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Grand Rounds

Cesarean Delivery and Risk of Neurodevelopmental Disorders: Is There a Real Link?

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BACKGROUND AND PURPOSE:

  • Recent studies suggest a link between cesarean delivery and attention-deficit/hyperactivity disorder (ADHD) or autism-spectrum disorder (ASD)
    • Studies did not control for cesarean indications or familial confounding
  • Zhang et al. (JAMA Network Open, 2021) examined the association between cesarean delivery and neurodevelopmental/psychiatric disorders in offspring

METHODS:

  • Swedish register-based cohort study
  • Participants
    • Term-birth | Singleton
    • Born between January 1, 1990 and December 31, 2003
    • Follow up through December 31, 2013
  • Exposures
    • Birth by cesarean (planned or intrapartum)
  • Study design
    • All included individuals were linked to their full siblings, maternal and paternal half siblings, and maternal full cousins
    • Neurodevelopmental disorders
      • ADHD | ASD | Intellectual disability | Tic disorders | Communication disorders | Learning disorders | Any neurodevelopmental disorder
    • Psychiatric disorders
      • Anxiety disorders | Obsessive-compulsive disorder | Depressive disorders | Eating disorders | Bipolar disorders | Psychotic disorders | Any psychiatric disorder
  • Primary outcomes
    • Registered diagnoses of neurodevelopmental disorders
    • Diagnoses of psychiatric disorders

RESULTS:

  • 1,179,341 individuals
    • Vaginal delivery: 1,048,838
      • Mean age at follow up: 17.7 years
    • Delivered via planned cesarean: 59,514
      • Mean age at follow up: 16.6 years
    • Delivered vis intrapartum cesarean: 70,989
      • Mean age at follow up 16.8 years

Not Adjusted for Familial Confounding

  • Compared with vaginal delivery, cesarean delivery was associated with higher risk for
    • Any neurodevelopmental disorder | ADHD | Intellectual disability
  • Only planned CD was associated with a higher risk for
    • ASD | Communication disorders | Learning disorders

Adjusted or Familial Confounding

  • The associations between cesarean delivery and any neurodevelopmental disorder, ADHD, ASD, and intellectual disability
    • Attenuated in full cousins and paternal half siblings
    • Further attenuated (became nonsignificant) in maternal half siblings and full siblings
    • Risk of any neurodevelopmental disorder in full siblings
      • Planned cesarean: HR, 0.93 (95% CI, 0.81 to 1.06)
      • Intrapartum cesarean: HR 1.07 (95% CI, 0.96 to 1.21)

CONCLUSION:

  • The association between cesarean delivery and increased risk for neurodevelopmental disorders found in previous studies is likely due to unmeasured familial confounding, not the procedure itself
  • The authors conclude

…observed associations attenuated to the null after adjusting for familial factors

Overall, the results do not suggest a causal association between CD and neurodevelopmental and psychiatric disorders

Learn More – Primary Sources:

Assessment of Cesarean Delivery and Neurodevelopmental and Psychiatric Disorders in the Children of a Population-Based Swedish Birth Cohort

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Related ObG Topics:

Is Macrolide Antibiotic Use During Pregnancy Linked to Increased Risk of Congenital Malformations?
HYPITAT-II Childhood Neurodevelopmental Outcomes: Delivery or Expectant Management for Non-Severe Late Preterm Hypertension?

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