Do prenatal sex hormones modulate MS risk?

The etiology of multiple sclerosis (MS) is complex, involving genetic and environmental risk factors and their interactions. Furthermore, evidence suggests that the timing of exposure to environmental factors may be important. The exploration of risk associated with exposures distant in time, e.g., in childhood, or even before birth, presents particular difficulties. For example, month of birth has been considered a proxy for early-life vitamin D status. Thus, the finding that people with MS are more likely to have been born in spring and less likely to have been born in autumn in both southern and northern hemispheres (reviewed in reference 1) has been interpreted as possibly indicating that early-life vitamin D deficiency increases the risk of MS in adulthood. Determining any change in risk associated with other in utero exposures has been more challenging because of a lack of suitable validated proxies and a need to rely on self-reported events that occurred many years previously, during the pregnancy of the patient's mother. For example, in the Nurses' Health Studies, late initiation of prenatal care, diabetes during pregnancy, and maternal prepregnancy overweight/obesity were associated with modest increases in MS risk, although in most instances, the number of affected persons was small