Publications by authors named "Helen L Barrett"

62 Publications

Capillary Triglycerides in Late Pregnancy-Challenging to Measure, Hard to Interpret: A Cohort Study of Practicality.

Nutrients 2021 Apr 13;13(4). Epub 2021 Apr 13.

The Royal Brisbane and Women's Hospital, Herston, QLD 4029, Australia.

Background: Maternal triglycerides are increasingly recognised as important predictors of infant growth and fat mass. The variability of triglyceride patterns during the day and their relationship to dietary intake in women in late pregnancy have not been explored. This prospective cohort study aimed to examine the utility of monitoring capillary triglycerides in women in late pregnancy.

Methods: Twenty-nine women (22 with gestational diabetes (GDM) and 7 without) measured capillary glucose and triglycerides using standard meters at home for four days. On two of those days, they consumed one of two standard isocaloric breakfast meals: a high-fat/low-carbohydrate meal (66% fat) or low fat/high carbohydrate meal (10% fat). Following the standard meals, glucose and triglyceride levels were monitored.

Results: Median capillary triglycerides were highly variable between women but did not differ between GDM and normoglycaemic women. There was variability in capillary triglycerides over four days of home monitoring and a difference in incremental area under the curve for capillary triglycerides and glucose between the two standard meals. The high-fat standard meal lowered the incremental area under the curve for capillary glucose ( < 0.0001). Fasting (rho 0.66, = 0.0002) and postpradial capillary triglycerides measured at home correlated with venous triglyceride levels.

Conclusions: The lack of differences in response to dietary fat intake and the correlation between capillary and venous triglycerides suggest that monitoring of capillary triglycerides before and after meals in pregnancy is unlikely to be useful in the routine clinical practice management of women with gestational diabetes mellitus.
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http://dx.doi.org/10.3390/nu13041266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070156PMC
April 2021

Probiotics for preventing gestational diabetes.

Cochrane Database Syst Rev 2021 04 19;4:CD009951. Epub 2021 Apr 19.

School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Australia.

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.
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http://dx.doi.org/10.1002/14651858.CD009951.pub3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094741PMC
April 2021

Pregnant women who develop preeclampsia have lower abundance of the butyrate-producer Coprococcus in their gut microbiota.

Pregnancy Hypertens 2021 Mar 26;23:211-219. Epub 2021 Jan 26.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia. Electronic address:

Preeclampsia is a pregnancy-specific disorder characterized by hypertension and dysfunction of several organs, that is associated with maternal and fetal complications. The human gut microbiota is related to health and disease including hypertension. Alterations in gut microbiota composition can change the short-chain fatty acid profile released by the bacteria and contribute to hypertension and metabolic syndrome. It is unclear if the composition of the gut microbiota is altered in women who develop late-onset preeclampsia. In this study, we investigated the composition of the gut microbiota at 28 weeks gestation in women who developed late-onset (>34 weeks gestation) preeclampsia (DPE) by 16S rRNA gene amplicon sequencing of fecal samples obtained from 213 pregnant women in the SPRING cohort (Study of Probiotics IN Gestational diabetes). Quantitative real-time PCR was used to assess the density of butyrate-producing genes. Gut microbiota composition was compared between women with and without DPE. The abundance of the butyrate-producing Coprococcus genus significantly decreased in DPE. Abundance of Coprococcus is significantly and positively correlated with the abundance of genes encoding the terminal step in bacterial butyrate formation (but and buk). Women with DPE also had significantly reduced levels of serum butyrate prior to the development of symptoms than controls. This study suggests that a reduction in the abundance of butyrate-producing bacteria, and Coprococcus spp. in particular, may contribute to an increased risk of developing preeclampsia in pregnant women.
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http://dx.doi.org/10.1016/j.preghy.2021.01.002DOI Listing
March 2021

Ketones in Pregnancy: Why Is It Considered Necessary to Avoid Them and What Is the Evidence Behind Their Perceived Risk?

Diabetes Care 2021 Jan;44(1):280-289

Mater Research Institute, The University of Queensland, and Mater Hospital Brisbane, South Brisbane, Queensland, Australia.

Current dietary advice for women with gestational diabetes mellitus is to avoid diets that result in elevated ketone levels. This guidance stems from a concern that maternal ketones are associated with poor fetal and childhood outcomes, including reduced childhood intelligence quota. The evidence behind these guidelines is conflicting and inconsistent. Given that dietary counseling is the initial treatment strategy for women with diabetes in pregnancy, it is important that clinicians understand the concern regarding maternal ketones. This review examines the physiology of ketogenesis in pregnancy, the prevalence of elevated maternal ketone levels, and the relationship between maternal ketones and fetal and childhood outcomes.
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http://dx.doi.org/10.2337/dc20-2008DOI Listing
January 2021

Dietary Fiber Intake Alters Gut Microbiota Composition but Does Not Improve Gut Wall Barrier Function in Women with Future Hypertensive Disorders of Pregnancy.

Nutrients 2020 Dec 17;12(12). Epub 2020 Dec 17.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.

Pregnancy alters the inflammatory state, metabolic hormones, and gut microbiota composition. It is unclear if the lower abundance of dietary fiber-fermenting, short-chain fatty acid-producing bacteria observed in hypertension also occurs in hypertensive disorders of pregnancy (HDP). This study investigated the relationship between dietary fiber intake and the gut microbiota profile at 28 weeks gestation in women who developed HDP in late pregnancy ( = 22) or remained normotensive ( = 152) from the Study of PRobiotics IN Gestational diabetes (SPRING). Dietary fiber intake was classified as above or below the median of 18.2 g/day. Gut microbiota composition was examined using 16S rRNA gene amplicon sequencing. The gut permeability marker zonulin was measured in a subset of 46 samples. In women with future HPD, higher dietary fiber intake was specifically associated with increased abundance of lower abundance of and and higher zonulin levels than normotensive women. Fiber intake and zonulin levels were negatively correlated in women with normotensive pregnancies but not in pregnancies with future HDP. In women with normotensive pregnancies, dietary fiber intake may improve gut barrier function. In contrast, in women who develop HDP, gut wall barrier function is impaired and not related to dietary fiber intake.
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http://dx.doi.org/10.3390/nu12123862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766248PMC
December 2020

Going in Early: Hypoxia as a Target for Kidney Disease Prevention in Diabetes?

Diabetes 2020 12;69(12):2578-2580

Mater Research - The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia

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http://dx.doi.org/10.2337/dbi20-0037DOI Listing
December 2020

ADIPS 2020 guideline for pre-existing diabetes and pregnancy.

Aust N Z J Obstet Gynaecol 2020 12 16;60(6):E18-E52. Epub 2020 Nov 16.

Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.

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.
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http://dx.doi.org/10.1111/ajo.13265DOI Listing
December 2020

Determinants of Cardiovascular Risk in 7000 Youth With Type 1 Diabetes in the Australasian Diabetes Data Network.

J Clin Endocrinol Metab 2021 Jan;106(1):133-142

School of Public Health and Preventive Medicine, Monash University, Clayton, VIC, Australia.

Context: Cardiovascular disease occurs prematurely in type 1 diabetes. The additional risk of overweight is not well characterized.

Objective: The primary aim was to measure the impact of body mass index (BMI) in youth with type 1 diabetes on cardiovascular risk factors. The secondary aim was to identify other determinants of cardiovascular risk.

Design: Observational longitudinal study of 7061 youth with type 1 diabetes followed for median 7.3 (interquartile range [IQR] 4-11) years over 41 (IQR 29-56) visits until March 2019.

Setting: 15 tertiary care diabetes centers in the Australasian Diabetes Data Network.Participants were aged 2 to 25 years at baseline, with at least 2 measurements of BMI and blood pressure.

Main Outcome Measure: Standardized systolic and diastolic blood pressure scores and non-high-density lipoprotein (HDL) cholesterol were co-primary outcomes. Urinary albumin/creatinine ratio was the secondary outcome.

Results: BMI z-score related independently to standardized blood pressure z- scores and non-HDL cholesterol. An increase in 1 BMI z-score related to an average increase in systolic/diastolic blood pressure of 3.8/1.4 mmHg and an increase in non-HDL cholesterol (coefficient + 0.16 mmol/L, 95% confidence interval [CI], 0.13-0.18; P < 0.001) and in low-density lipoprotein (LDL) cholesterol. Females had higher blood pressure z-scores, higher non-HDL and LDL cholesterol, and higher urinary albumin/creatinine than males. Indigenous youth had markedly higher urinary albumin/creatinine (coefficient + 2.15 mg/mmol, 95% CI, 1.27-3.03; P < 0.001) and higher non-HDL cholesterol than non-Indigenous youth. Continuous subcutaneous insulin infusion was associated independently with lower non-HDL cholesterol and lower urinary albumin/creatinine.

Conclusions: BMI had a modest independent effect on cardiovascular risk. Females and Indigenous Australians in particular had a more adverse risk profile.
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http://dx.doi.org/10.1210/clinem/dgaa727DOI Listing
January 2021

Factors Associated with Nonadherence to Inhaled Corticosteroids for Asthma During Pregnancy.

J Allergy Clin Immunol Pract 2021 Mar 8;9(3):1242-1252.e1. Epub 2020 Oct 8.

Priority Research Centre Grow Up Well, School of Medicine and Public Health, University of Newcastle, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia. Electronic address:

Background: Nonadherence is common among pregnant women prescribed inhaled corticosteroids (ICS) for asthma and may have serious consequences for mother and baby. Factors associated with ICS nonadherence have not been determined in this population.

Objectives: To determine factors associated with {1} nonadherence to ICS in early-mid pregnancy (cross-sectional) and {2} persistent nonadherence to ICS during pregnancy (longitudinal).

Methods: Data used come from 3 prospective studies (2004-2019) involving women with asthma recruited by 23 weeks' gestation (N = 1614). Demographics, asthma history, and current symptoms were assessed, and spirometry was performed at baseline and throughout pregnancy. Women self-reported current medication use and number of ICS doses missed in the past week. Nonadherence was defined as ≥20% of prescribed dosages missed in the past week (baseline) and on at least 2 occasions during follow-up (persistent). Factors associated with ICS nonadherence were examined using backward stepwise logistic regression.

Results: Of 610 (38%) women prescribed ICS at baseline, 236 (39%) were classified as nonadherent. Of 612 (38%) women prescribed ICS during at least 2 follow-up visits, 149 (24%) were classified as persistent nonadherent. Factors associated with nonadherence at baseline were current or ex-smoking, non-Caucasian/non-Indigenous ethnicity, adult diagnosis of asthma, and lower lung function. Factors associated with persistent nonadherence to ICS were lower maternal age, higher parity, and no prescribed ICS at baseline.

Conclusion: Young multiparous non-Caucasian/non-Indigenous mothers are at increased risk of being nonadherent to ICS during pregnancy. Strategies to improve ICS nonadherence should address maternal smoking and target women who (re-)initiate ICS use in pregnancy.
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http://dx.doi.org/10.1016/j.jaip.2020.09.045DOI Listing
March 2021

Altered Gut Microbiota Composition Is Associated With Back Pain in Overweight and Obese Individuals.

Front Endocrinol (Lausanne) 2020 2;11:605. Epub 2020 Sep 2.

Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC, Australia.

Back pain is the leading cause of disability worldwide and is associated with obesity and chronic low-grade inflammation. Alterations in intestinal microbiota may contribute to the pathogenesis of back pain through metabolites affecting immune and inflammatory responses. We compared the gut microbiota composition in a cohort of 36 overweight or obese individuals with or without self-reported back pain in the preceding month. Participants were characterized for anthropometry; bone health; metabolic health; inflammation; dietary intake; and physical activity. Demographic, clinical, biochemical characteristics, diet and physical activity were similar between participants with ( = 14) or without ( = 22) back pain. Individuals with back pain had a higher abundance of the genera ( = 0.0008; FDR = 0.027) ( = 0.0098; FDR = 0.17), and ( = 0.02; FDR = 0.27) than those without back pain. abundance remained higher in individuals with back pain in the past 2 weeks, 6 months, and 1 year. was positively correlated with BMI (rho = 0.35, = 0.03), serum adipsin (rho = 0.33, = 0.047), and serum leptin (rho = 0.38, = 0.02). Our findings suggest that back pain is associated with altered gut microbiota composition, possibly through increased inflammation. Further studies delineating the underlying mechanisms may identify strategies for lowering abundance to treat back pain.
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http://dx.doi.org/10.3389/fendo.2020.00605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492308PMC
September 2020

Self-reported periconception weight loss attempts do not alter infant body composition.

Nutrition 2020 09 29;77:110781. Epub 2020 Feb 29.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia. Electronic address:

Objectives: Maternal obesity increases the risk for adverse infant outcomes; therefore, achieving an optimal body mass index before conception is recommended. Periconceptional maternal weight loss, however, has been associated with adverse outcomes for the fetus, including altered body composition in animal studies. It is not clear whether periconception weight loss alters infant body composition in humans. The aim of this study was to compare body composition in offspring of women who attempted to lose or maintain weight in the periconception period.

Methods: Women who delivered a healthy term infant were grouped according to attempt to lose weight. Infant body composition was determined by air displacement plethysmography and anthropometric measurements.

Results: In a cohort of 73 women, 27 attempted to lose weight and 46 maintained weight in the periconception period. Infant birth weight, percent body fat, and head and arm circumference were not altered by maternal attempts to lose weight. Infant abdominal circumference was increased in the offspring of women who attempted to lose weight in the periconception period. Infant percent body fat was increased in overweight and obese mothers and in female infants.

Conclusion: The results of this study showed that attempts to lose weight in the periconception period do not significantly alter infant body composition. The increase in abdominal circumference may indicate a difference in fat distribution in offspring of women who attempted to lose weight, which may increase their risk for future metabolic and cardiovascular disease.
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http://dx.doi.org/10.1016/j.nut.2020.110781DOI Listing
September 2020

Effect of Vitamin D Supplementation on Faecal Microbiota: A Randomised Clinical Trial.

Nutrients 2019 Nov 27;11(12). Epub 2019 Nov 27.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Clayton, VIC 3168 Australia.

In animal studies, vitamin D supplementation has been shown to improve gut microbiota and intestinal inflammation. However, limited evidence exists on the effect of vitamin D supplementation on the human gut microbiota. We examined the effect of vitamin D supplementation on faecal microbiota in 26 vitamin D-deficient (25-hydroxyvitamin D (25(OH)D) ≤50 nmol/L), overweight or obese (BMI ≥25 kg/m) otherwise healthy adults. Our study was ancillary to a community based double-blind randomised clinical trial, conducted between 2014 and 2016. The participants provided stool samples at baseline and after 100,000 international units (IU) loading dose of cholecalciferol followed by 4000 IU daily or matching placebo for 16 weeks. Faecal microbiota was analysed using 16S rRNA sequencing; V6-8 region. There was no significant difference in microbiome α-diversity between vitamin D and placebo groups at baseline and follow-up (all > 0.05). In addition, no clustering was found based on vitamin D supplementation at follow-up ( = 0.3). However, there was a significant association between community composition and vitamin D supplementation at the genus level ( = 0.04). The vitamin D group had a higher abundance of genus , and lower abundance of genus (linear discriminate analysis >3.0). Moreover, individuals with 25(OH)D >75 nmol/L had a higher abundance of genus and lower abundance of genus compared to those with 25(OH)D <50 nmol/L. Our findings suggest that vitamin D supplementation has some distinct effects on faecal microbiota. Future studies need to explore whether these effects would translate into improved clinical outcomes.
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http://dx.doi.org/10.3390/nu11122888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950585PMC
November 2019

The effect of a low carbohydrate formula on glycaemia in critically ill enterally-fed adult patients with hyperglycaemia: A blinded randomised feasibility trial.

Clin Nutr ESPEN 2019 06 11;31:80-87. Epub 2019 Mar 11.

Mater Research Institute, The University of Queensland, Princess Alexandra Hospital, Australia.

Background: Enteral nutrition is a source of carbohydrate that may exacerbate hyperglycaemia. Its treatment, insulin, potentially exacerbates glycaemic variability.

Methods: This was a prospective, parallel group, blinded, randomised feasibility trial. Patients were eligible if 18 years or over when admitted to the intensive care unit and receiving enteral nutrition (EN) exclusively with two consecutive blood glucose > 10 mmol/L. A standardized glucose management protocol determined administration of insulin. Key outcome measures were insulin administered and glycaemic variability (coefficient of variation) over the first 48 h.

Results: 41 patients were randomized to either standard EN (14.1 g/100 mL carbohydrate; n = 20) or intervention EN (7.4 g/100 mL carbohydrate; n = 21). Overall 59% were male, mean (±SD) age of 62.3 years ± 10.4, APACHE II score of 16.5 ± 7.8 and a median (IQR) Body Mass Index 29.0 kg/m (25.2-35.5). Most patients (73%) were mechanically ventilated. Approximately half (51%) were identified as having diabetes prior to ICU admission. Patients in the intervention arm received less insulin over the 48 h study period than those in the control group (mean insulin units over study period (95% CI) 45.0 (24.4-68.7) vs. 107 (56.1-157.9) units; p = 0.02) and had lower mean glycaemic variability (12.6 vs. 15.9%, p = 0.01). There was a small difference in the mean percentage of energy requirements met (intervention: 72.9 vs. control: 79.1%; p = 0.4) or protein delivered (78.2 vs. 85.4%; p = 0.3).

Conclusions: A low carbohydrate formula was associated with reduced insulin use and glycaemic variability in enterally-fed critically ill patients with hyperglycaemia. Further large trials are required to determine the impact of this formula on clinical outcomes. Registered under Australian and New Zealand Clinical Trials Registry, ANZCTR number: 12614000166673.
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http://dx.doi.org/10.1016/j.clnesp.2019.02.013DOI Listing
June 2019

Maternal Metyrapone Use During Breastfeeding: Safe for the Breastfed Infant.

J Endocr Soc 2019 May 18;3(5):973-978. Epub 2019 Mar 18.

University of Queensland, Faculty of Medicine, Queensland, Australia.

Context: Metyrapone is an inhibitor of endogenous adrenal corticosteroid synthesis, which has been proven to be a viable option in controlling maternal serum cortisol concentrations during pregnancy. The infant exposure to maternally ingested metyrapone through breast milk is, however, largely unknown.

Case Description: We report the excretion of metyrapone into breast milk and subsequent infant exposure from a lactating woman on 250 mg of metyrapone three times daily. Due to limited supply of breast milk, the infant was fed ∼50% breast milk and 50% formula. At steady state, the average concentrations in the studied breast milk and absolute and relative infant doses were 176 µg/L, 26.45 µg/kg/d, and 0.7%, respectively, for metyrapone, and 310 µg/L, 46.52 µg/kg/d, and 1.21% for its active metabolite metyrapol. The breastfed infant was found to have a plasma metyrapone concentration of 0.05 µg/L, with no evidence of disruption to his adrenocortical axis biochemically.

Conclusion: These findings indicate that maternal metyrapone use during breastfeeding did not pose a notable risk to this breastfed infant. The infants' exposure to metyrapone was further minimized by avoiding nursing for 2 to 3 hours after each metyrapone dose.
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http://dx.doi.org/10.1210/js.2018-00355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486806PMC
May 2019

Faecal Microbiota Are Related to Insulin Sensitivity and Secretion in Overweight or Obese Adults.

J Clin Med 2019 Apr 4;8(4). Epub 2019 Apr 4.

Monash Centre for Health Research and Implementation, School of Public Health and Preventive Medicine, Monash University, Diabetes and Vascular Medicine Unit, Monash Health, Clayton 3168, Australia.

Emerging evidence suggests a role for the gut microbiota in glucose metabolism and diabetes. Few studies have examined the associations between the faecal microbiome and insulin sensitivity and secretion using gold-standard methods in high-risk populations prior to diabetes onset. We investigated the relationships between faecal microbiota composition (16S rRNA sequencing) and gold-standard measures of insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and insulin secretion (intravenous glucose tolerance test) in 38 overweight or obese otherwise healthy individuals. Genus was positively associated with insulin sensitivity, and genera and were related to both insulin sensitivity and secretion. Insulin sensitivity was associated with a higher abundance of and lower abundance of . Those with higher insulin secretion had a higher abundance of and lower abundance of , compared to those with lower insulin secretion. Body mass index (BMI) was positively correlated with abundance whereas abundance was negatively correlated to BMI and percent body fat. These results suggest that faecal microbiota is related to insulin sensitivity and secretion in overweight or obese adults. These correlations are distinct although partially overlapping, suggesting different pathophysiological pathways. Our findings can inform future trials aiming to manipulate gut microbiome to improve insulin sensitivity and secretion and prevent type 2 diabetes.
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http://dx.doi.org/10.3390/jcm8040452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6518043PMC
April 2019

Hepatic paraganglioma hiding as a slowly growing lesion for 24 years: a diagnostic conundrum.

BMJ Case Rep 2019 Mar 22;12(3). Epub 2019 Mar 22.

Queensland Diabetes and Endocrine Centre, Mater Misericordiae Brisbane Ltd, South Brisbane, Queensland, Australia.

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http://dx.doi.org/10.1136/bcr-2018-228947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6510125PMC
March 2019

Probiotics for the Prevention of Gestational Diabetes Mellitus in Overweight and Obese Women: Findings From the SPRING Double-Blind Randomized Controlled Trial.

Diabetes Care 2019 03 18;42(3):364-371. Epub 2019 Jan 18.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Australia.

Objective: Given the role of gut microbiota in regulating metabolism, probiotics administered during pregnancy might prevent gestational diabetes mellitus (GDM). This question has not previously been studied in high-risk overweight and obese pregnant women. We aimed to determine whether probiotics ( and subspecies ) administered from the second trimester in overweight and obese women prevent GDM as assessed by an oral glucose tolerance test (OGTT) at 28 weeks' gestation. Secondary outcomes included maternal and neonatal complications, maternal blood pressure and BMI, and infant body composition.

Research Design And Methods: This was a double-blind randomized controlled trial of probiotic versus placebo in overweight and obese pregnant women in Brisbane, Australia.

Results: The study was completed in 411 women. GDM occurred in 12.3% (25 of 204) in the placebo arm and 18.4% (38 of 207) in the probiotics arm ( = 0.10). At OGTT, mean fasting glucose was higher in women randomized to probiotics (79.3 mg/dL) compared with placebo (77.5 mg/dL) ( = 0.049). One- and two-hour glucose measures were similar. Preeclampsia occurred in 9.2% of women randomized to probiotics compared with 4.9% in the placebo arm ( = 0.09). Excessive weight gain occurred in 32.5% of women in the probiotics arm (55 of 169) compared with 46% in the placebo arm (81 of 176) ( = 0.01). Rates of small for gestational age (<10th percentile) were 2.4% in the probiotics arm (5 of 205) and 6.5% in the placebo arm (13 of 199) ( = 0.042). There were no differences in other secondary outcomes.

Conclusions: The probiotics used in this study did not prevent GDM in overweight and obese pregnant women.
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http://dx.doi.org/10.2337/dc18-2248DOI Listing
March 2019

Arm and finger measurements in the third trimester: Implications for blood pressure measurement.

Pregnancy Hypertens 2018 Oct 5;14:105-109. Epub 2018 Sep 5.

The Royal Brisbane and Women's Hospital, Butterfield St, Herston, 4006 Queensland, Australia; The University of Queensland, St Lucia 4067, Queensland, Australia.

Objectives: To obtain arm and finger measurements of women ≥32 weeks gestation to determine: the requirement for different arm cuff sizes; the suitability of available finger cuffs in this population; the best predictor of arm conicity; the frequency of cuff placement on the forearm or leg.

Study Design: Prospective observational pilot study.

Main Outcome Measures: Right and left mid-arm circumference (MAC) and to compare these to the recommended cuff sizes; right and left finger circumference; right and left arm conicity; the responses of women to a three-point Likert scale regarding cuff placement.

Results: Measurements were obtained for 450 women at an Australian tertiary hospital with a median (IQR) gestation of 35.7 (34.0-37.0); 299 (66.4%) were Caucasian and 35 (7.8%) had gestational hypertension. The median (IQR) body mass index (BMI) was 29.6 kg/m (26.2-33.4), range 18.0-62.2. Median (IQR) right MAC was 29.9 cm (27.4-33), range 19.6-53.2. Based on right MAC, 58 (12.9%) required a large cuff and 6 (1.3%) a thigh cuff. Maximum right finger circumference was 7.0 cm. BMI, weight and right MAC were positively correlated with right arm conicity: r = 0.51, 0.42 and 0.45, p < 0.001 for all. R for each were 0.26, 0.17 and 0.20. Fourteen (3.1%) reported cuff placement on the forearm or leg.

Conclusions: A small percentage of women are likely to be unsuited to traditional arm cuffs. Available finger-cuffs would suit this population. BMI could potentially be used to select women with cone-shaped arms for future studies of alternative devices.
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http://dx.doi.org/10.1016/j.preghy.2018.09.002DOI Listing
October 2018

Primary Hyperparathyroidism in Pregnancy: Maternofetal Outcomes at a Quaternary Referral Obstetric Hospital, 2000 Through 2015.

J Clin Endocrinol Metab 2019 03;104(3):721-729

Royal Brisbane and Women's Hospital, Herston, Queensland, Australia.

Context: Primary hyperparathyroidism (PHPT) in pregnancy has historically been associated with substantial maternofetal morbidity and mortality rates. The optimal treatment and timing of surgical intervention in pregnancy remain contested.

Objective: To compare maternofetal outcomes of medically and surgically treated patients with PHPT in pregnancy.

Design: Retrospective chart review.

Setting: Quaternary referral hospital.

Patients: Women with PHPT in pregnancy treated between 1 January 2000 and 31 December 2015.

Interventions: Medical therapy or parathyroid surgery.

Main Outcomes Measured: Timing of diagnosis; maternal corrected serum calcium concentrations; gestation, indication and mode of delivery; complications attributable to PHPT; birth weight; and admission to the neonatal intensive care unit (NICU).

Results: Twenty-two pregnancies were managed medically, and six patients underwent parathyroidectomy in pregnancy (five in trimester 2, and one at 32 weeks gestation). Most patients treated medically either had a corrected serum calcium concentration <2.85 mmol/L in early pregnancy or had PHPT diagnosed in trimester 3. Of viable medically managed pregnancies, 30% were complicated by preeclampsia, and preterm delivery occurred in 66% of this group. All preterm neonates required admission to the NICU for complications related to prematurity. All surgically treated patients delivered their babies at term, and there were no complications of parathyroid surgery.

Conclusion: Maternofetal outcomes have improved relative to that reported in early medical literature in patients treated medically and surgically, but the rates of preeclampsia and preterm delivery were higher in medically treated patients. The study was limited by its retrospective design and small sample sizes.
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http://dx.doi.org/10.1210/jc.2018-01104DOI Listing
March 2019

Management of Amiodarone-Induced Thyrotoxicosis at a Cardiac Transplantation Centre.

Front Endocrinol (Lausanne) 2018 22;9:482. Epub 2018 Aug 22.

Department of Endocrinology, St Vincent's Hospital Sydney, Darlinghurst, NSW, Australia.

Amiodarone-induced thyrotoxicosis (AIT) is associated with significant morbidity and mortality, particularly in patients with cardiac failure. The aim of the study was to evaluate the management of AIT at a tertiary hospital specialising in cardiac failure and transplantation. Retrospective audit of 66 patients treated for AIT by Endocrinology (2007-2016), classified as type 1 (T1) or type 2 (T2) based on radiological criteria. Main outcome measurements were response rate to initial treatment, time to euthyroidism, and frequency/safety of thyroidectomy. Mean age was 60 ± 2 years; 80% were male. Sixty-four patients commenced medical treatment: thionamides (THIO) in 23, glucocorticoids (GC) in 17 and combination (COMB) in 24. Median thyroxine (fT4) was 35.1 (31.2-46.7) in THIO, 43.1 (30.4 -60.7) in GC, and 60.0 (39.0 ->99.9) pmol/L in COMB ( = 0.01). Initial therapy induced euthyroidism in 52%: 70% THIO, 53% GC, and 33% COMB ( = 0.045) by 100 (49-167), 47 (35-61), and 53 (45-99) days, respectively ( = 0.02). A further 11% became euthyroid after transitioning from monotherapy to COMB. Thyroidectomy was undertaken in 33%. Patients who underwent thyroidectomy were younger (54 ± 3 vs. 63 ± 2 years; = 0.03), with higher prevalence of severely impaired left ventricular function prior to diagnosis of AIT (38 vs. 18%; = 0.08). Despite median American Society of Anaesthesiologists classification 4, no thyroidectomy patient experienced cardiorespiratory complications/death. Patients with AIT had limited response to medical treatment. The poorest response was observed in COMB group, likely related to greater hyperthyroidism severity. Thyroidectomy is safe in patients with severe cardiac failure if performed in a centre with cardiac anaesthetic expertise. There should be low threshold for proceeding to thyroidectomy in patients with severe AIT and/or cardiac failure.
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http://dx.doi.org/10.3389/fendo.2018.00482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6113588PMC
August 2018

A Vegetarian Diet Is a Major Determinant of Gut Microbiota Composition in Early Pregnancy.

Nutrients 2018 Jul 12;10(7). Epub 2018 Jul 12.

School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia.

The composition of the gut microbiota can be influenced by dietary composition. In pregnancy, the maternal gut microbiome has associations with maternal and infant metabolic status. There is little known regarding the impact of a vegetarian diet in pregnancy on maternal gut microbiota. This study explored the gut microbiota profile in women who were vegetarian or omnivorous in early gestation. Women were selected from participants in the Study of PRobiotics IN Gestational diabetes (SPRING) randomised controlled trial. Nine women identified as vegetarians were matched to omnivorous women in a 1:2 ratio. Microbiota analyses were performed using 16S rRNA gene amplicon sequencing and analysed using the Quantitative Insights Into Microbial Ecology (QIIME) and Calypso software tools. There was no difference in alpha diversity, but beta diversity was slightly reduced in vegetarians. There were differences seen in the relative abundance of several genera in those on a vegetarian diet, specifically a reduction in , , and increases in the relative abundances of and . In this sub-analysis of gut microbiota from women in early pregnancy, a vegetarian as compared to omnivorous diet, was associated with a different gut microbiome, with features suggesting alterations in fermentation end products from a mixed acid fermentation towards more acetate/butyrate.
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http://dx.doi.org/10.3390/nu10070890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073691PMC
July 2018

Prevalence of maternal urinary ketones in pregnancy in overweight and obese women.

Obstet Med 2018 Jun 5;11(2):79-82. Epub 2017 Dec 5.

UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia.

Background: Ketonuria may be associated with adverse fetal outcomes. This study aimed to determine the prevalence of ketonuria at three time points in pregnancy and to assess whether ketonuria correlates with a clinical indication for performing a urine test.

Methods: Women had fasting urinary ketone levels measured at 16 and 28 weeks gestation and random ketone levels measured close to 36 weeks gestation. All ketone levels in the third trimester were recorded along with the clinical indication for the test.

Results: One hundred and eighty-seven women were included in the study. Twenty-two per cent of women had ketonuria at either 16 or 28 weeks gestation and 8% at 36 weeks gestation. Ketonuria was significantly more likely if a test was performed for a clinical indication ( = 0.0002).

Conclusion: Ketonuria in pregnancy is common affecting at least one in five women. Ketonuria is more common in women who have a clinical indication for performing a urine test.
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http://dx.doi.org/10.1177/1753495X17743163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038017PMC
June 2018

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

Br J Nutr 2018 08 23;120(3):283-289. Epub 2018 May 23.

2UQ Centre for Clinical Research,The University of Queensland,Herston,QLD 4029,Australia.

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.
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http://dx.doi.org/10.1017/S0007114518001149DOI Listing
August 2018

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

J Asthma 2019 06 8;56(6):594-602. Epub 2018 Jun 8.

a Priority Research Centre Grow Up Well, School of Medicine and Public Health , University of Newcastle, Hunter Medical Research Institute , New Lambton Heights , NSW , Australia.

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.
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http://dx.doi.org/10.1080/02770903.2018.1471709DOI Listing
June 2019

Low dietary fiber intake increases Collinsella abundance in the gut microbiota of overweight and obese pregnant women.

Gut Microbes 2018 13;9(3):189-201. Epub 2018 Mar 13.

a UQ Centre for Clinical Research, The University of Queensland , Brisbane , Australia.

The gut microbiota contributes to the regulation of glucose metabolism in pregnancy. Abundance of the genus Collinsella is positively correlated with circulating insulin; however, it is unclear what determines Collinsella abundance. This study aims to validate the correlation between Collinsella and insulin and to elucidate if macronutrient intake alters Collinsella abundance and gut microbiota composition. Gut microbiota profiles were assessed by 16S rRNA sequencing in 57 overweight and 73 obese pregnant women from the SPRING (Study of PRobiotics IN Gestational diabetes) trial at 16 weeks gestation and correlated with metabolic hormone levels and macronutrient intake. Gut microbiota composition in the top and bottom 10% of dietary fiber intake was evaluated through network analysis. Collinsella abundance correlated positively with circulating insulin (rho = 0.30, p = 0.0006), independent of maternal BMI, but negatively with dietary fiber intake (rho = -0.20, p = 0.025) in this cohort. Low dietary fiber intake was associated with a gut microbiota favoring lactate fermentation while high fiber intake promotes short-chain fatty acid-producing bacteria. Low dietary fiber may enable overgrowth of Collinsella and alter the overall fermentation pattern in gut microbiota. This suggests that dietary choices during pregnancy can modify the nutritional ecology of the gut microbiota, with potential deleterious effects on the metabolic and inflammatory health of the host.

Trial Registration: ANZCTR 12611001208998, registered 23/11/2011.
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http://dx.doi.org/10.1080/19490976.2017.1406584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219589PMC
September 2018

Successful Resuscitation of Maternal Cardiac Arrest With Disseminated Intravascular Coagulation Guided by Rotational Thromboelastometry and Transesophageal Echocardiography: A Case Report.

A A Pract 2018 Mar;10(6):139-143

From the Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; and The University of Queensland, St. Lucia, Queensland, Australia.

We present a case of maternal cardiac arrest during an elective cesarean delivery. Transesophageal echocardiography identified a large pulmonary artery mass, and guided resuscitation efforts. After return of spontaneous circulation, the patient developed disseminated intravascular coagulation with massive hemorrhage. Blood product selection and volume replacement were guided by rotational thromboelastometry and transesophageal echocardiography, respectively. Correction of coagulopathy was observed clinically and confirmed by rotational thromboelastometry. The patient fully recovered without neurological deficit.
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http://dx.doi.org/10.1213/XAA.0000000000000662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5862006PMC
March 2018

Hypertensive disorders of pregnancy.

BMJ 2017 07 13;358:j3245. Epub 2017 Jul 13.

Obstetric Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia

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http://dx.doi.org/10.1136/bmj.j3245DOI Listing
July 2017

Contributions of the maternal oral and gut microbiome to placental microbial colonization in overweight and obese pregnant women.

Sci Rep 2017 06 6;7(1):2860. Epub 2017 Jun 6.

UQ Centre for Clinical Research, The University of Queensland, Brisbane, Australia.

A distinct bacterial signature of the placenta was reported, providing evidence that the fetus does not develop in a sterile environment. The oral microbiome was suggested as a possible source of the bacterial DNA present in the placenta based on similarities to the oral non-pregnant microbiome. Here, the possible origin of the placental microbiome was assessed, examining the gut, oral and placental microbiomes from the same pregnant women. Microbiome profiles from 37 overweight and obese pregnant women were examined by 16SrRNA sequencing. Fecal and oral contributions to the establishment of the placental microbiome were evaluated. Core phylotypes between body sites and metagenome predictive functionality were determined. The placental microbiome showed a higher resemblance and phylogenetic proximity with the pregnant oral microbiome. However, similarity decreased at lower taxonomic levels and microbiomes clustered based on tissue origin. Core genera: Prevotella, Streptococcus and Veillonella were shared between all body compartments. Pathways encoding tryptophan, fatty-acid metabolism and benzoate degradation were highly enriched specifically in the placenta. Findings demonstrate that the placental microbiome exhibits a higher resemblance with the pregnant oral microbiome. Both oral and gut microbiomes contribute to the microbial seeding of the placenta, suggesting that placental colonization may have multiple niche sources.
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http://dx.doi.org/10.1038/s41598-017-03066-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460277PMC
June 2017