Publications by authors named "Leonie K Callaway"

81 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

Fetal ultrasound scans to guide management of gestational diabetes: Improved neonatal outcomes in routine clinical practice.

Diabetes Res Clin Pract 2021 Mar 13;173:108696. Epub 2021 Feb 13.

Women's & Newborn Services, Royal Brisbane & Women's Hospital, Cnr Butterfield St and Bowen Bridge Rd, Herston, Queensland 4029, Australia; Faculty of Medicine, The University of Queensland, Mayne Medical Building, 288 Herston Road, Herston, Queensland 4006, Australia.

Aims: Some guidelines recommend altering glycemic targets in gestational diabetes mellitus (GDM) based on ultrasound measurements of fetal growth, but the impact on outcomes in clinical practice is unknown. The aim of this study was to compare the effects of ultrasound-guided and non-ultrasound-guided management on neonatal outcomes.

Methods: This was a retrospective, observational study of a random sample of women with GDM and their infants. Outcomes were compared between those who had GDM management tailored according to fetal growth and those who did not.

Results: In the sample of 221 women, 134 had documentation of ultrasound-guided management while 87 did not. There was no significant difference in size-for-gestational age between groups. Fewer neonates in the ultrasound-guided management group were admitted to the Special Care or Intensive Care Nursery (29.1% vs. 48.3%, P = 0.004), had a prolonged hospital stay (3.7% vs. 13.8%, P = 0.006), or had hypoglycemia after birth (42.5% vs. 56.3%, P = 0.045). The reduction in admission rates and prolonged hospital stays remained significant after controlling for confounding variables.

Conclusions: Ultrasound-guided management was independently associated with improvements in some neonatal outcomes.
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http://dx.doi.org/10.1016/j.diabres.2021.108696DOI Listing
March 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

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

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

The Role of Childhood Adversity in the Development of Gestational Diabetes.

Am J Prev Med 2019 09 25;57(3):302-310. Epub 2019 Jul 25.

School of Public Health, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.

Introduction: The influence of women's childhood psychosocial environment and subsequent preconception mental health on risk of developing gestational diabetes mellitus is unclear. This study examines this relationship.

Methods: Data from a population-based cohort study, the Australian Longitudinal Study on Women's Health, were used. A total of 6,317 women with no pre-existing diabetes were followed from 1996 (aged 18-23 years) until 2015. Gestational diabetes mellitus diagnosis was self-reported. Exposures to eight subcategories of adverse childhood experiences were recalled. Individual subcategories and total number of adverse childhood experiences were examined. Log-binomial regression models with generalized estimating equations were used to estimate RRs and 95% CIs. Analyses were adjusted for early life, preconception, and antenatal gestational diabetes mellitus risk factors. Effect modification by preconception mental health was tested using cross-product terms. Analyses were conducted in 2018.

Results: Among 11,556 pregnancies, 4.7% were complicated by gestational diabetes mellitus. Compared with women not exposed to adverse childhood experiences, exposure to any three adverse childhood experiences (6% of women, adjusted RR=1.73, 95% CI=1.02, 3.01) or four or more adverse childhood experiences (7%, adjusted RR=1.76, 95% CI=1.04, 2.99) was associated with elevated gestational diabetes mellitus risk in women with preconception depressive symptoms. Among the subcategories of adverse childhood experiences, physical abuse, and household substance abuse were associated with higher gestational diabetes mellitus risk. Adverse childhood experiences were not associated with gestational diabetes mellitus in women without depressive symptoms before pregnancy (p=0.01, for interaction).

Conclusions: These findings suggest that, in addition to primary prevention of childhood adversity, strategies to curb poor mental health trajectories among women exposed to adverse childhood experiences may contribute to prevention of gestational diabetes mellitus.
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http://dx.doi.org/10.1016/j.amepre.2019.04.028DOI Listing
September 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

Preconception risk of gestational diabetes: Development of a prediction model in nulliparous Australian women.

Diabetes Res Clin Pract 2018 Dec 5;146:48-57. Epub 2018 Oct 5.

School of Public Health, Faculty of Medicine, The University of Queensland, Brisbane, Australia.

Aim: To develop a prediction model for preconception identification of women at risk of gestational diabetes mellitus (GDM).

Methods: Data from a prospective cohort, the Australian Longitudinal Study on Women's Health, were used. Nulliparous women aged 18-23 who reported a pregnancy up to age 37-42 were included. Preconception predictors of GDM during a first pregnancy were selected using logistic regression. Regression coefficients were multiplied by a shrinkage factor estimated with bootstrapping to improve prediction in external populations.

Results: Among 6504 women, 314 (4.8%) developed GDM during their first pregnancy. The final prediction model included age at menarche, proposed age at future first pregnancy, ethnicity, body mass index, diet, physical activity, polycystic ovary syndrome, and family histories of type 1 or 2 diabetes and GDM. The model showed good discriminative ability with a C-statistic of 0.79 (95% CI 0.76, 0.83) after internal validation. More than half of the women (58%) were classified to be at risk of GDM (>2% predicted risk), with corresponding sensitivity and specificity values of 91% and 43%.

Conclusions: Nulliparous women at risk of GDM in a future first pregnancy can be accurately identified based on preconception lifestyle and health-related characteristics. Further studies are needed to test our model in other populations.
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http://dx.doi.org/10.1016/j.diabres.2018.09.021DOI Listing
December 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

Maternal overweight and obesity: where to from here?

Med J Aust 2018 02;208(3):112-113

Royal Brisbane and Women's Hospital, Brisbane, QLD.

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http://dx.doi.org/10.5694/mja17.01128DOI Listing
February 2018

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

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

Obstetric risk score - revalidated for triaging high-risk pregnancies in rural areas.

Aust N Z J Obstet Gynaecol 2017 Feb;57(1):63-67

The University of Queensland School of Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.

Background: A pregnancy risk score system in popular use in provincial and rural Queensland to assist with the triage decisions regarding the appropriate facility for pregnancy care has been upgraded with more recently recognised pregnancy risk factors.

Aims: To review the usefulness of the revised pregnancy risk score system and the integrity of its continuing use.

Materials And Methods: 459 women attending regional/rural hospitals and 1963 women attending a major specialist hospital for their pregnancy care had a prospective risk score assessed, and the resulting score was examined in relationship to pregnancy outcomes.

Results: There was a statistically significant positive relationship between a risk score of eight or more and an adverse outcome and a statistically significant negative relationship between a risk score of zero or one and adverse outcomes.

Conclusion: This study revalidates the risk score process for use in provincial and rural Queensland in delineating those women requiring care in a location with higher levels of clinical service capability. Women with a risk score of 8 or more have an increased likelihood of needing birth intervention and/or having an adverse neonatal outcome and should be recognised as needing the development of a multidisciplinary care plan and assessment in a facility that is appropriately resourced for their end of pregnancy care.
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http://dx.doi.org/10.1111/ajo.12579DOI Listing
February 2017

Antibiotic treatment at delivery shapes the initial oral microbiome in neonates.

Sci Rep 2017 02 27;7:43481. Epub 2017 Feb 27.

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

Oral microorganisms are important determinants of health and disease. The source of the initial neonatal microbiome and the factors dictating initial human oral microbiota development are unknown. This study aimed to investigate this in placental, oral and gut microbiome profiles from 36 overweight or obese mother-baby dyads as determined by 16S rRNA sequencing. Expression of five antibiotic resistance genes of the β-lactamase class was analysed in the infant oral microbiota samples by QPCR. The neonatal oral microbiota was 65.35% of maternal oral, 3.09% of placental, 31.56% of unknown and 0% of maternal gut origin. Two distinct neonatal oral microbiota profiles were observed: one strongly resembling the maternal oral microbiota and one with less similarity. Maternal exposure to intrapartum antibiotics explained the segregation of the profiles. Families belonging to Proteobacteria were abundant after antibiotics exposure while the families Streptococcaceae, Gemellaceae and Lactobacillales dominated in unexposed neonates. 26% of exposed neonates expressed the Vim-1 antibiotic resistance gene. These findings indicate that maternal intrapartum antibiotic treatment is a key regulator of the initial neonatal oral microbiome.
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http://dx.doi.org/10.1038/srep43481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378909PMC
February 2017

Prospective Relationships between Health Cognitions and Excess Gestational Weight Gain in a Cohort of Healthy and Overweight Pregnant Women.

J Acad Nutr Diet 2017 Aug 9;117(8):1198-1209. Epub 2017 Feb 9.

Background: Excess gestational weight gain (GWG) contributes to long-term obesity in mothers and children. To guide the tailoring of interventions to prevent excess GWG, a better understanding is needed of the lifestyle-related health cognitions that influence women's attempts to manage GWG.

Objective: To examine the relationship between health cognitions and excess GWG for women who enter pregnancy at a healthy weight (body mass index <25) or overweight (body mass index ≥25). It was hypothesized that health cognitions with a positive (negative) influence on health behavior would be associated with lower (higher) likelihood of excess GWG and that specific associations would differ between weight status groups.

Design: This prospective, observational study commenced when participants were <20 weeks' gestation, continuing until the end of their pregnancy. A self-administered quantitative survey at recruitment assessed prepregnancy weight and lifestyle-related health cognitions. Height was measured at 16 weeks and weight at 36 weeks using standard procedures.

Participants And Setting: A consecutive sample of pregnant women (n=715) were recruited from an Australian metropolitan hospital between August 2010 and January 2011. All women <20 weeks' gestation were eligible unless they had preexisting type 1 or 2 diabetes or insufficient English language skills to complete questionnaires.

Main Outcome Measures: Excess GWG defined according to Institute of Medicine 2009 recommendations and predisposing, reinforcing, and enabling cognitions for lifestyle health behaviors.

Statistical Analyses Performed: Logistic regression analyses examined associations between health cognitions and excess GWG stratified for prepregnancy weight status.

Results: For healthy-weight women, higher weight locus of control scores were protective against excess GWG (odds ratio 0.6, 95% CI 0.4 to 0.8), whereas higher perceived risk scores (personal risk and risk arising from prepregnancy weight) (odds ratio 1.3, 95% CI 1.1 to 1.7) were associated with excess GWG. For overweight women higher negative outcome expectation scores were associated with an increased risk of excess GWG (odds ratio 1.4, 95% CI 1.1 to 2.0).

Conclusions: Lifestyle-related health cognitions are associated with excess GWG and differed by prepregnancy weight status, suggesting the need to tailor behavior change interventions accordingly.
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http://dx.doi.org/10.1016/j.jand.2016.12.011DOI Listing
August 2017

Home Monitoring of Fasting and Postprandial Triglycerides in Late Pregnancy: A Pilot Study.

Diabetes Care 2017 01 8;40(1):e1-e2. Epub 2016 Nov 8.

School of Medicine, The University of Queensland, Brisbane, Australia.

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http://dx.doi.org/10.2337/dc16-2181DOI Listing
January 2017

Increased Systolic and Diastolic Blood Pressure Is Associated With Altered Gut Microbiota Composition and Butyrate Production in Early Pregnancy.

Hypertension 2016 10 15;68(4):974-81. Epub 2016 Aug 15.

From the School of Medicine (L.F.G.-A., H.L.B., H.D.M., L.K.C., M.D.N.), UQ Centre for Clinical Research (L.F.G.-A., H.L.B., L.K.C., M.D.N.), Mater Research Institute (H.D.M.), and Diamantina Institute, Faculty of Medicine and Biomedical Sciences (M.M.), The University of Queensland, Brisbane, Australia; and Obstetric Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia (H.L.B., L.K.C.).

The risk of developing pregnancy-induced hypertension and preeclampsia is higher in obese pregnant women. In obesity, the composition of the gut microbiota is altered. Obesity is also associated with low-grade inflammation. Metabolites from the gut microbiota may contribute to both hypertension and inflammation. The aim of this study is to investigate whether the composition of the gut microbiota in overweight and obese pregnant women is associated with blood pressure and levels of plasminogen activator inhibitor-1. The composition of the gut microbiota was determined with 16S ribosomal RNA sequencing in 205 women at 16 weeks gestation from the SPRING study (the Study of Probiotics in Gestational Diabetes). Expression of butyrate-producing genes in the gut microbiota was assessed by real-time polymerase chain reaction. Plasminogen activator inhibitor-1 levels were measured in fasting serum of a subset of 70 women. Blood pressure was slightly but significantly higher in obese compared with overweight women. The abundance of the butyrate-producing genus Odoribacter was inversely correlated with systolic blood pressure. Butyrate production capacity was decreased, but plasminogen activator inhibitor-1 concentrations increased in obese pregnant women. Plasminogen activator inhibitor-1 levels were inversely correlated with expression of butyrate kinase and Odoribacter abundance. This study shows that in overweight and obese pregnant women at 16 weeks gestation, the abundance of butyrate-producing bacteria and butyrate production in the gut microbiota is significantly negatively associated with blood pressure and with plasminogen activator inhibitor-1 levels. Increasing butyrate-producing capacity may contribute to maintenance of normal blood pressure in obese pregnant women.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.07910DOI Listing
October 2016

Connections Between the Gut Microbiome and Metabolic Hormones in Early Pregnancy in Overweight and Obese Women.

Diabetes 2016 08 23;65(8):2214-23. Epub 2016 May 23.

School of Medicine, The University of Queensland, Brisbane, Queensland, Australia The University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia

Overweight and obese women are at a higher risk for gestational diabetes mellitus. The gut microbiome could modulate metabolic health and may affect insulin resistance and lipid metabolism. The aim of this study was to reveal relationships between gut microbiome composition and circulating metabolic hormones in overweight and obese pregnant women at 16 weeks' gestation. Fecal microbiota profiles from overweight (n = 29) and obese (n = 41) pregnant women were assessed by 16S rRNA sequencing. Fasting metabolic hormone (insulin, C-peptide, glucagon, incretin, and adipokine) concentrations were measured using multiplex ELISA. Metabolic hormone levels as well as microbiome profiles differed between overweight and obese women. Furthermore, changes in some metabolic hormone levels were correlated with alterations in the relative abundance of specific microbes. Adipokine levels were strongly correlated with Ruminococcaceae and Lachnospiraceae, which are dominant families in energy metabolism. Insulin was positively correlated with the genus Collinsella. Gastrointestinal polypeptide was positively correlated with the genus Coprococcus but negatively with family Ruminococcaceae This study shows novel relationships between gut microbiome composition and the metabolic hormonal environment in overweight and obese pregnant women at 16 weeks' gestation. These results suggest that manipulation of the gut microbiome composition may influence pregnancy metabolism.
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http://dx.doi.org/10.2337/db16-0278DOI Listing
August 2016

Successful vaginal delivery following spontaneous adrenal haemorrhage at term.

BMJ Case Rep 2016 May 17;2016. Epub 2016 May 17.

University of Queensland School of Medicine, Herston, Queensland, Australia University of Queensland Centre for Clinical Research, Herston, Queensland, Australia Department of Obstetric and Internal Medicine, University of Queensland School of Medicine, Herston, Queensland, Australia.

Spontaneous adrenal haemorrhage (SAH) is a rare event in the general population, estimated to be around 0.3-1.8%. The exact incidence in pregnancy is unknown but rare. Most cases of SAH at or near term have presented with massive haemorrhage and haemodynamic instability, requiring emergency caesarean delivery or intrauterine fetal death. This is the first reported case of a successful vaginal delivery after acute, spontaneous, left adrenal haemorrhage at term.
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http://dx.doi.org/10.1136/bcr-2016-215096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4885332PMC
May 2016

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.

BMC Pregnancy Childbirth 2016 05 17;16:111. Epub 2016 May 17.

Department of Respiratory and Sleep Medicine, John Hunter Hospital, Lookout Road, New Lambton Heights, Newcastle, NSW, 2305, Australia.

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 .
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http://dx.doi.org/10.1186/s12884-016-0890-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869189PMC
May 2016

What does "futility" mean? An empirical study of doctors' perceptions.

Med J Aust 2016 May;204(8):318

University of Queensland, Brisbane, QLD.

Objective: To investigate how doctors define and use the terms "futility" and "futile treatment" in end-of-life care.

Design, Setting, Participants: A qualitative study using semi-structured interviews with 96 doctors from a range of specialties which treat adults at the end of life. Doctors were recruited from three large Brisbane teaching hospitals and were interviewed between May and July 2013.

Results: Doctors' conceptions of futility focused on the quality and prospect of patient benefit. Aspects of benefit included physiological effect, weighing benefits and burdens, and quantity and quality of life. Quality and length of life were linked, but many doctors discussed instances in which benefit was determined by quality of life alone. Most described assessing the prospects of achieving patient benefit as a subjective exercise. Despite a broad conceptual consensus about what futility means, doctors noted variability in how the concept was applied in clinical decision making. More than half the doctors also identified treatment that is futile but nevertheless justified, such as short term treatment that supports the family of a dying person.

Conclusions: There is an overwhelming preference for a qualitative approach to assessing futility, which inevitably involves variability in clinical decision making. Patient benefit is at the heart of doctors' definitions of futility. Determining patient benefit requires discussing with patients and their families their values and goals as well as the burdens and benefits of further treatment.
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http://dx.doi.org/10.5694/mja15.01103DOI Listing
May 2016