Birth weight, sex, and celiac disease: a nationwide twin study

Abstract

Objective

Earlier research suggests that birth weight may be associated with celiac disease (CD), but the direction of association has been unclear potentially due to confounding effect from genetic and intrafamilial factors. Through within-twin analyses, we aimed to minimize confounding effects such as twins that share genetic and early environmental exposures.

Materials and methods

Using the Swedish Twin Registry, we examined the birth weight of 146,830 twins according to the CD status. CD was defined as having villous atrophy according to a small intestinal biopsy reports.

Results

The prevalence of diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD–non-CD twins. Comparing the 669 CD patients with non-CD twins, the association between birth weight and future CD was not statistically significant (odds ratio [OR] per 1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97–1.38). In males, the association was positive and statistically significant (OR=1.50; 95% CI=1.11–2.02). However, the association was not significant in within-pair analyses for both dizygotic and monozygotic twins and for both sexes.

Conclusion

This population-based study found that in male twins, higher birth weight was associated with higher risk of CD. However, when comparing discordant twin pairs in within-twin pair analyses, there was no statistically significant association between birth weight, intrauterine growth, and future risk of CD.

Keywords:

• autoimmune
• gestational age
• gluten
• registries
• risk factors
• twins

Supplementary materials

Figure S1 Observed proportion with CD by birth weight in subsample born in 1980–2004.

Notes: Percentiles refer to the percentage of individuals with a birth weight lower than indicated. Linear refers to a modeled proportion in a logistic regression with an effect that is linear on the log-odds scale. 95% CI refers to 95% bootstrap CIs of modeled proportion with CD based on 10,000 repeats.

Abbreviations: CD, celiac disease; CI, confidence interval.

Table S1 Analyses of the association between birth weight and CD, estimate (95% CI)

Table S2 Analyses of the association between birth weight and CD in subsample born in 1980–2004 (N=58,771), estimate (95% CI)

Table S3 Analyses of the association between birth weight and CD among same-sexed twin pairs, estimate (95% CI)

Table S4 Analyses of the association between birth weight and CD stratified by whether twin pair was complete, estimate (95% CI)

Acknowledgments

JFL was supported by grants from the Swedish Society of Medicine and the Swedish Research Council. None of the funders had any influence on this study.

Author contributions

Agreed with the manuscript’s results and conclusion and approved the final version of the manuscript: JFL, RK-H, BL, JH, LE, and PKM. Designed the study: JFL, RK-H, LE, and PKM. Analyzed the data: RK-H. Wrote the first draft of the manuscript: JFL and RK-H. Contributed to the revision of the paper: BL, JH, LE, and PKM. Contributed to the design of the study and interpretation of the data analyses: BL and JH. Responsible for data integrity: JFL, RK-H, and PKM. Obtained funding: JFL. All the authors approved the final version of the manuscript.

Disclosure

The authors report no conflicts of interest in this work.