Women's Health Care PhysiciansAntenatal corticosteroid administration is one of the most effective methods to improve perinatal outcomes. It reduces the incidence of respiratory distress syndrome, intraventricular hemorrhage, periventricular leukomalacia and necrotizing enterocolitis in antenatal corticosteroids for preterm labor neonates. Antenatal corticosteroids are also effective in treating maternal hemolysis, elevated liver enzymes and low platelet count syndrome. However, complications in neonates and mothers may occur when antenatal coorticosteroids are given, including infection, sepsis and maternal pulmonary edema. The National Institutes of Health Consensus Development Conference recommends treatment regimens of either two 12 mg doses of betamethasone given coticosteroids 24 hours apart or four 6 mg doses of dexamethasone given intramuscularly 12 hours apart between 24 and 34 weeks of gestation in pregnancies at risk antenatal corticosteroids for preterm labor preterm buy injectable steroids online australia.
Antenatal steroid - Wikipedia
Background In high-income countries, administration of antenatal steroids is standard care for women with anticipated preterm labour. Objectives To review the evidence for and estimate the effect on cause-specific neonatal mortality of administration of antenatal steroids to women with anticipated preterm labour, with additional analysis for the effect in low- and middle-income countries.
Methods We conducted systematic reviews using standardized abstraction forms. Observational study mortality data were consistent. The control group in these equivalent studies was routine care ventilation and, in many cases, surfactant. In low-income countries, many preterm babies currently receive little or no medical care. It is plausible that antenatal steroids may be of even greater effect when tested in these settings. If fully scaled up, this intervention could save up to neonatal lives annually.
Antenatal steroid treatment for women who are at risk of preterm delivery has emerged as the most effective intervention for the prevention of RDS, reducing early neonatal mortality and morbidity. Given the evidence of benefit, antenatal steroid treatment is now considered standard practice, and in high-income countries, litigation is likely if antenatal steroids are not given when indicated.
As a result, the profile of RDS incidence and severity in high-income countries has altered allowing wider use of non-invasive ventilation and continuous airway pressure ventilation, reducing damage to the lungs. For over half of the world's births,ventilator support for RDS is very unlikely.
To date, no systematic reviews have focused on the potential benefit of antenatal steroid therapy in these settings. The objective of the present study was to review the evidence globally for and estimate the effect on neonatal mortality due to preterm birth complications of antenatal steroid administration to women before anticipated preterm labour, compared with placebo or no treatment, with specific focus on variation on the effect size in low- and middle-income countries.
Online searches of major conference proceedings were also conducted in order to identify unpublished literature. The key search terms were Steroid antenatal, newborn steroids, RDS newborn steroids, Antenatal steroids, newborn steroids, RDS newborn steroids and prenatal steroids. The systematic searches were for studies published between January and September After initial screening of titles and abstracts, we reviewed full-text publications of possible studies.
Synthesis of study identification in review of the effects of antenatal corticosteroids for the treatment of RDS morbidity and mortality in preterm labour.
The population of interest was neonates, and the intervention being studied was administration of corticosteroids to women in pretem labour. We included randomized controlled trials or observational studies, where antenatal steroids were given as therapy in premature labour and where birth occurred between 24 h and 7 days after treatment. All included studies incorporated a placebo or a suitable control group that was similar to the experimental group except that it did not receive antenatal steroids.
Studies were included if antenatal steroids were given alone or in combination with antibiotics and surfactants.
In trials including women with multiple pregnancies, the number of babies was used as the denominator for neonatal outcomes. We sought to identify randomized controlled trials, but due to lack of such studies, especially in low-income settings, we also reviewed observational studies fitting the above criteria. The outcomes of interest were i neonatal mortality due to complications of preterm birth as used in International Classification of Disease ICD version 10 and for global estimates for neonatal mortality; and ii serious neonatal morbidity related to prematurity RDS and necrotizing enterocolitis.
All studies, which met the inclusion criteria, were abstracted onto a standardized form. We abstracted key variables with regard to the study identifiers and context, study design and limitations, intervention specifics and outcome effects Supplementary Table 1. We planned a priori to conduct three meta-analyses, two for mortality outcomes one with RCT as input and one with observational studies and one for morbidity outcomes RCT only. We also planned to undertake additional sensitivity analysis to examine bias that may be introduced by excluding certain studies not meeting our criteria.
Heterogeneity between studies was summarized using the I 2 statistic. We summarized the overall quality of evidence for each outcome and each data input type using an adapted version of the GRADE protocol table. We conducted meta-analyses restricted to studies performed in middle-income countries to assess the effect of antenatal steroid administration on neonatal mortality and morbidity in such settings. We also reviewed the Cochrane neonatal mortality meta-analysis for high-income settings taking account of time period.
In addition, we conducted sensitivity meta-analyses for the studies included in the Cochrane but including two of the studies that had been excluded. We identified titles for screening Figure 1 and reviewed the full text of papers. Of these, 40 were not studies, 36 had no comparison group and 94 did not report on mortality or serious morbidity. A total of 42 papers were included in the final database Supplementary Table. We identified 20 RCTs that reported data on cause-specific mortality of which 18 14, 19—35 had been included in the Cochrane review.
We excluded two studies 36 , 37 for similar reasons to those given in the recent Cochrane, i. The remaining trials had few limitations. The majority 13 were placebo-controlled, usually with normal saline injection. For the remainder, the control group received management according to the local standard practice. In around half of the studies eight , randomization was well described and was adequately concealed, but for 10 studies, the randomization methods were not clearly described.
In web table, we summarize the details of these studies and assess the quality of each. Although 18 RCTs were identified, only four were from middle-income countries: Brazil, 32 South Africa, 33 Jordan 34 and Tunisia. No studies were identified from low-income countries. The only African study was from South Africa, and no studies were identified form South Asia, where around half of newborn deaths are found. This intervention is for women in preterm labour or at high risk of preterm labour e.
Studies included the gestational age at administration, ranging from 23 weeks to 36 weeks, and women with both spontaneous preterm labour or planned preterm delivery. Figure 2 shows the variation of effect on neonatal mortality according to gestational age. Before 30 weeks, the evidence for an effect is weaker and the benefit may be smaller. After 36 weeks of gestation, there is no evidence of a mortality benefit. Hence, this intervention has an effect only on preterm babies, is mediated through a reduction in preterm specific respiratory complications and can be assumed to relate to the category of direct preterm deaths used in ICD and in LiST.
The variation of mortality effect according to gestational age of administration of antenatal steroids to women in preterm labour compared with placebo. Figure created using data from 10 showing distinct risk by gestational age bands i. Six of the previous studies 21 , 23 , 30 , 31 , 33 , 34 used dexamethasone. This may reflect the increasing maturity of such babies. In 18 RCTs examined, eight had a protocol for a repeated course of treatment each week until birth.
In their study, comparing repeated steroid doses to women at risk of preterm labour, Crowther et al. In addition, babies that did develop respiratory problems had less severe episodes and lower requirement for ventilation. In the Cochrane review, 18 studies with mortality outcomes involving infants were included. No evidence of effects on maternal mortality or stillbirths were identified. Of the 18 studies with mortality outcomes, 14 are from HICs with current neonatal mortality rates NMR of less than 5 per and universal coverage of intensive care with ventilation for all babies and surfactant for all babies since mids.
Hence, the generalizability of these results to low- and middle-income countries is unclear. The mortality effect estimated by the Cochrane review might substantially underestimate the effect that could be expected in a setting in which preterm newborns currently receive little or no basic neonatal medical care, let alone intensive care.
We, therefore, hypothesized that earlier studies, in which the control groups received no surfactant and less complex intensive care and thus more closely resemble current conditions in low- and middle-income countries, might report larger effects than more recent studies.
Reordering the 18 studies in the Cochrane review by date, instead of author names in alphabetical order, does not reveal a clear trend, with relatively large effects seen in the four most recent studies Figure 3. However, the last four studies were from middle-income countries and so may confound any time trend in high-income countries. We undertook sub-analyses to see if earlier studies in the pre-surfactant era, and when intensive care was less complex, would indicate a greater effect size that may be more applicable for current low-income country settings meta-analysis not shown.
A meta-analysis fixed effects of 18 RCTs comparing administration of antenatal steroids for preterm labour with placebo and showing effect on preterm cause-specific mortality outcome. We then performed a separate meta-analysis restricted to four RCTs from middle-income countries Table 1. RCTs from middle-income countries comparing administration of antenatal steroids for preterm labour with placebo. Meta-analysis of four RCTs from middle-income countries comparing administration of antenatal steroids for preterm labour with placebo: Finally, we undertook a meta-analysis of the two identified observational studies from middle-income countries, which gave a summary risk ratio of 0.
Fixed effects meta-analysis of 14 RCTs from high-income countries comparing administration of antenatal steroids for preterm labour with placebo showing effect size on neonatal mortality outcome.
In summary, there is high-quality evidence of a substantial mortality effect of antenatal steroids, and this effect is greater in MICs than in high-income settings Table 2. However, there is a dearth of data from low-income countries Box 1. Quality assessment grade table of the effect of antenatal steroids for preterm labour on neonatal mortality due to direct complications of preterm birth.
Cause-specific mortality to act on: Cause-specific effect and range: Quality of input evidence: Mortality and morbidity data consistent. Observational study mortality data also consistent. The control group in all these studies was routine care, including ventilation and in many cases surfactant.
It is plausible that the effect of antenatal steroids may be even greater than that estimated above in settings where little other care is available. Preterm birth is the leading cause of neonatal mortality and morbidity in both high- and low-income countries.
Our meta-analysis, restricted to four RCTs from middle-income countries, suggests an even larger effect: The clearest evidence for an effect is for babies born between 31 weeks and 36 weeks gestation but, surprisingly, there may be benefit at even lower gestational ages, although it should be noted that in all these studies mechanical ventilation was routinely available in addition to antenatal steroids Figure 1. Importantly, the trials from settings with neonatal intensive care may underestimate the effect in low-income countries where there is little or no care for preterm neonates because neonatal intensive care was standard practice for the control group in all these trials Box 1.
The quality of estimate has a high evidence grade given the four RCTs from the middle-income countries and a large and consistent effect size. Considerably, more than 50 deaths are included in all these analysis.
The searches and abstraction of studies for this review were done by one author and checked by another author. We acknowledge this as a limitation compared with double abstraction.
The generalizability is moderate because there are no RCTs reported from low-income countries or any from South Asia. There has been some uptake of antenatal steroid therapy in middle-income countries such as South Africa 33 and Thailand.
Based on the Cochrane 10 review and additional meta-analyses for middle-income countries, there is high grade evidence that antenatal steroids are extremely effective in reducing deaths from direct complications of preterm birth. An injection to a woman in preterm labour of a drug that costs several dollars should be highly cost-effective as well as feasible.