The Causes of Autism

Who are the breathtaking authors, what is the title of the study, and what year was it published?

Authors: Li-Nien Chien, Hsiu-Chen Lin, Yu-Hsuan Joni Shao, Shu-Ti Chiou, Hung-Yi Chiou

Title: Risk of Autism Associated With General Anesthesia During
Cesarean Delivery: A Population-Based Birth-Cohort Analysis. Journal of Autism and Developmental Disorders. (2015) 45:932–942

Year: 2015

What is the study about?

This study looked at whether there is a link between autism and the type of anesthesia given during childbirth. Researched in this study are two types of anesthesia, general anesthesia (GA) and regional anesthesia (RA). GA is a type of anesthesia that renders a patient unconscious and unable to feel pain. It is typically given intravenously or through inhalation. RA, on the other hand, blocks pain in a specific region of the body while allowing the patient to remain conscious. Common types of RA used during cesarean sections include epidural and spinal anesthesia. These methods block sensation in the lower part of the body while enabling the patient to remain alert. GA affects the entire body, including brain function, while RA only affects the part of the body being operated on, allowing patients to remain awake and alert.

What previous research is there on this topic?

A Swedish study published in 2002 reported that children born by C-section were 1.6 times more likely to develop autism than those born vaginally. A 2009 study found a similar association between C-sections and autism, but the relationship was eliminated after adjusting for breech presentation. Another study published in 2011 with a population in Canada discovered that babies born by C-section were 1.23 times more likely to develop autism than those born vaginally. In contrast, a Taiwanese population-based study revealed that the risk of autism was significantly associated with delivery by C-section with General Anesthesia (GA), but not with delivery by C-section with RA, after adjusting for potential risks.

The association between autism and obstetric anesthesia during C-section remains unclear. Regional anesthesia (RA) and general anesthesia (GA) are both accepted modes of anesthesia during C-section delivery, but GA is less commonly used due to potential risks for both mother and child. However, the risk factor for autism remains unknown. A better understanding of this association is crucial for early detection and prevention of autism, but few studies have explored the link between obstetric anesthesia and autism.

What methods were used?

Participants

This study analyzed more than 800,000 single births recorded in the Taiwanese National Birth Reporting Database between 2004 and 2007 to investigate the association between mode of delivery and the risk of autism. Newborns with missing data or records, gestational age outside the range of 20-42 weeks, or birth weight below 500 g were excluded, as were newborns with parents aged <15 or >80 years, mothers aged >45 years, and deliveries not covered by the National Health Insurance. The final sample consisted of 383,426 newborns delivered vaginally and 103,470 delivered via cesarean section.

Dependent Variables & Covariates

This study examined various factors that could be associated with the risk of autism, including neonatal characteristics, parental demographics, and maternal risks and complications during pregnancy and labor. Child characteristics such as sex, birth weight, gestational age, level of urbanization of residence, and 5-min Apgar score were considered, as well as parental demographics like age, education, and marital status. Maternal risks and complications during pregnancy and labor, such as hypertension, diabetes, preeclampsia, placenta previa, and fetal distress, were also examined. All of these factors were considered as potential confounders in the analysis to determine their association with the risk of autism.

Apgar Scores

The Apgar score is a system that medical professionals use to assess the health of an infant in the first few minutes after birth. It is based on the newborn’s appearance, pulse, grimace, activity level, and respiratory function. The Apgar score ranges from 0 to 10, with 10 indicating the best possible condition and 0 indicating the most critical. The score is usually assessed at one minute and five minutes after birth. A low Apgar score indicates that the newborn may need medical attention or resuscitation, but the score alone does not offer a definitive diagnosis of a problem.

What were the findings?

Basic Differences

Children delivered by C-section with RA or GA were also more likely to have parents who were older, married, or had a mother who experienced risks and complications during pregnancy. The data showed that 7.1% of the C-sections were performed using GA.

C-Section & General Anesthesia (GA)

Babies delivered by Cesarean section (C-section) with general anesthesia (GA) had a 52% higher risk of developing autism than those delivered vaginally or by C-section with regional anesthesia (RA).

The PS-matched cohort, which had balanced potential confounders for RA and GA, also indicated a higher risk of autism in babies delivered by C-section with GA. These findings suggest that the use of GA during C-section is associated with an increased risk of neurological disorder in childhood.

C-Section & Regional Anesthesia (RA)

There was no significant difference in the risk of autism between babies born by C-section with regional anesthesia (RA) or vaginal birth, after adjusting for other factors such as neonatal characteristics, parental demographics, and maternal risks and complications.

Sex Differences

In comparison to vaginal deliveries, children delivered by C-section with RA or GA had a higher likelihood of being male or having a low 5-min Apgar score, and were less likely to have jaundice or to be carried to full term.

As mentioned above, babies delivered by Cesarean section (C-section) with general anesthesia (GA) had a higher risk of developing autism than those delivered vaginally or by C-section with regional anesthesia (RA). This incidence of autism among girls was two times higher in children delivered by C-section with GA than in those delivered vaginally. However, when using ICD-9-CM 290.xx diagnostic coding to identify autism, the risk was only increased in boys delivered by C-section with GA.

Diagnostic Codes

The study used ICD-9-CM diagnosis codes to identify the diagnosis of autism, with a broader range of diagnostic codes used to account for variability within the autism spectrum. The researchers used the diagnostic code 299.0 for autism and 299.xx for the broader range of diagnoses. The study found that the broader range of diagnostic codes did not weaken the initial findings that babies delivered by C-section with GA had a higher risk of autism. The study also used the diagnostic code 290.xx, which is not specific to autism, to assess the sensitivity of the initial results, and the findings remained robust even with this comparison diagnostic code.

What do the researchers recommend individuals do with this information?

To improve the chances of preventing autism in babies, the authors recommend that obstetricians educate mothers to avoid C-sections with general anesthesia (GA), unless it is medically necessary. Babies born by C-section with GA have a higher risk of developing autism, and therefore, children delivered via C-section with GA should undergo autism screening during early childhood. By avoiding unnecessary GA during C-sections, the incidence of autism in babies could potentially be reduced.

What other research in the library is this study related to?

The findings of this particular study, which was published in 2015, are in alignment with another study reviewed in this library by Ou et al. (2019), which found that mothers of children with autism were more likely to have had a C-section delivery, and although that study did not mention GA versus RA during the C-section, another finding in that study was that the use of medication during pregnancy was found to be associated with autism.

What are the limitations of this study?

This study was retrospective and collected information from pre-existing sources, such as electronic medical records and claims data. This may introduce biases and limit the accuracy of the data. Reliability of autism diagnosis: Diagnosis codes from medical records were used to identify patients with autism, and there may be variability in how accurately the diagnosis is made.

Underdiagnosis of autism: The incidence of autism in Taiwan was lower in this study compared to rates reported in Western countries, which may indicate that autism is underdiagnosed in Taiwan. Limited generalizability: The study was conducted in Taiwan, and the findings may not be generalizable to other populations with different healthcare systems or sociocultural backgrounds. Incomplete data: Data related to the type of anesthesia administered and the reasons for its selection were not available and could not be included in the analysis. Births resulting from assisted reproductive technology were also not included in the study.

What are the strengths of this study?

Large sample size: The study utilized data from more than 87,000 births, which is considered a large sample size compared to many other studies conducted on this subject. This increases the statistical power of the study and makes the findings more reliable. Retrospective cohort design: Although retrospective studies have certain limitations, they also have some advantages, such as the ability to collect data from a large population and analyze data over a relatively long period of time. Moreover, the use of a cohort design helped to minimize the potential influences of bias on the evaluation of the association between autism and mode of delivery.

Comprehensive adjustment for potential confounders: The study controlled for many potential confounding factors that could affect the risk of autism, such as neonatal characteristics, parental demographics, and maternal risks and complications. Propensity-score matching analysis: The study conducted a propensity-score matching analysis to match participants in the C-section with RA group to those in the C-section with GA group based on their probabilities of receiving each type of anesthesia. This helped to reduce the potential for selection bias and to control for some unmeasured confounding variables. Adequate follow-up: The study had a mean follow-up duration of 4.3 years, which was long enough to detect most cases of autism diagnosis.

Can I read the full study somewhere?

You will need institutional access, or to purchase the article. Which you can do here.