Prenatal DES Exposure and Increased Risk of Multiple Sclerosis

Prenatal and Perinatal Factors and Risk of Multiple Sclerosis

2011 Study Abstracts

A potential role of prenatal and perinatal exposures in autoimmunity has been hypothesized, but few studies have examined the relation between various prenatal and perinatal factors and risk of multiple sclerosis (MS).

The study population included participants in the Nurses’ Health Studies, 2 prospective cohorts that together comprise 238,381 female nurses, who self-reported exposure to prenatal and perinatal factors. In addition, 35,815 nurses’ mothers participated by providing detailed information regarding experiences surrounding their daughter’s birth. The following prenatal and perinatal factors were studied in relation to MS: fetal growth, birth season, preterm birth, mode of delivery, maternal weight gain, medical conditions, medication use, diethylstilbestrol exposure, prenatal health care, maternal activity level, maternal obstetric history, parental age, and prenatal and childhood passive smoke exposure.

The sample included 723 confirmed MS cases, including 383 with diagnosis after reporting prenatal and perinatal factors. Few associations were observed. These included an increased risk among women whose mothers reported late initiation of prenatal care (after the first trimester) (27 cases, rate ratio = 1.6; 95% confidence interval = 1.0–2.4), diabetes during pregnancy (2 cases; 10;2.5–42), and maternal prepregnancy overweight/obesity (20 cases; 1.7; 1.0–2.7). Results also suggested a possible increase in incident MS risk among women with prenatal diethylstilbestrol exposure (9 cases; 1.8; 0.93–3.5).

PMC full text: Epidemiology. Author manuscript; available in PMC3132937 2011 Jul 11.

This study provides modest support for a role of prenatal factors in MS risk. The results should be interpreted cautiously due to the limited statistical power, potential for exposure misclassification, and possibility of chance findings.

Exposure Assessment

For in utero diethylstilbestrol (DES) exposure, assessed in the NHS-II in 1993, a confirmation questionnaire was sent to all nurses who self-reported DES exposure to classify the level of certainty (very certain, somewhat certain, not certain, or not exposed). The current analysis uses a conservative approach and compares those who were very certain of DES exposure with those who self-reported as nonexposed.


This is the first study to assess directly the relation between prenatal DES exposure and risk of multiple sclerosis. Small preliminary studies have suggested an increased risk of any autoimmune disease  or, more broadly, of diseases involving impaired immune function, among individuals with prenatal DES exposure. Experimental studies in laboratory animals as well as human case series have also indicated altered immune cell function associated with DES exposure, such as abnormal natural killer cell activity, T cell-mediated immunity, and thymic development. Despite the limited statistical power with this very rare exposure, there was modest support for a positive association. Further examination is warranted, especially because the potential association may be generalized to other prenatal hormone exposures.

  • Download the full study (free access 15 pages PDF) Prenatal and Perinatal Factors and Risk of Multiple Sclerosis, US National Library of Medicine National Institutes of Health, Epidemiology, NCBI PubMed PMC3132937, 2011 Jul 11.
  • Featured image credit medicinenet.

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