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Objective To develop a practical evidence based list of clinical risk factors that can be assessed by a clinician at ≤16 weeks’ gestation to estimate a woman’s risk of pre-eclampsia.Design Systematic review and meta-analysis of cohort studies.Data sources PubMed and Embase databases, 2000-15.Eligibility criteria for selecting studies Cohort studies with ≥1000 participants that evaluated the risk of pre-eclampsia in relation to a common and generally accepted clinical risk factor assessed at ≤16 weeks’ gestation.Data extraction Two independent reviewers extracted data from included studies. A pooled event rate and pooled relative risk for pre-eclampsia were calculated for each of 14 risk factors.Results There were 25 356 688 pregnancies among 92 studies. The pooled relative risk for each risk factor significantly exceeded 1.0, except for prior intrauterine growth restriction. Women with antiphospholipid antibody syndrome had the highest pooled rate of pre-eclampsia (17.3%, 95% confidence interval 6.8% to 31.4%). Those with prior pre-eclampsia had the greatest pooled relative risk (8.4, 7.1 to 9.9). Chronic hypertension ranked second, both in terms of its pooled rate (16.0%, 12.6% to 19.7%) and pooled relative risk (5.1, 4.0 to 6.5) of pre-eclampsia. Pregestational diabetes (pooled rate 11.0%, 8.4% to 13.8%; pooled relative risk 3.7, 3.1 to 4.3), prepregnancy body mass index (BMI) >30 (7.1%, 6.1% to 8.2%; 2.8, 2.6 to 3.1), and use of assisted reproductive technology (6.2%, 4.7% to 7.9%; 1.8, 1.6 to 2.1) were other prominent risk factors.Conclusions There are several practical clinical risk factors that, either alone or in combination, might identify women in early pregnancy who are at “high risk” of pre-eclampsia. These data can inform the generation of a clinical prediction model for pre-eclampsia and the use of aspirin prophylaxis in pregnancy.

The relation between prepregnancy average glucose concentration and a woman's risk of severe maternal morbidity (SMM) is unknown. The current study evaluated whether an elevated preconception hemoglobin A1c (A1c) is associated with SMM or maternal death among women with and without known prepregnancy diabetes mellitus (DM). A population-based cohort study was completed in Ontario, Canada, where there is universal healthcare. The main cohort included 31,225 women aged 16-50 years with a hospital live birth or stillbirth from 2007 to 2015, and who had an A1c measured within 90 days before conception, including 28,075 women (90%) without known prepregnancy DM. The main outcome was SMM or maternal mortality from 23 weeks' gestation up to 42 days postpartum. Relative risks (RRs) were generated using modified Poisson regression, adjusting for the main covariates of maternal age, multifetal pregnancy, world region of origin, and tobacco/drug dependence. The mean maternal age was 31.1 years. Overall, SMM or death arose among 682 births (2.2%). The RR of SMM or death was 1.16 (95% CI 1.14-1.19; p < 0.001) per 0.5% increase in A1c and 1.16 (95% CI 1.13-1.18; p < 0.001) after adjusting for the main covariates. The adjusted relative risk (aRR) was increased among those with (1.11, 95% CI 1.07-1.14; p < 0.001) and without (1.15, 95% CI 1.02-1.29; p < 0.001) known prepregnancy diabetes, and upon further adjusting for body mass index (BMI) (1.15, 95% CI 1.11-1.20; p < 0.001), or chronic hypertension and prepregnancy serum creatinine (1.11, 95% CI 1.04-1.18; p = 0.002). The aRR of SMM or death was 1.31 (95% CI 1.06-1.62; p = 0.01) in those with a preconception A1c of 5.8%-6.4%, and 2.84 (95% CI 2.31-3.49; p < 0.001) at an A1c > 6.4%, each relative to an A1c < 5.8%. Among those without previously recognized prepregnancy diabetes and whose A1c was >6.4%, the aRR of SMM or death was 3.25 (95% CI 1.76-6.00; p < 0.001). Study limitations include that selection bias may have incorporated less healthy women tested for A1c, and BMI was unknown for many women. Our findings indicate that women with an elevated A1c preconception may be at higher risk of SMM or death in pregnancy or postpartum, including those without known prepregnancy DM.

ObjectiveTo compare outcomes between O and non-O blood groups, and by modified RNA (mRNA) and adenovirus-vectored (Ad-V) vaccines.DesignPopulation-based cohort study.SettingAll of Ontario, Canada. Linked data sets captured clinical encounters, vaccinations and laboratory testing for SARS-CoV-2.ParticipantsIndividuals aged 12+ years with known ABO blood group and free of SARS-CoV-2 before 15 January 2021.Main outcomes measuresThe 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.Results2 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.ConclusionsSARS-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.

BackgroundMany youth deaths occur in the first year of life, from prematurity and anomalies. Detailing mortality after age 1 year may differentially guide preventive strategies in children, adolescents and young adults.MethodsA cohort study in Ontario, Canada comprised 3 139 698 children born from 1990 to 2016. Adjusted HR (aHR) for death between 1 and 24 years were generated, comparing demographic variables and parity.ResultsAfter a median of 13.7 years of follow-up, 6930 deaths occurred between ages 1 and 24 years (incidence rate 17.0 per 100 000 person-years), peaking at age 23 years (43.7 per 100 000). The aHR for death was higher among males than females (1.44, 95% CI 1.37 to 1.51), rural versus urban areas (1.48, 95% CI 1.39 to 1.58), lowest versus highest income areas (1.39, 95% CI 1.29 to 1.51) and at parity 1 (1.16, 95% CI 1.10 to 1.23), parity 2 (1.34, 95% CI 1.23 to 1.45), parity 3+ (1.96, 95% CI 1.74 to 2.21), each relative to a child without an older sibling. Among males, the proportion of deaths due to injury jumped from 30% before age 15 years to 65% thereafter, and in females, from 28% to 51%. Intentional self-harm/assault explained 11% of injury-related deaths among males before age 15 years, and 20% thereafter, with respective figures of 18% and 17% for females. Deaths outside of hospital increased with age, from 35% at age 1 year, to 66% at age 22 years.ConclusionThere is a heightened susceptibility of dying starting at age 15 years, especially among males, from injury, and arising outside of hospital.

Cold-induced thermogenesis is known to improve insulin sensitivity, which may become increasingly relevant in the face of global warming. The aim of this study was to examine the relation between outdoor air temperature and the risk of gestational diabetes mellitus. We identified all births in the Greater Toronto Area from 2002 to 2014 using administrative health databases. Generalized estimating equations were used to examine the relation between the mean 30-day outdoor air temperature before the time of gestational diabetes mellitus screening and the likelihood of diagnosis of gestational diabetes mellitus based on a validated algorithm using hospital records and physician service claims. Over the 12-year period, there were 555 911 births among 396 828 women. Prevalence of gestational diabetes mellitus was 4.6% among women exposed to extremely cold mean outdoor air temperatures (≤ −10°C) in the 30-day period before screening and increased to 7.7% among those exposed to hot mean 30-day temperatures (≥ 24°C). Each 10°C increase in mean 30-day temperature was associated with a 1.06 (95% confidence interval [CI] 1.04–1.07) times higher odds of gestational diabetes mellitus, after adjusting for maternal age, parity, neighbourhood income quintile, world region and year. A similar effect was seen for each 10°C rise in outdoor air temperature difference between 2 consecutive pregnancies for the same woman (adjusted odds ratio 1.06, 95% CI 1.03–1.08). In our setting, there was a direct relation between outdoor air temperature and the likelihood of gestational diabetes mellitus. Future climate patterns may substantially affect global variations in the prevalence of diabetes, which also has important implications for the prevention and treatment of gestational diabetes mellitus.

IntroductionWomen 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.MethodsA 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.ResultsAmong 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).ConclusionsPre-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.

The extent to which infertility treatment predicts severe maternal morbidity is not well known. We examined the association between infertility treatment and severe maternal morbidity in pregnancy and the postpartum period. We conducted a cohort study using population-based registries from Ontario between 2006 and 2012. Pregnancies achieved using infertility treatment (ovulation induction, intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection) were compared with unassisted pregnancies using propensity score matching, based on demographic, reproductive and obstetric factors. The primary outcome was a validated composite of severe maternal morbidity or maternal death from 20 weeks’ gestation to 42 days postpartum. We also calculated the odds ratio of a woman having 1, 2, or 3 or more severe maternal morbidity indicators in relation to invasive (e.g., in vitro fertilization) or noninvasive (e.g., intrauterine insemination) infertility treatment. We matched 11 546 infertility treatment pregnancies with 47 553 untreated pregnancies. Severe maternal morbidity or maternal death occurred in 356 infertility-treated pregnancies (30.8 per 1000 deliveries) versus 1054 untreated pregnancies (22.2 per 1000 deliveries); relative risk 1.39 (95% confidence interval [CI] 1.23–1.56). The likelihood of a woman having 3 or more severe maternal morbidity indicators was increased in women who received invasive infertility treatment (odds ratio [OR] 2.28, 95% CI 1.56–3.33) but not in those who received noninvasive infertility treatment (OR 0.99, 95% CI 0.57–1.72). Women who undergo infertility treatment, particularly in vitro fertilization, are at somewhat higher risk of severe maternal morbidity or death. Efforts are needed to identify patient- and treatment-specific predictors of severe maternal morbidity that may influence the type of treatment a woman is offered.

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. To evaluate the risk of self-harm, overdose, and all-cause mortality among adolescents and young adults during the COVID-19 pandemic. 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. 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). 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. 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). 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.

Prepregnancy kidney dysfunction has been associated with preterm birth, which is the leading cause of neonatal morbidity and mortality; however, the relation is not well understood. We determined the risk of preterm birth in women with prepregnancy kidney dysfunction, defined using pregnancy-specific serum creatinine cut points. This population-based cohort study in the province of Ontario, Canada, involved women aged 16 to 50 years who had a singleton birth between 2006 and 2016 and measurement of serum creatinine within 10 weeks preceding their estimated conception date. The exposure was abnormally elevated prepregnancy serum creatinine, defined as greater than the 95th percentile (> 77 μmol/L), a value derived from a population-based sample of women without known kidney disease who became pregnant soon after the measurement was obtained. The main outcome was any preterm birth from 23 to 36 weeks’ gestation. Secondary outcomes included provider-initiated preterm birth before 37 weeks’ gestation and spontaneous preterm birth before 37 weeks. Among 55 946 pregnancies, preterm birth before 37 weeks’ gestation occurred in 3956 women (7.1%). The risk of preterm birth before 37 weeks was higher among women with prepregnancy creatinine above the 95th percentile, relative to those with prepregnancy creatinine at or below the 95th percentile (9.1% v. 7.0%; adjusted relative risk [RR] 1.23, 95% confidence interval [CI] 1.09 to 1.38). The effect was significant for provider-initiated preterm birth (adjusted RR 1.30, 95% CI 1.11 to 1.52) but not for spontaneous preterm birth (adjusted RR 1.12, 95% CI 0.91 to 1.37). Given that prepregnancy kidney dysfunction conferred an increased risk of preterm birth, measurement of serum creatinine (a relatively inexpensive blood test) may form part of the assessment of risk for preterm birth among those planning pregnancy.

Background Early-life low socioeconomic position (SEP) increases the risk of adult major depression; however, associations vary according to the measure of SEP and adults’ life stage. Although maternal education often predicts offspring health better than other SEP indicators, including paternal education, it is unclear how maternal and paternal education differentially influence early-adult depression, and how early-life and adult risk factors may mediate the association. Methods Longitudinal data come from the Canadian National Population Health Survey from 1994/1995 to 2006/2007, restricted to a sample ( N  = 1,267) that was aged 12–24 years in 1994/1995. Past-year major depressive episode (MDE) was assessed in 2004/2005 and 2006/2007 using the Composite International Diagnostic Interview Short Form for Major Depression. Logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for the association between both maternal and paternal education and MDE, adjusting for respondent’s demographics, early-life adversities, adult SEP, psychosocial factors, and physical health. Results Offsprings of mothers with less than secondary school education had higher odds of MDE (adjusted OR 2.04, 95 % CI 1.25–3.32) relative to those whose mothers had more education. Paternal education was not associated with MDE. Although adult income, student status, psychosocial stress, and several early-life adversities remained associated with MDE in the fully adjusted model, the estimate for maternal education was not reduced. Conclusions Maternal education was associated with MDE in early adulthood, independent of paternal education and other early-life and early-adult risk factors.