We compared the numbers of individuals with MS born in each month versus the other 11 months with population based controls. In the Canadian dataset (n = 17 874), 8.5% fewer people with MS were born in November; this was significant even after we corrected for the 12 monthly comparisons (1257 observed v 1373 expected, χ2 = 10.67, P = 0.0011 or P = 0.013 with Bonferroni correction) (). The peak birth month for people with MS was offset six months, in May, though this was not significant (P = 0.15). We found no difference within Canadian patients by sex, site of ascertainment, or decade of birth. Population control results, weighted to match patients with MS for year of birth, were similar to non-weighted controls (not shown). Among 67 Canadian patients with MS born in the southern hemisphere, eight were born in November and two in May, suggesting a reversal of the pattern in northern countries.
Observed number of people in Canada with multiple sclerosis (MS) compared with expected number, according to month of birth
When we compared the dataset of British patients with MS, ascertained through death certificates and from incident cases (n = 11 502), with controls obtained via similar methods we found significantly fewer people with MS had been born in November (10.0%, χ2 = 6.80, uncorrected P = 0.009) and significantly more had been born in May (16.3%, χ2 = 18.02, uncorrected P < 0.0001, corrected P = 0.0003) (). The number born in December was also significantly lower (χ2 = 4.8, P = 0.028), but this was not significant when we corrected for multiple comparisons. We combined the data for the 8702 cases from England and Wales according to death certificates, the 2356 cases from Scotland according to death certificates, and the 444 Scottish incident cases because each group had appropriately matched controls, all patients were from the same geographic region, and the confidence intervals of the odds ratios for May and November in each group substantially overlapped (odds ratio 1.30, 95% confidence interval 1.17 to 1.44, for cases from England and Wales; 1.17, 0.94 to 1.47, for Scottish death certificate cases; and 1.89, 1.09 to 3.28, for Scottish incident cases).
Observed number of people in Great Britain with multiple sclerosis (MS) compared with expected number, according to month of birth
We added Danish10
(n = 6276) and Swedish11
(n = 6393) samples to our Canadian (n = 17 874) and British samples (n = 11 502; total n = 42 045). In this combined sample significantly more people with MS were born in May (9.1%) and significantly fewer were born in November (8.5%) (uncorrected and corrected P values for May and November were all < 0.0001) (, ). This represents a 19% (odds ratio 1.19, 95% confidence interval 1.14 to 1.25) decreased risk of MS for those born in November compared with those born in May.
Pooled analysis of observed/expected births in people with multiple sclerosis in Canadian, British, Danish, and Swedish studies (n=42 045) with 95% confidence intervals
Observed number of people in northern hemisphere (Canada, Great Britain, Denmark, and Sweden) with multiple sclerosis (MS) compared with expected number, according to month of birth
In the Canadian dataset, we used a second control group of matched unaffected siblings. We had complete data on 9248 unaffected siblings from 7450 patients with MS. Index cases were matched with one non-twin sibling, which resulted in a dataset of 4232 affected-unaffected sibling pairs. We observed a slight correlation in the month of birth for closely spaced siblings, but not among more distantly spaced offspring (data not shown). To account for this effect, when there was more than one unaffected sibling we selected the one furthest in age from the index case. This group showed no significant correlation for month of birth in sibling pairs (P = 0.30). We compared affected siblings with their matched unaffected siblings using McNemar's test for November birth and observed 273 pairs in which the affected member of the pair was born in November and 343 where the unaffected sibling was born in November. The result was significant for difference in November births (P = 0.0048). Selection of the unaffected sibling closest in age also yielded a significant difference (P = 0.0018).
We tested whether the environmental component related to month of birth might contribute to familial risk, perhaps by interacting with susceptibility genes predictably enriched in families with multiple cases of MS.15
Among affected people with a family history of MS we found 16.2% fewer were born in November relative to population controls compared with 3.0% fewer among those with no family history of MS (χ2
= 3.92, P = 0.050). We found no difference when we divided affected individuals into fourths according to age of onset (data not shown).
We also compared the odds ratio for increased risk of MS for people born in May compared with November. We used incident cases only to allow consistency among the countries examined. The highest odds ratio for May/November risk was in Scotland (1.89, 1.09 to 3.28), followed by Denmark (1.22, 1.08 to 1.38), Sweden (1.18, 1.05 to 1.33), and Canada (1.13, 1.05 to 1.22) ().
Odds ratios for people with multiple sclerosis being born in May/November among incident cases in northern hemisphere countries