Offspring number, pregnancy, and risk of a first clinical demyelinating event

Ponsonby, Anne–Louise; Lucas, Robyn; Mei, Ingrid van der; Dear, Keith; Valery, Patricia C.; Pender, Michael P.; Taylor, BV; Kilpatrick, Trevor J.; Coulthard, Alan; Chapman, Caron; Williams, David B.; McMichael, Anthony J.; Dwyer, Terence

doi:10.1212/wnl.0b013e31824c4648

Cited by 126 publications

(117 citation statements)

References 33 publications

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“…It seems unlikely that other proposed hypotheses to explain the increased female-to-male ratio of MS in adults, like declining parity among women 23 or tobacco smoke among men, 24 can explain our findings. Parity in children is rare 25 (and pregnant girls were excluded from our study), as is cigarette smoking.…”

mentioning

confidence: 59%

Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome

et al. 2013

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Objective: To determine whether childhood obesity is a risk factor for developing pediatric multiple sclerosis (MS) or clinically isolated syndrome (CIS).Methods: Cases were identified through the Kaiser Permanente Southern California (KPSC) Pediatric Acquired Demyelinating Diseases Cohort between 2004 and 2010. For cases, body mass index (BMI) was obtained prior to symptom onset, for the underlying cohort BMI was obtained through the KPSC Children's health study (n 5 913,097). Weight classes of normal weight, overweight, moderate obesity, and extreme obesity were assigned based on BMI specific for age and sex.Results: We identified 75 newly diagnosed pediatric cases of MS or CIS, the majority of which were in girls (n 5 41, 55%), age 11-18 (n 5 54, 72%). Obesity was associated with a significantly increased risk of MS/CIS in girls (p 5 0.005 for trend) but not in boys (p 5 0.93). The adjusted odds ratio and 95% confidence intervals for CIS/MS among girls was 1.58 (0.71-3.50) for overweight compared to normal weight (reference category), 1.78 (0.70-4.49) for moderately obese, and 3.76 (1.54-9.16) for extremely obese. Moderately and extremely obese cases were more likely to present with transverse myelitis compared with normal/overweight children (p 5 0.003). Conclusion:Our findings suggest the childhood obesity epidemic is likely to lead to increased morbidity from MS/CIS, particularly in adolescent girls. Once thought to be rare in children, multiple sclerosis (MS) and its potential precursor, clinically isolated syndrome (CIS), which encompasses optic neuritis (ON) and transverse myelitis (TM), are increasingly recognized. Pediatric MS/CIS most often affects teenage girls. While once thought to be more common in whites, one study showed that the incidence is higher in blacks compared with whites and Hispanics.1 Whether this represents increased exposure to environmental triggers that increase with age, black race, or female sex during childhood is unclear.Over the last 30 years, the prevalence of pediatric obesity has tripled. It is well-known that obesity is characterized by a low-grade inflammatory state, 2 raising the possibility that the increasing reports of pediatric MS/CIS may be due at least in part to this alarming epidemic. Yet whether obesity is a risk factor for pediatric MS/CIS is unknown. Even in adults, the relationship between obesity and MS risk is not well understood. Only 2 studies have examined this question, both of which suggest that moderate obesity at age 20 but not at other times in life double the risk of adult-onset MS in women 3,4 and men. 4 However, the studies are limited by retrospective self-report of body size, 3,4 selection bias, 3 use of volunteer controls, 4 small number of obese subjects, 3,4 and inability to examine the risk among extremely obese individuals. 3,4 The purpose of this study was to estimate the magnitude of the association between overweight, moderate, and extreme childhood obesity and the risk of pediatric MS/CIS in our population-based,

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confidence: 59%

Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome

et al. 2013

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“…Clinical trials using sex steroids are currently underway [30,31]. Ponsonby et al [6] investigated subjects at their first demyelinating event, and found a reduced risk of developing definite MS as the number of pregnancies increased. Other studies have found a decreased risk of developing MS with having children, observed in both in females and males, arguing for a possible behavioral, social protective impact of parenting influence on the immune system and indirectly on the risk for developing MS [32][33][34].…”

Section: Discussionmentioning

confidence: 99%

“…A temporary increase in relapses is observed within the first months postpartum, after which the rate returns to pre-pregnancy baseline [3][4][5]. A recent case-control study found an association between both pregnancy and a higher number of offspring with a decreased risk of a first demyelinating event [6]. The protective effects of pregnancy on MS disease activity are thought in part to reflect the anti-inflammatory effects of sex hormones.…”

Section: Introductionmentioning

confidence: 99%

Parity Associated with Long-Term Disease Progression in Women with Multiple Sclerosis

Teter¹,

Kavak²,

Kolb³

2013

J Mult Scler

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“…46 Recently, our group showed that women with a higher number of offspring had a lower risk of a first clinical diagnosis of a demyelinating event. 47 Importantly, no association was observed in men, suggesting that the apparent protective effect of parity is more likely to relate to prenatal factors to do with the pregnancy, rather than postnatal factors pertaining to the offspring. If the association with parity is shown to be causal, it could partly explain the increase in incidence, particularly among women, as their number of offspring in western populations has decreased over the recent decades.…”

Section: Challenging Issues In Ms Epidemiological Researchmentioning

confidence: 98%

The role of epidemiology in MS research: Past successes, current challenges and future potential

2015

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Multiple sclerosis (MS) is a multifaceted condition, with a range of environmental, behavioural and genetic factors implicated in its aetiology and clinical course. Successes in advancing our appreciation of the roles of Epstein-Barr virus, vitamin D/UV and the HLA-DRB1 locus; and our greater understanding of these and related factors' modes of action in MS and other conditions, can be attributed in no small part to the work of generations of epidemiologists. Hardly content to rest on our laurels, however, there are yet a range of unsolved conundrums in MS, including some changes in epidemiological characteristics (e.g. increasing incidence and sex ratio), to say nothing of the unresolved parts regarding what underlies MS risk and its clinical course. There is evidence that epidemiology will continue to play a crucial role in unravelling the architecture of MS causation and clinical course. While classic epidemiological methods are ongoing, novel avenues for research include gene-environment interaction studies, the world of '-omic' research, and the utilisation of mobile and social media tools to both access and track study populations, which means that the epidemiological discoveries of the past century may be but a glimpse of our understanding in the next few decades.

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Offspring number, pregnancy, and risk of a first clinical demyelinating event

Abstract: These findings are consistent with a cumulative beneficial effect of pregnancy. Temporal changes toward an older maternal age of parturition and reduced offspring number may partly underlie the increasing female excess among MS cases over time.

Cited by 126 publications

References 33 publications

Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome

Childhood obesity and risk of pediatric multiple sclerosis and clinically isolated syndrome

Parity Associated with Long-Term Disease Progression in Women with Multiple Sclerosis

The role of epidemiology in MS research: Past successes, current challenges and future potential

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