Abstract Cyproterone acetate (CPA) is a synthetic steroid hormone. We assessed the association between the use of CPA and the risk of developing meningioma. In a historical prospective cohort study, using Danish national healthcare registers we included a cohort of 5,730,654 individuals, among whom 1,982 were exposed to CPA. During follow-up, we identified 8,957 cases of meningioma, of which 16 were exposed to CPA. From 2013 to 2019 the number of new users increased from 18.1 to 62.3 new users per million, while the proportion of new users who were transgender increased from 18.4 to 68.3%. Analyses showed a significantly increased risk of meningioma according to cumulative dose of CPA; 0.1-10 grams of CPA, incidence rate 78.8 (95% CI 15.7-141.9) per 100.000 person years and adjusted hazard ratio 7.0 (3.1-15.6); >10 grams of CPA, incidence 187.5 (71.3-303.7) and adjusted hazard ratio 19.2 (10.3-35.8), as compared to the background population. In conclusion, the cumulative dose of CPA was associated with an increased incidence and hazard ratio of meningioma, showing a dose-response relationship. The number of new CPA users increased more than 3-fold from 2013 to 2019, primarily driven by new transgender users.
In utero exposure to maternal cancer and cancer treatment might influence the child's cognitive development. This study investigated if exposure to maternal cancer during fetal life impacted school performance and educational achievement as adults.
PURPOSE In utero exposure to maternal cancer and cancer treatment might influence the child's short- and long-term health and development. The objective of the study was to investigate short- and long-term somatic and psychiatric outcomes in children exposed to maternal cancer in utero. METHODS This nationwide cohort study identified all liveborn children in Denmark between January 1978 and December 2018. Exposure was defined as maternal cancer diagnosis during pregnancy, and in a subgroup analysis, exposure to chemotherapy in utero. The main outcomes of interest were overall mortality, somatic diagnoses, and psychiatric diagnoses identified in the National Health Registers. Follow-up started at birth and ended at an event, death, emigration, or end of 2018. Hazard ratios of end points adjusted for potential confounders were estimated using Cox regression analysis. RESULTS Of 2,526,163 included liveborn children, 690 (0.03%) were exposed to maternal cancer in utero. Compared with unexposed fetuses, children exposed in utero had no higher overall mortality, adjusted hazard ratio 0.8 (95% CI, 0.4 to 1.5), nor increased risk of congenital malformations, overall somatic or psychiatric disease. During the period 2002-2018, of 378 (0.03%) children exposed to cancer in utero, 42 (12.5%) were exposed to chemotherapy. Among these 42 children, in utero exposure to chemotherapy was not associated with selected somatic diseases nor to congenital malformations when compared with in utero exposure to maternal cancer without chemotherapy. CONCLUSION Overall, findings did not indicate excess risk of mortality or severe morbidity among children exposed to cancer in utero. Fetal exposure to chemotherapy was not associated with adverse health outcomes in childhood.
Objectives. To investigate the obstetrical management of cancer in pregnancy and to determine adverse pregnancy and neonatal outcomes. Design. A register-based nationwide historical prospective cohort study. Setting and population. We assessed all pregnancies (N = 4,071,848) in Denmark from 1 January 1973 to 31 December 2018. Methods. We linked data on maternal cancer, obstetrical, and neonatal outcomes. Exposure was defined as pregnancies exposed to maternal cancer (n = 1,068). The control group comprised pregnancies without cancer. The groups were compared using logistic regression analysis and adjusted for potential confounders. Main outcome Measures. The primary outcome was the iatrogenic termination of the pregnancy (induced abortions/labor induction or elective caesarean section). Secondary outcomes were adverse neonatal outcomes. Results. More women with cancer in pregnancy, as compared to the control group, experienced first-trimester induced abortion; adjusted odds ratio (aOR) 3.7 (95% CI 2.8─4.7), second-trimester abortion; aOR 9.0 (6.4─12.6), iatrogenic preterm delivery; aOR 10.9 (8.1─14.7), and iatrogenic delivery below 32 gestational weeks; aOR 16.5 (8.5─32.2). Neonates born to mothers with cancer in pregnancy had a higher risk of respiratory distress syndrome; aOR 1.5 (1.2─2.0), but not of low birth weight; aOR 0.6 (0.4─0.8), admission to neonatal intensive care unit more than seven days; aOR 1.4 (1.1─1.9), neonatal infection; aOR 0.9 (0.5─1.5) nor neonatal mortality; aOR1.3 (0.6─2.6). Conclusion. Cancer in pregnancy implies an increased risk of iatrogenic termination of pregnancy and iatrogenic premature birth. Neonates born to mothers with cancer in pregnancy had no increased risk of severe adverse neonatal outcomes.
Fetal anti-Müllerian hormone (AMH) is responsible for normal male sexual differentiation, and circulating AMH is used as a marker of testicular tissue in newborns with disorders of sex development. Little is known about the mechanism of action in postnatal life. A recent genome wide association study (GWAS) reported genetic variation of AMH affecting AMH levels in young men. This study investigated the effect of genetic variation of AMH and AMH type II receptor (AMHR2) (AMHrs10407022 T>G and AMHR2rs11170547 C>T) on circulating reproductive hormone levels and pubertal onset in boys and girls.This study is a combined longitudinal and cross-sectional study in healthy Danish boys and girls from the general population. We included 658 boys aged 5.8-19.8 years and 320 girls aged 5.6-16.5 years. The main outcome measures were genotyping of AMH and AMHR2, pubertal staging and serum levels of reproductive hormones.AMHrs10407022T>G was associated with higher serum levels of AMH in prepubertal boys (TT: 575 pmol/L vs TG: 633 pmol/L vs GG: 837 pmol/L, P = 0.002) and adolescents (TT: 44 pmol/L vs TG: 58 pmol/L vs GG: 79 pmol/L, P < 0.001). Adolescent boys carrying the genetic variation also had lower levels of LH (TT: 3.0 IU/L vs TG: 2.8 IU/L vs GG: 1.8 IU/L, P = 0.012). Hormone levels in girls and pubertal onset in either sex did not seem to be profoundly affected by the genotypes.Our findings support recent GWAS results in young adults and expand our understanding of genetic variation affecting AMH levels even in boys prior to the pubertal decline of circulating AMH.
Abstract Cancer in pregnancy, defined as a cancer diagnosed during pregnancy, is a rare but severe condition presenting both clinical and ethical challenges. During the last two decades a paradigm shift has occurred towards recommending similar staging and treatment regimens of pregnant and non‐pregnant cancer patients. This strategy is a result of an increasing number of reassuring reports on chemotherapy treatment in pregnancy after the first trimester. The management of cancer in pregnancy should be managed in a multidisciplinary team where staging, oncological treatment, social and mental care, timing of delivery, and follow‐up of the infant should be planned. Due to the rarity, centralization is recommended to allow experience accumulation. Furthermore, national and international advisory boards are supportive when there is a lack of expertise.
Aortico-left ventricular tunnel (ALVT) is a rare congenital heart malformation representing approximately 0.001% of all congenital cardiac malformations (Okoroma EO et al. J Thorac Cardiovasc Surg. 1976; 71: 238–44). ALVT was first described as an abnormal communication between the ascending aorta and the left ventricle (Levy MJ et al. Circulation 1963; 27: 841–53). The tunnel begins above the sinus of Valsalva near the right coronary ostium and ends in the left ventricle below the right aortic cusp. The embryological basis is unknown. Diagnosis can be made by fetal echocardiography. Possible features of the lesion during fetal life include a dilated left ventricle, aortic regurgitation and a dilated ascending aorta. Postnatal treatment is early surgical patch closure of the defect. A good long-term outcome postoperatively is reported. However, the outcome is highly dependent on the antenatal presence of heart failure and hydrops (Singh A et al. Pediatr Cardiol 2011; 32: 822–5). The course of an untreated large ALVT is progressive heart failure leading to death. We present two second trimester cases with signs of severe heart failure due to ALVT which were diagnosed by autopsy.
To investigate the obstetrical management of cancer in pregnancy and to determine adverse pregnancy and neonatal outcomes.A nationwide cohort study.We included all pregnancies (n = 4 071 848) in Denmark from 1 January 1973 to 31 December 2018.Exposure was defined as pregnancies exposed to maternal cancer (n = 1068). The control group comprised pregnancies without cancer. The groups were compared using logistic regression analysis and adjusted for potential confounders.The outcomes were induced abortion, preterm birth and adverse neonatal outcomes.More women with cancer in pregnancy, as compared with the control group, experienced induced abortion (24.8% vs. 20.0%); first-trimester induced abortion adjusted odds ratio (aOR) 3.5 (95% confidence interval [CI] 2.7-4.5), second-trimester induced abortion; aOR 8.8 (95% CI 6.3-12.3), planned preterm birth (11.8% vs. 1.3%); aOR 10.8 (95% CI 8.0-14.6) and planned preterm birth at <32 gestational weeks; aOR 16.3 (95% CI 8.3-31.7). Neonates born to mothers with cancer in pregnancy had a higher risk of respiratory distress syndrome; aOR 3.5 (95% CI 2.8-4.4), low birthweight; aOR 3.8 (95% CI 3.1-4.8), admission to neonatal intensive care unit for >7 days; aOR 5.1 (95% CI 3.9-6.6), neonatal infection; aOR 1.8 (95% CI1.1-3.1) and neonatal mortality; aOR 4.7 (95% CI 2.7-8.2), but not of SGA; aOR 1.0 (95% CI 0.6-1.5) and malformations; 1.2 (95% CI 0.9-1.7).Cancer in pregnancy increases the risk of induced abortion and planned premature birth. Neonates born to mothers with cancer in pregnancy had an increased risk of neonatal morbidity and mortality, presumably due to prematurity.Cancer in pregnancy is associated with an increased risk of premature birth leading to adverse neonatal outcomes.
Objective To investigate if cancer in pregnancy causes a higher risk of venous thromboembolism (VTE) during pregnancy and postpartum compared with pregnant women without cancer. Design A historical prospective cohort study using data from nationwide registries. Setting and population We assessed all pregnancies in Denmark between 1 January 1977 and 31 December 2017. Methods We linked information concerning cancer diagnosis, pregnancy and VTE diagnosis and potential confounders. Event rates of VTE for women with pre‐pregnancy cancer, cancer in pregnancy and without cancer were calculated per 10 000 pregnancies and compared using logistic regression analysis. Main outcome measures Occurrence of VTE during pregnancy or the postpartum period. Results A total of 3 581 214 pregnancies were included in the study and we found 1330 women with cancer in pregnancy. In pregnant women with cancer, the event rate of VTE was 75.2 per 10 000 pregnancies compared with 10.7 per 10 000 pregnancies in the no cancer group. The findings correspond to an increased adjusted odds ratio of 6.50 (95% CI3.5–12.1) in the cancer in pregnancy group in comparison with the no cancer group. Conclusions Women with cancer in pregnancy have a markedly higher risk of pregnancy‐associated VTE compared with women without cancer. In pregnancy‐related VTE risk assessment, the presence of cancer alone may be sufficient to indicate thromboprophylaxis. Tweetable abstract Cancer in pregnancy increases the risk of VTE during pregnancy and the postpartum period.
