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.

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.

Severe Maternal Morbidity and Mental Health Hospitalizations or Emergency Department Visits.

Importance: Severe maternal morbidity (SMM) can have long-term health consequences for the affected mother. The association between SMM and future maternal mental health conditions has not been well studied. Objective: To assess the association between SMM in the first recorded birth and the risk of hospitalization or emergency department (ED) visits for a mental health condition over a 13-year period. Design, Setting, and Participants: This population-based retrospective cohort study used data from postpartum individuals aged 18 to 55 years with a first hospital delivery between 2008 and 2021 in 11 provinces and territories in Canada, except Québec. Data were analyzed from January to June 2023. Exposure: SMM, defined as a composite of conditions, such as septic shock, severe preeclampsia or eclampsia, severe hemorrhage with intervention, or other complications, occurring after 20 weeks' gestation and up to 42 days after a first delivery. Main Outcomes and Measures: The main outcome was a hospitalization or ED visit for a mental health condition, including mood and anxiety disorders, substance use, schizophrenia, and other psychotic disorder, or suicidality or self-harm event, arising at least 43 days after the first birth hospitalization. Cox regression models generated hazard ratios with 95% CIs, adjusted for baseline maternal comorbidities, maternal age at delivery, income quintile, type of residence, hospital type, and delivery year. Results: Of 2 026 594 individuals with a first hospital delivery, 1 579 392 individuals (mean [SD] age, 30.0 [5.4] years) had complete ED and hospital records and were included in analyses; among these, 35 825 individuals (2.3%) had SMM. Compared with individuals without SMM, those with SMM were older (mean [SD] age, 29.9 [5.4] years vs 30.7 [6.0] years), were more likely to deliver in a teaching tertiary care hospital (40.8% vs 51.1%), and to have preexisting conditions (eg, ≥2 conditions: 1.2% vs 5.3%), gestational diabetes (8.2% vs 11.7%), stillbirth (0.5% vs 1.6%), preterm birth (7.7% vs 25.0%), or cesarean delivery (31.0% vs 54.3%). After a median (IQR) duration of 2.6 (1.3-6.4) years, 1287 (96.1 per 10 000) individuals with SMM had a mental health hospitalization or ED visit, compared with 41 779 (73.2 per 10 000) individuals without SMM (adjusted hazard ratio, 1.26 [95% CI, 1.19-1.34]). Conclusions and Relevance: In this cohort study of postpartum individuals with and without SMM in pregnancy and delivery, there was an increased risk of mental health hospitalizations or ED visits up to 13 years after a delivery complicated by SMM. Enhanced surveillance and provision of postpartum mental health resources may be especially important after SMM.

Risk of birth defects in children of mothers with defects.

BACKGROUND: There is evidence that women with congenital anomalies are at risk of having an infant with the same defect. However, the risk of having an infant with a different type of defect is less well described. AIMS: We evaluated the extent to which offspring of women with congenital anomalies were at risk of having a birth defect, including defects that were similar to or different from their mother's. METHODS: We analyzed a retrospective cohort of 1,311,532 infants born in Canada between 2006 and 2022. The exposure was a maternal congenital anomaly, and the outcome included birth defects in the newborn. We estimated risk ratios (RR) and confidence intervals (CI) for the association of specific maternal anomalies with the risk of having an infant with a similar or different defect using log-binomial regression models adjusted for patient characteristics. RESULTS: While mothers with anomalies were at risk of having an infant with the same defect, associations with other types of defects were not as strong. For example, compared with no maternal anomaly, maternal urogenital defects were associated with up to 45 times the risk of having an infant with a similar urogenital defect (RR 45.33, 95 % CI 31.92-64.36), but <2 times the risk of having an infant with orofacial clefts (RR 1.89, 95 % CI 1.07-3.34) and clubfoot (RR 1.36, 95 % CI 1.02-1.81). CONCLUSION: The findings suggest that maternal congenital anomalies are only weakly associated with occurrence of a different type of defect in offspring.

Burn Patients and Mental Health: A Matched Cohort Study.

OBJECTIVE: To determine the association between burns and hospitalization for mental health disorders up to three decades later. SUMMARY BACKGROUND DATA: Burns are associated with pain, disability, and scarring, but the long-term impact on mental health is unclear. METHODS: We analyzed a cohort of 23,726 burn patients aged ≥10 years who were matched to 223,626 controls from Quebec, Canada, between 1989 and 2022. The main exposure was admission for a burn. We followed patients during 3,642,206 person-years of follow-up to identify future hospitalizations for psychiatric disorders, substance use disorders, and suicide attempts. We estimated adjusted hazard ratios (HR) with 95% confidence intervals (CI) for the association between burns and subsequent mental health hospitalization using Cox proportional hazards regression. RESULTS: Burn patients had 1.76 times greater risk of mental health hospitalization over time (95% CI 1.72-1.81), compared with controls. Associations were present regardless of burn site, but were greatest for burns covering ≥50% of the body (HR 3.29, 95% CI 2.61-4.15), third degree burns (HR 2.04, 95% CI 1.94-2.14), and burns requiring skin grafts (HR 2.00, 95% CI 1.90-2.10). Compared with controls, burn patients had more than two times the risk of hospitalization for eating disorders (HR 3.14, 95% CI 2.50-3.95), psychoactive substance use disorders (HR 2.27, 95% CI 2.17-2.39), and suicide attempts (HR 2.42, 95% CI 2.23-2.62). Risks were particularly elevated within 5 years of the burn, but persisted throughout follow-up. CONCLUSIONS: Burns are associated with an increased risk of hospitalization for mental health disorders up to 30 years later.

Genomic landscape of liquid biopsy mutations in TP53 and DNA damage genes in cancer patients.

Next-generation sequencing (NGS) assays based on plasma cell-free DNA (cfDNA) are increasingly used for clinical trials inclusion. Their optimized limit of detection applied to a large number of genes leads to the identification of mutations not confirmed in tissue. It becomes essential to describe the characteristics and consequences of these liquid biopsy-only mutations. In the STING protocol (Gustave Roussy, NCT04932525), 542 patients with advanced solid cancer had cfDNA-based and tissue-based NGS analysis (performed by FoundationOne® Liquid CDx and FoundationOne CDx™, respectively). Mutations identified in the liquid biopsy but not in the paired tissue were considered as liquid biopsy-only mutations irrespective of their variant allelic frequency (VAF). Out of 542 patients, 281 (51.8%) harbored at least one liquid biopsy-only mutation. These patients were significantly older, and more heavily pretreated. Liquid biopsy-only mutations occurring in TP53, and in DDR genes (ATM, CHEK2, ATR, BRCA2, and BRCA1) accounted for 90.8% of all the mutations. The median VAF of these mutations was generally low (0.37% and 0.40% for TP53 and DDR genes respectively). The variant type repartition depended on the gene. Liquid biopsy-only mutations affected hotspot in TP53 codon 273, 125, 195, 176, 237 or 280 and ATM codon 2891 and 3008. In a subset of 37 patients, 75.0%, 53.5% and 83.3% of the liquid biopsy-only mutations occurring respectively in ATM, TP53, and CHEK2 were confirmed in the matching whole blood sample. Although liquid biopsy-only mutations makes the interpretation of liquid biopsy results more complex, they have distinct characteristics making them more easily identifiable.

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.

Assisted Reproductive Technology and Cardiovascular Outcomes in Parents and Offspring.

BACKGROUND: The impact of assisted reproductive technology (ART) on the cardiovascular system is unclear. METHODS: We conducted a retrospective longitudinal cohort study of 1,001,593 pregnancies conceived naturally or through ART from 2008 to 2019 in Québec to assess the association of ART with cardiovascular disease in families. The exposure measure was ART. The outcome included severe maternal cardiovascular morbidity, congenital heart defects in offspring, and long-term risk of cardiovascular hospitalisation in mothers, fathers, and offspring during 11 years of follow-up. We estimated the association between ART and cardiovascular outcomes with the use of adjusted log-binomial regression (risk ratio, 95% confidence interval [CI]) and Cox proportional hazards regression models (hazard ratio [HR]). RESULTS: Compared with natural conception, ART was associated with 2.04 times the risk of severe cardiovascular morbidity in mothers (95% CI 1.86-2.23) and 1.38 times the risk of congenital heart defects in offspring (95% CI 1.26-1.50). ART was not associated with the risk of maternal cardiovascular hospitalisation following pregnancy (HR 1.03, 95% CI 0.88-1.21). However, ART was associated with an increased risk of paternal cardiovascular hospitalisation (HR 1.24, 95% CI 1.11-1.38) and offspring cardiovascular hospitalisation (HR 1.27, 95% CI 1.01-1.61), mainly due to an increased risk of hypertension. CONCLUSIONS: ART is associated with only a small increase in the risk of cardiovascular complications in families. Parents and offspring may be reassured that ART likely has no major impact on the cardiovascular system.

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.

Association of maternal cancer with congenital anomalies in offspring.

BACKGROUND: Congenital anomalies are common, but the possibility that maternal cancer increases the chance of having a child with a birth defect is not fully understood. OBJECTIVES: To examine the association between maternal cancer before or during pregnancy and the risk of birth defects in offspring. METHODS: We conducted a retrospective cohort study of live births in Quebec, Canada, between 1989 and 2022 using hospital data. The main exposure measure was maternal cancer before or during pregnancy. The outcome included birth defects detected in offspring during gestation or at birth. We estimated risk ratios (RR) and 95% confidence intervals (CI) for the association of maternal cancer with birth defects using log-binomial regression models adjusted for potential confounders. RESULTS: In this study of 2,568,120 newborns, birth defects were present in 6.0% and 6.7% of infants whose mothers had cancer before or during pregnancy, respectively, compared with 5.7% of infants whose mothers never had cancer. Cancer during pregnancy was associated with heart (RR 1.58, 95% CI 1.03, 2.44), nervous system (RR 4.05, 95% CI 2.20, 7.46) and urinary defects (RR 1.72, 95% CI 1.01, 2.95). Among specific types of malignancies during pregnancy, breast cancer was the most prominent risk factor for birth defects (RR 1.55, 95% CI 1.02, 2.37). Cancer before pregnancy was not associated with any type of birth defect or with defects overall (RR 1.01, 95% CI 0.92, 1.11). Moreover, no specific type of cancer before pregnancy was associated with an increased risk of birth defects. CONCLUSIONS: Maternal cancer during pregnancy is associated with the risk of congenital anomalies in offspring, however, cancer before pregnancy is not associated with this outcome.

Inequality in COVID-19 mortality in Quebec associated with neighbourhood-level vulnerability domains.

OBJECTIVES: We measured disparities in COVID-19 mortality associated with increasing vulnerability to severe outcomes of infectious disease at the neighbourhood level to identify domains for prioritization of public interventions. METHODS: In this retrospective ecological study, we calculated COVID-19 mortality rate ratios (RR) comparing neighbourhoods with the greatest vulnerability relative to lowest vulnerability using the five domains from the COVID-19 vulnerability index for Quebec using hospital data from the first year of the pandemic and vulnerability levels from 13,182 neighbourhoods. We estimated the attributable fraction to assess disparities in COVID-19 mortality associated with vulnerability. Domains covered biological susceptibility, sociocultural characteristics, socioeconomic characteristics, and indoor and outdoor risk factors for exposure to SARS-CoV-2. RESULTS: Vulnerable neighbourhoods accounted for 60.7% of COVID-19 deaths between March 2020 and February 2021. Neighbourhoods with biological susceptibility accounted for 46.1% and indoor exposure for 44.6% of deaths. Neighbourhoods with socioeconomic vulnerability experienced 23.5%, outdoor exposure 14.6%, and sociocultural vulnerability 9.0% of deaths. Neighbourhoods with high relative vulnerability had 4.66 times greater risk of COVID-19 mortality compared with those with low vulnerability (95%CI 3.82-5.67). High vulnerability in the biological (RR 3.33; 95%CI 2.71-4.09), sociocultural (RR 1.50; 95%CI 1.27-1.77), socioeconomic (RR 2.08; 95%CI 1.75-2.48), and indoor (RR 3.21; 95%CI 2.74-3.76) exposure domains were associated with elevated risks of mortality compared with the least vulnerable neighbourhoods. Outdoor exposure was unassociated with mortality (RR 1.17; 95%CI 0.96-2.43). CONCLUSION: Public intervention to protect vulnerable populations should be adapted to focus on domains most associated with COVID-19 mortality to ensure addressing local needs.

RéSUMé: OBJECTIFS: Nous avons mesuré les inégalités de mortalité de COVID-19 associées à la vulnérabilité croissante des conséquences sévères de maladies infectieuses au Québec. L'échelle de quartier permet d'identifier des domaines à prioriser lors d'interventions publiques. MéTHODES: Dans cette étude écologique rétrospective, nous avons calculé des ratios des taux (RT) en comparant les territoires de plus grande vulnérabilité avec ceux de plus faible vulnérabilité à l'aide de données d'hospitalisation de la première année de la pandémie et de mesures de vulnérabilité de 13 182 aires de diffusion (AD). Nous avons estimé la fraction attribuable pour évaluer les disparités de mortalité par la COVID-19. Les domaines examinés concernaient la susceptibilité biologique, les caractéristiques socioculturelles et socioéconomiques ainsi que des facteurs de risque d'exposition au SRAS-CoV-2 à l'intérieur et à l'extérieur. RéSULTATS: Dans l'ensemble, les territoires vulnérables couvraient 60,7 % des cas de mortalité de COVID-19 pendant la première année de la pandémie. Les AD avec une vulnérabilité élevée avaient un risque de mortalité par la COVID-19 4,66 fois plus élevé comparé aux territoires de faible vulnérabilité (IC de 95% 3,82-5,67). Les aires de diffusion avec une susceptibilité biologique comptaient pour 46,1 % des décès et celles avec une exposition au SRAS-CoV-2 à l'intérieur pour 44,6 %. La vulnérabilité socioéconomique comptait pour 23,5 %, l'exposition à l'extérieur pour 14,6 %, et la vulnérabilité socioculturelle pour 9,0 % des décès. Les domaines biologique (RT 3,33; IC de 95% 2,71-4,09), socioculturel (RT 1,50; IC de 95% 1,27-1,77), socioéconomique (RT 2,08; IC de 95% 1,75-2,48), et d'exposition intérieure (RT 3,21; IC de 95% 2,74-3,76) étaient associés à un risque élevé de mortalité par la COVID-19 comparé aux territoires les moins vulnérables. L'exposition extérieure n'était pas associée avec un risque de mortalité par la COVID-19 (RT 1,17; IC de 95% 0,96-2,43). CONCLUSION: Les interventions publiques visant à protéger les populations vulnérables devraient être adaptées aux domaines les plus associés avec la mortalité par la COVID-19 au Québec et ce, à l'échelle de quartier pour s'assurer que les besoins locaux soient couverts.

Preeclampsia and the Retina.

PURPOSE OF REVIEW: This review summarizes key findings relating to the association between preeclampsia and retinal disorders. RECENT FINDINGS: Preeclampsia is a major cause of maternal morbidity. Pregnant women with preeclampsia frequently describe having visual disturbances. Retinal changes can be identified on fundoscopy in most patients with preeclampsia. While retinal pathology secondary to preeclampsia usually resolves postpartum, there is growing evidence that women with preeclampsia have a higher long-term risk of developing retinal disorders after pregnancy. Pregnant women often experience visual changes. While these symptoms may be benign, careful attention should be paid to exclude retinal disorders secondary to preeclampsia. Pregnant women complaining of new-onset or worsening blurry vision, scotomata, diplopia, or photopsia require rapid and thorough evaluation to rule out hypertensive disorders. Management of preeclampsia, including administration of magnesium sulfate and delivery of the fetus, can reverse retinal pathologies in most cases.

Population-based birth cohort study on diabetes in pregnancy and infant hospitalisations in Cree, other First Nations and non-Indigenous communities in Quebec.

OBJECTIVES: Diabetes in pregnancy, whether pre-gestational (chronic) or gestational (de novo hyperglycaemia), increases the risk of adverse birth outcomes. It is unclear whether gestational diabetes increases the risk of postnatal morbidity in infants. Cree First Nations in Quebec are at high risk for diabetes in pregnancy. We assessed whether pre-gestational or gestational diabetes may increase infant hospitalisation (an infant morbidity indicator) incidence, and whether this may be related to more frequent infant hospitalisations in Cree and other First Nations in Quebec. DESIGN: Population-based birth cohort study through administrative health data linkage. SETTING AND PARTICIPANTS: Singleton infants (≤1 year) born to mothers in Cree (n=5070), other First Nations (9910) and non-Indigenous (48 200) communities in rural Quebec. RESULTS: Both diabetes in pregnancy and infant hospitalisation rates were much higher comparing Cree (23.7% and 29.0%) and other First Nations (12.4% and 34.1%) to non-Indigenous (5.9% and 15.5%) communities. Compared with non-diabetes, pre-gestational diabetes was associated with an increased risk of any infant hospitalisation to a greater extent in Cree and other First Nations (relative risk (RR) 1.56 (95% CI 1.28 to 1.91)) than non-Indigenous (RR 1.26 (1.15 to 1.39)) communities. Pre-gestational diabetes was associated with increased risks of infant hospitalisation due to diseases of multiple systems in all communities. There were no significant associations between gestational diabetes and risks of infant hospitalisation in all communities. The population attributable risk fraction of infant hospitalisations (overall) for pre-gestational diabetes was 6.2% in Cree, 1.6% in other First Nations and 0.3% in non-Indigenous communities. CONCLUSIONS: The study is the first to demonstrate that pre-gestational diabetes increases the risk of infant hospitalisation overall and due to diseases of multiple systems, but gestational diabetes does not. High prevalence of pre-gestational diabetes may partly account for the excess infant hospitalisations in Cree and other First Nations communities in Quebec.

Cytogenetics in the management of myelodysplastic neoplasms (myelodysplastic syndromes, MDS): Guidelines from the groupe francophone de cytogénétique hématologique (GFCH).

Myelodysplastic neoplasms (MDS) are clonal hematopoietic neoplasms. Chromosomal abnormalities (CAs) are detected in 40-45% of de novo MDS and up to 80% of post-cytotoxic therapy MDS (MDS-pCT). Lately, several changes appeared in World Health Organization (WHO) classification and International Consensus Classification (ICC). The novel 'biallelic TP53 inactivation' (also called 'multi-hit TP53') MDS entity requires systematic investigation of TP53 locus (17p13.1). The ICC maintains CA allowing the diagnosis of MDS without dysplasia (del(5q), del(7q), -7 and complex karyotype). Deletion 5q is the only CA, still representing a low blast class of its own, if isolated or associated with one additional CA other than -7 or del(7q) and without multi-hit TP53. It represents one of the most frequent aberrations in adults' MDS, with chromosome 7 aberrations, and trisomy 8. Conversely, translocations are rarer in MDS. In children, del(5q) is very rare while -7 and del(7q) are predominant. Identification of a germline predisposition is key in childhood MDS. Aberrations of chromosomes 5, 7 and 17 are the most frequent in MDS-pCT, grouped in complex karyotypes. Despite the ever-increasing importance of molecular features, cytogenetics remains a major part of diagnosis and prognosis. In 2022, a molecular international prognostic score (IPSS-M) was proposed, combining the prognostic value of mutated genes to the previous scoring parameters (IPSS-R) including cytogenetics, still essential. A karyotype on bone marrow remains mandatory at diagnosis of MDS with complementary molecular analyses now required. Analyses with FISH or other technologies providing similar information can be necessary to complete and help in case of karyotype failure, for doubtful CA, for clonality assessment, and for detection of TP53 deletion to assess TP53 biallelic alterations.

Second-trimester abortion and risk of live birth.

BACKGROUND: Second-trimester abortion may result in a live birth, but the extent to which this outcome occurs is unknown. OBJECTIVE: This study aimed to examine rates of live birth after pregnancy termination in the second trimester and identify associated risk factors. STUDY DESIGN: We conducted a retrospective cohort study of 13,777 second-trimester abortions occurring in hospital settings between April 1, 1989 and March 31, 2021 in Quebec, Canada. The exposure was induced abortion between 15 and 29 weeks of gestation, including the indication for (fetal anomaly, maternal emergency, other) and use of feticidal injection (intracardiac/intrathoracic or intraamniotic). The primary outcome was live birth following abortion. We measured the rate of live birth per 100 abortions and used adjusted log-binomial regression models to estimate risk ratios and 95% confidence intervals for the association of fetal and maternal characteristics with the risk of live birth. We assessed the extent to which feticidal injection reduced the risk. RESULTS: Among 13,777 abortions between 15 and 29 weeks of gestation, 1541 (11.2%) led to live birth. Fetal anomaly was a common indication for termination (48.1%), and most abortions were by labor induction (72.2%). Compared with abortion between 15 and 19 weeks, abortion between 20 and 24 weeks was associated with 4.80 times the risk of live birth (95% confidence interval, 4.20-5.48), whereas abortion between 25 and 29 weeks was associated with 1.34 times the risk (95% confidence interval, 1.00-1.79). Feticidal injection reduced the risk of live birth by 57% compared with no injection (risk ratio, 0.43; 95% confidence interval, 0.36-0.51). Intracardiac or intrathoracic injection was particularly effective at preventing live birth (risk ratio, 0.02; 95% confidence interval, 0.01-0.07). CONCLUSION: Second-trimester abortion carries a risk of live birth, especially at 20 to 24 weeks of gestation, although feticidal injection may protect against this outcome.

Cytogenetics in the management of bone marrow failure syndromes: Guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH).

Bone marrow failure syndromes are rare disorders characterized by bone marrow hypocellularity and resultant peripheral cytopenias. The most frequent form is acquired, so-called aplastic anemia or idiopathic aplastic anemia, an auto-immune disorder frequently associated with paroxysmal nocturnal hemoglobinuria, whereas inherited bone marrow failure syndromes are related to pathogenic germline variants. Among newly identified germline variants, GATA2 deficiency and SAMD9/9L syndromes have a special significance. Other germline variants impacting biological processes, such as DNA repair, telomere biology, and ribosome biogenesis, may cause major syndromes including Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, and Shwachman-Diamond syndrome. Bone marrow failure syndromes are at risk of secondary progression towards myeloid neoplasms in the form of myelodysplastic neoplasms or acute myeloid leukemia. Acquired clonal cytogenetic abnormalities may be present before or at the onset of progression; some have prognostic value and/or represent somatic rescue mechanisms in inherited syndromes. On the other hand, the differential diagnosis between aplastic anemia and hypoplastic myelodysplastic neoplasm remains challenging. Here we discuss the value of cytogenetic abnormalities in bone marrow failure syndromes and propose recommendations for cytogenetic diagnosis and follow-up.

Cytogenetics in the management of hematologic neoplasms with germline predisposition: guidelines from the Groupe Francophone de Cytogénétique Hématologique (GFCH).

The number of predisposing genes is continuously growing with the widespread availability of DNA sequencing, increasing the prevalence of hematologic malignancies with germline predisposition. Cytogenetic analyses provide an effective approach for the recognition of these malignancies with germline predisposition, which is critical for proper diagnosis, optimal treatment and genetic counseling. Based on the World Health Organization and the international consensus classifications as well as the European LeukemiaNet recommendations, this review first presents an advanced classification of neoplasms with germline predisposition focused on the acquired cytogenetic alterations during leukemogenesis. The various genetic rescue mechanisms and the progression to transformation are then explained. The review also outlines the specific constitutional and somatic cytogenetic aberrations indicative of germline predisposition disorders in B-acute lymphoblastic leukemia (ALL), T-ALL, bone marrow failure syndrome and myeloid neoplasms. An emphasis is made on monosomy 7 in the predisposition field, its frequency and diagnosis impact as well as its various circumstances of occurrence. Lastly, we propose cytogenetic technical recommendations and guidelines for clinical reporting of these specific aberrations.