Monday, 27 August 2012

Grand Challenges in MS (4): month of birth effect

Why does the month you are born in affect your risk of MS?

I assume you are aware that month of birth is a risk factor for MS. In the Northern hemisphere, if you are born in May you have a higher chance of developing MS compared to people born in November. This month of birth effect is now being attributed to the effect of low vitamin D levels in the womb. The low vitamin D affects how the immature immune system develops. In other words if your mother was pregnant during winter, a time when she was more likely to be vitamin D deficient, your immune system was unable to develop properly and resulted in you being more susceptible to developing an autoimmune disease in later life. In support of the vitamin D hypothesis is the observation that the month of birth effect gets larger the further you are away from the equator, i .e. it is greater in Scotland than it is in England. 

The month of birth effect is not unique to MS and has been observed in type 1 diabetes mellitus, rheumatoid arthritis, ulcerative colitis and systemic lupus erythematosus and schizophrenia. Is schizophrenia an autoimmune disease? This is an interesting question and beyond the scope if this blog, but worthy of some serious thought. The fact that the month of birth effect is found with other diseases implies that it is an important biological phenomenon and worthy of looking into in more detail. 

Therefore the grand challenge is to pin down the molecular and immunological mechanisms of the month of birth effect. This is very important as it will underpin strategies for prevention, for example, vD supplementation in pregnancy, and it will provide potential markers to assess the impact of MS preventative strategies in the future. In other words a successful MS preventative strategy should correct the defect that is associated with the month of birth effect. 

FromWiller et al. Timing of birth and risk of multiple sclerosis: population based study. BMJ. 2005 Jan 15;330(7483):120.

Disanto et al. Month of birth, vitamin D and risk of immune mediated disease: a case control study. BMC Med. 2012 Jul 6;10(1):69. 

BACKGROUND: A season of birth effect in immune-mediated diseases (ID) such as multiple sclerosis and type 1 diabetes has been consistently reported. We aimed to investigate whether season of birth influences the risk of rheumatoid arthritis, Crohn's disease, ulcerative colitis and systemic lupus erythematosus in addition to multiple sclerosis, and to explore the correlation between the risk of ID and predicted ultraviolet B (UVB) light exposure and vitamin D status during gestation.

METHODS: The monthly distribution of births of patients with ID from the UK (n = 115,172) was compared to that of the general population using the Cosinor test. Predicted UVB radiation and vitamin D status in different time windows during pregnancy were calculated for each month of birth and correlated with risk of ID using the Spearman's correlation coefficient.

RESULTS: The distributions of ID births significantly differed from that of the general population (P = 5e-12) with a peak in April (odds ratio = 1.045, 95% confidence interval = 1.024, 1.067, P <0.0001) and a trough in October (odds ratio = 0.945, 95% confidence interval = 0.925, 0.966, P <0.0001). Stratification by disease subtype showed seasonality in all ID but Crohn's disease. The risk of ID was inversely correlated with predicted second trimester UVB exposure (Spearman's rho = -0.49, P = 0.00005) and third trimester vitamin D status (Spearman's rho = -0.44, P = 0.0003).

CONCLUSIONS: The risk of different ID in the UK is significantly influenced by the season of birth, suggesting the presence of a shared seasonal risk factor or factors predisposing to ID. Gestational UVB and vitamin D exposure may be implicated in the aetiology of ID.

Other posts of interest

08 Jun 2012
The place of birth effect (preponderance for more Msers from the North verses the South USA) and month of birth effect (higher in May than November) was not evident. The place of Birth effect had been noticed previously in ...
09 Jul 2012
Month of birth, vitamin D and risk of immune mediated disease: a case control study. BMC Med. 2012;10(1):69. BACKGROUND: A season of birth effect in immune-mediated diseases (ID) such as MS and type 1 diabetes has ...
29 Apr 2011
There is now convincing evidence for an epigenetic component to MS, with maternal parent-of-origin, transgenerational (grandparental) and early life (month of birth) effects, as well as the increasing sex ratio of the disease.
19 Jan 2012
If part of the vitamin D effect is in utero (in the womb), as could be suggested by the month of birth effect. Then the issue of vitamin D levels in MSers at onset etc may be irrelevant. This adds an extra level of complexity. Sunday ...

12 Oct 2011
Vitamin D deficiency in pregnancy is very likely to be an important risk factor and may explain the month of birth effect; i.e. if you mother was pregnant during winter (last 6 months) and you were born in April you are at ...
02 Oct 2011
I suppose Dr Beggs can explain the genetics, latitudinal effect, OCBs, month-of-birth, sex ratio, migration effect, ectopic B cells follicles, gray matter pathology and the EBV-smoking-vD association by CCSVI.
14 Jun 2011
The month of birth and risk of MS are associated, more so in familial cases, implying that there is some interactions between genes and environment that may be related to climate. Such interactions may act during gestation or shortly after birth in individuals born in the countries studied. "The finding ... Vitamin D: effects on immune cell function in MS'e... Vascular aspects of multiple sclerosis: a review · Potential health care cost savings associated with... Research focus...
13 Jul 2011
It appears that the month of birth effect relates to vitamin D's effect on the developing foetus. ReplyDelete. Anonymous Wednesday, July 13, 2011 4:10:00 PM. Re: “What about hope? I still believe that some of the emerging, ...

16 May 2012
... for this effect. The negative associations observed with greater maternal parity and number of siblings are consistent with some other studies. Reasons for these associations may involve various pathways. Month of birth has ...
14 Jun 2012
They tested whether variation in UVR as determined by seasons (short term variation) and solar cycles (long term variation) is related to MS birth month and to survival as measured by lifespan. Methods: Cases were selected ...
28 Jun 2011
Results: At 12 months, the average serum vitamin D concentrations were 83 nmol/liter and 179 nmol/liter in control and treated participants, respectively (P < 0.001). In treated MS'ers, the abnormal immunological responses of ... But what other, less obvious, effects could there be? (Rhetorical question). Tuesday, June 28, 2011 12:15:00 PM. Anonymous said. .... Article of interest (3): month of birth and risk o... Symptomatic liver injury associated with complemen.

10 comments:

  1. I was born in May and have MS, but the Vitamin D explanation is not likely to hold since I was born in the tropics. My mother had lived in the tropics all her life. I find the graph curious since, if exposure to sunlight is the trigger, there should be a gentler slope up to and away from May. May is not suddenly more or less sunny than the adjacent months.

    ReplyDelete
    Replies
    1. I don't think being born in May is the problem- it's your mother being pregnant for most of your gestation through the darker months of the year- Autumn, Winter and early Spring.

      Delete
    2. There are no dark months in the tropics, where my mother lived.

      Delete
  2. I was born in November and have MS, but the Vitamin D explanation kind of does hold in my case. Although I was born and raised in one of the sunnier parts of the US, my mother never went outdoors. She had great skin.

    ReplyDelete
  3. The question as to whether schizophrenia is an auto-immine disease might upset as many psychologists as suggesting MS is a vascular disease!

    But you might have a point Prof G...

    Have you considered the impact of lithium on MS?

    http://www.jimmunol.org/content/181/1/338.short

    I think there is a trial underway for lithium and PPMS too...



    ReplyDelete
  4. I'd like to know about the impact of lithium too - there has been a paper from France this year with some good results (in mice though). Maybe Team G can update us on it?

    ReplyDelete
  5. That is correct; there is evidence that Lithium may be neuroprotective. It modifies sodium and other ion channels. There have been some positive EAE studies and it has been into ALS or motor neurone disease (unfortunately unsuccessfully). There is a small clinical trial recruiting at present for progressive MS to look at the effect of lithium on brain atrophy.

    http://clinicaltrials.gov/ct2/show/NCT01259388?term=lithium+and+multiple+sclerosis&rank=1

    Unfortunately, lithium has a very narrow therapeutic window and as a result is often associated with toxicity. Let's wait and see how the trial pans out. Results are due in 2015 or 2016.

    ReplyDelete
  6. I am surprised that the risk drops so sharply in June - could that be because of increased exposure to the sun by the pregnant mum during May/June, indicating that sun exposure in late pregnancy reduces risk to MS in the baby? I hope you understand what I mean!

    ReplyDelete
  7. This study fails to address an interesting issue: that of cultural influence on sun exposure. This is something that I am concerned is not addressed enough in the Vitamin D debate. Why is MS incidence low in Afghanistan for instance (or is it just not diagnosed)? Mothers and young daughters are routinely covered up - even in their own compounds.

    On the one hand this goes against a pure Vitamin D arguement.

    On the other, there has been seen to be a rise in auto immune disorders in places with an increasingly conservative Islamic dress code.

    And it is not just Islam. Orthodox Jewish communities also display low Vitamin D levels.

    I think it comes back to a viral thesis. Vitamin D exposure is not the only thing at play. You need a virus (saliva spread??) as well. And so in communities that have conservative dress codes but conservative sexual mores too you don't get sunlight exposure but you possibly also get limited viral exposure.

    Prof G - can you get MS if you have never kissed someone on the lips?

    ReplyDelete
    Replies
    1. "Can you get MS if you have never kissed someone on the lips?"
      Yes, you can. There are enough paediatric MS cases.

      Delete

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