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Can Mothers Alter Their Children's Risk for Developing Celiac Disease? :

October 11, 2016

The short answer to that question is a qualified "no," but this study raises some interesting questions about an increasingly commonly diagnosed disorder.

The short answer to that question is a qualified "no," but this study raises some interesting questions about an increasingly commonly diagnosed disorder.

Source: Namatovu F, Olsson C, Lindkvist M, et al. Maternal and perinatal conditions and the risk of developing celiac disease during childhood. BMC Pediatrics. 2016;16(1):77; doi:10.1186/s12887-016-0613-y. See AAP Grand Rounds commentary by Dr. Philip Rosenthal (subscription required).

This study's design, a retrospective cohort study, precludes making any conclusions about cause and effect, so one really shouldn't use the results to advise families on how to lessen the risk of their children developing celiac disease. However, the results do point the way forward to finding answers to this important question, and lends support to promoting physician behaviors already shown to be beneficial for other conditions.

This study, centered in Sweden and taking advantage of a well-oiled national health care system, had an enormous sample size: 1,912,204 births over a 19-year period and with 6596 children ultimately diagnosed with celiac disease. With the use of multivariate logistic regression analysis, a lower incidence of celiac disease was found in children born to mothers with advanced maternal age and high income, with a higher risk in being a second-born child. In post hoc analyses (more on this later), the authors found a statistically significant association of celiac disease with boys born by elective caesarean delivery and for girls born to mothers experiencing repeated urinary tract infections. Boys had lower rates associated with maternal overweight, premature membrane rupture, and low birth weight. Does any of this make sense with what we know about celiac disease?

The best biologically plausible answer lies in a possible relationship of intestinal microflora (the gut microbiome) and immune system development. (Some of you might be interested in another AAP Grand Rounds commentary from this month.) If some of these associated maternal factors led to differences in antibiotic use, it might explain how they could alter the risk of celiac disease development. Unfortunately, the authors didn't supply data on specific maternal or neonatal antibiotic exposure. Also, note that this study was carried out in Sweden, a relatively homogenous ethnic population that is an important consideration when discussing a disease that likely involves genetic factors as significant determinants of developing illness. The authors don't even mention an ethnic breakdown of their study population.

A word about post hoc analysis. As I've mentioned before, this term refers to performing statistical tests not initially planned for a study, based on results of standard analyses after the data are collected and analyzed. In this particular study, a possible gender difference in risk was explored with further statistical testing. Performing post hoc testing should direct the researchers to use a modified statistical approach, which it appears these authors did not perform.

Clearly this study sheds more light on this complex condition, even with the caveats mentioned above. What should clinicians do with this information?

Putting this into the context of primary care practice as a whole, the study points to yet another reason to avoid inappropriate antibiotic use. Let's all try to limit antibiotic use to situations where a child (and mother) truly benefit from treatment, in particular trying to avoid antibiotic use in illnesses of likely viral etiology and others that tend to resolve spontaneously. Also, no one would condone unnecessary caesarean delivery, and perhaps if mothers and fathers ask more questions about risks and benefits of their child's delivery options the rates of this surgical procedure will fall somewhat.

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