Maternal Thyroid Disease and the Risk of Childhood Cancer in the Offspring

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

Maternal Thyroid Disease and the Risk of Childhood Cancer in the Offspring

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

Preterm birth, neonatal therapies and the risk of childhood cancer

Our aim was to study the impact of preterm birth and neonatal therapies on the risk of childhood cancer using a nationwide, registry-based, case-control design. Combining population-based data from Finnish Medical Birth Registry (MBR) and Finnish Cancer Registry, we identified a total of 2029 patients diagnosed with cancer under the age of 20 years and 10 103 age- and sex-matched controls over the years 1996 to 2014. Information on the prenatal and perinatal conditions was obtained from the MBR. Gestational age was categorized into early (= 37 weeks). Cancer risk among the preterm compared to term neonates was evaluated using conditional logistic regression. We identified 141 cancers among the preterm (20.8% of 678) vs 1888 cancers in the term children (16.5% of 11 454). The risk of any cancer was increased for the preterm (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.06-1.57), especially for the early preterm (OR 1.84, 95% CI 1.16-2.92). The risk of acute myeloid leukemia (AML; OR 2.33, 95% CI 1.25-4.37), retinoblastoma (OR 3.21, 95% CI 1.22-8.41) and germ cell tumors (OR 5.89, 95% CI 2.29-15.18) was increased among the preterm compared to term. Germ cell tumors were diagnosed at a significantly younger age among the preterm. Neonatal therapies, for example, mechanical ventilation, were associated with an increased risk of childhood cancer independent of gestational age. Preterm, especially early preterm birth, is associated with an increased risk of childhood cancer, especially germ cell tumors and AML. Respiratory distress requiring neonatal intervention also appears to be associated with an increased risk.Peer reviewe

Medical SANSformers: Training self-supervised transformers without attention for Electronic Medical Records

We leverage deep sequential models to tackle the problem of predicting healthcare utilization for patients, which could help governments to better allocate resources for future healthcare use. Specifically, we study the problem of \textit{divergent subgroups}, wherein the outcome distribution in a smaller subset of the population considerably deviates from that of the general population. The traditional approach for building specialized models for divergent subgroups could be problematic if the size of the subgroup is very small (for example, rare diseases). To address this challenge, we first develop a novel attention-free sequential model, SANSformers, instilled with inductive biases suited for modeling clinical codes in electronic medical records. We then design a task-specific self-supervision objective and demonstrate its effectiveness, particularly in scarce data settings, by pre-training each model on the entire health registry (with close to one million patients) before fine-tuning for downstream tasks on the divergent subgroups. We compare the novel SANSformer architecture with the LSTM and Transformer models using two data sources and a multi-task learning objective that aids healthcare utilization prediction. Empirically, the attention-free SANSformer models perform consistently well across experiments, outperforming the baselines in most cases by at least $\sim 10$\%. Furthermore, the self-supervised pre-training boosts performance significantly throughout, for example by over $\sim 50$\% (and as high as $800$\%) on $R^2$ score when predicting the number of hospital visits.Comment: 25 pages, 8 figures, 5 tables, Submitted to a journa

Maternal Diabetes and Risk of Childhood Cancer in the Offspring

An association between maternal diabetes, its medication and childhood cancer has not been previously explored in a registry-based setting. With a case-control design, we aimed to explore whether maternal diabetes is associated with an increased risk of childhood cancer in the offspring. Combining data from population-based registries, we analyzed a total of 2,029 cases, i.e. persons with childhood cancer diagnosed under the age of 20?years between years 1996-2014 and a total of 10,103 matched population controls. The mothers of the cases/controls and their diagnoses of diabetes (DM) before/during pregnancy as well as their insulin/metformin prescriptions during pregnancy were identified. Conditional logistic regression modelling was used to analyze the risk of childhood cancer. The OR for childhood cancer among those exposed to any maternal diabetes was 1.32 (95% CI 1.14-1.54) compared to the offspring of the non-diabetic mothers. The effect of maternal diabetes on the risk of childhood cancer remained elevated even after adjusting for maternal age, parity and smoking. Our data suggest that maternal diabetes medication may reduce the risk for childhood cancer (adjusted OR 0.83, 95% CI 0.36-1.94), especially in gestational diabetes (adjusted OR 0.26, 95% CI 0.05-1.25), compared to the diabetic mothers without medication. The risk of childhood leukemia was significantly higher among children exposed to any maternal diabetes (OR 1.36, CI 1.04-1.77) compared to the unexposed. Maternal diabetes appears to be associated with an increased risk of childhood cancer in the offspring. The possible risk-reducing effect of an exposure to diabetes medication on offspring cancer risk warrants further investigation. This article is protected by copyright. All rights reserved.Peer reviewe

Maternal autoimmune disease is not associated with cancer in the offspring

Aim Autoimmune disease and its medication are associated with increased cancer risk in adults, but it is unknown whether maternal autoimmune disease and/or medication use in pregnancy are associated with increased cancer risk in offspring. Methods In this case-control study, we identified all patients under 20 years of age with their first cancer diagnosis in 1996-2014 from the Finnish Cancer Registry (n = 2029) and 1:5 population-based controls (n = 10,103) from the Medical Birth Register. We obtained information on maternal autoimmune disease and its medication from the relevant Finnish registries and used conditional logistic regression to analyse the risk of offspring cancer after maternal autoimmune disease exposure. Results The odds ratio (OR) for cancer in offspring following maternal autoimmune exposure was 0.76 (95% confidence interval [CI] 0.47-1.23). Individual ORs for inflammatory bowel and connective tissue diseases were 1.08 (95% CI 0.56-2.01) and 0.50 (95% CI 0.23-1.08), respectively. The OR for maternal autoimmune medication was 0.95 (95% CI 0.80-1.14) overall and similar by drug subtype. There was an increased risk with medication in late pregnancy but the ORs were unstable owing to small numbers. Conclusion Our study does not support an increased cancer risk among offspring of women with autoimmune disease or its medication during pregnancy.Peer reviewe

Second-generation antipsychotics and pregnancy complications

Purpose To study if second-generation antipsychotic (S-GA) use during pregnancy is associated with an increased risk of pregnancy and neonatal complications. Methods A population-based birth cohort study using national register data extracted from the "Drugs and Pregnancy" database in Finland, years 1996-2016. The sampling frame included 1,181,090 pregnant women and their singleton births. Women were categorized into three groups: exposed to S-GAs during pregnancy (n = 4225), exposed to first-generation antipsychotics (F-GAs) during pregnancy (n = 1576), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 21,125). Pregnancy outcomes in S-GA users were compared with those in the two comparison groups using multiple logistic regression models. Results Comparing S-GA users with unexposed ones, the risk was increased for gestational diabetes (adjusted odds ratio, OR 1.43; 95% CI 1.25-1.65), cesarean section (OR 1.35; 95% CI 1.18-1.53), being born large for gestational age (LGA) (OR 1.57; 95% CI 1.14-2.16), and preterm birth (OR 1.29; 95% CI 1.03-1.62). The risk for these outcomes increased further with continuous S-GA use. Infants in the S-GA group were also more likely to suffer from neonatal complications. Comparing S-GA users with the F-GA group, the risk of cesarean section and LGA was higher (OR 1.25, 95% CI 1.03-1.51; and OR 1.89, 95% CI 1.20-2.99, respectively). Neonatal complications did not differ between the S-GA and F-GA groups. Conclusions Prenatal exposure to S-GAs is associated with an increased risk of pregnancy complications related to impaired glucose metabolism. Neonatal problems are common and occur similarly in S-GA and F-GA users.Peer reviewe

Extended spectrum penicillins reduce the risk of omphalocele : A population-based case-control study

Peer reviewe

Second-generation antipsychotic use during pregnancy and risk of congenital malformations

Purpose To study if second-generation antipsychotic (S-GA) use during the first trimester of pregnancy is associated with an increased risk of major congenital malformations (MCM). Methods A population-based birth cohort study using national register data extracted from the Drugs and Pregnancy database in Finland, years 1996-2017. The sampling frame included 1,273,987 pregnant women. We included singleton pregnancies ending in live or stillbirth or termination of pregnancy due to severe malformation. Pregnancies with exposure to known teratogens were excluded. Women were categorized into three groups: exposed to S-GAs (n = 3478), exposed to first-generation antipsychotics (F-GAs) (n = 1030), and unexposed (no purchases of S-GAs or F-GAs during pregnancy, n = 22,540). We excluded genetic conditions and compared the prevalence of MCMs in S-GA users to the two comparison groups using multiple logistic regression models. Results Use of S-GAs during early pregnancy was not associated with an increased risk of overall MCMs compared to unexposed (adjusted odds ratio, OR 0.92; 95% CI 0.72-1.19) or to F-GA users (OR 0.82; 95% CI 0.56-1.20). Of individual S-GAs, olanzapine use was associated with an increased risk of overall MCMs (OR 2.12; 95% CI 1.19-3.76), and specifically, an increased risk of musculoskeletal malformations (OR 3.71; 95% CI 1.35-10.1) when compared to unexposed, while comparisons to F-GA users did not show significant results. Conclusions Olanzapine use is associated with an increased risk of major congenital malformations and specifically, musculoskeletal malformations. Use during pregnancy should be restricted to situations where no safer alternatives exist.</p