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Gluten, Pregnancy Problems, Birth Defects, and Reproductive Health

I had a conversation with a woman who is something of a knowledgeable cook. We were discussing how to cook without wheat. In the course, she commented, “Thankfully, I’ve never had a problem with wheat.” My heart sunk – I’ve known that she has had multiple miscarriages and was never able to have a child. I’m not entirely sure at this point how to bring the subject up to her.

Even beyond the emotional weight of this subject, this is a tough subject to tackle. There have been several studies (and certainly, further larger studies are needed), but the studies cover many different aspects of Reproductive Health and Coeliac Disease and Pregnancy Outcomes. To give you some idea, these are some of the reproductive effects of gluten sensitivity reported in the studies:

Miscarriage	Delayed Puberty	Early Menopause
Infertility In Women	Infertility in Men	Small Babies
Birth Defects	Stillbirth	Infant Death

Severity of the CD does not seem to matter; many cases had no symptoms. Only the lack of treatment for CD seems to cause the poor outcomes in the cases studied. [Ferguson], [Martinelli]

		No. of Celiacs in Study	High infertility	Low birth weight	High Miscar-riage	Short terms or pre-eclampsia	Short breast feeding	Anemia	Still birth Infant Death	Clear Improvement on GFD
Martinelli	1999	12	*	X	X	X		X	X	Yes
Ferguson	1982	74	X	X	X	X				Yes
Ciacci	1996	31		X	X		X			Yes

* Subjects were screened from a group of pregnant women.

Collection of Abstracts

Reproduction Abstracts from Celiac Disease Resources for Medical Professionals (University of Arkansas for Medical Sciences)

Infertility and Pregnancy 15 links from BrainTalk Communities

Literature Reviews

“Celiac disease during pregnancy.” Rebecca Hancock, 2005.

“Celiac disease appears to be a relatively common yet a neglected disorder during pregnancy. Undiagnosed and untreated celiac disease can pose health risks to both mother and fetus. Unfavourable pregnancy outcomes associated with celiac disease could be prevented with a gluten-free diet. Managing a gluten-free diet is difficult; proper supplementation must be achieved in women of reproductive age, especially of folic acid because the main dietary source (flour) is eliminated.” [Note: usually, the synthetic folic acid in enriched flour is malabsorbed anyway with Celiac Disease - HGK]

Miscarriage

As concluded in these studies, untreated gluten sensitivity increases the risk of miscarriage and treatment by gluten free diet reduces risk of miscarriage to normal levels:

(studies to be listed here)

Martinelli, et al, “Coeliac Disease And Unfavourable Outcome Of Pregnancy”

Ferguson, et al, “Coeliac disease, fertility, and pregnancy.”

Small, underweight, or underdeveloped Babies

As concluded in these studies, untreated gluten sensitivity reduces birth weight and treatment by gluten free diet results in more normal birth weight:

(studies to be listed here)

P Martinellib, et al, “Coeliac Disease And Unfavourable Outcome Of Pregnancy”

Ferguson, et al, “Coeliac disease, fertility, and pregnancy.”

Delayed Puberty

“Age at menarche in girls with celiac disease.” [Article in Polish], Rujner J. Kliniki Gastroenterologii i Zywienia, Instytut Pomnik-Centrum Zdrowia Dziecka. Ginekologiczne Polskie. 1999 May;70(5):359-6

This is a study in Poland of 59 mother/daughter pairs with the daughter but not the mother diagnosed with the celiac disease (classic celiac disease no doubt). The age of onset of the first menstrual period (menarche) was compared between mothers and daughters in two groups, one group with the daughters treated by gluten free diet before menarche and the other group not treated before menarche. The findings summarized in the table below suggest that untreated celiac disease delays menarche by roughly 2 years, on average!

Delay of Daughter’s Puberty by Untreated Celiac Disease.
	Daughter’s Age	Mother’s Age	Locale	Sample
Celiac Daughters Eating Gluten	16.16	15.49		10 pairs
Celiac Daughters On GFD	12.33	13.82	country	11 pairs
Celiac Daughters On GFD	13.08	13.49	little town	19 pairs
Celiac Daughters On GFD	12.90	13.33	town	19 pairs
Non-Celiacs Eating Gluten	13.06*

*Laska-Mierzejewska et al. (1982) in “International Variability of Ages at Menarche and Menopause”

For reference:

Average age at menarche in various cultures

International Variability of Ages at Menarche and Menopause

Infertility In Women

Morehead Memorial Hospital has a web document on “Infertility In Women”, The chapter on chapter on causes ends with a listing of “Other Causes”. What is interesting is how many of these “Other Causes” are also associated with or caused by untreated gluten intolerance: chronic disorders, depression, pain, and psychotic problems that are treated with medication, inflammatory bowel disease (particularly Crohn's disease or surgery for ulcerative colitis), Celiac Sprue, epilepsy, thyroid problems, abdominal obesity, low HDL (good) cholesterol levels, high triglyceride levels, high blood pressure, insulin resistance, and other medical conditions, including delayed puberty, amenorrhea, HIV, and diabetes.

Folate/Folic Acid

Two things related to gluten and birth defects are now unquestionable: First, malabsorption can definitely cause a deficiency in folate. Second, a deficiency in folate is the cause of neural tube defects of. Neural tube defects result in such problems as spinal bifida, anencephaly, meningomyelocele, and miscarriage. So, it is no surprise to be able to find reports of women who are diagnosed with Celiac Disease only after having a pregnancy that resulted in spina bifida or meningomyelocele.

Folic acid is the synthetic form of naturally occurring nutrient folate. The folate is critical in preventing miscarriages and birth defects, particularly those related to neural tube development.

“Well meaning but uninformed” doctors may warn women against the gluten free diet because enriched bread is an important source of folate. What such doctors do not realize is that untreated Celiacs have trouble absorbing folate if they eat bread! Furthermore, folate is naturally available in orange juice, grapefruit and several nutritious vegetables, beans, peas, beef, pork, chicken, and fish. A Celiac should consider supplements anyway, but eating enriched white bread is no different than taking a multi-vitamin pill along with a lot of starch.

Clippings

Coeliac Disease And Unfavourable Outcome Of Pregnancy [1]

“Coeliac disease is considerably more commonthan most of the diseases for which pregnant women are routinelyscreened.”

….

“Up to 50% of women with untreated coeliac disease experience miscarriage or an unfavourable outcome of pregnancy. In most cases, after 6-12 months of a gluten free diet, no excess of unfavourable outcome of pregnancy is observed.”

….

“Of 845 pregnant women [attending the obstetrics-gynaecology department of a large city hospital over a 90 day period], 12 were identified as having coeliac disease [by serum endomysial antibody screening]. Three had previously been diagnosed but were not following a gluten free diet. The remaining nine underwent a small intestinal biopsy, which confirmed the diagnosis. The outcome of pregnancy was unfavourable in seven of these 12 women. Six healthy babies were born with no problems after the women had been on a gluten free diet for one year.”

.…

“Overall, 1 in 70 women was affected by coeliac disease, either not diagnosed (nine cases) or not treated (three cases). Their history of miscarriages, anaemia, low birth weight babies, and unfavourable outcome of pregnancy suggests that testing for coeliac disease should be included in the battery of tests prescribed for pregnant women. Coeliac disease is considerably more common than most of the diseases for which pregnant women are routinely screened. Unfavourable events associated with coeliac disease may be prevented by a gluten free diet.”

….

None of the 12 cases observed here had overt signs of malnutrition, apart from low haemoglobin in four; there was no stunting and no patients were underweight. Therefore nutritional factors were probably not of major importance in the unfavourable outcomes. Malabsorption or malnutrition was not a consistent feature in women affected by coeliac disease who had an adverse outcome of pregnancy.”

….

“During the period over which this paper was being revised, we followed up the 12 women identified during the study. One was lost to follow up. Three had no further pregnancies; these were on a gluten free diet and healthy. Eight had a further pregnancy: one is still in progress, and seven reached term. Of these seven, six, five of whom were on a strict gluten free diet, gave birth to healthy babies, above 2500 g in weight, with no problems. The seventh had a baby with a major cardiac malformation; she was the only one on a gluten-containing diet.”

[Correspondence to: Dr L Greco, Department of Pediatrics, University of Naples Federico II, Via Pansini 5, 80131 Naples, Italy]

COMPARISON BETWEEN PATIENTS WITH PREGNANT COELIAC DISEASE AND PREGNANT CONTROLS

	Celiacs	Controls
Number in study	12	206
Average Age in Study	28 years	29 years
Average Age at Puberty	13.03 years	12.0 years
Menopause	-na-	-na-
Children born to patients
Born before diagnosis
Born after diagnosis
History of Miscarriage	33%	22%
History of 1 Miscarriage	17%	19%
History of 2 or more Miscarriages	17%	3%
Stillbirth or Infant Death	25%	1%
Infant Death or Perinatal Disease	25%	1%
Apgar score below 7 at 1 minute	21%	5.8%
Apgar score below 5 at 1 minute	17%	0.5%
Delivery before the 37th week *	33%	11.6%
Average gestation at delivery	36.7 weeks	36.7 weeks
Breech presentation	25%	1.4%
Mean birth weight	2601 g	3164 g

*Pre-term

Fatherhood

Coeliac Disease In The Father Affects The Newborn

Gut 2001;49:169-175 ( August )

In this study, infants whose father suffered from celiac disease

· averaged about half a pound lighter (226g),

· were 5 times more likely to be in the low birth weight category (LBW),

· were 3 times more likely to be pre-term, and

· were born an average of 5-6 days earlier than non-celiac controls.

They also weighed less than infants whose father suffered from other autoimmune diseases.

There were fewer Caesarean section deliveries of infants of celiac fathers, perhaps due to the smaller infants.

Infants whose mother suffered from celiac disease averaged about half a pound lighter (226g) and were over 6 times more likely to be in the LBW category than non-celiac controls. These infants were more often in the LBW category than infants whose mother suffered from non-diabetic autoimmune diseases. Coeliac disease in other relatives was not associated with any adverse effect on neonatal outcome. ...more...”

Further Commentary on the above paper:

The Father Figure In Coeliac Disease

Gut 2001;49:163-164 ( August )

“It is surprising that although clear reports were given ... about 20 years ago, coeliac disease (CD) has not yetgained popularity among obstetricians. In the subsequent two decades,many epidemiological studies clearly showed that it is a verycommon disease, that it affects women more than men, and thatit has to be considered in relation to reproductivefunction.

“In the past few years several groups have shown that untreated CD is an important cause of abortion, poor outcome of pregnancy, and intrauterine growth retardation.3 4 ...more...”

“Coeliac disease, fertility, and pregnancy.”, Ferguson R, Holmes GK, Cooke WT. Scandinavina Journal of Gastroenteroogy, 1982 Jan;17(1):65-8

The effect of coeliac disease and its treatment on fertility and pregnancy in 74 patients is reported. Those on a normal diet had a shorter reproductive period, were relatively infertile, and had a higher incidence of spontaneous abortions than those on a gluten-free diet. Although maternal health did not appear to be seriously impaired by pregnancy in undiagnosed coeliacs, those on a gluten-free diet had significantly fewer symptoms and had heavier babies.

“Celiac disease and pregnancy outcome.”, Ciacci C, Cirillo M, Auriemma G, Di Dato G, Sabbatini F, Mazzacca G., Gastroenterology, Medical School, Naples University "Federico II," Italy, American Journal Gastroenterology. 1996 Apr;91(4):718-22.

In the case-control study, comparison of 94 untreated with 31 treated celiac women indicated that the relative risk of abortion was 8.90 times higher (95% confidence limits: 1.19/66.3), the relative risk of low birth weight baby was 5.84 times higher (90% confidence limits: 1.07/31.9), and duration of breast feeding was 2.54 times shorter (p < 0.001) in untreated mothers. Abortion, low birth weight of baby, and duration of breast feeding did not significantly relate to the severity of celiac disease among untreated women. In the before-after study, 12 pregnant celiac women in either treated or untreated condition were compared. Results indicated that the gluten-free diet reduced the relative risk of abortion by 9.18 times (95% confidence limits: 1.05/79.9), reduced the number of low birth weight babies from 29.4% down to zero (p < 0.05), and increased duration of breast feeding 2.38 times (p < 0.10).

comparison of 94 untreated with 31 treated celiac women

abortion was 8.90 times higher

low birth weight 5.84 times higher

duration of breast feeding 2.54 times shorter.

12 Results indicated that the gluten-free diet

reduced abortion by 9.18 times

reduced the number of low birth weight babies from 29.4% down to zero

increased duration of breast feeding 2.38 times.

“Recurrent spontaneous abortion and intrauterine fetal growth retardation as symptoms of coeliac disease.”, Antonio Gasbarrini, et al, Lancet, Volume 356, Issue 9227, 29 July 2000, Pages 399-400.

Abstract: “Women having recurrent miscarriages or intrauterine growth retardation [small babies] could have subclinical coeliac disease, which can be detected by serological screening tests.”

Correspondence to: Dr Antonio Gasbarrini; email: angiologia@rm.unicatt.it

Wheat Sensitivity (Subclinical Gluten Intolerance) Linked To Repeated Miscarriages (A review of Gasbarrini)

“Women who experience repeat miscarriages, also known as recurrent spontaneous abortions (RSA) or intrauterine growth retardation (IUGR) -- a condition in which a baby is born significantly smaller than normal -- may have celiac disease that has gone undetected.

Researchers, led by Dr. Antonio Gasbarrini, explain that they decided to look at celiac disease since it is a common cause of malabsorption of food in western countries. And for some time, miscarriages have been correlated with celiac disease.

Gasbarrini and colleagues conducted blood tests for the condition in 44 patients with RSA, 39 with IUGR, and 50 healthy women. None of the healthy women were found to have celiac disease, but the condition was detected in 8% of the women with RSA and 15% of those with IUGR.”

Bell’s Palsy

The following conditions are associated with Bell’s Palsy, notice that these conditions are all strongly linked to gluten intolerance.

“Diabetes and thyroid conditions are also associated with facial palsy. Lupus, Sjogrens syndrome and congenital defects can, infrequently, cause facial paralysis.” (http://www.bellspalsy.ws/cause.htm)

Look up Celiac.com

http://www.celiac.com/st_prod.html?p_prodid=785&sid=91hH9H1ETH830rl-03105494430.0d

THE SPRUE-NIK PRESS

Published by the Tri-County Celiac Sprue Support Group,

a chapter of CSA/USA, Inc. serving southeastern Michigan

Twenty-Fourth Edition October 1995

http://www.enabling.org/ia/celiac/sn/spnk9510.html#Celiac%20Disease%20and%20Birth%20Defects

From: Markku Maki, MD

Date: September 15, 1995 5:25 am

Jim Lyles wrote:

>The question raised in the post is: Could the spina bifida in the

>daughter have been caused by malabsorption?....I'd welcome any

>comments you may have on this topic.

At the Celiac Disease Study Group in Tampere, we want to respond. We

have discussed this lately and we are going to do an inquiry to the

Finnish Coeliac Disease Society members about this. Dr. Kati Holm has

a case you might be interested in:

The first child of the mother suffered from spina bifida and

meningomyelocele (boy). Two pregnancies that followed resulted in

abortion because of intrauterine diagnosis (confirmed meningomyelocele

at autopsy). During the fourth pregnancy anemia and folic acid

deficiency were noticed. The mother was treated with vitamins, folic

acid and iron. The pregnancy resulted in a healthy girl. After this

there were again several abortions because of detected menigmyelocele.

The mother contacted Dr. Kati Holm (PhD on celiac disease) because of

diarrhea and anemia and subsequently celiac disease screening tests

were performed among other studies. IgA class reticulin autoantibody

tests were positive and a jejunal biopsy revealed the typical lesion

for celiac disease. She was prescribed a gluten-free diet, after

which symptoms disappeared. The iron and folic acid deficiencies

disappeared at the same time as the mucosa recovered. One pregnancy

resulted, without any other therapy, in a healthy child.

All this by chance alone??

Prof. Markku Maki

Institute of Medical Technology

University of Tampere

P.O. Box 607

FIN-33101 Tampere, Finland

* * * * *

The other response came from Dr. Karoly Horvath, Associate Professor

of Pediatrics and director of the Pediatric Gastrointestinal &

Nutrition Laboratory at University of Maryland:

* * * * *

From: Karoly Horvath, MD, PhD

Date: September 17, 1995 5:47 pm

The relation between folate deficiency and neural tube defects is well

documented. Several studies have demonstrated a significant reduction

of neural tube defects in the newborns of folate supplemented

pregnant woman. The risk reduction varies between 58-91%. The

different studies used different supplementation and doses. A recent

review article summarizes the up-to-date information in this subject

(Czeizel AE, "Folic acid in the prevention of neural tube defects",

Journal of Pediatric Gastroenterology and Nutrition 20: 4-16, 1995).

The other association between folate deficiency and absorptive problem

is not questionable, and does not need to be proven.

I do not have any doubt that that the babies of women with

non-diagnosed CD have an increased risk for neural tube defects. We

can collect information retrospectively, however, it will not be easy

and convincing. A prospective study is easier if we found a center

treating mostly children with neural tube defects and we can get blood

samples from the mother shortly after giving birth for folate level

determination and celiac serologic tests.

Karoly Horvath

University of Maryland