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.

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.

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.

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.

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.

The Breathing for Life Trial: a randomised controlled trial of fractional exhaled nitric oxide (FENO)-based management of asthma during pregnancy and its impact on perinatal outcomes and infant and childhood respiratory health.

BACKGROUND: Asthma exacerbations are common during pregnancy and associated with an increased risk of adverse perinatal outcomes. Adjusting asthma treatment based on airway inflammation rather than symptoms reduces the exacerbation rate by 50 %. The Breathing for Life Trial (BLT) will test whether this approach also improves perinatal outcomes. METHODS/DESIGN: BLT is a multicentre, parallel group, randomised controlled trial of asthma management guided by fractional exhaled nitric oxide (FENO, a marker of eosinophilic airway inflammation) compared to usual care, with prospective infant follow-up. Women with physician-diagnosed asthma, asthma symptoms and/or medication use in the previous 12 months, who are 12-22 weeks gestation, will be eligible for inclusion. Women randomised to the control group will have one clinical assessment of their asthma, including self-management education. Any treatment changes will be made by their general practitioner. Women randomised to the intervention group will have clinical assessments every 3-6 weeks during pregnancy, and asthma treatments will be adjusted every second visit based on an algorithm which uses FENO to adjust inhaled corticosteroid (ICS) dose (increase in dose when FENO >29 parts per billion (ppb), decrease in dose when FENO <19 ppb, and no change when FENO is between 19 and 29 ppb). A long acting beta agonist (LABA) will be added when symptoms remain uncontrolled. Both the control and intervention groups will report on exacerbations at a postpartum phone interview. The primary outcome is adverse perinatal outcome (a composite measure including preterm birth, intrauterine growth restriction, neonatal hospitalisation at birth or perinatal mortality), assessed from hospital records. Secondary outcomes will be each component of the primary outcome, maternal exacerbations requiring medical intervention during pregnancy (both smokers and non-smokers), and hospitalisation and emergency department presentation for wheeze, bronchiolitis or croup in the first 12 months of infancy. Outcome assessment and statistical analysis of the primary outcome will be blinded. To detect a reduction in adverse perinatal outcomes from 35 % to 26 %, 600 pregnant women with asthma per group are required. DISCUSSION: This trial will provide evidence for the effectiveness of a FENO-based management strategy in improving perinatal outcomes in pregnant women with asthma. If successful, this would improve the management of pregnant women with asthma worldwide. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000202763 .

A prospective pilot study in assessing the accuracy of ultrasound estimated fetal weight prior to delivery.

BACKGROUND: Perinatal mortality and morbidity related to growth restriction and macrosomia are predicted by birthweight. Estimated fetal weight is a surrogate measure for neonatal weight, and accurate measurement of this is central to providing counselling and managing preterm birth. AIMS: To assess the accuracy of estimated fetal weight (EFW) measured by two sonographers within 1 week of delivery using Hadlock formula. MATERIALS AND METHODS: Two sonographers independently scanned 150 women with singleton pregnancies, who were booked for elective delivery. The sonographers measured four biometric measurements in estimating fetal weight. The accuracy of EFW compared to the birthweight was examined. We also assessed the sensitivity and specificity for diagnosis of small-for-gestational age (SGA) and large-for-gestational age (LGA) according to the EFW. RESULTS: Estimated fetal weight was similar to actual birthweight, with a mean percentage difference (SD) of 1.4(7.0) (P = 0.44). The reliability coefficient of EFW compared to actual birthweight was 0.97 (95% CI (0.96, 0.98)). There was no significant difference between the sonographers for EFWs and among the sonographers from the ultrasound scan to delivery interval. The sensitivity and specificity for detection of SGA and LGA were 93.3% and 99.3%, 60% and 95.6%, respectively. CONCLUSIONS: There is high reproducibility with minimum discrepancy from actual birthweight among sonographers 1 week prior to delivery using Hadlock formula with better prediction of SGA neonates.

Placental fibroblast growth factor 21 is not altered in late-onset preeclampsia.

BACKGROUND: Preeclampsia (PE) is associated with alterations of placental function. The incidence of PE is higher in insulin resistant states. Women with PE have high circulating levels of the metabolic regulator fibroblast growth factor 21 (FGF21). FGF21 is synthesized in the placenta. The aim of this study was to compare the expression of FGF21, its receptors, downstream targets and transcriptional regulators in placental tissue from pregnancies with and without late-onset PE. Circulating FGF21 in maternal and cord blood was also studied. METHODS: mRNA expression was determined by semi-quantitative real-time PCR and normalized for cellular composition in 17 women with and 20 without PE. Protein expression was quantified by Western Blot. FGF21 levels were measured by ELISA in maternal and cord serum of ten mother-baby dyads per condition. RESULTS: Placental FGF21 mRNA and protein expression were similar in PE compared with control. Placental mRNA expression of the FGF receptors (1-4) and the co-receptor beta-Klotho was not different between the groups. There was no difference in the expression of the glucose transporters GLUT1, 3 or 4. PPAR-alpha but not PPAR-gamma expression was decreased in PE. Maternal FGF21 serum levels were not significantly different in PE. FGF21 was detected in cord blood of 6 infants (4 PE, 2 controls) but was undetectable in 14 infants. CONCLUSIONS: Late-onset PE is not associated with major changes to the expression of FGF21, its receptors or metabolic targets.

Placental lipase expression in pregnancies complicated by preeclampsia: a case-control study.

BACKGROUND: Preeclampsia (PE) is associated with maternal and neonatal morbidity and mortality. In PE, the physiological hyperlipidaemia of pregnancy is exaggerated. The purpose of this study was to examine the expression of adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), lipoprotein lipase (LPL) and endothelial lipase (EL) in pregnancies complicated by PE. METHODS: Placentae were collected from 16 women with PE and 20 women with uncomplicated pregnancies matched for maternal prepregnancy BMI and gestational age of delivery. Gene and protein expression of the placental lipases were measured by Q-PCR and Western blot. DNA methylation of the promoter of LPL was assessed by bisulfite sequencing. Lipase localisation and activity were analysed. RESULTS: Gene expression of all lipases was significantly reduced, as was HSL protein level in women with PE. All lipases were localised to trophoblasts and endothelial cells in PE and control placentae. There was no difference in methylation of the LPL promoter between PE and control placentae. Lipase activity was not altered in placentae from women with PE. CONCLUSION: These results suggest that the decreased placental lipase gene but not protein expression or lipase activity, which is associated with late-onset PE is not a major contributor to the abnormal lipids seen in PE.