Increasing HbA1c is associated with reduced CD8+ T cell functionality in response to influenza virus in a TCR-dependent manner in individuals with diabetes mellitus.

Diabetes mellitus is on the rise globally and is a known susceptibility factor for severe influenza virus infections. However, the mechanisms by which diabetes increases the severity of an influenza virus infection are yet to be fully defined. Diabetes mellitus is hallmarked by high glucose concentrations in the blood. We hypothesized that these high glucose concentrations affect the functionality of CD8+ T cells, which play a key role eliminating virus-infected cells and have been shown to decrease influenza disease severity. To study the effect of hyperglycemia on CD8+ T cell function, we stimulated peripheral blood mononuclear cells (PBMCs) from donors with and without diabetes with influenza A virus, anti-CD3/anti-CD28-coated beads, PMA and ionomycin (PMA/I), or an influenza viral peptide pool. After stimulation, cells were assessed for functionality [as defined by expression of IFN-γ, TNF-α, macrophage inflammatory protein (MIP)-1ß, and lysosomal-associated membrane protein-1 (CD107a)] using flow cytometry. Our results showed that increasing HbA1c correlated with a reduction in TNF-α production by CD8+ T cells in response to influenza stimulation in a TCR-specific manner. This was not associated with any changes to CD8+ T cell subsets. We conclude that hyperglycemia impairs CD8+ T cell function to influenza virus infection, which may be linked with the increased risk of severe influenza in patients with diabetes.

Habitual carbohydrate intake is not correlated with circulating ß-hydroxybutyrate levels in pregnant women with overweight and obesity at 28 weeks' gestation.

AIMS/HYPOTHESIS: Pregnant women are advised to consume a minimum of 175 g per day of carbohydrate to meet maternal and fetal brain glucose requirements. This recommendation comes from a theoretical calculation of carbohydrate requirements in pregnancy, rather than from clinical data. This study aimed to determine whether fasting maternal ketone levels are associated with habitual carbohydrate intake in a subset of participants of the Study of PRobiotics IN Gestational diabetes (SPRING) randomised controlled trial. METHODS: Food frequency questionnaires on dietary intake during pregnancy were completed by pregnant women with overweight or obesity at 28 weeks' gestation (considering their intake from the beginning of pregnancy). Dietary intake from early pregnancy through to 28 weeks was analysed for macronutrient intake. At the same time, overnight fasting serum samples were obtained and analysed for metabolic parameters including serum ß-hydroxybutyrate, OGTTs, insulin and C-peptide. RESULTS: Fasting serum ß-hydroxybutyrate levels amongst 108 women (mean BMI 34.7 ± 6.3 kg/m2) ranged from 22.2 to 296.5 µmol/l. Median fasting ß-hydroxybutyrate levels were not different between women with high (median [IQR] 68.4 [49.1-109.2 µmol/l]) and low (65.4 [43.6-138.0 µmol/l]) carbohydrate intake in pregnancy. Fasting ß-hydroxybutyrate levels were not correlated with habitual carbohydrate intake (median 155 [126-189] g/day). The only metabolic parameter with which fasting ß-hydroxybutyrate levels were correlated was 1 h venous plasma glucose (ρ=0.23, p=0.03) during a 75 g OGTT. CONCLUSIONS/INTERPRETATION: Fasting serum ß-hydroxybutyrate levels are not associated with habitual carbohydrate intake at 28 weeks' gestation in pregnant women with overweight and obesity.

OFFSPRING: A SPRING Follow-Up Study Assessing the Efficacy of Maternal Probiotics and Allergic Disease in the Child.

INTRODUCTION: There are a variety of factors that contribute to the development of allergic diseases in children, including environmental exposures during the maternal prenatal period. It has been proposed that probiotic supplementation during pregnancy could be used as a possible preventative measure to target childhood allergic disease. METHODS: Participants from a previously conducted prospective double-blind randomised control trial of probiotics versus placebo study (Study of PRrobiotics IN Gestation) were sent electronic questionnaires to complete about their child, who are now between 3 and 7 years of age. Demographic data and rates of allergic diseases were compared between the two groups. RESULTS: One hundred and seven women responded to the questionnaires. Between the two groups, there was no difference in the frequency of allergic diseases, with similar rates of eczema, asthma, and hospital presentations seen. CONCLUSION: In this follow-up study, infants of mothers who were exposed to probiotics during their pregnancy do not appear to have any paediatric health advantages in terms of allergic diseases.

A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

SOMANZ position statement for the investigation and management of sepsis in pregnancy 2023.

BACKGROUND: The Society of Australia and New Zealand (SOMANZ) published its first sepsis in pregnancy and the postpartum period guideline in 2017 (Aust N Z J Obstet Gynaecol, 57, 2017, 540). In the intervening 6 years, maternal mortality from sepsis has remained static. AIMS: To update clinical practice with a review of the subsequent literature. In particular, to review the definition and screening tools for the diagnosis of sepsis. MATERIALS AND METHODS: A multi-disciplinary group of clinicians with experience in all aspects of the care of pregnant women analysed the clinical evidence according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system following searches of Cochrane, Medline and EMBASE. Where there were conflicting views, the authors reviewed the topic and came to a consensus. All authors reviewed the final position statement. RESULTS: This position statement has abandoned the use of the quick Sequential Organ Failure Assessment score (qSOFA) score to diagnose sepsis due to its poor performance in clinical practice. Whilst New Zealand has a national maternity observation chart, in Australia maternity early warning system charts and vital sign cut-offs differ between states. Rapid recognition, early antimicrobials and involvement of senior staff remain essential factors to improving outcomes. CONCLUSION: Ongoing research is required to discover and validate tools to recognize and diagnose sepsis in pregnancy. Australia should follow New Zealand and have a single national maternity early warning system observation chart.

Agenda-setting by young adults with type 1 diabetes and associations with emotional well-being/social support: results from an observational study.

BACKGROUND: The Diabetes Psychosocial Assessment Tool (DPAT) was developed to assess the psychosocial well-being of young adults with type 1 diabetes in clinical practice. The DPAT includes three validated questionnaires (assessing diabetes distress, anxiety/depressive symptoms and emotional well-being) and an agenda-setting tool. It is currently used by the Queensland Statewide Diabetes Clinical Network (available at Clinical Excellence Queensland). AIMS: To describe agenda items set by young adults with type 1 diabetes and investigate their association with emotional well-being/social support. METHODS: The DPAT was completed by young adults attending routine diabetes outpatient appointments at the Mater Hospital (Brisbane) between November 2016 and January 2020. For the current analysis, data included responses on agenda-setting and outcomes from three validated questionnaires. RESULTS: Responses of 277 young adults (15-26 years) were analysed. Ninety-four (34%) reported one to three agenda item(s). Common agenda items were diabetes technology and medications, but other topics raised included pregnancy, body image and eating concerns. Participants with moderate diabetes distress or anxiety symptoms were more likely to list at least one agenda item (P = 0.006; P = 0.002), as were females and older participants. CONCLUSION: Several agenda items for young adults with type 1 diabetes were identified and were more likely to be raised by those with elevated diabetes distress and anxiety symptoms. The DPAT is a valuable and convenient tool that can be easily applied in routine clinical practice to enable clinicians to understand the concerns of the young adult population and deliver personalised medicine to optimise long-term outcomes.

Gut microbiome composition is similar between pregnant women with excess body fat with healthy and less healthy dietary intake patterns.

BACKGROUND: Dietary composition influences the composition of the gut microbiota in healthy adults. Little is known about the effect of dietary patterns on gut microbiota composition in pregnancy. This cross-sectional study aimed to investigate the associations between two diet quality scores adapted from the Australian Recommended Food Score (ARFS) and the Mediterranean Dietary Score (MDS) with the composition of the gut microbiota in pregnant women with excess body fat at 28 weeks' gestation. METHODS: Women from the Study of Probiotics IN Gestational diabetes (SPRING) who had completed a food frequency questionnaire (FFQ; n = 395) were classified according to tertiles of ARFS and the MDS. Higher dietary pattern scores in both the ARFS and the MDS represent better diet quality. Gut microbiota composition was assessed using 16S rRNA gene amplicon sequencing and analysed using MicrobiomeAnalyst in a subset of 196 women with faecal samples. RESULTS: No significant difference was found in alpha or beta diversity. A higher ARFS was associated with a higher abundance of Ruminococcus and lower abundance of Akkermansia, whereas a higher MDS was associated with a higher abundance of Ruminococcus and Butyricicoccus, though these changes disappeared after correction for multiple testing. CONCLUSION: These results suggest that dietary patterns defined by the ARFS and MDS were not associated with gut microbiota composition in pregnant women classified as overweight and obese at 28 weeks' gestation within this study.

Non-conventional laryngeal malignancies: a multicentre review of management and outcomes.

PURPOSE: Non-conventional laryngeal malignancies (NSCC) often have limited published data to guide management despite individual histopathological subtypes often exhibiting heterogeneous behaviour, characteristics, and treatment responses compared to laryngeal squamous cell carcinoma (SCC). This study aimed to compare oncological outcomes with SCC, specifically disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). Secondary objectives were to compare treatment differences and perform a state of the art review. METHODS: This was a multicentre retrospective cohort study at four tertiary head and neck centres. Survival outcomes between NSCC and SCC patients were analysed with Kaplan-Meier curves and compared by log rank testing. Univariate Cox regression analysis was performed to predict survival by histopathological subgroup, T-stage, N-stage and M-stage. RESULTS: There were no significant differences in 3-year DFS (p = 0.499), DSS (p = 0.329), OS (p = 0.360) or Kaplan Meier survival curves (DSS/OS) between SCC and overall NSCC groups. However, univariate Cox regression analysis identified "rare" histopathologies (mostly small cell carcinoma) to be predictive of less favourable OS (p = 0.035) but this result was not observed for other NSCC histopathological subgroups. N-stage (p = 0.027) and M-stage (p = 0.048) also predicted OS for NSCC malignancies. Significant differences in treatment modalities were identified with treatment of NSCC typically involving surgical resection and SCC often managed non-surgically (e.g., primary radiotherapy). CONCLUSIONS: Although overall NSCC is managed differently compared to SCC, there do not appear to be differences in survival outcomes between these groups. N-stage and M-stage appear to be more predictive of OS than histopathology than many NSCC subtypes.

Effect of asthma management with exhaled nitric oxide versus usual care on perinatal outcomes.

INTRODUCTION: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide (F ENO)-based asthma management improves perinatal outcomes compared to usual care. METHODS: The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided by F ENO (adjustment of asthma treatment according to exhaled nitric oxide and symptoms each 6-12 weeks) to usual care (no treatment adjustment as part of the trial). The primary outcome was a composite of adverse perinatal events (preterm birth, small for gestational age (SGA), perinatal mortality or neonatal hospitalisation) assessed using hospital records. Secondary outcomes included maternal asthma exacerbations. Concealed random allocation, stratified by study site and self-reported smoking status was used, with blinded outcome assessment and statistical analysis (intention to treat). RESULTS: Pregnant women with current asthma were recruited; 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention; OR 1.21, 95% CI 0.94-1.56; p=0.15), preterm birth (OR 1.14, 95% CI 0.78-1.68), SGA (OR 1.06, 95% CI 0.78-1.68), perinatal mortality (OR 3.62, 95% CI 0.80-16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89-1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69-2.05). CONCLUSION: F ENO-guided asthma pharmacotherapy delivered by a nurse or midwife in the antenatal clinic setting did not improve perinatal outcomes.

Is repeat fine needle aspiration required in thyroid nodules with initial benign cytology? Results from a large Irish series.

BACKGROUND : Fine needle aspiration (FNA) cytology is the preferred method for assessing thyroid nodules for malignancy. Concern remains about the rate of false negative results. The primary aim of this study is to investigate the malignancy rate of thyroid nodules initially classified as benign (Thy 2). METHODS: We retrospectively examined 658 nodules in 653 (429 female) patients between January 2013 to December 2017. All FNA biopsies (FNABs) were performed under ultrasound (US) guidance by a radiologist with expertise in thyroid pathology. Nodules were cytologically classified according to the UK Royal College of Pathologists guidelines. Decisions about further management were made at a regular thyroid multidisciplinary meeting. Follow up of the Thy 2 nodules was determined based on clinical and radiological criteria. RESULTS: The mean age (± SD) was 53.2 (14.6) years. Five hundred out of 658 (76.0%) nodules were classified as Thy 2 (benign) after the first FNAB. Of these thyroid nodules initially classified as benign, 208 (41.6%) underwent repeat FNAB and 9 (1.8%) were surgically removed without repeat FNAB. The remainder were followed up clinically and/or radiologically. Seven (1.4%) of nodules initially classified as Thy 2 were later shown to be or to harbor malignancy after a follow-up of 74.5 (± 19.7) months. Papillary thyroid microcarcinomas were found co-incidentally in two thyroid glands of benign nodules, giving a true prevalence of 5/500 (1.0%). CONCLUSIONS: With a well targeted FNAB, the false negative rate of an initial benign thyroid FNA is very low thus routine second FNAB is not required in patients with a thyroid nodule initially deemed benign. Multidisciplinary input is imperative in informing decision making.

The impact of a modified carbohydrate formula, and its constituents, on glycaemic control and inflammatory markers: A nested mechanistic sub-study.

BACKGROUND: Hyperglycaemia occurs frequently in the critically ill. Dietary intake of advanced glycation end-products (AGEs), specifically Nε-(carboxymethyl)lysine (CML), may exacerbate hyperglycaemia through perturbation of insulin sensitivity. The present study aimed to determine whether the use of nutritional formulae, with varying AGE loads, affects the amount of insulin administered and inflammation. METHODS: Exclusively tube fed patients (n = 35) were randomised to receive Nutrison Protein Plus Multifibre®, Diason® or Glucerna Select®. Insulin administration was standardised according to protocol based on blood glucose (<10 mmol L-1 ). Samples were obtained at randomisation and 48 h later. AGEs in nutritional formula, plasma and urine were measured using mass spectrometry. Plasma inflammatory markers were measured using an enzyme-linked immunosorbent assay and multiplex bead-based assays. RESULTS: AGE concentrations of CML in nutritional formulae were greatest with delivery of Nutrison Protein Plus® (mean [SD]; 6335 pmol mol-1 [2436]) compared to Diason® (4836 pmol mol-1 [1849]) and Glucerna Select® (4493 pmol mol-1 [1829 pmol mol-1 ]) despite patients receiving similar amounts of energy (median [interquartile range]; 12 MJ [8.2-13.7 MJ], 11.5 MJ [8.3-14.5 MJ], 11.5 MJ [8.3-14.5 MJ]). More insulin was administered with Nutrison Protein Plus® (2.47 units h-1 [95% confidence interval (CI) = 1.57-3.37 units h-1 ]) compared to Diason® (1.06 units h-1 [95% CI = 0.24-1.89 units h-1 ]) or Glucerna Select® (1.11 units h-1 [95% CI = 0.25-1.97 units h-1 ]; p = 0.04). Blood glucose concentrations were similar. There were associations between greater insulin administration and reductions in circulating interleukin-6 (r = -0.46, p < 0.01), tumour necrosis factor-α (r = -0.44, p < 0.05), high sensitivity C-reactive protein (r = -0.42, p < 0.05) and soluble receptor for advanced glycation end-products (r = -0.45, p < 0.01) concentrations. CONCLUSIONS: The administration of greater AGE load in nutritional formula potentially increases the amount of insulin required to maintain blood glucose within a normal range during critical illness. There was an inverse relationship between exogenous insulin and plasma inflammatory markers.

Continuous Glucose Monitoring in Young Adults With Type 1 Diabetes: Impact on Hypoglycemia Confidence and Fear.

Background: Fear of hypoglycemia in people with type 1 diabetes has a detrimental effect on glycemic control and quality of life. The association between continuous glucose monitoring (CGM) and hypoglycemia confidence and fear has not previously been assessed in the young adult population. Methods: This was a prospective cohort study using questionnaires to assess the impact of CGM on hypoglycemia confidence (using the Hypoglycemia Confidence Scale [HCS]) and hypoglycemia fear (using the Hypoglycemia Fear Survey II [HFS]) in 40 young adults with a preexisting diagnosis of type 1 diabetes. Results: Scores on the HCS were greater at baseline for those with a longer duration of diabetes. Participants with higher general anxiety scores on the Generalized Anxiety Disorder 7-item scale had higher hypoglycemia fear at baseline (total score and worry component, but not behavior component of the HFS). Between baseline and follow-up, HCS scores increased on average by 0.2 (95% CI 0.1-0.4, P = 0.01) on a scale of 1-4. HFS scores decreased by 1.8 (95% CI -3.0 to -0.5, P = 0.006) on a scale of 0-24 for the worry component and by 2.5 (95% CI -4.4 to -0.6, P = 0.01) on a scale of 0-44 for total (worry + behavior components). At follow up, 83% of participants planned to continue using CGM all or most of the time. There was a very high self-reported effect of CGM on life with diabetes (median 8.0 [interquartile range 6.5-10.0], where 10 indicated a very big difference). Conclusion: Hypoglycemia confidence and fear improve with CGM use in young adults.

Systematic Review: Diabetes Family Conflict in Young People With Type 1 Diabetes.

OBJECTIVE: To investigate the relationships between diabetes-specific family conflict and health outcomes of young people with type 1 diabetes (T1D). METHODS: A systematic review was performed according to the PRISMA statement (registration number: CRD42020164988). PubMed, Embase, PsycNET, reference lists of included studies, and other relevant reviews were searched (1990-2020). Two independent reviewers screened titles, abstracts, and full-texts. Studies were included if they sampled young people with T1D (mean age between 14 and 25 years) and examined the relationship between diabetes-specific family conflict and the following outcomes: glycated hemoglobin (HbA1c), treatment adherence, blood glucose monitoring, depression, anxiety, quality of life, and/or well-being. RESULTS: A total of 20 studies met the predetermined inclusion criteria. Greater diabetes-specific family conflict was significantly related to higher HbA1c values in 17 studies. Seven studies reported a significant association between greater diabetes family conflict and suboptimal treatment adherence and/or less frequent blood glucose monitoring. However, significant relationships between conflict and HbA1c and/or treatment adherence were not found in four studies. Seven studies in total reported that greater diabetes family conflict was significantly related to poorer quality of life or well-being and greater depressive and/or anxiety symptoms in young people. CONCLUSIONS: Diabetes-specific family conflict is associated with some adverse health outcomes for young people with T1D. However, more longitudinal studies of young people aged older than 16 years are needed. Screening for and addressing diabetes-specific family conflict is recommended, given the growing number of studies linking family conflict to various adverse health outcomes in young people with T1D.

Maternal gut microbiota displays minor changes in overweight and obese women with GDM.

BACKGROUND AND AIMS: Previous literature have shown a diversity of findings regarding the relationship between the maternal gut microbiota and gestational diabetes mellitus (GDM). We investigated the gut microbiota of overweight and obese women with gestational diabetes mellitus (GDM) against matched euglycaemic women at 16 and 28-weeks' gestation. METHODS AND RESULTS: This study included women from the SPRING (Study of PRobiotics IN Gestational diabetes) cohort. Overweight and obese women with no impaired glucose tolerance or impaired fasted glucose were enrolled prior to gestational age <16 weeks. Participants with a diagnosis of GDM (n = 29) were matched with euglycaemic (n = 29) women for body mass index, probiotic or placebo intervention, maternal age, parity and ethnicity. Anthropometric, clinical and fecal microbiota (16S rRNA amplicon-based sequencing of V6-V8 region) data was assessed at 16 and 28-weeks' gestation. The relative abundances of key bacterial genera were not significantly altered between euglycaemic women and women with GDM. Occurrence of bacterial taxa was similar between groups at both timepoints. GDM was associated with decreased Shannon diversity (p = 0.02) without differentiated clustering measured by beta diversity at 28-weeks' gestation. CONCLUSIONS: Overweight and obese women with GDM demonstrate minor variation in the gut microbiota at 16 and 28-weeks' gestation compared with matched euglycaemic women. This study expands on previous literature concluding the microbiota does not likely have a disease-specific characterisation in GDM.

Probiotics for preventing gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes for mother and infant. The prevention of GDM using lifestyle interventions has proven difficult. The gut microbiome (the composite of bacteria present in the intestines) influences host inflammatory pathways, glucose and lipid metabolism and, in other settings, alteration of the gut microbiome has been shown to impact on these host responses. Probiotics are one way of altering the gut microbiome but little is known about their use in influencing the metabolic environment of pregnancy. This is an update of a review last published in 2014. OBJECTIVES: To systematically assess the effects of probiotic supplements used either alone or in combination with pharmacological and non-pharmacological interventions on the prevention of GDM. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (20 March 2020), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised and cluster-randomised trials comparing the use of probiotic supplementation with either placebo or diet for the prevention of the development of GDM. Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over design studies were not eligible for inclusion in this review. Studies presented only as abstracts with no subsequent full report of study results were only included if study authors confirmed that data in the abstract came from the final analysis. Otherwise, the abstract was left awaiting classification. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, extracted data and assessed risk of bias of included studies. Data were checked for accuracy. MAIN RESULTS: In this update, we included seven trials with 1647 participants. Two studies were in overweight and obese women, two in obese women and three did not exclude women based on their weight. All included studies compared probiotics with placebo. The included studies were at low risk of bias overall except for one study that had an unclear risk of bias. We excluded two studies, eight studies were ongoing and three studies are awaiting classification. Six included studies with 1440 participants evaluated the risk of GDM. It is uncertain if probiotics have any effect on the risk of GDM compared to placebo (mean risk ratio (RR) 0.80, 95% confidence interval (CI) 0.54 to 1.20; 6 studies, 1440 women; low-certainty evidence). The evidence was low certainty due to substantial heterogeneity and wide CIs that included both appreciable benefit and appreciable harm. Probiotics increase the risk of pre-eclampsia compared to placebo (RR 1.85, 95% CI 1.04 to 3.29; 4 studies, 955 women; high-certainty evidence) and may increase the risk of hypertensive disorders of pregnancy (RR 1.39, 95% CI 0.96 to 2.01, 4 studies, 955 women), although the CIs for hypertensive disorders of pregnancy also indicated probiotics may have no effect. There were few differences between groups for other primary outcomes. Probiotics make little to no difference in the risk of caesarean section (RR 1.00, 95% CI 0.86 to 1.17; 6 studies, 1520 women; high-certainty evidence), and probably make little to no difference in maternal weight gain during pregnancy (MD 0.30 kg, 95% CI -0.67 to 1.26; 4 studies, 853 women; moderate-certainty evidence). Probiotics probably make little to no difference in the incidence of large-for-gestational age infants (RR 0.99, 95% CI 0.72 to 1.36; 4 studies, 919 infants; moderate-certainty evidence) and may make little to no difference in neonatal adiposity (2 studies, 320 infants; data not pooled; low-certainty evidence). One study reported adiposity as fat mass (MD -0.04 kg, 95% CI -0.12 to 0.04), and one study reported adiposity as percentage fat (MD -0.10%, 95% CI -1.19 to 0.99). We do not know the effect of probiotics on perinatal mortality (RR 0.33, 95% CI 0.01 to 8.02; 3 studies, 709 infants; low-certainty evidence), a composite measure of neonatal morbidity (RR 0.69, 95% CI 0.36 to 1.35; 2 studies, 623 infants; low-certainty evidence), or neonatal hypoglycaemia (mean RR 1.15, 95% CI 0.69 to 1.92; 2 studies, 586 infants; low-certainty evidence). No included studies reported on perineal trauma, postnatal depression, maternal and infant development of diabetes or neurosensory disability. AUTHORS' CONCLUSIONS: Low-certainty evidence from six trials has not clearly identified the effect of probiotics on the risk of GDM. However, high-certainty evidence suggests there is an increased risk of pre-eclampsia with probiotic administration. There were no other clear differences between probiotics and placebo among the other primary outcomes. The certainty of evidence for this review's primary outcomes ranged from low to high, with downgrading due to concerns about substantial heterogeneity between studies, wide CIs and low event rates. Given the risk of harm and little observed benefit, we urge caution in using probiotics during pregnancy. The apparent effect of probiotics on pre-eclampsia warrants particular consideration. Eight studies are currently ongoing, and we suggest that these studies take particular care in follow-up and examination of the effect on pre-eclampsia and hypertensive disorders of pregnancy. In addition, the underlying potential physiology of the relationship between probiotics and pre-eclampsia risk should be considered.

Update on pulmonary embolism in pregnancy and post-partum: The Society of Obstetric Medicine of Australia and New Zealand Position Statement on Pulmonary Embolism in Pregnancy and Post-partum.

In this clinical review we highlight aspects of the diagnosis and management of pulmonary embolism (PE) in pregnancy and post-partum and how this may impact on antenatal and postnatal management. Investigation for PE in pregnancy is challenging and includes appropriate patient selection and knowledge of the risks and benefits of pulmonary imaging modalities. The complete Society of Obstetric Medicine of Australia and New Zealand Position Statement on Pulmonary Embolism in Pregnancy and Post-Partum comprehensively reviews all aspects of diagnosis, investigation and management and is accessible at https://www.somanz.org/guidelines.asp. It includes a summary of all recommendations and a guide to developing a management plan for birth in women on anticoagulation.

Diabetes care: addressing psychosocial well-being in young adults with a newly developed assessment tool.

BACKGROUND: Psychosocial assessment should be part of clinic visits for people with diabetes mellitus (DM). AIMS: To assess the usage and acceptance of a diabetes psychosocial assessment tool (DPAT) and to profile the clinical and psychosocial characteristics of young people with diabetes. METHODS: Over a 12-month period, young adults (18-25 years) attending diabetes clinic were offered DPAT. The tool embeds validated screening tools including the Problem Areas in Diabetes 20 (PAID-20) questionnaire, the Patient Health Questionnaire-4 (PHQ-4) and the World Health Organization Well-Being Index-5 (WHO-5). Baseline clinical data were collected and questions regarding social support, body image, eating concerns, hypoglycaemia and finances were included. RESULTS: Over the 12 month, the form was offered to 155 participants (64.6% of eligible attendees). The majority (96.1%) had type 1 DM with a mean duration of 10.5 (±5.3 SD) years. Average glycated haemoglobin (HbA1c) was 8.7% (±1.5 SD) (or 71.2 mmol/mol ±16.5 SD). Severe diabetes-related distress (PAID-20 ≥ 40) was found in 19.4%. Low WHO-5 scores (28-50 points) were seen in 14.8%. PHQ-4 identified 25.8% with anxiety and 16.1% with depression. Significant weight, shape and eating concerns were identified in 27.1, 26.6 and 28.4%, respectively. Serious hypoglycaemia concerns were raised by 4.5%. CONCLUSION: DPAT revealed a high prevalence of psychosocial stress among young adults with DM. The tool was easy to use and accepted by patients and may aid streamlining referrals to relevant members of a multidisciplinary team.

ADIPS 2020 guideline for pre-existing diabetes and pregnancy.

This is the full version of the Australasian Diabetes in Pregnancy Society (ADIPS) 2020 guideline for pre-existing diabetes and pregnancy. The guideline encompasses the management of women with pre-existing type 1 diabetes and type 2 diabetes in relation to pregnancy, including preconception, antepartum, intrapartum and postpartum care. The management of women with monogenic diabetes or cystic fibrosis-related diabetes in relation to pregnancy is also discussed.

Trends in asthma self-management skills and inhaled corticosteroid use during pregnancy and postpartum from 2004 to 2017.

OBJECTIVE: Asthma exacerbations and medication non-adherence are significant clinical problems during pregnancy. While asthma self-management education is effective, the number of education sessions required to maximise asthma management knowledge and inhaler technique and whether improvements persist postpartum, are unknown. This paper describes how asthma knowledge, skills, and inhaled corticosteroid (ICS) use have changed over time. METHODS: Data were obtained from 3 cohorts of pregnant women with asthma recruited in Newcastle, Australia between 2004 and 2017 (N = 895). Medication use, adherence, knowledge, and inhaler technique were compared between cohorts. Changes in self-management knowledge/skills and women's perception of medication risk to the fetus were assessed in 685 women with 5 assessments during pregnancy, and 95 women who had a postpartum assessment. RESULTS: At study entry, 41%, 29%, and 38% of participants used ICS in the 2004, 2007, and 2013 cohorts, respectively (p = 0.017), with 40% non-adherence in each cohort. Self-management skills of pregnant women with asthma did not improve between 2004 and 2017 and possession of a written action plan remained low. Maximum improvements were reached by 3 sessions for medications knowledge and one session for inhaler technique, and were maintained postpartum. ICS adherence was maximally improved after one session, but not maintained postpartum. Perceived risk of asthma medications on the fetus was highest for corticosteroid-containing medication; and was significantly reduced following education. CONCLUSIONS: There was a high prevalence of non-adherence and poor self-management skills in all cohorts. More awareness of the importance of optimal asthma management during pregnancy is warranted, since no improvements were observed over the past decade.

Iron supplementation has minor effects on gut microbiota composition in overweight and obese women in early pregnancy.

Fe is an essential nutrient for many bacteria, and Fe supplementation has been reported to affect the composition of the gut microbiota in both Fe-deficient and Fe-replete individuals outside pregnancy. This study examined whether the dose of Fe in pregnancy multivitamin supplements affects the overall composition of the gut microbiota in overweight and obese pregnant women in early pregnancy. Women participating in the SPRING study with a faecal sample obtained at 16 weeks' gestation were included in this substudy. For each subject, the brand of multivitamin used was recorded. Faecal microbiome composition was assessed by 16S rRNA sequencing and analysed with the QIIME software suite. Dietary intake of Fe was assessed using a FFQ at 16 weeks' gestation. Women were grouped as receiving low (<60 mg/d, n 94) or high (≥60 mg/d; n 65) Fe supplementation. The median supplementary Fe intake in the low group was 10 (interquartile range (IQR) 5-10) v. 60 (IQR 60-60) mg/d in the high group (P<0·001). Dietary Fe intake did not differ between the groups (10·0 (IQR 7·4-13·3) v. 9·8 (IQR 8·2-13·2) mg/d). Fe supplementation did not significantly affect the composition of the faecal microbiome at any taxonomic level. Network analysis showed that the gut microbiota in the low Fe supplementation group had a higher predominance of SCFA producers. Pregnancy multivitamin Fe content has a minor effect on the overall composition of the gut microbiota of overweight and obese pregnant women at 16 weeks' gestation.