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Aim: With no current randomized trials, we explored the impact of tight compared with standard treatment targets on pregnancy outcomes in gestational diabetes mellitus (GDM). Method(s): This cohort study of singleton births >= 28 weeks' gestation was conducted at two major Australian maternity services (2009-2013). Standardized maternal, neonatal and birth outcomes were examined using routine healthcare data and compared for women with GDM at Service One (n = 2885) and Service Two (n = 1887). Services applied different treatment targets: Service One (standard targets, reference group) fasting < 5.5 mmol/l, 2-h postprandial < 7.0 mmol/l; Service Two (tight targets) fasting < 5.0 mmol/l, 2-h postprandial < 6.7 mmol/l. Multivariable regression with propensity score adjustment was used to examine associations between targets and outcomes. Result(s): GDM prevalence and insulin use were 7.9% and 31% at Service One, and 5.7% and 46% at Service Two. There were no differences in primary outcomes: birthweight > 90th centile [adjusted odds ratio (OR) 1.06, 95% confidence interval (CI) 0.87-1.30] and < 10th centile (OR 0.84, 95% CI 0.70-1.01), or secondary outcomes gestational hypertension, pre-eclampsia, shoulder dystocia or a perinatal composite. Service Two with tight targets had increased induction of labour (OR 3.63, 95% CI 3.17-4.16), elective Caesarean section (OR 1.75, 95% CI 1.37-2.23) and Apgar scores < 7 at 5 min (OR 1.54, 95% CI 1.05-2.25), decreased hypoglycaemia (OR 0.76, 95% CI 0.61-0.94]), jaundice (OR 0.47, 95% CI 0.35-0.63) and respiratory distress (OR 0.68, 95% CI 0.47-0.98). Conclusion(s): Tight GDM treatment targets were associated with greater insulin use and no difference in primary birthweight outcomes. The service with tight targets had higher obstetric intervention, lower rates of reported hypoglycaemia, jaundice, respiratory distress and lower Apgar scores. High-quality interventional data are required before tight treatment targets can be implemented

Background: Clinical risk prediction tools for gestational diabetes (GDM) may be enhanced by measuring biomarkers in early pregnancy. Aim(s): To evaluate a two-step GDM risk prediction tool incorporating fasting glucose (FG) and serum biomarkers in early pregnancy. Material(s) and Method(s): High molecular weight (HMW) adiponectin, omentin-1 and interleukin-6 (IL-6) were measured at 12-15 weeks gestation in women with high risk of GDM from a randomised trial using a clinical risk prediction tool. GDM diagnosis (24-28 weeks) was evaluated using 1998 Australian Diabetes in Pregnancy (ADIPS) criteria and newer International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria. Associations between biomarkers and development of GDM were examined using multivariable regression analysis. Area under the receiver-operator curve (AUC), sensitivity and specificity were calculated to determine classification ability of each model compared to FG and maternal characteristics. Result(s): HMW adiponectin improved prediction of ADIPS GDM (AUC 0.85, sensitivity 50%, specificity 96.2%, P = 0.04), compared to FG and maternal factors (0.78, 35% and, 98.1%, respectively). HMW adiponectin <1.53 mug/mL further improved the model (AUC 0.87, sensitivity 75%, specificity 88.2%, P = 0.01). HMW adiponectin did not improve prediction of IADPSG GDM (AUC 0.84, sensitivity 64%, specificity 97.9%, P = 0.22) compared to FG and maternal factors (0.79, 56%, 93.8%). Omentin-1 and IL-6 did not significantly improve classification ability for GDM. Conclusion(s): A two-step approach combining FG and HMW adiponectin to a validated clinical risk prediction tool improved sensitivity and predictive ability for ADIPS GDM. Further research is required to enhance GDM prediction using IADPSG criteria for application in clinical practice.Copyright © 2018 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists

Objective: To examine the role of high-molecular-weight (HMW) adiponectin and its relationship to sympathetic activity in women with polycystic ovary syndrome (PCOS). Design(s): Cross sectional study using biobanked samples. Setting(s): Not applicable. Patient(s): Premenopausal women with PCOS (n = 46, Rotterdam diagnostic criteria) and without PCOS (n = 22). Intervention(s): None. Main Outcome Measure(s): High-molecular-weight adiponectin levels with secondary outcomes of sympathetic activity and leptin levels. Result(s): The high-molecular-weight adiponectin level was lower in women with PCOS (median 2.2 [interquartile range (IQR)2.3] mug/mL) than in controls (median 3 [IQR2.5] mug/mL) (age and BMI adjusted), and it correlated inversely with the values measured for homeostatic model of assessment of insulin resistance (HOMA-IR), fasting insulin, triglycerides, and free androgen index and positively with sex hormone-binding globulin (SHBG) and high-density lipoprotein cholesterol in all participants and in the PCOS group. In the PCOS group, sympathetic activity (burst frequency) was statistically significantly higher than in controls (median 26 [IQR11] vs. median 22 [IQR14], respectively) and correlated inversely with HMW adiponectin (r = -0.230). The leptin levels were similar between the women with PCOS and controls and did not statistically significantly correlate with HMW adiponectin or sympathetic activity. On multiple regression analysis, burst frequency and SHBG explained 40% of the HMW adiponectin variability (B = -0.7; 95% CI -1.2 to -0.2; and B = 0.01; 95% CI 0.004-0.01) in PCOS. Conclusion(s): Alongside insulin resistance, increased sympathetic activity is associated with and may modulate HMW adiponectin levels in women with PCOS.Copyright © 2017 American Society for Reproductive Medicine

Background: The association between Institute of Medicine (IOM) guidelines and pregnancy outcomes across ethnicities is uncertain. We evaluated the associations of gestational weight gain (GWG) outside 2009 IOM guidelines, with maternal and infant outcomes across the USA, western Europe and east Asia, with subgroup analyses in Asia. The aim was to explore ethnic differences in maternal prepregnancy body mass index (BMI), GWG and health outcomes across these regions. Method(s): Systematic review, meta-analysis and meta-regression of observational studies were used for the study. MEDLINE, MEDLINE In-Process, Embase and all Evidence-Based Medicine (EBM) Reviews were searched from 1999 to 2017. Studies were stratified by prepregnancy BMI category and total pregnancy GWG. Odds ratio (ORs) 95% confidence intervals (CI) applied recommended GWG within each BMI category as the reference. Primary outcomes were small for gestational age (SGA), preterm birth and large for gestational age (LGA). Secondary outcomes were macrosomia, caesarean section and gestational diabetes. Result(s): Overall, 5874 studies were identified and 23 were included (n=1,309,136). Prepregnancy overweight/obesity in the USA, Europe and Asia was measured at 42%, 30% and 10% respectively, with underweight 5%, 3% and 17%. GWG below guidelines in the USA, Europe and Asia was 21%, 18% and 31%, and above was 51%, 51% and 37% respectively. Applying regional BMI categories in Asia showed GWG above guidelines (51%) was similar to that in the USA and Europe. GWG below guidelines was associated with a higher risk of SGA (USA/Europe [OR 1.51; CI 1.39, 1.63]; Asia [1.63; 1.45, 1.82]) and preterm birth (USA/Europe [1.35; 1.17, 1.56]; Asia [1.06; 0.78, 1.44]) than GWG within guidelines. GWG above guidelines was associated with a higher risk of LGA (USA/Europe [1.93; 1.81, 2.06]; Asia [1.68; 1.51 , 1.87]), macrosomia (USA/Europe [1.87; 1.70, 2.06]; Asia [2.18; 1.91, 2.49]) and caesarean (USA/Europe [1.26; 1.21, 1.33]

Polycystic ovary syndrome (PCOS) is a common condition characterised by both reproductive and metabolic features (obesity, insulin resistance, diabetes risk). Some evidence suggests that women with PCOS have lower vitamin D levels compared to healthy controls. Vitamin D binding protein (DBP) is the main carrier of vitamin D in circulation and plays an important role in regulating vitamin D concentration and bioavailability for target tissues. To our knowledge, no previous studies have examined DBP, bioavailable and free 25-hydroxyvitamin D (25(OH)D) in women with PCOS. The primary aim of this study was to compare DBP, bioavailable and free 25(OH)D concentrations in women with PCOS and controls. The secondary aim was to investigate relationships between DBP, bioavailable and free 25(OH)D and metabolic features (anthropometric measures, insulin resistance, and lipid profile). In a cross sectional study using bio-banked samples, we measured 25(OH)D, DBP and albumin. Bioavailable and free 25(OH)D were calculated using previously validated formula. BMI, body composition (dual X-ray absorptiometry, DXA), insulin resistance (homeostatic model assessment of insulin resistance (HOMA-IR)) and glucose infusion rate (GIR) from hyperinsulinaemic euglycaemic clamp and serum lipids (ELISA) were also measured in a physically and biochemically well-characterised cohort of women with and without PCOS. We studied 90 women with PCOS and 59 controls aged 18-48 years. DBP concentrations were lower in PCOS compared to controls (median [IQR]: 443.40 [314.4] vs 482.4 [156.8] mug/ml, p = 0.02). No significant differences were found in bioavailable or free 25(OH)D concentrations between groups. DBP was not associated with BMI, percent body fat or markers of insulin resistance (all p > 0.2). High-density lipoprotein (HDL) was the main determinant of DBP in the overall cohort (beta = -0.12, p = 0.02), after adjusting for covariates including PCOS/control status, age, BMI, total 25(OH)D and HOMA

Background: To investigate the association of adipocytokines and other inflammatory markers with development of GDM. Method(s): Serum adipocytokines and inflammatory markers were studied at 12 to 15 weeks gestation using biobanked control samples from a randomised trial. Study participants were identified as high risk for GDM using a validated clinical risk prediction tool. Markers were tested using commercial ELISA kits for high molecular weight (HMW) adiponectin, interleukin-6 (IL-6), plasminogen activator inhibitor-1, visfatin, omentin-1, sex-hormone binding globulin, monocyte chemoattractant protein, and asymmetrical dimethylarginine. The association between each biomarker and development of GDM at 24 to 28 weeks was evaluated using multivariable logistic regression analysis adjusted for maternal factors. Result(s): There were no differences in age, parity, country of birth, smoking, body mass index, or family history of diabetes in women with normal glucose tolerance (n = 78) and women who developed GDM (n = 25). Women with GDM were more likely to have a past history of GDM (P = 0.004). HMW adiponectin (odds ratio OR 0.37 [95% confidence interval 0.19-0.74]), omentin-1 (0.97 [0.94-0.99]), and IL-6 (1.87[1.03-3.37]) were associated with development of GDM, after adjustment for maternal age, body mass index, and past history of GDM. The other markers were not associated with GDM development. Conclusion(s): Decreased high molecular weight adiponectin and omentin-1 and increased IL-6 may enhance sensitivity of early risk prediction tools for women at high risk of GDM. This may allow early identification and opportunities for prevention of GDM and adverse outcomes. Further research is required in large validation studies to confirm these results.Copyright © 2017 John Wiley & Sons, Ltd.

Background: There are no contemporary cohorts examining pregnancy outcomes in women with type 2 diabetes (T2D) in Australia. Aim(s): To compare pregnancy outcomes in women with and without T2D, and assess effects of body mass index (BMI) and glycaemic control on outcomes. Material(s) and Method(s): An historical cohort study was conducted of all singleton births > 20 weeks gestation at a specialist maternity network in Australia from 2010 to 2013. Data were extracted from the Birthing Outcomes System database. Multivariable logistic regression analysis was used to examine associations between presence of T2D and pregnancy outcomes. Result(s): Outcomes for 138 pregnancies with T2D and 27 075 pregnancies in women without diabetes were compared (type 1 diabetes and gestational diabetes excluded). Women with T2D were older and more overweight compared to women without diabetes (P < 0.01). Their babies were born earlier (P < 0.01) with increased risk of large for gestational age (adjusted odds ratio 2.13 (95% CI 1.37-3.32)), hypoglycaemia (4.90 (2.79-8.61)), jaundice (2.58 (1.61-4.13)) and shoulder dystocia (2.72 (1.09-6.78)), but not congenital malformations or perinatal death. Women with T2D had a higher risk of induction (4.03 (2.71-5.99)), caesarean section (2.10 (1.44-3.04)), preterm birth (2.74 (1.78-4.24)) and pre-eclampsia (2.75 (1.49-5.10)). An HbA1c >= 6.0% (42 mmol/mol) was associated with increased preterm birth, special care nursery admission, hypoglycaemia and jaundice. Conclusion(s): Despite availability of preconception care, good glycaemic control and specialist management, T2D remains associated with increased adverse obstetric and neonatal outcomes. Further research to examine predictors of adverse outcomes may assist in targeted antenatal surveillance and management.Copyright © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists

Controversy remains surrounding International Association of Diabetes and Pregnancy Study Group (IADPSG) diagnostic criteria for gestational diabetes mellitus (GDM), including perceived improvement in perinatal outcomes and health service implications. We compared perinatal outcomes for untreated women meeting IADPSG-only criteria and women without GDM in Victoria. Women meeting IADPSG-only criteria were characterised according to fasting and one hour glucose thresholds and by region of birth. IADPSG criteria identified women with increased risk of adverse perinatal outcomes, particularly women born in Australia compared to Asian regions.Copyright © 2017 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists

Background: We aimed to compare glycemic control, insulin requirements, and outcomes in women with type 1 diabetes in pregnancy treated with continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI). Method(s): A retrospective cohort study was conducted of singleton pregnancies (>20 weeks gestation) in women with type 1 diabetes (2010-2015) at a specialist multidisciplinary maternity network in Australia. Antenatal characteristics, diabetes history and treatment details, and maternal and neonatal outcomes were compared for women with type 1 diabetes using CSII and MDI. Bolus calculator settings were reviewed for CSII. Data were obtained from individual medical records, linkage to pathology, and the Birthing Outcomes System database. Result(s): There were no differences in maternal characteristics or diabetes history between women managed with CSII (n = 40) and MDI (n = 127). Women treated with CSII required less insulin and less increase in total daily insulin dose/kg than MDI (40% vs. 52%). Both groups achieved similar glycemic control and no differences in pregnancy outcome. In the CSII group, carbohydrate:insulin ratios were intensified across gestation (30% breakfast, 27% lunch, 22% dinner), and insulin sensitivity factors (ISFs) changed little (7% breakfast, 0% lunch, -10% dinner). Conclusion(s): There was no difference in glycemic control or pregnancy outcomes in women using CSII or MDI managed in a multidisciplinary setting. Greater adjustments are needed to ISFs with CSII therapy. Overall, these data do not support recommending CSII in pregnancy with potentially higher patient and staff demands and costs and lack of improvement in HbA1c and pregnancy outcomes.© Copyright 2017, Mary Ann Liebert, Inc.

IMPORTANCE: Body mass index (BMI) and gestational weight gain are increasing globally. In 2009, the Institute of Medicine (IOM) provided specific recommendations regarding the ideal gestational weight gain. However, the association between gestational weight gain consistent with the IOM guidelines and pregnancy outcomes is unclear. OBJECTIVE(S): To perform a systematic review, meta-analysis, and metaregression to evaluate associations between gestational weight gain above or below the IOM guidelines (gain of 12.5-18 kg for underweight women [BMI <18.5]; 11.5-16 kg for normal-weight women [BMI18.5-24.9]; 7-11 kg for overweight women [BMI 25-29.9]; and 5-9 kg for obese women [BMI >=30]) and maternal and infant outcomes. DATA SOURCES AND STUDY SELECTION: Search of EMBASE, Evidence-Based Medicine Reviews, MEDLINE, and MEDLINE In-Process between January 1, 1999, and February 7, 2017, for observational studies stratified by prepregnancy BMI category and total gestational weight gain. DATA EXTRACTION AND SYNTHESIS: Data were extracted by 2 independent reviewers. Odds ratios (ORs) and absolute risk differences (ARDs) per live birth were calculated using a random-effects model based on a subset of studies with available data. MAIN OUTCOMES AND MEASURES: Primary outcomes were small for gestational age (SGA), preterm birth, and large for gestational age (LGA). Secondary outcomes were macrosomia, cesarean delivery, and gestational diabetes mellitus. RESULT(S): Of 5354 identified studies, 23 (n = 1309136 women) met inclusion criteria. Gestational weight gain was below or above guidelines in 23% and 47% of pregnancies, respectively. Gestational weight gain below the recommendations was associated with higher risk of SGA (OR, 1.53 [95% CI, 1.44-1.64]; ARD, 5% [95% CI, 4%-6%]) and preterm birth (OR, 1.70 [1.32-2.20]; ARD, 5% [3%-8%]) and lower risk of LGA (OR, 0.59 [0.55-0.64]; ARD, -2% [-10% to -6%]) and macrosomia (OR, 0.60 [0.52-0.68]; ARD, -2% [-3% to -1%]); cesarean delivery s

Objective: To compare contemporary pregnancy outcomes in women with and without type 1 diabetes, and to examine the effects of obesity and glycaemic control on these outcomes. Design and setting: Historical cohort study in a specialist diabetes and maternity network in Victoria. Participant(s): All singleton births (at least 20 weeks' gestation), 2010e2013, were analysed: 107 pregnancies to women with type 1 diabetes and 27 075 pregnancies to women without diabetes. Women with type 2 diabetes or gestational diabetes were excluded. Method(s): Data were extracted from the Birthing Outcomes System database; associations between type 1 diabetes and pregnancy outcomes were analysed by multivariable regression. Main Outcome Measure(s): Mode of birth; maternal and neonatal outcomes. Result(s): The mean body mass index was higher for women with type 1 diabetes than for women without diabetes (mean, 27.3 kg/m2 [SD, 5.0] v 25.7 kg/m2 [SD, 5.9]; P = 0.01); the median gestation period for their babies was shorter (median, 37.3 weeks [IQR, 34.6e38.1] v 39.4 weeks [IQR, 38.4e40.4]; P<0.001)and they were more likely to be large for gestational age (LGA) (adjusted odds ratio [aOR], 7.9; 95% CI, 5.3e11.8). Women with type 1 diabetes were more likely to have had labour induced (aOR, 3.0; 95% CI, 2.0e4.5), a caesarean delivery (aOR, 4.6; 95% CI, 3.1e7.0), or a pre-term birth (aOR, 6.7; 95% CI, 4.5e10.0); their babies were more likely to have shoulder dystocia (aOR, 8.2; 95% CI, 3.6e18.7), hypoglycaemia (aOR, 10.3; 95% CI, 6.8e15.6), jaundice (aOR, 5.1; 95% CI, 3.3e7.7), respiratory distress (aOR, 2.5; 95% CI, 1.4e4.4) or to suffer perinatal death (aOR, 4.3; 95% CI, 1.9e9.9). In women with type 1 diabetes, greater obesity was associated with increased odds for an LGA baby or congenital malformation, and increased HbA1c levels were associated with pre-term birth and perinatal death. Conclusion(s): Women with type 1 diabetes, even when managed in a specialist setting, still experience ad

Background Few contemporary studies have compared pregnancy outcomes in women with type 1 diabetes (T1D) and women without diabetes. The independent effects of obesity and glycaemic control on adverse outcomes remain unclear. We sought to address these gaps. Methods A large observational study was conducted of singleton births >20 weeks gestation from 2010-2013 at Monash Health, one of the largest health services in Australia. Data were extracted from the Birthing Outcomes System database. Multivariable regression analysis was used to examine associations between T1D and pregnancy outcome, adjusting for confounders including age, body mass index (BMI), parity, smoking, country of birth and gestational age. Results Outcomes for 107 pregnancies with T1D and 27 074 pregnancies with normal glucose tolerance were analyzed. Women with T1D were more overweight than women without diabetes (mean+/-SD: 27.3+/-5.0 vs 25.7+/-5.9 kg/m2,p=0.01), but there were no differences in age, parity or smoking. Women with T1D had earlier birth (median+IQR: 37.3+3.5 vs 39.4+2.0 weeks, p<0.001), increased risk of induction of labour (adjusted OR 3.05 [95% CI 2.06-4.50]), caesarean section (4.66 [3.10-7.00]) and preterm birth (7.42 [4.99-11.04]) compared to women without diabetes. Babies of women with T1D had increased macrosomia (7.93 [5.33-11.81]), shoulder dystocia (8.16 [3.57-18.65]), hypoglycaemia (10.33 [6.84-15.58]), jaundice (5.05 [3.30-7.73]), respiratory distress (2.47 [1.40-4.36]), intensive care admission (3.37 [1.55- 7.34]) and perinatal death (4.32 [1.88-9.92]) compared to babies of women without diabetes. In women with T1D, mean HbA1c was 7.0+/-1.2% during pregnancy. A 1kg/m2 increase in maternal BMI was associated with increased risk of macrosomia (1.12 [1.01-1.24]) and congenital malformations (1.26 [1.02-1.55]). A 1% increase in mean HbA1c was associated with increased risk of preterm birth (1.85 [1.13-3.02]) and perinatal death (5.09 [1.48-17.48]), but was not associated wi

Preexisting diabetes in pregnancy results in increased risks to the mother, fetus, and neonate. Preconception care is vital to reduce risk of miscarriage, congenital malformations, and perinatal mortality. Preconception care should empower women with realistic goal setting, healthy lifestyle, and diabetes self-management skills, to ensure a positive experience of the pregnancy and to reduce diabetes-related distress. In high-risk women without known diabetes, preconception and early antenatal screening is crucial to enable prompt treatment of hyperglycemia and any complications. The prevalence of obesity in reproductive age women is rising, further increasing risk of poor pregnancy outcomes in women with diabetes. Adverse lifestyle factors should be addressed preconception and in the antenatal period, allowing opportunity to improve physical health, manage weight, and improve neonatal outcomes. Management of diabetes in pregnancy involves individualized and intensified insulin therapy, accounting for expected changes in insulin sensitivity, and minimizing glucose variability and hypoglycemia. Diabetes complications must be screened for and managed as necessary. Delivery timing will depend on fetal surveillance and obstetric considerations. It is important to maintain engagement and motivation of these women in the postpartum period, encouraging breastfeeding and postpartum weight management and supporting diabetes management.Copyright © 2016 by Thieme Medical Publishers, Inc.

Background There is limited data on pregnancy outcomes with continuous subcutaneous insulin infusion (CSII) compared to multiple daily injections (MDI) in women with type 1 diabetes (T1D). Recent reviews of observational studies have found a possible increase in birthweight, but no difference in pregnancy outcomes, although included studies were small and potentially biased. We explored a broad range of pregnancy outcomes in a large cohort of women treated with CSII or MDI managed in a specialist multidisciplinary diabetes and maternity clinic. Methods An observational study was conducted of singleton pregnancies >20 weeks gestation in women with T1D (n=107) from 2010-2013 at Monash Health, one of the largest health services in Australia. Demographic and outcome data were extracted from the Birthing Outcomes System database, and details of diabetes treatment were obtained from the medical record. Univariable and multivariable logistic regression analysis was used to examine associations between mode of insulin delivery and pregnancy outcome, adjusting for potential confounders including age, body mass index (BMI), parity, smoking, country of birth and gestational age. Results Twenty pregnancies were managed with CSII and 87 were managed with MDI in women with T1D. Total daily dose of insulin was lower in the CSII compared to MDI group (median+IQR: 56+28 units versus 84+60 units, p<0.01). There were no significant differences in age, BMI or parity between groups. Women treated with CSII had similar glycaemic control to women treated with MDI in each trimester and throughout the pregnancy (mean+/-SD: HbA1c 7 3 +/- 0 9% vs 72+/-12%, p=0.75). Babies were born at a median gestation of 37 weeks in both groups, and there was no difference in birthweight in women managed with CSII compared to MDI (3211+/-1106g vs 3237+/-972g, p=0.92). There was no significant difference between groups in regards to maternal outcomes (gestational hypertension and pre-eclampsia), mode of birt

Understanding pathophysiology and identifying mothers at risk of major pregnancy complications is vital to effective prevention and optimal management. However, in current antenatal care, understanding of pathophysiology of complications is limited. In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Hence, universal screening is widely recommended. Here, we will explore the literature on GDM and biomarkers including inflammatory markers, adipokines, endothelial function and lipids to advance understanding of pathophysiology and explore risk prediction, with a goal to guide prevention and treatment of GDM.Copyright © 2015, MDPI AG. All rights Reserved.