Recurrence Risk of Autism in Siblings and Cousins: A Multinational, Population-Based Study.
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SUBMITTER: Hansen SN
PROVIDER: S-EPMC6708733 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
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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]
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Project description:ImportanceTo date, this is the first population-based study to examine the recurrence risk for autism spectrum disorders (ASDs), including time trends, and the first study to consider the ASDs recurrence risk for full- and half-siblings.ObjectivesTo estimate the relative recurrence risk for ASDs in a Danish population, including recurrence in full- and half-siblings, and to examine time trends in ASDs relative to the recurrence risk.Design, setting, and participantsPopulation-based cohort study in Denmark. All children (about 1.5 million) born in Denmark between January 1, 1980, and December 31, 2004, were identified and followed up to December 31, 2010. We identified a maternal sibling subcohort derived from mothers with at least 2 children and a paternal sibling subcohort derived from fathers with at least 2 children.ExposuresChildren having an older sibling with ASDs are compared with children not having an older sibling with ASDs.Main outcomes and measuresThe adjusted hazard ratio for ASDs among children having an older sibling with ASDs compared with children not having an older sibling with ASDs. RESULTS The overall relative recurrence risk for ASDs was 6.9 (95% CI, 6.1-7.8), and it did not change significantly over time; similar risks were observed in maternal and paternal full-siblings. The relative recurrence risks were 2.4 (95% CI, 1.4-4.1) for maternal half-siblings and 1.5 (95% CI, 0.7-3.4) for paternal half-siblings.Conclusions and relevanceOur population-based recurrence risk estimate is lower than the recently reported estimates from clinical samples. Our results demonstrate no time trend in the ASDs recurrence risk as seen in the ASDs prevalence. The difference in the recurrence risk between full- and half-siblings supports the role of genetics in ASDs, while the significant recurrence risk in maternal half-siblings may support the role of factors associated with pregnancy and the maternal intrauterine environment in ASDs.
| S-EPMC4610344 | biostudies-literature
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.
| S-EPMC6450282 | biostudies-literature
Project description:Joint attention (JA)-the human ability to coordinate our attention with that of other people-is impaired in the early stage of Autism Spectrum Disorder (ASD). However, little is known about the JA skills in the younger siblings of children with ASD who do not develop ASD at 36 months of age [high-risk (HR)-noASD]. In order to advance our understanding of this topic, a prospective multicenter observational study was conducted with three groups of toddlers (age range: 18-33 months): 17 with ASD, 19 with HR-noASD and 16 with typical development (TD). All subjects underwent a comprehensive clinical assessment and an eye-tracking experiment with pre-recorded stimuli in which the visual patterns during two tasks eliciting initiating joint attention (IJA) were measured. Specifically, fixations, transitions and alternating gaze were analyzed. Clinical evaluation revealed that HR-noASD subjects had lower non-verbal cognitive skills than TD children, while similar levels of restricted and repetitive behaviors and better social communication skills were detected in comparison with ASD children. Eye-tracking paradigms indicated that HR-noASD toddlers had visual patterns resembling TD in terms of target-object-to-face gaze alternations, while their looking behaviors were similar to ASD toddlers regarding not-target-object-to-face gaze alternations. This study indicated that high-risk, unaffected siblings displayed a shared profile of IJA-eye-tracking measures with both ASD patients and TD controls, providing new insights into the characterization of social attention in this group of toddlers.
| S-EPMC9699372 | biostudies-literature
Project description:ObjectiveTo explore risk profiles of the different types of postpartum hemorrhage (PPH >500ml or severe PPH >1500ml) and their recurrence risks in a subsequent delivery.MethodsWith data from The Medical Birth Registry of Norway and Statistics Norway we performed a population-based cohort study including all singleton deliveries in Norway from 1967-2017. Multilevel logistic regression was used to calculate odds ratio (OR), with 95% confidence interval (CI), with different PPH types (PPH >500ml or PPH >1500ml (severe PPH) combined with retained placenta, uterine atony, obstetric trauma, dystocia, or undefined cause) as outcomes.ResultWe identified 277 746 PPH cases of a total of 3 003 025 births (9.3%) from 1967 to 2017. Retained placenta (and/or membranes) was most often registered as severe PPH (29.3%). Maternal, fetal, and obstetric characteristics showed different associations with the PPH types. Male sex of the neonate was associated with reduced risk of PPH. This effect was strongest on PPH due to retained placenta (adjusted OR, (aOR): 0.80, 95% CI 0.78-0.82), atony (aOR 0.92, 95% CI: 0.90-0.93) and PPH with undefined cause (aOR 0.96, 95% CI: 0.95-0.97). Previous cesarean section showed a strong association with PPH due to dystocia (aOR of 13.2, 95% CI: 12.5-13.9). Recurrence risks were highest for the same type: PPH associated with dystocia (aOR: 6.8, 95% CI: 6.3-7.4), retained placenta and/or membranes (aOR: 5.9, 95% CI: 5.5-6.4), atony (aOR: 4.0, 95% CI: 3.8-4.2), obstetric trauma (aOR: 3.9, 95% CI: 3.5-4.3) and PPH of undefined cause (aOR: 2.2, 95% CI: 2.1-2.3).ConclusionMaternal, fetal and obstetric characteristics had differential effects on types of PPH. Recurrence differed considerably between PPH types. Retained placenta was most frequently registered with severe PPH, and showed strongest effect of sex; delivery of a boy was associated with lower risk of PPH. Previous cesarean increased the risk of PPH due to dystocia.
| S-EPMC9565392 | biostudies-literature
Project description:Sexual dimorphism in autism spectrum disorders (ASD) is a well-recognized but poorly understood phenomenon. Females are four times less likely to be diagnosed with ASD than males and, when diagnosed, are more likely to exhibit comorbid anxiety symptoms. One of the key phenotypic features of ASD is atypical attention to socially relevant stimuli. Eye-tracking studies indicate atypical patterns of spontaneous social orienting during the prodromal and early syndromic stages of ASD. However, there have been no studies evaluating sex differences in early social orienting and their potential contribution to later outcomes.We examined sex differences in social orienting in 6-, 9-, and 12-month-old infants at high genetic risk for ASD (n = 101) and in low-risk controls (n = 61), focusing on neurobehavioral measures of function across a spectrum of autism risk.Results suggest that, between 6 and 12 months of age, a period highly consequential for the development of nonverbal social engagement competencies, high-risk females show enhanced attention to social targets, including faces, compared to both high-risk males and low-risk males and females. Greater attention to social targets in high-risk infants was associated with less severe social impairments at 2 years.The results suggest an alternative expression of autism risk in females, which manifests in infancy as increased attention toward socially relevant stimuli. This increased attention may serve as a female protective factor against ASD by providing increased access to social experiences in early development.
| S-EPMC5812780 | biostudies-literature
Project description:ImportanceAutism spectrum disorder (ASD) is a neurodevelopmental disorder associated with different genetic etiologies. Prospective examination of familial-risk infants informs understanding of developmental trajectories preceding ASD diagnosis, potentially improving early detection.ObjectiveTo compare outcomes and trajectories associated with varying familial risk for ASD across the first 3 years of life.Design, setting, and participantsThis longitudinal, prospective cohort study used data from 11 sites in the Baby Siblings Research Consortium database. Data were collected between 2003 and 2015. Infants who were younger siblings of children with ASD were followed up for 3 years. Analyses were conducted in April 2018. Of the initial 1008 infants from the database, 573 were removed owing to missing necessary data, diagnostic discrepancies, or only having 1 older sibling.ExposuresNumber of siblings with ASD.Main outcomes and measuresOutcomes included ASD symptoms, cognitive abilities, and adaptive skills. Diagnosis (ASD or no ASD) was given at 36-month outcome. The no-ASD group was classified as atypical (developmental delays and/or social-communication concerns) or typical for some analyses. Generalized linear mixed models examined developmental trajectories by ASD outcome and familial-risk group.ResultsIn the 435 analyzed participants (age range at outcome, 32-43 months; 246 male [57%]), 355 (82%) were from single-incidence families (1 sibling with ASD and ≥1 sibling without ASD) and 80 (18%) were from multiplex families (≥2 siblings with ASD). There were no significant group differences in major demographics. Children from multiplex families were more likely than those from single-incidence families to be classified as having ASD (29 of 80 [36%] vs 57 of 355 [16%]; 95% CI, 9%-31%; P < .001) and less likely as typical (26 of 80 [33%] vs 201 of 355 [57%]; 95% CI, -36% to -13%; P < .001), with similar rates of atypical classifications (25 of 80 [31%] vs 97 of 355 [27%]; 95% CI, -7% to 15%; P = .49). There were no differences in ASD symptoms between multiplex and single-incidence groups after controlling for ASD outcome (95% CI, -0.02 to 0.20; P = .18). During infancy, differences in cognitive and adaptive abilities were observed based on ASD outcome in the single-incidence group only. At 36 months, the multiplex/no-ASD group had lower cognitive abilities than the single-incidence/no-ASD group (95% CI, -11.89 to -2.20; P = .02), and the multiplex group had lower adaptive abilities than individuals in the single-incidence group after controlling for ASD outcome (95% CI, -9.01 to -1.48; P = .02).Conclusions and relevanceInfants with a multiplex family history of ASD should be monitored early and often and referred for early intervention at the first sign of concern. Direct examination of genetic contributions to neurodevelopmental phenotypes in infants with familial risk for ASD is needed.
| S-EPMC6784852 | biostudies-literature
Project description:We characterized developmental outcomes of a large sample of siblings at familial high-risk of autism spectrum disorder (ASD), who themselves did not have ASD (n?=?859), and low-risk controls with no family history of ASD (n?=?473). We report outcomes at age 3 years using the Mullen Scales of Early Learning, the Autism Diagnostic Observation Schedule (ADOS), the Autism Diagnostic Interview-Revised (ADI-R) and adaptive functioning on the Vineland Adaptive Behavior Scales. Around 11% of high-risk siblings had mild-to-moderate levels of developmental delay, a rate higher than the low-risk controls. The groups did not differ in the proportion of toddlers with mild-to-moderate language delay. Thirty percent of high-risk siblings had elevated scores on the ADOS, double the rate seen in the low-risk controls. High-risk siblings also had higher parent reported levels of ASD symptoms on the ADI-R and lower adaptive functioning on the Vineland. Males were more likely to show higher levels of ASD symptoms and lower levels of developmental ability and adaptive behavior than females across most measures but not mild-to-moderate language delay. Lower maternal education was associated with lower developmental and adaptive behavior outcomes. These findings are evidence for early emerging characteristics related to the "broader autism phenotype" (BAP) previously described in older family members of individuals with ASD. There is a need for ongoing clinical monitoring of high-risk siblings who do not have an ASD by age 3 years, as well as continued follow-up into school age to determine their developmental and behavioral outcomes. Autism Res 2017, 10: 169-178. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
| S-EPMC5993543 | biostudies-literature
Project description:Advancing paternal age has been linked to autism.To further expand knowledge about the association between paternal age and autism by studying the effect of grandfathers' age on childhood autism.Population-based, multigenerational, case-control study.Nationwide multigeneration and patient registers in Sweden.We conducted a study of individuals born in Sweden since 1932. Parental age at birth was obtained for more than 90% of the cohort. Grandparental age at the time of birth of the parent was obtained for a smaller subset (5936 cases and 30 923 controls).International Classification of Diseases diagnosis of childhood autism in the patient registry.A statistically significant monotonic association was found between advancing grandpaternal age at the time of birth of the parent and risk of autism in grandchildren. Men who had fathered a daughter when they were 50 years or older were 1.79 times (95% CI, 1.35-2.37; P < .001) more likely to have a grandchild with autism, and men who had fathered a son when they were 50 years or older were 1.67 times (95% CI, 1.35-2.37; P < .001) more likely to have a grandchild with autism, compared with men who had fathered children when they were 20 to 24 years old, after controlling for birth year and sex of the child, age of the spouse, family history of psychiatric disorders, highest family educational level, and residential county. A statistically significant monotonic association was also found between advancing paternal age and risk of autism in the offspring. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on grandparental age.Advanced grandparental age was associated with increased risk of autism, suggesting that risk of autism could develop over generations. The results are consistent with mutations and/or epigenetic alterations associated with advancing paternal age.
| S-EPMC3701020 | biostudies-literature
Project description:Background Adjuvant tamoxifen therapy approximately halves the risk of estrogen receptor-positive (ER+) breast cancer recurrence, but many women do not respond to therapy. Observational studies nested in clinical trial populations suggest that overexpression or nuclear localization of p21-activated kinase 1 (Pak1) in primary tumors predicts tamoxifen failure. Material and methods We measured the association between Pak1 expression and breast cancer recurrence in a Danish population-based case-control study. Pak1 cytoplasmic expression level and nuclear positivity were determined by immunohistochemical staining of primary breast tumors from recurrence cases and matched controls from two breast cancer populations; women diagnosed with ER-positive tumors who received at least one year of tamoxifen therapy (ER+/TAM+), and women diagnosed with ER-negative tumors who survived for at least one year (ER-/TAM-). Pak1 staining was assessed by a single, blinded pathologist, and associations were estimated with conditional logistic regression models. Results We included 541 recurrence cases and 1:1 matched controls from the ER+/TAM + group and 300 recurrence cases and 1:1 matched controls from the ER-/TAM - group. Pak1 cytoplasmic intensity was not associated with breast cancer recurrence in either group (ER+/TAM + ORadj for strong vs. no cytoplasmic staining = 0.91, 95% CI 0.57, 1.5; ER-/TAM - ORadj for strong vs. no cytoplasmic staining = 0.74, 95% CI 0.39, 1.4). Associations between Pak1 nuclear positivity and breast cancer recurrence were similarly near null in both groups. Conclusion Pak1 positivity in primary breast tumors was neither predictive nor prognostic in this prospective, population-based study.
| S-EPMC4943575 | biostudies-literature
Project description:BackgroundEscherichia coli is the most common cause of bloodstream infections (BSIs) and mortality is an important aspect of burden of disease. Using a multinational population-based cohort of E. coli BSIs, our objectives were to evaluate 30-day case fatality risk and mortality rate, and determine factors associated with each.MethodsDuring 2014-2018, we identified 30-day deaths from all incident E. coli BSIs from surveillance nationally in Finland, and regionally in Sweden (Skaraborg) and Canada (Calgary, Sherbrooke, western interior). We used a multivariable logistic regression model to estimate factors associated with 30-day case fatality risk. The explanatory variables considered for inclusion were year (2014-2018), region (five areas), age (< 70-years-old, ≥70-years-old), sex (female, male), third-generation cephalosporin (3GC) resistance (susceptible, resistant), and location of onset (community-onset, hospital-onset). The European Union 28-country 2018 population was used to directly age and sex standardize mortality rates. We used a multivariable Poisson model to estimate factors associated with mortality rate, and year, region, age and sex were considered for inclusion.ResultsFrom 38.7 million person-years of surveillance, we identified 2961 30-day deaths in 30,923 incident E. coli BSIs. The overall 30-day case fatality risk was 9.6% (2961/30923). Calgary, Skaraborg, and western interior had significantly increased odds of 30-day mortality compared to Finland. Hospital-onset and 3GC-resistant E. coli BSIs had significantly increased odds of mortality compared to community-onset and 3GC-susceptible. The significant association between age and odds of mortality varied with sex, and contrasts were used to interpret this interaction relationship. The overall standardized 30-day mortality rate was 8.5 deaths/100,000 person-years. Sherbrooke had a significantly lower 30-day mortality rate compared to Finland. Patients that were either ≥70-years-old or male both experienced significantly higher mortality rates than those < 70-years-old or female.ConclusionsIn our study populations, region, age, and sex were significantly associated with both 30-day case fatality risk and mortality rate. Additionally, 3GC resistance and location of onset were significantly associated with 30-day case fatality risk. Escherichia coli BSIs caused a considerable burden of disease from 30-day mortality. When analyzing population-based mortality data, it is important to explore mortality through two lenses, mortality rate and case fatality risk.
| S-EPMC8229717 | biostudies-literature