BACKGROUND AND PURPOSE:

• Unclear whether repeat courses of prenatal corticosteroids can reduce risks and outcomes associated with preterm birth
• Crowther et al. (PLoS Medicine, 2019) assessed whether the effects of repeat corticosteroid treatments in women with an ongoing risk of preterm birth effects varied depending on participant and treatment factors

METHODS:

• Individual participant meta-analysis
  • Prenatal Repeat Corticosteroid International IPD-MA Study (PRECISE)
• Study inclusion criteria
  • RCTs including women at risk of preterm birth
  • Participants had received single course of prenatal corticosteroid seven or more days prior
  • Outcomes compared with either placebo or no placebo
• Primary outcomes
  • Infant outcomes: Overall serious outcome | Use of respiratory support | Birth weight z-scores
  • Childhood outcomes: Death | Neurosensory disability
  • Maternal outcomes: Maternal sepsis
• Serious outcomes: Death | Severe respiratory disease | Grade 3 or 4 IVH | Chronic lung disease (oxygen dependent at 36 weeks postmenstrual age) | NEC | Stage 3 or worse ROP | Cystic periventricular leucomalacia)
• Data collection and analysis
  • Studies found using the Cochrane Pregnancy and Childbirth search strategy
  • Individual patient data requested from investigators
  • Risk of bias was assessed using criteria from the Cochrane Collaboration
• Authors sought to determine if the following individual characteristics impacted treatment effects 
  • Reason for preterm birth (e.g., hemorrhage vs preterm labor)
  • Gestational age at time of repeat prenatal
  • Number of repeat doses
  • Amount of time prior to birth

RESULTS:

• 11 trials | 4,857 | 5,915 infants
  • Mean gestational age at entry: 27.4 weeks to 30.2 weeks
• No difference in infants with a serious outcome
  • Relative risk [RR] 0.92 (95% CI, 0.82 to 1.04)
• Respiratory support less common in infants exposed to repeat corticosteroid
  • RR 0.91 (95% CI 0.85 to 0.97)
  • NNT to prevent respiratory support: 21 (95% CI 14 to 41)
  • Beneficial impact increased with number of doses
• Birth weight z-scores were lower in infants exposed to repeat corticosteroid
  • Mean difference −0.12 (95%CI −0.18 to −0.06)
  • The more doses, the greater the negative impact on weight, length and head circumference
• Maternal and child outcomes: No differences were identified
• Treatment effect did not vary based on  
  • Reason for preterm birth risk
  • Number of fetuses
  • Gestational age at treatment
  • Time prior to birth of last dose
• Not all subgroups could be assessed due to low ‘n’

CONCLUSION:

• Repeat antenatal corticosteroids for those at increased risk of preterm birth
  • Reduces use of infant respiratory support
  • Lowers weight, length and head circumference
• The authors conclude that

To provide clinical benefit with the least effect on growth, the number of repeat treatment courses should be limited if possible. We suggest a maximum of three repeat treatments and a total dose of between 24 mg and 48 mg.

Learn More – Primary Sources:

Effects of repeat prenatal corticosteroids given to women at risk of preterm birth: An individual participant data meta-analysis

Related ObG Topics:

Antenatal Corticosteroids – When to Administer?

In Women at Risk of Late Preterm Delivery, is Corticosteroid Therapy Still Cost-Effective?

Is There Value to the Use of Corticosteroids in Women with Short Cervix Who Are Asymptomatic?

Does FGR Impact Neurocognitive Function in Childhood Following Repeat Antenatal Betamethasone Dosing?