The implication of serum HLA-G in angiogenesis of multiple myeloma.

BACKGROUND: Despite the advances of therapies, multiple myeloma (MM) remains an incurable hematological cancer that most patients experience relapse. Tumor angiogenesis is strongly correlated with cancer relapse. Human leukocyte antigen G (HLA-G) has been known as a molecule to suppress angiogenesis. We aimed to investigate whether soluble HLA-G (sHLA-G) was involved in the relapse of MM. METHODS: We first investigated the dynamics of serum sHLA-G, vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) in 57 successfully treated MM patients undergoing remission and relapse. The interactions among these angiogenesis-related targets (sHLA-G, VEGF and IL-6) were examined in vitro. Their expression at different oxygen concentrations was investigated using a xenograft animal model by intra-bone marrow and skin grafts with myeloma cells. RESULTS: We found that HLA-G protein degradation augmented angiogenesis. Soluble HLA-G directly inhibited vasculature formation in vitro. Mechanistically, HLA-G expression was regulated by hypoxia-inducible factor-1α (HIF-1α) in MM cells under hypoxia. We thus developed two mouse models of myeloma xenografts in intra-bone marrow (BM) and underneath the skin, and found a strong correlation between HLA-G and HIF-1α expressions in hypoxic BM, but not in oxygenated tissues. Yet when stimulated with IL-6, both HLA-G and HIF-1α could be targeted to ubiquitin-mediated degradation via PARKIN. CONCLUSION: These results highlight the importance of sHLA-G in angiogenesis at different phases of multiple myeloma. The experimental evidence that sHLA-G as an angiogenesis suppressor in MM may be useful for future development of novel therapies to prevent relapse.

Analysis of mutation profiles in extranodal NK/T-cell lymphoma: clinical and prognostic correlations.

The molecular pathogenesis of extranodal NK/T-cell lymphoma (NKTCL) remains obscured despite the next-generation sequencing (NGS) studies explored on ever larger cohorts in the last decade. We addressed the highly variable mutation frequencies reported among previous studies with comprehensive amplicon coverage and enhanced sequencing depth to achieve higher genomic resolution for novel genetic discovery and comparative mutational profiling of the oncogenesis of NKTCL. Targeted exome sequencing was conducted to interrogate 415 cancer-related genes in a cohort of 36 patients with NKTCL, and a total of 548 single nucleotide variants (SNVs) and 600 Copy number variances (CNVs) were identified. Recurrent amplification of the MCL1 (67%) and PIM1 (56%) genes was detected in a dominant majority of patients in our cohort. Functional mapping of genetic aberrations revealed that an enrichment of mutations in the JAK-STAT signaling pathway, including the cytokine receptor LIFR (copy number loss) upstream of JAK3, STAT3 (activating SNVs), and downstream effectors of MYC, PIM1 and MCL1 (copy number gains). RNA in situ hybridization showed the significant consistence of MCL1 RNA level and copy number of MCL1 gene. We further correlated molecular and clinical parameters with overall survival (OS) of these patients. When correlations were analyzed by univariate followed by multivariate modelling, only copy number loss of LIFR gene and stage (III-IV) were independent prognostic factors of reduced OS. Our findings identified that novel loss of LIFR gene significantly correlated with the adverse clinical outcome of NKTCL patients and provided therapeutic opportunities for this disease through manipulating LIFR.

Effectiveness of fentanyl buccal soluble film in cancer patients with inadequate breakthrough pain control.

BACKGROUND: Clinical evidence for the rapidity and effectiveness of fentanyl buccal soluble film (FBSF) in reducing pain intensity of breakthrough cancer pain (BTcP) remains inadequate. This study aimed to evaluate the efficacy of FBSF proportional to the around-the-clock (ATC) opioid regimens in rapidly relieving the intensity of BTcP episodes by determining the percentage of patients requiring further dose titration. METHODS: The study procedure included a dose-finding period followed by a 14-day observation period. Pain intensity was recorded with a Numeric Rating Scale (NRS) at onset and 5, 10, 15, and 30 min after FBSF self-administration. Meaningful pain relief was defined as the final NRS score ≤ 3. Satisfaction survey was conducted for each patient after treatment using the Global Satisfaction Scale. RESULTS: A total of 63 BTcP episodes occurred in 30 cancer patients. Only one patient required rescue medication at first BTcP episode and then achieved meaningful pain relief after titrating FBSF by 200 µg. Most BTcP episodes relieved within 10 min. Of 63 BTcP episodes, 30 (47.6%), 46 (73.0%), and 53 (84.1%) relieved within 5, 10, and 15 min after FBSF administration. Only grade 1/2 adverse events were reported, including somnolence, malaise, and dizziness. Of the 63 BTcP episodes, 82.6% were rated as excellent/good satisfaction with FBSF. CONCLUSION: FBSF can be administrated "on demand" by cancer patients at the onset of BTcP, providing rapid analgesia by achieving meaningful pain relief within 10 min. TRIAL REGISTRATION: This study was retrospectively registered 24 December, 2021 at Clinicaltrial.gov (NCT05209906): https://clinicaltrials.gov/study/NCT05209906 .

Investigating Potential Cardiovascular Toxicity of Two Anti-Leukemia Drugs of Asciminib and Ponatinib in Zebrafish Embryos.

BCR-ABL, a fusion protein kinase, is a druggable target exclusively expressed in patients with chronic myeloid leukemia (CML). Several anti-leukemia medicines targeting this protein have been developed in recent years. However, therapeutic options are limited for CML patients bearing multiple BCR-ABL1 mutations. Ponatinib (PON), a potent tyrosinase inhibitor, was one of the approved drugs for managing BCR-ABL1 T315I mutant disease. However, treatment of patients with PON reported severe side effects related to cardiovascular events. Asciminib (ASC) was the first allosteric inhibitor approved to target the myristoyl pocket of BCR-ABL protein to inhibit protein activity. The different mechanism of inhibition opens the possibility of co-exposure with both medicines. Reports on cardiovascular side effects due to the combination use of PON + ASC in pre-clinical and clinical studies are minimal. Thus, this study aimed to observe the potential cardiovascular-related side effect after co-exposure to ASC and PON using zebrafish as an animal model. In this study, zebrafish were acutely exposed to both compounds. The cardiovascular physiology parameters and gene expression related to cardiovascular development were evaluated. We demonstrate that combining ASC with PON at no observed effect concentration (NOEC) did not cause any significant change in the cardiac performance parameter in zebrafish. However, a significant increase in nkx2.5 expression level and a substantial decrease in blood flow velocity were recorded, suggesting that combining these compounds at NOEC can cause mild cardiovascular-related side effects.

Nicotine exhausts CD8+ T cells against tumor cells through increasing miR-629-5p to repress IL2RB-mediated granzyme B expression.

The mechanism exhausting CD8+ T cells is not completely clear against tumors. Literature has demonstrated that cigarette smoking disables the immunological activity, so we propose nicotine is able to exhaust CD8+ T cells. The CD8+ T cells from healthy volunteers with and without cigarette smoking and the capacity of CD8+ T cells against tumor cells were investigated. RNAseq was used to investigate the gene profiling expression in CD8+ T cells. Meanwhile, small RNAseq was also used to search novel microRNAs involved in the exhaustion of CD8+ T cells. The effect of nicotine exhausting CD8+ T cells was investigated in vitro and in the humanized tumor xenografts in vivo. We found that CD8+ T cells were able to reduce cell viability in lung cancer HCC827 and A549 cells, that secreted granzyme B, but CD8+ T cells from the healthy cigarette smokers lost anti-HCC827 effect. Moreover, nicotine suppressed the anti-HCC827 effect of CD8+ T cells. RNAseq revealed lower levels of IL2RB and GZMB in the exhausted CD8+ T cells. We identified that miR-629-5p was increased by nicotine, that targeted IL2RB. Transfection of miR-629-5p mimic reduced IL2RB and GZMB levels. We further validated that nicotine reduced granzyme B levels using a nuclear imaging technique, and demonstrated that nicotine exhausted peripheral blood mononuclear cells against HCC827 growth in the humanized tumor xenografts. This study demonstrated that nicotine exhausted CD8+ T cells against HCC827 cells through increasing miR-629-5p to suppress IL2RB.

Outcomes for the first wave of hospitalised patients with COVID-19 in the South Australian context: a retrospective audit.

BACKGROUND: The first case of corona virus disease (COVID-19) was detected in South Australia on 1 February 2020. The Royal Adelaide Hospital (RAH) is the state's designated quarantine hospital. AIM: To determine the characteristics, outcomes and predictors of outcomes for hospitalised patients with coronavirus disease (COVID-19) within the RAH. METHODS: We performed a retrospective audit of 103 patients diagnosed with COVID-19 who were discharged from the RAH between 14 February and 21 May 2020. We collected demographic, clinical and laboratory data through an audit of electronic medical records. The main outcome measures were: (i) the need for oxygen supplementation; (ii) need for intensive care unit (ICU) care; and (iii) death in hospital. RESULTS: The median age of patients was 60 years (range 19-85). A total of 55 (53%) patients was male. All patients were independent at baseline; 37 (36%) patients suffered from hypertension. Cardiovascular disease, respiratory disease and diabetes were present in fewer than 19 (18%) patients. Obesity was present in 24 (23%) patients; 39 (38%) patients required supplemental oxygen, 18 (17%) required ICU care and 4 (4%) patients died. Older patients were significantly more at risk of oxygen requirement (median 68 vs 57.5 years, P < 0.01), ICU admission (median 66.5 vs 60 years, P = 0.04) and death (median 74.5 vs 60 years, P = 0.02). We did not find a statistically significant association between gender, body mass index and poor outcomes. Lactate dehydrogenase (LDH) was the only parameter at admission associated with oxygen requirement, ICU care and death. Peak LDH, aspartate aminotransferase, alanine aminotransferase, C-reactive protein and neutrophil lymphocyte ratio were significantly associated with oxygen requirement, ICU admission and death (P < 0.05 for all of the above laboratory markers). CONCLUSIONS: Although our sample size was small, we found that certain comorbidities and laboratory values were associated with poor outcomes. This occurred in a setting where care was not influenced by limited hospital and intensive care beds.

Prenatal Detection of a Sublingual Lymphatic Malformation in a Fetus: A Rare Case.

BACKGROUND: Lymphatic malformations are benign cystic lesions that, while rare, tend to affect the pediatric age group. There are no reported cases diagnosed prenatally. CASE: A 28-year-old G1 woman at 34 weeks gestation was scanned for placental localization at a community ultrasound clinic. A fetal cystic, sublingual structure was identified. The patient was referred to our tertiary care centre, where a small (1.3 cm) avascular, cystic structure under the tongue of the fetus was confirmed. Antenatal course and delivery were unremarkable. The lesion resolved spontaneously with time. CONCLUSION: This report highlights a unique case in which a sublingual lymphatic malformation was detected prenatally during a third-trimester ultrasound.

STAT3 induces G9a to exacerbate HER3 expression for the survival of epidermal growth factor receptor-tyrosine kinase inhibitors in lung cancers.

BACKGROUND: HER3 mediates drug resistance against epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs), resulting in tumor relapse in lung cancers. Previously, we demonstrated that EGFR induces HER3 overexpression, which facilitates the formation of cancer stem-like tumorspheres. However, the cellular mechanism through which EGFR regulates HER3 expression remains unclear. We hypothesized that EGFR downstream of STAT3 participates in HER3 expression because STAT3 contributes to cancer stemness and survival of EGFR-TKI resistant cancers. METHODS: First, RNAseq was used to uncover potential genes involved in the formation of lung cancer HCC827-derived stem-like tumorspheres. EGFR-positive lung cancer cell lines, including HCC827, A549, and H1975, were individually treated with a panel containing 172 therapeutic agents targeting stem cell-associated genes to search for potential agents that could be applied against EGFR-positive lung cancers. In addition, gene knockdown and RNAseq were used to investigate molecular mechanisms through which STAT3 regulates tumor progression and the survival in lung cancer. RESULTS: BBI608, a STAT3 inhibitor, was a potential therapeutic agent that reduced the cell viability of EGFR-positive lung cancer cell lines. Notably, the inhibitory effects of BBI608 were similar with those associated with YM155, an ILF3 inhibitor. Both compounds reduced G9a-mediated HER3 expression. We also demonstrated that STAT3 upregulated G9a to silence miR-145-5p, which exacerbated HER3 expression in this study. CONCLUSIONS: The present study revealed that BBI608 could eradicate EGFR-positive lung cancers and demonstrated that STAT3 enhanced the expression of HER3 through miR-145-5p repression by G9a, indicating that STAT3 is a reliable therapeutic target against EGFR-TKI-resistant lung cancers.

No 374 - Évaluation systématique de la longueur cervicale.

OBJECTIF: Passer en revue les données probantes et fournir une opinion indiquant si l'évaluation systématique de la longueur cervicale pour la prévention de l'accouchement prématuré devrait être adoptée au Canada. RéSULTATS: Les issues évaluées comprennent la prévention de l'accouchement prématuré. DONNéES PROBANTES: Nous avons interrogé les bases de données Knowledge Finder, Medline et Cochrane pour en tirer les articles publiés jusqu'en avril 2018 sur la mesure de la longueur cervicale pour la prévention de l'accouchement prématuré. CRITèRES: Les données obtenues ont été examinées et évaluées par le Comité d'imagerie diagnostique de la SOGC sous la direction des auteurs principaux, et les recommandations ont été formulées selon les lignes directrices rédigées par le Groupe d'étude canadien sur les soins de santé préventifs. AVANTAGES, DéSAVANTAGES, ET COûTS: La prévention de l'accouchement prématuré sans coûts excessifs est très importante pour la santé des mères et des familles. La présente opinion de comité résume les données probantes actuelles sur l'évaluation systématique de la longueur cervicale pour prévenir l'accouchement prématuré au Canada, détermine si elle satisfait les critères de Jungner et Wilson pour un test de dépistage et formule des recommandations pour son utilisation au Canada. VALIDATION: La présente opinion a été révisée et approuvée par le comité d'imagerie diagnostique de la SOGC et la Société des obstétriciens et gynécologues du Canada (SOGC). COMMANDITAIRE: La Société des obstétriciens et gynécologues du Canada (SOGC).

No. 374-Universal Cervical Length Screening.

OBJECTIVE: To review the evidence and provide an opinion as to whether universal cervical length screening to prevent preterm birth should be adopted across Canada. OUTCOMES: Outcomes evaluated include prevention of preterm birth. EVIDENCE: Literature searches using Knowledge Finder, Medline and Cochrane databases were searched for articles published up to April 2018 on cervical length screening for prevention of preterm birth. VALUES: The evidence obtained was reviewed and evaluated by the Diagnostic Imaging Committee of the SOGC under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. BENEFITS, HARMS, AND COSTS: The prevention of preterm birth in a cost-effective manner is of significant importance to the health of mothers and their families. This committee opinion will summarize the current evidence for universal cervical length screening to prevent preterm birth in Canada, determine whether it meets the Junger and Wilson criteria for screening tests, and make recommendations as to its use in Canada. VALIDATION: These guidelines have been reviewed and approved by the Diagnostic Imaging Committee of the SOGC and The Society of Obstetricians and Gynaecologists of Canada (SOGC). SPONSORS: The Society of Obstetricians and Gynaecologists of Canada (SOGC).

Epidermal growth factor induces STAT1 expression to exacerbate the IFNr-mediated PD-L1 axis in epidermal growth factor receptor-positive cancers.

The epidermal growth factor (EGF) receptor (EGFR) overexpressed in many cancers, including lung and head and neck cancers, and is involved in cancer cell progression and survival. PD-L1, increases in tumor cells to evade and inhibit CD8+ T cells, is a clinical immunotherapeutic target. This study investigated the molecular mechanism of EGF on regulating PD-L1 in EGFR-positive cancers and determined potential agents to reduce PD-L1 expression. RNA sequencing (RNAseq) and bioinformatics analysis were performed to determine potential driver genes that regulate PD-L1 in tumor cells-derived tumorspheres which mimicking cancer stem cells. Then, the specific inhibitors targeting EGFR were applied to reduce the expression of PD-L1 in vitro and in vivo. We validated that EGF could induce PD-L1 expression in the selected EGFR-positive cancers. RNAseq results revealed that STAT1 increased as a driver gene in KOSC-3-derived tumorspheres; these data were analyzed using PANTHER followed by NetworkAnalyst. The blockade of EGFR by afatinib resulted in decreased STAT1 and IRF-1 levels, both are transcriptional factors of PD-L1, and disabled the IFNr-STAT1-mediated PD-L1 axis in vitro and in vivo. Moreover, STAT1 knockdown significantly reduced EGF-mediated PD-L1 expression, and ruxolitinib, a JAK1/JAK2 inhibitor, significantly inhibited STAT1 phosphorylation to reduce the IFNr-mediated PD-L1 axis. These results indicate that EGF exacerbates PD-L1 by increasing the protein levels of STAT1 to enforce the IFNr-JAK1/2-mediated signaling axis in selected EGFR-positive cancers. The inhibition of EGFR by afatinib significantly reduced PD-L1 and may be a potential strategy for enhancing immunotherapeutic efficacy.

STAT3 exacerbates survival of cancer stem-like tumorspheres in EGFR-positive colorectal cancers: RNAseq analysis and therapeutic screening.

BACKGROUND: Cancer stem cells are capable of undergoing cell division after surviving cancer therapies, leading to tumor progression and recurrence. Inhibitory agents against cancer stem cells may be therapeutically used for efficiently eradicating tumors. Therefore, the aim of this study was to identify the relevant driver genes that maintain cancer stemness in epidermal growth factor receptor (EGFR)-positive colorectal cancer (CRC) cells and to discover effective therapeutic agents against these genes. METHODS: In this study, EGFR-positive cancer stem-like cells (CSLCs) derived from HCT116 and HT29 cells were used as study models for in vitro inductions. To identify the differential genes that maintain CSLCs, RNAseq analysis was conducted followed by bioinformatics analysis. Moreover, a panel containing 172 therapeutic agents targeting the various pathways of stem cells was used to identify effective therapeutics against CSLCs. RESULTS: RNAseq analysis revealed that 654 and 840 genes were significantly upregulated and downregulated, respectively, in the HCT116 CSLCs. Among these genes, notably, platelet-derived growth factor A (PDGFA) and signal transducer and activator of transcription 3 (STAT3) were relevant according to the cancer pathway analyzed using NetworkAnalyst. Furthermore, therapeutic screening revealed that the agents targeting STAT3 and Wnt signaling pathways were efficient in reducing the cell viabilities of both HCT116 and HT29 cells. Consequently, we discovered that STAT3 inhibition using homoharringtonine and STAT3 knockdown significantly reduced the formation and survival of HT29-derived tumorspheres. We also observed that STAT3 phosphorylation was regulated by epidermal growth factor (EGF) to induce PDGFA and Wnt signaling cascades. CONCLUSIONS: We identified the potential genes involved in tumorsphere formation and survival in selective EGFR-positive CRCs. The results reveal that the EGF-STAT3 signaling pathway promotes and maintains CRC stemness. In addition, a crosstalk between STAT3 and Wnt activates the Wnt/ß-catenin signaling pathway, which is also responsible for cancer stemness. Thus, STAT3 is a putative therapeutic target for CRC treatment.

Variations from morning to afternoon of middle cerebral and umbilical artery blood flow, and fetal heart rate variability, and fetal characteristics in the normally developing fetus.

OBJECTIVE: To determine if there are changes in maternal uterine blood flow, fetal brain blood flow, fetal heart rate variability, and umbilical blood flow between morning (AM) and afternoon (PM) in healthy, uncomplicated pregnancies. STUDY DESIGN: In this prospective study, 68 uncomplicated singleton pregnancies (mean 35 + 0.7 weeks gestation) underwent a standard observational protocol at both 08:00 (AM) and 13:30 (PM) of the same day. This protocol included Doppler measurements of uterine, umbilical, and fetal middle cerebral artery (MCA) volume flow parameters (flow, HR, peak systolic velocity [PSV], PI, and RI) followed by computerized cardiotocography. Standard descriptive statistics, χ2 and t tests were used where appropriate. P < .05 was considered significant. RESULTS: A significant increase in MCA flow and MCA PSV was observed in the PM compared to the AM. This was accompanied by a fall in MCA resistance. Higher umbilical artery resistance indices were also observed in the PM compared to AM. In contrast, fetal heart rate characteristics, maternal uterine artery Doppler flow and resistance indices did not vary significantly between the AM and PM. CONCLUSION: In normal pregnancies, variations in fetal cerebral and umbilical blood flow parameters were observed between AM and PM independent of other fetal movements or baseline fetal heart rate. In contrast, uterine flow parameters remained stable across the day. These findings may have implications for the use of serial Doppler parameters used to guide clinical management in high-risk pregnancies.

Effect of Folic Acid Food Fortification in Canada on Congenital Heart Disease Subtypes.

BACKGROUND: Previous studies have yielded inconsistent results for the effects of periconceptional multivitamins containing folic acid and of folic acid food fortification on congenital heart defects (CHDs). METHODS: We carried out a population-based cohort study (N=5 901 701) of all live births and stillbirths (including late-pregnancy terminations) delivered at ≥20 weeks' gestation in Canada (except Québec and Manitoba) from 1990 to 2011. CHD cases were diagnosed at birth and in infancy (n=72 591). We compared prevalence rates and temporal trends in CHD subtypes before and after 1998 (the year that fortification was mandated). An ecological study based on 22 calendar years, 14 geographic areas, and Poisson regression analysis was used to quantify the effect of folic acid food fortification on nonchromosomal CHD subtypes (n=66 980) after controlling for changes in maternal age, prepregnancy diabetes mellitus, preterm preeclampsia, multiple birth, and termination of pregnancy. RESULTS: The overall birth prevalence rate of CHDs was 12.3 per 1000 total births. Rates of most CHD subtypes decreased between 1990 and 2011 except for atrial septal defects, which increased significantly. Folic acid food fortification was associated with lower rates of conotruncal defects (adjusted rate ratio [aRR], 0.73, 95% confidence interval [CI], 0.62-0.85), coarctation of the aorta (aRR, 0.77; 95% CI, 0.61-0.96), ventricular septal defects (aRR, 0.85; 95% CI, 0.75-0.96), and atrial septal defects (aRR, 0.82; 95% CI, 0.69-0.95) but not severe nonconotruncal heart defects (aRR, 0.81; 95% CI, 0.65-1.03) and other heart or circulatory system abnormalities (aRR, 0.98; 95% CI, 0.89-1.11). CONCLUSIONS: The association between food fortification with folic acid and a reduction in the birth prevalence of specific CHDs provides modest evidence for additional benefit from this intervention.

No. 352-Technical Update: The Role of Early Comprehensive Fetal Anatomy Ultrasound Examination.

OBJECTIVE: This guideline presents an evidence-based technical update and recommendations for the performance of early comprehensive fetal anatomic scanning (ECFAS) at 11 to 16 weeks' gestation. OPTIONS: Patients at high risk for fetal anomalies and in whom traditional mid-second trimester transabdominal imaging may be challenging or who may benefit from earlier identification of fetal anomalies may be suitable for early fetal anatomy scanning. OUTCOMES: This practice may result in earlier identification of fetal anomalies and provide earlier intervention options in high-risk populations and/or in populations where mid-second trimester transabdominal scanning is challenging. TARGET POPULATION: This population consists of obstetrical patients in whom mid-second trimester ultrasound scanning will be technically challenging and patients who are at higher risk for major fetal anomalies. EVIDENCE: Published literature was retrieved through searches of PubMed and Medline in 2016 using key words. Results were restricted to controlled clinical trials, reviews, and observational studies published in English. There were no date restrictions, and searches were updated in the guideline to 2016. Grey (unpublished) literature was identified through searching the websites of health technology assessment and clinical practice guidelines and national and international medical specialty societies. No relevant studies were found. VALIDATION METHODS: The content and recommendations were drafted and agreed on by the principal authors. The Board of the SOGC approved the final draft for publication. The quality of evidence was rated using the criteria described in the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology framework. BENEFITS, HARMS, AND/OR COSTS: It is anticipated that there will be an increase in earlier detection of major fetal anomalies in the target population with the benefits of earlier interventions for those individuals. In areas where the service is not available the patient may need to travel to a nearby centre. Early fetal anatomy scanning is considered to be safe and is not expected to cause a risk to the pregnancy. GUIDELINE UPDATE: Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published before the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations. SPONSORS: This technical update was developed with resources funded by the SOGC. SUMMARY STATEMENTS: RECOMMENDATIONS.

Insulin pump use in pregnancy is associated with lower HbA1c without increasing the rate of severe hypoglycaemia or diabetic ketoacidosis in women with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to compare glycaemic control and maternal-fetal outcomes in women with type 1 diabetes managed on insulin pumps compared with multiple daily injections of insulin (MDI). METHODS: In a retrospective study, glycaemic control and outcomes of 387 consecutive pregnancies in women with type 1 diabetes who attended specialised clinics at three centres 2006-2010 were assessed. RESULTS: Women using insulin pumps (129/387) were older and had a longer duration of diabetes, more retinopathy, smoked less in pregnancy, and had more preconception care (p < 0.01 for each). Among 113 pregnancies >20 weeks' gestation in women on insulin pumps and 218 in women on MDI, there was a significant difference in HbA1c in the first trimester (mean HbA1c 6.90 ± 0.71% (52 ± 7.8 mmol/mol) vs 7.60 ± 1.38% (60 ± 15.1 mmol/mol), p < 0.001), which persisted until the third trimester (mean HbA1c 6.49 ± 0.52% (47 ± 5.7 mmol/mol) vs 6.81 ± 0.85% (51 ± 9.3 mmol/mol), p = 0.002). Rates of diabetic ketoacidosis were similar in women on insulin pumps vs MDI (1.8% vs 3.0%, p = 0.72). Despite lower HbA1c, women on insulin pumps did not have an increased incidence of severe hypoglycaemia (8.0% vs 7.6%, p = 0.90) or more weight gain (16.3 ± 8.7 vs 15.2 ± 6.2 kg, p = 0.18). More large-for-gestational-age infants in the pump group (55.0% vs 39.2%, p = 0.007) may have resulted from confounding by parity. CONCLUSIONS/INTERPRETATION: In this large multicentre study, women using insulin pumps in pregnancy had lower HbA1c without increased risk of severe hypoglycaemia or diabetic ketoacidosis but no improvement in other pregnancy outcomes. This information can help inform care providers and patients about the glycaemic effectiveness and safety of insulin pumps in pregnancy.

RETIRED: Determination of gestational age by ultrasound.

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Ce document a été archivé, car il contient des informations périmées. Il ne devrait pas être consulté pour un usage clinique, mais uniquement pour des recherches historiques. Veuillez consulter le site web du journal pour les directives les plus récentes.