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Effect of cesarean section on the risk of autism spectrum disorders/attention deficit hyperactivity disorder in offspring: a meta-analysis

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Abstract

Purpose

This study was conducted to investigate the relationship between cesarean section (CS) offspring and autism spectrum disorders (ASD)/attention deficit hyperactivity disorder (ADHD).

Methods

Searching of the databases (PubMed, Web of Science, Embase, and Cochrane Library) for studies on the relationship between mode of delivery and ASD/ADHD until August 2022. The primary outcome was the incidence of ASD/ADHD in the offspring.

Results

This meta-analysis included 35 studies (12 cohort studies and 23 case–control studies). Statistical results showed a higher risk of ASD (odds ratio (OR) = 1.25, P < 0.001) and ADHD (OR = 1.11, P < 0.001) in CS offspring compared to the VD group. Partial subgroup analysis showed no difference in ASD risk between CS and VD offspring in sibling-matched groups (OR = 0.98, P = 0.625). The risk of ASD was higher in females (OR = 1.66, P = 0.003) than in males (OR = 1.17, P = 0.004) in the CS offspring compared with the VD group. There was no difference in the risk of ASD between CS under regional anesthesia group and VD group (OR = 1.07, P = 0.173). However, the risk of ASD was higher in the CS offspring under general anesthesia than in the VD offspring (OR = 1.62, P < 0.001). CS offspring developed autism (OR = 1.38, P = 0.011) and pervasive developmental disorder-not otherwise specified (OR = 1.46, P = 0.004) had a higher risk than VD offspring, but there was no difference in Asperger syndrome (OR = 1.19, P = 0.115). Offspring born via CS had a higher incidence of ADHD in different subgroup analyses (sibling-matched, type of CS, and study design).

Conclusions

In this meta-analysis, CS was a risk factor for ASD/ADHD in offspring compared with VD.

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Availability of data and materials

The datasets supporting this article's conclusions are included within the article and its additional files.

Abbreviations

ASD:

Autism spectrum disorders

ADHD:

Attention deficit hyperactivity disorder

ID:

Intellectual disability

CS:

Cesarean section

VD:

Vaginal delivery

PRISMA:

Preferred reporting items for systematic reviews and meta-analyses

NOS:

Newcastle–Ottawa scale

PDD-NOS:

Pervasive developmental disorder-not otherwise specified

CI:

Confidence interval

OR:

Odds ratio

GA:

General anesthesia

RA:

Regional anesthesia

UCP:

Mitochondrial uncoupling protein

5-HT:

5-Hydroxytryptamine

NA:

Not available

ICD:

International classification of diseases

DSM:

Diagnostic and statistical manual of mental disorders

ADOS-G:

Autism diagnostic observation schedule–generetic

ADI-R:

Autism diagnostic interview–revised

CARS:

Childhood autism rating scale

K-SADS:

Schedule for affective disorders and schizophrenia for school-aged children

CPAP:

Continuous positive airway pressure

BMI:

Body mass index

ALSPAC:

Avon longitudinal study of parents and children

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  1. Meiling Chen, Yeting Lin, Chiyuan Yu and Rongrong Fu are contributed equally to this work.

Authors and Affiliations

  1. The Public Health College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

    Meiling Chen, Jie Yao & Jianing Huang

  2. Anesthesiology Department, Ningbo Yinzhou No. 2 Hospital, Ningbo, Zhejiang, China

    Yeting Lin

  3. The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

    Chiyuan Yu & Yujing He

  4. The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China

    Rongrong Fu

  5. The Medical Imaging College, Hangzhou Medical College, Hangzhou, Zhejiang, China

    Haojie Shentu

  6. Emergency Medical Center, Ningbo Yinzhou No. 2 Hospital, 998 North Qianhe Road, Yinzhou District, Ningbo, 315100, Zhejiang, China

    Mengjiao Yu

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Contributions

MJY designed the research process. MLC and YTL searched the database for corresponding articles. RRF and CYY extracted useful information from the articles above. YTL and HJST used statistical software for analysis. MLC, CYY and JY drafted the meta-analysis. MJY, JNH and YJH polished this article. All authors had read and approved the manuscript and ensured that this was the case.

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Correspondence to Mengjiao Yu.

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Supplementary Information

Below is the link to the electronic supplementary material.

404_2023_7059_MOESM1_ESM.docx

Supplementary file1 (DOCX 19 KB) Supplementary Table 1. Characteristics of all the studies included in the meta-analysis

Supplementary file2 (DOCX 16 KB) Supplementary Table 2. Quality assessment of cohort studies included

Supplementary file3 (DOCX 18 KB) Supplementary Table 3. Quality assessment of case-control studies included

404_2023_7059_MOESM4_ESM.tif

Supplementary file4 (TIF 78 KB) SFigure. 1. Publication bias of the relationship between cesarean section and risk of autism spectrum disorders (P=0.237)

404_2023_7059_MOESM5_ESM.tif

Supplementary file5 (TIF 230 KB) SFigure. 2. Sensitivity analysis of the association between cesarean section and risk of autism spectrum disorders

404_2023_7059_MOESM6_ESM.tif

Supplementary file6 (TIF 76 KB) SFigure. 3. Publication bias of the relationship between cesarean section and risk of attention deficit hyperactivity disorder (P=0.650)

404_2023_7059_MOESM7_ESM.tif

Supplementary file7 (TIF 520 KB) SFigure. 4. Sensitivity analysis of the association between cesarean section and risk of attention deficit hyperactivity disorder

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Chen, M., Lin, Y., Yu, C. et al. Effect of cesarean section on the risk of autism spectrum disorders/attention deficit hyperactivity disorder in offspring: a meta-analysis. Arch Gynecol Obstet 309, 439–455 (2024). https://doi.org/10.1007/s00404-023-07059-9

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