Risk of congenital anomalies in children who have a sibling with cancer: A matched cohort study.

PURPOSE: We assessed the risk of congenital anomalies in children who have a sibling with cancer. METHODS: We performed a matched cohort study of children born between 2006 and 2022 in Quebec. The exposure was having a sibling with cancer. Exposed children were matched to unexposed children based on sex, number of siblings, birth order, and year. The outcome included heart defects, orofacial clefts, and other anomalies. Using conditional logistic regression, we estimated odds ratios (OR) and 95 % confidence intervals (CI) for the association between having a sibling with cancer and the likelihood of having a congenital anomaly. RESULTS: A total of 2403 children who had a sibling with cancer were matched to 240,257 unexposed children. Congenital anomalies were more frequent in children who had a sibling with cancer compared with unexposed children (10.3 % vs 8.9 %). Overall, having a sibling with cancer was only weakly associated with congenital anomalies (OR 1.18, 95 % CI 1.04-1.35). Exposed children tended to have greater odds of polydactyly/syndactyly (OR 1.89, 95 % CI 1.11-3.21) and urinary defects (OR 1.50, 95 % CI 1.09-2.08) compared with unexposed children. CONCLUSIONS: Children who have a sibling with cancer have an only weakly elevated risk of congenital anomalies.

Underlying Causes of Ethnocultural Inequality in Pregnancy Outcomes: Role of Hospital Proximity.

We evaluated the contribution of place of birth to ethnocultural inequality in pregnancy outcomes. We analyzed a cohort of 1,487,723 births between 1998 and 2019 among minority Anglophones and majority Francophones in Quebec, Canada. We estimated the association (adjusted risk ratio, RR; 95% confidence interval, CI) of language with preterm birth and stillbirth, and incorporated interaction terms to determine the contribution of place of birth and distance traveled. Compared with Francophones, minority Anglophones had a greater risk of preterm birth (RR 1.03; 95% CI 1.01-1.06) and were less likely to deliver farther from home (RR 0.95; 95% CI 0.94-0.95). Anglophones who delivered close to home had a higher risk of preterm birth (RR 1.07; 95% CI 1.04-1.11), whereas Anglophones who delivered farther had a lower risk (RR 0.69; 95% CI 0.64-0.75). Patterns were similar for stillbirth. Ethnocultural inequality in adverse birth outcomes may be influenced by place of birth.

Access to perinatal healthcare in minority Anglophones: Hospital type and birth outcomes.

OBJECTIVES: We assessed the relationship between hospital characteristics and risk of adverse birth outcomes among minority Anglophones in Montreal, Canada. METHODS: The study included 124,670 births among Anglophones in metropolitan Montreal between 1998 and 2019. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between hospital characteristics, including residential proximity to hospitals and language in which medical services are provided, and risks of preterm birth and stillbirth. Models were adjusted for maternal socioeconomic status and other characteristics. RESULTS: In this study, 8% of Anglophones had a preterm birth and 0.4% a stillbirth. Anglophone women who delivered at a farther French hospital had a greater risk of stillbirth (RR 1.67, 95% CI 1.28-2.18) than preterm birth (RR 1.21, 95% CI 1.14-1.30), compared with delivery at hospitals closer to home. In contrast, delivery at a farther English hospital was associated with similar risks of stillbirth (RR 1.36, 95% CI 1.08-1.71) and preterm birth (RR 1.36, 95% CI 1.29-1.44). The greater risk of stillbirth with delivery at a farther French hospital, versus greater risk of preterm birth at a farther English hospital, remained present in analyses stratified by maternal age, education, material deprivation, and region of origin. CONCLUSION: Minority Anglophones in Montreal who travel to a farther French hospital for delivery have a greater risk of stillbirth than Anglophones who travel to a farther English hospital. This novel observation suggests the need to determine if access to perinatal healthcare in a woman's language may help reduce the risk of stillbirth.

Association of Endometriosis and Severe Maternal Morbidity.

OBJECTIVE: To evaluate the association between endometriosis and risk of severe maternal morbidity (SMM). METHODS: We conducted a population-based retrospective cohort study of 2,412,823 deliveries at hospitals in Quebec, Canada, between 1989 and 2019. The exposure was surgically confirmed endometriosis. Patients were classified as having active endometriosis during pregnancy, inactive endometriosis during pregnancy, a diagnosis of endometriosis postpregnancy, or no endometriosis. The outcome was SMM, including by a range of life-threatening maternal conditions during pregnancy or up to 42 days postdelivery. We computed rates of SMM and used log binomial regression to assess the association with endometriosis (risk ratio [RR]; 95% CI), adjusted for maternal characteristics. RESULTS: Severe maternal morbidity occurred in 46.2 of 1,000 patients with endometriosis, compared with 30.7 of 1,000 patients without endometriosis. Relative to no exposure, endometriosis was associated with 1.43 times the risk of SMM (95% CI 1.36-1.51). Patients with endometriosis that was active during pregnancy had a greater risk of SMM (RR 1.93; 95% CI 1.76-2.11). Active endometriosis was associated with the risk of severe preeclampsia and eclampsia, severe hemorrhage, hysterectomy, cardiac complications, embolism, shock, sepsis, and intensive care unit admission. Inactive endometriosis was less strongly associated with these outcomes. CONCLUSION: Pregnant patients with endometriosis, especially active endometriosis, have a greater risk of SMM and may benefit from closer follow-up to prevent severe complications of pregnancy.

Systemic L-ornithine supplementation specifically increases ovarian putrescine levels during ovulation in mice†.

In all mammalian species examined thus far, the ovaries produce a burst of ornithine decarboxylase (ODC) and putrescine during ovulation or after application of human chorionic gonadotropin (hCG). Aged mice have significantly reduced levels of this periovulatory ODC and putrescine rise. Putrescine supplementation, in vitro during oocyte maturation or in mouse drinking water during the periovulatory period, reduces egg aneuploidies and embryo resorption, improving fertility of aged mice. These studies suggest that periovulatory putrescine supplementation may be a simple and effective therapy for reproductive aging for women. However, putrescine supplementation is expected to increase widespread tissue putrescine levels, raising concerns of nonspecific and unwanted side effects. Given that ODC is highly expressed in the ovaries during ovulation but otherwise exhibits low activity in most tissues, we hypothesized that periovulatory supplementation of L-ornithine, the substrate of ODC, might be suitable for delivering putrescine specifically to the ovaries. In this study, we have demonstrated that systemic application of L-ornithine via oral gavage or subcutaneous injection increased ovarian putrescine levels; the increase was restricted to animals that had been injected with hCG. Furthermore, L-ornithine specifically increased ovarian putrescine levels without affecting putrescine levels in any other tissues. However, our attempts to improve fertility of aged mice through L-ornithine supplementation in mouse drinking water produced either no effects (1% L-ornithine) or negative impact on fertility (4% ornithine). Our results suggest that it might not be feasible to achieve fertility-enhancing ovarian putrescine levels via L-ornithine supplementation in drinking water without encountering undesired consequences of high dose of exogenous L-ornithine.