NIHR Signal Antenatal corticosteroids reduce breathing problems in late preterm babies

Published on 21 February 2017

Giving corticosteroids to women at risk of preterm birth at 34 weeks of pregnancy or later reduced the risk of severe breathing problems in the baby after birth from 1.9% to 1.1%. Steroids also reduced the risk for babies born by planned caesarean section after 37 weeks (so not premature).

Steroids are known to be beneficial if given to pregnant women at risk of preterm birth before 34 weeks and are already advised for babies born by caesarean section. This meta-analysis of six large trials provides new evidence that steroids might also benefit premature babies born after the 34th week. However, the review also found steroids increased the risk of low blood sugar in the new-born, which would need monitoring.

The risks and benefits need to be considered before further recommendations can be made extending the use of antenatal corticosteroids to this late preterm age. This includes exploring the long-term effects and consequences for specific groups of women such as those with diabetes or pregnant with more than one baby. 

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Why was this study needed?

In the UK, about one baby in every 13 is born prematurely, before 37 weeks of pregnancy. Preterm new-borns, particularly those born before 34 weeks of pregnancy, are at high risk of respiratory distress syndrome. They may need help to breathe and can be at risk of long-term problems such as learning difficulties.

Giving corticosteroids to women at risk of preterm labour helps the unborn baby’s lungs to mature quicker and reduces the chance of respiratory distress syndrome.

To date evidence has suggested that antenatal corticosteroids give most benefit if the baby is between 26 and 34 weeks plus six days of pregnancy. There has been uncertainty whether antenatal corticosteroids could benefit late preterm babies, born at 34 weeks or later. This is what this review aimed to address. It also looked at outcomes for babies born by planned caesarean section at 37 weeks of pregnancy or more.

What did this study do?

This systematic review and meta-analysis identified six randomised controlled trials involving 5698 women who were pregnant with one baby. The trials compared the use of antenatal corticosteroids with placebo or no treatment. Four trials used the corticosteroid betamethasone and two used dexamethasone, both given my muscular injection.

Three trials (3200 women) examined the effect of steroids in babies born between 34 and 36 weeks plus six days of pregnancy. The other three trials (2498 women) included babies born by planned caesarean at 37 weeks of pregnancy or later.

The researchers’ main outcome of interest was severe respiratory distress, but none of the individual trials were reported to have assessed this as their main outcome.

Most of the trials had a low risk of bias. Only one trial was carried out in the UK.

What did it find?

  • Antenatal corticosteroids reduced risk of severe respiratory distress in babies delivered at 34 weeks or later (vaginally or by caesarean section). This occurred in 1.1% of babies whose received antenatal corticosteroids compared with 1.9% who didn’t (relative risk [RR] 0.55, 95% confidence interval [95% CI] 0.33 to 0.91). Four trials had examined this outcome.
  • Antenatal steroids also reduced risk of overall respiratory distress syndrome in babies born at 34 weeks or later. The condition at any level of severity from mild to severe developed in the babies of 5.5% of treated mothers compared to 7.2% of untreated (RR 0.74, CI 0.61 to 0.91). These results were from meta-analysis of all six trials.
  • In the three trials of babies delivered vaginally between the start of 34 weeks and 36 weeks plus six days, antenatal corticosteroids also reduced risk of severe respiratory distress syndrome, which developed in 1.4% compared with 2.2% (RR 0.60, 95% CI 0.33 to 0.94).
  • Babies delivered by planned caesarean section at 37 weeks had reduced risk of overall respiratory distress syndrome if their mother received corticosteroids (2.7% vs. 6.7%, RR 0.40, 95% CI 0.27 to 0.59).
  • The three trials of babies delivered between 34 and 36 weeks plus six days found that antenatal corticosteroids increased risk of low blood sugar in the new-born. This complication occurred in 22.8% compared with 14.2% of babies whose mothers didn’t receive antenatal corticosteroids (RR 1.61, 95% CI 1.38 to 1.87).
  • Antenatal corticosteroids had no effect on risk of new-born death.

What does current guidance say on this issue?

The Royal College of Obstetricians and Gynaecologists recommend that antenatal corticosteroids are offered to women between 24 and 34 weeks plus 6 days of pregnancy who are at risk of preterm birth (spontaneous or induced). Use prior to 24 weeks is only considered by senior doctors.

The guidelines do not give a recommendation on use of corticosteroids for risk of spontaneous birth after 34 weeks of pregnancy. However, they do recommend that corticosteroids be given to all women up to 38 weeks plus six days of pregnancy for whom an elective caesarean section is planned.

What are the implications?

Antenatal corticosteroids might benefit late preterm babies born after 34 weeks, as well as those born earlier. It could mean fewer babies need respiratory support and leave hospital sooner, with reduced risk of associated complications.

However, the mixed findings by pregnancy age and low outcome rates – particularly for severe respiratory distress – combined with the risk of low blood sugar, limit the strength of conclusions. There is no evidence on the long-term effects, or the effects in specific groups of women, such as those pregnant with multiple babies. These issues need to be clarified before further recommendations can be made.

Citation and Funding

Saccone G, Berghella V. Antenatal corticosteroid for maturity of term or near term foetuses: systemic review and meta-analysis of randomized controlled trials. BMJ. 2016;355:i5044

This study received no funding.

Bibliography

NHS Choices. Neonatal respiratory distress syndrome. London: Department of Health; 2015.

NHS Choices. Premature labour and birth. London: Department of Health; 2015.

Patient. Infant Respiratory Distress Syndrome. EMIS Group PLC. Leeds; 2016.

RCOG. Antenatal Corticosteroids to Reduce Neonatal Morbidity and Mortality. Green-top Guideline No.7. Royal College of Obstetricians and Gynaecologists. London; 2010.

WHO. Preterm birth. Factsheet No.363. Geneva: World Health Organization; 2015.

Why was this study needed?

In the UK, about one baby in every 13 is born prematurely, before 37 weeks of pregnancy. Preterm new-borns, particularly those born before 34 weeks of pregnancy, are at high risk of respiratory distress syndrome. They may need help to breathe and can be at risk of long-term problems such as learning difficulties.

Giving corticosteroids to women at risk of preterm labour helps the unborn baby’s lungs to mature quicker and reduces the chance of respiratory distress syndrome.

To date evidence has suggested that antenatal corticosteroids give most benefit if the baby is between 26 and 34 weeks plus six days of pregnancy. There has been uncertainty whether antenatal corticosteroids could benefit late preterm babies, born at 34 weeks or later. This is what this review aimed to address. It also looked at outcomes for babies born by planned caesarean section at 37 weeks of pregnancy or more.

What did this study do?

This systematic review and meta-analysis identified six randomised controlled trials involving 5698 women who were pregnant with one baby. The trials compared the use of antenatal corticosteroids with placebo or no treatment. Four trials used the corticosteroid betamethasone and two used dexamethasone, both given my muscular injection.

Three trials (3200 women) examined the effect of steroids in babies born between 34 and 36 weeks plus six days of pregnancy. The other three trials (2498 women) included babies born by planned caesarean at 37 weeks of pregnancy or later.

The researchers’ main outcome of interest was severe respiratory distress, but none of the individual trials were reported to have assessed this as their main outcome.

Most of the trials had a low risk of bias. Only one trial was carried out in the UK.

What did it find?

  • Antenatal corticosteroids reduced risk of severe respiratory distress in babies delivered at 34 weeks or later (vaginally or by caesarean section). This occurred in 1.1% of babies whose received antenatal corticosteroids compared with 1.9% who didn’t (relative risk [RR] 0.55, 95% confidence interval [95% CI] 0.33 to 0.91). Four trials had examined this outcome.
  • Antenatal steroids also reduced risk of overall respiratory distress syndrome in babies born at 34 weeks or later. The condition at any level of severity from mild to severe developed in the babies of 5.5% of treated mothers compared to 7.2% of untreated (RR 0.74, CI 0.61 to 0.91). These results were from meta-analysis of all six trials.
  • In the three trials of babies delivered vaginally between the start of 34 weeks and 36 weeks plus six days, antenatal corticosteroids also reduced risk of severe respiratory distress syndrome, which developed in 1.4% compared with 2.2% (RR 0.60, 95% CI 0.33 to 0.94).
  • Babies delivered by planned caesarean section at 37 weeks had reduced risk of overall respiratory distress syndrome if their mother received corticosteroids (2.7% vs. 6.7%, RR 0.40, 95% CI 0.27 to 0.59).
  • The three trials of babies delivered between 34 and 36 weeks plus six days found that antenatal corticosteroids increased risk of low blood sugar in the new-born. This complication occurred in 22.8% compared with 14.2% of babies whose mothers didn’t receive antenatal corticosteroids (RR 1.61, 95% CI 1.38 to 1.87).
  • Antenatal corticosteroids had no effect on risk of new-born death.

What does current guidance say on this issue?

The Royal College of Obstetricians and Gynaecologists recommend that antenatal corticosteroids are offered to women between 24 and 34 weeks plus 6 days of pregnancy who are at risk of preterm birth (spontaneous or induced). Use prior to 24 weeks is only considered by senior doctors.

The guidelines do not give a recommendation on use of corticosteroids for risk of spontaneous birth after 34 weeks of pregnancy. However, they do recommend that corticosteroids be given to all women up to 38 weeks plus six days of pregnancy for whom an elective caesarean section is planned.

What are the implications?

Antenatal corticosteroids might benefit late preterm babies born after 34 weeks, as well as those born earlier. It could mean fewer babies need respiratory support and leave hospital sooner, with reduced risk of associated complications.

However, the mixed findings by pregnancy age and low outcome rates – particularly for severe respiratory distress – combined with the risk of low blood sugar, limit the strength of conclusions. There is no evidence on the long-term effects, or the effects in specific groups of women, such as those pregnant with multiple babies. These issues need to be clarified before further recommendations can be made.

Citation and Funding

Saccone G, Berghella V. Antenatal corticosteroid for maturity of term or near term foetuses: systemic review and meta-analysis of randomized controlled trials. BMJ. 2016;355:i5044

This study received no funding.

Bibliography

NHS Choices. Neonatal respiratory distress syndrome. London: Department of Health; 2015.

NHS Choices. Premature labour and birth. London: Department of Health; 2015.

Patient. Infant Respiratory Distress Syndrome. EMIS Group PLC. Leeds; 2016.

RCOG. Antenatal Corticosteroids to Reduce Neonatal Morbidity and Mortality. Green-top Guideline No.7. Royal College of Obstetricians and Gynaecologists. London; 2010.

WHO. Preterm birth. Factsheet No.363. Geneva: World Health Organization; 2015.

Antenatal corticosteroids for maturity of term or near term fetuses: systematic review and meta-analysis of randomized controlled trials

Published on 14 October 2016

Saccone, G.,Berghella, V.

Bmj Volume 355 , 2016

OBJECTIVE: To evaluate the effectiveness of antenatal corticosteroids given at >/=34 weeks' gestation. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Electronic databases were searched from their inception to February 2016. ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomized clinical trials comparing antenatal corticosteroids with placebo or no treatment in women with a singleton pregnancy at >/=34 weeks' gestation. Trials on antenatal steroids in women expected to deliver late preterm (340-366 weeks) and trials given before planned cesarean delivery at term (>/=37 weeks) were included. DATA SYNTHESIS: The primary outcome was the incidence of severe respiratory distress syndrome (RDS). The summary measures were reported as relative risks or mean differences with 95% confidence intervals. RESULTS: Six trials, including 5698 singleton pregnancies, were analyzed. Three included 3200 women at 340-366 weeks' gestation and at risk of imminent premature delivery at the time of hospital admission. The three other trials included 2498 women undergoing planned cesarean delivery at >/=37 weeks. Overall, infants of mothers who received antenatal corticosteroids at >/=34 weeks had a significantly lower risk of RDS (relative risk 0.74, 95% confidence interval 0.61 to 0.91), mild RDS (0.67, 0.46 to 0.96), moderate RDS (0.39, 0.18 to 0.89), transient tachypnea of the newborn (0.56, 0.37 to 0.86), severe RDS (0.55, 0.33 to 0.91), use of surfactant, and mechanical ventilation, and a significantly lower time receiving oxygen (mean difference -2.06 hours, 95% confidence interval -2.17 to -1.95), lower maximum inspired oxygen concentration (-0.66%, -0.69% to -0.63%), shorter stay on a neonatal intensive care unit (-7.64 days, -7.65 to -7.64), and higher APGAR scores compared with controls. Infants of mothers who received antenatal betamethasone at 340-366 weeks' gestation had a significantly lower incidence of transient tachypnea of the newborn (relative risk 0.72, 95% confidence interval 0.56 to 0.92), severe RDS (0.60, 0.33 to 0.94), and use of surfactant (0.61, 0.38 to 0.99). Infants of mothers undergoing planned cesarean delivery at >/=37 weeks' gestation who received prophylactic antenatal corticosteroids 48 hours before delivery had a significantly lower risk of RDS (0.40, 0.27 to 0.59), mild RDS (0.43, 0.26 to 0.72), moderate RDS (0.40, 0.18 to 0.88), transient tachypnea of the newborn (0.38, 0.25 to 0.57), and mechanical ventilation (0.19, 0.08 to 0.43), and significantly less time receiving oxygen (mean difference -2.06 hours, 95% confidence interval -2.17 to -1.95), lower percentage of maximum inspired oxygen concentration (-0.66%, -0.69% to -0.63%), shorter stay in neonatal intensive care (-7.44 days, -7.44 to -7.43), and a higher APGAR score at one and at five minutes. CONCLUSIONS: Antenatal steroids at >/=34 weeks' gestation reduce neonatal respiratory morbidity. A single course of corticosteroids can be considered for women at risk of imminent late premature delivery 340-366 weeks' gestation, as well as for women undergoing planned cesarean delivery at >/=37 weeks' gestation. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016035234.

Preterm birth is defined as a live baby born before 37 completed weeks of pregnancy. A baby is considered extremely premature when born before 28 weeks, very preterm at 28 to 32 weeks, and moderate to late preterm at 32 to 37 weeks.

Respiratory distress syndrome is a condition where the under-developed lungs do not produce enough surfactant, a substance rich in fat and protein that helps prevent the airways from collapsing. In these trials respiratory distress syndrome was defined as compatible clinical signs (such as shallow and rapid breathing, blue lips and extremities), typical signs on chest X-ray, and need for oxygen. No specific definitions were given for mild, moderate or severe.

Expert commentary

This review should prompt immediate review of practice in all settings where women give birth. Administration of corticosteroids to women before a baby is born at extreme prematurity is a highly effective way to improve outcomes for a vulnerable group of babies. This review reinforces the value of administering steroids before planned birth at term or near term. While individual babies are at low risk when born after 33 weeks gestation the burdens to the baby, family and society of near-term birth are considerable. These burdens, particularly time spent on neonatal intensive care, can be reduced with a simple intervention.

Dr Mark Turner, Senior Lecturer and Consultant in Neonatology, University of Liverpool

Expert commentary

Guidelines from the Royal College of Obstetricians and Gynaecologists, written in 2010, recommend corticosteroids to reduce the risk of respiratory morbidity in babies delivered by elective caesarean section prior to 38+6 weeks (based on one randomised controlled trial). This meta-analysis of three trials suggests this recommendation remains appropriate. No specific UK guidance exists for corticosteroid use in women at risk of imminent late premature delivery at 34+0 to 36+6 weeks. This systematic review and meta-analysis suggests steroids reduce the risk of severe respiratory distress syndrome but increase the risk of neonatal hypoglycaemia – women therefore need to be counselled about the benefits and risks. Evidence of long-term effects in these groups is lacking and further studies are urgently needed.

Stephen Robson, Professor of Fetal Medicine, Newcastle University