Supplementary Material for: CHILDHOOD DEVELOPMENTAL MILESTONES AND RISK OF ADULT CEREBROVASCULAR DISEASE - The Northern Finland Birth Cohort 1966

Introduction
To the best of our knowledge, no previous studies have examined the relationship between childhood developmental milestones and risk of adulthood cerebrovascular disease (CeVD). We studied whether the risk of adult CeVD is associated with delayed attainment of motor and language milestones.
Methods
Within the Northern Finland Birth Cohort 1966, a total of 11,688 persons were followed from birth to either death, moving abroad or 54 years of age. CeVD diagnoses, i.e., ischemic and hemorrhagic strokes and transient ischemic attacks, were extracted from national registers with diagnostic coding based on recommendations of the World Health Organization. Cox proportional hazard models stratified by sex were used to estimate associations of motor development and language milestones between ages 0 to 4 years and adult CeVD Women-to-men relative hazard ratios (RHR) were estimated for each developmental milestone. Analyses were adjusted for family socioeconomic status and birth weight for gestational age.
Results
Altogether 498 (4.3%) CeVDs were recorded during follow-up. Among both sexes, later turning from back to tummy was associated with ischemic CeVD in adulthood with an adjusted hazard ratio (aHR) of 1.25 and 95% confidence interval (CI) 1.06-1.46 for men and an aHR 1.20 (CI 1.02-1.42) for women per one month delay in achievement. Delayed overall motor development, modeled by motor milestone principal component score, was related to increased risk of ischemic CeVD (aHR 1.50; CI 1.03-2.19) among men. Later achievement of making sounds was associated with any CeVD (aHR 2.74; CI 1.39-5.40) and especially ischemic CeVD (aHR 3.41; CI 1.65-7.06) among men with women-to-men RHR’s of 0.17 (95% CI 0.04–0.81) for any CeVD and RHR 0,18 (95% CI 0,04-0,89) for ischemic stroke indicating risk to be lower in women compared to men.
Conclusions
These findings suggest that later achievement of childhood milestones could be a predictor for development of CeVD risk. The results point towards a common neurodevelopmental background and could in part explain lifetime CeVD risk accumulation.