Effectiveness of Influenza Vaccination During Pregnancy Against Laboratory-Confirmed Seasonal Influenza Among Infants Under 6 Months of Age in Ontario, Canada.

BACKGROUND: Randomized trials conducted in low- and middle-income settings demonstrated efficacy of influenza vaccination during pregnancy against influenza infection among infants <6 months of age. However, vaccine effectiveness (VE) estimates from settings with different population characteristics and influenza seasonality remain limited. METHODS: We conducted a test-negative study in Ontario, Canada. All influenza virus tests among infants <6 months from 2010 to 2019 were identified and linked with health databases to ascertain information on maternal-infant dyads. VE was estimated from the odds ratio for influenza vaccination during pregnancy among cases versus controls, computed using logistic regression with adjustment for potential confounders. RESULTS: Among 23 806 infants tested for influenza, 1783 (7.5%) were positive and 1708 (7.2%) were born to mothers vaccinated against influenza during pregnancy. VE against laboratory-confirmed infant influenza infection was 64% (95% confidence interval [CI], 50%-74%). VE was similar by trimester of vaccination (first/second, 66% [95% CI, 40%-80%]; third, 63% [95% CI, 46%-74%]), infant age at testing (0 to <2 months, 63% [95% CI, 46%-75%]; 2 to <6 months, 64% [95% CI, 36%-79%]), and gestational age at birth (≥37 weeks, 64% [95% CI, 50%-75%]; < 37 weeks, 61% [95% CI, 4%-86%]). VE against influenza hospitalization was 67% (95% CI, 50%-78%). CONCLUSIONS: Influenza vaccination during pregnancy offers effective protection to infants <6 months, for whom vaccines are not currently available.

Recent Immigrants With Inflammatory Bowel Disease Have Significant Healthcare Utilization From Preconception to Postpartum: A Population Cohort Study.

INTRODUCTION: Immigrants with inflammatory bowel disease (IBD) may have increased healthcare utilization during pregnancy compared with non-immigrants, although this remains to be confirmed. We aimed to characterize this between these groups. METHODS: We accessed administrative databases to identify women (aged 18-55 years) with IBD with a singleton pregnancy between 2003 and 2018. Immigration status was defined as recent (<5 years of the date of conception), remote (≥5 years since the date of conception), and none. Differences in ambulatory, emergency department, hospitalization, endoscopic, and prenatal visits during 12 months preconception, pregnancy, and 12 months postpartum were characterized. Region of immigration origin was ascertained. Multivariable negative binomial regression was performed for adjusted incidence rate ratios (aIRRs) with 95% confidence intervals (CIs). RESULTS: A total of 8,880 pregnancies were included, 8,304 in non-immigrants, 96 in recent immigrants, 480 in remote immigrants. Compared with non-immigrants, recent immigrants had the highest rates of IBD-specific ambulatory visits during preconception (aIRR 3.06, 95% CI 1.93-4.85), pregnancy (aIRR 2.15, 95% CI 1.35-3.42), and postpartum (aIRR 2.21, 1.37-3.57) and the highest rates of endoscopy visits during preconception (aIRR 2.69, 95% CI 1.64-4.41) and postpartum (aIRR 2.01, 95% CI 1.09-3.70). There were no differences in emergency department and hospitalization visits between groups, although those arriving from the Americas were the most likely to be hospitalized for any reason. All immigrants with IBD were less likely to have a first trimester prenatal visit. DISCUSSION: Recent immigrants were more likely to have IBD-specific ambulatory care but less likely to receive adequate prenatal care during pregnancy.

Temporal Trends in Gestational Diabetes Mellitus and Associated Risk Factors in Ontario, Canada, 2012-2020: A Population-Based Cohort Study.

OBJECTIVES: The prevalence of gestational diabetes mellitus (GDM) has been increasing globally over recent decades; however, underlying reasons for the increase remain unclear. We analyzed trends in GDM rates and evaluated risk factors associated with the observed trends in Ontario, Canada. METHODS: We conducted a retrospective population-based cohort study using the Better Outcomes Registry and Network Ontario, linked with the Canadian Institute for Health Information Discharge Abstract Database. All pregnant individuals who had a singleton hospital delivery from 1 April 2012 to 31 March 2020 were included. We calculated rates and 95% CIs for GDM by year of delivery and contrasted fiscal year 2019/20 with 2012/13. Temporal trends in GDM were quantified using crude and adjusted risk ratios by modified Poisson regression. We further quantified the temporal increase attributable to changes in maternal characteristics by decomposition analysis. RESULTS: Among 1 044 258 pregnant individuals, 82 896 (7.9%) were diagnosed with GDM over the 8 years. GDM rate rose from 6.1 to 10.4 per 100 deliveries between fiscal years 2012/13 and 2019/20. The risk of GDM in 2019/20 was 1.53 times (95% CI 1.50-1.56) higher compared with 2012/13. 27% of the increase in GDM was due to changes in maternal age, 8 BMI, and Asian ethnicity. CONCLUSIONS: The GDM rate has been consistently increasing in Ontario, Canada. The contribution of increasing maternal age, pre-pregnancy obesity, and Asian ethnicity to the recent increase in GDM is notable. Further investigation is required to better understand the contributors to increasing GDM.

Ultrasonographic Fetal Nuchal Translucency Measurements and Cytogenetic Outcomes.

Importance: Ultrasonographic measurement of fetal nuchal translucency is used in prenatal screening for trisomies 21 and 18 and other conditions. A cutoff of 3.5 mm or greater is commonly used to offer follow-up investigations, such as prenatal cell-free DNA (cfDNA) screening or cytogenetic testing. Recent studies showed a possible association with chromosomal anomalies for levels less than 3.5 mm, but extant evidence has limitations. Objective: To evaluate the association between different nuchal translucency measurements and cytogenetic outcomes on a population level. Design, Setting, and Participants: This population-based retrospective cohort study used data from the Better Outcomes Registry & Network, the perinatal registry for Ontario, Canada. All singleton pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, were included. Data were analyzed from March 17 to August 14, 2023. Exposures: Nuchal translucency measurements were identified through multiple-marker screening results. Main Outcomes and Measures: Chromosomal anomalies were identified through all Ontario laboratory-generated prenatal and postnatal cytogenetic tests. Cytogenetic testing results, supplemented with information from cfDNA screening and clinical examination at birth, were used to identify pregnancies without chromosomal anomalies. Multivariable modified Poisson regression with robust variance estimation and adjustment for gestational age was used to compare cytogenetic outcomes for pregnancies with varying nuchal translucency measurement categories and a reference group with nuchal translucency less than 2.0 mm. Results: Of 414 268 pregnancies included in the study (mean [SD] maternal age at estimated delivery date, 31.5 [4.7] years), 359 807 (86.9%) had a nuchal translucency less than 2.0 mm; the prevalence of chromosomal anomalies in this group was 0.5%. An increased risk of chromosomal anomalies was associated with increasing nuchal translucency measurements, with an adjusted risk ratio (ARR) of 20.33 (95% CI, 17.58-23.52) and adjusted risk difference (ARD) of 9.94% (95% CI, 8.49%-11.39%) for pregnancies with measurements of 3.0 to less than 3.5 mm. The ARR was 4.97 (95% CI, 3.45-7.17) and the ARD was 1.40% (95% CI, 0.77%-2.04%) when restricted to chromosomal anomalies beyond the commonly screened aneuploidies (excluding trisomies 21, 18, and 13 and sex chromosome aneuploidies). Conclusions and Relevance: In this cohort study of 414 268 singleton pregnancies, those with nuchal translucency measurements less than 2.0 mm were at the lowest risk of chromosomal anomalies. Risk increased with increasing measurements, including measurements less than 3.5 mm and anomalies not routinely screened by many prenatal genetic screening programs.

Prenatal Exposure to Ambient Air Pollution and Cerebral Palsy.

Importance: Air pollution is associated with structural brain changes, disruption of neurogenesis, and neurodevelopmental disorders. The association between prenatal exposure to ambient air pollution and risk of cerebral palsy (CP), which is the most common motor disability in childhood, has not been thoroughly investigated. Objective: To evaluate the associations between prenatal residential exposure to ambient air pollution and risk of CP among children born at term gestation in a population cohort in Ontario, Canada. Design, Setting, and Participants: Population-based cohort study in Ontario, Canada using linked, province-wide health administrative databases. Participants were singleton full term births (≥37 gestational weeks) born in Ontario hospitals between April 1, 2002, and March 31, 2017. Data were analyzed from January to December 2022. Exposures: Weekly average concentrations of ambient fine particulate matter with a diameter 2.5 µm (PM2.5) or smaller, nitrogen dioxide (NO2), and ozone (O3) during pregnancy assigned by maternal residence reported at delivery from satellite-based estimates and ground-level monitoring data. Main outcome and measures: CP cases were ascertained by a single inpatient hospitalization diagnosis or at least 2 outpatient diagnoses for children from birth to age 18 years. Results: The present study included 1 587 935 mother-child pairs who reached term gestation, among whom 3170 (0.2%) children were diagnosed with CP. The study population had a mean (SD) maternal age of 30.1 (5.6) years and 811 745 infants (51.1%) were male. A per IQR increase (2.7 µg/m3) in prenatal ambient PM2.5 concentration was associated with a cumulative hazard ratio (CHR) of 1.12 (95% CI, 1.03-1.21) for CP. The CHR in male infants (1.14; 95% CI, 1.02-1.26) was higher compared with the CHR in female infants (1.08; 95% CI, 0.96-1.22). No specific window of susceptibility was found for prenatal PM2.5 exposure and CP in the study population. No associations or windows of susceptibility were found for prenatal NO2 or O3 exposure and CP risk. Conclusions and relevance: In this large cohort study of singleton full term births in Canada, prenatal ambient PM2.5 exposure was associated with an increased risk of CP in offspring. Further studies are needed to explore this association and its potential biological pathways, which could advance the identification of environmental risk factors of CP in early life.

Outlier analysis for accelerating clinical discovery: An augmented intelligence framework and a systematic review.

Clinical discoveries largely depend on dedicated clinicians and scientists to identify and pursue unique and unusual clinical encounters with patients and communicate these through case reports and case series. This process has remained essentially unchanged throughout the history of modern medicine. However, these traditional methods are inefficient, especially considering the modern-day availability of health-related data and the sophistication of computer processing. Outlier analysis has been used in various fields to uncover unique observations, including fraud detection in finance and quality control in manufacturing. We propose that clinical discovery can be formulated as an outlier problem within an augmented intelligence framework to be implemented on any health-related data. Such an augmented intelligence approach would accelerate the identification and pursuit of clinical discoveries, advancing our medical knowledge and uncovering new therapies and management approaches. We define clinical discoveries as contextual outliers measured through an information-based approach and with a novelty-based root cause. Our augmented intelligence framework has five steps: define a patient population with a desired clinical outcome, build a predictive model, identify outliers through appropriate measures, investigate outliers through domain content experts, and generate scientific hypotheses. Recognizing that the field of obstetrics can particularly benefit from this approach, as it is traditionally neglected in commercial research, we conducted a systematic review to explore how outlier analysis is implemented in obstetric research. We identified two obstetrics-related studies that assessed outliers at an aggregate level for purposes outside of clinical discovery. Our findings indicate that using outlier analysis in clinical research in obstetrics and clinical research, in general, requires further development.

Risk of Severe Maternal Morbidity Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection During Pregnancy.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy increases the risk of adverse fetal and neonatal outcomes, but the contribution to severe maternal morbidity (SMM) has been less frequently documented. Methods: We conducted a national cohort study of 93 624 deliveries occurring between 11 March 2020 and 1 July 2021 using medical claims information from the OptumLabs Data Warehouse. SARS-CoV-2 infection was identified from diagnostic and laboratory testing claims records. We identified 21 SMM conditions using International Classification of Diseases, Tenth Revision, Clinical Modification and procedure codes and compared SMM conditions by SARS-CoV-2 status using Poisson regression with robust variance, adjusting for maternal sociodemographic and health factors, onset of labor, and week of conception. Results: Approximately 5% of deliveries had a record of SARS-CoV-2 infection: 27.0% <7 days before delivery, 13.5% within 7-30 days of delivery, and 59.5% earlier in pregnancy. Compared to uninfected pregnancies, the adjusted risk of SMM was 2.22 times higher (95% confidence interval [CI], 1.97-2.48) among those infected <7 days before delivery and 1.66 times higher (95% CI, 1.23-2.08) among those infected 7-30 days before delivery. The highest risks were observed for acute respiratory distress syndrome (adjusted risk ratio [aRR], 13.24 [95% CI, 12.86-13.61]) and acute renal failure (aRR, 3.91 [95% CI, 3.32-4.50]). Conclusions: COVID-19 is associated with increased rates of SMM.

Characteristics and outcomes of pregnant women with SARS-CoV-2 infection and other severe acute respiratory infections (SARI) in Brazil from January to November 2020

ABSTRACT Background: Knowledge about COVID-19 in pregnancy is limited, and evidence on the impact of the infection during pregnancy and postpartum is still emerging. Aim: To analyze maternal morbidity and mortality due to severe acute respiratory infections (SARI), including COVID-19, in Brazil. Methods: National surveillance data from the SIVEP-Gripe (Sistema de Informação de Vigilância Epidemiológica da Gripe) was used to describe currently and recently pregnant women aged 10-49 years hospitalized for SARI from January through November, 2020. SARI cases were grouped into: COVID-19; influenza or other detected agent SARI; and SARI of unknown etiology. Characteristics, symptoms and outcomes were presented by SARI type and region. Binomial proportion and 95% confidence intervals (95% CI) for outcomes were obtained using the Clopper-Pearson method. Results: Of 945,460 SARI cases in the SIVEP-Gripe, we selected 11,074 women aged 10-49 who were pregnant (7964) or recently pregnant (3110). COVID-19 was confirmed in 49.4% cases; 1.7% had influenza or another etiological agent; and 48.9% had SARI of unknown etiology. The pardo race/ethnic group accounted for 50% of SARI cases. Hypertension/Other cardiovascular diseases, chronic respiratory diseases, diabetes, and obesity were the most common comorbidities. A total of 362 women with COVID-19 (6.6%; 95%CI 6.0-7.3) died. Mortality was 4.7% (2.2-8.8) among influenza patients, and 3.3% (2.9-3.8) among those with SARI of unknown etiology. The South-East, Northeast and North regions recorded the highest frequencies of mortality among COVID-19 patients. Conclusion: Mortality among pregnant and recently pregnant women with SARIs was elevated among those with COVID-19, particularly in regions where maternal mortality is already high.