Season of birth and multiple sclerosis: a systematic review and multivariate meta-analysis.

Season of birth is considered to be associated with multiple sclerosis (MS) although some findings opposing to this assumption raise doubts about the seasonality pattern in MS births. The present work synthesizes the evidence of previous published studies aiming at examining whether the month of birth is associated with a higher number of MS births. Pubmed and Scopus were systematically searched and a multivariate meta-analysis of case-control studies was conducted. Data of healthy controls births were retrieved from census reports when not included in the studies. For comparisons, October was set as a reference month and autumn (September-October-November) as a reference season. The meta-analysis included studies that provided the number of MS births for each month or season. Twenty-two eligible studies were included in the meta-analysis involving twenty-four different populations and overall 145,672 MS patients and 75,169,550 healthy controls. The multivariate analysis supports that MS births in spring are higher compared to autumn [odds ratio (OR) 1.14, 95% confidence interval (CI) 1.04, 1.24]. Univariate analyses confirm the same for April (OR 1.12, 95% CI 1.05, 1.21), March (OR 1.05, 95% CI 1.00, 1.11) and May (OR 1.07, 95% CI 1.00, 1.14). A reduction of MS births was found in November (OR 0.96, 95% CI 0.93, 0.99). The month and the season of birth are significantly associated with MS births.