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.

Validation of the Passive Surveillance Stroke Severity Score in Three Canadian Provinces.

BACKGROUND: Stroke outcomes research requires risk-adjustment for stroke severity, but this measure is often unavailable. The Passive Surveillance Stroke SeVerity (PaSSV) score is an administrative data-based stroke severity measure that was developed in Ontario, Canada. We assessed the geographical and temporal external validity of PaSSV in British Columbia (BC), Nova Scotia (NS) and Ontario, Canada. METHODS: We used linked administrative data in each province to identify adult patients with ischemic stroke or intracerebral hemorrhage between 2014-2019 and calculated their PaSSV score. We used Cox proportional hazards models to evaluate the association between the PaSSV score and the hazard of death over 30 days and the cause-specific hazard of admission to long-term care over 365 days. We assessed the models' discriminative values using Uno's c-statistic, comparing models with versus without PaSSV. RESULTS: We included 86,142 patients (n = 18,387 in BC, n = 65,082 in Ontario, n = 2,673 in NS). The mean and median PaSSV were similar across provinces. A higher PaSSV score, representing lower stroke severity, was associated with a lower hazard of death (hazard ratio and 95% confidence intervals 0.70 [0.68, 0.71] in BC, 0.69 [0.68, 0.69] in Ontario, 0.72 [0.68, 0.75] in NS) and admission to long-term care (0.77 [0.76, 0.79] in BC, 0.84 [0.83, 0.85] in Ontario, 0.86 [0.79, 0.93] in NS). Including PaSSV in the multivariable models increased the c-statistics compared to models without this variable. CONCLUSION: PaSSV has geographical and temporal validity, making it useful for risk-adjustment in stroke outcomes research, including in multi-jurisdiction analyses.

Defining a low-risk birth cohort: a cohort study comparing two perinatal data sets in Ontario, Canada.

Introduction: There are two main data sources for perinatal data in Ontario, Canada: the BORN BIS and CIHI-DAD. Such databases are used for perinatal health surveillance and research, and to guide health care related decisions. Objectives: Our primary objective was to examine the level of agreement between the BIS and CIHI-DAD. Our secondary objectives were to identify the differences between the data sources when identifying a low-risk birth (LRB) cohort and to understand their implications. Methods: We conducted a population-based cohort study comparing characteristics and clinical outcomes of all linkable births in BIS and CIHI-DAD between 1st April 2012 and 31st March 2018. We excluded out-of-hospital births, those with invalid healthcare numbers, non-Ontario residents and gestational age <20 weeks. We compared the portion of the cohort that met the criteria of a provincial definition of LRB based on each data source and compared clinical outcomes between the groups. Results: During the study period, 779,979 eligible births were linkable between the two data sources. After applying the LRB exclusions, there were 129,908 cases in the BIS and 136,184 cases in CIHI-DAD. Most exclusion criteria had almost perfect, substantial or moderate agreement. The agreement for non-cephalic presentation and BMI ≥ 40 kg/m2 (kappa coefficients 0.409 and 0.256, respectively) was fair. Comparison between the two LRB cohorts identified differences in the prevalence of cesarean (14.3% BIS versus 12.0% CIHI-DAD) and NICU admission (8.7% BIS versus 7.5% CIHI-DAD) and only 0.01% difference in the prevalence of ICU admission. Conclusions: Overall, we found high levels of agreement between the BIS and CIHI-DAD. Identifying a LRB cohort in either database may be appropriate, with the caveat of appropriate understanding of the collection, coding and definition of certain outcomes. The decision for selecting a database may depend on which variables are most important in a particular analysis.

Change in Hospital Risk-standardized Stroke Mortality Performance With and Without the Passive Surveillance Stroke Severity Score.

BACKGROUND: Adjustment for baseline stroke severity is necessary for accurate assessment of hospital performance. We evaluated whether adjusting for the Passive Surveillance Stroke SeVerity (PaSSV) score, a measure of stroke severity derived using administrative data, changed hospital-specific estimated 30-day risk-standardized mortality rate (RSMR) after stroke. METHODS: We used linked administrative data to identify adults who were hospitalized with ischemic stroke or intracerebral hemorrhage across 157 hospitals in Ontario, Canada between 2014 and 2019. We fitted a random effects logistic regression model using Markov Chain Monte Carlo methods to estimate hospital-specific 30-day RSMR and 95% credible intervals with adjustment for age, sex, Charlson comorbidity index, and stroke type. In a separate model, we additionally adjusted for stroke severity using PaSSV. Hospitals were defined as low-performing, average-performing, or high-performing depending on whether the RSMR and 95% credible interval were above, overlapping, or below the cohort's crude mortality rate. RESULTS: We identified 65,082 patients [48.0% were female, the median age (25th,75th percentiles) was 76 years (65,84), and 86.4% had an ischemic stroke]. The crude 30-day all-cause mortality rate was 14.1%. The inclusion of PaSSV in the model reclassified 18.5% (n=29) of the hospitals. Of the 143 hospitals initially classified as average-performing, after adjustment for PaSSV, 20 were reclassified as high-performing and 8 were reclassified as low-performing. Of the 4 hospitals initially classified as low-performing, 1 was reclassified as high-performing. All 10 hospitals initially classified as high-performing remained unchanged. CONCLUSION: PaSSV may be useful for risk-adjusting mortality when comparing hospital performance. External validation of our findings in other jurisdictions is needed.

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.

Outcomes of COVID-19 Infection and Vaccination Among Individuals With Myasthenia Gravis.

Importance: There are limited data regarding COVID-19 outcomes and vaccine uptake and safety among people with myasthenia gravis (MG). Objective: To investigate COVID-19-related outcomes and vaccine uptake among a population-based sample of adults with MG. Design, Setting, and Participants: This population-based, matched cohort study in Ontario, Canada, used administrative health data from January 15, 2020, and August 31, 2021. Adults with MG were identified using a validated algorithm. Each patient was matched by age, sex, and geographic area of residence to 5 controls from the general population and from a cohort of individuals with rheumatoid arthritis (RA). Exposure: Patients with MG and matched controls. Main Outcomes and Measures: Main outcomes were COVID-19 infection and related hospitalizations, intensive care unit admissions, and 30-day mortality among patients with MG vs controls. Secondary outcomes were uptake of COVID-19 vaccination among patients with MG vs controls. Results: Among 11 365 233 eligible Ontario residents, 4411 patients with MG (mean [SD] age, 67.7 [15.6] years; 2274 women [51.6%]) were matched to 22 055 general population controls (mean [SD] age, 67.7 [15.6] years; 11 370 women [51.6%]) and 22 055 controls with RA (mean [SD] age, 67.7 [15.6] years; 11 370 women [51.6%]). In the matched cohort, 38 861 of 44 110 individuals (88.1%) were urban residents; in the MG cohort, 3901 (88.4%) were urban residents. Between January 15, 2020, and May 17, 2021, 164 patients with MG (3.7%), 669 general population controls (3.0%), and 668 controls with RA (3.0%) contracted COVID-19. Compared with general population controls and controls with RA, patients with MG had higher rates of COVID-19-associated emergency department visits (36.6% [60 of 164] vs 24.4% [163 of 669] vs 29.9% [200 of 668]), hospital admissions (30.5% [50 of 164] vs 15.1% [101 of 669] vs 20.7% [138 of 668]), and 30-day mortality (14.6% [24 of 164] vs 8.5% [57 of 669] vs 9.9% [66 of 668]). By August 2021, 3540 patients with MG (80.3%) vs 17 913 general population controls (81.2%) had received 2 COVID-19 vaccine doses, and 137 (3.1%) vs 628 (2.8%), respectively had received 1 dose. Of 3461 first vaccine doses for patients with MG, fewer than 6 individuals were hospitalized for MG worsening within 30 days of vaccination. Vaccinated patients with MG had a lower risk than unvaccinated patients with MG of contracting COVID-19 (hazard ratio, 0.43; 95% CI, 0.30-0.60). Conclusions and Relevance: This study suggests that adults with MG who contracted COVID-19 had a higher risk of hospitalization and death compared with matched controls. Vaccine uptake was high, with negligible risk of severe MG exacerbations after vaccination, as well as evidence of effectiveness. The findings support public health policies prioritizing people with MG for vaccination and new COVID-19 therapeutics.

Maternal Emergency Department Use Before Pregnancy and Infant Emergency Department Use After Birth.

Importance: Maternal emergency department (ED) use before or during pregnancy is associated with worse obstetrical outcomes, for reasons including preexisting medical conditions and challenges in accessing health care. It is not known whether maternal prepregnancy ED use is associated with higher use of the ED by their infant. Objective: To study the association between maternal prepregnancy ED use and risk of infant ED use in the first year of life. Design, Setting, and Participants: This population-based cohort study included all singleton livebirths in all of Ontario, Canada, from June 2003 to January 2020. Exposures: Any maternal ED encounter within 90 days preceding the start of the index pregnancy. Main Outcomes and Measures: Any infant ED visit up to 365 days after the index birth hospitalization discharge date. Relative risks (RR) and absolute risk differences (ARD) were adjusted for maternal age, income, rural residence, immigrant status, parity, having a primary care clinician, and number of prepregnancy comorbidities. Results: There were 2 088 111 singleton livebirths; the mean (SD) maternal age was 29.5 (5.4) years, 208 356 (10.0%) were rural dwelling, and 487 773 (23.4%) had 3 or more comorbidities. Among singleton livebirths, 206 539 mothers (9.9%) had an ED visit within 90 days before the index pregnancy. ED use in the first year of life was higher among infants whose mother had visited the ED before pregnancy (570 per 1000) vs those whose mother had not (388 per 1000) (RR, 1.19 [95% CI, 1.18-1.20]; ARD, 91.1 per 1000 [95% CI, 88.6-93.6 per 1000]). Compared with mothers without a prepregnancy ED visit, the RR of infant ED use in the first year was 1.19 (95% CI, 1.18-1.20) if its mother had 1 prepregnancy ED visit, 1.18 (95% CI, 1.17-1.20) following 2 visits, and 1.22 (95% CI, 1.20-1.23) after at least 3 maternal visits. A low-acuity maternal prepregnancy ED visit was associated with an adjusted odds ratio (aOR) of 5.52 (95% CI, 5.16-5.90) for a low-acuity infant ED visit, which was numerically higher than the pairing of a high-acuity ED use between mother and infant (aOR, 1.43, 95% CI, 1.38-1.49). Conclusions and Relevance: In this cohort study of singleton livebirths, prepregnancy maternal ED use was associated with a higher rate of ED use by the infant in the first year of life, especially for low-acuity ED use. This study's results may suggest a useful trigger for health system interventions aimed at reducing some ED use in infancy.

Severity of obstructive coronary artery stenosis after pre-eclampsia.

INTRODUCTION: Women with a history of pre-eclampsia are at higher risk of premature coronary artery disease. Assessment of obstructive coronary artery stenosis by invasive coronary angiography has not been evaluated after pre-eclampsia. METHODS: A population-based cohort study was completed in Ontario, Canada, where there is universal healthcare and collection of angiographic data. Included were women with a live birth or stillbirth from 2002 to 2020, and without known heart disease. One birth was randomly selected per woman. The main exposure compared women with versus without pre-eclampsia. The primary outcome was angiographically established obstructive coronary artery stenosis, assessed starting 42 days after the index birth. Cause-specific hazard models accounting for competing risks generated HRs, adjusted for age, parity, income, rurality, diabetes, chronic hypertension, renal disease, substance use and dyslipidaemia. RESULTS: Among 42 252 women ever with pre-eclampsia and 1359 122 never with pre-eclampsia, mean age was 31.1 years and 30.6 years, respectively. After 9 years of follow-up, obstructive coronary artery stenosis occurred in 186 women with pre-eclampsia (4.53 per 10 000 person-years) versus 1237 women without pre-eclampsia (0.97 per 10 000 person-years)-an unadjusted HR 4.41 (95% CI 3.78 to 5.14) and adjusted HR 2.07 (95% CI 1.77 to 2.43). Relative to those with neither, the adjusted HR for coronary stenosis was highest in women with pre-eclampsia and preterm birth (3.11, 95% CI 2.51 to 3.87), or pre-eclampsia and stillbirth (2.80, 95% CI 1.05 to 7.47). CONCLUSIONS: Pre-eclampsia is associated with a greater risk of premature-onset obstructive coronary artery stenosis, especially when it is complicated by a preterm birth or a stillbirth.

Prepregnancy Emergency Department Use and Risks of Severe Maternal and Neonatal Morbidity in Canada.

Importance: Emergency department (ED) use during pregnancy may be associated with worse obstetrical outcomes, possibly because of differences in access to health care. It is not known whether ED use before pregnancy is associated with serious adverse maternal and perinatal outcomes. Objective: To study the association between prepregnancy ED use and adverse maternal and perinatal outcomes. Design, Setting, and Participants: This population-based cohort study was conducted in Ontario, Canada, and included all livebirths and stillbirths from April 2003 to January 2020. Exposures: Main exposure was any ED encounter within 90 days preceding the start of the index pregnancy. Main Outcomes and Measures: Primary outcome was a composite of severe maternal morbidity (SMM) from 20 weeks' gestation to 42 days' post partum. Secondary outcomes included severe neonatal morbidity (SNM) from 0 to 27 days, neonatal death, and stillbirth. Relative risks (RRs) were adjusted for maternal age, income, and rurality. Results: Of 2 130 245 births, there were 2 119 335 livebirths (99.5%) and 10 910 stillbirths (0.5%). The mean (SD) maternal age was 29.6 (5.4) years, 212 478 (9.9%) were rural dwelling, and 498 219 (23%) had 3 or more comorbidities. Among all births, 218 011 (9.7%) had a prepregnancy ED visit. The rate of SMM was higher among women with a prepregnancy ED visit than those without (22.3 vs 16.5 per 1000 births), with an RR of 1.34 (95% CI, 1.30-1.38) and an adjusted RR (aRR) of 1.37 (95% CI, 1.33-1.42). Compared with no prepregnancy ED visit, the aRR was higher in those with 1 (1.29; 95% CI, 1.24-1.34), 2 (1.51; 95% CI, 1.42-1.61), and 3 or more (1.74; 95% CI, 1.61-1.90) ED visits. Prepregnancy ED visits for a hematological (aRR, 13.60; 95% CI, 10.48-17.64), endocrine (aRR, 4.96; 95% CI, 3.72-6.62), and circulatory (aRR, 2.27; 95% CI, 1.68-3.07) conditions were associated with the highest aRRs for SMM. The rate of SNM was higher among newborns whose mother visited the ED within 90 days before pregnancy (68.2 vs 55.4 per 1000 births; aRR, 1.24; 95% CI, 1.22-1.26) as was the risk of neonatal death (aRR, 1.26; 95% CI, 1.16-1.37) and stillbirth (aRR, 1.18; 95% CI, 1.11-1.25). Conclusions and Relevance: In this study, ED use was common before pregnancy. These findings suggest that ED use may not only reflect a woman's access to prepregnancy care but also higher future risk of severe maternal and perinatal morbidity, potentially offering a useful trigger for health system interventions to decrease adverse pregnancy outcomes.

SARS-CoV-2 vaccination, ABO blood group and risk of COVID-19: population-based cohort study.

OBJECTIVE: To compare outcomes between O and non-O blood groups, and by modified RNA (mRNA) and adenovirus-vectored (Ad-V) vaccines. DESIGN: Population-based cohort study. SETTING: All of Ontario, Canada. Linked data sets captured clinical encounters, vaccinations and laboratory testing for SARS-CoV-2. PARTICIPANTS: Individuals aged 12+ years with known ABO blood group and free of SARS-CoV-2 before 15 January 2021. MAIN OUTCOMES MEASURES: The main exposure, first SARS-CoV-2 vaccination, was modelled in a time-varying manner. O and non-O blood group was known prior to vaccination. SARS-CoV-2 infection, and severe COVID-19 (hospitalisation or death), were assessed starting 14 days after vaccination, up to 27 June 2021. RESULTS: 2 472 261 individuals were included. 1 743 916 (70.5%) had at least one vaccination, of which 24.6% were fully vaccinated. Those vaccinated were more likely to be women, older in age, residing in a higher-income area and have higher rates of certain comorbid conditions, like cancer, diabetes and hypertension. Relative to unvaccinated, after receiving their first mRNA (adjusted HR (aHR) 0.46, 95% CI 0.44 to 0.47) or Ad-V (aHR 0.49, 95% CI 0.44 to 0.54) vaccine, the risk of SARS-CoV-2 infection was lower, as was severe COVID-19 (aHR 0.29, 95% CI 0.20 to 0.43 (mRNA); aHR 0.29, 95% CI 0.26 to 0.33 (Ad-V)). Stratifying by blood group produced similar results. For example, after first mRNA vaccination, the aHR of severe COVID-19 was 0.31 (95% CI 0.27 to 0.36) among non-O blood groups, and 0.27 (95% CI 0.22 to 0.32) among O blood groups, relative to unvaccinated. Fully vaccinated individuals had the lowest risk of SARS-CoV-2 and severe COVID-19. CONCLUSIONS: SARS-CoV-2 infection and severe COVID-19 are reduced by vaccination. This effect does not vary by vaccine type or blood group, but is more pronounced among fully, than partially, vaccinated individuals.

Obstetrical and Perinatal Outcomes in Female Survivors of Childhood and Adolescent Cancer: A Population-Based Cohort Study.

BACKGROUND: The likelihood of pregnancy and risk of obstetrical or perinatal complications is inadequately documented in female survivors of pediatric cancer. METHODS: We assembled a population-based cohort of female survivors of cancer diagnosed at age 21 years and younger in Ontario, Canada, between 1985 and 2012. Survivors were matched 1:5 to women without prior cancer. Multivariable Cox proportional hazards and modified Poisson models assessed the likelihood of a recognized pregnancy and perinatal and maternal complications. RESULTS: A total of 4062 survivors were matched to 20 308 comparisons. Median (interquartile range) age was 11 (4-15) years at cancer diagnosis and 25 (19-31) years at follow-up. By age 30 years, the cumulative incidence of achieving a recognized pregnancy was 22.3% (95% confidence interval [CI] = 20.7% to 23.9%) among survivors vs 26.6% (95% CI = 25.6% to 27.3%) among comparisons (hazard ratio = 0.80, 95% CI = 0.75 to 0.86). A lower likelihood of pregnancy was associated with a brain tumor, alkylator chemotherapy, cranial radiation, and hematopoietic stem cell transplantation. Pregnant survivors were as likely as cancer-free women to carry a pregnancy >20 weeks (relative risk [RR] = 1.01, 95% CI = 0.98 to 1.04). Survivors had a higher relative risk of severe maternal morbidity (RR = 2.31, 95% CI = 1.59 to 3.37), cardiac morbidity (RR = 4.18, 95% CI = 1.89 to 9.24), and preterm birth (RR = 1.57, 95% CI = 1.29 to 1.92). Preterm birth was more likely in survivors treated with hematopoietic stem cell transplantation (allogenic: RR = 8.37, 95% CI = 4.83 to 14.48; autologous: RR = 3.72, 95% CI = 1.66 to 8.35). CONCLUSIONS: Survivors of childhood or adolescent cancer are less likely to achieve a pregnancy and, once pregnant, are at higher risk for severe maternal morbidity and preterm birth.

Comparison of Self-harm or Overdose Among Adolescents and Young Adults Before vs During the COVID-19 Pandemic in Ontario.

Importance: Self-harm and deaths among adolescents and young adults are notably related to drug poisonings and suicide. With the emergence of the COVID-19 pandemic, there are projections about a greater likelihood of such events arising among adolescents and young adults. Objective: To evaluate the risk of self-harm, overdose, and all-cause mortality among adolescents and young adults during the COVID-19 pandemic. Design, Setting, and Participants: This population-based cohort study took place in Ontario, Canada, where a universal health care system captures all emergency department (ED) visits, hospitalizations, and deaths. The participants included all adolescents and young adults born in Ontario between 1990 and 2006, who were aged 14 to 24 years between March 1, 2018, and June 30, 2021. Exposures: The COVID-19 pandemic era (April 1, 2020 to June 30, 2021), relative to the 2 years preceding the pandemic (March 1, 2018 to February 28, 2020). Main Outcomes and Measures: ED encounters or hospitalizations for self-harm or overdose. A secondary outcome was self-harm, overdose, or all-cause mortality. Cause-specific hazard models to estimate hazard ratios (HR) and 95% CIs were used for the primary outcome. Follow-up started at March 1, 2018, or the individual's 14th birthday, whichever was later, and age was used as the time scale. Results: In this study, 1 690 733 adolescents and young adults (823 904 [51.3%] female participants) were included with a median (IQR) age of 17.7 (14.1-21.4) years at start of follow-up. After 4 110 903 person-years of follow-up, 6224 adolescents and young adults experienced the primary outcome of self-harm or overdose during the pandemic (39.7 per 10 000 person-years) vs 12 970 (51.0 per 10 000 person-years) prepandemic, with an HR of 0.78 (95% CI, 0.75-0.80). The risk of self-harm, overdose, or death was also lower during than before the pandemic (HR, 0.78; 95% CI, 0.76-0.81), but not all-cause mortality (HR, 0.95; 95% CI, 0.86-1.05). Conclusions and Relevance: Among adolescents and young adults, the initial 15-month period of the COVID-19 pandemic was associated with a relative decline in hospital care for self-harm or overdose.

Association Between Blunted Glomerular Hyperfiltration in Pregnancy and Severe Maternal Morbidity-A Research Letter.

BACKGROUND: Glomerular hyperfiltration is one physiological adaptation to pregnancy, marked by a decline in serum creatinine (SCr) concentration by 16 weeks' gestation. It is not known whether blunted glomerular hyperfiltration leads to adverse maternal outcomes, including severe maternal morbidity (SMM). OBJECTIVE: To evaluate the association between blunted glomerular hyperfiltration and subsequent SMM or death. DESIGN: Population-based cohort study. SETTING: Ontario, Canada, from 2008 to 2019. PARTICIPANTS: Included were births among women who had ≥ 1 SCr measured as an outpatient within 10 weeks before conception ("preconception"), and again, at 110/7 to 206/7 weeks' gestation ("in-pregnancy"). Excluded were women who died before birth, who had end-stage renal disease or kidney transplantation before conception, or whose pre-pregnancy SCr was 125 µmol/L. EXPOSURE: Net glomerular hyperfiltration defined as the preconception minus the in-pregnancy SCr. MEASURES: The primary study outcome was SMM or death arising from 23 weeks' gestation up to 42 days after the index birth. METHODS: Adjusted relative risks (aRRs) were calculated using Modified Poisson regression per 1-SD net blunting of glomerular hyperfiltration adjusting for important covariates. RESULTS: A total of 10,323 births met all inclusion criteria. The mean (SD) SCr was 61.7 (11.0) µmol/L preconception, 48.0 (9.2) µmol/L in-pregnancy, and the mean net difference 13.6 (8.2) µmol/L. Among these births, the adjusted RR of SMM or death from 23 weeks' gestation up to 42 days post-partum was 1.16 (95% confidence interval 1.14-1.30) per 1-SD (8.2 µmol/L) net blunting of glomerular hyperfiltration. LIMITATIONS: As SCr assessment is not a routine part of pregnancy care, its measurement could have been for a specific health condition thereby imparting selection bias. CONCLUSIONS: Blunted glomerular hyperfiltration in pregnancy may identify some women at higher risk of SMM. Further prospective research is needed about the implications of glomerular hyperfiltration in early pregnancy.

CONTEXTE: L'hyperfiltration glomérulaire est une adaptation physiologique à la grossesse qui se caractérise par une baisse du taux de créatinine sérique (CrS) à 16 semaines de gestation. On ignore toutefois si l'hyperfiltration glomérulaire atténuée entraîne des résultats indésirables pour la mère, notamment des cas graves de morbidité maternelle (morbidité maternelle grave­MMG). OBJECTIF: Examiner le lien entre l'hyperfiltration glomérulaire atténuée et une MMG subséquente ou le décès. TYPE D'ÉTUDE: Étude de cohorte basée sur une population. CADRE: Étude menée en Ontario (Canada) entre 2008 et 2019. SUJETS: Ont été retenues pour l'étude les naissances liées à des femmes qui disposaient d'au moins une mesure de la CrS en consultation externe dans les 10 semaines précédant la conception (« préconception ¼) et d'une autre entre les semaines 110/7 et 206/7 de la grossesse (« pendant la grossesse ¼). Ont été exclues les femmes décédées avant l'accouchement, celles qui étaient atteintes d'insuffisance rénale terminale ou qui avaient subi une transplantation rénale avant la conception, ainsi que celles qui présentaient une mesure de la créatinine sérique supérieure à 125 µmol/L avant la grossesse. EXPOSITION: La valeur de l'hyperfiltration glomérulaire nette a été définie comme la différence entre la mesure de CrS préconception et celle mesurée pendant la grossesse. MESURES: Le principal critère d'évaluation était une MMG ou le décès dans la période couvrant de la 23e semaine de grossesse jusqu'à 42 jours après l'accouchement. MÉTHODOLOGIE: Les risques relatifs corrigés (RRc) ont été calculés à l'aide d'un modèle de régression de Poisson modifié pour 1-ÉT pour l'hyperfiltration glomérulaire atténuée corrigée en tenant compte des covariables importantes. RÉSULTATS: Au total, 10 323 naissances répondaient à tous les critères d'inclusion. Le taux de créatinine sérique moyen (ÉT) était de 61,7 (11,0) µmol/L préconception et de 48,0 (9,2) µmol/L pendant la grossesse. La différence nette moyenne s'établissait à 13,6 (8,2) µmol/L. Le RRc de MMG ou de décès pendant la période couvrant de la 23e semaine de grossesse jusqu'à 42 jours après l'accouchement s'établissait à 1,16 (IC 95 %: 1,14-1,30) pour 1-ÉT (8,2 µmol/L) d'hyperfiltration glomérulaire atténuée. LIMITES: La mesure de la CrS n'étant pas une composante courante des soins liés au suivi d'une grossesse, les mesures disponibles pourraient avoir été faites dans un cadre spécifique, ce qui entraîne un biais de sélection. CONCLUSION: L'hyperfiltration glomérulaire atténuée pendant la grossesse pourrait permettre de détecter les femmes qui présentent un risque accru de MMG. D'autres recherches prospectives portant sur les conséquences de l'hyperfiltration glomérulaire au début de la grossesse sont nécessaires.

Development and internal validation of a model predicting severe maternal morbidity using pre-conception and early pregnancy variables: a population-based study in Ontario, Canada.

BACKGROUND: Improvement in the prediction and prevention of severe maternal morbidity (SMM) - a range of life-threatening conditions during pregnancy, at delivery or within 42 days postpartum - is a public health priority. Reduction of SMM at a population level would be facilitated by early identification and prediction. We sought to develop and internally validate a model to predict maternal end-organ injury or death using variables routinely collected during pre-pregnancy and the early pregnancy period. METHODS: We performed a population-based cohort study using linked administrative health data in Ontario, Canada, from April 1, 2006 to March 31, 2014. We included women aged 18-60 years with a livebirth or stillbirth, of which one birth was randomly selected per woman. We constructed a clinical prediction model for the primary composite outcome of any maternal end-organ injury or death, arising between 20 weeks' gestation and 42 days after the birth hospital discharge date. Our model included variables collected from 12 months before estimated conception until 19 weeks' gestation. We developed a separate model for parous women to allow for the inclusion of factors from previous pregnancy(ies). RESULTS: Of 634,290 women, 1969 experienced the primary composite outcome (3.1 per 1000). Predictive factors in the main model included maternal world region of origin, chronic medical conditions, parity, and obstetrical/perinatal issues - with moderate model discrimination (C-statistic 0.68, 95% CI 0.66-0.69). Among 333,435 parous women, the C-statistic was 0.71 (0.69-0.73) in the model using variables from the current (index) pregnancy as well as pre-pregnancy predictors and variables from any previous pregnancy. CONCLUSIONS: A combination of factors ascertained early in pregnancy through a basic medical history help to identify women at risk for severe morbidity, who may benefit from targeted preventive and surveillance strategies including appropriate specialty-based antenatal care pathways. Further refinement and external validation of this model are warranted and can support evidence-based improvements in clinical practice.

Non-ABO red cell antibodies and risk of COVID-19.

It is not known whether non-ABO antibodies confer any protective effect against SARS-CoV-2 infection or COVID-19 severe illness alone or in conjunction with O blood group. This cohort study included 413 576 persons in Ontario, Canada with known ABO blood group and non-ABO antibody screen status, who subsequently underwent SARS-CoV-2 viral RNA polymerase chain reaction testing between January and November 2020. The risk of SARS-CoV-2 infection or COVID-19 severe illness was not associated with the presence of non-ABO antibodies, even among persons with O blood group.

Identifying maternal deaths with the use of hospital data versus death certificates: a retrospective population-based study.

BACKGROUND: Accurate identification of maternal deaths is paramount for audit and policy purposes. Our aim was to determine the accuracy and completeness of data on maternal deaths in hospital and those recorded on a death certificate, and the level of agreement between the 2 data sources. METHODS: We conducted a retrospective population-based study using data for Ontario, Canada, from Apr. 1, 2002, to Dec. 31, 2015. We used Canadian Institute for Health Information (CIHI) databases to identify deaths during inpatient, emergency department and same-day surgery encounters. We captured Vital Statistics deaths in the Office of the Registrar General, Deaths (ORGD) data set. Deaths were considered within 42 days and within 365 days after a pregnancy outcome (live birth, miscarriage, ectopic pregnancy or induced abortion) for all multiple and singleton pregnancies. We calculated agreement statistics and 95% confidence intervals (CIs). RESULTS: Among 1 679 455 live births and stillbirths, 398 pregnancy-related deaths in the ORGD data set were mapped to a birth in CIHI databases, and 77 (16.2%) were not. Among 2 039 849 recognized pregnancies, 534 pregnancy-related deaths in the ORGD data set were linked to CIHI records, and 68 (11.3%) were not. Among live births and stillbirths, after pregnancy-related deaths in the ORGD data set not matched to a maternal death in the CIHI databases were removed, concordance measures between CIHI and ORGD records for maternal death within 42 days after delivery included a κ value of 0.87 (95% CI 0.82-0.91) and positive percent agreement of 0.88 (95% CI 0.83-0.94). The corresponding measures were similar for maternal death within 42 days after the end of a recognized pregnancy. When unlinked pregnancy-related deaths in the ORGD data set were retained, agreement measures declined for death within 42 days after a live birth or stillbirth (κ = 0.68, 95% CI 0.62-0.74). For maternal death within 365 days after a live birth or stillbirth, or after the end of a recognized pregnancy, the concordance statistics were generally favourable when unlinked pregnancy-related deaths in the ORGD data set were removed but were substantially declined when they were retained. INTERPRETATION: Maternal mortality cannot be ascertained solely with the use of hospital data, including beyond 42 days after the end of pregnancy. To improve linkage, we propose including health insurance numbers on provincial and territorial medical death certificates.

Risk of Severe Maternal Morbidity or Death in Relation to Prenatal Biochemical Screening: Population-Based Cohort Study.

OBJECTIVE: This study aimed to examine whether prenatal biochemical screening analytes are associated with an increased risk of severe maternal morbidity (SMM) or maternal mortality. STUDY DESIGN: This population-based cohort study includes all women in Ontario, Canada, who underwent prenatal screening from 2001 to 2011. Increasing fifth percentiles of the multiple of the median (MoM) for alphafetoprotein (AFP), total human chorionic gonadotropin, unconjugated estriol (uE3), dimeric inhibin-A (DIA), and pregnancy-associated plasma protein A were evaluated. An abnormally high concentration (>95th percentile MoM) for each analyte, individually and combined, was also evaluated. The main outcome assessed was the adjusted relative risk (aRR) of SMM or maternal mortality from 20 weeks' gestation up to 26 weeks thereafter. RESULTS: Among 748,972 pregnancies, 11,177 resulted in SMM or maternal mortality (1.5%). Except for uE3, the aRR of SMM or maternal mortality increased in association with increasing fifth percentiles of the MoM for all analytes. AFP (aRR: 2.10; 95% confidence interval [CI]: 1.97-2.25) and DIA (aRR: 2.33; 95% CI: 1.98-2.74) > 95th versus ≤ 5th percentile of the MoM were especially associated with SMM or death. CONCLUSION: Women with abnormally high concentrations of certain prenatal biochemical analytes may be at a higher risk of SMM or death in pregnancy or postpartum.

Maternal Visceral Adipose Tissue and Risk of Having a Small or Large for Gestational Age Infant.

OBJECTIVE: To determine whether first-trimester visceral adipose tissue (VAT) depth is associated with small-for-gestational-age (SGA; <10th percentile) or large-for-gestational-age (LGA; >90th percentile) birthweight, including when taking into consideration ethnicity-specific birthweight curves. METHODS: We conducted a prospective cohort study involving 452 women with a singleton livebirth. Maternal VAT depth was measured by ultrasound at 11 to 14 weeks gestation. Newborn weight was plotted on population-based and ethnicity-specific birthweight percentile curves. Modelling was performed using linear and logistic regression, adjusting for parity, smoking status, and weight gain. RESULTS: Mean maternal age was 32.9 ± 4.7 years, and mean VAT depth was 4.1 ± 1.7 cm. Using a population-based curve, each 1-cm increase in VAT depth was associated with a 1.5 (95% CI 0.03-3.0) higher birthweight percentile. Taking into account ethnicity-specific curves, a 1-cm higher VAT depth was associated with a 1.7 (95% CI 0.02-3.3) greater birthweight percentile. Using a population-based curve, comparing VAT depth Q4 with VAT depth Q1-3, the adjusted odds ratio (aOR) for LGA was 1.9 (95% CI 0.8-4.1); with ethnicity-specific curves, the aOR for LGA was 1.5 (95% CI 0.7-3.2). The aOR for SGA was 0.8 (95% CI 0.4 to 1.7) comparing Q1 with Q2-4 VAT depth. CONCLUSION: Higher first-trimester maternal VAT depth was associated with a somewhat greater newborn weight percentile, which varies by which birthweight curve is used. There were marginally higher odds of giving birth to an LGA infant for women in highest quartile for VAT depth, with no evident association with SGA.