Social Media Recruitment Strategies to Recruit Pregnant Women Into a Longitudinal Observational Cohort Study: Usability Study.

BACKGROUND: Use of social media for study recruitment is becoming increasingly common. Previous studies have typically focused on using Facebook; however, there are limited data to support the use of other social media platforms for participant recruitment, notably in the context of a pregnancy study. OBJECTIVE: Our study aimed to evaluate the effectiveness of Facebook, Twitter, and Instagram in recruiting a representative sample of pregnant women in a longitudinal pregnancy cohort study in Calgary, Alberta, between September 27, 2021, and April 24, 2022. METHODS: Paid advertisements were targeted at 18- to 50-year-old women in Calgary, with interests in pregnancy. Data regarding reach, link clicks, and costs were collected through Facebook Ads Manager (Meta Platforms, Inc) and Twitter Analytics (Twitter, Inc). The feasibility of each platform for recruitment was assessed based on the recruitment rate and cost-effectiveness. The demographic characteristics of the participants recruited through each source were compared using the chi-square test. RESULTS: Paid advertisements reached 159,778 social media users, resulting in 2390 link clicks and 324 participants being recruited. Facebook reached and recruited the highest number of participants (153/324, 47.2%), whereas Instagram saw the highest number of link clicks relative to the number of users who saw the advertisement (418/19,764, 2.11%). Facebook and Instagram advertisements were cost-effective, with an average cost-per-click of CAD $0.65 (US $0.84; SD $0.27, US $0.35) and cost-per-completer of CAD $7.89 (US $10.25; SD CAD $4.08, US $5.30). Twitter advertisements were less successful in terms of recruitment and costs. Demographic characteristics of participants did not differ based on recruitment source, except for education and income, where more highly educated and higher-income participants were recruited through Instagram or Twitter. Many issues related to fraudulent responses were encountered throughout the recruitment period. CONCLUSIONS: Paid social media advertisements (especially Facebook and Instagram) are feasible and cost-effective methods for recruiting a large sample of pregnant women for survey-based research. However, future research should be aware of the potential for fraudulent responses when using social media for recruitment and consider strategies to mitigate this problem.

Cyclooxygenase inhibitors for treating preterm labour: What is the molecular evidence? 1.

Preterm birth (<37 weeks of gestation) significantly increases the risk of neonatal mortality and morbidity. As many as half of all preterm births occur following spontaneous preterm labour. Since in such cases there are no known reasons for the initiation of labour, treatment of preterm labour (tocolysis) has sought to stop labour contractions and delay delivery. Despite some success, the use of cyclooxygenase (COX) inhibitors is associated with maternal/fetal side effects, and possibly increased risk of preterm birth. Clinical use of these drugs predates the collection of molecular and biochemical evidence in vitro, examining the expression and activity of COX enzymes in pregnant uterine tissues with and without labour. Such evidence is important to the rationale that COX enzymes are, or are not, appropriate targets for the tocolysis. The current study systematically searched existing scientific evidence to address the hypothesis that COX expression/activity is increased with the onset of human labour, in an effort to determine whether there is a rationale for the use of COX inhibitors as tocolytics. Our review identified 44 studies, but determined that there is insufficient evidence to support or refute a role of COX-1/-2 in the onset of preterm labour that supports COX-targeted tocolysis.

Comparison of the Fagerström Test for Cigarette Dependence and the Heaviness of Smoking Index in the Second and Third Trimester of Pregnancy.

INTRODUCTION: Smoking cessation at any stage of pregnancy can benefit the mother and fetus. Cigarette dependence is a significant factor in women who continue to smoke during pregnancy and accurate assessment of cigarette dependence can be helpful in planning smoking cessation programs. The objective of our study was to investigate the validity of the Fagerstrom Test for Cigarette Dependence (FTCD) and Heaviness of Smoking Index (HSI) as measures of cigarette dependence in the second and third trimesters of pregnancy by comparing them to serum cotinine levels. METHODS: Prospective cohort study of 167 women in their second and third trimester of pregnancy who self-reported cigarette smoking. They were administered the FTCD questionnaire and blood was drawn for cotinine measurements using a direct enzyme linked immunoassay. Linear regression was used to adjust for maternal age, body mass index, gestation, and parity to investigate the association between cotinine levels and the two scores. RESULTS: Both the FTCD and HSI correlated significantly with serum cotinine levels (Spearman coefficient 0.42 and 0.37, respectively, p < .001). The correlation coefficients of both scores were higher in primigravidas (n = 51) compared to multigravidas, but the difference was statistically nonsignificant. Using multiple linear regression, both scores were significantly related to serum cotinine levels. For each unit increase in the FTCD and HSI, the serum cotinine level increased by 21.4 ng/mL (95% confidence interval 10.1-32.7, p <0.001) and 37 ng/mL (95% confidence interval 18.6-55.4, p < 0.001), respectively. CONCLUSIONS: Both the FTCD and HSI can be used to assess cigarette dependence in the second and third trimester of pregnancy. IMPLICATIONS: There is lack of data on the validity of the FTCD and the HSI as markers of cigarette dependence during the second and third trimester of pregnancy. Our study suggests that both the FTCD and HSI perform well in assessing cigarette dependence in the second and third trimester of pregnancy and can be used to plan smoking cessation programs.

PGF2α modulates the output of chemokines and pro-inflammatory cytokines in myometrial cells from term pregnant women through divergent signaling pathways.

Prostaglandin F2α (PGF2α) plays a critical role in the initiation and process of parturition. Since human labor has been described as an inflammatory event, we investigated the role of PGF2α in the inflammatory process using cultured human uterine smooth muscle cells (HUSMCs) isolated from term pregnant women as a model. Using a multiplex assay, HUSMCs treated with PGF2α changed their output of a number of cytokines and chemokines, with a distinct response pattern that differed between HUSMCs isolated from the upper and lower segment region of the uterus. Confirmatory enzyme-linked immunosorbent assays (ELISAs) showed that PGF2α stimulated increased output of interleukin (IL) 1ß, IL6, IL8 (CXCL8) and monocyte chemotactic protein-1 (MCP1, also known as chemokine (c-c motif) ligand 2, CCL2) by HUSMCs isolated from both upper and lower uterine segments. In contrast, PGF2α inhibited tumor necrosis factor α (TNFα) release by HUMSCs from the lower uterine segment while the output of TNFα was undetectable in the upper segment. Small interfering (si) RNA mediated knockdown of the PGF2α receptor prevented the changes in cytokine and chemokine output by the HUSMCs. Since the PGF2α receptor (PTGFR) couples via the Gq protein and subsequently activates the phospholipase C (PLC) and protein kinase C (PKC) signaling pathways, we examined the role of these pathways in PGF2α modulation of the cytokines. Inhibition of PLC and PKC reversed the effects of PGF2α. PGF2α activated multiple signaling pathways including extracellular signal-regulated kinases (ERK) 1/2, phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), P38, calcineurin/nuclear factor of activated T-cells (NFAT) and NF-κB signaling. Inhibition of ERK reversed PGF2α-induced IL1ß, IL6 and CCL2 output, while inhibition of PI3K blocked the effect of PGF2α on IL6, CXCL8 and CCL2 output and inhibition of NF-κB reversed PGF2α-induced IL1ß and CCL2 output. NFAT was involved in PGF2α modulation of CCL2 and TNFα output. In conclusion, our results support a role of PGF2α in creating an inflammatory environment during the late stage of human pregnancy.

Nuclear factor of activated T-cell isoform expression and regulation in human myometrium.

BACKGROUND: During pregnancy, myometrial gene and protein expression is tightly regulated to accommodate fetal growth, promote quiescence and ultimately prepare for the onset of labour. It is proposed that changes in calcium signalling, may contribute to regulating gene expression and that nuclear factor of activated T-cell (NFAT) transcription factors (isoforms c1-c4) may be involved. Currently, there is little information regarding NFAT expression and regulation in myometrium. METHODS: This study examined NFAT isoform mRNA expression in human myometrial tissue and cells from pregnant women using quantitative PCR. The effects of the Ca(2+) ionophore A23187 and in vitro stretch (25 % elongation, static strain; Flexercell FX-4000 Tension System) on NFAT expression were determined in cultured human myometrial cells. RESULTS: Human myometrial tissue and cultured cells expressed NFATc1-c4 mRNA. NFATc2 gene expression in cultured cells was increased in response to 6 h stretch (11.5 fold, P < 0.001, n = 6) and calcium ionophore (A23187, 5 µM) treatment (20.6 fold, P < 0.001, n = 6). This response to stretch was significantly reduced (90 %, P < 0.001, n = 10) in the presence of an intracellular calcium chelator, BAPTA-AM (20 µM). CONCLUSIONS: These data suggest that NFATc2 expression is regulated by intracellular calcium and in vitro stretch, and that the stretch response in human myometrial cells is dependent upon intracellular calcium signalling pathways. Our findings indicate a potentially unique role for NFATc2 in mediating stretch-induced gene expression per se and warrant further exploration in relation to the mechanisms promoting uterine smooth muscle growth in early pregnancy and/or labour.

Pre-pregnancy Body Mass Index (BMI) and delivery outcomes in a Canadian population.

BACKGROUND: Worldwide there has been a dramatic increase in the prevalence of overweight and obesity in women of childbearing age. Growing evidence suggests that maternal overweight and obesity is associated with poor maternal and perinatal outcomes. This study evaluated the impact of maternal pre-pregnancy overweight and obesity on pregnancy, labour and delivery outcomes in a cohort of women with term, singleton pregnancies cared for by family physicians in community based practices. METHODS: This study is a secondary analysis of the All Our Babies Cohort, a prospective, community-based pregnancy cohort in Calgary, Alberta. Maternal self-reported data on height and pre-pregnancy weight from term, singleton, cephalic pregnancies (n = 1996) were linked to clinical data on pregnancy and birth events retrieved from electronic health records. Descriptive and bivariate regression analysis were used to compare pregnancy and birth outcomes between women categorized as normal weight, overweight and obese based on the pre-pregnancy BMI. Multinomial regression analysis stratified by type of labour onset examined the association between pre-pregnancy BMI and mode of delivery controlling for maternal age, pre-existent health conditions, parity, fertility treatments, history of C-section and pregnancy complications. RESULTS: The cohort consisted of 65.8% normal weight, 23.6% overweight and 10.6% obese women. Women with increased pre-pregnancy BMI were more likely to develop pregnancy complications such as preeclampsia (OR 3.5, CI 2.0-4.6 for overweight; OR 5.3, CI 3.3-8.5 for obese) and gestational diabetes (OR 3.0, CI 1.8-5.0 for overweight; OR 6.5, CI 3.7-11.2 for obese) than normal weight women. Spontaneous onset of labour was recorded in 71.2% of women with normal pre-pregnancy BMI, whereas 39.3% of overweight and 49% of obese women had their labour induced. For women with spontaneous labour, pre-pregnancy BMI was not a significant risk factor for mode of delivery, controlling for covariates. Among women with induced labor, obesity was a significant risk factor for delivery by C-section (adjusted OR 2.2; CI 1.2-4.1). CONCLUSIONS: Even among women with term, singleton pregnancies obtaining prenatal care in community-based settings, obese women who undergo labour induction are at increased risk of obstetrical interventions at delivery. These findings highlight the importance of tailored maternal care in pregnancy and at delivery of pregnant women with increased BMI in order to improve the outcomes and wellbeing of these women and their children.

Maternal Acylcarnitine Disruption as a Potential Predictor of Preterm Birth in Primigravida: A Preliminary Investigation.

Preterm birth, defined as any birth before 37 weeks of completed gestation, poses adverse health risks to both mothers and infants. Despite preterm birth being associated with several risk factors, its relationship to maternal metabolism remains unclear, especially in first-time mothers. Aims of the present study were to identify maternal metabolic disruptions associated with preterm birth and to evaluate their predictive potentials. Blood was collected, and the serum harvested from the mothers of 24 preterm and 42 term births at 28-32 weeks gestation (onset of the 3rd trimester). Serum samples were assayed by untargeted metabolomic analyses via liquid chromatography/mass spectrometry (QTOF-LC/MS). Metabolites were annotated by inputting the observed mass-to-charge ratio into the Human Metabolome Database (HMDB). Analysis of 181 identified metabolites by PLS-DA modeling using SIMCA (v17) showed reasonable separation between the two groups (CV-ANOVA, p = 0.02). Further statistical analysis revealed lower serum levels of various acyl carnitines and amino acid metabolites in preterm mothers. Butenylcarnitine (C4:1), a short-chain acylcarnitine, was found to be the most predictive of preterm birth (AUROC = 0.73, [CI] 0.60-0.86). These observations, in conjuncture with past literature, reveal disruptions in fatty acid oxidation and energy metabolism in preterm primigravida. While these findings require validation, they reflect altered metabolic pathways that may be predictive of preterm delivery in primigravida.

Development and validation of primary human myometrial cell culture models to study pregnancy and labour.

BACKGROUND: The development of the in vitro cell culture model has greatly facilitated the ability to study gene expression and regulation within human tissues. Within the human uterus, the upper (fundal) segment and the lower segment may provide distinct functions throughout pregnancy and during labour. We have established primary cultured human myometrial cells, isolated from both upper and lower segment regions of the pregnant human uterus, and validated them for the purpose of studying human pregnancy and labour. The specific objectives of this study were to monitor the viability and characterize the expression profile using selected cellular, contractile and pregnancy associated markers in the primary cultured human myometrial cells. Labour has been described as an inflammatory process; therefore, the ability of these cells to respond to an inflammatory stimulus was also investigated. METHODS: Myometrial cells isolated from paired upper segment (US) and lower segment (LS) biopsies, obtained from women undergoing Caesarean section deliveries at term prior to the onset of labour, were used to identify expression of; α smooth muscle actin, calponin, caldesmon, connexin 43, cyclo-oxygenase-2 (COX-2), oxytocin receptor, tropomyosin and vimentin, by RT-PCR and/or immunocytochemistry. Interleukin (IL)-1ß was used to treat cells, subsequently expression of COX-2 mRNA and release of interleukin-8 (CXCL8), were measured. ANOVA followed by Bonferroni's multiple comparisons test was performed. RESULTS: We demonstrate that US and LS human myometrial cells stably express all markers examined to at least passage ten (p10). Connexin 43, COX-2 and vimentin mRNA expression were significantly higher in LS cells compared to US cells. Both cell populations respond to IL-1ß, demonstrated by a robust release of CXCL8 and increased expression of COX-2 mRNA from passage one (p1) through to p10. CONCLUSIONS: Isolated primary myometrial cells maintain expression of smooth muscle and pregnancy-associated markers and retain their ability to respond to an inflammatory stimulus. These distinct myometrial cell models will provide a useful tool to investigate mechanisms underlying the process of human labour and the concept of functional regionalization of the pregnant uterus.

Potential molecular and cellular mechanisms for adverse placental outcomes in pregnancies complicated by SARS-CoV-2 infection-A scoping review.

BACKGROUND: Emerging evidence suggests that SARS-CoV-2 infection during pregnancy can result in placental damage and poor placental outcomes. However, the mechanisms by which SARS-CoV-2 infection leads to placental damage are not well understood. With a rapid expansion of literature on this topic, it is critical to assess the quality and synthesize the current state of literature. The objective of this scoping review is to highlight underlying mechanisms of SARS-CoV-2 mediated placental pathology in pregnant individuals and identify literature gaps regarding molecular and cellular mechanisms of poor placental outcomes. METHODS: The review was conducted and reported following the recommendations of the PRISMA extension for Scoping Reviews. The study protocol was registered with Open Science Framework (https://osf.io/p563s/). Five databases (MEDLINE, EMBASE, Scopus, CINAHL, PubMed) were searched for studies published between September 2019 until April 2022. Studies assessing placental outcomes with respect to SARS-CoV-2 infection in pregnancy were eligible for inclusion. Outcomes of interest included histopathology, and molecular or cellular analysis. All records were uploaded into Covidence and extracted using the Joanna Briggs Institute method. Studies were assessed for risk of bias using the Newcastle Ottawa scale and a narrative synthesis of results was generated. RESULTS: Twenty-seven studies reporting on molecular and/or cellular mechanisms of SARS-CoV-2 mediated placental outcomes were included in this review. SARS-CoV-2 infection was associated with perturbations in the ACE2 pathway, inflammatory mediators and immune cell populations and mitochondrial function in placentas. CONCLUSIONS: Our findings suggest that changes in the ACE2 pathway, mitochondrial dysfunction, and/or inflammatory processes may lead to placental damage observed in SARS-CoV-2 infection during pregnancy. More research is needed to understand the role of these pathways further, in addition to data collection related to trimester, severity, and strain.

Prostaglandin E2 represses interleukin 1 beta-induced inflammatory mediator output from pregnant human myometrial cells through the EP2 and EP4 receptors.

Inflammatory mediators, including prostaglandins, cytokines, and chemokines, are strongly implicated in the mechanism of human labor, though their precise roles remain unknown. Here we demonstrate that interleukin 1 beta (IL-1beta) significantly increased the expression and release of interleukin-8 (CXCL8), monocyte chemotactic protein-1 (CCL2), and granulocyte macrophage colony-stimulating factor (CSF2) by primary human myometrial cells. However, this effect was repressed by prostaglandin E(2) (PGE(2)). As PGE(2) can activate four distinct PGE(2) receptors (EP(1), EP(2), EP(3), and EP(4)) to elicit various responses, we sought to define the EP receptor(s) responsible for this repression. Using selective EP receptor agonists and a selective EP(4) antagonist, we show that PGE(2) mediates the repression of IL-1beta-induced release of CXCL8, CCL2, and CSF2 via activation of the EP(2) and EP(4) receptors. The use of siRNA gene-specific knockdown further confirmed a role for both receptors. Real-time RT-PCR demonstrated that EP(2) was the most highly expressed of all four EP receptors at the mRNA level in human myometrial cells, and immunocytochemistry showed that EP(2) protein is abundantly present throughout the cells. Interestingly, PGE(2) does not appear to reduce mRNA expression of CXCL8, CCL2, and CSF2. Our results demonstrate that PGE(2) can elicit anti-inflammatory responses via activation of the EP(2) and EP(4) receptors in lower segment term pregnant human myometrial cells. Further elucidation of the EP receptor-mediated signaling pathways in the pregnant human uterus may be beneficial for optimizing the maintenance of pregnancy, induction of labor or indeed treatment of preterm labor.

Is there a maternal blood biomarker that can predict spontaneous preterm birth prior to labour onset? A systematic review.

INTRODUCTION: The ability to predict spontaneous preterm birth (sPTB) prior to labour onset is a challenge, and it is currently unclear which biomarker(s), may be potentially predictive of sPTB, and whether their predictive power has any utility. A systematic review was conducted to identify maternal blood biomarkers of sPTB. METHODS: This study was conducted according to PRISMA protocol for systematic reviews. Four databases (MEDLINE, EMBASE, CINAHL, Scopus) were searched up to September 2021 using search terms: "preterm labor", "biomarker" and "blood OR serum OR plasma". Studies assessing blood biomarkers prior to labour onset against the outcome sPTB were eligible for inclusion. Risk of bias was assessed based on the Newcastle Ottawa scale. Increased odds of sPTB associated with maternal blood biomarkers, as reported by odds ratios (OR), or predictive scores were synthesized. This review was not prospectively registered. RESULTS: Seventy-seven primary research articles met the inclusion criteria, reporting 278 unique markers significantly associated with and/or predictive of sPTB in at least one study. The most frequently investigated biomarkers were those measured during maternal serum screen tests for aneuploidy, or inflammatory cytokines, though no single biomarker was clearly predictive of sPTB based on the synthesized evidence. Immune and signaling pathways were enriched within the set of biomarkers and both at the level of protein and gene expression. CONCLUSION: There is currently no known predictive biomarker for sPTB. Inflammatory and immune biomarkers show promise, but positive reporting bias limits the utility of results. The biomarkers identified may be more predictive in multi-marker models instead of as single predictors. Omics-style studies provide promising avenues for the identification of novel (and multiple) biomarkers. This will require larger studies with adequate power, with consideration of gestational age and the heterogeneity of sPTB to identify a set of biomarkers predictive of sPTB.

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.

Maternal Metabolites Indicative of Mental Health Status during Pregnancy.

Approximately 25% of individuals report poor mental health during their pregnancy or postpartum period, which may impact fetal neurodevelopment, birth outcomes, and maternal behaviors. In the present study, maternal serum samples were collected from pregnancies at 28-32 weeks gestation from the All Our Families (Alberta, Canada) cohort and assessed using nuclear magnetic resonance spectroscopy (1H-NMR) and inductively coupled plasma-mass spectrometry (ICP-MS). Individuals with poor mental health at 34-36 weeks gestation were age-matched with mentally healthy pregnant controls. Metabolites were examined against validated self-reported mental health questionnaires for associations with depressive symptoms (Edinburgh Perinatal Depression Scale) and anxiety symptoms (Spielberger State-Trait Anxiety Inventory). 1H-NMR metabolites were identified for depression (alanine, leucine, valine, methionine, phenylalanine, glucose, lactate, 3-hydroxybutyrate, and pyruvate) and anxiety (3-hydroxybutyrate). For ICP-MS, antimony and zinc were significant for depression and anxiety, respectively. Upon false discovery rate (FDR) correction at 10%, five 1H-NMR metabolites (alanine, leucine, lactate, glucose, and phenylalanine) for depression remained significantly increased. Although results warrant further validation, the identified metabolites may serve as a predictive tool for assessing mental health during pregnancy as earlier identification has the potential to aid intervention and management of poor mental health symptomology, thus avoiding harmful consequences to both mother and offspring.

Prostaglandins in biofluids in pregnancy and labour: A systematic review.

Prostaglandins are thought to be important mediators in the initiation of human labour, however the evidence supporting this is not entirely clear. Determining how, and which, prostaglandins change during pregnancy and labour may provide insight into mechanisms governing labour initiation and the potential to predict timing of labour onset. The current study systematically searched the existing scientific literature to determine how biofluid levels of prostaglandins change throughout pregnancy before and during labour, and whether prostaglandins and/or their metabolites may be useful for prediction of labour. The databases EMBASE and MEDLINE were searched for English-language articles on prostaglandins measured in plasma, serum, amniotic fluid, or urine during pregnancy and/or spontaneous labour. Studies were assessed for quality and risk of bias and a qualitative summary of included studies was generated. Our review identified 83 studies published between 1968-2021 that met the inclusion criteria. As measured in amniotic fluid, levels of PGE2, along with PGF2α and its metabolite 13,14-dihydro-15-keto-PGF2α were reported higher in labour compared to non-labour. In blood, only 13,14-dihydro-15-keto-PGF2α was reported higher in labour. Additionally, PGF2α, PGF1α, and PGE2 were reported to increase in amniotic fluid as pregnancy progressed, though this pattern was not consistent in plasma. Overall, the evidence supporting changes in prostaglandin levels in these biofluids remains unclear. An important limitation is the lack of data on the complexity of the prostaglandin pathway outside of the PGE and PGF families. Future studies using new methodologies capable of co-assessing multiple prostaglandins and metabolites, in large, well-defined populations, will help provide more insight as to the identification of exactly which prostaglandins and/or metabolites consistently change with labour. Revisiting and revising our understanding of the prostaglandins may provide better targets for clinical monitoring of pregnancies. This study was supported by the Canadian Institutes of Health Research.

Better Me Within Randomized Trial: Faith-Based Diabetes Prevention Program for Weight Loss in African American Women.

PURPOSE: Previous DPP translations in African American women have been suboptimal. This trial evaluated a community-based participatory research developed faith-based diabetes prevention program (DPP) to improve weight loss in African American women. DESIGN: This cluster randomized trial allocated churches to faith-based (FDPP) or standard (SDPP) DPP interventions. Setting. African American churches. Subjects. Eleven churches with 221 African American women (aged 48.8 ± 11.2 years, BMI = 36.7 ± 8.4) received the FDPP (n = 6) or SDPP (n = 5) intervention. INTERVENTION: FDPP incorporated 5 faith-based components, including pastor involvement, into the standard DPP curriculum. The SDPP used the standard DPP curriculum. Lay health leaders facilitated interventions at church sites. MEASURES: Weight and biometrics were collected by blinded staff at baseline, 4- and 10-months. ANALYSIS: A multilevel hierarchical regression model compared the FDPP and SDPP groups on outcomes. RESULTS: FDPP and SDPP churches significantly lost weight at 10-months (overall -2.6%, p < .01). Women in FDPP churches who attended at least 15 sessions lost an additional 6.1 pounds at 4-months compared to SDPP corresponding to a 5.8% reduction at 10-months (p < .05). Both groups had significant improvements in health behaviors and biometrics. CONCLUSIONS: Faith-based and standard DPP interventions led by lay health leaders successfully improved weight, health behaviors, and chronic disease risk. However, the faith-based DPP when fully implemented met the CDC's recommendation for weight loss for diabetes prevention in African American women.

Labour is associated with decreased expression of the PGF2alpha receptor (PTGFR) and a novel PTGFR splice variant in human myometrium but not decidua.

The prostaglandin F(2α) receptor (PTGFR) is believed to play a role in the process of parturition. The main support for this comes from animal studies; however, in humans, the evidence is less clear. The gene coding for PTGFR may be subject to alternative splicing to generate alternate variants with different signalling pathways. We have determined regional (upper versus lower segment) and labour-associated expression of PTGFR mRNA and a recently identified splice variant of PTGFR in human myometrium and decidua. We also examined the effect of the inflammatory cytokine interleukin-1ß (IL-1ß) on PTGFR mRNA expression in a model of cultured human myometrial smooth muscle cells. We identified a PTGFR transcript variant 2 (PTGFR-v2) generated by alternate splicing in human myometrium and decidua. The PTGFR-v2 contains an additional 71 base pair exon, which results in a truncated protein at 297 amino acids compared with the PTGFR transcript variant 1 (PTGFR-v1) at 359 amino acids. In contrast to our hypothesis, we demonstrate that PTGFR-v1 and PTGFR-v2 mRNA expression is not significantly higher in upper segment compared with lower segment paired samples. We also show a labour-associated decrease in PTGFR-v1 and PTGFR-v2 mRNA expression in lower segment myometrial samples. IL-1ß-stimulated mRNA expression of both PTGFR variants in a distinct time-dependent manner in myometrial cell cultures. We suggest that the role of the PTGFR in the human uterus requires further validation prior to pursuing it as a target for the treatment of preterm labour. In addition, the presence of distinct variants suggests further levels of gene regulation within the pregnant uterus.

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.

Prediction and Understanding of Resilience in Albertan Families: Longitudinal Study of Disaster Responses (PURLS) - Protocol.

Exposure to a natural disaster in childhood can have serious, long-lasting consequences, impacting physical and mental health, development, and learning. Although many children experience negative effects after a disaster, the majority do not, and what differentiates these groups is not well understood. Some of the factors that influence disaster-related outcomes in the midst of adversity include parents' mental health, the home environment, and socioeconomic status. Furthermore, genetics has also a role to play in how children respond to stressors. We had the opportunity to conduct a natural experiment of disaster recovery following the Alberta 2013 Flood. This paper presents the detailed protocol on prediction of resilience in Albertan families, and validation with cortisol data. In addition, data collection procedures, developing resiliency screening tools, candidate gene identification, genotyping, DNA methylation, and genomic analyses are described to achieve the research objectives. This study produced new knowledge by using pre- and post-disaster information on children's health and development, including children's genetics and responses to stress. This information has been identified as important to governments and other organizations invested in early child development. Our comprehensive research plan generates evidence that can be mobilized population-based approaches to improve child and family resiliency.

Relationship Between Psychosocial Distress in Pregnancy and Two Genes Associated With Human Social Interaction: A Pilot Study.

BACKGROUND: Prenatal depression, anxiety, and stress (prenatal psychosocial distress) are common, and several environmental risk factors have been implicated in their development. Variation in genes, specifically single nucleotide polymorphisms (SNPs), may explain why some women develop maternal mental health concerns while others do not. PURPOSE: The purpose of this pilot study was to determine the feasibility of completing SNP analyses using whole blood collected prenatally between 2008 and 2011. We examined the association between SNPs in two genes (FKBP5 and OXTR) among women with low and high prenatal psychosocial distress. METHODS: A subset (N = 50, 25 high and 25 low prenatal psychosocial distress) of participants was selected from the All Our Families pregnancy cohort. DNA was extracted from maternal blood and used for selected SNP analysis. Participants' scores on the Edinburgh Prenatal Depression Scale, Spielberger State Anxiety Inventory, and Perceived Stress Scale were used along with demographic variables. RESULTS: Genotype distribution was not significantly different between the low and high prenatal psychosocial distress groups for either the FKBP5 or the OXTR SNP (p = .699 and p = .125). After controlling for maternal age and income, women with the GG genotype at the OXTR SNP (rs237885) were statistically less likely to be in the high prenatal psychosocial distress group (p = .037). CONCLUSION: OXTR SNP rs237885, maternal age, and lower income were associated with prenatal psychosocial distress. This pilot study demonstrated the feasibility of continuing to a larger study that incorporates additional environmental and genetic information.

Patterns of change in anxiety and depression during pregnancy predict preterm birth.

BACKGROUND: To determine whether changes in anxiety and depression during pregnancy influence the risk of having a preterm birth (PTB), and whether chronic stress modifies this relationship. METHODS: The data source for the current study is the All Our Babies prospective cohort (AOB). Anxiety and depression were measured at 17-24 weeks and again at 32-36 weeks' gestation using the Spielberg State Anxiety Scale and the Edinburgh Postnatal Depression Scale, respectively. Chronic stress was assessed at 17-24 weeks' gestation as a potential covariate, and was measured using the Perceived Stress Scale. Multivariable logistic regression modeling was used to assess each relationship RESULTS: Women who experienced an increase in anxiety scores, (time point 32-36 weeks, compared to the earlier time point 17-24 weeks), had 2.70 times higher odds of preterm delivery, compared to those with a reduction in anxiety scores (95% CI 1.28, 5.69). Consistent low or high depression scores did not significantly influence the odds of PTB compared to a decrease in depression scores. A co-occurring increase in anxiety and depression scores was not found to increase the risk of PTB, and chronic stress did not modify any of these relationships. LIMITATIONS: This study was limited by a relatively small sample of women who delivered preterm, and therefore it was not possible to conduct additional analyses. Further, the analyses were limited to mostly late preterm infants (32-36 weeks' gestation). CONCLUSIONS: These findings should be validated with additional cohorts and a larger sample size. Ultimately, primary prevention could address anxiety during pregnancy.