Optimal interpregnancy interval in autism spectrum disorder: A multi-national study of a modifiable risk factor

It is biologically plausible that risk of autism spectrum disorder (ASD) is elevated by both short and long interpregnancy intervals (IPI). We conducted a retrospective cohort study of singleton, non-nulliparous live births, 1998–2007 in Denmark, Finland, and Sweden (N = 925,523 births). Optimal IPI was defined as the IPI at which minimum risk was observed. Generalized additive models were used to estimate relative risks (RR) of ASD and 95% Confidence Intervals (CI). Population impact fractions (PIF) for ASD were estimated under scenarios for shifts in the IPI distribution. We observed that the association between ASD (N = 9302) and IPI was U-shaped for all countries. ASD risk was lowest (optimal IPI) at 35 months for all countries combined, and at 30, 33, and 39 months in Denmark, Finland, and Sweden, respectively. Fully adjusted RRs at IPIs of 6, 12, and 60 months were 1.41 (95% CI: 1.08, 1.85), 1.26 (95% CI: 1.02, 1.56), and 1.24 (95% CI: 0.98, 1.58) compared to an IPI of 35 months. Under the most conservative scenario PIFs ranged from 5% (95% CI: 1%–8%) in Denmark to 9% (95% CI: 6%–12%) in Sweden. The minimum ASD risk followed IPIs of 30–39 months across three countries. These results reflect both direct IPI effects and other, closely related social and biological pathways. If our results reflect biologically causal effects, increasing optimal IPIs and reducing their indications, such as unintended pregnancy and delayed age at first pregnancy has the potential to prevent a salient proportion of ASD cases. Lay Summary: Waiting 35 months to conceive again after giving birth resulted in the least risk of autism. Shorter and longer intervals resulted in risks that were up to 50% and 85% higher, respectively. About 5% to 9% of autism cases might be avoided by optimizing birth spacing

Interactive Statistical Mechanics and Nonlinear Filtering

This paper connects non-equilibrium statistical mechanics and optimal nonlinear filtering. The latter concerns the observation-conditional behaviour of Markov signal processes, and thus provides a tool for investigating statistical mechanics with partial observations. These allow entropy reduction, illustrating Landauer's Principle in a quantitative way. The joint process comprising a signal and its nonlinear filter is irreversible in its invariant distribution, which therefore corresponds to a non-equilibrium stationary state of the associated joint system. Macroscopic entropy and energy flows are identified for this state. Since these are driven by observations internal to the system, they do not cause entropy increase, and so the joint system makes statistical mechanical sense in reverse time. Time reversal yields a dual system in which the signal and filter exchange roles. Despite the structural similarity of the original and dual systems, there is a substantial asymmetry in their complexities. This reveals the direction of time, despite the systems being in stationary states that do not produce entropy. © 2008 Springer Science+Business Media, LLC