Diabetes mellitus in pregnancy across Canada.

BACKGROUND: Contemporary estimates of diabetes mellitus (DM) rates in pregnancy are lacking in Canada. Accordingly, this study examined trends in the rates of type 1 (T1DM), type 2 (T2DM) and gestational (GDM) DM in Canada over a 15-year period, and selected adverse pregnancy outcomes. METHODS: This study used repeated cross-sectional data from the Canadian Institute of Health Information (CIHI) hospitalization discharge abstract database (DAD). Maternal delivery records were linked to their respective birth records from 2006 to 2019. The prevalence of T1DM, T2DM and GDM were calculated, including relative changes over time, assessed by a Cochrane-Armitage test. Also assessed were differences between provinces and territories in the prevalence of DM. RESULTS: Over the 15-year study period, comprising 4,320,778 hospital deliveries in Canada, there was a statistically significant increase in the prevalence of GDM and T1DM and T2DM. Compared to pregnancies without DM, all pregnancies with any form of DM had higher rates of hypertension and Caesarian delivery, and also adverse infant outcomes, including major congenital anomalies, preterm birth and large-for-gestational age birthweight. CONCLUSION: Among 4.3 million pregnancies in Canada, there has been a rise in the prevalence of DM. T2DM and GDM are expected to increase further as more overweight women conceive in Canada.

Multifetal Pregnancy After Implementation of a Publicly Funded Fertility Program.

Importance: A publicly funded fertility program was introduced in Ontario, Canada, in 2015 to increase access to fertility treatment. For in vitro fertilization (IVF), the program mandated an elective single-embryo transfer (eSET) policy. However, ovulation induction and intrauterine insemination (OI/IUI)-2 other common forms of fertility treatment-were more difficult to regulate in this manner. Furthermore, prior epidemiologic studies only assessed fetuses at birth and did not account for potential fetal reductions that may have been performed earlier in pregnancy. Objective: To examine the association between fertility treatment and the risk of multifetal pregnancy in a publicly funded fertility program, accounting for both fetal reductions and all live births and stillbirths. Design, Setting, and Participants: This population-based, retrospective cohort study used linked administrative health databases at ICES to examine all births and fetal reductions in Ontario, Canada, from April 1, 2006, to March 31, 2021. Exposure: Mode of conception: (1) unassisted conception, (2) OI/IUI, or (3) IVF. Main Outcomes and Measures: The main outcome was multifetal pregnancy (ie, a twin or higher-order pregnancy). Modified Poisson regression generated adjusted relative risks (ARRs) and derived population attributable fractions (PAFs) for multifetal pregnancies attributable to fertility treatment. Absolute rate differences (ARDs) were used to compare the era before eSET was promoted (2006-2011) with the era after the introduction of the eSET mandate (2016-2021). Results: Of all 1 724 899 pregnancies, 1 670 825 (96.9%) were by unassisted conception (mean [SD] maternal age, 30.6 [5.2] years), 24 395 (1.4%) by OI/IUI (mean [SD] maternal age, 33.1 [4.4] years), and 29 679 (1.7%) by IVF (mean [SD] maternal age, 35.8 [4.7] years). In contrast to unassisted conception, individuals who received OI/IUI or IVF tended to be older, reside in a high-income quintile neighborhood, or have preexisting health conditions. Multifetal pregnancy rates were 1.4% (95% CI, 1.4%-1.4%) for unassisted conception, 10.5% (95% CI, 10.2%-10.9%) after OI/IUI, and 15.5% (95% CI, 15.1%-15.9%) after IVF. Compared with unassisted conception, the ARR of any multifetal pregnancy was 7.0 (95% CI, 6.7-7.3) after OI/IUI and 9.9 (95% CI, 9.6-10.3) after IVF, with corresponding PAFs of 7.1% (95% CI, 7.1%-7.2%) and 13.4% (95% CI, 13.3%-13.4%). Between the eras of 2006 to 2011 and 2016 to 2021, multifetal pregnancy rates decreased from 12.9% to 9.1% with OI/IUI (ARD, -3.8%; 95% CI, -4.2% to -3.4%) and from 29.4% to 7.1% with IVF (ARD, -22.3%; 95% CI, -23.2% to -21.6%). Conclusions and Relevance: In this cohort study of more than 1.7 million pregnancies in Ontario, Canada, a publicly funded IVF program mandating an eSET policy was associated with a reduction in multifetal pregnancy rates. Nevertheless, ongoing strategies are needed to decrease multifetal pregnancy, especially in those undergoing OI/IUI.

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.

Mental Illness in the 2 Years Prior to Pregnancy in a Population With Traumatic Brain Injury: A Cross-Sectional Study: La maladie mentale dans les deux ans précédant une grossesse dans une population souffrant de lésion cérébrale traumatique : une étude transversale.

OBJECTIVE: Existing studies, in mostly male samples such as veterans and athletes, show a strong association between traumatic brain injury (TBI) and mental illness. Yet, while an understanding of mental health before pregnancy is critical for informing preconception and perinatal supports, there are no data on the prevalence of active mental illness before pregnancy in females with TBI. We examined the prevalence of active mental illness ≤2 years before pregnancy (1) in a population with TBI, and (2) in subgroups defined by sociodemographic, health, and injury-related characteristics, all compared to those without TBI. METHOD: This population-based cross-sectional study was completed in Ontario, Canada, from 2012 to 2020. Modified Poisson regression generated adjusted prevalence ratios (aPRs) of active mental illness ≤2 years before pregnancy in 15,585 females with TBI versus 846,686 without TBI. We then used latent class analysis to identify subgroups with TBI according to sociodemographic, health, and injury-related characteristics and subsequently compared them to females without TBI on their outcome prevalence. RESULTS: Females with TBI had a higher prevalence of active mental illness ≤2 years before pregnancy than those without TBI (44.1% vs. 25.9%; aPR 1.46, 95% confidence interval, 1.43 to 1.49). There were 3 TBI subgroups, with Class 1 (low-income, past assault, recent TBI described as intentional and due to being struck by/against) having the highest outcome prevalence. CONCLUSIONS: Females with TBI, and especially those with a recent intentional TBI, have a high prevalence of mental illness before pregnancy. They may benefit from mental health screening and support in the post-injury, preconception, and perinatal periods. PLAIN LANGUAGE TITLE: Mental illness in the 2 years before pregnancy in a population with traumatic brain injury. PLAIN LANGUAGE SUMMARY: Research has shown a strong association between traumatic brain injury (TBI) and mental illness. Most previous studies have been conducted in primarily male samples, like veterans and professional athletes. Understanding mental health before pregnancy is important for deciding what supports people need before and during pregnancy. However, there are no studies on the frequency of mental illness in females with TBI before a pregnancy. We examined the frequency of mental illness 2 years before pregnancy in a population with TBI, and in subgroups defined by different social, health, and injury-related characteristics, compared to those without TBI. We undertook a population-wide study of all females with and without TBI in Ontario, Canada, with a birth in 2012-2020. We used statistical models to compare these groups on the presence of mental illness in the 2 years before pregnancy, before and after accounting for social and health characteristics. We also identified subgroups with TBI according to their social (e.g., poverty), health (e.g., chronic conditions), and injury-related characteristics (e.g., cause of injury) and subsequently compared them to females without TBI on their frequency of mental illness in the 2 years before pregnancy. Forty-four percent of females with TBI had mental illness in the 2 years before pregnancy compared to 25% of those without TBI. There were 3 TBI subgroups. Females with low-income, past assault, and injuries that were described as being intentional had the highest frequency of mental illness in the 2 years before pregnancy. Females with TBI may benefit from mental health screening and support post-injury and around the time of pregnancy.

Postpartum Emergency Department Use Following Midwifery-Model vs Obstetrics-Model Care.

Importance: Emergency department (ED) use postpartum is a common and often-preventable event. Unlike traditional obstetrics models, the Ontario midwifery model offers early care postpartum. Objective: To assess whether postpartum ED use differs between women who received perinatal care in midwifery-model care vs in traditional obstetrics-model care. Design, Setting, and Participants: This retrospective population-based cohort study took place in Ontario, Canada, where public health care is universally funded. Participants included women who were low risk and primiparous and gave birth to a live baby in an Ontario hospital between 2012 and 2018. Data were collected from April 2012 to March 2018 and analyzed from June 2022 to April 2023. Exposures: Perinatal care clinician, namely, a midwife or obstetrician. Main Outcome and Measures: : Any unscheduled ED visit 42 days postpartum or less. Poisson regression models compared ED use between women with midwifery-model care vs obstetrics-model care, weighting by propensity score-based overlap weights. Results: Among 104 995 primiparous women aged 11 to 50 years, those in midwifery-model care received a median (IQR) of 7 (6-8) postpartum visits, compared with 0 (0-1) visits among those receiving obstetrics-model care. Unscheduled ED visits 42 days or less postpartum occurred for 1549 of 23 124 women (6.7%) with midwifery-model care compared with 6902 of 81 871 women (8.4%) with traditional obstetrics-model care (adjusted relative risks [aRR], 0.78; 95% CI, 0.73-0.83). Similar aRRs were seen in women with a spontaneous vaginal birth (aRR, 0.71; 95% CI, 0.65-0.78) or assisted vaginal birth (aRR, 0.70; 95% CI, 0.59-0.82) but not those with a cesarean birth (aRR, 0.94; 95% CI, 0.86-1.03) or those with intrapartum transfer of care between a midwife and obstetrician (aRR, 0.94; 95% CI, 0.87-1.04). ED use 7 days or less postpartum was also lower among women receiving midwifery model care (aRR, 0.70; 95% CI, 0.65-0.77). Conclusions and Relevance: In this cohort study, midwifery-model care was associated with less postpartum ED use than traditional obstetrics-model care among women who had low risk and were primiparous, which may be due to early access to postpartum care provided by Ontario midwives.

Teen Pregnancy and Risk of Premature Mortality.

Importance: Unintentional injury, suicide, and homicide are leading causes of death among young females. Teen pregnancy may be a marker of adverse life experiences. Objective: To evaluate the risk of premature mortality from 12 years of age onward in association with number of teen pregnancies and age at pregnancy. Design, Setting, and Participants: This population-based cohort study was conducted among all females alive at 12 years of age from April 1, 1991, to March 31, 2021, in Ontario, Canada (the most populous province, which has universal health care and data collection). The study period ended March 31, 2022. Exposures: The main exposure was number of teen pregnancies between 12 and 19 years of age (0, 1, or ≥2). Secondary exposures included how the teen pregnancy ended (birth or miscarriage vs induced abortion) and age at first teen pregnancy. Main Outcomes and Measures: The main outcome was all-cause mortality starting at 12 years of age. Hazard ratios (HRs) were adjusted for year of birth, comorbidities at 9 to 11 years of age, and area-level education, income level, and rurality. Results: Of 2 242 929 teenagers, 163 124 (7.3%) experienced a pregnancy at a median age of 18 years (IQR, 17-19 years). Of those with a teen pregnancy, 60 037 (36.8%) ended in a birth (of which 59 485 [99.1%] were live births), and 106 135 (65.1%) ended in induced abortion. The median age at the end of follow-up was 25 years (IQR, 18-32 years) for those without a teen pregnancy and 31 years (IQR, 25-36 years) for those with a teen pregnancy. There were 6030 deaths (1.9 per 10 000 person-years [95% CI, 1.9-2.0 per 10 000 person-years]) among those without a teen pregnancy, 701 deaths (4.1 per 10 000 person-years [95% CI, 3.8-4.5 per 10 000 person-years]) among those with 1 teen pregnancy, and 345 deaths (6.1 per 10 000 person-years [95% CI, 5.5-6.8 per 10 000 person-years]) among those with 2 or more teen pregnancies; adjusted HRs (AHRs) were 1.51 (95% CI, 1.39-1.63) for those with 1 pregnancy and 2.14 (95% CI, 1.92-2.39) for those with 2 or more pregnancies. Comparing those with vs without a teen pregnancy, the AHR for premature death was 1.25 (95% CI, 1.12-1.40) from noninjury, 2.06 (95% CI, 1.75-2.43) from unintentional injury, and 2.02 (95% CI, 1.54-2.65) from intentional injury. Conclusions and Relevance: In this population-based cohort study of 2.2 million female teenagers, teen pregnancy was associated with future premature mortality. It should be assessed whether supports for female teenagers who experience a pregnancy can enhance the prevention of subsequent premature mortality in young and middle adulthood.

Use of Latent Class Analysis to Predict Intensive Care Unit Admission and Mortality in Children with a Major Congenital Anomaly.

OBJECTIVE: To define major congenital anomaly (CA) subgroups and assess outcome variability based on defined subgroups. STUDY DESIGN: This population-based cohort study used registries in Denmark for children born with a major CA between January 1997 and December 2016, with follow-up until December 2018. We performed a latent class analysis (LCA) using child and family clinical and sociodemographic characteristics present at birth, incorporating additional variables occurring until age of 24 months. Cox proportional hazards regression models estimated hazard ratios (HRs) of pediatric mortality and intensive care unit (ICU) admissions for identified LCA classes. RESULTS: The study included 27 192 children born with a major CA. Twelve variables led to a 4-class solution (entropy = 0.74): (1) children born with higher income and fewer comorbidities (55.4%), (2) children born to young mothers with lower income (24.8%), (3) children born prematurely (10.0%), and (4) children with multiorgan involvement and developmental disability (9.8%). Compared with those in Class 1, mortality and ICU admissions were highest in Class 4 (HR = 8.9, 95% CI = 6.4-12.6 and HR = 4.1, 95% CI = 3.6-4.7, respectively). More modest increases were observed among the other classes for mortality and ICU admissions (Class 2: HR = 1.7, 95% CI = 1.1-2.5 and HR = 1.3, 95% CI = 1.1-1.4, respectively; Class 3: HR = 2.5, 95% CI = 1.5-4.2 and HR = 1.5, 95% CI = 1.3-1.9, respectively). CONCLUSIONS: Children with a major CA can be categorized into meaningful subgroups with good discriminative ability. These groupings may be useful for risk-stratification in outcome studies.

Differences in maternal-newborn ABO blood groups and risk of serious infant infection.

BACKGROUND: During pregnancy, various maternal IgG antibodies are transferred to the developing fetus, some of which may protect the newborn against infection. If a mother and her fetus have different ABO blood groups, then transferred maternal antibodies may plausibly protect the infant against infection. AIM: To determine if maternal-newborn ABO blood group incongruence vs. congruence is associated with a lower risk of serious infection in the infant. DESIGN: Retrospective population-based cohort. METHODS: We used linked patient-level datasets for all singleton hospital livebirths from 2008-2022 in Ontario, Canada, with known maternal and newborn ABO blood groups. We used a dichotomous exposure state, either ABO blood group congruent (N = 114,507) or incongruent (N = 43,074). The main outcome of interest was the risk of serious infant infection within 27 days, and from 28-365 days, after birth. Cox proportional hazard models generated hazard ratios and 95% confidence intervals, and were adjusted for maternal age, world region of origin, residential income quintile, and gestational age at birth. RESULTS: Relative to maternal-newborn congruency, incongruent ABO blood group was associated with aHR of 0.88 (95% CI 0.80 to 0.97) for serious neonatal infection within 27 days of birth, and 0.93 (95% CI 0.90 to 0.96) for serious infection between 28-365 days after birth. CONCLUSIONS: Maternal-newborn ABO incongruence may be associated with a lower relative risk of a serious infant infection within 27 days, and from 28 to 365 days, after birth.

Maternal Deaths Using Coroner's Data: A Latent Class Analysis.

OBJECTIVE: Knowledge regarding the antecedent clinical and social factors associated with maternal death around the time of pregnancy is limited. This study identified distinct subgroups of maternal deaths using population-based coroner's data, and that may inform ongoing preventative initiatives. METHODS: A detailed review of coroner's death files was performed for all of Ontario, Canada, where there is a single reporting mechanism for maternal deaths. Deaths in pregnancy, or within 365 days thereafter, were identified within the Office of the Chief Coroner for Ontario database, 2004-2020. Variables related to the social and clinical circumstances surrounding the deaths were abstracted in a standardized manner from each death file, including demographics, forensic information, nature and cause of death, and antecedent health and health care factors. These variables were then entered into a latent class analysis (LCA) to identify distinct types of deaths. RESULTS: Among 273 deaths identified in the study period, LCA optimally identified three distinct subgroups, namely, (1) in-hospital deaths arising during birth or soon thereafter (52.7% of the sample); (2) accidents and unforeseen obstetric complications also resulting in infant demise (26.3%); and (3) out-of-hospital suicides occurring postpartum (21.0%). Physical injury (22.0%) was the leading cause of death, followed by hemorrhage (16.8%) and overdose (13.3%). CONCLUSION: Peri-pregnancy maternal deaths can be classified into three distinct sub-types, with somewhat differing causes. These findings may enhance clinical and policy development aimed at reducing pregnancy mortality.

Periconceptional Serum Creatinine and Risk of Childhood Autism Spectrum Disorder: A Research Letter.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition that manifests in early childhood, in which the maternal metabolic syndrome may be a risk factor. The kidney is a barometer of maternal metabolic syndrome duration and severity. Objective: The main objective of this study is to determine whether periconceptional kidney function is associated with ASD in early childhood. Design Setting and Participants: This retrospective population-based cohort study was completed in Ontario, Canada. Included were singleton children born in an Ontario hospital between April 2007 and March 2021, who were alive at age 48 months and whose mother had a recorded prepregnancy body mass index (BMI) and a measured serum creatinine (SCr) between 120 days preconception and 28 days postconception. Measurement: The main study outcome was a diagnosis of ASD between ages 24 and 48 months. Methods: Relative risks (RRs) of ASD in association with periconceptional SCr were generated using modified Poisson regression and adjusted for several confounders. Results: The cohort comprised 86 054 women, who had 89 677 liveborn children surviving to at least 48 months of age. There was no significant association between periconceptional SCr and ASD (RR: 0.86; 95 % confidence interval: [0.67, 1.10]). Limitations: Selection bias may have arisen had SCr been ordered on clinical grounds. Conclusions: Further study is warranted to determine whether prepregnancy glomerular hyperfiltration is a marker of ASD and other behavioral conditions in childhood. To do so, a more accurate measure of hyperfiltration is needed than SCr.

Contexte: Des problèmes d'innocuité sont détectés dans environ un tiers des médicaments d'ordonnance au cours des années qui suivent leur approbation par l'organisme de réglementation. Les personnes âgées, en particulier celles qui sont atteintes d'insuffisance rénale chronique, sont particulièrement exposées aux effets indésirables des médicaments d'ordonnance. Ce protocole décrit une nouvelle approche qui, à partir des données administratives du système de santé, pourrait permettre d'identifier plus efficacement les signaux crédibles sur la sécurité des médicaments. Objectif: Utiliser l'informatique à haut débit et l'automatisation pour mener plus de 700 études de cohorte sur l'innocuité des médicaments chez les adultes âgés résidant en Ontario (Canada). Chaque étude comparera 74 résultats aigus (30 jours) chez des patients qui commencent un nouveau médicament sur ordonnance (nouveaux utilisateurs) à ceux d'un groupe de non-utilisateurs avec des caractéristiques de santé initiales similaires. Les risques seront évalués par strates de la fonction rénale initiale. Cadre et type d'étude: Études populationnelles de cohortes de nouveaux utilisateurs de médicaments menées à l'aide des bases de données administratives couplées du système de santé ontarien (Canada). Période étudiée: du 1er janvier 2008 au 1er mars 2020. Population source: les Ontariens de 66 ans ou plus ayant rempli au moins une ordonnance pour patient non hospitalisé par l'entremise du Program de médicaments de l'Ontario (PMO) pendant la période de l'étude (tous les résidents de la province bénéficient d'un système de soins de santé universel; les personnes âgées de 65 ans et plus bénéficient d'une couverture universelle des médicaments d'ordonnance par l'intermédiaire du PMO). Sujets: Nous avons identifié 3,2 millions d'adultes âgés dans la population source au cours de la période d'étude et constitué plus de 700 cohortes de médicaments, chacune contenant des groupes mutuellement exclusifs de nouveaux utilisateurs et de non-utilisateurs. Les non-utilisateurs se sont vu attribuer au hasard des dates d'entrée dans la cohorte qui suivaient les dates de début d'ordonnance des nouveaux utilisateurs. Les critères d'admissibilité étaient d'avoir une mesure initiale du débit de filtration glomérulaire estimé [DFGe] dans les 12 mois précédant la date d'entrée dans la cohorte (dans le groupe des nouveaux utilisateurs, le délai médian était de 71 jours avant l'entrée dans la cohorte), ne pas suivre de dialyze chronique, ne pas avoir eu de greffe rénale et n'avoir jamais eu de prescription d'un médicament de la même sous-classe que le médicament à l'étude. Les nouveaux utilisateurs et les non-utilisateurs seront jumelés selon environ 400 caractéristiques de santé initiales à l'aide de la probabilité inverse de traitement pondérée selon les scores de propension dans les trois strates de mesure du DFGe initial: ≥60 ml/min/1,73 m2; 45 à <60 ml/min/1,73 m2 et <45 ml/min/1,73 m2. Résultats: Nous comparerons les groupes de nouveaux utilisateurs et de non-utilisateurs selon 74 critères de jugement cliniquement pertinents (17 critères composites et 57 critères individuels) pendant les 30 jours suivant l'entrée dans la cohorte. Une approche prédéfinie a permis de déterminer ces 74 résultats. Plan d'analyze statistique: Dans chaque cohorte, nous calculerons les différences de risque (par régression de Poisson) et les rapports de risque (par régression binomiale) pondérés pour chaque strate de DFGe. Les interactions additives et multiplicatives par catégorie de DFGe seront examinées. Les associations médicaments-résultats répondant à des critères prédéfinis (signaux identifiés) seront examinées plus avant dans des analyses supplémentaires (survie, exposition à des témoins négatifs, analyses de la valeur E, etc.) et des visualizations. Résultats: Dans les cohortes initiales de médicaments, les médianes sont de 6 120 nouveaux utilisateurs (intervalle interquartile de 1 469 à 38 839) et de 1 088 301 non-utilisateurs (intervalle interquartile de 751 697 à 1 267 009). Les médicaments comptant le plus grand nombre de nouveaux utilisateurs sont le trihydrate d'amoxicilline (n = 1 000 032), la céfalexine (n = 571 566), l'acétaminophène sur ordonnance (n = 571 563) et la ciprofloxacine (n = 504 374). De 19 à 29 % des nouveaux utilisateurs dans ces cohortes présentaient un DFGe < 60 ml/min/1,73 m2. Limites: Malgré l'utilization de techniques robustes pour équilibrer les indicateurs de base et pour contrôler le risque de confusion par indication, il pourrait subsister des facteurs de confusion résiduels. Seuls les résultats aigus (30 jours) seront examinés. Nos sources de données ne comprennent pas les médicaments sans ordonnance (en vente libre) ni les médicaments prescrits dans les hôpitaux, et n'incluent pas l'utilization de médicaments sur ordonnance en ambulatoire chez les enfants ou les adultes de moins de 65 ans. Conclusion: Cette approche accélérée pour la réalisation d'études d'innocuité des médicaments après leur mise en marché a le potentiel de détecter efficacement les effets indésirables de ces médicaments dans une population vulnérable. Les résultats de ce protocole serviront à améliorer l'innocuité des médicaments.

Miscarriage after SARS-CoV-2 vaccination: A population-based cohort study.

OBJECTIVE: To evaluate the risk of miscarriage following SARS-CoV-2 vaccination, while accounting for the competing risk of induced abortion. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PARTICIPANTS: Women aged 15-50 years with a confirmed pregnancy at ≤19 completed weeks' gestation. METHODS: Exposure to first SARS-CoV-2 vaccination, handled in a time-varying manner, was defined as (i) unvaccinated, (ii) remotely vaccinated >28 days before the estimated conception date or (iii) recently vaccinated ≤28 days before conception and up to 120 days after conception. MAIN OUTCOME MEASURES: The outcome was miscarriage, occurring between the estimated date of conception and up to 19 completed weeks of pregnancy. Fine-Grey hazard models, accounting for the competing risk of induced abortion, generated hazard ratios (aHR), adjusted for socio-demographic factors, comorbidities, and biweekly periods. RESULTS: Included were 246 259 pregnant women, of whom 34% received a first SARS-CoV-2 vaccination. Miscarriage occurred at a rate of 3.6 per 10 000 person-days among remotely vaccinated women and 3.2 per 10 000 person-days among those recently vaccinated, in contrast to a rate of 1.9 per 10 000 person-days among unvaccinated women, with corresponding aHR of 0.98 (95% confidence interval [CI] 0.91-1.07) and 1.00 (95% CI 0.93-1.08). CONCLUSIONS: SARS-CoV-2 vaccination was not associated with miscarriage while accounting for the competing risk of induced abortion. This study reiterates the importance of including pregnant women in new vaccine clinical trials and registries, and the rapid dissemination of vaccine safety data.

Patterns of multiple chronic conditions in pregnancy: Population-based study using latent class analysis.

BACKGROUND: Adults with multiple chronic conditions (MCC) are a heterogeneous population with elevated risk of future adverse health outcomes. Yet, despite the increasing prevalence of MCC globally, data about MCC in pregnancy are scarce. OBJECTIVES: To estimate the population prevalence of MCC in pregnancy and determine whether certain types of chronic conditions cluster together among pregnant women with MCC. METHODS: We conducted a population-based cohort study in Ontario, Canada, of all 15-55-year-old women with a recognised pregnancy, from 2007 to 2020. MCC was assessed from a list of 22 conditions, identified using validated algorithms. We estimated the prevalence of MCC. Next, we used latent class analysis to identify classes of co-occurring chronic conditions in women with MCC, with model selection based on parsimony, clinical interpretability and statistical fit. RESULTS: Among 2,014,508 pregnancies, 324,735 had MCC (161.2 per 1000, 95% confidence interval [CI] 160.6, 161.8). Latent class analysis resulted in a five-class solution. In four classes, mood and anxiety disorders were prominent and clustered with one additional condition, as follows: Class 1 (22.4% of women with MCC), osteoarthritis; Class 2 (23.7%), obesity; Class 3 (15.8%), substance use disorders; and Class 4 (22.1%), asthma. In Class 5 (16.1%), four physical conditions clustered together: obesity, asthma, chronic hypertension and diabetes mellitus. CONCLUSIONS: MCC is common in pregnancy, with sub-types dominated by co-occurring mental and physical health conditions. These data show the importance of preconception and perinatal interventions, particularly integrated care strategies, to optimise treatment and stabilisation of chronic conditions in women with MCC.

Adverse perinatal events and maternal interpregnancy weight change: A population-based observational study.

OBJECTIVE: Mothers whose newborn experiences adversity may neglect their own health to care for their affected infant or following a perinatal death. Weight gain after pregnancy is one measure of maternal self-care. We measured interpregnancy weight gain among women whose child had an adverse perinatal event. METHODS: This population-based observational study included 192 154 primigravid women with two consecutive singleton births in Ontario, Canada. Outcomes included net weight gain, and adjusted odds ratios (aOR) of moving to a higher body mass index (BMI) category between pregnancies, comparing women whose child did versus did not experience either a perinatal death, prematurity, severe neonatal morbidity, major congenital anomaly, or severe neurologic impairment. RESULTS: Perinatal death was associated with a +3.5 kg (95% confidence interval [CI]: 2.1-4.9) net higher maternal weight gain in the subsequent pregnancy. Relative to term births, preterm birth <32 weeks (+3.2 kg, 95% CI: 1.9-4.6), 32-33 weeks (+1.8 kg, 95% CI: 0.7-2.8) and 34-36 weeks (+0.9 kg, 95% CI: 0.6-1.3) were associated with higher net weight gain. Having an infant with severe neonatal morbidity was associated with a +1.2 kg (95% CI: 0.3-2.1) weight gain. Likewise, the aOR of moving to a higher BMI category was 1.27 (95% CI, 1.14-1.42) following a perinatal death, 1.21 (95% CI: 1.04-1.41) after a preterm birth <32 weeks, and 1.11 (95% CI: 1.02-1.22) with severe neonatal morbidity. CONCLUSION: Greater interpregnancy weight gain, and movement to a higher BMI category, are each more likely in a woman whose first-born was affected by certain major adverse perinatal events.

How other countries can improve Canada's maternal mortality statistics.

Maternal mortality is the death of a woman while pregnant or within 42 days of the end of pregnancy. Late maternal deaths are from 42 to 365 days thereafter. Maternal mortality is an important surrogate indicator of a woman's overall health, social and economic status, and the provision of antenatal and emergency obstetric care at regional and national levels. Canada does not have a national system to report on maternal mortality; rather, maternal death investigations fall under the legal purview of coroners and medical examiners within each individual province or territory. Furthermore, the Canadian Perinatal Surveillance System is limited by its access to a comprehensive dataset. Hence, there is no accurate national picture of mortality prevalence or trends. The implementation of a national confidential enquiry system is a crucial step toward detailing pregnancy and post-pregnancy maternal mortality in Canada and should be organized in accordance with existing successful international systems.

ABO and Rh blood groups and risk of infection: systematic review and meta-analysis.

BACKGROUND: Persons with non-O and Rh-positive blood types are purported to be more susceptible to infection, including SARS-CoV-2, but there remains uncertainty about the degree to which this is so for both non-viral and viral infections. METHODS: We systematically reviewed Embase and PubMed from January 1st 1960 to May 31st 2022. English-language publications were selected that separately investigated the relation between ABO and/or Rh blood group and risk of SARS-CoV-2 and non-SARS-CoV-2 infection. Pooled odds ratios (ORp) and 95% confidence intervals (CI) were then generated for each. RESULTS: Non-O blood groups had a higher ORp for SARS-CoV-2 than O blood groups, both within 22 case-control studies (2.13, 95% CI 1.49- 3.04) and 15 cohort studies (1.89, 95% CI 1.56- 2.29). For non-SARS-CoV-2 viral infections, the respective ORp were 1.98 (95% CI 1.49-2.65; 4 case-control studies) and 1.87 (95% CI 1.53-2.29; 12 cohort studies). For non-viral infections, the ORp were 1.56 (95% CI 0.98-2.46; 13 case-control studies) and 2.11 (95% CI 1.67-6.67; 4 cohort studies). Rh-positive status had a higher ORp for SARS-CoV-2 infection within 6 case-control studies (13.83, 95% CI 6.18-30.96) and 6 cohort studies (19.04, 95% CI 11.63-31.17), compared to Rh-negative persons. For Rh status, non-SARS-CoV-2 infections, the ORp were 23.45 (95% CI 16.28-33.76) among 7 case-control studies, and 9.25 (95% CI 2.72-31.48) within 4 cohort studies. High measures of heterogeneity were notably observed for all analyses. CONCLUSIONS: Non-O and Rh-positive blood status are each associated with a higher risk of SARS-CoV-2 infection, in addition to other viral and non-viral infections.

Infertility and Risk of Autism Spectrum Disorder in Children.

Importance: Previous studies on the risk of childhood autism spectrum disorder (ASD) following fertility treatment did not account for the infertility itself or the mediating effect of obstetrical and neonatal factors. Objective: To assess the association between infertility and its treatments on the risk of ASD and the mediating effect of selected adverse pregnancy outcomes on that association. Design, Setting, and Participants: This was a population-based cohort study in Ontario, Canada. Participants were all singleton and multifetal live births at 24 or more weeks' gestation from 2006 to 2018. Data were analyzed from October 2022 to October 2023. Exposures: The exposure was mode of conception, namely, (1) unassisted conception, (2) infertility without fertility treatment (ie, subfertility), (3) ovulation induction (OI) or intrauterine insemination (IUI), or (4) in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Main Outcome and Measures: The study outcome was a diagnosis of ASD at age 18 months or older. Cox regression models generated hazard ratios (HR) adjusted for maternal and infant characteristics. Mediation analysis further accounted for the separate effect of (1) preeclampsia, (2) cesarean birth, (3) multifetal pregnancy, (4) preterm birth at less than 37 weeks, and (5) severe neonatal morbidity. Results: A total of 1 370 152 children (703 407 male [51.3%]) were included: 1 185 024 (86.5%) with unassisted conception, 141 180 (10.3%) with parental subfertility, 20 429 (1.5%) following OI or IUI, and 23 519 (1.7%) following IVF or ICSI. Individuals with subfertility or fertility treatment were older and resided in higher-income areas; the mean (SD) age of each group was as follows: 30.1 (5.2) years in the unassisted conception group, 33.3 (4.7) years in the subfertility group, 33.1 (4.4) years in the OI or IUI group, and 35.8 (4.9) years in the IVF or ICSI group. The incidence rate of ASD was 1.93 per 1000 person-years among children in the unassisted conception group. Relative to the latter, the adjusted HR for ASD was 1.20 (95% CI, 1.15-1.25) in the subfertility group, 1.21 (95% CI, 1.09-1.34) following OI or IUI, and 1.16 (95% CI, 1.04-1.28) after IVF or ICSI. Obstetrical and neonatal factors appeared to mediate a sizeable proportion of the aforementioned association between mode of conception and ASD risk. For example, following IVF or ICSI, the proportion mediated by cesarean birth was 29%, multifetal pregnancy was 78%, preterm birth was 50%, and severe neonatal morbidity was 25%. Conclusions and Relevance: In this cohort study, a slightly higher risk of ASD was observed in children born to individuals with infertility, which appears partly mediated by certain obstetrical and neonatal factors. To optimize child neurodevelopment, strategies should further explore these other factors in individuals with infertility, even among those not receiving fertility treatment.

Preconception SGLT2 or DPP4 inhibitor use and adverse pregnancy outcomes.

AIMS: To compare preconception use of sodium-glucose cotransporter-2 (SGLT2i) and dipeptidyl peptidase-4 (DPP4i) inhibitors to sulfonylurea agents, and associated peri-conceptional A1c concentration, and risk of pregnancy loss and congenital anomalies. METHODS: This population-based cohort study used administrative datasets for all of Ontario, Canada, and included women eligible for free medication coverage and who achieved a recognized pregnancy from April 2007-November 2021. Exposure was a SGLT2i, DPP4i or sulfonylurea (referent) dispensed at least 90 days preconception. Study outcomes included differences in periconceptional A1c; miscarriage, induced abortion, or stillbirth; and any congenital anomaly - the latter two outcomes assessed using propensity score overlap weighting. RESULTS: The mean (SD) periconceptional A1c was 8.1 % (2.0) among those prescribed any sulfonylurea, compared with 8.3 % (2.0) with a DPP4i and 7.8 % (1.6) with any SGLT2i. The risk of pregnancy loss was lowest among those exclusively prescribed a SGLT2i (relative risk [RR] 0.51, 95 % CI 0.22 to 0.91). Risk of a congenital anomaly at birth did not differ significantly comparing DPP4i or SGLT2i to sulfonylurea agents. CONCLUSIONS: Neither SGLT2i nor DPP4i use before pregnancy was associated with a difference in A1c, or a higher risk of selective adverse outcomes, compared to sulfonylureas. Future larger studies are required, including assessment of medication use after conception, during the critical period of embryogenesis.