The Association Between Parental Age and Autism-Related Outcomes in Children at High Familial Risk for Autism.
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ABSTRACT:
SUBMITTER: Lyall K
PROVIDER: S-EPMC7396152 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
Publications
The Association Between Parental Age and Autism-Related Outcomes in Children at High Familial Risk for Autism.
Lyall Kristen K Song Lanxin L Botteron Kelly K Croen Lisa A LA Dager Stephen R SR Fallin M Daniele MD Hazlett Heather C HC Kauffman Elizabeth E Landa Rebecca R Ladd-Acosta Christine C Messinger Daniel S DS Ozonoff Sally S Pandey Juhi J Piven Joseph J Schmidt Rebecca J RJ Schultz Robert T RT Stone Wendy L WL Newschaffer Craig J CJ Volk Heather E HE
Autism research : official journal of the International Society for Autism Research 20200421 6
Advanced parental age is a well-replicated risk factor for autism spectrum disorder (ASD), a neurodevelopmental condition with a complex and not well-defined etiology. We sought to determine parental age associations with ASD-related outcomes in subjects at high familial risk for ASD. A total of 397 younger siblings of a child with ASD, drawn from existing prospective high familial risk cohorts, were included in these analyses. Overall, we did not observe significant associations of advanced par ...[more]
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Project description:Importance:Advanced parental age has been associated with autism spectrum disorders (ASDs) in children. However, little is known about the association between grandparental age at the time of birth of the parent and the risk of ASD in the grandchildren. Objective:To estimate the associations between parental and grandparental age and ASD risk in children. Design, Setting, and Participants:This population-based, multigenerational cohort study used data from Danish national health registries. A parental age cohort was constructed to evaluate the association between parental age and ASD in 1 476 783 singleton children born from 1990 to 2013, and a multigenerational cohort was also constructed including 362 438 fathers and 458 234 mothers born from 1973 to 1990 for whom information on grandparental age was available. Data analyses were conducted from November 1, 2018, through February 7, 2020. Exposures:Parental age at childbirth and grandparental age at the time of the birth of the parent. Main Outcomes and Measures:Diagnoses of ASD in children were obtained from the Danish Psychiatric Central Register (1994-2017). Logistic regression analysis was used to estimate the associations between parental or grandparental age and ASD in children. Results:Of the 1 476 783 children born from 1990 to 2013, 758?066 (51.3%) were male, and 27 616 (1.9%) had ASD (20 467 [74.1%] were male). Advanced paternal or maternal age over 30 years was monotonically associated with increased ASD risk, with odds ratios (ORs)?of 1.56 (95% CI, 1.45-1.68) for maternal age 40 years and older and 1.57 (95% CI, 1.39-1.78) for paternal age 50 years and older, compared with parents aged 25 to 29 years. In the multigenerational cohort, 9364 grandchildren (1.7%) had ASD. This study found U-shaped associations, in that ASD risk was higher among grandchildren of younger (?19 years) maternal grandmothers (OR,?1.68; 95% CI, 1.52-1.85), younger maternal grandfathers (OR,?1.50; 95% CI, 1.26-1.78), and younger paternal grandmothers (OR, 1.18; 95% CI, 1.04-1.34), and older (?40 years) paternal grandmothers (OR,?1.40; 95% CI, 1.03-1.90) compared with the grandchildren of grandparents who were aged 25 to 29 years at the time of giving birth to the parents. Conclusions and Relevance:These findings corroborate previous studies suggesting that advanced parental age is independently associated with increased ASD risk in children. This study also found that children with young maternal grandparents and children with young and old paternal grandparents had elevated ASD risk. Possible transmission of ASD risk across generations should be considered in etiological research on ASD.
| S-EPMC7160691 | biostudies-literature
Project description:Advancing paternal and maternal age have both been associated with risk for autism spectrum disorders (ASD). However, the shape of the association remains unclear, and results on the joint associations is lacking. This study tests if advancing paternal and maternal ages are independently associated with ASD risk and estimates the functional form of the associations. In a population-based cohort study from five countries (Denmark, Israel, Norway, Sweden and Western Australia) comprising 5 766 794 children born 1985-2004 and followed up to the end of 2004-2009, the relative risk (RR) of ASD was estimated by using logistic regression and splines. Our analyses included 30 902 cases of ASD. Advancing paternal and maternal age were each associated with increased RR of ASD after adjusting for confounding and the other parent's age (mothers 40-49 years vs 20-29 years, RR=1.15 (95% confidence interval (CI): 1.06-1.24), P-value<0.001; fathers⩾50 years vs 20-29 years, RR=1.66 (95% CI: 1.49-1.85), P-value<0.001). Younger maternal age was also associated with increased risk for ASD (mothers <20 years vs 20-29 years, RR=1.18 (95% CI: 1.08-1.29), P-value<0.001). There was a joint effect of maternal and paternal age with increasing risk of ASD for couples with increasing differences in parental ages. We did not find any support for a modifying effect by the sex of the offspring. In conclusion, as shown in multiple geographic regions, increases in ASD was not only limited to advancing paternal or maternal age alone but also to differences parental age including younger or older similarly aged parents as well as disparately aged parents.
| S-EPMC5414073 | biostudies-literature
Project description:BACKGROUND:The onset age of physiological puberty is greatly variable. This variability has been attributed to environmental factors and to genetic factors although a very little is explained by genome-wide associations studies. Previously, we reported the existence of an association between the onset age of puberty and final height. It is known that final height is associated with parental height (specifically, with the "target height"). We hypothesized that the variability of the onset age of puberty contributes to the attainment of a final height which is similar to the target height. We hypothesized that whenever a child's height-percentile differs from the target height percentile (we called this difference the "height gap"), the onset of puberty is advanced or delayed so that they are closer or even equal at the end of pubertal growth. The association between height gap and onset age of puberty was investigated in the reported study. METHODS:The study is an observational retrospective study on growth during puberty in 170 Israeli (60 girls) and 335 Polish children (162 girls). Anthropometric measurements were analyzed by multivariable linear regression with the onset age of the pubertal growth spurt (PGS) as the dependent variable, and two independent variables "height gap" and body mass index (BMI)-both standardized. RESULTS:The adjusted coefficient of determination (adj R2) between the onset age of the PGS and the two independent variables was 0.69 (Israeli girls), 0.50 (Israeli boys, BMI excluded), 0.25 (Polish girls) and 0.13 (Polish boys). A prediction model for the onset age of puberty is presented. CONCLUSIONS:The association between the "height gap" and the onset age of puberty suggests that the variability of this age is part of the targeted process of statural growth. The proposed model may explain idiopathic cases of precocious and delayed puberty.
| S-EPMC6347184 | biostudies-literature
Project description:Evidence linking parental inflammatory bowel disease (IBD) with autism in children is inconclusive. We conducted four complementary studies to investigate associations between parental IBD and autism in children, and elucidated their underlying etiology. Conducting a nationwide population-based cohort study using Swedish registers, we found evidence of associations between parental diagnoses of IBD and autism in children. Polygenic risk score analyses of the Avon Longitudinal Study of Parents and Children suggested associations between maternal genetic liability to IBD and autistic traits in children. Two-sample Mendelian randomization analyses provided evidence of a potential causal effect of genetic liability to IBD, especially ulcerative colitis, on autism. Linkage disequilibrium score regression did not indicate a genetic correlation between IBD and autism. Triangulating evidence from these four complementary approaches, we found evidence of a potential causal link between parental, particularly maternal, IBD and autism in children. Perinatal immune dysregulation, micronutrient malabsorption and anemia may be implicated.
| S-EPMC9307481 | biostudies-literature
Project description:AimsThe neural cell adhesion molecule (NCAM) has been reported to be involved in the development of the central nervous system and its mRNA level might decrease in the serum of autistic patients. However, there was no evidence of the association of the NCAM1 gene polymorphisms with autism. In the present study, we enrolled 237 children with autism and 451 healthy control subjects. Then, we used the direct DNA sequencing for genotyping five tag single-nucleotide polymorphisms (SNPs) in the NCAM1 gene.ResultsBy using case-control association analyses, we found that three SNPs at the NCAM1 gene were associated with autism (rs 4937786, p=0.015; rs 12418058, p=0.0076; rs 1436109, p=0.0023). Two of them remained significant after the Bonferroni multiple testing correction (rs 12418058, P(corrected) =0.038; rs 1436109, P(corrected) =0.012). Moreover, two of the SNPs were associated with the parental age at conception in autism (rs 12418058, p=0.037; rs 1436109, p=0.01).ConclusionThese results showed that NCAM1 might play an important role in the pathogenesis of autism.
| S-EPMC4183898 | biostudies-literature
Project description:Almost 20% of infants with an older sibling with autism spectrum disorder (ASD) exhibit ASD themselves by age 3 years. The longer-term outcomes of high-risk infants are less clear. We examined symptoms of ASD, attention-deficit/hyperactivity disorder (ADHD) and anxiety, language, IQ, and adaptive behaviour at age 7 years in high- and low-risk children prospectively studied since the first year of life. Clinical outcomes were compared between high-risk children who met diagnostic criteria for ASD at age 7 (HR-ASD-7 group, n = 15), high-risk children without ASD (HR-Non-ASD-7 group, n = 24), and low-risk control children (LR group, n = 37). Diagnostic stability between age 3 and 7 years was moderate, with five children who did not meet diagnostic criteria for ASD at age 3 years being assigned the diagnosis at age 7, and three children showing the opposite pattern. The HR-ASD-7 group showed elevated ADHD and anxiety symptoms and had lower adaptive behaviour scores than LR controls. The HR-Non-ASD-7 group had higher repetitive behaviour, lower adaptive functioning and elevated scores on one anxiety subscale (Separation Anxiety) compared to LR controls, but evidence for subclinical ASD symptoms (the broader autism phenotype, BAP) was limited in the group as a whole, although we identified a subgroup with elevated ASD traits. The difficulties experienced by high-risk siblings at school-age extend beyond ASD symptoms. The pattern of difficulties exhibited by the HR-ASD-7 group may inform our understanding of developmental trajectories of co-occurring psychopathology in ASD. Autism Res 2017, 10: 546-557. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
| S-EPMC5408391 | biostudies-literature
Project description:BackgroundAsperger syndrome (AS) and high-functioning autism (HFA) are pervasive developmental disorders (PDD) in individuals of normal intelligence. Childhood AS/HFA is considered to be often associated with disturbed sleep, in particular with difficulties initiating and/or maintaining sleep (insomnia). However, studies about the topic are still scarce. The present study investigated childhood AS/HFA regarding a wide range of parent reported sleep-wake behaviour, with a particular focus on insomnia.MethodsThirty-two 8-12 yr old children with AS/HFA were compared with 32 age and gender matched typically developing children regarding sleep and associated behavioural characteristics. Several aspects of sleep-wake behaviour including insomnia were surveyed using a structured paediatric sleep questionnaire in which parents reported their children's sleep patterns for the previous six months. Recent sleep patterns were monitored by use of a one-week sleep diary and actigraphy. Behavioural characteristics were surveyed by use of information gleaned from parent and teacher-ratings in the High-Functioning Autism Spectrum Screening Questionnaire, and in the Strengths and Difficulties Questionnaire.ResultsParent-reported difficulties initiating sleep and daytime sleepiness were more common in children with AS/HFA than in controls, and 10/32 children with AS/HFA (31.2%) but none of the controls fulfilled our definition of paediatric insomnia. The parent-reported insomnia corresponded to the findings obtained by actigraphy. Children with insomnia had also more parent-reported autistic and emotional symptoms, and more teacher-reported emotional and hyperactivity symptoms than those children without insomnia.ConclusionParental reports indicate that in childhood AS/HFA insomnia is a common and distressing symptom which is frequently associated with coexistent behaviour problems. Identification and treatment of sleep problems need to be a routine part of the treatment plan for children with AS/HFA.
| S-EPMC1479331 | biostudies-literature
Project description:ImportanceThe prevalence and attributes of positive outcomes (or doing well) among children with autism spectrum disorder (ASD) in midchildhood are not well known.ObjectiveTo estimate the prevalence of doing well according to metrics of proficiency and growth and to investigate the extent to which significant associations exist between child- and family-level variables and doing well.Design, setting, and participantsThis longitudinal cohort study included children with ASD from regional clinics across Canada. Participants were sampled 3 times between ages 2 and 4.9 years (T1) and twice in follow-up into middle childhood (T2). Data were analyzed March 2018 through January 2020.ExposuresLanguage and IQ assessments at first sample; household income, parent coping, and family functioning.Main outcomes and measuresKey outcome domains of developmental health included measures of socialization, communication, independent living skills, and measures of internalizing and externalizing behaviors. Thresholds for doing well in these domains by either proficiency or growth were established. The extent to which language, IQ, household income, parent coping, and family functioning were associated with assessed outcomes was determined by logistic regression. The association between outcomes and concurrent Autism Diagnostic Observation Schedule (ADOS) classification scores was also estimated.ResultsIn a total cohort of 272 children (234 [86.0%] boys; mean [SD] age, 10.76 [0.26] years), approximately 78.8% (95% CI, 73.2%-84.4%) of the sample were estimated to be doing well by either metric on at least 1 domain, and 23.6% (95% CI, 17.7%-29.4%) were doing well in 4 or 5 domains. It was possible to be doing well by either proficiency or growth and still meet ADOS criteria for ASD. For the growth metric, between 61.5% (95% CI, 40.7%-79.1%) and 79.6% (95% CI, 66.0%-88.9%) of participants had ADOS scores of 4 or greater; for the proficiency metric, between 63.8% (95% CI, 48.4%-76.9%) and 75.8% (95% CI, 63.0%-85.4%) had scores of 4 or greater. Doing well by either metric for all domains was associated with T1 scores on that outcome domain (eg, T1 daily living skills associated with doing well at T2 daily living by the proficiency metric as measured by the Vineland Adaptive Behavior Scales-Second Edition daily living skills scale [202 participants]: β = 0.07; OR, 1.07; 95% CI, 1.03-1.11; P < .001). Doing well in socialization by the growth metric was also associated with better T1 language skills scores (202 participants) (β = 0.04; OR, 1.04; 95% CI, 1.00-1.07, P = .04). Doing well in externalizing by the growth metric was also associated with higher household income at T1 (178 participants) (β = 0.10; OR, 1.10; 95% CI, 1.06-1.15; P < .001). Better family functioning at T1 was associated with doing well on both socialization and externalizing by proficiency metric and on internalizing by growth metric (socialization by proficiency [202 participants]: β = -1.01; OR, 0.36; 95% CI, 0.14-0.93; P = .04; externalizing by proficiency [178 participants]: β = 1.00; OR, 0.37; 95% CI, 0.16-0.82; P = .02; internalizing by growth [178 participants]: β = -1.03; OR, 0.36; 95% CI, 0.16-0.79; P = .01).Conclusions and relevanceThis cohort study found that a substantial proportion of children with ASD were doing well by middle childhood in at least 1 key domain of developmental health, and that doing well was possible even in the context of continuing to meet criteria for ASD. These results support a strengths-based approach to treatment planning that should include robust support for families to increase the potential likelihood of doing well later in life.
| S-EPMC8008283 | biostudies-literature
Project description:BackgroundIndividuals born preterm may experience difficulties beyond the neonatal period, such as poorer school outcomes. However, whether these outcomes are modified by family factors is less well-known.ObjectivesTo investigate whether parental educational level modify the relationship of gestational age with completion of final examinations and grade point average in compulsory education.MethodsThis nationwide register-based cohort study included singletons born in Denmark during 1995-2001. We investigated the differences in the associations between gestational age (24-44 weeks) and two school outcomes at 16 years according to parental educational level (lower (≤10 years), intermediate (11-13 years), and higher (>13 years)). Mixed-effect logistic regression and mixed-effect linear regression were used to model completion of final examination and grade point average, respectively.ResultsOf the 425 101 singletons, 4.7% were born before 37 weeks. The risk of not completing final examination increased with shorter gestational age and lower parental educational level. For instance, among adolescents whose parents had a lower educational level, the risk increased from 23.9% (95% CI, 23.1, 24.6) for those born in week 40 to 36.6% (95% CI, 31.5, 42.1) for those born in week 28. For adolescents whose parents had a higher educational level, the corresponding risk increase was 5.9% (95% CI, 5.7, 6.1) to 10.5% (95% CI, 8.6, 12.8), respectively. Grade point average decreased with shorter gestational age in adolescents born before 30 weeks and with lower parental educational level. The associations between gestational age and grade point average were similar across parental educational levels. For completions of final examination, the associations with gestational age were weaker with higher parental educational level.ConclusionsShorter gestational age and lower parental educational level were associated with poorer school outcomes. Our findings suggest that parental educational level mitigates the adverse effects of shorter gestational age on some school outcomes.
| S-EPMC8597013 | biostudies-literature
Project description:BackgroundIn endemic areas, leptospirosis is more common and more severe in adults compared with children. Reasons to explain this discrepancy remain unclear and limited data focusing on adolescents are available. The objective of the study was to describe disease spectrum and outcome differences in children and adolescents admitted for leptospirosis in a large at-risk population.MethodsClinical and laboratory data were obtained on hospitalized cases in New Caledonia from 2006 to 2012.ResultsData of 60 patients <18 years of age (25 children under 14 and 35 adolescents aged 14 to 17) with confirmed leptospirosis were analyzed. Compared with children, adolescents presented more often with classic features of Weil disease (p = 0.02), combining hepatic and renal involvement with or without pulmonary participation. Jarisch-Herxheimer reactions were observed more often among adolescents (p<0.01). The overall case fatality rate was low (1 adolescent versus 0 children).ConclusionSevere leptospirosis in adolescents may be more likely to show adults' characteristics compared with children. Further studies are required to explore age-dependant host factors, including puberty-related physiological changes.
| S-EPMC3784464 | biostudies-literature