Antenatal steroids in preterm labour for the prevention of neonatal deaths due to complications of preterm birth

Abstract

Background: In high-income countries, administration of antenatal steroids is standard care for women with anticipated preterm labour. However, although >1 million deaths due to preterm birth occur annually, antenatal steroids are not routine practice in low-income countries where most of these deaths occur.

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. Quality of evidence was assessed using an adapted GRADE approach. Existing meta-analyses were reviewed for relevance to low/middle-income countries, and new meta-analysis was performed.

Results: We identified 44 studies, including 18 randomised control trials (RCTs) (14 in high-income countries) in a Cochrane meta-analysis, which suggested that antenatal steroids decrease neonatal mortality among preterm infants (<36 weeks gestation) by 31% [relative risk (RR) = 0.69; 95% confidence interval (CI) 0.58-0.81]. Our new meta-analysis of four RCTs from middle-income countries suggests 53% mortality reduction (RR = 0.47; 95% CI 0.35-0.64) and 37% morbidity reduction (RR = 0.63; 95% CI 0.49-0.81). 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.

Conclusions: Based on high-grade evidence, antenatal steroid therapy is very effective in preventing neonatal mortality and morbidity, yet remains at low coverage in low/middle-income countries. If fully scaled up, this intervention could save up to 500 000 neonatal lives annually.

Figure 1

Synthesis of study identification in review of the effects of antenatal corticosteroids for the treatment of RDS morbidity and mortality in preterm labour. Bold/italic text shows new meta-analysis undertaken until May 2009

Figure 2

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 showing distinct risk by gestational age bands (i.e. not cumulative risk). For gestational age of >36 weeks, the 95% CI is not shown (RR = 2.2; 0.79, 8.96; 896 babies)

Figure 3

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. Total events = 491; heterogeneity χ = 21.54 (df = 17); P = 0.203; test of RR = 1; z = 4.50; P = 0.000. Fixed effect meta-analysis. Note: 18 RCTs the same inputs as Cochrane review but meta-analysis revised to order by date of study instead of author alphabetical order

Figure 4

Meta-analysis of four RCTs from middle-income countries comparing administration of antenatal steroids for preterm labour with placebo: (a) effect size on preterm cause-specific mortality outcome [total events = 142; heterogeneity χ = 0.08 (d.f. = 3); P = 0.994; test of RR = 1; z = 4.87; P = 0.000; fixed effect meta-analysis]; and (b) effect size on RDS (severe morbidity outcome) [total events = 185; heterogeneity χ = 13.40 (d.f. = 3); P = 0.004; test of RR = 1; z = 3.58; P = 0.000; random effects meta-analysis]

Figure 5

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. Total events = 349; fixed effect meta-analysis; heterogeneity χ = 12.48 (df = 13); P = 0.489; test of RR = 1; z = 2.33; P = 0.020

Figure 6

Fixed effect meta-analysis of two observational studies from low/middle-income countries comparing administration of antenatal steroids for preterm labour with placebo showing effect size on neonatal mortality outcome. Total events = 135; fixed effect meta-analysis; heterogeneity χ = 1.09 (df = 1); P = 0.297; test of RR = 1; z = 3.70; P = 0.000