 16.2%, P =.02), with no increase in rate of proven neonatal sepsis (18.3% compared with 14%, P =.24). CONCLUSION: Histologic chorioamnionitis increases major perinatal morbidity through its association with preterm birth and is independently associated with neonatal death. In the presence of histologic chorioamnionitis, antenatal steroids significantly decreased the incidence of RDS, intraventricular hemorrhage and periventricular leukomalacia, major brain lesions, and neonatal mortality, without increasing neonatal sepsis.     

Controversies in the use of antenatal steroids for fetal maturation

After decades of caution and reticence, by the early 1990s, the use of antenatal corticosteroids was accepted as a pharmacologic intervention to reduce neonatal morbidity and mortality associated with prematurity. Many prospective studies yielded robust evidence to support the use of corticosteroids for fetal maturation. Their use is no longer disputed. Nevertheless, many unanswered questions remain regarding issues such as the ideal dose, drug form, regimen, or timing of treatment. This article explores many of the unanswered questions associated with antenatal corticosteroid use.     

Timing of antenatal steroids exposure and its effects on neonates

Objective

Antenatal corticosteroid (ACS) has long been regarded as the standard of care for women at risk of preterm labour. There are, however, varying practices and regimes in ACS administration. It is unclear if “a window of efficacy” truly exists and if the benefits of ACS would diminish after 7 days from the first dose. The objective of this study is to determine if the time interval between antenatal corticosteroids and delivery influences the neonatal outcomes in preterm deliveries from 23⁺⁵ to 36⁺⁶ weeks’ gestation.

Methods

This is a retrospective analysis of 302 women and 352 infants who delivered from 23⁺⁵ to 36⁺⁶ weeks’ gestation in KK Women’s and Children’s Hospital from 1st November 2014 to 31st January 2015. The timings of the first two doses of corticosteroids and the delivery were retrieved. Neonatal outcomes were compared between those delivering within 7 days and those delivering beyond 7 days of first dose of ACS.

Results

61.2% of preterm infants received at least one dose of antenatal corticosteroids, of which 23.6% received it within the window of efficacy. Overall incidence of respiratory distress asyndrome in our study is 17.6%. Significantly, neonates with ACS exposure beyond 7 days were seven times more likely to have RDS as compared to those exposed to ACS within the window of efficacy (RR 0.535, 95% CI 0.166–1.72), after adjusting for potential confounders.

Conclusion

The results of this study support the current practice among obstetricians to aim to administer ACS within 7 days of delivery.

     

The fetal cardiovascular response to antenatal steroids in severe early-onset intrauterine growth restriction

OBJECTIVE: Our aim was to study the hemodynamic effects of betamethasone on fetuses with intrauterine growth restriction (IUGR) with absent or reversed end-diastolic (ARED) umbilical artery flow. STUDY DESIGN: Color/pulsed Doppler waveforms were obtained before and after intramuscular injections of betamethasone in 19 consecutive fetuses with IUGR/ARED and 6 control fetuses. Peak velocities and pulsatility index (PI) values were obtained from the umbilical (UA) and middle cerebral (MCA) arteries and intrahepatic umbilical vein (UV). RESULTS: Ten ARED fetuses developed transient positive umbilical end-diastolic flow after steroids, whereas nine fetuses showed persistent ARED. The persistent ARED subgroup demonstrated increased UA and UV peak velocities after steroids, which may indicate fetal hypertension. Fetal death (n=2) and severe acidosis (n=2) were confined to the subgroup with persistent ARED. CONCLUSION: Preterm IUGR/ARED fetuses exhibit divergent cardiovascular responses to prenatal steroids. Intensive Doppler-based fetal monitoring may identify a subset of fetuses prone to decompensation after maternal steroid administration.     

Effectiveness of antenatal corticosteroid administration after preterm premature rupture of the membranes

OBJECTIVE: This study was undertaken to determine the effect of antenatal betamethasone administration on the incidences of respiratory distress syndrome, intraventricular hemorrhage, and perinatal infectious morbidity in the setting of preterm premature rupture of membranes. STUDY DESIGN: We performed a nonconcurrent prospective analysis of women with singleton pregnancies who were delivered between 24 and 32 weeks' gestation after preterm premature rupture of membranes. Patients were subdivided into 2 groups according to betamethasone exposure: (1) none (control group) and (2) two 12-mg doses in a 24-hour interval on admission (single-course group). Patients who received >2 doses of betamethasone were excluded. All patients received broad-spectrum prophylactic antibiotics. Data were analyzed with the Student t test, the chi(2) test, and the Fisher exact test. Multiple logistic regression analyses incorporated multiple variables considered risk factors for respiratory distress syndrome and intraventricular hemorrhage. P <.05 for all 2-tailed tests was considered significant. RESULTS: A total of 362 patients were included, with 203 in the control group and 159 in the single-course group. Patients in these groups were delivered at 31.0 +/- 3.0 and 30.2 +/- 2.7 (mean +/- SD) weeks' gestation, respectively. The groups were similar with respect to selected demographic characteristics, latency until delivery, mode of delivery, birth weight, and maternal group B streptococcal colonization status. Univariate analysis demonstrated significant decreases in the frequencies of both respiratory distress syndrome (odds ratio, 0.31; 95% confidence interval, 0.2-0.5) and grade III/IV intraventricular hemorrhage (odds ratio, 0.14; 95% confidence interval, 0.1-0.6) in the single-course group. The frequencies of early neonatal sepsis, chorioamnionitis, endometritis, and neonatal death were similar between groups. Multiple logistic regression analyses determined that a single course of betamethasone was independently associated with reductions in the frequencies of both respiratory distress syndrome (odds ratio, 0.16; 95% confidence interval, 0.1-0.4) and grade III/IV intraventricular hemorrhage (odds ratio, 0.18; 95% confidence interval, 0.1-0.4). CONCLUSIONS: A single course of betamethasone administered antenatally to patients with preterm premature rupture of membranes was associated with decreases in the frequencies of both respiratory distress syndrome and advanced grades of intraventricular hemorrhage without any increase in perinatal infectious morbidity.     

Neonatal hearing assessment in very low birth weight infants exposed to antenatal steroids.

OBJECTIVE: We sought to evaluate neonatal hearing assessment by the otoacoustic emission (OAE) test in very low birth weight (VLBW) infants exposed to antenatal steroids. STUDY DESIGN: This is a retrospective cohort study of infants <1500 g delivered between July 1998 and July 2004 who completed hearing screens on discharge. All screens were performed by the OAE. Only infants who failed or passed the exam were included in the analysis. Infants with a partial or an inadequate exam were excluded. Neonates exposed to antenatal steroids were then compared to unexposed infants for the results of their OAE. RESULT: A total of 68,000 deliveries were performed during the study period. There were 703 VLBW infants who had hearing exams, of which 548 (78%) passed the screen, 95 (14%) failed and 59 (8%) were indeterminate. Gestational age, birth weight, score for neonatal acute physiology and severe intraventricular hemorrhage were associated with a failed screen (P<0.01). Antenatal steroid exposure was not associated with a failed screen (odds ratio: 0.83 (95% confidence interval 0.5-1.4), P=0.43). CONCLUSION: In our population, antenatal steroids were not associated with a positive or negative effect on hearing assessment of VLBW infants.     

Single versus repeat courses of antenatal steroids to improve neonatal outcomes: risks and benefits

Recent additions to the literature provide evidence supporting the use of repeat courses of antenatal steroids. Both human and animal studies offer evidence that repeat courses of corticosteroids improve neonatal pulmonary outcomes, especially for the infants delivered at earlier gestational ages. Although there is also evidence to suggest altered neuronal maturation and intrauterine growth restriction in animals treated with repeat steroids, randomized controlled studies in humans have shown that birth weight reduction was only seen in those infants treated with 4 or more courses of corticosteroids. In addition, the reduction in neonatal birth weight and head circumference seen after multiple courses of antenatal corticosteroids normalizes by the time of hospital discharge. Studies are ongoing to investigate the 24-month post delivery physical and neurodevelopmental outcomes in infants exposed to repeat courses of antenatal corticosteroids. Although there is evidence demonstrating the safety of a single repeat, or 'rescue', dose of antenatal corticosteroids, this must be tempered against the adverse effects seen after multiple courses of weekly repeat steroids. Randomized controlled trials are needed to determine the optimal number of courses of antenatal steroids to reduce the frequency of neonatal respiratory distress syndrome (RDS) without adversely affecting other neonatal outcomes.     

Neurodevelopmental outcome of extremely premature infants exposed to incomplete,no or complete antenatal steroids

Abstract

Objective: To compare the neurodevelopmental outcomes at 18–22 months’ corrected age of extremely premature infants exposed to a complete course, an incomplete course or no dose of antenatal steroids (ANS).

Methods: Retrospective chart review of extremely premature (<28 weeks gestational age) neonates over a 3-year period. Neurodevelopmental assessment at 18–22 months’ corrected age included a standardized neurologic examination and the Bayley Scales of Infant and Toddler development II or III. Intact survival was defined as survival without cerebral palsy (CP), blindness or deafness and mental developmental index (MDI)/cognitive score ≥85. Neurodevelopmental impairment (NDI) was defined as any of the following: moderate or severe CP, MDI/cognitive score <70, deafness or blindness. Patients were categorized into three groups: (A) no ANS; (B) incomplete course and (C) complete course of ANS.

Results: Outcome data were available for 134 (88%) patients of our cohort (n?=?153). Severe intraventricular hemorrhage (IVH) was significantly lower and intact survival was higher in the complete ANS group (p?<?0.01). On logistic regression, with gestational age, gender, maternal insurance and ANS exposure as covariates, an incomplete (versus complete) course of ANS (p?=?0.006) and gestational age were significantly associated with lower intact survival at 18–22 months.

Conclusions: A complete course of ANS was associated with an increased likelihood of intact survival at a corrected age of 18–22 months among extremely premature infants, compared with an incomplete course. Follow-up studies should account for the differential benefit of complete versus incomplete course of ANS administration.     

Effectiveness of a peer support intervention for antenatal depression: a feasibility study

ABSTRACT

Objective

A feasibility study for a randomised controlled trial to assess the acceptability, recruitment, feasibility and effectiveness of a peer support intervention for women with antenatal depression. The key premise of peer support is based upon the trust and empathetic understanding engendered by common experiences.     

Neonatal morbidity and growth in very low birth-weight infants after multiple courses of antenatal steroids.

OBJECTIVE:To evaluate the neonatal morbidity and the growth in very low birth-weight (VLBW) infants after exposure to multiple courses of antenatal steroids.STUDY DESIGN:A total of 319 VLBW infants were placed in one of the two groups based on exposure to antenatal steroids: Group 1: less than two complete courses; Group 2: two complete courses or more. Anthropometric measurements at birth and discharge and neonatal morbidity were recorded. Composite morbidity was defined as presence of any of the following: death, chronic lung disease, major intraventricular hemorrhage and periventricular leukomalacia.RESULTS:The composite morbidity was not significantly different between the two groups (p=0.26). A significantly higher percentage of infants born after multiple courses of antenatal steroids had head circumference below 10th percentile at discharge (23 vs 9%, adjusted OR, 3.25, (95% CI, 1.4, 7.3); p=0.015).CONCLUSIONS:Multiple courses of antenatal steroids may predispose VLBW infants to impairment of postnatal somatic growth without providing any additional benefit for immediate neonatal outcome.