There was a large variation in average total daily ambient ultraviolet radiation, from 1.6 minimum erythemal dose units/day in Hobart, Tasmania in July to 30.4 units/day in Perth, Western Australia in January. Overall, the seasonal variation in total daily ambient ultraviolet radiation increased with increasing latitude from Brisbane, Queensland at lowest south latitude to Hobart, Tasmania at highest latitude (table 1).
For year of birth from 1920 to 1950, we identified 1524 cases in the prevalence study from a denominator population of 2
779. As expected from the previous Australian surveys,2
the incidence rate of multiple sclerosis was higher among women than men (incidence rate ratio 2.28, 95% confidence interval 2.03 to 2.55). There was also a latitudinal gradient in cumulative incidence rate by region of birth. Compared with the reference birth region, New South Wales/Australian Capital Territory, the risk was lower for those born in Queensland (0.59, 0.51 to 0.69) and higher for those born in Tasmania (2.70, 2.06 to 3.51). The capital cities of these northernmost and southernmost states are located at 27.5º south and 42.9º south, respectively (table 1).
Figure 1 shows the pattern of risk for multiple sclerosis for each two month period of birth, expressed as an incidence rate ratio for each period of birth relative to the reference incidence rate ratio (1.0) for May-June. The risk was 1.23-fold to 1.34-fold higher (P<0.05) for people born in all periods other than May-June; the highest magnitude of risk was for those born in the early summer months of November-December compared with the early winter months of May-June (1.34, 1.10 to 1.63; P<0.01). This pattern of month of birth persisted after adjustment for sex, age, and region of birth in Australia (1.32, 1.10 to 1.58; P<0.01, for November-December compared with May-June). We also examined whether the November-December to May-June risk ratio differed by region of birth; this ratio of around 1.3 was the same over the Queensland-Tasmania range, with no effect modification by region of birth (P=0.25).
We then examined the role of prenatal exposure to ambient ultraviolet radiation. We found no association between daily ambient ultraviolet radiation at the time of birth and subsequent risk of multiple sclerosis (table 2). Similarly, lags of one to four months before birth (late second to third trimesters) were not informative. For lags of five to nine months (first to early second trimesters), however, there were inverse associations between prenatal ambient ultraviolet radiation levels and multiple sclerosis (unadjusted incidence rate ratio ranging from 0.74 (0.63 to 0.85) to 0.81 (0.70 to 0.94); P<0.01). Table 2 summarises these results and shows a strong inverse association for the first trimester (0.72, 0.62 to 0.84), P<0.001).
Table 2 Risk of multiple sclerosis as unadjusted and adjusted incidence rate ratio for ambient ultraviolet radiation at and before time of birth
We examined the shape of the association between inversed first trimester exposure and risk of multiple sclerosis in greater detail by using six categories of ultraviolet radiation (in minimum erythemal dose units/day, see table 1) and comparing each of the five lowest levels with the highest (table 3). The association was non-linear with a particular increase in risk for levels below a monthly average of 20 minimum erythemal dose units/day (fig 2). This “threshold” level is reached only in January in Hobart, Tasmania, but from November to February in Brisbane, Queensland.
Table 3 Risk of multiple sclerosis as incidence rate ratio for six levels of ambient ultraviolet radiation during first trimester, with and without other factors
Fig 2 Risk of multiple sclerosis by average level of daily ambient ultraviolet radiation during first trimester. Incidence rate ratio adjusted for age (year of birth) and sex
Table 3 also shows the increase in risk for women and people born at higher latitudes; the result for decade of birth, showing a deficit in more recently born affected people, probably reflects ascertainment because for some in this group onset of multiple sclerosis might not have occurred by the time of the 1981 survey. The association between first trimester ultraviolet radiation and multiple sclerosis persisted, however, after adjustment for region of birth and the other factors listed in table 3.
We examined the association between prenatal exposure to ultraviolet radiation and risk of multiple sclerosis related to month of birth. Figure 3 shows the inverse relation between first trimester ultraviolet radiation and risk related to months of birth. That is, when we lagged the ultraviolet radiation values by seven to eight months, there was overall similarity between the two curves, such that infants experiencing low levels of ultraviolet radiation in the first trimester are associated with a higher risk of multiple sclerosis by birth month.
Fig 3 Multiple sclerosis risk by two month periods of birth with monthly averages of daily ambient ultraviolet radiation in first trimester of pregnancy on inverse scale. Time interval is two annual cycles
After adjustment for ultraviolet radiation in the first trimester, we found no residual association between period of birth and risk of multiple sclerosis. That is, once we accounted for first trimester ultraviolet radiation (as in table 3) there was no improvement in model fit by also including variation in period of birth (likelihood ratio χ2 (5 df) =3.79; P=0.58). In contrast, region of birth remained significantly associated with risk of multiple sclerosis even after adjustment for ultraviolet radiation in the first trimester (table 3).
There was no effect modification of the association between ultraviolet radiation in the first trimester and multiple sclerosis by sex (P=0.71) or region of birth (P=0.80).