Background/Purpose

Patients with SLE have an increased risk of hematological malignancies, particularly non-Hodgkin lymphoma, compared to the general population. Recently, in utero exposures, such as chronic maternal autoimmune conditions, have been associated with the development of childhood hematological malignancies. However, until now, no one has assessed the risk of hematological cancers in children born to women with SLE. Thus, in a large population-based study, we aimed to determine if SLE offspring have an increased risk of hematological malignancies, versus controls.

Methods

The “Offspring of SLE mothers Registry (OSLER)” includes all women who had ≥1 hospitalization for delivery after SLE diagnosis, identified through Quebec’s universal healthcare databases (1989-2009). OSLER also includes a randomly selected control group of women, matched at least 4:1 for age and year of delivery, who did not have a diagnosis of SLE prior to or at the time of delivery. We identified children born live to SLE mothers and their matched controls, and ascertained hematological malignancies based on ≥1 hospitalization or physician visit with a relevant diagnostic code, through to end of database follow-up.

We performed multivariate logistic regression analyses, using generalized estimating equations, to adjust for maternal demographics and comorbidities, sex of child, and gestational diabetes. In a subsample analysis of children with maternal drug coverage throughout pregnancy, we further assessed relevant in utero medication exposures.

Results

509 women with SLE had 719 children, while 5824 matched controls had 8493 children. Mean maternal age and follow-up were respectively 30.3 (SD 5.0) and 9.1 (SD 5.8) years. Children born to women with SLE experienced more hematological malignancies (9/719) compared to controls (38/8493) [1.25% (95% CI 0.61, 2.45) versus 0.45% (95% CI 0.32, 0.62), difference 0.80% (95% CI 0.14, 2.01)]. The most frequent type of hematological cancer in both groups was acute lymphoblastic leukemia. Of note, primary non-Hodgkin lymphoma of bone was observed in 2/719 SLE offspring as opposed to 6/8493 control children [0.28% (95% CI 0.05, 1.12) versus 0.07% (95% CI 0.01, 0.16), difference 0.21% (95% CI -0.04, 1.05)]. In multivariate analyses (n=9212), children born to women with SLE appeared to have an increased risk of hematological cancers versus controls (OR 2.80, 95% CI 1.33, 5.92).

In the subsample of children with drug coverage (n=1925), in utero medication exposures were rare in the 10 hematological cancer cases: none was exposed to antimalarials, corticosteroids, or immunosuppressants.

Conclusion

Our data suggest that compared to children from the general population, children born to women with SLE may have an increased risk of hematological malignancies. However, it must be emphasized that this outcome is extremely rare, and our findings remain to be confirmed by other study methods. The lack of association with in utero drug exposures may be viewed as somewhat re-assuring, though this too is preliminary.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/increased-risk-of-hematological-malignancies-in-children-born-to-women-with-sle/