瑞典全国队列研究：孕早期母亲BMI较高与子代多发性硬化风险升高相关

Abstract

Objective To examine whether prospectively recorded maternal BMI in early pregnancy is associated with offspring multiple sclerosis (MS) risk, including childhood-onset and adult-onset MS. Design Nationwide population-based cohort study. Setting Swedish national health and demographic registers. Participants 1,524,863 singleton children born in Sweden from 1992 to 2007 and followed through 2025. Exposures Maternal BMI recorded at the first antenatal visit, categorised as underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9), and obesity (≥30.0), and also modelled continuously. Main outcome measures MS in offspring, identified as at least three ICD-10 G35 codes recorded on separate dates. Cox models estimated adjusted hazard ratios (HR) and 95% confidence intervals (CI) adjusting for confounders. Results During follow-up, 1539 offspring (0.1%) were diagnosed with MS at a median age of 24 years (interquartile range, 20-27 years). MS incidence rates by maternal BMI category were 0.37 per 10,000 person-years for both underweight, and normal weight, 0.42 for overweight, and 0.45 for obesity. Compared with normal weight women, maternal overweight and obesity were associated with higher hazards of offspring MS, with adjusted HRs of 1.20 (95% CI, 1.05 to 1.37) and 1.35 (95% CI, 1.11 to 1.64), respectively. Onset-specific analyses showed similar findings for adult-onset MS and less precise but directionally consistent estimates for paediatric-onset MS. Each 1-unit increase in maternal BMI was associated with a 3%, 4%, and 3% higher hazard of overall, paediatric-onset, and adult-onset offspring MS, respectively. Conclusions In this population-based cohort study, higher maternal BMI were associated with an increased rate of MS in offspring. The findings provide large-scale prospective evidence that maternal adiposity may be related to offspring MS risk and support further investigation of the prenatal metabolic environment in the early-life origins of MS.

Competing Interest Statement

Dr McKay receives research support from the Swedish Research Council, ALF Medicine, and Bjarne Ahlstroms Foundation. Dr Fink has received research support from the Swedish Research Council, CIMED, ALF Medicine, Merck, Amicus, Novartis and UCB. Dr Razaz is funded by the ALF Medicine, and Swedish Research Council. Jimin J Lee receives research support from Fonds de Recherche de Sante Quebec and MS Canada. Dr Xu receives research support from the Swedish Neurofonden Foundation. The other authors have no competing interests to state.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The study was approved by the Swedish Ethical Review Authority. The requirement for informed consent was waived as only anonymized registry data were used.

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Data Availability

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Funder Information Declared

Swedish Research Council, https://ror.org/03zttf063