Association between prenatal air pollutant exposure and autism spectrum disorders in young children: A matched case-control study in Canada.

The direction and magnitude of association between maternal exposure to ambient air pollutants across gestational windows and offspring risk of autism spectrum disorders (ASD) remains unclear. We sought to evaluate the time-varying effects of prenatal air pollutant exposure on ASD. We conducted a matched case-control study of singleton term children born in Ontario, Canada from 1-Apr-2012 to 31-Dec-2016. Provincial birth registry data were linked with applied behavioural analysis services and ambient air pollutant datasets to ascertain prenatal exposure to nitrogen dioxide (NO2), ground-level ozone (O3), fine particulate matter (PM2.5), and ASD diagnoses. Covariate balance between cases and controls was established using coarsened exact matching. Conditional logistic regression was used to assess the association between prenatal air pollutant exposure and ASD. Distributed lag non-linear models (DLNM) were used to examine the effects of single-pollutant exposure by prenatal week. Sensitivity analyses were conducted to assess the impact of exposure period on the observed findings. The final sample included 1589 ASD cases and 7563 controls. Compared to controls, cases were more likely to be born to mothers living in urban areas, delivered by Caesarean section, and assigned male sex at birth. NO2 was a consistent and significant contributor to ASD risk after accounting for co-exposure to O3, PM2.5 and covariates. The odds ratio per interquartile range increase was 2.1 (95%CI 1.8-2.3) pre-conception, 2.2 (2.0-2.5) for the 1st trimester, 2.2 (1.9-2.5) for the 2nd trimester, and 2.1 (1.9-2.4) for the 3rd trimester. In contrast, findings for O3 and PM2.5 with ASD were inconsistent. Findings from DLNM and sensitivity analyses were similar. Exposure to NO2 before and during pregnancy was significantly associated with ASD in offspring. The relationship between prenatal O3 and PM2.5 exposure and ASD remains unclear. Further investigation into the combined effects of multi-pollutant exposure on child neurodevelopment is warranted.

Associations of neighborhood greenspace, and active living environments with autism spectrum disorders: A matched case-control study in Ontario, Canada.

BACKGROUND: Increasing evidence links early life residential exposure to natural urban environmental attributes and positive health outcomes in children. However, few studies have focused on their protective effects on the risk of autism spectrum disorder (ASD). The aim of this study was to investigate the associations of neighborhood greenspace, and active living environments during pregnancy with ASD in young children (≤6 years). METHODS: We conducted a population-based matched case-control study of singleton term births in Ontario, Canada for 2012-2016. The ASD and environmental data was generated using the Ontario Autism Spectrum Profile, the Better Outcomes Registry & Network Ontario, and Canadian Urban Environmental Health Research Consortium. We employed conditional logistic regressions to estimate the odds ratio (OR) between ASD and environmental factors characterizing selected greenspace metrics and neighborhoods conducive to active living (i.e., green view index (GVI), normalized difference vegetation index (NDVI), tree canopy, park proximity and active living environments index (ALE)). RESULTS: We linked 8643 mother-child pairs, including 1554 cases (18%). NDVI (OR 1.034, 0.944-1.024, per Inter Quartile Range [IQR] = 0.08), GVI (OR 1.025, 95% CI 0.953-1.087, per IQR = 9.45%), tree canopy (OR 0.992, 95% CI 0.903-1.089, per IQR = 6.24%) and the different categories of ALE were not associated with ASD in adjusted models for air pollution. In contrast, living closer to a park was protective (OR 0.888, 0.833-0.948, per 0.06 increase in park proximity index), when adjusted for air pollution. CONCLUSIONS: This study reported mixed findings showing both null and beneficial effects of green spaces and active living environments on ASD. Further investigations are warranted to elucidate the role of exposure to greenspaces and active living environments on the development of ASD.

Infant Infections Following Cesarean Delivery on Maternal Request: A Population-Based Cohort Study.

OBJECTIVES: Investigations about cesarean delivery (CD) on maternal request (CDMR) and infant infection risk frequently rely on administrative data with poorly defined indications for CD. We sought to determine the association between CDMR and infant infection using an intent-to-treat approach. METHODS: This was a population-based cohort study of low-risk singleton pregnancies with a term live birth in Ontario, Canada between April 2012 and March 2018. Subjects with prior CD were excluded. Outcomes included upper and lower respiratory tract infections, gastrointestinal infections, otitis media, and a composite of these 4. Relative risk and 95% CI were calculated for component and composite outcomes up to 1 year following planned CDMR versus planned vaginal deliveries (VDs). Subgroup and sensitivity analyses included age at infection (≤28 vs. >28 days), type of care (ambulatory vs. hospitalisation), restricting the cohort to nulliparous pregnancies, and including individuals with previous CD. Last, we re-examined outcome risk on an as-treated basis (actual CD vs. actual VD). RESULTS: Of 422 134 pregnancies, 0.4% (1827) resulted in a planned CDMR. After adjusting for covariates, planned CDMR was not associated with a risk of composite infant infections (adjusted relative risk 1.02; 95% CI 0.92-1.11). Findings for component infection outcomes, subgroup, and sensitivity analyses were similar. However, the as-treated analysis of the role of delivery mode on infant risk for infection demonstrated that actual CD (planned and unplanned) was associated with an increased risk for infant infections compared to actual VD. CONCLUSIONS: Planned CDMR is not associated with increased risk for neonatal or infant infections compared with planned VD. Study design must be carefully considered when investigating the impact of CDMR on infant infection outcomes.

Worries, beliefs and factors influencing perinatal COVID-19 vaccination: a cross-sectional survey of preconception, pregnant and lactating individuals.

BACKGROUND: COVID-19 vaccines are recommended for pregnant and lactating individuals, and there is substantial evidence for their safety and effectiveness. As the pandemic continues, information on worries and beliefs surrounding perinatal COVID-19 vaccination remains important to inform efforts aimed at improving vaccine uptake. Our objectives were to assess factors associated with COVID-19 vaccination among perinatal individuals; and to explore motivational factors associated with willingness to be vaccinated among unvaccinated perinatal individuals. METHODS: This was a cross-sectional web-based survey of preconception, pregnant, and lactating individuals in Canada. The outcomes of interest were vaccination with at least one dose of any COVID-19 vaccine and willingness to be vaccinated among unvaccinated individuals. Sample characteristics were summarized using frequencies and percentages. The association between eight prespecified risk factors and two outcomes (vaccination status and willingness to be vaccinated) was assessed by logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for the total sample, and across perinatal sub-groups. RESULTS: Among 3446 survey respondents, there were 447 (13.0%) preconception, 1832 (53.2%) pregnant, and 1167 (42.4%) lactating. There were 1460 (42.4%) and 1982 (57.5%) who were vaccinated and unvaccinated, respectively. Factors positively associated with COVID-19 vaccine status were speaking to a healthcare provider about vaccination during the perinatal period (aOR:2.35, 95% CI:1.97-2.80) and believing that the COVID-19 vaccine is effective (aOR:1.91, 95% CI:1.46-2.48). Factors negatively associated with vaccine status included worries about fetal growth and development (aOR:0.55, 95% CI:0.43-0.70) and future child behavioral/neurodevelopmental problems (aOR:0.59, 95% CI:0.46-0.75). Among unvaccinated individuals specifically, characteristics positively associated with willingness to vaccinate were speaking to a healthcare provider (aOR:1.67, 95% CI:1.32-2.12) and believing the COVID-19 vaccine is effective (aOR:3.56, 95% CI:2.70-4.69). Factors negatively associated with willingness were concerns over infertility (aOR:0.66, 95% CI:0.49-0.88), fetal growth and development (aOR:0.33, 95% CI:0.24-0.46), and future child behavioral/neurodevelopmental problems (aOR:0.64, 95% CI:0.48-0.84). CONCLUSIONS: In this Canadian perinatal population, approximately 42% reported COVID-19 vaccination. Among unvaccinated individuals, willingness to receive vaccination was high (73%). Factors enhancing vaccine willingness included discussions with healthcare providers and believing the vaccine was effective. Concerns regarding vaccine safety, particularly with respect to fetal/child development, were the greatest barriers to vaccine uptake.

Giving Birth in the Early Phases of the COVID-19 Pandemic: The Patient Experience.

OBJECTIVE: Obstetrical patients are at risk of complications from COVID-19 and face increased stress due to the pandemic and changes in hospital birth setting. The objective was to describe the perinatal care experiences of obstetrical patients who gave birth during the early phases of the COVID-19 pandemic. METHODS: A descriptive epidemiological survey was administered to consenting patients who gave birth at The Ottawa Hospital (TOH) between March 16th and June 16th, 2020. The participants reported on prenatal, in-hospital, and postpartum care experiences. COVID-19 pandemic related household stress factors were investigated. Frequencies and percentages are presented for categorical variables and median and interquartile range (IQR) for continuous variables. RESULTS: A total of 216 participants were included in the analyses. Median participants age was 33 years (IQR: 30-36). Collectively, 94 (43.5%) participants felt elevated stress for prenatal appointments and 105 (48.6%) for postpartum appointments because of COVID-19. There were 108 (50.0%) were scared to go to the hospital for delivery, 97 (44.9%) wore a mask during labour and 54 (25.0%) gave birth without a support person. During postpartum care, 125 (57.9%) had phone appointments (not offered prior to COVID-19), and 18 (8.3%) received no postpartum care at all. CONCLUSION: COVID-19 pandemic and public health protocols created a stressful healthcare environment for the obstetrical population where many were fearful of accessing services, experienced changes to standard care, or no care at all. As the pandemic continues, careful attention should be given to the perinatal population to reduce stress and improve continuity of care.

RéSUMé: OBJECTIF: Les patients obstétriques sont à risque de complications de la COVID-19 et font face à un stress accru en raison de la pandémie et des changements dans le cadre de l'accouchement en milieu hospitalier. L'objectif était de décrire les expériences de soins périnataux des patients obstétriques qui ont accouché au cours des premières phases de la pandémie de COVID-19. MéTHODES: Un sondage épidémiologique descriptif a été menée auprès de patients qui ont accouché à L'Hôpital d'Ottawa (TOH) entre le 16 mars et le 16 juin 2020. Les participants ont fait un compte rendu de leurs expériences en matière de soins prénataux, hospitaliers et post-partum. Les facteurs de stress domestique liés à la COVID-19 ont été étudiés. Les fréquences et les pourcentages sont présentés pour les variables catégorielles et la médiane et l'écart interquartile (IQR) sont présentés pour les variables continues. RéSULTATS: Au total, 261 participants ont répondu au sondage. L'âge maternel médian était de 33 ans (IQR: 30­36). Collectivement, 94 participants (43,5%) ressentaient un stress élevé en lien avec les rendez-vous prénataux et 105 (48,6%) pour les rendez-vous post-partum en raison de la COVID-19. Il y avait 108 patients (50,0%) qui avaient peur d'aller à l'hôpital pour accoucher, 97 (44,9%) qui portaient un masque pendant leur travail et 54 (25,0%) qui ont accouché sans personne de soutien. En lien avec les soins post-partum, 125 (57,9%) ont eu des rendez-vous téléphoniques (non offerts avant la pandémie COVID-19) et 18 (8,3%) n'ont reçu aucun soin post-partum. CONCLUSION: La pandémie de COVID-19 et les politiques de santé publique ont créé un environnement de soins de santé stressant pour la population obstétrique où beaucoup avaient peur d'accéder aux services de soins, ont connu des changements dans les soins de base ou n'ont pas eu de soins du tout. Alors que la pandémie se poursuit, une attention particulière doit être accordée à la population périnatale afin de réduire le stress et améliorer la continuité des soins.

Gestational Folate and Folic Acid Intake among Women in Canada at Higher Risk of Pre-Eclampsia.

BACKGROUND: Periconceptional folic acid (FA) supplementation is recommended to prevent neural tube defects; however, the extent to which recommendations are met through dietary sources and supplements is not clear. OBJECTIVES: Our objective was to evaluate the dietary and supplemental intakes of FA in a Canadian pregnancy cohort and to determine the proportions of pregnant women exceeding the Estimated Average Requirement (EAR) and Tolerable Upper Intake Level (UL). METHODS: FACT (the Folic Acid Clinical Trial) was an international multicenter, randomized, double-blinded, placebo-controlled, phase III trial investigating FA for the prevention of pre-eclampsia in high-risk pregnancies. Participants were enrolled from Canadian sites at 8-16 weeks of gestation. Dietary and supplemental FA intake data were collected through participant interviews and FFQs at the time of FACT enrollment. Categorical data were summarized as n (%) and continuous data as median (IQR). RESULTS: This study included 1198 participants. Participants consumed 485 µg dietary folate equivalents (DFE)/d (IQR: 370-630 µg DFE/d) from dietary sources of folate and FA. Through diet alone, 43.4% of participants consumed ≥520 µg DFE/d, the EAR for pregnant individuals. Of the 91.9% of participants who consumed daily FA supplements, 0.4% consumed <400 µg FA/d and 96.0% consumed ≥1000 µg/d, the UL for FA. Median (IQR) total folate intake was 2167 µg DFE/d (2032-2325 µg DFE/d); 95.3% of participants met or exceeded the EAR from all sources, but 1069 (89.2%) participants exceeded the UL. CONCLUSIONS: The majority of participants in this Canadian pregnancy cohort did not consume the recommended amount of folate from dietary sources. However, most prenatal supplements contained 1000 µg FA, resulting in the majority of women exceeding the UL. With no additional benefit associated with FA intakes beyond the UL for most women, modification of prenatal supplement formulations may be warranted to ensure women meet but do not exceed recommended FA intakes.FACT was registered at clinicaltrials.gov as NCT01355159 and at isrctn.com as ISRCTN23781770.

Birth outcomes following cesarean delivery on maternal request: a population-based cohort study.

BACKGROUND: Data on the effect of cesarean delivery on maternal request (CDMR) on maternal and neonatal outcomes are inconsistent and often limited by inadequate case definitions and other methodological issues. Our objective was to evaluate the trends, determinants and outcomes of CDMR using an intent-to-treat approach. METHODS: We designed a population-based retrospective cohort study using data on low-risk pregnancies in Ontario, Canada (April 2012-March 2018). We assessed temporal trends and determinants of CDMR. We estimated the relative risks for component and composite outcomes used in the Adverse Outcome Index (AOI) related to planned CDMR compared with planned vaginal delivery using generalized estimating equation models. We compared the Weighted Adverse Outcome Score (WAOS) and the Severity Index (SI) across planned modes of delivery using analysis of variance. RESULTS: Of 422 210 women, 0.4% (n = 1827) had a planned CDMR and 99.6% (n = 420 383) had a planned vaginal delivery. The prevalence of CDMR remained stable over time at 3.9% of all cesarean deliveries. Factors associated with CDMR included late maternal age, higher education, conception via in vitro fertilization, anxiety, nulliparity, being White, delivery at a hospital providing higher levels of maternal care and obstetrician-based antenatal care. Women who planned CDMR had a lower risk of adverse outcomes than women who planned vaginal delivery (adjusted relative risk 0.42, 95% confidence interval [CI] 0.33 to 0.53). The WAOS was lower for planned CDMR than planned vaginal delivery (mean difference -1.28, 95% CI -2.02 to -0.55). The SI was not statistically different between groups (mean difference 3.6, 95% CI -7.4 to 14.5). INTERPRETATION: Rates of CDMR have not increased in Ontario. Planned CDMR is associated with a decreased risk of short-term adverse outcomes compared with planned vaginal delivery. Investigation into the long-term implications of CDMR is warranted.

Postnatal gestational age estimation via newborn screening analysis: application and potential.

Introduction: Preterm birth is a major global health concern, contributing to 35% of all neonatal deaths in 2016. Given the importance of accurately ascertaining estimates of preterm birth and in light of current limitations in postnatal gestational age (GA) estimation, novel methods of estimating GA postnatally in the absence of prenatal ultrasound are needed. Previous work has demonstrated the potential for metabolomics to estimate GA by analyzing data captured through routine newborn screening. Areas covered: Circulating analytes found in newborn blood samples vary by GA. Leveraging newborn screening and demographic data, our group developed an algorithm capable of estimating GA postnatally to within approximately 1 week of ultrasound-validated GA. Since then, we have built on the model by including additional analytes and validating the model's performance through internal and external validation studies, and through implementation of the model internationally. Expert opinion: Currently, using metabolomics to estimate GA postnatally holds considerable promise but is limited by issues of cost-effectiveness and resource access in low-income settings. Future work will focus on enhancing the precision of this approach while prioritizing point-of-care testing that is both accessible and acceptable to individuals in low-resource settings.

Trends in IVIG use at a tertiary care Canadian center and impact of provincial use mitigation strategies: 10-year retrospective study with interrupted time series analysis.

BACKGROUND: Intravenous immunoglobulin (IVIG) is a fractionated plasma product used to treat a range of autoimmune or inflammatory conditions, as well as immunodeficiency. Demand for this high-cost product is increasing worldwide. Understanding historical changes in IVIG use is important for inventory management and demand forecasting as well as for the development of initiatives aimed at optimizing blood product use. STUDY DESIGN AND METHODS: This was a 10-year retrospective cohort study of all patient encounters involving an IVIG transfusion from 2007 to 2016 at a four-site tertiary care hospital in Ontario, Canada. IVIG use was reported, including number of hospital encounters and amounts of IVIG prescribed. An interrupted time series analysis was performed to evaluate temporal changes in product use coinciding with the release of 2009-2010 provincial initiatives to optimize IVIG. RESULTS: A total of 1,658,159.50 g of IVIG was administered from 2007 to 2016. Total annual volume administered initially decreased after implementation of new policies (-2032 g/quarter). The number of IVIG patient encounters also decreased (-49.8 encounters/quarter) but was mirrored by an increase in the total volume administered per patient encounter (+0.88 g/quarter). Use increased 820 g/quarter from 2013 to 2016 but was 21% lower than projected before implementation of provincial policies. CONCLUSION: Trends in IVIG use show ongoing increases in the number of patients treated with the product. Development and implementation of provincial initiatives to optimize IVIG use coincided with significant short-term changes at a large tertiary care hospital. Novel initiatives aimed at dose minimization and prescription rationalization for this therapy are needed on local as well as larger scales.

Risks and trends of red blood cell transfusion in obstetric patients: a retrospective study of 45,213 deliveries using administrative data.

BACKGROUND: Transfusion data for obstetric patients are scarce. Identifying characteristics associated with red blood cell transfusion (RBCT) is of importance to better identify patients who would benefit from blood conservation strategies as the risk of alloimmunization from RBCT has the potential to affect the fetus and newborn. STUDY DESIGN AND METHODS: We conducted a retrospective cohort study using hospital administrative data to identify trends and risk factors of RBCT in obstetric patients. Data were analyzed according to the mode of delivery. RESULTS: A total of 45,213 deliveries were captured between January 1, 2007, and December 31, 2013. A higher proportion of patients undergoing cesarean sections (C/Ss) received an RBCT (2.3%) compared to other modes of delivery (0.7% for spontaneous vaginal delivery, 1.5% for instrumental delivery; p < 0.001). In addition, the risk of RBCT increased over the 7-year period for those patients undergoing C/S (relative risk [RR], 1.56; 95% confidence interval [CI], 1.14-2.15). An unavailable hemoglobin (Hb) level (RR, 12.94; 95% CI, 7.39-22.66) and Hb level of 70 to 80 g/L (RR, 7.78; 95% CI = 5.21-11.60) were strongly associated with RBCT among women undergoing C/S. Earlier gestational age at induction increased the risk of RBCT across all modes of delivery. CONCLUSIONS: The higher frequency of RBCT for unknown and low Hb supports the need for predelivery patient blood management at the time of delivery. The additional risk factors associated with RBCT identified may be used to develop risk stratification tools by mode of delivery to assist in the identification of patients at the highest risk of requiring RBCT.

Risk of exposure to blood products during pregnancy: guidance for Zika and other donor deferral policies.

BACKGROUND: Exposure to blood products during pregnancy carries a potential risk of transfusion transmission of infectious agents. Blood agencies have historically sought optimal deferral and testing strategies to protect blood supplies in part to ensure the protection of pregnant women and their unborn infants. The Zika virus outbreak of 2016 has heightened attention to these concerns. In the current context of the recent Zika outbreak, and also more broadly, data are needed to shed light on the likelihood of exposure to blood products throughout pregnancy to inform policy. STUDY DESIGN AND METHODS: Hospital administrative data from a large tertiary care center were examined for outpatient and nondelivery inpatient transfusion events in pregnant women between January 1, 2007, and December 31, 2013. Those pregnancies resulting in miscarriage were excluded from analysis. RESULTS: A total of 45,179 pregnancies resulting in delivery of a live or stillborn infant were documented at The Ottawa Hospital during the study period. Our findings indicate that 0.124%, or 1240 in 1,000,000, expectant mothers received transfusion at some point during their pregnancies with 0.04%, or 400 per 1,000,000, expectant mothers receiving a transfusion in the first trimester. CONCLUSION: Data from a large tertiary care center suggest that the risk of maternal and fetal exposure to blood products by transfusion during any stage of pregnancy is very low. Such a low likelihood of transfusion should be taken into consideration when developing donor deferral policies designed to protect women against transfusion-associated infection transmission during pregnancy and could inform evaluations of the risk of prenatal transfusion transmission of the Zika virus.

Using Mobile Apps to Communicate Vaccination Records: A City-wide Evaluation with a National Immunization App, Maternal Child Registry and Public Health Authorities.

Medicine is experiencing a paradigm shift, where patients are increasingly involved in the management of their health data. We created a mobile app which permitted parental reporting of immunization status to public health authorities. We describe app use as a proxy for feasibility and acceptability as well as data utility for public health surveillance. The evaluation period ran from April 27, 2015, to April 18, 2017, during which time 2,653 unique children's records were transmitted, containing 36,105 vaccinations. Our findings suggest that mobile immunization reporting is feasible and may be an acceptable complement to existing reporting methods. Measures of data utility suggest that mobile reporting could enable more accurate assessments of vaccine coverage.

Pre-eclampsia and Cardiovascular Disease Risk Assessment in Women.

The underlying contributors of many cardiovascular events are often present decades before the onset of clinical symptoms, and the presence of risk factors in early life significantly influences risk of premature cardiovascular disease (CVD). The considerable burden of CVD in women and on health care resources necessitates an emphasis on prevention and early risk screening in women, before the development of the disease itself. The 2011 update to the American Heart Association's Effectiveness-Based Guidelines for the prevention of CVD acknowledges the contribution of the common pregnancy-related medical complications to a woman's cardiovascular risk, identifying pre-eclampsia (PE), gestational hypertension, and gestational diabetes mellitus as risk factors for heart disease and stroke. The aims of this review are to examine risk factors in young women and their role in the development of premature CVD, with particular attention paid to PE as a marker of a woman's cardiovascular risk. Current screening practices will be discussed, as will their influences on identifying and reducing cardiovascular risk and subsequent disease in younger women.

Differential expression of plasma microRNA in preeclamptic patients at delivery and 1 year postpartum.

OBJECTIVE: Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by widespread maternal endothelial dysfunction. Although clinical signs subside following delivery, long-term risks associated with PE include hypertension, stroke, and cardiovascular disease. MicroRNAs (miRNAs) are emerging as critical regulators of biological function, and while alterations to the miRNAome have been described in the context of pregnancy and PE, the postpartum implications of PE on miRNA expression is unknown. The goal of this study was to characterize circulating miRNA profiles at the time of delivery and at 1 year postpartum for women who did and did not develop PE. STUDY DESIGN: Using a targeted reverse transcription polymerase chain reaction approach, selected miRNAs putatively involved in the pathophysiology of PE were examined in 17 normotensive control and 13 PE maternal plasma samples at the time of delivery and 1 year postpartum. Ingenuity Pathway Analysis was used to map putative messenger RNA targets of differentially expressed miRNA to global molecular networks based on gene function. RESULTS: Significant increases (P < .05) in 7 miRNAs with antiangiogenic, inflammatory, and apoptotic functions (miR-98-5p, miR-222-3p, miR-210-3p, miR-155-5p, miR-296-3p, miR-181a-5p, miR-29b-3p) were evident in maternal plasma at the time of severe PE compared to time-matched controls. Plasma samples from individuals who developed mild PE exhibited no changes compared to control samples for the subset of miRNAs analyzed here. Differential expression of plasma miRNA at the time of delivery for women with PE were largely resolved at 1 year postpartum, and reduced expression of only miR-221-3p (P < .05) was evident. Network analysis of putative targets of differentially regulated miRNA identified 11 interacting networks with enrichment for proteins involved in cardiovascular disease, organ system development and function, and cell signaling and interaction. CONCLUSION: The systemic effect of PE on maternal systems is evident in the circulating miRNAome with substantial alterations in miRNA expression in women who develop severe PE. In addition we provide novel evidence of disruption to miR-221 expression 1 year postpartum following a pregnancy complicated by PE compared to normotensive time-matched controls, which may allude to persistent inflammation in these women after delivery.

Alterations to the maternal circulating proteome after preeclampsia.

OBJECTIVE: The long-term maternal cardiovascular and metabolic implications associated with preeclampsia (PE) include risk of hypertension, heart disease, and metabolic syndrome. The objective of this study was to investigate if a recent history of PE was associated with detectable alterations in the circulating maternal proteome. STUDY DESIGN: Six-month postpartum plasma from women with a history of PE (n = 12) and women with uncomplicated obstetrical history (n = 12) were used for analysis. Depleted maternal plasma was analyzed by label-free liquid chromatography-mass spectrometry assay. Identified peptides were searched against the International Protein Index human database version 3.87. Exponentially modified protein abundance indices were used for comparison. Results were analyzed using pathway analysis software. RESULTS: A total of 126 eligible peptides were identified for analysis; 3 peptides were differentially expressed in the PE proteome, and an additional 5 peptides were unique to control subjects and 7 to PE subjects. PE peptide profiles were more strongly associated with markers of coagulation and complement activation compared to controls and mapped more significantly to cardiovascular disease (CVD) functions. Stratification of subjects by low (<39%) and high (≥39%) lifetime risk of CVD rather than by diagnosis produced similar findings. Comparison of controls (n = 6) to PE subjects (n = 6) without traditional cardiovascular risk factors found that while similar for body mass indices, blood pressure, and fasting lipid profiles at 6 months postpartum, PE peptide profiles continued to display stronger associations for coagulation and CVD functions. Global network analysis found that unique peptides to low-risk PE subjects were associated with cardiac infarction, CVD, and organismal injury and abnormalities. CONCLUSION: Markers of CVD risk and progression are evident in the maternal circulating proteome 6 months postpartum after PE. Augmentations in circulating peptide profiles occur in patients with previous PE who otherwise do not have clinically measurable cardiovascular risk factors. Our data highlight the need for the implementation of postpartum prevention programs in the PE population and identifies molecules that may be targeted for screening or therapeutic benefit.

Investigating factors influencing decision-making around use of breastmilk substitutes by health care professionals: a qualitative study.

BACKGROUND: Breastfeeding is recognized as the gold standard of infant feeding and nutrition. The World Health Organization recommends exclusive breastfeeding (EBF) of infants for the first 6 months of life. A variety of factors may impact breastfeeding practices in-hospital which may continue after hospital discharge, such as the use of breastmilk substitutes (BMS). The Baby-Friendly Initiative (BFI), which aims to promote and support breastfeeding practices, established a target rate of 75% for EBF from birth to hospital discharge. Currently, this target is not being met at The Ottawa Hospital (TOH), indicating there is room for improvement in EBF rates. The purpose of this study is to explore health care professionals (HCP) decision-making around use of BMS and identify factors that drive the use of BMS with and without medical indications. METHODS: In this qualitative study, semi-structured interviews were conducted with HCPs within TOH from January to June 2022. All participants had experience in maternity or postpartum care and were probed on factors influencing use of BMS at this institution. Interview transcripts were coded using an inductive approach. RESULTS: A total of 18 HCPs were interviewed including physicians, midwives, lactation consultants, and registered nurses. Multilevel barriers influencing the use of BMS were categorized into patient, HCP, and institution-level factors. Subthemes that emerged ranged from parental preferences, training differences amongst HCPs, to budget and staffing issues. Over half of HCPs were prepared to answer questions on EBF and were familiar with the BFI. Although most were supportive of this institution receiving BFI designation, a few providers raised concerns of its impact on parents who would like to supplement. CONCLUSIONS: Several modifiable factors influencing decision-making for use of BMS were identified. These findings will be used to inform unit leads, help identify effective strategies to address modifiable barriers, and develop tailored breastfeeding supports to improve EBF rates.

Chronic carbon monoxide inhalation during pregnancy augments uterine artery blood flow and uteroplacental vascular growth in mice.

End-tidal breath carbon monoxide (CO) is abnormally low in women with preeclampsia (PE), while women smoking during pregnancy have shown an increase in CO levels and a 33% lower incidence of PE. This effect may be, in part, due to lowered sFLT1 plasma levels in smokers, and perhaps low-level CO inhalation can attenuate the development of PE in high-risk women. Our previous work showed maternal chronic CO exposure (<300 ppm) throughout gestation had no maternal or fetal deleterious effects in mice. Our current study evaluated the uteroplacental vascular effects in CD-1 maternal mice that inhaled CO (250 ppm) both chronically, gestation day (GD) 0.5 to 18.5, and acutely, 2.5 h on each of GD 10.5 and 14.5. We demonstrated, using microultrasound measurements of blood velocity and microcomputed tomography imaging of the uteroplacental vasculature, that chronic maternal exposure to CO doubled uterine artery blood flow and augmented uteroplacental vascular diameters and branching. This finding may be of benefit to women with PE, as they exhibit uteroplacental vascular compromise. The ratio of VEGF protein to its FLT1 receptor was increased in the placenta, suggesting a shift to a more angiogenic state; however, maternal circulating levels of VEGF, sFLT1, and their ratio were not significantly changed. Doppler blood velocities in the maternal uterine artery and fetal umbilical artery and vein were unaltered. This study provides in vivo evidence that chronic inhalation of 250 ppm CO throughout gestation augments uterine blood flow and uteroplacental vascular growth, changes that may protect against the subsequent development of preeclampsia.

Pregnancy and neonatal outcomes following malignancy in pregnancy at a tertiary care Canadian center: a retrospective chart review.

Objective: Data on pregnancy-associated cancers (PACs) are lacking. The objectives of this study were to determine the incidence of PACs and describe the characteristics and outcomes of pregnancies affected by malignancy at a single tertiary care center in Ottawa, Canada.Methods: This was a retrospective chart review of individuals with PAC at The Ottawa Hospital (TOH) between 2011-2022. Eligible cases were identified from the TOH Data Warehouse, the TOH instance of the Better Outcomes Registry & Network Ontario, and the TOH Division of Maternal Fetal Medicine's Perinates database. Chart reviews were conducted to confirm case eligibility and to extract demographic, oncologic, obstetrical, and neonatal measures. The annual incidence of PAC over the 11-year period was reported per 1000 deliveries. Descriptive statistics were used to describe the sample, including frequency (n) and proportions (%) for categorical variables and mean and standard deviation (SD) for continuous variables.Results: The final cohort included 59 individuals with PAC at TOH between 2011-2022. The annual incidence of PAC ranged from 0.47 to 1.54 per 1000 deliveries. The most common PACs were breast cancer (28.8%), Hodgkin lymphoma (10.2%), and thyroid cancer (8.5%). Common interventions during pregnancy included chemotherapy (33.9%) and surgical intervention (32.2%). A total of 19 individuals (32.2%) did not undergo PAC-related treatment during pregnancy. There were 55 livebirths (91.7%), 2 spontaneous abortions (3.3%), 3 induced abortions (5.0%), and no stillbirths. Among livebirths, the mean gestational age was 37.4 ± 2.8 weeks and the mean birthweight was 2920.3 ± 650.0 g. All neonates had reassuring 5-minute Apgar scores, 18 (32.7%) were admitted to the Neonatal Intensive Care Unit/Special Care Nursery (NICU/SCN), and 8 (14.5%) were noted to have a mild congenital abnormality.Conclusion: This study shows promising perinatal outcomes for patients with PAC and their neonates. Ongoing surveillance of PAC is needed to better inform care for this patient population.

Interventions for intimate partner violence during the perinatal period: a scoping review protocol.

INTRODUCTION: Globally, the prevalence and incidence of perinatal intimate partner violence (IPV) are well documented and substantiated; however, there is an urgent need to identify interventions to prevent recurrence or revictimisation, and decrease the harms of perinatal IPV. This scoping review is designed to broadly capture all potential interventions for the secondary prevention of IPV, review them in detail, and assess what can reduce revictimisation and foster improvements in both maternal and neonatal outcomes. METHODS AND ANALYSIS: With the structure of the Joanna Briggs Institute and Arksey and O'Malley methodology for scoping reviews, the search will be conducted in: MEDLINE(R) ALL (OvidSP), Embase (OvidSP), CINAHL (EBSCOHost), APA PsycInfo (OvidSP), Cochrane Central Register of Controlled Trials (OvidSP), Web of Science, and Applied Social Sciences Index & Abstracts (ProQuest). A manual search of the reference lists of the retrieved articles will be conducted to capture all relevant studies for potential inclusion. A year limit of January 2000-June 2022 will be applied to retrieve most current peer-reviewed articles. No search filters or language limits will be used, but only publications in English and French will be eligible for inclusion. Interventions include but are not limited to: psychotherapy, educational sessions, home visitation, etc. Outcomes include but are not limited to: (1) harms of IPV among survivors (eg, revictimisation) and (2) adverse perinatal outcomes (eg, preterm birth). Interventions will be excluded if they target the perpetrator or child(ren) alone. Titles and abstracts of included studies will be screened in duplicate. Full-text documents will be extracted and reviewed by two independent reviewers. Conflicts between reviewers will be resolved by a third independent reviewer. Findings will be presented with descriptive statistics and narrative synthesis. ETHICS AND DISSEMINATION: Ethics approval is not required for this scoping review. The results will be disseminated through peer-reviewed publication and conference presentations. STUDY REGISTRATION: Open Science Framework (OSF) registry (https://osf.io/e294r) in Centre for Open Science (OSF) on 27 May 2022.