Population-level changes in perinatal death for pregnancies prior to and during the COVID-19 pandemic: A pregnancy cohort analysis.

BACKGROUND: Results of population-level studies examining the effect of the COVID-19 pandemic on the risks of perinatal death have varied considerably. OBJECTIVES: To explore trends in the risk of perinatal death among pregnancies beginning prior to and during the pandemic using a pregnancy cohort approach. METHODS: This secondary analysis included data from singleton pregnancies ≥20 weeks' gestation in Alberta, Canada, beginning between 5 March 2017 and 4 March 2021. Perinatal death (i.e. stillbirth or neonatal death) was the primary outcome considered. The risk of this outcome was calculated for pregnancies with varying gestational overlap with the pandemic (i.e. none, 0-20 weeks, entire pregnancy). Interrupted time series analysis was used to further determine temporal trends in the outcome by time period of interest. RESULTS: There were 190,853 pregnancies during the analysis period. Overall, the risk of perinatal death decreased with increasing levels of pandemic exposure; this outcome was experienced in 1.0% (95% confidence interval [CI] 0.9, 1.0), 0.9% (95% CI 0.8, 1.1) and 0.8% (95% CI 0.7, 0.9) of pregnancies with no overlap, partial overlap and complete pandemic overlap respectively. Pregnancies beginning during the pandemic that had high antepartum risk scores less frequently led to perinatal death compared to those beginning prior; 3.3% (95% CI 2.7, 3.9) versus 5.7% (95% CI 5.0, 6.5) respectively. Interrupted time-series analysis revealed a decreasing temporal trend in perinatal death for pregnancies beginning ≤40 weeks prior to the start of the COVID-19 pandemic (i.e. with pandemic exposure), with no trend for pregnancies beginning >40 weeks pre-pandemic (i.e. no pandemic exposure). CONCLUSION: We observed a decrease in perinatal death for pregnancies overlapping with the COVID-19 pandemic in Alberta, particularly among those at high risk of these outcomes. Specific pandemic control measures and government response programmes in our setting may have contributed to this finding.

Exclusion of pregnant and lactating persons from breast cancer clinical trials: a review of active trials registered on ClinicalTrials.gov.

INTRODUCTION: Treatment of pregnancy-associated breast cancer is complex, as providers try to balance risks to the pregnant person and the developing fetus. Given increased case fatality and increasing incidence, there is a pressing need understand the efficacy and safety of different treatment regimens in this population; however, pregnant and lactating people have traditionally been excluded from participating in randomized controlled trials (RCTs). Given recent efforts to expand the inclusion criteria for oncology RCTs, this study aimed to review the inclusion/exclusion criteria of current breast cancer RCTs to assess what proportion of trials permitted enrollment of pregnant and lactating persons. MATERIAL AND METHODS: We conducted a comprehensive search of ClinicalTrials.gov in January 2022 to identify interventional studies of breast cancer in adults that were actively recruiting. The primary outcomes were the exclusion of pregnant and lactating people. RESULTS: The search identified 1706 studies, of which 1451 met eligibility criteria. Overall, 69.4% and 54.8% of studies excluded pregnant and lactating people, respectively. The exclusion of pregnant and lactating persons differed by study characteristics but extended across all trial designs, locations, phases and interventions. Exclusion of pregnant and lactating persons was most common in trials where the intervention was biological (86.3%), drug (83.5%) or radiation (81.5%). CONCLUSIONS: The exclusion of pregnant and lactating people from clinical trials contributes to evidence gaps in how to treat this population. A paradigm shift is needed that focuses on how research can be used to protect pregnant people from future harms, instead of protecting pregnant people from research-related risks.

The association of gestational age at birth with trajectories of early childhood developmental delay among late preterm and early term born children: A longitudinal analysis of All Our Families pregnancy cohort.

BACKGROUND: Like infants born very preterm (<32 weeks), late preterm (≥34 and <37 weeks) and early term (≥37 and <39 weeks) births have been associated with increased risk of developmental delay (DD); yet, the evidence remains heterogeneous across the continuum of gestational ages, hindering early identification and intervention. OBJECTIVE: To estimate the association of gestational age at birth with early childhood trajectories of DD in early childhood for infants born ≥34 and <41 weeks, and determine how various maternal, pregnancy and infant characteristics relate to these trajectory groups. METHODS: Analysis of mother-child dyad data with infants born ≥34 and <41 weeks gestational age within an observational pregnancy cohort in Alberta, Canada, from 2008 to 2011 (n = 2644). The association between gestational age and trajectories of the total number of Ages and Stages Questionnaire domains indicating risk of DD from 1 through 5 years of age were estimated using group-based trajectory modelling along with other perinatal risk factors. RESULTS: Three distinct trajectory groups were identified: low-risk, moderate-risk (transiently at risk of DD in one domain over time) and high-risk (consistently at risk of delay in ≥2 domains over time). Per week of decreasing gestational age, the risk ratio of membership in the high-risk group increases by 1.77 (95% confidence interval [CI] 1.43, 2.20) or 1.84 (95% CI 1.49, 2.27) relative to the moderate-risk and low-risk respectively. Increasing maternal age, identifying as Black, indigenous or a person of colour, elevated maternal depressive symptoms in pregnancy, and male infant sex were associated with high- and moderate-risk trajectories compared to the low-risk trajectory. CONCLUSIONS: In combination with decreasing gestational age, poor maternal mental health and social determinants of health increase the probability of membership in trajectories with increased risk of DD, suggesting that additional monitoring of children born late preterm and early term is warranted.

Mitigation of Participant Loss to Follow-Up Using Facebook: All Our Families Longitudinal Pregnancy Cohort.

BACKGROUND: Facebook, a popular social media site, allows users to communicate and exchange information. Social media sites can also be used as databases to search for individuals, including cohort participants. Retaining and tracking cohort participants are essential for the validity and generalizability of data in longitudinal research. Despite numerous strategies to minimize loss to follow-up, maintaining contact with participants is time-consuming and resource-intensive. Social media may provide alternative methods of contacting participants who consented to follow-up but could not be reached, and thus are potentially "lost to follow-up." OBJECTIVE: The aim of this study was to determine if Facebook was a feasible method for identifying and contacting participants of a longitudinal pregnancy cohort who were lost to follow-up and re-engaging them without selection bias. METHODS: This study used data from the All Our Families cohort. Of the 2827 mother-child dyads within the cohort, 237 participants were lost to follow-up. Participants were considered lost to follow-up if they had agreed to participate in additional research, completed at least one of the perinatal questionnaires, did not complete the 5-year postpartum questionnaire, and could not be contacted after numerous attempts via phone, email, or mail. Participants were considered to be matched to a Facebook profile if 2 or more characteristics matched information previously collected. Participants were sent both a friend request and a personal message through the study's Facebook page and were invited to verify their enrollment in the study. The authors deemed a friend request was necessary because of the reduced functionality of nonfriend direct messaging at the time. If the participant accepted the study's friend request, then a personalized message was sent. Participants were considered reconnected if they accepted the friend request or responded to any messages. Participants were considered re-engaged if they provided up-to-date contact information. RESULTS: Compared with the overall cohort, participants who were lost to follow-up (n=237) were younger (P=.003), nonmarried (P=.02), had lower household income (P<.001), less education (P<.001), and self-identified as being part of an ethnic minority (P=.02). Of the 237 participants considered lost to follow-up, 47.7% (113/237) participants were identified using Facebook. Among the 113 identified participants, 77.0% (87/113) were contacted, 32.7% (37/113) were reconnected, and 17.7% (20/113) were re-engaged. No significant differences were found between those identified on Facebook (n=113) and those who were not able to be identified (n=124). CONCLUSIONS: Facebook identified 47.6% (113/237) of participants who were considered lost to follow-up, and the social media site may be a practical tool for reconnecting with participants. The results from this study demonstrate that social networking sites, such as Facebook, could be included in the development of retention practices and can be implemented at any point in cohort follow-up.

Childcare use and the social-emotional and behavioural outcomes of late-preterm and early-term born children at age 5: An analysis of the All Our Families longitudinal cohort.

OBJECTIVES: Gestational age at birth (GA) shows an inverse gradient of risk with social-emotional and behavioural outcomes among children born late preterm (≥ 34 and < 37 weeks) and early term (≥ 37 and < 39 weeks). Childcare has the potential to influence this association. This study aimed to estimate the association between GA and social-emotional/behavioural problems among children born between ≥ 34 and < 41 weeks gestation, determine whether this association was modified by childcare use, and describe the relationship between childcare and behavioural and social-emotional functioning at age 5. METHODS: Using data from the All Our Families cohort (n = 1324), logistic regression models were used to model the association between GA and social-emotional/behavioural problems (BASC-2 composite scales at age 5). Models were fit with interaction terms between GA and childcare variables (amount, multiplicity, and type of childcare at age 3) to assess effect modification. RESULTS: GA showed no significant associations with social-emotional/behavioural problems at age 5, though the type of childcare significantly modified the association between GA and externalizing and internalizing problems. Neither the number of hours spent in childcare (amount) nor the number of childcare arrangements used (multiplicity) modified the association between GA and social-emotional/behavioural problems. However, multiplicity was associated with externalizing behavioural problems (aOR = 2.09, 95% CI 1.14‒3.83). CONCLUSION: This study found no significant association between GA and social-emotional/behavioural problems at age 5, though childcare type modified this association. Factors such as using multiple childcare arrangements to meet families' childcare needs have the potential to influence a child's social-emotional and behavioural functioning at age 5.

RéSUMé: OBJECTIFS: L'âge gestationnel à la naissance (AG) présente un gradient du risque inversé pour les résultats socioaffectifs et comportementaux entre les naissances prématurées tardives (entre ≥ 34 et < 37 semaines) et les naissances précoces (entre ≥ 37 et < 39 semaines). Les services de garde pourraient influencer cette association. Notre étude visait à estimer l'association entre l'AG et les troubles socioaffectifs/comportementaux chez les enfants nés entre ≥ 34 et < 41 semaines de gestation, à déterminer si cette association est modifiée par le recours aux services de garde et à décrire la relation entre les services de garde et le fonctionnement comportemental et socioaffectif à l'âge de cinq ans. MéTHODE: Des modèles de régression logistique utilisant les données de la cohorte All Our Families (n = 1 324) ont servi à modéliser l'association entre l'AG et les troubles socioaffectifs/comportementaux (échelles composées BASC-2 à l'âge de cinq ans). Les modèles ont été ajustés avec des paramètres d'interaction entre l'AG et les variables des services de garde (nombre, multiplicité et type de services de garde à l'âge de trois ans) pour évaluer les facteurs modifiant l'effet. RéSULTATS: L'AG n'a présenté aucune association significative avec les troubles socioaffectifs/comportementaux à l'âge de cinq ans, mais le type de services de garde a sensiblement modifié l'association entre l'AG et les troubles d'extériorisation et d'intériorisation. Ni le nombre d'heures passées dans les services de garde (nombre), ni le nombre de modes de garde d'enfants utilisés (multiplicité) n'ont modifié l'association entre l'AG et les troubles socioaffectifs/comportementaux. Toutefois, la multiplicité était associée aux troubles comportementaux d'extériorisation (RCa = 2,09, IC de 95% : 1,14‒3,83). CONCLUSION: L'étude n'a trouvé aucune association significative entre l'AG et les troubles socioaffectifs/comportementaux à l'âge de cinq ans, mais le type de services de garde a modifié cette association. Des facteurs comme le recours à plusieurs modes de garde d'enfants pour combler les besoins de services de garde de la famille pourraient influencer le fonctionnement socioaffectif et comportemental d'un enfant à l'âge de cinq ans.

Early childhood trajectories of domain-specific developmental delay and gestational age at birth: An analysis of the All Our Families cohort.

OBJECTIVE: To describe developmental domain-specific trajectories from ages 1 through 5 years and to estimate the association of trajectory group membership with gestational age for children born between ≥34 and <41 weeks gestation. METHODS: Using data from the All Our Families cohort, trajectories of the domain-specific Ages & Stages Questionnaire scores were identified and described using group-based trajectory modeling for children born ≥34 and <41 weeks of gestation (n = 2664). The trajectory groups association with gestational age was estimated using multinomial logistic regression. RESULTS: Across the five domains, 4-5 trajectory groups were identified, and most children experienced changing levels of risk for delay over time. Decreasing gestational age increases the Relative risk of delays in fine motor (emerging high risk: 1.46, 95% CI: 1.19-1.80; resolving moderate risk: 1.11, 95% CI: 1.03-1.21) and gross motor (resolving high risk: 1.21, 95% CI: 1.04-1.42; and consistent high risk: 1.64, 95% CI: 1.20-2.24) and problem solving (consistent high risk: 1.58 (1.09-2.28) trajectory groups compared to the consistent low risk trajectory groups. CONCLUSION: This study highlights the importance of longitudinal analysis in understanding developmental processes; most children experienced changing levels of risk of domain-specific delay over time instead of having a consistent low risk pattern. Gestational age had differential effects on the individual developmental domains after adjustment for social, demographic and health factors, indicating a potential role of these factors on trajectory group membership.

Food Marketing and Power: Teen-Identified Indicators of Targeted Food Marketing.

Food marketing is powerful and prevalent, influencing young people's food attitudes, preferences, and dietary habits. Teenagers are aggressively targeted by unhealthy food marketing messages across a range of platforms, prompting recognition of the need to monitor such marketing. To monitor, criteria for what counts as teen-targeted food marketing content (i.e., persuasive techniques) must first be established. This exploratory study engaged teenagers to explore the "power" of food marketing by identifying what they consider to be teen-targeted marketing techniques within various food marketing examples. Fifty-four teenagers (ages 13-17) participated in a tagging exercise of 19 pre-selected food/beverage advertisements. Assessed in light of age and gender, the results showed clear consistency with what indicators the participants identified when it comes to selecting "teen-targeted" ads-with advertisements most frequently chosen as "teen-targeted" containing humor (particularly irony) and celebrities. When it comes to specific indicators used by teenagers, visual style dominated, standing as the marketing technique with the most "power" for teenagers. The findings shed much needed insight into the elements of power-and more precisely, the specific marketing techniques persuasive to teenagers-which are necessary to inform monitoring efforts and to create evidence-based policy.

Second trimester cytokine profiles associated with gestational diabetes and hypertensive disorders of pregnancy.

Healthy pregnancy requires a coordinated immune response, yet complications can arise, putting both the mother's and child's health at risk. Hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) are pregnancy-related complications that account for most maternal morbidity and mortality. Cytokines are proteins released as part of the immune response to disease or infection and regulate inflammation. Certain pregnancy complications cause localized and systemic inflammation; however, cytokine profiles specific to such complications are not well understood. This study aims to examine associations between pregnancy complications of HDP and GDM and cytokine profiles in the second trimester of pregnancy. Data was obtained from the All Our Families birth cohort in Calgary, Alberta, Canada. The cohort collected questionnaires at the time of participant enrollment and maternal blood samples at 17-23 weeks gestation. Cases of HDP (n = 27) and GDM (n = 31) were matched to controls on BMI, maternal age, and smoking status in the preconception period at a 1:3 ratio. Cytokine levels were measured in blood samples using Luminex xMAP technology using a panel of 42 cytokines. Using R software, a Classification and Regression Tree (CART) analysis was conducted to identify cytokine profiles and levels associated with each complication. Four cytokines were identified in the HDP CART (in descending order of importance): Monocyte Chemoattractant Protein-1 (cut-off: <480pg/mL), Macrophage Inflammatory Protein-1ß (cut-off: ≥26pg/mL), Eotaxin (cut-off: <27/≥27&<36/≥36pg/mL), and Soluble Cluster of Differentiation 40 Ligand (cut-off: <1342pg/mL). Six cytokine levels were identified in the GDM CART: Interleukin-1 Receptor Antagonist (IL-1Ra; cut-off: <25pg/mL), Interleukin-5 (cut-off: ≥0.4pg/mL), Interferon-γ (cut-off: <4.9pg/mL), IL-1Ra (cut-off: ≥111pg/mL), Eotaxin (cut-off: ≥21pg/mL), and Interleukin-18 (cut-off: ≥155pg/mL). By examining the complex inter-relationships between cytokines, findings of cytokine profiles guide further research in identifying biomarkers of pregnancy complications relevant to the design of the future management or prevention of these conditions.

Quality assessment of RNA in long-term storage: The All Our Families biorepository.

BACKGROUND: The All Our Families (AOF) cohort study is a longitudinal population-based study which collected biological samples from 1948 pregnant women between May 2008 and December 2010. As the quality of samples can decline over time, the objective of the current study was to assess the association between storage time and RNA (ribonucleic acid) yield and purity, and confirm the quality of these samples after 7-10 years in long-term storage. METHODS: Maternal whole blood samples were previously collected by trained phlebotomists and stored in four separate PAXgene Blood RNA Tubes (PreAnalytiX) between 2008 and 2011. RNA was isolated in 2011 and 2018 using PAXgene Blood RNA Kits (PreAnalytiX) as per the manufacturer's instruction. RNA purity (260/280), as well as RNA yield, were measured using a Nanodrop. The RNA integrity number (RIN) was also assessed from 5-25 and 111-130 months of storage using RNA 6000 Nano Kit and Agilent 2100 BioAnalyzer. Descriptive statistics, paired t-test, and response feature analysis using linear regression were used to assess the association between various predictor variables and quality of the RNA isolated. RESULTS: Overall, RNA purity and yield of the samples did not decline over time. RNA purity of samples isolated in 2011 (2.08, 95% CI: 2.08-2.09) were statistically lower (p<0.000) than samples isolated in 2018 (2.101, 95% CI: 2.097, 2.104), and there was no statistical difference between the 2011 (13.08 µg /tube, 95% CI: 12.27-13.89) and 2018 (12.64 µg /tube, 95% CI: 11.83-13.46) RNA yield (p = 0.2964). For every month of storage, the change in RNA purity is -0.01(260/280), and the change in RNA yield between 2011 and 2018 is -0.90 µ g / tube. The mean RIN was 8.49 (95% CI:8.44-8.54), and it ranged from 7.2 to 9.5. The rate of change in expected RIN per month of storage is 0.003 (95% CI 0.002-0.004), so while statistically significant, these results are not relevant. CONCLUSIONS: RNA quality does not decrease over time, and the methods used to collect and store samples, within a population-based study are robust to inherent operational factors which may degrade sample quality over time.

Health-related quality of life in pregnancy and postpartum among women with assisted conception in Canada.

OBJECTIVE: To study the effects of mode of conception (spontaneous vs. assisted) on health-related quality of life (HRQoL) throughout pregnancy and in the postpartum period. DESIGN: Secondary analysis of data from the All Our Babies cohort. SETTING: Not applicable. PATIENT(S): A total of 243 women with assisted conception and 3,309 women with spontaneous conception. INTERVENTION(S): Short Form 12 (SF-12) health survey administered by means of questionnaires at <25 weeks, 34-36 weeks of gestation, and 4 months postpartum. MAIN OUTCOME MEASURE(S): Changes in the SF-12 Physical (PCS) and Mental (MCS) Component Summary scores from pregnancy to postpartum. RESULT(S): The PCS scores were lower during pregnancy and at <25 weeks and 34-36 weeks of gestation among women with assisted conception, but were equivalent to those of women with spontaneous conception by 4 months postpartum. The MCS scores were higher at <25 weeks among women with assisted conception, but by 34-36 weeks of gestation and at 4 months postpartum they were similar regardless of the method of conception. Analysis of covariance showed no significant differences for the changes in PCS and MCS scores from pregnancy to postpartum between assisted and spontaneous conception groups, after adjusting for covariates. CONCLUSION(S): Women with assisted conception may report lower physical and better mental health during pregnancy than women with spontaneous conception. At 4 months postpartum, there were no differences in self-reported HRQoL between modes of conception. Women with assisted conception may benefit from support and reassurance that perception of suboptimal health may improve over pregnancy and into the postpartum period.