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Background: Maternal pre-gestational diabetes (PGDM), gestational diabetes mellitus (GDM), and overweight/obesity have been associated with increased risks of offspring neurodevelopmental conditions (NDCs) including autism, intellectual disability (ID), and attention deficit/hyperactivity disorder (ADHD). Less is known about whether and how obstetric and neonatal complications (e.g., preterm birth, neonatal asphyxia) could mediate these associations. Methods: In this Swedish register-based cohort study, we examined complications during pregnancy, delivery, and the neonatal period as potential mediators of the relationships between maternal metabolic conditions and offspring NDCs. We quantified the extent to which these obstetric and neonatal factors could mediate the associations of maternal metabolic conditions with offspring NDCs by applying parametric regression models for single mediation analyses and weighting-based methods for multiple mediation analyses under counterfactual frameworks. Results: The study sample included 2,352,969 singleton children born to 1,299,692 mothers from 1987–2010 who were followed up until December 31, 2016, of whom 135,832 children (5.8%) were diagnosed with at least one NDC. A substantial portion of the association between maternal PGDM and children's odds of NDCs could be explained by the combined group of obstetric and neonatal complications in the multiple mediation analysis. For instance, these complications explained 44.4% of the relationship between maternal PGDM and offspring ID risk. The proportion of the relationship between maternal overweight/obesity and children's risk of NDCs that could be explained by obstetric and neonatal complications was considerably smaller, ranging from 1.5 to 8.1%. Some complications considered on their own, including pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities, could explain at least 10% of the associations between maternal PGDM and offspring NDCs. Complications during the neonatal period showed a stronger joint mediating effect for the relationship between PGDM and offspring NDCs than those during pregnancy or delivery. Conclusions: Obstetric and neonatal complications could explain nearly half of the association between maternal PGDM and offspring risk of NDCs. The mediating effects were more pronounced for complications during the neonatal period and for specific complications such as pregnancy hypertensive diseases, preterm birth, neonatal asphyxia, and hematological comorbidities. Effective preventive strategies for offspring NDCs should holistically address both the primary metabolic issues related to PGDM and the wide array of potential complications, especially those in the neonatal period. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is associated with both short- and long-term risks, although it is unknown if risks vary by severity, timing, and duration of gestational hyperglycemia. We aimed to identify trajectories of random capillary glucose (RCG) levels throughout pregnancy and assess their associations with both obstetric/neonatal outcomes and children's risk of neurodevelopmental conditions (NDCs) (i.e., autism, intellectual disability, and attention-deficit/hyperactivity disorders [ADHD]). Methods: A population-based cohort study was conducted involving 76,228 children born to 68,768 mothers without pregestational diabetes. Group-based trajectory modeling was utilized to identify distinct glucose trajectories across RCG values throughout the course of pregnancy. The associations between these trajectory groups and obstetric/neonatal outcomes as well as children's NDCs were then assessed using generalized estimating equation models with a logit link. The Benjamini-Hochberg (BH) procedure was employed to adjust P-values for multiple comparisons, controlling the false discovery rate (FDR). Results: Five distinct glucose trajectory groups were identified, each with varying percentages diagnosed with GDM. Their associations with obstetric/neonatal outcomes as well as children's NDCs varied. For example, when compared to the "Persistently Low" group, other groups exhibited varying degrees of increased risk for large-for-gestational-age babies, with the exception of the "High in Early Pregnancy" group. Compared to the "Persistently Low" group, all other trajectory groups were associated with NDC outcomes, except the "High in Mid-Pregnancy" group. However, none of the associations with offspring NDCs remained significant after accounting for the FDR correction. Conclusions: Persistent high glucose levels or moderately elevated glucose levels throughout pregnancy, as well as transient states of hyperglycemia in early or mid-pregnancy, were found to be associated with increased risks of specific obstetric and neonatal complications, and potentially offspring NDCs. These risks varied depending on the severity, timing, duration, and management of hyperglycemia. The findings underscore the need for continuous surveillance and individualized management strategies for women displaying different glucose trajectories during pregnancy. Limitations such as potential residual confounding, the role of mediators, and small sample size should be addressed in future studies. [ABSTRACT FROM AUTHOR]

Objective: Original case descriptions of autism noted that parents of the affected children tended to be highly educated and intelligent, a characterization that has endured publicly. Recent genetic studies indicate that risk for autism spectrum disorders (ASD) is associated with high intelligence. We examined the association between paternal intelligence and ASD, considering co-occurring intellectual disability (ID) and attention-deficit/hyperactivity disorder (ADHD).Method: We used a register-based cohort study design including 360,151 individuals with fathers conscripted to the Swedish military, resident in Stockholm, Sweden, born from 1984 to 2008, and followed until December 31, 2011, for diagnosis of ASD, ADHD, and/or ID. Risk of neurodevelopmental disorders relative to paternal IQ (rated on a 9-point scale) was assessed using a score of 5 (average intelligence) as the referent in models accounting for potentially nonlinear relationships and clustering of siblings.Results: We observed an association between high paternal IQ and offspring risk of ASD without ID/ADHD in models adjusted for individual and family characteristics (ORIQ=9 1.32, 95% CI 1.15-1.52), an association that appeared to be driven largely by the fathers' score on the technical comprehension portion of the test (ORTechnical IQ = 9 1.53, 95% CI 1.31-1.78). Conversely, low paternal IQ was associated with ASD+ID (ORIQ = 11.78, 95% CI 1.27-2.49) and ASD+ADHD (ORIQ = 11.40, 95% CI 1.16-1.70); low paternal IQ was strongly associated with ID (ORIQ = 1 4.46, 95% CI 3.62-5.49) and present also for ADHD (ORIQ = 11.56, 95% CI 1.42-1.72)] without co-occurring ASD or ID.Conclusion: The relationship between paternal IQ and offspring risk of ASD was nonmonotonic and varied by the presence of co-occurring disorders, probably reflecting phenotypic diversity among affected individuals. [ABSTRACT FROM AUTHOR]

Background: Preterm birth has been linked to increased risk of autism spectrum disorders (ASD), but how this risk changes with gestational age at birth has not been well characterised, especially with regard to co-occurring intellectual disability (ID).Methods: Register-based cohort study of singleton births in 1984-2007 in Stockholm County, Sweden (N total: 480 728; n ASD: 10 025). We assessed overall and sex-specific, gestational week-specific prevalence estimates and risk ratios of ASD with and without ID.Results: Preterm and postterm births were associated with elevated risk of ASD, and the relationship between gestational age at birth and ASD with and without ID differed in males and females. Risk of ASD without ID was higher in preterm births among both sexes and decreased continuously with increasing length of gestation. Risk of ASD with ID was higher in both preterm and postterm births among both sexes, with postterm birth in females being more highly associated with ASD with ID than that in males.Conclusions: The relationship between gestational age at birth and ASD differs by the presence/absence of co-occurring ID and fetal sex. Both preterm and postterm birth are associated with increased risk of ASD. Risk of ASD is not constant within conventionally defined gestational age at birth periods. Further research on mechanism underlying these associations is needed. [ABSTRACT FROM AUTHOR]

Background: The objectives of this study were to examine the independent and dependent associations of maternal and paternal age and risk of offspring autism spectrum disorders (ASD), with and without intellectual disability (ID).Methods: The sample consisted of 417 303 Swedish children born 1984–2003. ASD case status (N = 4746) was ascertained using national and regional registers. Smoothing splines in generalized additive models were used to estimate associations of parental age with ASD.Results: Whereas advancing parental age increased the risk of child ASD, maternal age effects were non-linear and paternal age effects were linear. Compared with mothers at the median age 29 years, those <29 had similar risk, whereas risk increased after age 30, with an odds ratio (OR) of 1.75 [95% (CI): 1.63–1.89] at ages 40–45. For fathers, compared with the median age of 32 years, the OR for ages 55–59 was 1.39 (1.29–1.50). The risk of ASD was greater for older mothers as compared with older fathers. For example, mothers aged 40–45 (&geq;97.2th percentile) had an estimated 18.63 (95% CI: 17.25–20.01) ASD cases per 1000 births, whereas fathers aged 55–59 (&geq;99.7th percentile) had 16.35 (95% CI: 15.11–17.58) ASD cases per 1000 births. In analyses stratified by co-parental age, increased risk due to advancing paternal age was evident only with mothers &leq;35 years. In contrast, advancing maternal age increased risk regardless of paternal age. Advancing parental age was more strongly associated with ASD with ID, compared with ASD without ID.Conclusions: We confirm prior findings that advancing parental age increases risk of ASD, particularly for ASD with ID, in a manner dependent on co-parental age. Although recent attention has emphasized the effects of older fathers on ASD risk, an increase of n years in maternal age has greater implications for ASD risk than a similar increase in paternal age. [ABSTRACT FROM PUBLISHER]