Category Archives: Pregnancy and Breastfeeding

InfantRisk Center

Early Feeding and Risk of Celiac Disease in a Prospective Birth Cohort

**This is the first guest post on my page by Cristen Pantano, an incredibly talented scientist and mother of two children. Her youngest child was diagnosed with Celiac disease earlier this year. Many thanks to Cristen for tackling this challenging topic! 

Celiac is known to have a large genetic component and people with Celiac disease carry the HLA-DQ2 or HLA-DQ8 genes. However, only around 4% of people that carry these genes develop Celiac. The big question then is, what else is contributing to the development of Celiac?

Scientists are currently looking at other candidate genes, and so far, seven additional genes that make individuals more susceptible to developing Celiac have been identified. Genes are a great place to start, but as we all know, gluten is the big culprit in Celiac. It is the known environmental “trigger” for Celiac. Why is it that some people that carry the “Celiac genes” develop the disease after gluten exposure while others don’t?

Scientists and doctors are asking this question a lot these day. One area that is being investigated is infant feeding. Studies looking back on the Swedish Celiac epidemic of the 1980-1990s have shown that more than half of the epidemic could be explained by infant feeding practices (see link). During the time of the epidemic, Swedish infants were being introduced to gluten, on average, at around five months of age. Breastfeeding ended around this time and was replaced with formula thickened with wheat flour. When breastfeeding averages extended toward seven months and the popularity of wheat-laden formulas decreased, so did the rates of Celiac.

The Swedish epidemic got researchers thinking about infant feeding and many studies have since been published showing an effect of the age of gluten introduction, the amount of gluten introduced, and breast feeding on Celiac development.

A new study looking at the effect of these factors on the development of Celiac was recently published in the journal Pediatrics. This study, out of Norway, looked at the early feeding practices in 324 children that developed Celiac disease compared to a cohort with 81,843 children that did not develop the disease. The strength of the study is that it was prospective. Unlike most population studies where parents have to look back in time and remember details of early milestones, in a prospective study, parents fill out surveys to provide information in real time.

So what did this most recent study find? The authors found that 3.68/1000 children developed Celiac when introduced to gluten at six months compared to 4.24/1000 when introduced at four months and 4.15/1000 after six months. The increased risk for Celiac disease when gluten is introduced before four months, or after six, has been previously observed.

In this new study, the average length of breastfeeding in children that developed Celiac was 10.4 months compared to 9.9 months in the control population. The researchers found a positive association of prolonged (greater than 12 months) breastfeeding and  the development of Celiac disease. When all their breastfeeding data was adjusted for confounding factors such as maternal Celiac disease, this increased risk was borderline significant. That means that statistically speaking, the data set is on the weaker side and needs to be interpreted with caution. However, it does still demonstrate that in this data set, children that were nursed for twelve months or more had a greater risk for developing Celiac.

These findings have been met with frustration by many mothers of children with Celiac. Are women responsible for the development of their child’s Celiac disease because they chose to hold off solid foods and nurse up to, or past, one year? Of course they aren’t, and the authors of this study are not saying that they are. In their discussion, the authors caution that while their data on age of gluten introduction closely matches data from earlier studies, their data on breastfeeding does not.

Many, if not all, previous studies looking at breastfeeding and Celiac disease have found a protective effect from nursing. A 2006 review of the literature found that breastfeeding at the time of gluten introduction provided a 52% reduction in the development of Celiac disease. In 2005, two Swedish studies found a significant reduction in the onset of Celiac in babies that were nursed at the time of gluten introduction and continued to be nursed after that first introduction.

This latest study found that breastfeeding did not protect against Celiac and that nursing past twelve months increased the risk. Sounds strange right? In their discussion, the authors hypothesize that the greater risk in those breastfed past 12 months may have more to do with gluten than with breast milk. When a child is breastfed longer, the introduction of gluten may be later, after six months of age. Furthermore, since the child is older at gluten introduction, he may be exposed to larger amounts. The authors also mention that some mothers may have nursed longer due to perceived food sensitivities.

In the end, what is the take away from this study, and others, looking at infant feeding and the development of Celiac? It seems that there may be a window for gluten introduction between 5-6 months. Introduction before and after this time seem to increase the risk of Celiac. As far as breastfeeding, most studies point toward a large protective effect.

The development of Celiac Disease seems to be a perfect storm of genetic and environmental factors. Factors that may be out of any one person’s control. Studies should continue to look at early infant feeding and disease development, but all data should also be interpreted knowing that as hard as we try, some times, some things just can’t be prevented.

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Let’s Talk about Celiac Disease and Infertility

One of my favorite Celiac Disease-related pages on Facebook is that of the University of Chicago’s Celiac Disease Center. One of the first “tidbits” that I read on this page, after discovering it last fall, was the following statement: “Women who have experienced persistent miscarriages or infertility without a known medical cause should be tested for celiac disease.” I had no idea that there was such a strong association between Celiac Disease and infertility until I read this sentence.

I have encountered tons of women, both professionally and personally, who have struggled to get pregnant and/or carry a pregnancy to term. Recent estimates have shown that up to 10.9% of women of childbearing age (15-44) in the U.S. seek treatment for infertility in any given year. I wrote a post about the effects of Celiac Disease on pregnancy in January 2013, and since then have read quite a bit more about topic. Here are some things which I have learned about Celiac Disease and infertility:

-Studies published within the last two years have shown that between 6 and 10% of women with unexplained infertility have (undiagnosed) Celiac Disease. Previously, it was believed that the numbers were much lower, around 2-4%.

-Many women with Celiac-related infertility do have a prior history of irritable bowel syndrome or other GI complaints, but they do not necessarily have these symptoms while undergoing treatment for infertility.  It is well known that signs and symptoms of Celiac Disease can appear and then disappear for years (and even decades) before diagnosis.

-It is believed that Celiac impacts fertility due to a combination of malnutrition (nutrient deficiencies interfere with sex hormone function) and the formation of small placental blood clots (thromboses) due to Vitamin B12 deficiency. It has also been shown that anti-TTG antibodies do bind to placental tissues and can interfere with placental formation and function.

-If a woman has infertility due to Celiac Disease, fertility should resume between 3 to 9 months after going gluten free.

-Many researchers conclude that all women with unexplained infertility should be screened for Celiac Disease. Based on discussions with several people, this does not seem to be happening in all parts of the U.S.

The average cost for one cycle of IVF is $12,400. Many women go through multiple rounds of IVF before conceiving. Surrogacy can cost up to $100,000. If the research studies are correct, many women who are paying for these expensive treatments may actually have undiagnosed Celiac Disease. We need to continue to inform and discuss this with our families, friends, and neighbors as so many are potentially impacted.

General infertility statistics are found on the CDC site: http://www.cdc.gov/nchs/fastats/fertile.htm.

Other references which may be of interest:

1. Undiagnosed celiac disease in women with infertility. Machado AP, Silva LR, Zausner B, Oliveira Jde A, Diniz DR, de Oliveira J. J Reprod Med. 2013 Jan-Feb; 58(1-2):61-6

2. Increased prevalence of celiac disease in patients with unexplained infertility in the United States. Choi JM, Lebwohl B, Wang J, Lee SK, Murray JA, Sauer MV, Green PH. J Reprod Med. 2011 May-Jun; 56(5-6):199-203.

3. Immediate effect on fertility of a gluten-free diet in women with untreated coeliac disease. Raffaella Nenna, Maurizio Mennini, Laura Petrarca, Margherita Bonamico. Gut 2011;60:1023-1024.

4. Anti-tissue transglutaminase antibodies from celiac patients are responsible for trophoblast damage via apoptosis in vitro. Di Simone N, Silano M, Castellani R, Di Nicuolo F, D’Alessio MC, Franceschi F, Tritarelli A, Leone AM, Tersigni C, Gasbarrini G, Silveri NG, Caruso A, Gasbarrini A. Am J Gastroenterol. 2010 Oct; 105(10):2254-61.

5. Infertility Treatment in a Population-Based Sample: 2004–2005. Sara E. Simonsen, Laurie Baksh, Joseph B. Stanford. Maternal and Child Health Journal. May 2012, Volume 16, Issue 4, pp 877-886.

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The Prevent Celiac Disease Study

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I recently wrote about the best available recommendations for when to introduce gluten to babies who may be at risk of developing Celiac Disease. Although most babies are exposed to small amounts of gluten in breast milk, for my 4th baby (first born after my diagnosis), my breast milk was gluten free. Based on the best available evidence in the medical literature, small amounts of gluten should be given between 4 to 6 months of age, as it seems this is a critical window for the development of the immune system. If gluten is introduced later than this, the consensus is that it is important for breastfeeding to still be taking place during gluten introduction (see references in my previous post for more info).

I understand that this is a controversial area, as many parents feel that they should never introduce gluten to the at-risk child. I believe that, despite our best efforts to shield our children from gluten, they are eventually going to be exposed one way or another.

I did recently discover that the question of the timing of gluten introduction is being explored in Europe right now through the PreventCD study (www.preventCD.com).

This study has been sponsored by the European Union and involves 11 countries. More than 1000 infants were enrolled in the study from 2007 through 2011, and they are now being followed for the development of Celiac Disease from infancy until age 3. Based on the latest newsletter on the study website, the last participant will turn 3 in 2013, and the results will be “unblinded” at this point.

The 1000 infants in the study were all considered to be “at risk” for CD by having a first-degree relative (parent and/sibling) with Celiac Disease and being HLA-DQ2 and/or DQ8 positive. The study “intervention” started at 4 months of age and went for 8 weeks. Half of the babies were given a gluten-containing baby food on a daily basis and half were given a placebo. Breastfeeding was encouraged for both groups during the 8 week period.

The endpoint of the study is to see if there is any difference in frequency of Celiac Disease between the two groups at age 3. As a mom, Celiac, and pediatrician, I am eagerly awaiting these results. I am also intereseted to see if they will have the funding and resources to be able to follow the children into later childhood and adolescence. Either way, the results which they share will be valuable for all of us!

Although the study results will not be published for a while, the researchers have published an interesting review paper on infant feeding and Celiac Disease:

Systematic review: early infant feeding and the prevention of coeliac disease. Szajewska H, Chmielewska A, Pieścik-Lech M, Ivarsson A, Kolacek S, Koletzko S, Mearin ML, Shamir R, Auricchio R, Troncone R; PREVENTCD Study Group.Aliment Pharmacol Ther. 2012 Oct;36(7):607-18.

The full details of their study are described in this paper:

The PreventCD Study design: towards new strategies for the prevention of coeliac disease. Hogen Esch CE, Rosén A, Auricchio R, Romanos J, Chmielewska A, Putter H, Ivarsson A, Szajewska H, Koning F, Wijmenga C, Troncone R, Mearin ML; PreventCD Study Group.Eur J Gastroenterol Hepatol. 2010 Dec;22(12):1424-30.

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Celiac Disease and Pregnancy

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Although I am pretty sure that I had Celiac Disease for more than two decades before my diagnosis, I was not diagnosed until after my 3rd child was born. Looking back, my diet during my first 3 pregnancies was a gluten-filled nightmare. I am actually glad that I have no idea how sky-high my celiac antibodies probably were while I was pregnant with my oldest kids.

There has not been a ton of research on celiac disease and pregnancy, but based on the work that has been done, I have learned that celiac disease has effects on fertility, miscarriage rates, fetal growth, and the ability to carry a pregnancy to term.

Celiac disease is associated with early menopause, endometriosis, irregular menstrual cycles, and amenorrhea (missed periods), similar to what is seen in many other autoimmune diseases.

Between 4 to 8% of unexplained infertility is due to undiagnosed celiac disease. Many celiacs with infertility as their main problem do not have the “classic” digestive symptoms that would normally lead to diagnosis.

Once pregnant, women with undiagnosed celiac disease have between a 2-4x higher risk of miscarriage than women who do not.

During pregnancy, women with untreated celiac disease are at a higher risk of anemia, preterm labor, stillbirth, and having infants with low birth weights (growth restriction). These problems are related to a combination of maternal nutrient deficiencies during pregnancy, as well as effects from the attack of the placenta by maternal auto antibodies (TTG).

As a part of taking care of premature babies, it is important for me to review the medical and obstetric histories of my patients’ mothers. I have come across women more times than I can keep track of who, upon review of their medical records, may have celiac disease (some combination of irritable bowel syndrome, anemia, thyroid disease, depression, infertility, diabetes, and/or asthma). I have a friend who did a small research study during her fellowship in which she evaluated the mothers of low birth weight babies for celiac disease. Through her study, one mother was diagnosed with celiac disease. Similar research has recently been conducted in Italy, with results mirroring my friend’s.

Based on the information on the University of Chicago Celiac Disease Center website, once a woman is diagnosed with celiac disease and on a strict gluten free diet, fertility should return. Experts have recommended waiting between 6 months to 2 years once being gluten free before trying to conceive, in order to give the body time to heal. It is essential for celiacs to be on appropriate vitamin and mineral supplementation while pregnant.

It is assumed that pregnancy outcomes for women with treated celiac disease are similar to those of women without it. The only exception is that celiacs are still at a higher risk of miscarriage, even when we are gluten free during pregnancy. I have personally experienced this; back in 2011 I miscarried within days of bad “glutening” episode.

In summary, women with unexplained infertility should be screened for celiac disease. Once diagnosed, it is important to remain strictly gluten free and take a good gluten free prenatal vitamin while pregnant. One of the best resources to check the gluten status of a medication is at www.glutenfreedrugs.com. Last of all, try not to worry about the effects of celiac disease on your baby! Treated maternal celiac disease has no association with birth defects, heart problems, cerebral palsy, etc. However, if you are like me, you will worry about your baby throughout your entire pregnancy…this is a totally normal part of being a mom!

For additional reading on celiac disease and pregnancy, I recommend the following links:

1. The National Foundation for Celiac Awareness’ 2009 article “Pregnancy and Celiac Disease.”

2. “Celiac Disease: An underappreciated issue in women’s health” by Shah, S (2010).

Thank you for continuing to read and providing inspiration for posts!

Update September 2013: A group of Italian researchers has discovered that the type 2 tissue transglutaminase (TTG) antibodies seen in Celiac Disease interfere with the development of placental blood vessels. Reference is Simone, et al. Potential New Mechanisms of Placental Damage in Celiac Disease: Anti-Transglutaminase Antibodies Impair Human Endometrial Angiogenesis. Biol Reprod. Sept. 5, 2013. E-pub, ahead of print.

 

 

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Introducing Gluten to the Baby At-Risk for Celiac Disease

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This is Claire. She is my fourth baby, my “last” baby, and one of the greatest gifts of my life. She is the first baby I’ve had since being diagnosed with Celiac Disease and going gluten free. Because of this, I spent a lot of time during the postpartum period obsessing/fretting/freaking out about if/when I should expose my dear baby to gluten. I felt that I needed to do everything that I could to protect her from developing celiac disease. As usual, my husband was much more laid back and calm about the whole situation!

I researched my question and discovered the following:

1. Based on the best available information, gluten should be introduced to the “at risk” baby between 4 and 6 months of age. This runs counter to the current notion that infants should be exclusively breastfed for 6+ months and not have solids introduced until after 6 months.

2. Babies should be breastfed when gluten is first introduced and should continue to receive breast milk for at least 2-3 months after the first introduction to gluten.

Here is some of the science behind what I discovered:

-Anti-gliadin antibodies (antibodies against the major gluten protein) are present in breast milk of all women. The highest antibody titers are in colostrum, or early breastmilk, and levels decrease with time. It is hypothesized that these antibodies, which are passed from mother to baby, provide immunity to babies when gluten is introduced. Please refer to my post from November 2012 for additional information.

-Norris, et al. followed a large cohort of infants (>1500) in the U.S. who were at risk of developing celiac disease between the years 1994 and 2004. Feeding practices were analyzed and their research showed a much higher risk of celiac disease if gluten was introduced between 1 and 3 months of age or after 6 months of age.

- The rates of celiac disease skyrocketed in Sweden between 1984 and 1996; 3% of children born during this time developed celiac disease. This epidemic coincided with a nationwide change in feeding practice recommendations from starting solids between 4-6 months until after 6 months of age. This led to many infants having gluten introduced after being weaned from breastfeeding. See link for more information.

- The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) recommends avoiding both early (<4 months) and late (>7 months) introduction of gluten and to introduce gluten while the infant is still being breastfed. This mirrors the advice given by the University of Chicago Celiac Center (see website). The American Academy of Pediatrics emphasizes the importance of introducing gluten while breastfeeding in their 2012 “Breastfeeding and the Use of Human Milk” policy statement.

Overall, there seems to be a current consensus for an optimal “window” for introducing gluten to the “at-risk” baby between 4 and 7 months.

Back to sweet, little Claire. We started her on wheat-contaminated baby oatmeal at 4.5 months one time/day for about 4 weeks. She received exclusive breast milk for the next 2.5 months and is now a gluten-free baby. We’ll see what develops with time, but at if she develops Celiac Disease, at least I will know that I tried my best to prevent it!

Happy New Year and thank you for reading!

*Also, a quick reminder that this is a blog. I am summarizing medical literature, but also adding in my own thoughts and opinions on what I have read. I am not trying to tell anyone what they should do for their own health, nor am I giving medical advice through this page. Thank you!

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Breastfeeding and Celiac Disease

As a mother of four children ages 7 and under, I have spent a lot of time over the past few years breastfeeding and expressing breast milk. I did not get diagnosed with celiac disease until after my 3rd was born in 2009, so it was not until my last pregnancy that I was actually gluten free…although, looking back, my “craving” during my 3rd pregnancy was for Rice Chex with milk (my body must have been trying to tell me something!) If you are interested, my pregnancy cravings during my other pregnancies were as follows: fillet-o-fish sandwiches with cheese (1st), Golden Grahams cereal (2nd), sweet potatoes (4th). I admit the fillet-o-fish thing is disgusting.

Thus far, I have not noticed any differences between my three oldest children and Baby Claire, my gluten free baby, in terms of the pregnancies, labors, deliveries, birth weights, colic vs. no colic, breast milk production, or growth during infancy.  I have spent a lot of time thinking about this as I’ve had irrational fears that my undiagnosed celiac had somehow secretly “damaged” my three oldest kids. In researching information on breastfeeding and celiac disease I came across the following link on the www.infantrisk.com site. This website, part of the Texas Tech University Health Sciences Center,  is a great resource for information on the exposure of infants to medications, nutrients, herbs, etc. through breast milk. I have called their toll free number several times in my work with with newborn babies, and have always found them to be helpful in terms of giving advice about medications in mothers’ milk.

The crux of the article is that anti-gliadin antibodies (antibodies against the major protein in gluten) are present in the breast milk of all women, even those without celiac disease. The numbers of anti-gliadin antibodies are highest in the colostrum, or early breast milk, and decrease as the months go on. These antibodies seem to be important to babies because they provide early immunity against gluten, and thus, possibly decrease the risk of later developing gluten intolerance and/or celiac disease. This helps to explain the “protective” effect of breast milk which has been shown in study after study. So now, while I still feel terrible that I was not gluten free while pregnant and breastfeeding my oldest kids, I know that I probably gave them huge titers of anti-gliadin antibodies in my celiac-diseased breast milk!

I struggled to figure out when to introduce gluten to Claire’s diet (she was just born in early 2012) and went ahead and bit the bullet. I’ll discuss this more in upcoming weeks.

 

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