Wagner BA; Columbia University Vagelos College of Physicians and Surgeons, New

York, USA.
Zork N; Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology,
Columbia University Vagelos College of Physicians and Surgeons, New York, USA.
Blackett JW; Division of Digestive and Liver Diseases, Department of Medicine, Celiac
Disease Center, Columbia University Vagelos College of Physicians and Surgeons,
New York, USA.
Green PHR; Division of Digestive and Liver Diseases, Department of Medicine, Celiac
Disease Center, Columbia University Vagelos College of Physicians and Surgeons,
New York, USA.
Lebwohl B; Division of Digestive and Liver Diseases, Department of Medicine, Celiac
Disease Center, Columbia University Vagelos College of Physicians and Surgeons,
New York, USA. bl114@cumc.columbia.edu.; Department of Epidemiology, Mailman
School of Public Health, Columbia University, New York, USA.
bl114@cumc.columbia.edu.
Fonte:
Digestive diseases and sciences [Dig Dis Sci] 2020 Oct; Vol. 65 (10), pp. 2970-
2978. Date of Electronic Publication:  2020 Apr 01.
Tipo de publicação:
Journal Article; Observational Study; Research Support, Non-U.S. Gov't
Idioma:
English
Inform
ações
de
revista
científi
ca:
Publisher:  Springer Science + Business Media Country of Publication: United
States NLM ID: 7902782 Publication Model:  Print-Electronic Cited
Medium:  Internet ISSN: 1573-2568 (Electronic) Linking ISSN:  01632116 NLM ISO
Abbreviation:  Dig Dis Sci Subsets: Core Clinical (AIM); MEDLINE
Nome(s)
impresso(s):
Publication: 2005- : New York, NY : Springer Science + Business Media
Original Publication: New York, Plenum Pub. Corp.
Termos de MeSH:
Diet, Gluten-Free*
Feeding Behavior*
Maternal Nutritional Physiological Phenomena*
Nutritional Status*
Nutritive Value*
Adult ; Female ; Humans ; Hypothyroidism/epidemiology ; Irritable Bowel
Syndrome/epidemiology ; Parity ; Pregnancy ; Pregnancy Outcome ; Retrospective
Studies
Resumo:
Background: Gluten avoidance among patients without celiac disease has become
increasingly popular, especially among young and female demographics; however, no
research has explored gluten avoidance during pregnancy, when nutrition is particularly
important.
Aims: To determine whether avoiding gluten in pregnancy is associated with any
medical, obstetric, or neonatal characteristics.
Methods: In this single-center retrospective cohort study, we identified women with
singleton pregnancies who avoid gluten based on antenatal intake questionnaire
responses and inpatient dietary orders, excluding those with celiac disease. Certain
demographic, medical, obstetric, and neonatal characteristics were compared to
matched controls who do not avoid gluten.
Results: From July 1, 2011 to July 1, 2019, 138 pregnant women who
avoid gluten were admitted for delivery of singleton gestations. Compared to
controls, gluten-avoidant women had fewer prior pregnancies (p = 0.005), deliveries (p 
 < 0.0005), and living children (p < 0.0005), higher rates of hypothyroidism (OR = 3.22; p 
= 0.001) and irritable bowel syndrome (OR = 6.00; p = 0.019), higher second trimester
hemoglobin (p = 0.018), and lower body mass index at delivery (p = 0.045). Groups did
not differ in any obstetric or fetal characteristics.
Conclusions: Gluten avoidance in pregnancy is common and, in women without celiac
disease, is associated with higher rates of hypothyroidism and irritable bowel syndrome,
fewer pregnancies, term births, and living children, and lower peripartum BMI, but is not
associated with any obstetric or neonatal comorbidities. Avoiding gluten does not
appear to adversely affect maternal or fetal health, but reasons for gluten avoidance,
as well as long-term maternal and pediatric outcomes after gluten avoidance in
pregnancy, warrant further study.
ios:
Comment in: Dig Dis Sci. 2020 Oct;65(10):2751-2753. (PMID: 32651744)
Abstract Background: Gluten‐free (GF) diet during pregnancy ameliorates autoimmune
diabetes in nonobese diabetic (NOD) mouse offspring. Due to comorbidity of celiac
disease in type 1 diabetes, we hypothesized that GF diet in utero alleviates the
humoral and histopathological signs of celiac disease in NOD mice. We aimed to
establish the mechanisms behind the diabetes‐protective effect of GF diet in utero.
Methods: Breeding pairs of NOD mice were fed a GF or gluten‐containing standard
(STD) diet until parturition. The offspring were nursed by mothers on STD diet and
continued on this diet until ages 4 and 13 weeks. Analyses of serum antitissue
transglutaminase (anti‐tTG) intestine and islet histology, islet transglutaminase (TG)
activity, and cytokine expression in T cells from lymphoid organs were performed.
Results: GF versus STD diet in utero led to reduced serum anti‐tTG titre and increased
villus‐ to‐crypt ratio at both ages. Insulitis along with systemic and local inflammation
were decreased, but islet TG activity was unchanged in 13‐week‐old GF mice. These
mice had unchanged beta‐cell volumes, but increased islet numbers throughout the
prediabetic period. Conclusions: Collectively, GF diet administered during pregnancy
improves signs of celiac disease and autoimmune diabetes in the offspring. The
diabetes‐ameliorative effect of GF diet in utero is followed by dampening of
inflammation, unchanged beta‐cell volume, but increased islet numbers. KEYWORDS
beta‐cell, celiac disease, gluten‐free diet, islet of Langerhans, NOD mice, type 1
diabetes

Journal Article; Research Support, Non-U.S. Gov't

Idioma:
English
Informações de revista científica:
Publisher:  American Diabetes Association Country of Publication:  United States NLM
ID: 0372763 Publication Model:  Print-Electronic Cited Medium:  Internet ISSN: 1939-
327X (Electronic) Linking ISSN:  00121797 NLM ISO
Abbreviation:  Diabetes Subsets:  Core Clinical (AIM); MEDLINE
Nome(s) impresso(s):
Publication: Alexandria, VA : American Diabetes Association
Original Publication: [New York, American Diabetes Association]
Termo
s de
MeSH:
Diet, Gluten-Free*
Diabetes Mellitus/*prevention & control
Inflammation/*prevention & control
Animal Feed/analysis ; Animal Nutritional Physiological
Phenomena ; Animals ; Antigens, CD/genetics ; Antigens,
CD/metabolism ; Female ; Gastrointestinal Tract/microbiology ; Lactation ; Maternal
Nutritional Physiological Phenomena ; Mice ; Mice, Inbred
NOD ; Pregnancy ; Proteobacteria/physiology ; Verrucomicrobia/physiology
 Resumo:
Early-life interventions in the intestinal environment have previously been shown to
influence diabetes incidence. We therefore hypothesized that a gluten-free (GF) diet,
known to decrease the incidence of type 1 diabetes, would protect against the
development of diabetes when fed only during the pregnancy and lactation period.
Pregnant nonobese diabetic (NOD) mice were fed a GF or standard diet until all pups
were weaned to a standard diet. The early-life GF environment dramatically decreased
the incidence of diabetes and insulitis. Gut microbiota analysis by 16S rRNA gene
sequencing revealed a pronounced difference between both mothers and their offspring
on different diets, characterized by increased numbers of Akkermansia, Proteobacteria,
and TM7 in the GF diet group. In addition, pancreatic forkhead box P3 regulatory T cells
were increased in GF-fed offspring, as were M2 macrophage gene markers and tight
junction-related genes in the gut, while intestinal gene expression of proinflammatory
cytokines was reduced. An increased proportion of T cells in the pancreas expressing
the mucosal integrin α4β7 suggests that the mechanism involves increased trafficking
of gut-primed immune cells to the pancreas. In conclusion, a GF diet during fetal and
early postnatal life reduces the incidence of diabetes. The mechanism may involve
changes in gut microbiota and shifts to a less proinflammatory immunological milieu in
the gut and pancreas.
(© 2014 by the American Diabetes Association. Readers may use this article as long as
the work is properly cited, the use is educational and not for profit, and the work is not
altered.)

Mice born to mothers from normal, gluten-containing diet colonies had significantly greater
systemic immune responses to gliadin after parenteral immunization than mice born to mothers
from a gluten-free diet colony. Furthermore, feeding mothers gluten-containing diet for defined
periods before and during pregnancy and during lactation also resulted in priming of the
specific systemic immune responses of the offspring. These findings indicate that, in mice,
sensitization to maternal dietary antigens readily occurs in utero or shortly after birth. This
animal model should allow investigation of the immunological mechanisms concerned.

Objective: To examine the association between prenatal gluten exposure and offspring risk of

type 1 diabetes in humans.
Design: National prospective cohort study.
Setting: National health information registries in Denmark.
Participants: Pregnant Danish women enrolled into the Danish National Birth Cohort, between
January 1996 and October 2002, MAIN OUTCOME MEASURES: Maternal gluten intake,
based on maternal consumption of gluten containing foods, was reported in a 360 item food
frequency questionnaire at week 25 of pregnancy. Information on type 1 diabetes occurrence in
the participants' children, from 1 January 1996 to 31 May 2016, were obtained through registry
linkage to the Danish Registry of Childhood and Adolescent Diabetes.
Results: The study comprised 101 042 pregnancies in 91 745 women, of whom 70 188 filled
out the food frequency questionnaire. After correcting for
multiple pregnancies, pregnancies ending in abortions, stillbirths, lack of information regarding
the pregnancy, and pregnancies with implausibly high or low energy intake, 67 
565 pregnancies (63 529 women) were included. The average gluten intake was 13.0 g/day,
ranging from less than 7 g/day to more than 20 g/day. The incidence of type 1 diabetes among
children in the cohort was 0.37% (n=247) with a mean follow-up period of 15.6 years (standard
deviation 1.4). Risk of type 1 diabetes in offspring increased proportionally with
maternal gluten intake during pregnancy (adjusted hazard ratio 1.31 (95% confidence interval
1.001 to 1.72) per 10 g/day increase of gluten). Women with the highest gluten intake versus
those with the lowest gluten intake (≥20 v <7 g/day) had double the risk of type 1 diabetes
development in their offspring (adjusted hazard ratio 2.00 (95% confidence interval 1.02 to
4.00)).
Conclusions: High gluten intake by mothers during pregnancy could increase the risk of their
children developing type 1 diabetes. However, confirmation of these findings are warranted,
preferably in an intervention setting.
Background & Aims: There have been inconsistent reports of prenatal and perinatal factors
that affect risk for development of celiac disease. We assessed the association of fetal
growth, birth weight, and mode of delivery with development of celiac disease within the
Norwegian Mother and Child (MoBa) Cohort Study.
Methods: The MoBa cohort contains pregnancy information on 95,200 women and data on
their 114,500 children, which were collected in Norway from 1999 through 2008; it is linked to
the Medical Birth Registry. Women and children with celiac disease were identified from the
National Patient Registry and from women's responses to MoBa questionnaires. We calculated
odds ratios (ORs) for celiac disease by using a multivariable logistic regression model, adjusting
for maternal celiac disease, sex of children, and children's age (model 1); in a second model,
we adjusted for age of gluten introduction and duration of breastfeeding (model 2).
Results: We identified 650 children with celiac disease and 107,828 controls in the MoBa
database. We found no association between birth weight or height with celiac disease (born
small for gestational age was not associated). Celiac disease was not associated with mode of
delivery (cesarean section, model 1: OR, 0.84; 95% confidence interval [CI], 0.65-1.09, and
model 2: OR, 0.83; 95% CI, 0.63-1.09). Maternal celiac disease, adjusted for age and sex of the
children (OR, 12.45; 95% CI, 8.29-18.71) and type 1 diabetes (model 1: OR, 2.58; 95% CI,
1.19-5.53, and model 2: OR, 2.61; 95% CI, 1.14-5.98) were associated with development of
celiac disease in children, whereas maternal type 2 diabetes and gestational diabetes were not.
Conclusions: On the basis of analysis of the Norwegian MoBa cohort, development of celiac
disease in children is significantly associated with sex of the child, maternal celiac disease, and
type 1 diabetes but not with intrauterine growth.

Objective: The authors analyzed archival dried blood spots obtained from newborns to assess
whether levels of immunoglobulin G (IgG) directed at dietary antigens were associated with a
later diagnosis of a nonaffective psychotic disorder.
Method: The study population consisted of individuals born in Sweden between 1975 and 1985
with verified register-based diagnoses of nonaffective psychoses made between 1987 and 2003
and comparison subjects matched on sex, date of birth, birth hospital, and municipality. A total
of 211 case subjects and 553 comparison subjects consented to participate in the study. Data
on factors associated with maternal status, pregnancy, and delivery were extracted from the
Swedish Medical Birth Register. Levels of IgG directed at gliadin (a component of gluten) and
casein (a milk protein) were analyzed in eluates from dried blood spots by enzyme-linked
immunosorbent assay. Odds ratios were calculated for levels of IgG directed at gliadin or casein
for nonaffective psychosis.
Results: Levels of anti-gliadin IgG (but not anti-casein IgG) above the 90th percentile of levels
observed among comparison subjects were associated with nonaffective psychosis (odds
ratio=1.7, 95% CI=1.1-2.8). This association was not confounded by differences in maternal
age, immigrant status, or mode of delivery. Similarly, gestational age at birth, ponderal index,
and birth weight were not related to maternal levels of anti-gliadin IgG.
Conclusions: High levels of anti-gliadin IgG in the maternal circulation are associated with an
elevated risk for the development of a nonaffective psychosis in offspring. Research is needed
to identify the mechanisms underlying this association in order to develop preventive strategies.