Maternal BMI Linked to Multiple Sclerosis Risk in Offspring

TORONTO — Higher BMI in early pregnancy is associated with a significantly increased risk for multiple sclerosis (MS) in offspring.Results of a nationwide, observational cohort study of more than 1.5 million births in Sweden showed that compared with a normal weight, maternal obesity was associated with a 35% higher rate of MS in offspring (adjusted hazard ratio [aHR], 1.35; 95% CI, 1.11-1.64) and maternal overweight was associated with a 20% higher rate (aHR, 1.20; 95% CI, 1.05-1.37).Each 1-unit increase in maternal BMI was associated with a 3% higher hazard of offspring MS (aHR, 1.03; 95% CI, 1.02-1.04), with similar associations for paediatric- and adult-onset disease. Absolute incidence remained low, ranging from 0.37 to 0.45 per 10,000 person-years across BMI groups.“This study is contributing to the evidence that MS susceptibility may actually begin very, very early in life, even before birth,” study investigator Kyla Anne McKay, PhD, assistant professor of neuroepidemiology at Karolinska Institutet in Stockholm, Sweden, told Medscape Medical News.A growing body of evidence suggests the in utero environment is meaningful, McKay said, and that the findings add maternal weight to the list of prenatal factors associated with MS risk in offspring.The findings were presented on October 21 at the 10th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2026.Prenatal InfluencesMS risk is influenced by genetic and environmental factors, with growing evidence suggesting that susceptibility may begin early in life. Maternal BMI in early pregnancy has been linked to autoimmune and neurologic outcomes in children, but its association with MS risk in offspring remains unclear.To investigate this relationship, the researchers conducted the population-based cohort study, which included 1,524,863 singleton births in Sweden from 1992 to 2007, with follow-up via national registers through the end of 2025.Maternal BMI was characterized at the first antenatal visit at a median of 10 weeks of gestation as underweight (< 18.5), normal weight (18.5-24.9), overweight (25.0-29.9), and obesity (≥ 30.0).McKay noted that in Sweden, midwives are required to record maternal BMI in the Swedish National Medical Birth Register at the first antenatal visit.Investigators identified offspring MS through Sweden’s National Patient Register, requiring at least three MS diagnostic codes (ICD-10 G35) recorded on separate dates.Analyses were adjusted for maternal age, parity, region of birth, education level, cohabitation with a partner, height, smoking status, and MS, as well as year of delivery.Of the total number of births, 1539 offspring were subsequently diagnosed with MS. Of these, 69% were female. The incidence of MS per 100,000 person-years was 0.37 in the underweight and normal weight groups, 0.42 in the overweight group, and 0.45 in the obesity group.Compared with offspring of mothers with normal weight, those of mothers with overweight had a higher rate of MS (aHR, 1.20; 95% CI, 1.05-1.37), as did those of mothers with obesity (aHR, 1.35; 95% CI, 1.11-1.64).Each 1-unit increase in maternal BMI was associated with a 3% higher rate of MS in offspring overall (aHR, 1.03; 95% CI, 1.02-1.04), a 4% higher rate of pediatric-onset MS (aHR, 1.04; 95% CI, 1.01-1.07), and a 3% higher rate of adult-onset MS (aHR, 1.03; 95% CI, 1.01-1.04).An analysis restricted to mothers without pregnancy complications yielded comparable results.The Role of InflammationThe research had several limitations. Children of mothers with overweight or obesity are more likely to have overweight or obesity themselves, and that is a well-established risk factor for MS, McKay said. Residual confounding also can’t be ruled out.In addition, the study included only 220 pediatric-onset MS cases, and because the oldest offspring were about 33 years old at the end of follow-up, later-onset disease wasn’t captured.A proinflammatory intrauterine environment and low maternal vitamin D levels during pregnancy may help explain the link between maternal BMI and MS risk in offspring, McKay said. Both are tied to excess weight, given that adipose tissue promotes chronic low-grade inflammation and that obesity is associated with lower circulating vitamin D levels.McKay said the strongest evidence for other offspring outcomes linked to maternal BMI involves inflammatory diseases. “Type 1 diabetes and asthma are the two big ones that have been studied, and there’s increasing evidence that IBD [inflammatory bowel disease] may also be impacted.”Emerging evidence also implicates neurodevelopmental disorders, such as attention-deficit/hyperactivity disorder and autism, she noted. “So maternal BMI can have wide-ranging consequences.”The investigators had BMI data only from the first antenatal visit. But that visit, at about 10 weeks of gestation, occurs early enough to reflect prepregnancy BMI, McKay said.Intriguing but ComplexThe findings are “intriguing” and add to a growing number of studies linking offspring outcomes to factors during pregnancy, from maternal sun exposure to BMI, said Emmanuelle L. Waubant, MD, professor of neurology at UC San Francisco, who co-chaired the session featuring the study.“It really conveys the idea that there might be risk factors that occur very early on,” she said.Still Waubant cautioned that shared genetics could help explain the findings. About 150 genes are associated with obesity, and some of them may also increase MS risk, she said. A mother could pass enough of those genes to her child to raise the child’s risk for obesity.“We know that young people with obesity are more likely to develop MS, regardless of the mother’s weight,” she said.The Swedish Research Council funded the study. McKay reported receiving research funding from the Swedish Research Council, Bjarne Ahlströms Minnesfond, and ALF Medicine.Waubant reported no relevant disclosures.