Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: Longitudinal analysis

Objectives: To investigate the distribution of month of birth in people with multiple sclerosis in Australia. To use the large regional and seasonal variation in ambient ultraviolet radiation in Australia to explore the association between exposure to ultraviolet radiation during pregnancy and subsequent risk of multiple sclerosis in offspring. Design: Data were gathered on birth month and year (1920-1950), sex, and state of birth for all patients surveyed in 1981 in Queensland, Western Australia, New South Wales (including Australian Capital Territory), South Australia, and Hobart (Tasmania). Population denominators were derived from the 1981 census and supplementary birth registration data. A variable for exposure to ambient ultraviolet radiation "at birth" was generated from monthly averages of daily total ambient ultraviolet radiation for each region. Negative binomial regression models were used to investigate exposure to ambient ultraviolet radiation at birth and at various intervals before birth. Setting: Patient data from multiple sclerosis prevalence surveys carried out in 1981; 1981 Australian census (giving the total number of people born in Australia and still alive and living in Australia in 1981 by year of birth 1920-50); supplementary Australian birth registration data covering the same birth years by month and state. Participants: 1524 patients with multiple sclerosis born in Australia 1920-50 from total population of 2 468 779. Main outcome measure: Cumulative incidence rate of multiple sclerosis. Results: There was a pattern of risk of multiple sclerosis with month of birth (adjusted incidence rate ratio 1.32, 95% confidence interval 1.10 to 1.58, P<0.01, for those born in November-December compared with those born in May-June). This pattern mirrored that previously reported in the northern hemisphere. Region of birth was related to risk. After adjustment for region of birth and other factors, there was an inverse association between ambient ultraviolet radiation in the first trimester and risk of multiple sclerosis (with ≥25 erythemal (skin reddening) dose units as reference (that is, adjusted incidence rate ratio=1.00), the rates were 1.54 (1.10 to 2.16) for 20-<25 units; 1.58 (1.12 to 2.22) for 15-<20 units; 1.65 (1.17 to 2.33) for 10-<15 units; 1.65 (1.18 to 2.29) for 5-<10 units; and 1.67 (1.18 to 2.37) for <5 units). After adjustment for this exposure during early pregnancy, there was no residual association between month of birth and multiple sclerosis. Conclusion: Region of birth and low maternal exposure to ultraviolet radiation in the first trimester are independently associated with subsequent risk of multiple sclerosis in offspring in Australia.