Association of pre-existing maternal cardiovascular diseases with neurodevelopmental disorders in offspring: a cohort study in Sweden and British Columbia, Canada
Bibliographic record
Abstract
Abstract Importance Maternal cardiac disease is associated with impaired placentation and adverse neonatal outcomes, but whether it increases the risk of subsequent neurodevelopmental disorders in offspring remains unknown. Objective To assess the associations between pre-existing maternal cardiovascular disease (CVD) and attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID) in offspring. Design Population-based cohort study. Setting Sweden and British Columbia (BC), Canada. Participants Singletons live-born without major malformations between 1990 and 2019. The Swedish Medical Birth Register and the BC Vital Statistics were linked to hospital and physician billing records for identification of exposure and outcomes. All children were followed from age 1 until the outcome, death, emigration, or December 2020. Exposure A composite of pre-conception maternal CVDs: cerebrovascular disease, arrhythmia, heart failure, valvular, and congenital heart diseases. Main Outcomes and Measures Diagnoses of ADHD, ASD, and ID. The incidence of ADHD, ASD, and ID, comparing offspring of mothers with versus without CVD, was calculated as adjusted hazard ratios (aHRs). These results were compared to models using paternal CVD as negative-control exposure. Fixed-effect meta-analysis was performed to combine the aHRs from Sweden and BC. Results We analysed 3,587,257 offspring (48.9% female) – 2,699,675 in Sweden and 887,582 in BC. The meta-analysis suggests that compared with offspring of mothers without CVD, offspring of mothers with CVD had 1.15-fold higher aHRs of ADHD (95% CI: 1.10-1.20) and ASD (95% CI: 1.07-1.22). No association was found between maternal CVD and ID. Stratification by maternal CVD subtypes showed increased hazards of ADHD for maternal heart failure (aHR 1.31; 95% CI: 1.02-1.61), cerebrovascular disease (aHR 1.20; 95% CI: 1.08-1.32), congenital heart disease (aHR 1.18; 95% CI: 1.08-1.27), arrhythmia (aHR 1.13; 95% CI: 1.08-1.19), and valvular heart disease (aHR 1.12; 95% CI: 1.00-1.24). Increased hazards of ASD were observed for maternal cerebrovascular disease (aHR 1.25; 95% CI: 1.04-1.46), congenital heart disease (aHR 1.17; 95% CI: 1.01-1.33), and arrythmia (HR 1.12; 95% CI: 1.01-1.21). Paternal CVDs, except for cerebrovascular disease, did not show associations. Conclusion and Relevance Pre-existing maternal CVD was associated with excess risk of ADHD and ASD in offspring. The associations were broadly robust to genetic confounding, warranting further research to identify the underlying intrauterine mechanisms.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".