Abstract
Simple SummaryMaternal thyroid disease, especially hypothyroidism, is known to affect pregnancy and its outcome. We evaluated the risk of childhood cancer in the offspring following exposure to maternal thyroid disease in a case-control setting using registry data. In our study, maternal hypothyroidism was associated with an increased risk of lymphoma in the offspring. The association remained stable when possible familial cancers were excluded.Maternal thyroid disease, especially hypothyroidism, affects pregnancy and its outcome. In-utero exposure to autoimmune thyroid disease has been reported to associate with childhood ALL in the offspring. We evaluated the risk of childhood cancer in the offspring following exposure to maternal thyroid disease in a case-control setting using registry data. All patients with their first cancer diagnosis below the age of 20 years were identified from the Finnish Cancer Registry (n = 2037) and matched for sex and birth year at a 1:5 ratio to population controls identified from the Medical Birth Registry (n = 10,185). We collected national information on maternal thyroid disease from the Medical Birth Registry, Care Register for Health Care, Register for Reimbursed Drug Purchases and Register of Special Reimbursements. We used conditional logistic regression to analyze childhood cancer risk in the offspring. The adjusted OR for any childhood cancer was 1.41 (95%, CI 1.00–2.00) comparing the offspring of mothers with hypothyroidism and those with normal thyroid function. The risk of lymphomas was increased (adjusted OR for maternal hypothyroidism 3.66, 95%, CI 1.29–10.38). The results remained stable when mothers with cancer history were excluded from the analyses. Maternal hypothyroidism appears to be associated with an increased risk for childhood lymphoma in the offspring. The association exists even after excluding possible familial cancers.
Highlights
In-utero exposure to maternal disease and its medication has been recognized as potential risk factors for the development of childhood cancer in the offspring
Population-based case-control studies report no association between maternal autoimmune disease other than thyroid and childhood cancer in the offspring [14,15,16,17]
Large for gestational age neonates (LGA), small for gestational age (SGA), and neonatal intensive care are more common among the offspring of mothers with hypo- and hyperthyroidism compared to those of euthyroid mothers [19]
Summary
In-utero exposure to maternal disease and its medication has been recognized as potential risk factors for the development of childhood cancer in the offspring. Established risk factors for childhood cancer are sparse with only 10% of the cases being associated with recognized, hereditary predisposition syndromes [1], this proportion can be an underestimate [2]. Previously introduced risk factors, include both high and low birth weight [3,4,5,6], preterm birth [7,8,9,10], maternal diabetes [11,12], and some environmental factors, i.e., pesticides [13]. Population-based case-control studies report no association between maternal autoimmune disease other than thyroid and childhood cancer in the offspring [14,15,16,17]. Large for gestational age neonates (LGA), small for gestational age (SGA), and neonatal intensive care are more common among the offspring of mothers with hypo- and hyperthyroidism compared to those of euthyroid mothers [19]
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