Effects of anti-malarial prophylaxes on maternal transfer of Immunoglobulin-G (IgG) and association to immunity against Plasmodium falciparum infections among children in a Ugandan birth cohort.

BACKGROUND: The in-utero transfer of malaria specific IgG to the fetus in Plasmodium falciparum infected pregnant women potentially plays a role in provision of immune protection against malaria in the first birth year. However, the effect of Intermittent Prophylactic Treatment in Pregnancy (IPTp) and placental malaria on the extent of in-utero antibody transfer in malaria endemic regions like Uganda remain unknown. The aim of this study was thus to establish the effect of IPTp on in-utero transfer of malaria specific IgG to the fetus and the associated immune protection against malaria in the first birth year of children born to mothers who had P. falciparum infection during pregnancy in Uganda. METHODS: We screened a total of 637 cord blood samples from a double blinded randomized clinical trial on Sulfadoxine-Pyrimethamine (SP) and Dihydroartemisinin-Piperaquine (DP) IPTp in a Ugandan birth cohort; study conducted from Busia, Eastern Uganda. Luminex assay was used to measure the cord levels of IgG sub-types (IgG1, IgG2, IgG3 and IgG4) against 15 different P. falciparum specific antigens, with tetanus toxoid (t.t) as a control antigen. Man-Whitney U test (non-parametric) in STATA (ver15) was used in statistical analysis of the samples. In addition, Multivariate cox regression analysis was used to determine the effect of maternal transfer of IgG on the incidence of malaria in the first birth year of children under study. RESULTS: Mothers on SP expressed higher levels of cord IgG4 against erythrocyte binding antigens (EBA140, EBA175 and EBA181) (p<0.05). Placental malaria did not affect cord levels of IgG sub-types against selected P. falciparum specific antigens (p>0.05). Children who expressed higher levels (75th percentile) of total IgG against the six key P. falciparum antigens (Pf SEA, Rh4.2, AMA1, GLURP, Etramp5Ag1 and EBA 175) had higher risk of malaria in the first birth year; AHRs: 1.092, 95% CI: 1.02-1.17 (Rh4.2); 1.32, 95% CI: 1.00-1.74 (PfSEA); 1.21, 95%CI: 0.97-1.52 (Etramp5Ag1); 1.25, 95%CI: 0.98-1.60 (AMA1); 1.83, 95%CI: 1.15-2.93 (GLURP) (GLURP), and 1.35,; 95%CI: 1.03-1.78 (EBA175). Children born to mothers categorized as poorest had the highest risk of malaria infections in the first birth year (AHR: 1.79, 95% CI: 1.31-2.4). Children born to mothers who had malaria infections during gestation had higher risk of getting malaria in the first birth year (AHR 1.30; 95%CI: 0.97-1.7). CONCLUSION: Malaria prophylaxis in pregnant mothers using either DP or SP does not affect expression of antibodies against P. falciparum specific antigens in the cord blood. Poverty and malaria infections during pregnancy are key risk factors of malaria infections in the first birth year of growth of children. Antibodies against P. falciparum specific antigens does not protect against parasitemia and malaria infections in the first birth year of children born in malaria endemic areas.

The ADIPS Pilot National Diabetes in Pregnancy Benchmarking Programme.

BACKGROUND: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia. METHODS: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services. RESULTS: The audit included 10,144 pregnancies (gestational diabetes mellitus (GDM) = 8696; type 1 diabetes (T1D) = 435; type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8-57.3%), metformin alone in 18.8% (0.4-43.7%), and metformin and insulin in 10.1% (1.5-23.4%); when compared between sites, all p < 0.001. Birth was by elective caesarean in 12.1% (3.6-23.7%) or emergency caesarean in 9.5% (3.5-21.2%) (all p < 0.001). Preterm births (<37 weeks) ranged from 3.7% to 9.4% (p < 0.05), large for gestational age 10.3-26.7% (p < 0.001), admission to special care nursery 16.7-25.0% (p < 0.001), and neonatal hypoglycaemia (<2.6 mmol/L) 6.0-27.0% (p < 0.001). Many women with T1D and T2D had limited pregnancy planning including first trimester hyperglycaemia (HbA1c > 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively (p < 0.001). CONCLUSION: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy.

Gestational diabetes - Major problems with post-partum testing.

BACKGROUND: Post-partum follow up testing of women with gestational diabetes mellitus (GDM) is important. All women, and their family doctors, receive written reminders. There are no recent major Australian reviews of the efficacy and compliance with this advice conducted in an ethnically representative population and using the current diagnostic criteria. AIM: The aim was to examine a cohort of women with recently diagnosed GDM and a completed pregnancy to determine what proportion had been tested and what were the difficulties in having testing carried out. METHODS: Women who were diagnosed with gestational diabetes and attended the Diabetes Service in 2017 were followed up in 2019. Attempted contact was made using an unidentified land line, an identifiable mobile phone and a postal survey. Compliance with testing advice was the major parameter considered. RESULTS: There were 714 women with GDM, 75 were excluded: 64 after pass one and 11 after pass two. In total, only 339/639 (53.1%) could be contacted. Of these women, 334 agreed to be surveyed; 207 (62.0%) had a post-partum test. Of the 127 women who had not had a test, 113 agreed to have an HbA1c. Only 13/113 (11.5%) had this done within a month. CONCLUSION: Contacting women, even within a short time after the pregnancy, is difficult. The number of post-partum tests carried out is suboptimal. Written advice to all women and their doctors does not appear to be working. A review of the cost effectiveness of this approach and development of new methods may be worthwhile.

Effectiveness and acceptability of a text message intervention (DTEXT) on HbA1c and self-management for people with type 2 diabetes. A randomized controlled trial.

OBJECTIVE: Determine the effectiveness and acceptability of a text message intervention (DTEXT) on HbA1c and self-management behaviors for Australian adults with type 2 diabetes. METHODS: Using intention to treat analysis and generalized estimating equations, this randomized controlled trial of 395 adults determined change in HbA1c at 3 and 6 months between the intervention and control group. Secondary outcomes included change in nutrition, physical activity, blood lipid profile, body mass index, quality of life, self-efficacy, medication taking and program acceptability. RESULTS: No significant difference was observed between the intervention or control group for HbA1c at 3 months (P = 0.23) or 6 months (P = 0.22). Significant improvements were seen in consumption of vegetables at 3 months (P < 0.001) and 6 months (P = 0.04); fruit at 3 months (P = 0.046) and discretionary sweet foods at 3 months (P = 0.02). No other significant effects seen. The intervention demonstrated high rates of acceptability (94.0%) and minimal withdrawal (1.5%). CONCLUSIONS: DTEXT was an acceptable text message intervention that improved some nutritional behaviors in people with type 2 diabetes, but did not significantly improve HbA1c or other outcomes. Further research is required to optimize DTEXT. PRACTICE IMPLICATIONS: DTEXT provides an acceptable, feasible form of self-management support that may complement existing diabetes care.

Gestational diabetes mellitus testing in the COVID-19 pandemic: The problems with simplifying the diagnostic process.

BACKGROUND: Multiple professional bodies have temporarily revised recommendations for gestational diabetes mellitus (GDM) testing during the COVID-19 pandemic to reduce person-to-person contact. The current Australian temporary criteria advise that if the fasting glucose is ≤4.6 mmol/L, then no glucose tolerance test (GTT) is required. AIMS: The aim of this study is to examine the extent of underdiagnosis of GDM using a fasting glucose ≤4.6 mmol/L as a cut-off to determine that a GTT is not necessary. MATERIALS AND METHODS: De-identified data from pregnant women having a GTT test in the Illawarra area during a six-year period was used to determine the number of women with GDM and the proportion of positive cases that would be missed for different fasting glucose values. RESULTS: There were 16 522 results identified and GDM was diagnosed in 12.2%. The majority of women were more than 30 years of age (85.2%) and diagnosed at ≥20 weeks gestation (81.1%). Of those diagnosed with GDM, 29% had a fasting glucose of ≤4.6 mmol/L and would have been missed. CONCLUSIONS: Our results show that using a fasting glucose of 4.6 mmol/L or less would miss nearly a third of women who would otherwise be diagnosed with GDM.

Routine glucose assessment in the emergency department for detecting unrecognised diabetes: a cluster randomised trial.

OBJECTIVE: To determine whether routine blood glucose assessment of patients admitted to hospital from emergency departments (EDs) results in higher rates of new diagnoses of diabetes and documentation of follow-up plans. DESIGN, SETTING: Cluster randomised trial in 18 New South Wales public district and tertiary hospitals, 31 May 2011 - 31 December 2012; outcomes follow-up to 31 March 2016. PARTICIPANTS: Patients aged 18 years or more admitted to hospital from EDs. INTERVENTION: Routine blood glucose assessment at control and intervention hospitals; automatic requests for glycated haemoglobin (HbA1c ) assessment and notification of diabetes services about patients at intervention hospitals with blood glucose levels of 14 mmol/L or more. MAIN OUTCOME MEASURE: New diagnoses of diabetes and documented follow-up plans for patients with admission blood glucose levels of 14 mmol/L or more. RESULTS: Blood glucose was measured in 133 837 patients admitted to hospital from an ED. The numbers of new diabetes diagnoses with documented follow-up plans for patients with blood glucose levels of 14 mmol/L or more were similar in intervention (83/506 patients, 16%) and control hospitals (73/278, 26%; adjusted odds ratio [aOR], 0.83; 95% CI 0.42-1.7; P = 0.61), as were new diabetes diagnoses with or without plans (intervention, 157/506, 31%; control, 86/278, 31%; aOR, 1.51; 95% CI, 0.83-2.80; P = 0.18). 30-day re-admission (31% v 22%; aOR, 1.34; 95% CI, 0.86-2.09; P = 0.21) and post-hospital mortality rates (24% v 22%; aOR, 1.07; 95% CI, 0.74-1.55; P = 0.72) were also similar for patients in intervention and control hospitals. CONCLUSION: Glucose and HbA1c screening of patients admitted to hospital from EDs does not alone increase detection of previously unidentified diabetes. Adequate resourcing and effective management pathways for patients with newly detected hyperglycaemia and diabetes are needed. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12611001007921.

Brief Report: Yield and Efficiency of Intensified Tuberculosis Case-Finding Algorithms in 2 High-Risk HIV Subgroups in Uganda.

BACKGROUND: Tuberculosis (TB) risk varies among different HIV subgroups, potentially impacting intensified case finding (ICF) performance. We evaluated the performance of the current ICF algorithm [symptom screening, followed by Xpert MTB/RIF (Xpert) testing] in 2 HIV subgroups and evaluated whether ICF performance could be improved if TB screening was based on C-reactive protein (CRP) concentrations. METHODS: We enrolled consecutive adults with CD4 counts ≤350 cells/µL initiating antiretroviral therapy and performed symptom screening, CRP testing using a low-cost point-of-care (POC) assay, and collected sputum for Xpert testing. We compared the yield and efficiency of the current ICF algorithm to POC CRP-based ICF among patients new to HIV care and patients engaged in care. RESULTS: Of 1794 patients, 126/1315 (10%) new patients and 21/479 (4%) engaged patients had Xpert-positive TB. The current ICF algorithm detected ≥98% of all TB cases in both subgroups but required ≥85% of all patients to undergo Xpert testing. POC CRP-based ICF halved the proportion of patients in both subgroups requiring Xpert testing relative to the current ICF algorithm and had lower yield among patients engaged in care [81% vs. 100%, difference -19% (95% confidence interval: -41 to 3)]. Among patients new to care, POC CRP-based ICF had similar yield as the current ICF algorithm [93% vs. 98%, difference -6% (95% confidence interval: -11 to 0)]. CONCLUSIONS: Among patients new to care, POC CRP-based screening can improve ICF efficiency without compromising ICF yield, whereas symptom-based screening may be necessary to maximize ICF yield among patients engaged in care.

Seasonality, temperature and pregnancy oral glucose tolerance test results in Australia.

BACKGROUND: The oral glucose-tolerance test (OGTT) is currently the standard method for diagnosis of gestational diabetes (GDM). We conducted a post hoc analysis using the Australian Hyperglycemia and Adverse Pregnancy Outcome (HAPO) data to determine seasonal variations in OGTT results, the consequent prevalence of GDM, and association with select perinatal parameters. METHOD: Women enrolled in the Australian HAPO study sites (Brisbane and Newcastle) from 2001 to 2006 were included if OGTT results between 24 to 32 weeks gestation were available (n = 2120). Fasting plasma glucose, 1-h plasma glucose, 2-h plasma glucose, HbA1c, HOMA-IR, and umbilical cord C-peptide and glucose values were categorized by season and correlated to monthly temperature records from the Australian Bureau of Meteorology for Brisbane and Newcastle. GDM was defined post hoc using the IADPSG/WHO criteria. RESULTS: Small but significant (p <  0.01 on ANOVA) elevations in fasting glucose (+ 0.12 mM), HbA1c (+ 0.09%), and HOMA-IR (+ 0.88 units) were observed during the winter months. Conversely, higher 1-h (+ 0.19 mM) and 2-h (+ 0.33 mM) post-load glucose values (both p <  0.01) were observed during the summer months. The correlations between fasting glucose, 1-h glucose, 2-h glucose, and HbA1c with average monthly temperatures confirmed this trend, with positive Pearson's correlations between 1-h and 2-h glucose with increasing average monthly temperatures, and negative correlations with fasting glucose and HbA1c. Further, umbilical cord C-peptide and glucose displayed negative Pearson's correlation with average monthly temperature, aligned with trends seen in the fasting plasma glucose. Overall prevalence of GDM did not display significant seasonal variations due to the opposing trends seen in the fasting versus 1-h and 2-h post-load values. CONCLUSION: A significant winter increase was observed for fasting plasma glucose, HbA1c, and HOMA-IR, which contrasted with changes in 1-h and 2-h post-load venous plasma glucose values. Interestingly, umbilical cord C-peptide and glucose displayed similar trends to that of the fasting plasma glucose. While overall prevalence of GDM did not vary significantly by seasons, this study illustrates that seasonality is indeed an additional factor when interpreting OGTT results for the diagnosis of GDM and provides new direction for future research into the seasonal adjustment of OGTT results.

DTEXT - text messaging intervention to improve outcomes of people with type 2 diabetes: protocol for randomised controlled trial and cost-effectiveness analysis.

BACKGROUND: Diabetes prevalence is rapidly increasing, with type 2 diabetes predicted to be the leading contributor of non-communicable disease in Australia by 2020. It is anticipated that rates of type 2 diabetes will continue to increase if factors such as overweight and obesity, low physical activity and poor nutrition are not addressed. The majority of Australians with type 2 diabetes do not meet the guidelines for optimal diabetes management, and access to diabetes education is limited. This highlights the need for new interventions that can reduce existing barriers to diabetes education, attain greater population reach and support self-management strategies for people with type 2 diabetes. Mobile phone text messages have shown promising results as an intervention for people with chronic disease. They have the ability to achieve high levels of engagement and broad population reach, whilst requiring minimal resources. There is however, no evidence on the effect of text messaging to improve the health of people with type 2 diabetes in Australia. METHODS/DESIGN: This randomised controlled trial aims to investigate if a 6 month text message intervention (DTEXT) can lead to improvements in glycated haemoglobin (HbA1c) and diabetes self-management among Australian residents in New South Wales (NSW) with type 2 diabetes. Community dwelling adults (n = 340) will be recruited with the primary outcome being change in HbA1c at 6 months. Secondary outcomes include behaviour change for diabetes self-management, self-efficacy, quality of life and intervention acceptability. An economic evaluation will be conducted using a funder plus patient perspective. DISCUSSION: This study will provide evidence on the effectiveness and cost effectiveness of a text message intervention to reduce HbA1c and enhance self-management of type 2 diabetes in the Australian population. If successful, this intervention could be used as a model to complement and extend existing diabetes care in the Australian health care system. TRIAL REGISTRATION: The study has been registered with the Australian New Zealand Clinical Trials Registry, Trial ID: ACTRN12617000416392 . Registered: 23 March 2017.

A cautionary response to SMFM statement: pharmacological treatment of gestational diabetes.

Use of oral agents to treat gestational diabetes mellitus remains controversial. Recent recommendations from the Society for Maternal-Fetal Medicine assert that metformin may be a safe first-line alternative to insulin for gestational diabetes mellitus treatment and preferable to glyburide. However, several issues should give pause to the widespread adoption of metformin use during pregnancy. Fetal concentrations of metformin are equal to maternal, and metformin can inhibit growth, suppress mitochondrial respiration, have epigenetic modifications on gene expression, mimic fetal nutrient restriction, and alter postnatal gluconeogenic responses. Because both the placenta and fetus express metformin transporters and exhibit high mitochondrial activity, these properties raise important questions about developmental programming of metabolic disease in offspring. Animal studies have demonstrated that prenatal metformin exposure results in adverse long-term outcomes on body weight and metabolism. Two recent clinical randomized controlled trials in women with gestational diabetes mellitus or polycystic ovary syndrome provide evidence that metformin exposure in utero may produce a metabolic phenotype that increases childhood weight or obesity. These developmental programming effects challenge the conclusion that metformin is equivalent to insulin. Although the Society for Maternal-Fetal Medicine statement endorsed metformin over glyburide if oral agents are used, there are few studies directly comparing the 2 agents and it is not clear that metformin alone is superior to glyburide. Moreover, it should be noted that prior clinical studies have dosed glyburide in a manner inconsistent with its pharmacokinetic properties, resulting in poor glycemic control and high rates of maternal hypoglycemia. We concur with the American Diabetes Association and American Congress of Obstetricians and Gynecologists, which recommend insulin as the preferred agent, but we believe that it is premature to embrace metformin as equivalent to insulin or superior to glyburide. Due to the uncertainty of the long-term metabolic risks of either metformin or glyburide, we call for carefully controlled studies that optimize oral medication dosing according to their pharmacodynamic and pharmacokinetic properties in pregnancy, appropriately target medications based on individual patterns of hyperglycemia, and follow the offspring long-term for metabolic risk.