Atopic dermatitis and fecundity: a Danish National Birth Cohort study.

study questionDo women with atopic dermatitis have higher fecundity than those without? SUMMARY ANSWER: Pregnant women with a history of atopic dermatitis had a slightly shorter time-to-pregnancy (TTP) and a lower risk of conceiving using infertility treatment than those without. WHAT IS KNOWN ALREADY: Atopic dermatitis has a characteristic T-helper-2-cell-skewed immune response that mirrors the immune shift in pregnancy, which is necessary for the pregnant woman's immune response to tolerate the fetus. Therefore, it has been hypothesized that atopic dermatitis may be advantageous for conception and pregnancy maintenance. However, this has not yet been investigated. STUDY DESIGN SIZE DURATION: This cohort study included 88 713 pregnant women from the population-based Danish National Birth Cohort (DNBC), who were enrolled between 1996 and 2002. PARTICIPANTS/MATERIALS SETTING

methodsThe women were defined as having atopic dermatitis if, in a computer-assisted interview conducted around gestational week 17, they reported having ever been diagnosed with atopic dermatitis by a doctor. The women were also asked whether the pregnancy was planned or unplanned, to report their TTP within one of five prespecified categories, and whether they had conceived with the use of infertility treatment. We used multinomial logistic regression models to assess associations between atopic dermatitis and fecundity in seven categories: (TTP <1 month, 1-2 months, 3-5 months, 6-12 months, >12 months, pregnant after infertility treatment or unplanned). In addition, we modeled TTP as dichotomous outcomes using logistic regression: subfecundity (TTP ≥6 months vs <6 months) and infertility (TTP >12 months vs ≤12 months). We also assessed women with an atopic constitution (atopic dermatitis, allergic rhinitis, asthma, and food allergies), as this is associated with more severe atopic dermatitis. MAIN RESULTS AND THE ROLE OF CHANCE: Overall, 3641 (4.1%) women reported ever having had atopic dermatitis. Compared to women without atopic dermatitis, women with atopic dermatitis had a lower relative risk ratio (RRR) of having a TTP >12 months: 0.83 (95% CI: 0.72; 0.96), and use of infertility treatment, RRR: 0.81 (95% CI: 0.69; 0.94). Moreover, women with atopic dermatitis had a lower odds ratio (OR) of subfecundity: 0.89 (95% CI: 0.82; 0.96) and infertility: 0.85 (95% CI: 0.77; 0.95) than women without in the logistic regression model. Results were robust across several sub-analyses. LIMITATIONS REASONS FOR CAUTION: The results can only be generalized to women who eventually conceive, since the DNBC consists only of women who successfully conceived. WIDER IMPLICATIONS OF THE

findingsThe findings support the hypothesis of an immunological benefit in conceiving when having atopic dermatitis. The results are reassuring for women with atopic dermatitis trying to conceive. However, the hypothesis should be further tested in a broader population of women without conditioning on pregnancy. STUDY FUNDING/COMPETING INTERESTS: The work was supported by the Danish Council for Independent Research (grant number DFF-1030-00164B), Aarhus University, and Fonden af Fam. Kjærsgaard, Sunds, the Research Council of Norway (project no. 320656), through its Centres of Excellence funding scheme (project no. 262700), and co-funded by the European Union (ERC, BIOSFER, 101071773). However, views and opinions expressed herein are those of the author(s) only and do not necessarily reflect those of the European Union or the European Research Council. Neither the European Union nor the granting authority can be held responsible. This publication is part of the ReproUnion collaborative study, co-financed by the European Union, Intereg V ÖKS (20200407). M.D. has received consulting fees (including participation on advisory boards) from AbbVie, LEO Pharma, Eli Lilly, Incyte, La Roche Posay, NUMAB Therapeutics, Pfizer, Regeneron Pharmaceuticals Inc., Sanofi Genzyme, Almirall, Union Therapeutics, Kymab, and UCB; travel support from LEO Pharma and Sanofi Genzyme; speaker fees from Mustela, Galderma, Leo Pharma, Sanofi Genzyme, and La Roche Posay; Section editor for Journal of the European Academy of Dermatology and Venereology (JEADV). None of these COIs is relevant to the present article. The remaining authors declare that they have no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.