Prenatal Risk Factors of Autism Spectrum Disorder Compared to Congenital Visual and Hearing Loss: A Case-Control Study

Autism spectrum disorder (ASD) is heritable neurodevelopmental disorders (NDDs), but environmental risk factors have also been suggested to a play a role in its development. Prenatal, perinatal and parental factors have been associated with an increased risk of ASD in children. The aim of the present study was to explore the prenatal, perinatal, and parenting risk factors in children with autism spectrum disorder (ASD) from Beijing, China by comparing them with typically developing (TD) children. A sample of 151 ASD children's parents who from rehabilitation institutions in Beijing were enrolled in this study, and an additional 151 children from kindergartens in Beijing were recruited as a control group (child age: mean = 4.4 years). TD children were matched according to age, sex and maternal education. We explored the maternal AQ (Autism Spectrum Quotient) scores (mean:19.40-19.71, no significant difference between two groups) to referring the genetic baseline. This study evaluated 17 factors with unadjusted and adjusted analyses. Birth asphyxia was associated with a more than a thirteen-fold higher risk of ASD (adjusted odds ratio (AOR) = 13.42). Breastfeeding difficulties were associated with a higher risk of ASD(AOR = 3.46). Parenting influenced the risk of ASD, with low responding (LR) and harsh or neglectful parenting associated with a higher risk of ASD in offspring (AOR = 2.37 for LR, AOR = 3.42 for harsh parenting and AOR = 3.01 for neglectful parenting). Maternal fever during pregnancy was associated with a higher risk of ASD in offspring (AOR = 3.81). Many factors were associated with ASD in offspring. Further assessment is needed to elucidate the role of modifiable environmental factors to inform prevention strategies.

To investigate prenatal, perinatal, and neonatal risk factors for autism spectrum disorders by using participants identified through broad ascertainment and reliable classification methods. The targeted population was 8-year-old children born in 1994 and residing in 1 of the 3 most populous counties in Utah who were identified as having an autism spectrum disorder on the basis of methodology used by the 2002 Autism and Developmental Disabilities Monitoring Network. Of those identified, 132 children (115 boys, 17 girls) had birth certificate records available. Each child was matched by gender and birth year to 100 controls (11 500 boys, 1700 girls) from the birth certificate database in a nested case-control design. Birth certificate records of participants and controls were surveyed for 23 potentially pathologic prenatal, perinatal, and neonatal factors. The prenatal factors that occurred significantly more frequently among children with autism spectrum disorders were advanced maternal age and parity. Increased duration of education among mothers of children with autism spectrum disorders was small but statistically significant. Significant perinatal factors were breech presentation and primary cesarean delivery. When corrected for breech presentation, a known indication for cesarean delivery, the association between primary cesarean delivery and autism spectrum disorders was eliminated. There were no significant associations found between autism spectrum disorders and neonatal factors. In the absence of other complications suggesting fetal distress, the association between breech presentation and autism spectrum disorders in this study suggests a shared etiology rather than causal relationship. Additional investigation focused on both genetic and environmental factors that link these autism spectrum disorder risk factors individually or collectively is needed.

Prenatal, perinatal and neonatal risk factors of Autism Spectrum Disorder: A comprehensive epidemiological assessment from India

Assisted reproductive technology and risk for autism spectrum disorder

Background Vitamin D is an important risk factor for autism spectrum disorder (ASD). However, research on hypovitaminosis D as a risk factor for severe ASD has been limited. To our knowledge, no such studies have been done in Indonesia.
 Objective To evaluate hypovitaminosis D as a risk factor for severe ASD.
 Methods This cross-sectional study included children aged 2-18 years who fulfilled the ASD DSM-5 diagnostic criteria. Subjects were consecutively sampled from April - June 2019 at the Child Growth and Polyclinic, Dr. Sardjito General Hospital, Yogyakarta. Assessment of ASD severity was carried out using the Childhood Autism Rating Scale Second Edition (CARS-2) questionnaire. Serum 25(OH)D examination was done in the Clinical Laboratory, Dr. Sardjito General Hospital. 
 Results Of 36 children with ASD, 36.1% had hypovitaminosis D (<30 ng/mL) and 69.4% had severe ASD, based on the CARS-2 questionnaire (≥37-60). Bivariate analysis revealed that children with hypovitaminosis D had more severe CARS-2 values ​​(92.3%) compared to those with normal vitamin D levels (56.5%) (PR 1.633; 95%CI 1.10 to 2.42; P=0.031). Multivariate analysis with logistic regression revealed that hypovitaminosis D increased the risk of severe ASD (PR 1.65; 95%CI 1.06 to 2.56; P=0.037). However, other variables such as gender, parental education, attention deficit and hyperactivity disorder (ADHD), epilepsy, sleep disorders, pharmacotherapy and non-pharmacotherapy had no significant relationships with severe ASD.
 Conclusion Children with ASD and hypovitaminosis D have a 1.65 times higher risk of severe ASD compared to children with ASD and sufficient vitamin D levels. We recommend that children with ASD undergo serum 25(OH)D monitoring.

Previous studies regarding the prevalence of Autism Spectrum Disorder (ASD) in patients with Prader-Willi Syndrome (PWS) have implicated heterogenous findings. Additionally, the early screening of ASD high-risk population for ASD and identifying ASD risk factors in PWS patients have not been explored. This study included 218 Chinese PWS patients aged 3 months to 18 years old. 78% of subjects were identified as high risk for ASD by ASQ-3 Communication domain score for those younger than 3 years of age and 84% of subjects were classified as high risk for ASD by the GARS-3 for those aged 3 years and older. Among PWS clinical measurements, under-height (P = 0.0186), overweight (P = 0.0248), and obstructive sleep apnea (P = 0.0259) were each significantly correlated with ASD risk. These risk factors and their internal relationship with ASD or ASD traits warrant further studies.

New insights into epigenetics as an influencer: An associative study between maternal prenatal factors in Autism Spectrum Disorder (ASD)

BackgroundThe aim of the present study was to explore the prenatal, perinatal, and postnatal risk factors in children with autism spectrum disorder (ASD) from Xuzhou, China by comparing them with healthy children.MethodsChildren with ASD who received rehabilitation training at special education schools and rehabilitation institutions in Xuzhou were selected as the ASD group, and healthy children during the same period were selected as the healthy non-ASD group. A questionnaire based on the possible causes and susceptibility factors of ASD in children was issued and given to all children in this study.ResultsThe findings of the present study revealed a higher prevalence of prenatal, perinatal, and postnatal factors in children with ASD compared with healthy children. There were significantly more males than females in the ASD group, and the proportion of boys to girls was 5.81:1 (P<0.05). Logistic regression analysis suggested that the risk factors of male children developing ASD were feeding difficulties, poor living environment during pregnancy, maternal exposure to cigarette smoking during pregnancy, and perinatal hypoxia. Factors associated with ASD risk among were identified, such as living environment during pregnancy, delivery method, feeding difficulties, and epilepsy (P<0.05). Feeding difficulties and living in the countryside during pregnancy might be risk factors for ASD in girls according to the logistic regression analysis.ConclusionsThis survey confirmed the high prevalence of prenatal, perinatal, and postnatal factors in children with ASD. Some of these factors may be effective entry points for the prevention and treatment of ASD.

BackgroundMigration has been implicated as a risk factor for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), but evidence is still limited and inconsistent. We aim to investigate the relationship between migration status and risk of ASD and ADHD.MethodsElectronic databases including PubMed, EMBASE, Web of Science, and PsychINFO were searched to identify observational studies on this topic, from inception to February 2021. Random-effects meta-analysis models were used to pool the summary odds ratio (OR) and 95% confidence interval (95% CI), and subgroup analyses were conducted to detect possible discrepancies in associations. Certainty of evidence was assessed as per the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines.ResultsA total of 13 studies (6,532,546 participants) for ASD, five studies (2,875,070 participants) for ADHD, and six studies (31,158 participants) for hyperactivity were included. Overall, the pooled results indicated that migration was associated with increased risk of ASD (pooled OR: 1.32; 95% CI: 1.07–1.63; P for Z test = 0.010), but no association was found between migration and ADHD (pooled OR: 0.84; 95% CI: 0.53–1.32; P for Z test = 0.452) or hyperactivity (pooled standardized mean difference: -0.073; 95% CIs: − 0.383–0.236; P for Z test = 0.642). Subgroup analyses further demonstrated that maternal migration was ASD risk factor (pooled OR: 1.49; 95% CI: 1.19–1.87), and migrant children were more likely to develop ASD with comorbid intellectual disability (ID) (pooled OR: 1.21, P for interaction = 0.006) than ASD without ID. After standardized the origin of migrants, European migrant children from Americas were at higher risk of ASD and ADHD (pooled OR were 4.13 and 1.26), and increased ASD risk was also observed in African children (pooled OR: 2.72). The GRADE of evidence was very low.ConclusionsMaternal migration is a risk factor for ASD, and migrant ASD children are more likely comorbid ID. The role of migration on ADHD remains controversial, more studies are needed to assess the association between migration status and ADHD. Health care practitioners should consider screening and providing extra resources for migrant children.

Imbalances in metal elements have been identified as a potential risk factor for autism spectrum disorder (ASD), and shortened telomere length (TL) is commonly observed in children with ASD. Metal elements may influence telomere homeostasis through oxidative stress, which could contribute to the pathogenesis of autism. However, studies examining the combined effects of metal elements on TL in children with ASD are limited. To fill the gaps in the current literature, this study aimed to investigate the relationship between six metallic elements: manganese (Mn), copper (Cu), zinc (Zn), calcium (Ca), magnesium (Mg), and iron (Fe), and TL in the whole blood of children with ASD. A total of 83 children with ASD and 95 typically developing children were recruited. TL was measured using digital PCR, while metal concentrations were assessed using inductively coupled plasma mass spectrometry (ICP-MS). Linear regression analysis was first conducted to explore the correlations between metal elements and TL in both groups. Additionally, Bayesian Kernel Machine Regression (BKMR) was used to further examine the combined effects and potential interactions of these metals on TL in the ASD group. In the ASD group, Ca was found to have a protective effect on TL (β = 0.07, 95% CI [0.01-0.13], P = 0.027). In contrast, Mg showed a protective effect on TL in the control group (β = 0.10, 95% CI [0.01-0.18], P = 0.027). The BKMR model revealed a significant positive combined effect of the metal mixtures on TL in the ASD group, with Ca having the largest individual effect (PIP = 0.45). Further analysis indicated that increases in Zn and Mn concentrations from the 25th to the 75th percentile were negatively correlated with TL, while higher concentrations of Cu, Ca, Mg, and Fe were positively associated with TL. No significant interactions among the metals were observed. This study suggests a potential link between metallic elements and TL in children with ASD, with Ca having the greatest effect. Our findings highlight the potential benefits of appropriate calcium supplementation as a protective strategy for lengthening telomeres in children with ASD, emphasizing the importance of early nutritional interventions to improve their overall health.

Background: Autism spectrum disorder (ASD) is a multifactorial neurodevelopment disorder. Several prenatal, perinatal, and postnatal factors are suggested as risk factors for ASD. This study aimed to correlate prenatal, perinatal, and postnatal factors in a limited number of cases in Palestine. Methods: A case-control study involved 120 children (60 typically diagnosed with ASD and 60 healthy matched with the ASD group). The parents of the children in both groups were asked to fill out the questionnaire. Results: The study showed a higher male-to-female ratio in the ASD group. A family history of ASD was reported in 38.3% of the ASD group and 11.7% in the healthy group. Three prenatal risk factors, including maternal passive smoking, preserving follow-up prenatal visits, and experiencing psychological stress by mothers, were significantly associated with ASD. Most of the postnatal factors were significantly associated with increased ASD risk. The studied perinatal factors were not significantly associated with ASD. The parental factors, such as paternal age greater than 30 years and lower levels of education, displayed significant risk factors associated with ASD. Conclusion: This study found significant associations between several prenatal, postnatal, and parental factors and ASD in a sample of Palestinian children. المقدمة: اضطراب طيف التوحد هو اضطراب نمائي عصبي متعدد العوامل. تم تحديد العديد من العوامل قبل الولادة و أثناء الولادة و بعد الولادة كعوامل قد تكون مرتبطة بالاصابة باضطراب طيف التوحد. هدفت هذه الدراسة لفحص ارتباط عدة عوامل قبل الولادة و أثناء الولادة و بعد الولادة في عدد محدود من حالات التوحد في فلسطين. المنهجية: تمت الدراسة من خلال جمع معلومات من عينة ضمت 120 طفل (60 تم تشخيصهم بطيف التوحد و 60 طفل سليم و متطابقين مع مجموعة التوحد). تمت الاجابة على الاستبيان من قبل أولياء الأمور في المجموعتين. النتائج: أظهرت الدراسة أن نسبة الذكور الى الاناث في مجموعة طيف التوحد كانت أعلى. تم تحديد نسبة وجود تاريخ عائلي في 38.3% من مجموعة طيف التوحد و 11.7% من مجموعة الاطفال السليمين. تم تحديد ثلاثة عوامل خطورة قبل الولادة مرتبطة بشكل وثيق مع اضطراب طيف التوحد و تشمل التدخين السلبي للأم، متابعة زيارات الرعاية قبل الولادة، و التعرص للاجهاد النفسي من قبل الأمهات. معظم عوامل الخطر بعد الولادة كانت مرتبطة بشكل وثيق بزيادة خطر الاصابة بطيف التوحد. عوامل الخطر أثناء الولادة التي تمت دراستها لم ترتبط بشكل وثيق باضطراب طيف التوحد. العوامل المتعلقة بالوالدين مثل عمر الأب أكثر من 30 عام و مستويات التعليم المتدنية أظهرت ارتباطا وثيقا بالإصابة بطيف التوحد. الاستنتاج: وجدت الدراسة ارتباطات وثيقة بين عدة عوامل قبل الولادة و أثناء الولادة و بعد الولادة مع طيف التوحد في عينة من الأطفال الفلسطينيين.

A growing body of literature has begun to explore social attention in infant siblings of children with autism spectrum disorder (ASD) with hopes of identifying early differences that are associated with later ASD or other aspects of development. The present study used eye-tracking to familiar (mother) and unfamiliar (stranger) faces in two groups of 6-month-old infants: infants with no family history of ASD (low-risk controls; LRC), and infants at high risk for ASD (HRA), by virtue of having an older sibling with ASD. HRA infants were further characterized based on autism classification at 24 months or older as HRA- (HRA without an ASD outcome) or HRA+ (HRA with an ASD outcome). For time scanning faces overall, HRA+ and LRC showed similar patterns of attention, and this was significantly greater than in HRA-. When examining duration of time spent on eyes and mouth, all infants spent more time on eyes than mouth, but HRA+ showed the greatest amount of time looking at these regions, followed by LRC, then HRA-. LRC showed a positive association between 6-month attention to eyes and 18-month social-communicative behavior, while HRA- showed a negative association between attention to eyes at 6 months and expressive language at 18 months (all correlations controlled for non-verbal IQ; HRA- correlations held with and without the inclusion of the small sample of HRA+). Differences found in face scanning at 6 months, as well as associations with social communication at 18 months, point to potential variation in the developmental significance of early social attention in children at low and high risk for ASD.

Advances in Our Understanding of Genetic Risk Factors for Autism Spectrum Disorders

To measure upper-extremity and gross motor skill development in infants with and without risk factors for autism spectrum disorder (ASD). Data were coded retrospectively from 39 infants who participated in longitudinal structured early developmental assessments. Twenty-five infants were at high risk for ASD, and the remaining 14 infants were classified as low risk. Upper-extremity and motor skill development were coded at ages 2, 4, and 6 mo. Five infants went on to receive an ASD diagnosis at age 2-4 yr. Infants at high risk for ASD demonstrated fewer midline behaviors with the upper extremities and delayed motor skill development than the low-risk group. Differences in motor skills were most apparent at age 4 mo. Early monitoring for motor delay in infants at high risk for ASD is warranted. Midline control and play with the upper extremities and overall motor skill development are possible assessment and therapeutic targets.

ObjectivesThis study aimed at evaluating advanced parental age as a risk factor for autism spectrum disorder (ASD) in an Omani cohort.MethodsThis case-control study compared 278 ASD cases with 722 gender-matched controls, retrieved from the electronic records of the Developmental Paediatric Clinic, Sultan Qaboos University Hospital, Muscat, Oman, between January 2015 and June 2016.ResultsMost ASD cases were male (76.6%) and mostly diagnosed between 3–4 years of age, with more than 50% of the cases originating from Muscat and Batinah governorates. Compared to controls, mothers from the case group had significantly higher educational levels (post-secondary education versus high school/no formal education: odds ratio [OR] = 1.62, 95% confidence interval [CI]: 1.197–2.192). In a multivariate logistic regression, the OR of maternal age as a risk for ASD increased dramatically with advancing age category (using age <25 as reference, OR = 3.39, 6.12, 7.86 and 13.13 for age categories 25–29, 30–34, 35–39 and ≥40 years, respectively). The ORs of advancing paternal age as a risk for ASD were also statistically significant (using age <30 as reference, OR = 2.20, 2.36 and 3.12 for age categories 30–34, 35–39 and 40–44 years, respectively); however, there was a drop in the effect with paternal age ≥45 years (OR = 1.42; 95% CI: 0.64–3.15).ConclusionBoth maternal and paternal increased age were associated with a higher risk of ASD; however, the association was more pronounced and more consistent with advanced maternal age compared to paternal age.