Month of birth and risk of multiple sclerosis: confounding and adjustments

Abstract

A month of birth effect on multiple sclerosis (MS) risk has been reported from different countries. Recent critics have suggested that this finding is caused by confounding and that adequately adjusting for year and place of birth would markedly reduce this effect. All inhabitants in Norway are registered in the Norwegian Population Registry (Statistics Norway), making this an ideal area for performing adjusted analyses. Using the entire Norwegian population born between 1930 and 1979 (n = 2,899,260), we calculated the excess between observed and expected number of births for each month for 6649 Norwegian MS patients, 5711 mothers, 5247 fathers, and 8956 unaffected siblings. The analyses were adjusted for year of birth and place of birth according to the 19 counties in Norway. An unadjusted analysis revealed 13% fewer MS births than expected in February (P = 0.0015; Bonferroni corrected P = 0.018), 10% more in April (P = 0.0083; Bonferroni corrected P = 0.0996) and 15% more in December (P = 0.00058; Bonferroni corrected P = 0.007). Adjustments for both year and place of birth significantly altered our results for February and December, but even after these adjustments there were still 10% more MS births than expected in April (P = 0.00796; Bonferroni corrected P = 0.096). MS patients had a higher incidence of April births than their siblings (Fisher-exact test; P = 0.011), mothers (Fisher-exact test; P = 0.004), and fathers (Fisher-exact test; P = 0.011) without MS. Adjustments for confounding significantly affected our results. However, even after adjustments, there appears to be a persistent higher than expected frequency of April births in the MS population.

Environmental and genetic risk factors for MS: an integrated review

“…For example, the risk of pediatric‐onset MS is increased in association with maternal illness other than diabetes and preeclampsia during pregnancy, and a father with an agricultural profession during pregnancy . Post‐winter birth is more common, and post‐summer birth less common, in people with MS, although there is some debate whether this finding may be due to residual confounding . Lower vitamin D status during pregnancy or infancy is associated with increased risk of MS in Whites …”

Is Season of Birth Important for Multiple Sclerosis Risk?

“…Prior studies [4][5][6][7] have demonstrated a higher risk for MS in infants born in the spring, whether in the Northern or Southern hemispheres. Recent work [8][9][10] has questioned these associations based on unaccounted-for biases from birth patterns in the general population. Concern has centered on the concept that birth rates are not homogeneously distributed throughout the year and may vary by region or latitude within a country.…”

The Norwegian Multiple Sclerosis Registry and Biobank

“…Education analysis, however, showed a marked and linear inverse relationship between level of education and the risk of MS in the total study population . Registry data have been included in analyses of month of birth and gender differences in MS incidence .…”