Original Article| Volume 45, P34-40, February 2021

Download started.


General anesthesia for cesarean delivery and childhood neurodevelopmental and perinatal outcomes: a secondary analysis of a randomized controlled trial

Published:August 25, 2020DOI:


      • Few data on neurologic outcomes after in utero exposure to general anesthesia (GA).
      • Secondary analysis of randomized trial of maternal magnesium and cerebral palsy.
      • Exposure to GA was not associated with impaired neurodevelopment overall.
      • Only severe motor delay was significantly more common among infants exposed to GA.
      • Findings are reassuring regarding a single, short in utero exposure to GA.



      In 2016, the U.S. Food and Drug Administration expressed concern that neurodevelopment may be negatively affected by anesthesia or sedation exposure in pregnancy or before three years of age. We examined the association between general anesthesia at the time of cesarean delivery and early childhood neurodevelopment.


      A secondary analysis of a multicenter randomized controlled trial assessing magnesium for prevention of cerebral palsy in infants at risk for preterm delivery. Exposure was general compared to neuraxial anesthesia. The primary outcome was motor or mental delay at two years of age, assessed by Bayley Scales of Infant Development II (BSIDII). Secondary outcomes included BSIDII subdomains and perinatal outcomes. Multivariable logistic regression models were performed to control for confounders.


      Of 557 women undergoing cesarean delivery, 119 (21%) received general anesthesia. There were no differences in the primary composite outcome of developmental delay (aOR 0.93, 95% CI 0.61 to 1.43) or the BSIDII subdomains of mild, moderate, or severe mental delay, or mild or moderate motor delay. Severe motor delay was more common among infants exposed to general anesthesia (aOR 1.98, 95% CI 1.06 to 3.69). Infants exposed to general anesthesia had longer neonatal intensive care stays (51 vs 37 days, P=0.010).


      General anesthesia for cesarean delivery was not associated with overall neurodevelopmental delay at two years of age, except for greater odds of severe motor delay. Future studies should evaluate this finding, as well as the impact on neurodevelopment of longer or multiple anesthetic exposures across all gestational ages.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to International Journal of Obstetric Anesthesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Bloom S.
        • Spong C.
        • Weiner S.
        • et al.
        Complications of anesthesia for cesarean delivery.
        Obstet Gynecol. 2005; 106: 281-287
        • Butwick A.
        • El-Sayed Y.
        • Blumenfeld Y.
        • Osmundson S.
        • Weiniger C.
        Mode of anaesthesia for preterm Cesarean delivery: secondary analysis from the Maternal-Fetal Medicine Units Network Caesarean Registry.
        Br J Anaesth. 2015; 115: 267-274
      1. FDA Drug Safety Communication: FDA review results in new warnings about using general anesthetics and sedation drugs in young children and pregnant women. Available at December 14, 2016. Accessed July 2020.

        • Olutoye O.
        • Baker B.
        • Belfort M.
        • Olutoye O.
        Food and Drug Administration warning on anesthesia and brain development: implications for obstetric and fetal surgery.
        Am J Obstet Gynecol. 2018; 218: 98-102
        • Creeley C.
        • Dikranian K.
        • Dissen G.
        • Martin L.
        • Olney J.
        • Brambrink A.
        Propofol-induced apoptosis of neurons and oligodendrocytes in fetal and neonatal rhesus macaque brain.
        Br J Anaesth. 2013; 110: i29-i38
        • De Tina A.
        • Palanisamy A.
        General anesthesia during the third trimester: any link to neurocognitive outcomes?.
        Anesthesiol Clin. 2013; 35: 69-80
        • Palanisamy A.
        • Baxter M.
        • Keel P.
        • Xie Z.
        • Crosby G.
        • Culley D.
        Rats exposed to isoflurane in utero during early gestation are behaviorally abnormal as adults.
        Anesthesiology. 2011; 114: 521-528
        • Istaphanous G.
        • Loepke A.
        General anesthetics and the developing brain.
        Curr Opin Anaesthesiol. 2009; 22: 368-373
        • Block R.
        • Thomas J.
        • Bayman E.
        • Choi J.
        • Kimble K.
        • Todd M.
        Are anesthesia and surgery during infancy associated with altered academic performance during childhood?.
        Anesthesiology. 2012; 117: 494-503
        • McCann M.
        • de Graaff J.
        • Dorris L.
        • et al.
        GAS Consortium. Neurodevelopmental outcome at 5 years of age after general anaesthesia or awake-regional anaesthesia in infancy (GAS): an international, multicentre, randomised, controlled equivalence trial.
        Lancet. 2019; 393: 664-677
        • Sun L.
        • Li G.
        • Miller T.
        • et al.
        Association between a single general anesthesia exposure before age 36 months and neurocognitive outcomes in later childhood.
        JAMA. 2016; 315: 2312-2320
        • Warner D.
        • Zaccariello M.
        • Katusic S.
        • et al.
        Neuropsychological and behavioral outcomes after exposure of young children to procedures requiring general anesthesia: The Mayo Anesthesia Safety in Kids (MASK) Study.
        Anesthesiology. 2018; 129: 89-105
        • Glatz P.
        • Sandin R.
        • Pedersen N.
        • Bonamy A.
        • Eriksson L.
        • Granath F.
        Association of anesthesia and surgery during childhood with long-term academic performance.
        JAMA Pediatr. 2017; 171e163470
        • O'Leary J.
        • Janus M.
        • Duku E.
        • et al.
        A population-based study evaluating the association between surgery in early life and child development at primary school entry.
        Anesthesiology. 2016; 125: 272-279
        • O'Leary J.
        • Janus M.
        • Duku E.
        • et al.
        Influence of surgical procedures and general anesthesia on child development before primary school entry among matched sibling pairs.
        JAMA Pediatr. 2019; 173: 29-36
        • Afolabi B.
        • Lesi F.
        Regional versus general anaesthesia for caesarean section (review).
        Cochrane Database Syst Rev. 2012; 10 (CD004350)
        • Sprung J.
        • Flick R.
        • Wilder R.
        • et al.
        Anesthesia for cesarean delivery and learning disabilities in a population-based birth cohort.
        Anesthesiology. 2009; 111: 302-310
        • Rouse D.
        • Hirtz D.
        • Thom E.
        • et al.
        A randomized, controlled trial of magnesium sulfate for the prevention of cerebral palsy.
        N Engl J Med. 2008; 359: 895-905
        • Vohr B.
        • Stephens B.
        • Higgins R.
        • et al.
        Are outcomes of extremely preterm infants improving? Impact of Bayley assessment on outcomes.
        J Pediatr. 2012; 161: 222-228
        • Johnson S.
        • Moore T.
        • Marlow N.
        Using the Bayley-III to assess neurodevelopmental delay: which cut-off should be used?.
        Pediatr Res. 2014; 75: 670-674
        • Sanchez-Pinto L.
        • Venable L.
        • Fahrenbach J.
        • Churpek M.
        Comparison of variable selection methods for clinical predictive modeling.
        Int J Med Inform. 2018; 116: 10-17
        • McPherson C.
        • Inder T.
        Perinatal and neonatal use of sedation and analgesia.
        Semin Fetal Neonatal Med. 2017; 22: 314-320
        • Rollins M.
        • Lucero J.
        Overview of anesthetic considerations for cesarean delivery.
        Br Med Bull. 2012; 101: 105-125
        • Devroe S.
        • Van de Velde M.
        • Rex S.
        General anesthesia for caesarean section.
        Curr Opin Anaesthesiol. 2015; 28: 240-246
        • Chien L.
        • Lin H.
        • Shao Y.
        • Chiou S.
        • Chiou H.
        Risk of autism associated with general anesthesia during cesarean delivery: a population-based birth-cohort analysis.
        J Autism Dev Disord. 2015; 45: 932-942
        • Creagh O.
        • Torres H.
        • Rivera K.
        • Morales-Franqui M.
        • Altieri-Acevedo G.
        • Warner D.
        Previous exposure to anesthesia and autism spectrum disorder (ASD): a Puerto Rican population-based sibling cohort study.
        Bol Asoc Med P R. 2015; 107: 29-37
        • Sampaio T.
        • de Oliveira L.
        • Constantino L.
        • et al.
        Long-term neurobehavioral consequences of a single ketamine neonatal exposure in rats: effects on cellular viability and glutamate transport in frontal cortex and hippocampus.
        Neurotox Res. 2018; 34: 649-659