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Grand Rounds

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

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BACKGROUND AND PURPOSE:

  • Concern exists that in the setting of FGR, repeat corticosteroid exposure may have long term consequences adverse neurocognitive outcomes
  • Cartwright et al. (JAMA Network Open Pediatrics, 2019) examined the effect of fetal growth restriction (FGR) on neurocognitive function in children, following repeat antenatal betamethasone injections

METHODS:

  • Preplanned secondary analysis RCT
    • Multicenter Australasian Collaborative Trial of Repeat Doses of Corticosteroids (ACTORDS) study
  • Parent RCT
    • <32 weeks’ gestation
    • Ongoing risk of preterm birth ≥7 days following first course of antenatal corticosteroids randomized to either
      • IM betamethasone
      • Saline placebo
    • Repeat injections weekly if continued risk
  • Follow-up
    • Up to 6 to 8 years of age
    • Pediatrician and psychologist assessment
      • Neurosensory and cognitive function
    • Parents completed standardized questionnaires
  • Main outcomes of the present study
    • Survival free of any disability and death or
    • Survival with moderate to severe disability

RESULTS:

  • 988 children
    • 55.0% male | mean [SD] age at follow-up 7.5 [1.1] years
  • There was no difference in the FGR rate between groups (P = .20)
    • Repeated betamethasone treatment group: 139 of 493 children (28.2%)
    • Placebo group 122 of 495 (24.6%) in the placebo group
  • No difference in survival free of any disability (P = .77)
    • FGR group: 75% for repeated betamethasone group vs 72.2% for placebo group
      • odds ratio [OR] 1.1 (95% CI, 0.6-1.9)
    • Non-FGR group: 79.7% for repeated betamethasone group vs 79.0% for placebo group
      • OR 1.0 (95% CI, 0.7-1.5)
  • No difference in death or moderate to severe disability (P = .84)
    • FGR group: 14.6% for repeated betamethasone group vs 15.9% for placebo group
      • OR 0.9 (95% CI, 0.4-1.9)
    • Non-FGR group: 8.6% for repeated betamethasone group vs 10.0% for placebo group
      • OR 0.8 (95% CI, 0.4-1.3)  

CONCLUSION:

  • Fetal growth restriction did not impact association between antenatal betamethasone exposure and neurodevelopment in children with 6 to 8 year follow up
  • Authors hypothesize that infants with FGR may have increased benefit from repeated antenatal corticosteroid therapy (2-fold reduction in serious neonatal morbidity)
    • Benefits may balance out risks of repeat antenatal corticosteroid exposure
  • The authors conclude

Physicians should use repeated doses of antenatal corticosteroids when indicated before preterm birth, regardless of FGR, in view of the associated neonatal benefits and absence of later adverse effects.

Learn More – Primary Sources:

Association of Fetal Growth Restriction With Neurocognitive Function After Repeated Antenatal Betamethasone Treatment vs Placebo: Secondary Analysis of the ACTORDS Randomized Clinical Trial.

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Related ObG Topics:

Antenatal Corticosteroids – When to Administer?
ACOG Guidance Update: Diagnosis and Management of PROM (Prelabor Rupture of Membranes)
Does General Anesthesia Exposure in Infancy Impact Neurodevelopment?

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