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Objective: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype., Methods: We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996-2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose. The outcome was nongenetic MCM and specific subtypes. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) with log-binomial regression and propensity score weights., Results: There was a higher crude risk of any MCM in pregnancies exposed to lamotrigine monotherapy (n = 8,339) compared to ASM-unexposed pregnancies (n = 4,866,362), but not after confounder adjustment (aRR = 0.97, 95% CI = 0.87-1.08). Compared to lamotrigine, there was an increased risk of malformations associated with valproate (n = 2,031, aRR = 2.05, 95% CI = 1.70-2.46) and topiramate (n = 509, aRR = 1.81, 95% CI = 1.26-2.60), which increased in a dose-dependent manner. We found no differences in malformation risk for carbamazepine (n = 2,674, aRR = 0.91, 95% CI = 0.72-1.15), oxcarbazepine (n = 1,313, aRR = 1.09, 95% CI = 0.83-1.44), or levetiracetam (n = 1,040, aRR = 0.78, 95% CI = 0.53-1.13). Valproate was associated with several malformation subtypes, including nervous system, cardiac, oral clefts, clubfoot, and hypospadias, whereas lamotrigine and carbamazepine were not., Interpretation: Topiramate is associated with an increased risk of MCM similar to that associated with valproate, but lower doses may mitigate the risks for both drugs. Conversely, we found no increased risks for lamotrigine, carbamazepine, oxcarbazepine, or levetiracetam, which is reassuring. ANN NEUROL 2023;93:551-562., (© 2022 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

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 (<32) and late preterm (32-36) and term (≥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., (© 2020 Union for International Cancer Control.)

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, that is, 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 modeling 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 nondiabetic 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., (© 2019 UICC.)

We analysed patterns in the incidence of cervical intraepithelial neoplasia grades 2 and 3 (CIN2, CIN3) and adenocarcinoma in situ (AIS) by age and histology in 1992-2016 in Norway and described changes in screening tests. Incident cases of CIN2, CIN3, AIS and cervical cancer were identified in the Cancer Registry of Norway, as were all women with at least one screening test. The annual percentage change statistic was used to assess point estimates and changes in age-specific and age-standardised incidence rates (IR). Women aged 25-29 years had the highest incidence of cervical precancerous lesions (CIN2: 192.9/10, CIN3: 737.2/10, AIS: 32.5/10 5 in 2016). The IR of CIN2 increased for all screening ages (25-69 years) from 3.6% to 6.7% per year. CIN3 incidence increased by 1.6% (95% confidence interval [CI] 0.6-2.6) annually. A steep increase in AIS incidence was observed in all age groups (7.1% per year, 95% CI 5.3-8.8). Changes in screening tests and the histological verification of cervical precancerous lesions alone cannot explain the steady increase in incidence we observed over the 25-year study period, and increased exposure to human papillomavirus (HPV) likely plays a role. Age-appropriate treatment of screening-detected cervical precancerous lesions is needed for effective cervical cancer control while avoiding overtreatment and related health risks. In order to perform an appropriate harm-benefit evaluation of cervical cancer control efforts, detailed information on screening technology and background risks, including HPV vaccination status, is needed to create optimal public health policy., (© 2019 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

A latex agglutination test (LX) using antisera prepared against Nebraska calf diarrhea virus (NCDV) is described for the detection of rotavirus in stool of children with acute gastroenteritis. The test was compared with electron microscopy (EM) and radioimmunoassay (RIA) with 100 stools positive or negative for rotavirus. Out of 53 stools positive in RIA or EM, 49 were positive in LX and 4 were negative. Two specimens negative in EM and RIA were falsely positive in LX. The method was also tested in two clinical series with 115 stools from 101 children. Altogether 67/115 stools were positive in RIA, and 62/115 in LX. Out of 7 stools with contradictory results, 6 were negative in LX but positive in RIA, and 1 was positive in LX but negative in RIA. The results indicate that the LX is suitable for rapid screening of rotavirus gastroenteritis in clinical practice.