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. |
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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
|
-
|
-
|
|