Birth defect risk low in celiac disease

Pregnant mothers with celiac disease have little to fear when it comes to birth defects, despite previous underpowered reports to the contrary, wrote Daniela Zugna, Ph.D., and her colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi.org/10.1016/j.cgh.2013.10.012).

Dr. Zugna of University of Turin, in Italy, looked at a total of 5,774 mothers with celiac disease (CD) and 3,039 fathers with CD, cross-referenced with the Swedish Medical Birth Register, the Patient Register, the Register of Congenital Malformations and the Multigeneration Register.

From 1973 through 2009, the mothers gave birth to 11,382 children, and 6,002 children were born to fathers with CD.

These were compared with nearly 41,000 and 20,000 children of healthy mothers and fathers born over the same time period, respectively.

The authors found that 672 babies of mothers with CD (5.9%) and 2,098 control offspring (5.1%) were born with congenital malformations; these included heart defects, neural tube defects, limb deficiencies, and orofacial clefts, among others.

That amounted to an adjusted prevalence odds ratio of having a child with birth defects of 1.15 for mothers with CD (95% confidence interval, 1.05-1.26).

For fathers, the figures were 352 children with birth defects born to CD patients (5.9%) and 1,009 to healthy controls (5.1%), for a similar odds ratio of 1.14 (95% CI, 1.00-1.29).

However, when the data were restricted to births between 2000 and 2009, the significance of these differences vanished: in this most modern era, mothers with CD carried a nonsignificant OR of 1.11 (95% CI, 0.79-1.56).

By the same token, fathers of babies born between 2000 and 2009 had an OR of 1.01 for having a child with birth defects (95% CI, 0.81-1.26).

In postulating reasons for the slightly increased number of birth defects seen over the span of the study, the authors wrote: "While folic acid deficiency is common in newly diagnosed CD, it is sometimes seen after diagnosis, perhaps because of a lack of folic acid in the gluten-free diet."

And regarding the possible connection between fathers with CD and their children, "If spouses to men with CD are also primarily on a gluten-free diet, this may actually explain the excess risk for congenital malformation in paternal offspring."

Alternatively, "Low sperm quality in men with CD could potentially influence the risk of malformations."

The authors conceded several important weaknesses in this study. For one, they did not have data on diet adherence in CD, nor on the periconceptional or perinatal use of folic acid supplementation.

Moreover, a substantial proportion of pregnancies with neural tube defects discovered during prenatal screening were likely to have been terminated, potentially resulting in artificially low rates of this malformation: indeed, the authors pointed to data showing that between 1999 and 2009, between 51% and 93% of all NTD pregnancies were terminated, depending on the specific defect.

Finally, "Over time, symptoms have changed in CD," they wrote.

"It is possible that, with increased use of celiac serology, milder cases of CD are now diagnosed in which there is no association with congenital malformation."

The authors disclosed no conflicts of interest; individual authors disclosed several grants from nonprofit and research agencies in Europe, including the Italian Association for Cancer Research, the Stockholm County Council, the Danish Medical Research Council, and the Karolinska Institutet, among others.

Pregnant mothers with celiac disease have little to fear when it comes to birth defects, despite previous underpowered reports to the contrary, wrote Daniela Zugna, Ph.D., and her colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi.org/10.1016/j.cgh.2013.10.012).

Dr. Zugna of University of Turin, in Italy, looked at a total of 5,774 mothers with celiac disease (CD) and 3,039 fathers with CD, cross-referenced with the Swedish Medical Birth Register, the Patient Register, the Register of Congenital Malformations and the Multigeneration Register.

From 1973 through 2009, the mothers gave birth to 11,382 children, and 6,002 children were born to fathers with CD.

These were compared with nearly 41,000 and 20,000 children of healthy mothers and fathers born over the same time period, respectively.

The authors found that 672 babies of mothers with CD (5.9%) and 2,098 control offspring (5.1%) were born with congenital malformations; these included heart defects, neural tube defects, limb deficiencies, and orofacial clefts, among others.

That amounted to an adjusted prevalence odds ratio of having a child with birth defects of 1.15 for mothers with CD (95% confidence interval, 1.05-1.26).

For fathers, the figures were 352 children with birth defects born to CD patients (5.9%) and 1,009 to healthy controls (5.1%), for a similar odds ratio of 1.14 (95% CI, 1.00-1.29).

However, when the data were restricted to births between 2000 and 2009, the significance of these differences vanished: in this most modern era, mothers with CD carried a nonsignificant OR of 1.11 (95% CI, 0.79-1.56).

By the same token, fathers of babies born between 2000 and 2009 had an OR of 1.01 for having a child with birth defects (95% CI, 0.81-1.26).

In postulating reasons for the slightly increased number of birth defects seen over the span of the study, the authors wrote: "While folic acid deficiency is common in newly diagnosed CD, it is sometimes seen after diagnosis, perhaps because of a lack of folic acid in the gluten-free diet."

And regarding the possible connection between fathers with CD and their children, "If spouses to men with CD are also primarily on a gluten-free diet, this may actually explain the excess risk for congenital malformation in paternal offspring."

Alternatively, "Low sperm quality in men with CD could potentially influence the risk of malformations."

The authors conceded several important weaknesses in this study. For one, they did not have data on diet adherence in CD, nor on the periconceptional or perinatal use of folic acid supplementation.

Moreover, a substantial proportion of pregnancies with neural tube defects discovered during prenatal screening were likely to have been terminated, potentially resulting in artificially low rates of this malformation: indeed, the authors pointed to data showing that between 1999 and 2009, between 51% and 93% of all NTD pregnancies were terminated, depending on the specific defect.

Finally, "Over time, symptoms have changed in CD," they wrote.

"It is possible that, with increased use of celiac serology, milder cases of CD are now diagnosed in which there is no association with congenital malformation."

The authors disclosed no conflicts of interest; individual authors disclosed several grants from nonprofit and research agencies in Europe, including the Italian Association for Cancer Research, the Stockholm County Council, the Danish Medical Research Council, and the Karolinska Institutet, among others.

Pregnant mothers with celiac disease have little to fear when it comes to birth defects, despite previous underpowered reports to the contrary, wrote Daniela Zugna, Ph.D., and her colleagues in the July issue of Clinical Gastroenterology and Hepatology (doi.org/10.1016/j.cgh.2013.10.012).

Dr. Zugna of University of Turin, in Italy, looked at a total of 5,774 mothers with celiac disease (CD) and 3,039 fathers with CD, cross-referenced with the Swedish Medical Birth Register, the Patient Register, the Register of Congenital Malformations and the Multigeneration Register.

From 1973 through 2009, the mothers gave birth to 11,382 children, and 6,002 children were born to fathers with CD.

These were compared with nearly 41,000 and 20,000 children of healthy mothers and fathers born over the same time period, respectively.

The authors found that 672 babies of mothers with CD (5.9%) and 2,098 control offspring (5.1%) were born with congenital malformations; these included heart defects, neural tube defects, limb deficiencies, and orofacial clefts, among others.

That amounted to an adjusted prevalence odds ratio of having a child with birth defects of 1.15 for mothers with CD (95% confidence interval, 1.05-1.26).

For fathers, the figures were 352 children with birth defects born to CD patients (5.9%) and 1,009 to healthy controls (5.1%), for a similar odds ratio of 1.14 (95% CI, 1.00-1.29).

However, when the data were restricted to births between 2000 and 2009, the significance of these differences vanished: in this most modern era, mothers with CD carried a nonsignificant OR of 1.11 (95% CI, 0.79-1.56).

By the same token, fathers of babies born between 2000 and 2009 had an OR of 1.01 for having a child with birth defects (95% CI, 0.81-1.26).

In postulating reasons for the slightly increased number of birth defects seen over the span of the study, the authors wrote: "While folic acid deficiency is common in newly diagnosed CD, it is sometimes seen after diagnosis, perhaps because of a lack of folic acid in the gluten-free diet."

And regarding the possible connection between fathers with CD and their children, "If spouses to men with CD are also primarily on a gluten-free diet, this may actually explain the excess risk for congenital malformation in paternal offspring."

Alternatively, "Low sperm quality in men with CD could potentially influence the risk of malformations."

The authors conceded several important weaknesses in this study. For one, they did not have data on diet adherence in CD, nor on the periconceptional or perinatal use of folic acid supplementation.

Moreover, a substantial proportion of pregnancies with neural tube defects discovered during prenatal screening were likely to have been terminated, potentially resulting in artificially low rates of this malformation: indeed, the authors pointed to data showing that between 1999 and 2009, between 51% and 93% of all NTD pregnancies were terminated, depending on the specific defect.

Finally, "Over time, symptoms have changed in CD," they wrote.

"It is possible that, with increased use of celiac serology, milder cases of CD are now diagnosed in which there is no association with congenital malformation."

The authors disclosed no conflicts of interest; individual authors disclosed several grants from nonprofit and research agencies in Europe, including the Italian Association for Cancer Research, the Stockholm County Council, the Danish Medical Research Council, and the Karolinska Institutet, among others.