Dataset Information

Recurrence Risk of Autism in Siblings and Cousins: A Multinational, Population-Based Study.

ABSTRACT:

Objective

Familial recurrence risk is an important population-level measure of the combined genetic and shared familial liability of autism spectrum disorder (ASD). Objectives were to estimate ASD recurrence risk among siblings and cousins by varying degree of relatedness and by sex.

Method

This is a population-based cohort study of livebirths from 1998 to 2007 in California, Denmark, Finland, Israel, Sweden and Western Australia followed through 2011 to 2015. Subjects were monitored for an ASD diagnosis in their older siblings or cousins (exposure) and for their ASD diagnosis (outcome). The relative recurrence risk was estimated for different sibling and cousin pairs, for each site separately and combined, and by sex.

Results

During follow-up, 29,998 cases of ASD were observed among the 2,551,918 births used to estimate recurrence in ASD and 33,769 cases of childhood autism (CA) were observed among the 6,110,942 births used to estimate CA recurrence. Compared with the risk in unaffected families, there was an 8.4-fold increase in the risk of ASD following an older sibling with ASD and a 17.4-fold increase in the risk of CA following an older sibling with CA. A 2-fold increase in the risk for cousin recurrence was observed for the 2 disorders. There also was a significant difference in sibling ASD recurrence risk by sex.

Conclusion

The present estimates of relative recurrence risks for ASD and CA will assist clinicians and families in understanding autism risk in the context of other families in their population. The observed variation by sex underlines the need to deepen the understanding of factors influencing ASD familial risk.

SUBMITTER: Hansen SN

PROVIDER: S-EPMC6708733 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Publications

Recurrence Risk of Autism in Siblings and Cousins: A Multinational, Population-Based Study.

Hansen Stefan N SN Schendel Diana E DE Francis Richard W RW Windham Gayle C GC Bresnahan Michaeline M Levine Stephen Z SZ Reichenberg Abraham A Gissler Mika M Kodesh Arad A Bai Dan D Yip Benjamin Hon Kei BHK Leonard Helen H Sandin Sven S Buxbaum Joseph D JD Hultman Christina C Sourander Andre A Glasson Emma J EJ Wong Kingsley K Öberg Rikard R Parner Erik T ET

Journal of the American Academy of Child and Adolescent Psychiatry 20190306 9

<h4>Objective</h4>Familial recurrence risk is an important population-level measure of the combined genetic and shared familial liability of autism spectrum disorder (ASD). Objectives were to estimate ASD recurrence risk among siblings and cousins by varying degree of relatedness and by sex.<h4>Method</h4>This is a population-based cohort study of livebirths from 1998 to 2007 in California, Denmark, Finland, Israel, Sweden and Western Australia followed through 2011 to 2015. Subjects were monito ...[more]

PMID: 30851399

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Project description:Importance:Maternal use of folic acid supplements has been inconsistently associated with reduced risk for autism spectrum disorder (ASD) in the child. No study to date has examined this association in the context of ASD recurrence in high-risk families. Objective:To examine the association between maternal prenatal vitamin use and ASD recurrence risk in younger siblings of children with ASD. Design, Setting, and Participants:This prospective cohort study analyzed data from a sample of children (n = 332) and their mothers (n = 305) enrolled in the MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) study. Participants in the MARBLES study were recruited at the MIND Institute of the University of California, Davis and were primarily from families receiving services for children with ASD in the California Department of Developmental Services. In this sample, the younger siblings at high risk for ASD were born between December 1, 2006, and June 30, 2015, and completed a final clinical assessment within 6 months of their third birthday. Prenatal vitamin use during pregnancy was reported by mothers during telephone interviews. Data analysis for this study was conducted from January 1, 2017, to December 3, 2018. Main Outcomes and Measures:Autism spectrum disorder, other nontypical development (non-TD), and typical development (TD) were algorithmically defined according to Autism Diagnostic Observation Schedule and Mullen Scales of Early Learning subscale scores. Results:After exclusions, the final sample comprised 241 younger siblings, of which 140 (58.1%) were male and 101 (41.9%) were female, with a mean (SD) age of 36.5 (1.6) months. Most mothers (231 [95.9%]) reported taking prenatal vitamins during pregnancy, but only 87 mothers (36.1%) met the recommendations to take prenatal vitamins in the 6 months before pregnancy. The prevalence of ASD was 14.1% (18) in children whose mothers took prenatal vitamins in the first month of pregnancy compared with 32.7% (37) in children whose mothers did not take prenatal vitamins during that time. Children whose mothers reported taking prenatal vitamins during the first month of pregnancy were less likely to receive an ASD diagnosis (adjusted relative risk [RR], 0.50; 95% CI, 0.30-0.81) but not a non-TD 36-month outcome (adjusted RR, 1.14; 95% CI, 0.75-1.75) compared with children whose mothers reported not taking prenatal vitamins. Children in the former maternal prenatal vitamin group also had statistically significantly lower autism symptom severity (adjusted estimated difference, -0.60; 95% CI, -0.97 to -0.23) and higher cognitive scores (adjusted estimated difference, 7.1; 95% CI, 1.2-13.1). Conclusions and Relevance:Maternal prenatal vitamin intake during the first month of pregnancy may reduce ASD recurrence in siblings of children with ASD in high-risk families. Additional research is needed to confirm these results; to investigate dose thresholds, contributing nutrients, and biologic mechanisms of prenatal vitamins; and to inform public health recommendations for ASD prevention in affected families.

Project description:BackgroundMany studies have reported an increased risk of autism spectrum disorder (ASD) associated with some maternal diagnoses in pregnancy. However, such associations have not been studied systematically, accounting for comorbidity between maternal disorders. Therefore our aim was to comprehensively test the associations between maternal diagnoses around pregnancy and ASD risk in offspring.MethodsThis exploratory case-cohort study included children born in Israel from 1997 to 2008, and followed up until 2015. We used information on all ICD-9 codes received by their mothers during pregnancy and the preceding year. ASD risk associated with each of those conditions was calculated using Cox proportional hazards regression, adjusted for the confounders (birth year, maternal age, socioeconomic status and number of ICD-9 diagnoses during the exposure period).ResultsThe analytic sample consisted of 80 187 individuals (1132 cases, 79 055 controls), with 822 unique ICD-9 codes recorded in their mothers. After extensive quality control, 22 maternal diagnoses were nominally significantly associated with offspring ASD, with 16 of those surviving subsequent filtering steps (permutation testing, multiple testing correction, multiple regression). Among those, we recorded an increased risk of ASD associated with metabolic [e.g. hypertension; HR = 2.74 (1.92-3.90), p = 2.43 × 10-8], genitourinary [e.g. non-inflammatory disorders of cervix; HR = 1.88 (1.38-2.57), p = 7.06 × 10-5] and psychiatric [depressive disorder; HR = 2.11 (1.32-3.35), p = 1.70 × 10-3] diagnoses. Meanwhile, mothers of children with ASD were less likely to attend prenatal care appointment [HR = 0.62 (0.54-0.71), p = 1.80 × 10-11].ConclusionsSixteen maternal diagnoses were associated with ASD in the offspring, after rigorous filtering of potential false-positive associations. Replication in other cohorts and further research to understand the mechanisms underlying the observed associations with ASD are warranted.

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Dataset Information

Recurrence Risk of Autism in Siblings and Cousins: A Multinational, Population-Based Study.

Objective

Method

Results

Conclusion

Publications

Recurrence Risk of Autism in Siblings and Cousins: A Multinational, Population-Based Study.

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