Document Type : Original Articles
Authors
- Zahra Farsi 1
- Masoud Jabari Morooei 2, 3
- Samaneh Farnia 2, 3
- Ali Abbaskhanian 2
- Sara Dehbozorgi 4
- Amir Asadi 5
1 Research and Community Health Departments, Nursing School, 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 -
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
- Sadock BJ, Ahmad S, VA S. Kaplan & Sadock’s pocket handbook of clinical psychiatry. Sixth ed. China: Wolters Kluwer; 2019.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Zwaigenbaum L, Bryson S, Garon N. Early identification of autism spectrum disorders. Behav Brain Res. 2013;251:133-46.
- 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.
- 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.
- 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.
- Shahraki M, Agheli L, Assari AA, H S. Children’s health and parental socioeconomic factors. Teb Va Tazkyeh. 2017;25(2):95-106.
- 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.
- 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.
- Quantifying Health. Which Variables Should You Include in a Regression Model? 2021. Available from: https://quantifyinghealth.com/variables-to-include-in-regression/.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 |
|
|
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 |
- |
- |
)