Complex chronic conditions among children born to women with schizophrenia.

PURPOSE: Maternal schizophrenia is linked to complications in offspring near the time of birth. Whether there is also a higher future risk of the child having a complex chronic condition (CCC) - a pediatric condition affecting any bodily system expected to last at least 12 months that is severe enough to require specialty care and/or a period of hospitalization - is not known. METHODS: In this population-based health administrative data cohort study (Ontario, Canada, 1995-2018), the risk for CCC was compared in 5066 children of women with schizophrenia (the exposed) vs. 2,939,320 unexposed children. Adjusted hazard ratios (aHR) were generated for occurrence of any CCC, by CCC category, and stratified by child sex, and child prematurity. RESULTS: CCC was more frequent in the exposed (7.7 per 1000 person-years [268 children]) than unexposed (4.2 per 100 person-years [124,452 children]) - an aHR of 1.25 (95% CI 1.10-1.41). aHRs were notably higher in 5 of 9 CCC categories: neuromuscular (1.73, 1.28-2.33), cardiovascular (1.94, 1.64-2.29), respiratory (1.83, 1.32-2.54), hematology/immunodeficiency (2.24, 1.24-4.05) and other congenital or genetic defect (1.59, 1.16-2.17). The aHR for CCC was more pronounced among boys (1.32, 1.13-1.55) than girls (1.16, 0.96-1.40), and of similar magnitude in term (1.22, 1.05-1.42) and preterm infants (1.18, 0.95-1.46). CONCLUSIONS: The risk for a CCC appears to be higher in children born to women with schizophrenia. This finding introduces opportunities for targeted preconception counselling, optimization of maternal risk factors, and intervention to support a vulnerable parent population who will experience unique challenges caring for a child with CCCs.

Selected medical interventions in women with a deleterious BRCA mutation: a population-based study in British Columbia.

Background: We examined the uptake of risk-reducing interventions, including bilateral mastectomy, risk-reducing salpingo-oophorectomy, oral contraceptive pills, tamoxifen, and raloxifene, for the entire population of women with a deleterious BRCA1 or BRCA2 mutation in the Canadian province of British Columbia. Methods: This retrospective population-based study used data available in British Columbia for all women who, between 1996 and 2014, were tested and found to have a BRCA mutation. Rates of risk-reducing interventions stratified according to the type of BRCA mutation and prior history of breast or gynecologic cancer (ovary, fallopian tube, peritoneal) are presented. Cancers diagnosed in women with a BRCA mutation after disclosure of their mutation status are also presented. Results: The final study cohort consisted of 885 patients with a deleterious BRCA1 (n = 474) or BRCA2 (n = 411) mutation. Of the women with no prior breast cancer, 30.8% carrying a BRCA1 mutation and 28.3% carrying a BRCA2 mutation underwent bilateral mastectomy. Of women with no prior gynecologic cancer, 64.7% carrying a BRCA1 mutation and 62.2% carrying a BRCA2 mutation underwent risk-reducing bilateral salpingo-oophorectomy. Rates of chemoprevention with oral contraceptive pills and tamoxifen or raloxifene were low in all groups. In this cohort, 23 gynecologic and 70 breast cancers were diagnosed after disclosure of BRCA mutation status. Conclusions: Our results suggest reasonable uptake of risk-reducing interventions in high-risk women. To minimize the occurrence of breast and ovarian cancer in women with a BRCA1 or BRCA2 mutation, more attention could be paid to ensuring that affected women receive proper counselling and follow-up.

alpha 1-Adrenoceptors on rabbit aortic smooth muscle cells in culture and in experimental intimal thickening.

1. This study has defined alpha 1-adrenoceptors and their reactivity in rabbit aorta, following removal of the endothelium and formation of a myointimal thickening, and also in smooth muscle cells (SMC) in cell culture which had undergone serial passaging and changes in phenotype. 2. [3H]-prazosin binding to SMC from control aorta, vessels 2 weeks after endothelial denudation and sub-cultured SMC (passage 3-6) was specific (displaceable with 10 mumol/L phentolamine), and of high affinity to a single class of sites (KD range: 71-114 pmol/L). The maximum binding density (Bmax) of alpha 1-adrenoceptors on SMC from the neointima (11,105 +/- 771 sites/cell) was not significantly different to that of control medial SMC (14,014 +/- 2472 sites/cell). However, SMC cultured to passage 6, showed a 2-fold increase in Bmax (30,227 +/- 4349 sites/cell). 3. The production of inositol phosphates (IP1, IP2 and IP3) by SMC following 10 mumol/L phenylephrine was assayed. Both freshly-dispersed aortic SMC and sub-cultured SMC were stimulated to produce increased inositol phosphates by the addition of phenylephrine which was completely inhibited by pre-incubation with 10 mumol/L phentolamine, suggesting that the stimulation was via alpha 1-adrenoceptors. 4. Maximal contractile responses of isolated thoracic and abdominal aortic rings to KCl (100 mmol/L), 5-HT and phenylephrine were unchanged two weeks after endothelial denudation. However, phenylephrine was significantly less potent (2.7-fold) in both areas of the aorta, while the potency of 5-HT was significantly enhanced (2.7-fold) after endothelial denudation only in the abdominal aorta. 5. The decreased sensitivity of the rabbit aorta to alpha 1-adrenoceptor agonists following endothelial denudation and the formation of a myointimal thickening is not due to changes in affinity or density of alpha 1-adrenoceptors. However multiple passaging of SMC in culture leads to an increase in alpha 1-adrenoceptor density. This change can be related to the altered cytodifferentiation of irreversible synthetic state SMC which are similar to those in atherosclerotic lesions.