Document Type : Original Articles

Authors

1 Aja University of Medical Sciences - Research and Community Health Department, Faculty of Nursing, Aja University of Medical Sciences, Kaj St., Shariati St, Tehran, Iran.

2 Department of Psychiatry, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran

3 Psychiatry and Behavioral Sciences Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran

4 Department of Psychiatry, Faculty of Medicine, Shiraz University of Medical Sciences

5 Department of Psychiatry, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran -

10.30476/jrsr.2023.98529.1364

Abstract

Background: Identifying the risk factors and protective measures for Autism Spectrum Disorders (ASD) can significantly contribute to their prevention. This study aimed to ascertain the risk factors and protective measures associated with ASD.
Methods: This retrospective case-control study was conducted in Sari, Iran, from 2020 to 2021. A total of 196 children, aged 2-17 years, were recruited by convenience sampling from the Baghban (Touba) Clinic, Zareh Psychiatric Hospital Clinic, and Bu-Ali Child and Adolescent Psychiatric Clinic. The case group consisted of 98 children with ASD, diagnosed based on the DSM-V criteria, while the control group included 98 children without ASD. Subsequently, potential risk factors in both groups were examined. The odds ratio was calculated at a 95% confidence level, with a significance level of P<0.05.
Results: After adjusting the odds ratio (95% CI), ASD was found to be significantly associated with relatives’ consanguinity [0.625 (0.409, 0.953)], breastfeeding [0.743 (0.582, 0.950)], and the child’s history of head trauma [15.911 (1.78, 142.238)]. A closer degree of relatives’ consanguinity increased the risk of autism in children by 1.6 times. Children who were breastfed for a longer period (up to 2 years) were 1.34 times less likely to develop autism. Moreover, children with a history of head trauma were approximately 16 times more likely to develop autism compared to children without such a history.
Conclusion: Breastfeeding has been identified as a protective factor, while the existence of closer relatives’ consanguinity and a history of head trauma have been identified as risk factors for ASD. Further studies on these factors are recommended.
 

Highlights

Zahra Farsi:googel scholar

Samaneh Farnia:googel scholar

Keywords

  1. Sadock BJ, Ahmad S, VA S. Kaplan & Sadock’s pocket handbook of clinical psychiatry. Sixth ed. China: Wolters Kluwer; 2019.
  2. World Health Organization. Autism spectrum disorders. 2021. Available from: https://www.who.int/news-room/fact-sheets/detail/autism-spectrum-disorders. Accessed 1 June 2021.
  3. Centers for Diseases Control and Prevention. Data & Statistics on Autism Spectrum Disorder. 2021. Available from: https://www.cdc.gov/ncbddd/autism/data.html. Accessed 1 June 2021.
  4. Mohammadi MR, Ahmadi N, Khaleghi A, Zarafshan H, Mostafavi S-A, Kamali K, et al. Prevalence of autism and its comorbidities and the relationship with maternal psychopathology: A national population-based study. Arch Iran Med. 2019;22(10):546-53.
  5. Gao L, Xi QQ, Wu J, Han Y, Dai W, Su YY, et al. Association between prenatal environmental factors and child autism: A case-control study in Tianjin, China. Biomed Environ Sci. 2015 Sep;28(9):642-50. 
  6. Hisle-Gorman E, Susi A, Stokes T, Gorman G, Erdie-Lalena C, Nylund CM. Prenatal, perinatal, and neonatal risk factors of autism spectrum disorder. Pediatr Res. 2018;84(2):190-8.
  7. Modabbernia A, Velthorst E, Reichenberg A. Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol Autism. 2017;8(3): 1-16.
  8. Zwaigenbaum L, Bryson S, Garon N. Early identification of autism spectrum disorders. Behav Brain Res. 2013;251:133-46.
  9. Mamaghanieh M, Pour-Etemad HR, Ahmadi F, Khoushabi K. The effectiveness of picture exchange communication system on behavioral problems of children with autism. Archives of Rehabilitation. 2011;12(1):19-26.
  10. Lord C, Corsello C, R G. Diagnostic instruments in autistic spectrum disorders-handbook of autism and pervasive developmental disorders. Hoboken, New Jersey: John Wiley & Sons; 2014.
  11. Karimzadeh M, Baneshi AR, Dehghan Tezerjani M, Tayyebi Sough Z. Normalization of pervasive developmental disorder screening test. Archives of Rehabilitation. 2018;19(2):116-25.
  12. Shahraki M, Agheli L, Assari AA, H S. Children’s health and parental socioeconomic factors. Teb Va Tazkyeh. 2017;25(2):95-106.
  13. Shahrivar Z, Kousha M, Moallemi S, Tehrani-Doost M, Alaghband-Rad J. The Reliability and Validity of Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Life-time Version - Persian Version. Child Adolesc Ment Health. 2010 May;15(2):97-102. doi: 10.1111/j.1475-3588.2008.00518.x. Epub 2009 Feb 26. PMID: 32847248.
  14. Maia F, Oliveira L, Almeida M, Alves M, Saeger V, Silva V, et al. Autism spectrum disorder and postnatal factors: A case-control study in Brazil. Rev Paul Pediatr 2019;2019 July:1-8.
  15. Quantifying Health. Which Variables Should You Include in a Regression Model? 2021. Available from: https://quantifyinghealth.com/variables-to-include-in-regression/.
  16. Mohammadian-Khoshnoud M, Omidi T, Shirmohammadi-Khorram N, Poorolajal J. Autism spectrum disorder and associated risk factors: A matched case-control study. IJER. 2019;6(1):14-9.
  17. von Ehrenstein OS, Ling C, Cui X, Cockburn M, Park AS, Yu F, et al. Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population-based case-control study. BMJ. 2019;364(l962): 1-10.
  18. Malek A, Farhang S, Amiri S, Abdi S, Razzaghi Rezaih A, Asadian M. Risk factors for autistic disorder: A case-control study. Iran J Pediatr. 2019;29(3):e80935.
  19. Mamidala MP, Polinedi A, P.T.V PK, Rajesh N, Vallamkonda OR, Udani V, et al. Prenatal, perinatal and neonatal risk factors of Autism Spectrum Disorder: A comprehensive epidemiological assessment from India. Research in Developmental Disabilities. 2013;34(9):3004-13.
  20. Kim JY, Son MJ, Son CY, Radua J, Eisenhut M, Gressier F, et al. Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence. Lancet Psychiatry. 2019;6(7):590-600.
  21. Fajardo J, Albores-Gallo L, Genis-Mendoza AD, Martínez-Magaña JJ, Nicolini H. Advanced paternal age as a risk factor for autism spectrum disorder in a Mexican population. Salud Ment. 2020;43(3):113-8.

 

 

 

 

 

 

Table 1. The difference in the individual characteristics of the newborn and childhood events in the case and control groups

Variables

Case (n=98)

n (%)

Control (n=98)

n (%)

Test

Statistics value, P-value

Characteristics of the newborn

Gestational age, mean (SD), w

37.44 (2.23)

37.81 (1.84)

Independent t-test

t = 1.237

P = 0.218

Head circumference, mean (SD), cm

34.07 (1.75)

34.88 (4.22)

Independent t-test

t = 0.720

P = 0.475

Weight at birth, mean (SD), gr

3204.4 (599.5)

3209.7 (464.9)

Independent t-test

t = 0.067

P = 0.974

Height at birth, mean (SD), cm

50.25 (2.56)

50.03 (1.24)

Independent t-test

t = 0.567

P = 0.573

Events occurring in childhood

Jaundice

Chi-square

X2 = 8.186

*P = 0.042

No

41 (41.8)

42 (42.9)

Yes (Jaundice at birth)

6 (6.1)

18 (18.4)

Yes (Healing without medical treatment)

23 (23.5)

15 (15.3)

Yes (Healing with phototherapy)

28 (28.6)

23 (23.5)

Congenital malformation

4 (4.1)

4 (4.1)

Fisher’s exact test

P = 1.000

Microcephaly

0 (0.0)

1 (1.0)

Fisher’s exact test

P = 1.000

Macrocephaly

1 (1.0)

1 (1.0)

Fisher’s exact test

P = 1.000

Epilepsy

11 (11.2)

1 (1.0)

Fisher’s exact test

*P = 0.005

Head trauma

Fisher’s exact test

Value = 14.238

*P < 0.0001

No

83 (84.7)

97 (99.0)

Yes (without  loss of consciousness)

14 (14.3)

1 (1.0)

Yes (with loss of consciousness)

1 (1.0)

0 (0.0)

Admission to the NICU

6 (6.1)

3 (3.1)

Fisher’s exact test

P = 0.497

Breastfeeding

Fisher’s exact test

Value = 7.631

P = 0.102

No

12 (12.2)

4 (4.1)

Less than 6 months

11 (11.2)

5 (5.1)

6-12 months

3 (3.1)

4 (4.1)

12-18 months

6 (6.1)

9 (9.2)

18-24 months

66 (67.3)

76 (77.6)

Allergy to mother’s milk

1 (1.0)

0 (0.0)

Fisher’s exact test

P = 1.000

Allergy to mother grain

5 (5.1)

2 (2.0)

Fisher’s exact test

P = 0.445

Rubella vaccination side effect

1 (1.0)

0 (0.0)

Fisher’s exact test

P = 1.000

C-section delivery

66 (67.3)

63 (64.3)

Fisher’s exact test

P = 0.763

*P < 0.05; SD: Standard deviation, NICU: Neonatal Intensive Care Unit 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 2. Comparison of health-related conditions in the family and maternal exposures during pregnancy in case and control groups

Variables

Case (n=98)

n (%)

Control (n=98)

n (%)

Test

P-value

Health-related conditions in the family as risk factors for ASD

Maternal age at delivery, mean (SD), y

27.17 (5.72)

26.29 (4.79)

Independent t-test

t = -1.176

P = 0.241

Paternal age at delivery, mean (SD), y

31.47 (6.59)

31.13 (5.18)

Independent t-test

t = -0.402

P = 0.688

Consanguinity

Chi-square

X2 = 14.097

*P = 0.001

Unrelated

74 (75.5)

61 (62.2)

Third relatives

18 (18.4)

12 (12.2)

Fourth relatives

6 (6.1)

25 (25.5)

Father’s mental disorders

10 (10.2)

6 (6.1)

Fisher’s exact test

P = 0.435

Mother’s mental disorders

20 (20.4)

19 (19.4)

Fisher’s exact test

P = 1.000

Sibling’s mental disorders

0 (0.0)

1 (1.0)

Fisher’s exact test

P = 1.000

Abortion before the birth of ASD child

86 (87.8)

93 (94.9)

Fisher’s exact test

P = 0.126

Abortion after the birth of ASD child

12 (12.2)

5 (5.1)

Fisher’s exact test

P = 0.134

Maternal exposures during pregnancy

Assisted fertility (IVF)

2 (2.0)

3 (3.1)

Fisher’s exact test

P = 1.000

Bleeding in pregnancy

17 (17.3)

16 (16.3)

Fisher’s exact test

P = 1.000

X-Ray

3 (3.1)

2 (2.0)

Fisher’s exact test

P = 1.000

Active smoker

1 (1.0)

0 (0.0)

Fisher’s exact test

P = 1.000

Passive smoker

6 (6.1)

14 (14.3)

Fisher’s exact test

P = 0.097

Folic acid

79 (80.6)

81 (82.7)

Fisher’s exact test

P = 0.854

Trauma to mother’s abdomen in pregnancy

5 (5.1)

1 (1.0)

Fisher’s exact test

P = 0.212

Fever in pregnancy

0 (0.0)

1 (1.0)

Fisher’s exact test

P = 1.000

Hyperthermia in pregnancy

1 (1.0)

0 (0.0)

Fisher’s exact test

P = 1.000

*P < 0.05; SD: Standard deviation, ASD: autism spectrum disorders, IVF: in vitro fertilization

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Table 3. Risk factors associated with autism spectrum disorder in the fifth step of the logistic regression model

Variables

B

Standard error (SE)

Wald

df

P-value

Exp (B)

95% CI for Exp (B)

Lower

Upper

Relatives’ Consanguinity

-0.471

0.216

4.755

1

0.029

0.625

0.409

0.953

Abortion after the birth of ASD child

-1.663

0.893

3.465

1

0.063

0.190

0.033

1.092

Breastfeeding

-0.297

0.125

5.635

1

0.018

0.743

0.582

0.950

Child’s Epilepsy

1.990

1.102

3.263

1

0.071

7.314

0.844

63.364

Child’s head trauma

2.767

1.118

6.129

1

0.013

15.911

1.780

142.238

Constant

1.052

0.445

5.580

1

0.018

2.864

-

-