'It's not me, it's them' - a report describing the weight-related attitudes towards obesity in pregnancy among maternal healthcare providers.

BACKGROUND: Occurrences of weight stigma have been documented in prenatal clinical settings from the perspective of pregnant patients, however little is known from the viewpoint of healthcare providers themselves. Reported experiences of weight stigma caused by maternal healthcare providers may be due to negative attitudes towards obesity in pregnancy and a lack of obesity specific education. The objective of this study was to assess weight-related attitudes and assumptions towards obesity in pregnancy among maternal healthcare providers in order to inform future interventions to mitigate weight stigma in prenatal clinical settings. METHODS: A cross-sectional survey was administered online for maternal healthcare providers in Canada that assessed weight-related attitudes and assumptions towards lifestyle behaviours in pregnancy for patients who have obesity. Participants indicated their level of agreement on a 5-point likert scale, and mean scores were calculated with higher scores indicating poorer attitudes. Participants reported whether they had observed weight stigma occur in clinical settings. Finally, participants were asked whether or not they had received obesity-specific training, and attitude scores were compared between the two groups. RESULTS: Seventy-two maternal healthcare providers (midwives, OBGYNs, residents, perinatal nurses, and family physicians) completed the survey, and 79.2% indicated that they had observed pregnant patients with obesity experience weight stigma in a clinical setting. Those who had obesity training perceived that their peers had poorer attitudes (3.7 ± 0.9) than those without training (3.1 ± 0.7; t(70) = 2.23, p = 0.029, Cohen's d = 0.86). CONCLUSIONS: Weight stigma occurs in prenatal clinical environments, and this was confirmed by maternal healthcare providers themselves. These findings support advocacy efforts to integrate weight stigma related content and mitigation strategies in medical education for health professionals, including maternal healthcare providers. Future work should include prospective examination of weight related attitudes among maternal healthcare providers and implications of obesity specific education, including strategies on mitigating weight stigma in the delivery of prenatal care.

Diagnostic accuracy of Kleihauer-Betke (Kb) testing to predict fetal outcomes associated with fetomaternal hemorrhage: a retrospective cohort study.

OBJECTIVE: To evaluate the diagnostic and screening utility of Kleihauer-Betke (KB) testing as a triage tool in predicting adverse fetal outcomes associated with fetomaternal hemorrhage (FMH). STUDY DESIGN: Single center retrospective cohort study evaluated a primary composite outcome of fetal complications associated with FMH between KB-negative and KB-positive test groups. Screening tests for sensitivity, specificity, positive predictive value and negative predictive value were determined. RESULTS: 641 women (97%) had KB-negative and 22 (3%) had KB-positive tests. The primary composite outcome between KB-negative and KB-positive pregnancies was similar (30% vs. 36%, p = 0.54). Screening exhibited high specificity (97%), however, test sensitivity was poor (4%) with only moderate positive and negative predictive values (36.4 and 69.7%). CONCLUSION: Fetal outcomes associated with FMH were not significantly different between KB-positive and KB-negative test cohorts; KB testing offers no diagnostic precision in the emergency triage evaluation of women with suspected FMH.

Increased IGFBP-1 phosphorylation in response to leucine deprivation is mediated by CK2 and PKC.

Insulin-like growth factor binding protein-1 (IGFBP-1), secreted by fetal liver, is a key regulator of IGF-I bioavailability and fetal growth. IGFBP-1 phosphorylation decreases IGF-I bioavailability and diminishes its growth-promoting effects. Growth-restricted fetuses have decreased levels of circulating essential amino acids. We recently showed that IGFBP-1 hyperphosphorylation (pSer101/119/169) in response to leucine deprivation is regulated via activation of the amino acid response (AAR) in HepG2 cells. Here we investigated nutrient-sensitive protein kinases CK2/PKC/PKA in mediating IGFBP-1 phosphorylation in leucine deprivation. We demonstrated that leucine deprivation stimulated CK2 activity (enzymatic assay) and induced IGFBP-1 phosphorylation (immunoblotting/MRM-MS). Inhibition (pharmacological/siRNA) of CK2/PKC, but not PKA, prevented IGFBP-1 hyperphosphorylation in leucine deprivation. PKC inhibition also prevented leucine deprivation-stimulated CK2 activity. Functionally, leucine deprivation decreased IGF-I-induced-IGF-1R autophosphorylation when CK2/PKC were not inhibited. Our data strongly support that PKC promotes leucine deprivation-induced IGFBP-1 hyperphosphorylation via CK2 activation, mechanistically linking decreased amino acid availability and reduced fetal growth.

IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by the AAR pathway.

Insulin-like growth factor-1 (IGF-I) is the key regulator of fetal growth. IGF-I bioavailability is markedly diminished by IGF binding protein-1 (IGFBP-1) phosphorylation. Leucine deprivation strongly induces IGFBP-1 hyperphosphorylation, and plays an important role in fetal growth restriction (FGR). FGR is characterized by decreased amino acid availability, which activates the amino acid response (AAR) and inhibits the mechanistic target of rapamycin (mTOR) pathway. We investigated the role of AAR and mTOR in mediating IGFBP-1 secretion and phosphorylation in HepG2 cells in leucine deprivation. mTOR inhibition (rapamycin or raptor + rictor siRNA), or activation (DEPTOR siRNA) demonstrated a role of mTOR in leucine deprivation-induced IGFBP-1 secretion but not phosphorylation. When the AAR was blocked (U0126, or ERK/GCN2 siRNA), both IGFBP-1 secretion and hyperphosphorylation (pSer101/pSer119/pSer169) due to leucine deprivation were prevented. CK2 inhibition by TBB also attenuated IGFBP-1 phosphorylation in leucine deprivation. These results suggest that the AAR and mTOR independently regulate IGFBP-1 secretion and phosphorylation in response to decreased amino acid availability.

Western Database of Lipid Variants (WDLV): a catalogue of genetic variants in monogenic dyslipidemias.

BACKGROUND: Next-generation sequencing (NGS) is nearing routine clinical application, especially for diagnosis of rare monogenic cardiovascular diseases. But NGS uncovers so much variation in an individual genome that filtering steps are required to streamline data management. The first step is to determine whether a potential disease-causing variant has been observed previously in affected patients. METHODS: To facilitate this step for lipid disorders, we developed the Western Database of Lipid Variants (WDLV) of 2776 variants in 24 genes that cause monogenic dyslipoproteinemias, including conditions characterized primarily by either high or low low-density lipoprotein cholesterol, high or low high-density lipoprotein cholesterol, high triglyceride, and some miscellaneous disorders. We incorporated quality-control steps to maximize the likelihood that a listed mutation was disease causing. RESULTS: The details of each mutation found in a dyslipidemia, together with a mutation map of the causative genes, are shown in graphical display items. CONCLUSIONS: WDLV will help clinicians and researchers determine the potential pathogenicity of mutations discovered by DNA sequencing of patients or research participants with lipid disorders.