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Association between general anesthesia for cesarean delivery and subsequent developmental disorders in children: a

Yi-Chen Chen¹, Fu-Wen Liang^2,3, Ping-Heng Tan^4,5

¹Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan.

|February 26, 2025

Insights

General anesthesia (GA) for cesarean delivery may increase the risk of developmental disorders in children within 4 years. This association appears linked to poorer Apgar scores, not direct neurotoxicity.

Area of Science:

Anesthesiology
Pediatrics
Developmental Neuroscience

Background:

In-utero exposure to general anesthetics (GA) during cesarean delivery is understudied regarding offspring developmental disorders.
Early childhood GA exposure is linked to developmental issues, prompting investigation into prenatal exposure risks.

Purpose of the Study:

To determine if general anesthesia (GA) used for cesarean delivery is associated with developmental disorders in children.
To compare developmental disorder incidence in infants exposed to GA versus neuraxial anesthesia (NA) during cesarean delivery.

Main Methods:

Nationwide retrospective cohort study using linked health databases (2015-2020).
Compared developmental disorder incidence (ICD codes) in singleton infants delivered via cesarean under GA vs. NA.
Used propensity score-based fine stratification weighting to adjust for confounders.

Main Results:

325,309 infants included; 6,973 under GA, 318,336 under NA.
GA-delivered infants showed a higher risk of developmental disorders within 2-4 years (aOR 1.12-1.17).
This association disappeared when Apgar scores were included in the model, suggesting Apgar scores as a mediator.

Conclusions:

General anesthesia for cesarean delivery may be associated with developmental disorders diagnosed within 2-4 years, potentially mediated by lower Apgar scores.
No direct evidence of GA-related neurotoxicity causing subsequent developmental disorders was found.

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Abstract

Background:

Exposure to general anesthetics (GA) in early childhood is associated with developmental disorders. However, few studies have addressed in-utero exposure to anesthetics during delivery and subsequent developmental disorders in the offspring. This study aimed to investigate whether GA for cesarean delivery is associated with developmental disorders in children.

Methods:

Using data retrieved from the National Health Insurance Research Database linked to the Birth Reporting Database and the Maternal and Child Health Database between 2015 and 2020, this nationwide retrospective cohort study compared the incidence of developmental disorders following cesarean delivery under GA with that under neuraxial anesthesia (NA). Developmental disorders were diagnosed using the corresponding International Classification of Diseases codes traced 2-6 years after delivery.

Results:

After excluding twins, children born with congenital anomalies or diseases and those with missing data, 325,309 eligible singleton pregnancies delivered through cesarean section under either GA or NA were enrolled. Of the total, 6973 of them were delivered under GA and 318,336 under NA. After propensity score-based fine stratification weighting with a model including age, socioeconomic deprivation, gestational status, infant sex, preterm delivery, low birth weight, and cesarean delivery duration, children delivered under GA were associated with a higher risk of developmental disorders diagnosed within 2 years (adjusted odds ratio [aOR], 1.17; 95% confidence interval [CI], 1.07-1.28), 3 years (aOR, 1.12; 95% CI, 1.04-1.21), and 4 years (aOR, 1.12; 95% CI, 1.04-1.21) compared with those under NA. This association was no longer present when the confounding effect of Apgar scores was included in the propensity-score model.

Conclusions:

GA for cesarean delivery may be associated with developmental disorders diagnosed within 2-4 years after birth manifested through poorer 1- and 5-min Apgar scores. There is no evidence of a direct relationship between GA-related neurotoxicity and subsequent developmental disorders.

Keywords:

Anesthesia Apgar scores Developmental disorders Neurotoxicity

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