Non-cardiac birth defects and long-term risk of cardiovascular hospitalisation.

BACKGROUND: Patients with heart defects are at risk of developing cardiovascular disease. Our objective was to determine if non-cardiac birth defects are associated with the risk of cardiovascular hospitalisation. METHODS: We conducted a longitudinal cohort study of 1 451 409 parous women in Quebec, Canada. We compared patients with cardiac and non-cardiac birth defects of the urinary, central nervous and other systems against patients without defects between 1989 and 2022. The main outcome was hospitalisation for coronary artery disease, ischaemic stroke and other cardiovascular outcomes during 33 years of follow-up. We computed cardiovascular hospitalisation rates and used Cox proportional hazards regression models to measure the association (HR; 95% CI) between non-cardiac defects and later risk of cardiovascular hospitalisation, adjusted for patient characteristics. RESULTS: Women with any birth defect had a higher rate of cardiovascular hospitalisation than women without defects (7.0 vs 3.3 per 1000 person-years). Non-cardiac defects overall were associated with 1.61 times the risk of cardiovascular hospitalisation over time, compared with no defect (95% CI 1.56 to 1.66). Isolated urinary (HR 3.93, 95% CI 3.65 to 4.23), central nervous system (HR 3.33, 95% CI 2.94 to 3.76) and digestive defects (HR 2.39, 95% CI 2.16 to 2.65) were associated with the greatest risk of cardiovascular hospitalisation. These anomalies were associated with cardiovascular hospitalisation whether they presented alone or clustered with other defects. Nevertheless, heart defects were associated with the greatest risk of cardiovascular hospitalisation (HR 10.30, 95% CI 9.86 to 10.75). CONCLUSION: The findings suggest that both cardiac and non-cardiac birth defects are associated with an increased risk of developing cardiovascular disease among parous women.

Congenital anomalies during Covid-19: artifact of surveillance or a real TORCH?

Infections in the first trimester of pregnancy can be teratogenic, but the possibility that Covid-19 could lead to birth defects is unclear. We examined whether SARS-CoV-2 infection during pregnancy or exposure to pandemic conditions were associated with the risk of congenital anomalies. We carried out a retrospective study of 420,222 neonates born in Quebec, Canada in two time periods: prepandemic (January 1, 2017 to March 12, 2020) vs. pandemic (March 13, 2020 to March 31, 2022). We classified pandemic births as early (first trimester completed before the pandemic) or late (first trimester during the pandemic), and identified patients with SARS-CoV-2 infections during pregnancy. We applied (1) adjusted log-binomial regression models to assess the association between SARS-CoV-2 infection and congenital anomalies, and (2) autoregressive interrupted time series regression to analyze temporal trends in the monthly number of defects in all patients regardless of infection. In total, 29,263 newborns (7.0%) had a congenital anomaly. First trimester SARS-CoV-2 infections were not associated with a greater risk of birth defects compared with no infection (RR 1.07, 95% CI 0.59-1.95). However, births during the late pandemic period were more likely to be diagnosed with congenital microcephaly compared with prepandemic births (RR 1.44, 95% CI 1.21-1.71). Interrupted time series analysis confirmed that the frequency of microcephaly increased during the late pandemic period, whereas other anomalies did not. We conclude that Covid-19 is likely not teratogenic, but enhanced surveillance of anomalies among late pandemic births may have heightened the detection of infants with microcephaly.

Multisystem inflammatory syndrome in 1.2 million children: longitudinal cohort study of risk factors.

BACKGROUND: We identified patient characteristics associated with an increased risk of developing MIS-C. METHODS: We conducted a longitudinal cohort study of 1,195,327 patients aged 0-19 years between 2006 and 2021, including the first two waves of the pandemic (February 25-August 22, 2020 and August 23, 2020-March 31, 2021). Exposures included prepandemic morbidity, birth outcomes, and family history of maternal disorders. Outcomes included MIS-C, Kawasaki disease, and other Covid-19 complications during the pandemic. We calculated risk ratios (RRs) and 95% confidence intervals (CIs) for the association between patient exposures and these outcomes using log-binomial regression models adjusted for potential confounders. RESULTS: Among 1,195,327 children, 84 developed MIS-C, 107 Kawasaki disease, and 330 other Covid-19 complications during the first year of the pandemic. Prepandemic hospitalizations for metabolic disorders (RR 11.3, 95% CI 5.61-22.6), atopic conditions (RR 3.34, 95% CI 1.60-6.97), and cancer (RR 8.11, 95% CI 1.13-58.3) were strongly associated with the risk of MIS-C, compared with no exposure. These same exposures were also associated with Kawasaki disease and other Covid-19 complications. However, birth characteristics and history of maternal morbidity were not associated with MIS-C development. CONCLUSIONS: Children with pre-existing morbidity have a considerably elevated risk of MIS-C. IMPACT: Morbidities that predispose children to multisystem inflammatory syndrome (MIS-C) are unclear. In this study, prepandemic hospitalizations for metabolic disorders, atopic conditions, and cancer were associated with an elevated risk of MIS-C. Birth characteristics and family history of maternal morbidity were not, however, associated with MIS-C. Pediatric morbidities may play a greater role in MIS-C onset than maternal or perinatal characteristics, and may help clinicians better recognize children at risk for this complication.

Impact of Covid-19 on risk of severe maternal morbidity.

BACKGROUND: We examined the risk of severe life-threatening morbidity in pregnant patients with Covid-19 infection. METHODS: We conducted a population-based study of 162,576 pregnancies between March 2020 and March 2022 in Quebec, Canada. The main exposure was Covid-19 infection, including the severity, period of infection (antepartum, peripartum), and circulating variant (wildtype, alpha, delta, omicron). The outcome was severe maternal morbidity during pregnancy up to 42 days postpartum. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association between Covid-19 infection and severe maternal morbidity using adjusted log-binomial regression models. RESULTS: Covid-19 infection was associated with twice the risk of severe maternal morbidity compared with no infection (RR 2.02, 95% CI 1.76-2.31). Risks were elevated for acute renal failure (RR 3.01, 95% CI 1.79-5.06), embolism, shock, sepsis, and disseminated intravascular coagulation (RR 1.35, 95% CI 0.95-1.93), and severe hemorrhage (RR 1.49, 95% CI 1.09-2.04). Severe antepartum (RR 13.60, 95% CI 10.72-17.26) and peripartum infections (RR 20.93, 95% CI 17.11-25.60) were strongly associated with severe maternal morbidity. Mild antepartum infections also increased the risk, but to a lesser magnitude (RR 3.43, 95% CI 2.42-4.86). Risk of severe maternal morbidity was around 3 times greater during circulation of wildtype and the alpha and delta variants, but only 1.2 times greater during omicron. CONCLUSIONS: Covid-19 infection during pregnancy increases risk of life-threatening maternal morbidity, including renal, embolic, and hemorrhagic complications. Severe Covid-19 infection with any variant in the antepartum or peripartum periods all increase the risk of severe maternal morbidity.

Risk of Cardiovascular Disease in Women With a History of Hyperemesis Gravidarum, With and Without Preeclampsia.

Background Hyperemesis gravidarum is associated with preeclampsia, but it is unclear whether hyperemesis gravidarum is a risk factor for cardiovascular disease. We assessed the long-term risk of cardiovascular disease in women who experienced hyperemesis gravidarum with or without preeclampsia. Methods and Results We analyzed a longitudinal cohort of 1 413 166 pregnant women in Quebec between 1989 and 2021. Women were followed from their first pregnancy up to 3 decades later. We computed hazard ratios (HRs) and 95% CIs for the association of hyperemesis gravidarum, preeclampsia, or both conditions with subsequent risk of cardiovascular hospitalization using Cox regression models adjusted for baseline characteristics. Among 1 413 166 women, 16 288 (1.2%) had hyperemesis gravidarum only, 69 645 (4.9%) preeclampsia only, and 1103 (0.08%) had both conditions. After 32 years of follow-up, cardiovascular disease incidence was 17.7 per 100 women with hyperemesis gravidarum only, 28.2 per 100 women with preeclampsia only, 30.9 per 100 women with both exposures, and 14.0 per 100 women with neither exposure. Compared with no exposure, women with both hyperemesis and preeclampsia had the greatest risk of cardiovascular hospitalization (HR, 3.54 [95% CI, 3.03-4.14]), followed by women with preeclampsia only (HR, 2.58 [95% CI, 2.51-2.64]) and hyperemesis only (HR, 1.46 [95% CI, 1.38-1.54]). Having both hyperemesis gravidarum and preeclampsia was strongly associated with valve disease (HR, 3.38 [95% CI, 1.69-6.75]), heart failure (HR, 3.43 [95% CI, 1.79-6.59]), and cardiomyopathy (HR, 4.17 [95% CI, 1.99-8.76]). Conclusions Hyperemesis gravidarum is associated with the development of cardiovascular disease, whether preeclampsia is present or not.

Shifting age of child eating disorder hospitalizations during the Covid-19 pandemic.

BACKGROUND: We studied the effect of the Covid-19 pandemic on child eating disorder hospitalizations in Quebec, Canada. Quebec had one of the strictest lockdown measures targeting young people in North America. METHODS: We analyzed eating disorder hospitalizations in children aged 10-19 years before and during the pandemic. We used interrupted time series regression to assess trends in the monthly number of hospitalizations for anorexia nervosa, bulimia nervosa, and other eating disorders before the pandemic (April 2006 to February 2020), and during the first (March to August 2020) and second waves (September 2020 to March 2021). We determined the types of eating disorders requiring hospital treatment and identified the age, sex and socioeconomic subgroups that were most affected. RESULTS: Hospitalization rates for eating disorders increased during the first (6.5 per 10,000) and second waves (12.8 per 10,000) compared with the period before the pandemic (5.8 per 10,000). The increase occurred for anorexia nervosa as well as other types of eating disorders. The number of girls and boys aged 10-14 years admitted for eating disorders increased during wave 1. Wave 2 triggered an increase in eating disorder admissions among girls aged 15-19 years. Hospitalization rates increased earlier for advantaged than disadvantaged youth. CONCLUSIONS: The Covid-19 pandemic affected hospitalizations for anorexia nervosa as well as other eating disorders, beginning with girls aged 10-14 years during wave 1, followed by girls aged 15-19 years during wave 2. Boys aged 10-14 years were also affected, as well as both advantaged and disadvantaged youth.

Suicide Attempts in Children Aged 10-14 Years During the First Year of the COVID-19 Pandemic.

PURPOSE: To determine if suicide attempts increased during the first year of the pandemic among young adolescents in Quebec, Canada. METHODS: We analyzed children aged 10-14 years who were hospitalized for a suicide attempt between January 2000 and March 2021. We calculated age-specific and sex-specific suicide attempt rates and the proportion of hospitalizations for suicide attempts before and during the pandemic and compared rates with patients aged 15-19 years. We used interrupted time series regression to measure changes in rates during the first (March 2020 to August 2020) and second (September 2020 to March 2021) waves and difference-in-difference analysis to determine if the pandemic had a greater impact on girls than boys. RESULTS: Suicide attempt rates decreased for children aged 10-14 years during the first wave. However, rates increased sharply during the second wave for girls, without changing for boys. Girls aged 10-14 years had an excess of 5.1 suicide attempts per 10,000 at the start of wave 2, with rates continuing to increase by 0.6 per 10,000 every month thereafter. Compared with the prepandemic period, the increase in the proportion of girls aged 10-14 years hospitalized for a suicide attempt was 2.2% greater than that of boys during wave 2. The pattern seen in girls aged 10-14 years was not present in girls aged 15-19 years. DISCUSSION: Hospitalizations for suicide attempts among girls aged 10-14 years increased considerably during the second wave of the pandemic, compared with boys and older girls. Young adolescent girls may benefit from screening and targeted interventions to address suicidal behavior.

Impact of Covid-19 on rates of gestational diabetes in a North American pandemic epicenter.

AIMS: We assessed the impact of Covid-19 on gestational diabetes rates in Quebec, the pandemic epicenter of Canada. METHODS: We conducted a population-based study of 569,686 deliveries in Quebec between 2014 and 2021. We measured gestational diabetes rates in wave 1 (March 1, 2020-August 22, 2020) and wave 2 (August 23, 2020-March 31, 2021), compared with the prepandemic period. We used interrupted time series regression to assess changes in gestational diabetes rates during each wave, and log-binomial regression models to estimate adjusted risk ratios (RR) and 95% confidence intervals (CI) for the association of the pandemic with gestational diabetes. We identified the types of patients that contributed to the change in gestational diabetes rates using Kitagawa's decomposition. RESULTS: Gestational diabetes rates were higher during the first (13.2 per 100 deliveries) and second waves (14.3 per 100 deliveries) than during the prepandemic period (12.4 per 100 deliveries). Risk of gestational diabetes increased both in wave 1 (RR 1.05, 95% CI 1.02-1.09) and wave 2 (RR 1.14, 95% CI 1.10-1.18), compared with the prepandemic period. However, most of the increase in gestational diabetes rates was driven by low-risk women without Covid-19 infections who were socioeconomically advantaged, had no comorbidity, and were 25-34 years of age. CONCLUSIONS: Gestational diabetes rates increased during the pandemic, mainly among women traditionally at low risk of hyperglycemia who did not have Covid-19 infections. Sudden widespread changes in screening or lifestyle can have a large impact on gestational diabetes rates in a population.

Multisystem inflammatory syndrome in adults: Comparison with other inflammatory conditions during the Covid-19 pandemic.

BACKGROUND: Multisystem inflammatory syndrome in adults (MIS-A) is an increasingly recognized complication of Covid-19. We assessed risk factors, clinical characteristics, and outcomes of patients with MIS-A compared with other inflammatory conditions. METHODS: We analyzed a cohort of patients ≥21 years hospitalized with MIS-A in Quebec, Canada between February 2020 and March 2021. We included comparison groups that share symptomatology or pathophysiology with MIS-A, including Kawasaki disease, toxic shock syndrome, and other Covid-19 complications. We examined characteristics of men and women at admission, and identified preexisting factors associated with MIS-A through odds ratios (OR) and 95% confidence intervals (CI) from adjusted logistic regression models. RESULTS: Among 22,251 patients in this study, 52 had MIS-A, 90 Kawasaki disease, 500 toxic shock syndrome, and 21,609 other Covid-19 complications. MIS-A was associated with an elevated risk of respiratory failure compared with Kawasaki disease (OR 7.22, 95% CI 1.26-41.24), toxic shock syndrome (OR 4.41, 95% CI 1.73-11.23), and other Covid-19 complications (OR 3.03, 95% CI 1.67-5.50). Patients with MIS-A had a greater risk of cardiac involvement, renal failure, and mortality. The data pointed towards sex-specific differences in presentation, with more respiratory involvement in women and cardiac involvement in men compared with patients that had other Covid-19 complications. Except for allergic disorders and cancer, prior medical risk factors were not associated with a greater likelihood of MIS-A. CONCLUSIONS: Patients with MIS-A have an elevated risk of mortality compared with other inflammatory conditions, with women having a predominance of respiratory complications and men cardiovascular complications.

Black-White disparity in severe cardiovascular maternal morbidity: A systematic review and meta-analysis.

BACKGROUND: To synthesize existing evidence on Black-White disparities in the prevalence of severe cardiovascular maternal morbidity. METHODS: We searched MEDLINE, EMBASE, and CINAHL for observational studies published before July 31, 2021 that compared the risk of severe cardiovascular maternal morbidity between Black and White women. The outcome was severe cardiovascular maternal morbidity, including acute myocardial infarction, peripartum cardiomyopathy, and stroke during pregnancy, delivery, or postpartum. We extracted relevant information including adjusted and unadjusted effect estimates. We used random-effects models to estimate the pooled association between race and severe cardiovascular maternal morbidity, presented as odds ratios with 95% confidence intervals for the comparison of Black women relative to White women. RESULTS: We included 18 studies that met the eligibility criteria for systematic review and meta-analysis. All studies were conducted in the United States and included a total of 7,656,876 Black women and 26,412,600 White women. Compared with White women, Black women had an increased risk of any severe cardiovascular maternal morbidity (adjusted odds ratio, 1.90; 95% confidence interval, 1.54-2.33). Black women were at risk of acute myocardial infarction (adjusted odds ratio, 1.38; 95% confidence interval, 1.14-1.68), peripartum cardiomyopathy (adjusted odds ratio, 1.71; 95% confidence interval, 1.51-1.94), and stroke (adjusted odds ratio, 2.13; 95% confidence interval, 1.39-3.26). CONCLUSIONS: Black women have a considerably higher risk of severe cardiovascular maternal morbidity than White women, including acute myocardial infarction, peripartum cardiomyopathy, and stroke. Reducing inequality in adverse cardiovascular outcomes of pregnancy between Black and White women should be prioritized.

Hyperemesis Gravidarum and the Potential for Cancer: A Longitudinal Cohort Study over Three Decades.

BACKGROUND: Our objective was to assess whether hyperemesis gravidarum is associated with the risk of endodermal, mesodermal, and ectodermal human chorionic gonadotropin (hCG) receptor+ cancer in women. METHODS: We performed a longitudinal cohort study of 1,343,040 women who were pregnant between 1989 and 2019 in Quebec, Canada. We identified women with and without hyperemesis gravidarum and followed them over time to capture incident cancers, grouped by embryonic germ cell layer of origin and organ hCG receptor positivity. We used time-varying Cox regression to model hazard ratios (HR) and 95% confidence intervals (CI) for the association between hyperemesis gravidarum and cancer onset, adjusted for maternal age, comorbidity, multiple gestation, fetal congenital anomaly, socioeconomic deprivation, and time period. RESULTS: Women with hyperemesis gravidarum had a greater risk of endodermal cancer compared with no hyperemesis gravidarum (5.8 vs. 4.8 per 10,000 person-years; HR, 1.36; 95% CI, 1.17-1.57), but not mesodermal or ectodermal cancer. Severe hyperemesis with metabolic disturbance was more strongly associated with cancer from the endodermal germ layer (HR, 1.97; 95% CI, 1.51-2.58). The association between hyperemesis gravidarum and endodermal cancer was driven by bladder (HR, 2.49; 95% CI, 1.37-4.53), colorectal (HR, 1.41; 95% CI, 1.08-1.84), and thyroid (HR, 1.43; 95% CI, 1.09-1.64) cancer. CONCLUSIONS: Women with hyperemesis gravidarum have an increased risk of cancers arising from the endodermal germ cell layer, particularly bladder, colorectal, and thyroid cancers. IMPACT: Future studies identifying the pathways linking hyperemesis gravidarum with endodermal tumors may help improve the detection and management of cancer in women.

Black-White Inequality in Outcomes of In Vitro Fertilization: a Systematic Review and Meta-analysis.

This study aims to systematically review disparities in outcomes of in vitro fertilization between Black and White patients. We searched CINAHL, Cochrane Library, EMBASE, Global Health, PsycINFO, PubMed, and Web of Science for observational studies published before August 2021. Outcomes included implantation, clinical pregnancy, spontaneous abortion, and live birth following in vitro fertilization in Black versus White patients. We used random-effects models for meta-analysis and the Mantel-Haenszel method to calculate unadjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between race and in vitro fertilization outcomes, comparing Black relative to White patients. We used the generic inverse variance method to calculate adjusted ORs. Nine observational studies met eligibility criteria, including 696 Black and 7,458 White patients. All were retrospective studies of US cohorts. In unadjusted meta-analyses, Black patients had a greater likelihood of spontaneous abortion (OR 2.08, 95% CI 1.59-2.71) and lower likelihood of live birth (OR 0.67, 95% CI 0.47-0.95) compared with White patients but no difference in implantation (OR 0.95, 95% CI 0.32-2.77) or clinical pregnancy (OR 0.78, 95% CI 0.54-1.12). In adjusted meta-analyses, Black patients had lower odds of live birth (OR 0.57, 95% CI 0.43-0.75) and no difference in clinical pregnancy (OR 0.87, 95% CI 0.51-1.48). This meta-analysis suggests that in vitro fertilization services achieve similar pregnancy rates in Black and White patients. However, Black patients have more spontaneous abortions and fewer live births, suggesting there may be disparities in the quality of achieved pregnancies or other factors associated with pregnancy loss. Systematic review registration: PROSPERO (ID CRD42021256250).

Varying Impact of Gestational Diabetes Mellitus on Incidence of Childhood Cancers: An Age-Stratified Retrospective Cohort Study.

OBJECTIVE: We studied the association between gestational diabetes mellitus and early versus late childhood cancer. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study of 1 million children born between 2006 and 2019 in Quebec, Canada. We identified children who were exposed to gestational diabetes mellitus in utero and followed them from birth up to 14 years of age to identify new-onset cancers. We estimated hazard ratios (HRs) for the association between gestational diabetes mellitus and childhood cancer using Cox proportional regression models with adjustment for covariates through inverse propensity score weights. RESULTS: A total of 83,626 children (8.2%) were exposed to gestational diabetes mellitus, and 1,702 developed cancer during 7.6 million person-years of follow-up. Children exposed to gestational diabetes mellitus had a higher risk of any cancer (HR 1.19, 95% CI 1.01-1.40), with signals present for blood cancer (HR 1.27, 95% CI 0.92-1.76) and solid tumors (HR 1.14, 95% CI 0.94-1.40). The association between gestational diabetes mellitus and cancer was strongest early in life and decreased with age. Gestational diabetes mellitus was associated with 1.47 times the risk of any cancer (95% CI 1.21-1.79), 1.44 times the risk of solid cancer (95% CI 1.12-1.87), and 1.61 times the risk of blood cancer (95% CI 1.09-2.36) in children age <2 years. Gestational diabetes mellitus was not significantly associated with blood or solid cancers after 2 years of age, and all associations disappeared after 6 years. CONCLUSIONS: Hyperglycemia may be carcinogenic in utero and may be a novel risk factor for early childhood cancer.

Maternal autoimmune disease and risk of hospitalization for autoimmune disease, allergy, and cancer in offspring.

BACKGROUND: Children whose mothers have autoimmune disease may be at risk of developing immune-mediated disorders. We assessed the association between maternal autoimmune disease and risk of autoimmune disease, allergy, and cancer in offspring. METHODS: We analyzed a cohort of 1,011,623 children born in Canada between 2006 and 2019. We identified mothers who had autoimmune diseases and assessed hospitalizations for autoimmune disease, allergy, and cancer in offspring between birth and 14 years of age. We estimated hazard ratios (HR) for the association of maternal autoimmune disease with child hospitalization in adjusted Cox regression models. We used within-sibling analysis to control for genetic and environmental confounders. RESULTS: A total of 20,354 children (2.0%) had mothers with an autoimmune disease. Compared with no autoimmune disease, maternal autoimmune disease was associated with the risk of childhood hospitalization for autoimmune disease (HR 1.96, 95% CI 1.66-2.31) and allergy (HR 1.30, 95% CI 1.21-1.40), but was not significantly associated with cancer (HR 1.31, 95% CI 0.96-1.80). Type 1 diabetes, celiac disease, inflammatory arthritis, and systemic lupus erythematosus were among specific maternal autoimmune diseases most strongly associated with childhood hospitalization for autoimmune disease and allergy. The associations disappeared after controlling for genetic and environmental confounders in the within-sibling analysis. CONCLUSIONS: Maternal autoimmune disease is associated with an increased risk of autoimmune disease and allergy hospitalization in offspring, but the relationship appears to be confounded by genetic and environmental factors. Prenatal exposure to immunologic or pharmacologic products is not likely a direct cause of immune-mediated disease in children.

Matched cohort study of hospitalization in children who have siblings with cancer.

BACKGROUND: Health outcomes of children in families affected by cancer are poorly understood. The authors assessed the risk of hospitalization in children who have a sibling with cancer. METHODS: This was a longitudinal cohort study in which 1600 children who had a sibling with cancer were matched to 32,000 children who had unaffected siblings in Quebec, Canada, from 2006 to 2020. The exposure of interest was having a sibling with cancer. Outcomes included hospitalization for pneumonia, asthma, fracture, and other morbidities any time after the sibling was diagnosed with cancer. The children were followed over time, and Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the impact of having a sibling with cancer on the risk of hospitalization before age 14 years, adjusted for patient characteristics. RESULTS: Children who had a sibling with cancer had an increased risk of hospitalization compared with unaffected children (HR, 1.15; 95% CI, 1.02-1.29). Conditions associated with a greater risk of hospitalization included pneumonia, hemangioma, other skin conditions, sleep apnea, and inflammatory bowel disease. The risk of hospitalization was greatest for children whose older sibling had cancer (HR, 1.16; 95% CI, 1.01-1.32) and for children whose sibling had hematopoietic cancer (HR, 1.22; 95% CI, 1.01-1.48). CONCLUSIONS: Children who have a sibling with cancer are at risk of hospitalization for conditions such as pneumonia, inflammatory bowel disease, and other morbidities. Families affected by childhood cancer may benefit from additional support to facilitate care for all children in the family. LAY SUMMARY: Little is known about the health of children who have a brother or sister with cancer. The authors studied the types of hospitalization experienced by children who have siblings with cancer. The results indicated that having a sibling with cancer increased the chance of being hospitalized for pneumonia and other conditions that could have been preventable. The results also indicated that children who had an older sibling with cancer or a sibling with blood cancer had a greater chance of being hospitalized. The findings highlight the importance of providing timely care for children in families affected by childhood cancer.

Association of first trimester anaesthesia with risk of congenital heart defects in offspring.

BACKGROUND: A substantial number of pregnant women require anaesthesia for non-obstetric surgery, but the risk to fetal heart development is unknown. We assessed the relationship between first trimester anaesthesia and risk of congenital heart defects in offspring. METHODS: We conducted a longitudinal cohort study of 2 095 300 pregnancies resulting in live births in hospitals of Quebec, Canada, between 1990 and 2016. We identified women who received general or local/regional anaesthesia in the first trimester, including anaesthesia between 3 and 8 weeks post-conception, the critical weeks of fetal cardiogenesis. The main outcome measures were critical and non-critical heart defects in offspring. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association of first trimester anaesthesia with congenital heart defects, using log-binomial regression models adjusted for maternal characteristics. RESULTS: There were 107.3 congenital heart defects per 10 000 infants exposed to anaesthesia, compared with 87.2 per 10 000 unexposed infants. Anaesthesia between 3 and 8 weeks post-conception was associated with 1.50 times the risk of congenital heart defects (95% CI 1.11-2.03), compared with no anaesthesia. Anaesthesia between 5 and 6 weeks post-conception was associated with 1.84 times the risk (95% CI 1.10-3.08). Associations were driven mostly by general anaesthesia, which was associated with 2.49 times the risk between weeks 5 and 6 post-conception (95% CI 1.40-4.44). CONCLUSIONS: General anaesthesia during critical periods of fetal heart development may increase the risk of congenital heart defects. Further research is needed to confirm that anaesthetic agents are cardiac teratogens.

Premature mortality after pregnancy loss: Trends at 1, 5, 10 years, and beyond.

OBJECTIVE: Little is known on the long-term risk of mortality following pregnancy loss. We assessed risks of premature mortality up to three decades after miscarriage, induced abortion, ectopic or molar pregnancy, and stillbirth relative to live birth. STUDY DESIGN: We carried out a longitudinal cohort study of 1,293,640 pregnant women with 18,896,737 person-years of follow-up in Quebec, Canada, from 1989 to 2018. We followed the women up to 29 years after their last pregnancy event to determine the time and cause of future in-hospital deaths before age 75 years. We used adjusted Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of miscarriage, induced abortion, ectopic pregnancy, molar pregnancy, and stillbirth with premature mortality, compared with live birth. RESULTS: Premature mortality rates were higher for most types of pregnancy loss than live birth. Compared with live birth, pregnancy loss was associated with an elevated risk of premature mortality (HRmiscarriage 1.48, 95% CI 1.33, 1.65; HRinduced abortion 1.50, 95% CI 1.39, 1.62; HRectopic 1.55, 95% CI 1.35, 1.79; and HRstillbirth 1.68, 95%. CI 1.17, 2.41). Molar pregnancy was not associated with premature mortality (HR 0.87, 95% CI 0.33, 2.32). Miscarriage and induced abortion were associated with most causes of death, whereas ectopic pregnancy was associated with cardiovascular (HR 2.18, 95 % CI 1.39, 3.42), cancer (HR 1.38, 95 % CI 1.11, 1.73), and suicide-related mortality (HR 4.94, 95 % CI 2.29, 10.68). Stillbirth was associated with cardiovascular mortality (HR 4.91, 95 % CI 2.33, 10.36). CONCLUSION: Pregnancy loss is associated with an elevated risk of premature mortality up to three decades later, particularly cardiovascular, cancer, and suicide-related deaths.