COPENHAGEN—Most, if not all, of the previous claims for association between multiple sclerosis (MS) and month of birth are false positive, according to a study presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). According to researchers, the reported association is more likely to have arisen through confounding factors rather than biology.
Barnaby D. Fiddes, MD, from the Department of Clinical Neurosciences at the University of Cambridge, and colleagues recognized that association studies can generate false positive results if cases and controls are not adequately matched for confounding variables. Given how heterogeneous month of birth is with respect to both year and place of birth, the researchers investigated whether uncompensated variables might underlie the previously reported association between MS and month of birth.
The researchers used publicly available national records for 271 million births in the United Kingdom and Europe to establish birth rates in the general population and their own databases of patients with MS to establish the age and regional origin distribution seen in a typical MS case collection. The investigators also used simulations to make a highly conservative estimate of the false positive rate expected in an analysis of month of birth following the approach used in previously published studies that showed an association between MS and month of birth.
Dr. Fiddes and his research colleagues confirmed that month of birth in the general population shows marked seasonal variation and that this seasonality is highly heterogeneous over time and both between and within countries. Simulations based on UK Government Office Region data showed that failing to correct for within-population variations in month of birth results in a high probability of false positive association.
“We confirmed that in spring months, birth rate shows a positive correlation with latitude and a negative correlation with year of birth, while the reverse is true in winter months,” the researchers reported. “These correlations explain the superficial consistency between month-of-birth studies.”
Dr. Fiddes and colleagues concluded that “although it is impossible to completely exclude any possibility of a month-of-birth effect, our data indicate that previous claims of association between month of birth and MS are almost certain to be false positives.”
—Glenn S. Williams
Vice President/Group Editor