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.

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.

Association Between ABO and Rh Blood Groups and SARS-CoV-2 Infection or Severe COVID-19 Illness : A Population-Based Cohort Study.

BACKGROUND: The ABO and rhesus (Rh) blood groups may influence risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVE: To determine whether ABO and Rh blood groups are associated with risk for SARS-CoV-2 infection and severe coronavirus disease 2019 (COVID-19) illness. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. PATIENTS: All adults and children who had ABO blood group assessed between January 2007 and December 2019 and who subsequently had SARS-CoV-2 testing between 15 January and 30 June 2020. MEASUREMENTS: The main study outcome was SARS-CoV-2 infection, determined by viral RNA polymerase chain reaction testing. A second outcome was severe COVID-19 illness or death. Adjusted relative risks (aRRs) and absolute risk differences (ARDs) were adjusted for demographic characteristics and comorbidities. RESULTS: A total of 225 556 persons were included, with a mean age of 54 years. The aRR of SARS-CoV-2 infection for O blood group versus A, AB, and B blood groups together was 0.88 (95% CI, 0.84 to 0.92; ARD, -3.9 per 1000 [CI, -5.4 to -2.5]). Rhesus-negative (Rh-) blood type was protective against SARS-CoV-2 infection (aRR, 0.79 [CI, 0.73 to 0.85]; ARD, -6.8 per 1000 [CI, -8.9 to -4.7]), especially for those who were O-negative (O-) (aRR, 0.74 [CI, 0.66 to 0.83]; ARD, -8.2 per 1000 [CI, -10.8 to -5.3]). There was also a lower risk for severe COVID-19 illness or death associated with type O blood group versus all others (aRR, 0.87 [CI, 0.78 to 0.97]; ARD, -0.8 per 1000 [CI, -1.4 to -0.2]) and with Rh- versus Rh-positive (aRR, 0.82 [CI, 0.68 to 0.96]; ARD, -1.1 per 1000 [CI, -2.0 to -0.2]). LIMITATION: Persons who rapidly died of severe COVID-19 illness may not have had SARS-CoV-2 testing. CONCLUSION: The O and Rh- blood groups may be associated with a slightly lower risk for SARS-CoV-2 infection and severe COVID-19 illness. PRIMARY FUNDING SOURCE: Ontario Academic Health Sciences Centre AFP Innovation Fund and the Ontario Ministry of Health and Long-Term Care.

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.

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.

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.

Risk of severe maternal morbidity or death in relation to elevated hemoglobin A1c preconception, and in early pregnancy: A population-based cohort study.

BACKGROUND: 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). METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

Prepregnancy renal function and risk of preterm birth and related outcomes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). INTERPRETATION: 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.

Population-based study of serum ferritin in early pregnancy and adverse perinatal outcomes.

BACKGROUND: Chronic placental inflammation is associated with preterm birth (PTB) and perinatal mortality. Ferritin is often elevated in chronic inflammatory conditions, but prior studies of its relation to PTB were restricted to ferritin measurement within pregnancy, were underpowered to detect rarer outcomes, and did not account for pre-existing maternal inflammatory conditions, such as inflammatory bowel or rheumatological disease. OBJECTIVES: To evaluate whether an elevated ferritin level prior to pregnancy is associated with major adverse pregnancy outcomes. METHODS: A population-based cohort study was completed using Ontario, Canada. Included were all Ontarian women with a hospital livebirth or stillbirth at ≥20 weeks' gestation, 2007-2018, and serum haemoglobin and ferritin measured as an outpatient within 120 days before conception. Excluded were women with a diagnosed iron overload disorder or a ferritin concentration <15 µg/L. The main exposure was a pre-pregnancy serum ferritin ≥95th percentile. Study outcomes included PTB < 37 weeks' gestation, including clinician-initiated and spontaneous PTB; PTB < 32 weeks; chorioamnionitis; and perinatal death. Relative risks (RR) and 95% confidence intervals (CI) were calculated for each study outcome, comparing a serum ferritin concentration ≥95th vs <5th percentile (the referent), while adjusting maternal age, residence, haemoglobin concentration, diabetes mellitus, inflammatory bowel disease, illicit drug/tobacco use, chronic kidney disease, chronic hypertension, sickle-cell disease or thalassaemia, and rheumatological conditions. RESULTS: Among 89 847 births, a preconceptional maternal serum ferritin ≥95th (112.0 µg/L) vs <5th (16.9 µg/L) percentile was associated with an adjusted relative risk (aRR) of 1.34 (95% CI 1.15, 1.57) for PTB, including spontaneous and clinician-initiated PTB. Results were equivocal for chorioamnionitis (aRR 1.23, 95% CI 0.81, 1.86), and there was no association with perinatal mortality (aRR 0.94, 95% CI 0.55, 1.61). CONCLUSION: A high preconceptional ferritin concentration is associated with some adverse perinatal outcomes.

Neighbourhood Income and Risk of Having an Infant With Concomitant Preterm Birth and Severe Small for Gestational Age Birth Weight.

OBJECTIVE: Socioeconomic position gradients have been individually demonstrated for preterm birth (PTB) at <37 weeks gestation and severe small for gestational age birth weight at <5th percentile (SGA). It is not known how neighbourhood income is related to the combination of PTB and severe SGA, a state reflective of greater placental dysfunction and higher risk of neonatal morbidity and mortality than PTB or severe SGA alone. METHODS: This population-based study comprised all 1 367 656 singleton live births in Ontario from 2002 to 2011. Multinomial logistic regression was used to estimate the odds of PTB with severe SGA, PTB without severe SGA, and severe SGA without PTB, compared with neither PTB nor severe SGA, in relation to neighbourhood income quintile (Q). The highest income quintile, Q5, served as the exposure referent. Adjusted odds ratios (aORs) were adjusted for maternal age at delivery, parity, marital status, and world region of birth (Canadian Task Force Classification II-2). RESULTS: Relative to women residing in Q5 (2.3 per 1000), the rate of PTB with severe SGA was highest among those in Q1 (3.6 per 1000), with an aOR of 1.34 (95% confidence interval [CI] 1.20-1.50). The corresponding aORs were 1.23 (95% CI 1.09-1.37) for Q2, 1.14 (95% CI 1.02-1.28) for Q3, and 1.06 (95% CI 0.95-1.20) for Q4. Less pronounced aORs were seen for each individual outcome of PTB and severe SGA. CONCLUSION: Women residing in the lowest-income areas are at highest risk of having a fetus born too small and too soon. Future research should focus on identifying those women most predisposed to combined PTB and severe SGA.

Infertility treatment and risk of severe maternal morbidity: a propensity score-matched cohort study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). INTERPRETATION: 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.

Hormone Levels in Pregnancy and Subsequent Risk of Maternal Breast and Ovarian Cancer: A Systematic Review.

OBJECTIVE: Some maternal hormone levels in pregnancy are associated with a higher risk of breast and ovarian cancer. This study systematically assessed the association between blood hormone levels measured in pregnancy and future risk of these cancers. METHODS: Two reviewers independently conducted a literature search of MEDLINE and EMBASE databases from January 1970 to August 2017. Studies were included that measured one or more serum hormone levels in pregnancy and later assessed for cancer. Cancer outcomes were considered by cancer type, each in relation to a specific maternal hormone. RESULTS: Eleven studies were included, comprising a total of 57 967 women. The interval between pregnancy and cancer onset varied from 4.1 to 20.5 years. Elevated serum chorionic gonadotropin (two of four studies) and alpha fetoprotein (two of three studies) were each associated with a lower risk of maternal breast cancer, whereas elevated estrone levels suggested a higher risk (one of three studies). Elevated testosterone (one of one study) and androstenedione (one of one study) were each associated with a significantly greater risk of sex-cord stromal ovarian tumours. Higher serum 17-hydroxyprogesterone was associated with an increased risk of sex-cord stromal (one of one study) and epithelial (one of one study) ovarian cancer. CONCLUSION: Observational studies suggest some degree of association between serum hormones measured in pregnancy and a woman's future risk of breast and ovarian cancer. More data are needed to determine sufficiently whether certain blood hormone levels measured in pregnancy are predictive of future cancer risk.

Infant feeding practices within a large electronic medical record database.

BACKGROUND: The emerging adoption of the electronic medical record (EMR) in primary care enables clinicians and researchers to efficiently examine epidemiological trends in child health, including infant feeding practices. METHODS: We completed a population-based retrospective cohort study of 8815 singleton infants born at term in Ontario, Canada, April 2002 to March 2013. Newborn records were linked to the Electronic Medical Record Administrative data Linked Database (EMRALD™), which uses patient-level information from participating family practice EMRs across Ontario. We assessed exclusive breastfeeding patterns using an automated electronic search algorithm, with manual review of EMRs when the latter was not possible. We examined the rate of breastfeeding at visits corresponding to 2, 4 and 6 months of age, as well as sociodemographic factors associated with exclusive breastfeeding. RESULTS: Of the 8815 newborns, 1044 (11.8%) lacked breastfeeding information in their EMR. Rates of exclusive breastfeeding were 39.5% at 2 months, 32.4% at 4 months and 25.1% at 6 months. At age 6 months, exclusive breastfeeding rates were highest among mothers aged ≥40 vs. < 20 years (rate ratio [RR] 2.45, 95% confidence interval [CI] 1.62-3.68), urban vs. rural residence (RR 1.35, 95% CI 1.22-1.50), and highest vs. lowest income quintile (RR 1.18, 95% CI 1.02-1.36). Overall, immigrants had similar rates of exclusive breastfeeding as non-immigrants; yet, by age 6 months, among those residing in the lowest income quintile, immigrants were more likely to exclusively breastfeed than their non-immigrant counterparts (RR 1.43, 95% CI 1.12-1.83). CONCLUSIONS: We efficiently determined rates and factors associated with exclusive breastfeeding using data from a large EMR database.

Ethnic Differences in Visceral Adiposity Measured in Early Pregnancy.

OBJECTIVE: To determine if visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) depth in early pregnancy differs by maternal ethnicity. METHODS: We prospectively evaluated 482 women without pre-pregnancy diabetes. All underwent sonographic measurement of VAT and SAT depth at 11 to 14 weeks' gestation. RESULTS: SAT did not differ between groups, but VAT did. Compared with Canadian-born women (3.9 cm, 95% CI 3.7-4.1), mean VAT depth was higher among Latin American (4.6 cm, 95% CI 4.1-5.2), Sub-Saharan African (5.0 cm, 95% CI 4.0-6.1), and Caribbean (6.0 cm, 95% CI 4.8-7.3) women. Adjusting for age, parity, and 1/height2, the relative risks of having a VAT depth >80th percentile were 1.69 (95% CI 1.05-2.73) for Latin American, 2.24 (95% CI 1.28-3.93) for Sub-Saharan African, and 3.34 (95% CI 1.91-5.84) for Caribbean women, relative to Canadian-born women. Women from these world regions also had a greater percentage of preterm births and emergency CSs. CONCLUSION: VAT differs appreciably among certain ethnic groups, which may reflect their predisposition to adverse pregnancy outcomes.

Influence of environmental temperature on risk of gestational diabetes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). INTERPRETATION: 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.

Differences in growth of Canadian children compared to the WHO 2006 Child Growth Standards.

BACKGROUND: To evaluate if there are departures from the WHO Child Growth Standards (WHO-CGS) in postnatal growth of healthy 'Canadian' children in Ontario up to age 2 years, including by infant feeding and ethnicity. METHODS: We included data on 9964 healthy, singleton children born in Ontario, Canada. Smoothed weight, length and body mass index (BMI) percentile curves were generated using quantile regression for the Canadian cohort from birth to age 2 years. Differences in percentile values were calculated comparing Canadian children vs. the WHO-CGS. RESULTS: Canadian children under age 2 years were longer than the WHO-CGS at the 10th (0.8 cm), 50th (1.3 cm) and 90th (1.9 cm) percentiles. Canadian children incrementally surpassed the WHO-CGS in weight after age 6 months, and in BMI after 9 months. By age 2 years, the 50th percentile weight of Canadian males was 823 g (95% confidence interval (CI) 680, 965) higher than the WHO-CGS 50th percentile. Weight differences were seen regardless of feeding practice, and were greatest among children of mothers born in Canada and Europe/Western nations, and least for those of East Asian/Pacific or South Asian heritage. Among Canadian breastfed males, 18% (95% CI 16, 19) of newborns and 26% (95% CI 20, 33) toddlers aged 2 years were classified by WHO-CGS as weighing >90th percentile - much higher than the expected rate of 10%. Similarities were seen for differences in BMI. CONCLUSIONS: Healthy Canadian infants/toddlers are longer and heavier than the WHO-CGS norms. Explanations for these discrepancies require further elucidation.

Preeclampsia and Preterm Birth Associated With Visceral Adiposity in Early Pregnancy.

OBJECTIVE: To determine if an increasing amount of visceral adipose tissue, measured by ultrasound in early pregnancy, is associated with a higher risk of preeclampsia and preterm birth (PTB). METHODS: We completed a prospective cohort study of 463 pregnant women. Maternal visceral adiposity tissue (VAT) depth was measured by ultrasound at 11 to 14 weeks' gestation. Relative risks (RR) were adjusted for age, parity, chronic hypertension, pre-pregnancy BMI, and use of acetylsalicylic acid. RESULTS: The rate of preeclampsia was much higher at quintile (Q) 5 of VAT depth (9.8%) than at Q1 to Q4 (1.6%) but not significantly so in the adjusted model (RR 3.39, 95% CI 0.86 to 13.39). The adjusted RR of PTB was significantly elevated at Q5 VAT depth (6.53, 95% CI 1.47 to 6.53), as was preeclampsia with PTB (16.91, 95% CI 1.24 to 231.07). CONCLUSION: Higher amounts of VAT in pregnancy may play a direct role in the pathogenesis of preeclampsia, including early onset preeclampsia necessitating preterm delivery.

Maternal Origin and Risk of Neonatal and Maternal ICU Admission.

OBJECTIVES: To evaluate maternal world region of birth, as well as maternal country of origin, and the associated risk of admission of 1) a mother to a maternal ICU, 2) her infant to a neonatal ICU, or 3) both concurrently to an ICU. DESIGN: Retrospective population-based cohort study. SETTING: Entire province of Ontario, Canada, from 2003 to 2012. PATIENTS: All singleton maternal-child pairs who delivered in any Ontario hospital. MEASUREMENTS AND MAIN RESULTS: We explored how maternal world region of birth, and specifically, maternal country of birth for the top 25 countries, was associated with the outcome of 1) neonatal ICU, 2) maternal ICU, and 3) both mother and newborn concurrently admitted to ICU. Relative risks were adjusted for maternal age, parity, income quintile, chronic hypertension, diabetes mellitus, obesity, dyslipidemia, drug dependence or tobacco use, and renal disease. Compared with infants of Canadian-born mothers (110.7/1,000), the rate of neonatal ICU admission was higher in immigrants from South Asia (155.2/1,000), Africa (140.4/1,000), and the Caribbean (167.3/1,000; adjusted relative risk, 1.41; 95% CI, 1.36-1.46). For maternal ICU, the adjusted relative risk was 1.79 (95% CI, 1.43-2.24) for women from Africa and 2.21 (95% CI, 1.78-2.75) for women from the Caribbean. Specifically, mothers from Ghana (adjusted relative risk, 2.71; 95% CI, 1.75-4.21) and Jamaica (adjusted relative risk, 2.74; 95% CI, 2.12-3.53) were at highest risk of maternal ICU admission. The risk of both mother and newborn concurrently admitted to ICU was even more pronounced for Ghana and Jamaica. CONCLUSIONS: Women from Africa and the Caribbean and, in particular, Ghana and Jamaica, are at higher risk of admission to ICU around the time of delivery, as are their newborns.

Preterm Delivery in Relation to Neighbourhood-Level Adult Premature Mortality.

OBJECTIVE: To assess the influence of neighbourhood-level adult premature mortality on a woman's risk of preterm delivery (PTD). METHODS: We included 286 872 singleton live birth deliveries in Toronto, Ontario, between 2002 and 2011. The study exposure was neighbourhood premature mortality rate, expressed in quintiles (Q), among adults aged 20 to 49 years living within each of Toronto's 140 neighbourhoods. The primary study outcome was PTD at 24 to 36 weeks' gestation. Logistic regression analysis generated unadjusted ORs, adjusted ORs, and 95% CIs, controlling for maternal age, parity, marital status, material deprivation index Q, maternal and paternal birthplace, and infant sex. RESULTS: For all 140 neighbourhoods, the mean rate of premature deaths was 0.66 per 100 females and 1.17 per 100 males aged 20 to 49 years. The rate of PTD increased linearly in relation to the neighbourhood rate of premature mortality among adult females, from 5.3 per 100 in Q1 with the lowest rate of premature mortality to 6.3 per 100 in Q5 (OR 1.22; 95% CI 1.13 to 1.31). The adjusted ORs were attenuated but remained significant (1.13; 95% CI 1.05 to 1.22). A similar pattern was demonstrated for the relation between neighbourhood premature mortality among adult males and PTD. CONCLUSION: Women residing in neighbourhoods with high rates of premature adult mortality are at elevated risk of PTD, even after adjusting for measured socioeconomic factors that include marital status and material deprivation.

Association Between MRI Exposure During Pregnancy and Fetal and Childhood Outcomes.

IMPORTANCE: Fetal safety of magnetic resonance imaging (MRI) during the first trimester of pregnancy or with gadolinium enhancement at any time of pregnancy is unknown. OBJECTIVE: To evaluate the long-term safety after exposure to MRI in the first trimester of pregnancy or to gadolinium at any time during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Universal health care databases in the province of Ontario, Canada, were used to identify all births of more than 20 weeks, from 2003-2015. EXPOSURES: Magnetic resonance imaging exposure in the first trimester of pregnancy, or gadolinium MRI exposure at any time in pregnancy. MAIN OUTCOMES AND MEASURES: For first-trimester MRI exposure, the risk of stillbirth or neonatal death within 28 days of birth and any congenital anomaly, neoplasm, and hearing or vision loss was evaluated from birth to age 4 years. For gadolinium-enhanced MRI in pregnancy, connective tissue or skin disease resembling nephrogenic systemic fibrosis (NSF-like) and a broader set of rheumatological, inflammatory, or infiltrative skin conditions from birth were identified. RESULTS: Of 1 424 105 deliveries (48% girls; mean gestational age, 39 weeks), the overall rate of MRI was 3.97 per 1000 pregnancies. Comparing first-trimester MRI (n = 1737) to no MRI (n = 1 418 451), there were 19 stillbirths or deaths vs 9844 in the unexposed cohort (adjusted relative risk [RR], 1.68; 95% CI, 0.97 to 2.90) for an adjusted risk difference of 4.7 per 1000 person-years (95% CI, -1.6 to 11.0). The risk was also not significantly higher for congenital anomalies, neoplasm, or vision or hearing loss. Comparing gadolinium MRI (n = 397) with no MRI (n = 1 418 451), the hazard ratio for NSF-like outcomes was not statistically significant. The broader outcome of any rheumatological, inflammatory, or infiltrative skin condition occurred in 123 vs 384 180 births (adjusted HR, 1.36; 95% CI, 1.09 to 1.69) for an adjusted risk difference of 45.3 per 1000 person-years (95% CI, 11.3 to 86.8). Stillbirths and neonatal deaths occurred among 7 MRI-exposed vs 9844 unexposed pregnancies (adjusted RR, 3.70; 95% CI, 1.55 to 8.85) for an adjusted risk difference of 47.5 per 1000 pregnancies (95% CI, 9.7 to 138.2). CONCLUSIONS AND RELEVANCE: Exposure to MRI during the first trimester of pregnancy compared with nonexposure was not associated with increased risk of harm to the fetus or in early childhood. Gadolinium MRI at any time during pregnancy was associated with an increased risk of a broad set of rheumatological, inflammatory, or infiltrative skin conditions and for stillbirth or neonatal death. The study may not have been able to detect rare adverse outcomes.