Facilitators and barriers to behaviour change within a lifestyle program for women with obesity to prevent excess gestational weight gain: a mixed methods evaluation.

BACKGROUND: Maternal obesity is associated with health risks for women and their babies and is exacerbated by excess gestational weight gain. The aim of this study was to describe women's experiences and perspectives in attending a Healthy Pregnancy Service designed to optimise healthy lifestyle and support recommended gestational weight gain for women with obesity. METHODS: An explanatory sequential mixed methods study design utilised two questionnaires (completed in early and late pregnancy) to quantify feelings, motivation and satisfaction with the service, followed by semi-structured interviews that explored barriers and enablers of behaviour change. Data were analysed separately and then interpreted together. RESULTS: Overall, 49 women attending the service completed either questionnaire 1, 2 or both and were included in the analysis. Fourteen women were interviewed. Prior to pregnancy, many women had gained weight and attempted to lose weight independently, and reported they were highly motivated to achieve a healthy lifestyle. During pregnancy, diet changes were reported as easier to make and sustain than exercise changes. Satisfaction with the service was high. Key factors identified in qualitative analysis were: service support enabled change; motivation to change behaviour, social support, barriers to making change (intrinsic, extrinsic and clinic-related), post-partum lifestyle and needs. On integration of data, qualitative and quantitative findings aligned. CONCLUSIONS: The Healthy Pregnancy service was valued by women. Barriers and enablers to the delivery of an integrated model of maternity care that supported healthy lifestyle and recommended gestational weight gain were identified. These findings have informed and improved implementation and further scale up of this successful service model, integrating healthy lifestyle into routine antenatal care of women with obesity. TRIAL REGISTRATION: This trial is registered with the Australian New Zealand Clinical Trials Registry (no.12620000985987). Registration date 30/09/2020, retrospectively registered. http://www.anzctr.org.au/.

The Healthy Pregnancy Service to Optimise Excess Gestational Weight Gain for Women with Obesity: A Qualitative Study of Health Professionals' Perspectives.

Maternal obesity is associated with health risks for women and their babies, exacerbated by excess gestational weight gain. We describe health professionals' perspectives in the provision of a Healthy Pregnancy service designed to optimise healthy lifestyle and support recommended gestational weight gain for women with obesity. Semi-structured interviews were conducted with health professionals. Questions were based on the Theoretical Domains Framework (TDF) and deductive thematic analysis was performed. A total of 14 multidisciplinary staff were interviewed. Six themes were identified: 1. health professionals view themselves as part of a team; 2. health professionals reported having necessary skills; 3. experience generated confidence in discussing gestational weight gain; 4. gestational weight gain is considered of variable importance; 5. health professionals want women to be comfortable; 6. the environmental context and resources presented some barriers. Staff were supportive of the Healthy Pregnancy service and valued developing teamwork with staff and rapport with women. Most felt relatively comfortable discussing weight gain with women. Barriers included ability to navigate sensitive topics with women, limited awareness of the intervention among new staff, communication between teams, and waiting time for women. Barriers and enablers to the delivery of an integrated model of maternity care were identified. These findings should inform and improve implementation of service models integrating healthy lifestyle in the antenatal care of women with obesity.

Gestational weight gain across continents and ethnicity: systematic review and meta-analysis of maternal and infant outcomes in more than one million women.

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. METHODS: 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. RESULTS: 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]; Asia [1.37; 1.30, 1.45]). Risks remained elevated when regional BMI categories were applied for GWG recommendations. More women in Asia were categorised as having GWG below guidelines using World Health Organization (WHO) (60%) compared to regional BMI categories (16%), yet WHO BMI was not accompanied by increased risks of adverse outcomes. CONCLUSIONS: Women in the USA and western Europe have higher prepregnancy BMI and higher rates of GWG above guidelines than women in east Asia. However, when using regional BMI categories in east Asia, rates of GWG above guidelines are similar across the three continents. GWG outside guidelines is associated with adverse outcomes across all regions. If regional BMI categories are used in east Asia, IOM guidelines are applicable in the USA, western Europe and east Asia.

Association of Gestational Weight Gain With Maternal and Infant Outcomes: A Systematic Review and Meta-analysis.

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 theIOM guidelines and pregnancy outcomes is unclear. OBJECTIVE: 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 [BMI 18.5-24.9]; 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. RESULTS: Of 5354 identified studies, 23 (n = 1 309 136 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 showed no significant difference (OR, 0.98 [0.96-1.02]; ARD, 0% [-2% to 1%]). Gestational weight gain above the recommendations was associated with lower risk of SGA (OR, 0.66 [0.63-0.69]; ARD, -3%; [-4% to -2%]) and preterm birth (OR, 0.77 [0.69-0.86]; ARD, -2% [-2% to -1%]) and higher risk of LGA (OR, 1.85 [1.76-1.95]; ARD, 4% [2%-5%]), macrosomia (OR, 1.95 [1.79-2.11]; ARD, 6% [4%-9%]), and cesarean delivery (OR, 1.30 [1.25-1.35]; ARD, 4% [3%-6%]). Gestational diabetes mellitus could not be evaluated because of the nature of available data. CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of more than 1 million pregnant women, 47% had gestational weight gain greater than IOM recommendations and 23% had gestational weight gain less than IOM recommendations. Gestational weight gain greater than or less than guideline recommendations, compared with weight gain within recommended levels, was associated with higher risk of adverse maternal and infant outcomes.

Satisfaction with diagnosis process for gestational diabetes mellitus and risk perception among Australian women.

OBJECTIVE: To evaluate satisfaction with diagnosis, risk perceptions, and health beliefs among women with gestational diabetes mellitus (GDM). METHODS: In a cross-sectional questionnaire-based study, participants with GDM diagnosed after 26weeks of pregnancy were recruited from hospital-based services at Monash Health (Melbourne, VIC, Australia) and through newspaper advertisements between 2008 and 2010. Eligible participants-aged at least 18years and able to read English-completed a questionnaire. RESULTS: Among 46 women who completed the questionnaire, 38 (83%) were satisfied with the explanation of the GDM screening test and 31 (67%) felt that the results were explained well. Generally, women were satisfied with the information provided about lifestyle management (29 [81%] of 36) and medical therapy (26 [72%] of 36). Most women (41 [89%]) associated poor GDM control with perinatal complications. Additionally, many participants thought that insulin (35 [76%]) and lifestyle changes (30 [65%]) could reduce macrosomia. A total of 37 (82%) of 45 women perceived that they were at risk of future GDM, and 33 (73%) thought they had an increased risk of type 2 diabetes. Most women believed that they could change these risks (29 [64%] and 37 [82%] of 45, respectively). CONCLUSION: Women were largely positive about their experience of GDM diagnosis. Explanation of the screening test and provision of information could be improved. Risk perception was reasonable.

Serum selenium status in Graves' disease with and without orbitopathy: a case-control study.

OBJECTIVE: Selenium is effective in improving quality of life and reducing the progression of active Graves' orbitopathy. The effect of correcting relative selenium deficiency on improving Graves' orbitopathy is unknown, as baseline selenium levels have not previously been measured. The study aims to determine whether serum selenium levels are reduced in patients with Graves' disease with orbitopathy (GO) compared with without orbitopathy (GD). DESIGN: A prospective, case-control study performed between 2009 and 2012 at endocrine and ophthalmology clinics in Australia. PATIENTS: A total of 198 patients with Graves' disease participated in the study: 101 with Graves' orbitopathy and 97 without Graves' orbitopathy. MEASUREMENTS: Serum selenium levels in both groups. RESULTS: Mean serum selenium levels were significantly lower in GO (1·10 ± 0·18 µm) than in GD (1·19 ± 0·20 µm) (P = 0·001). Mean selenium levels appeared to decrease in parallel with increasing severity of GO; selenium level was 1·19 ± 0·20 µm in GD, 1·10 ± 0·19 µm in moderate-to-severe GO and 1·09 ± 0·17 µm in sight-threatening GO (P = 0·003). Serum selenium levels remained significantly lower in GO after adjusting for age, smoking status, thyroidectomy, radioactive iodine treatment and residential location. CONCLUSION: Serum selenium levels are lower in patients with GO compared with GD in an Australian study population with marginal selenium status. Relative selenium deficiency may be an independent risk factor for orbitopathy in patients with Graves' disease.

Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp.

STUDY QUESTION: What is the prevalence of insulin resistance (IR) and the contributions of intrinsic and extrinsic IR in women diagnosed with polycystic ovary syndrome (PCOS) according to the Rotterdam criteria? SUMMARY ANSWER: We report novel clamp data in Rotterdam diagnosed PCOS women, using World Health Organization criteria for IR showing that women with PCOS have a high prevalence of IR, strengthening the evidence for an aetiological role of IR in both National Institutes of Health (NIH) and Rotterdam diagnosed PCOS in lean and overweight women. WHAT IS KNOWN ALREADY: PCOS is a complex endocrine condition with a significant increased risk of gestational diabetes and type 2 diabetes. STUDY DESIGN, SIZE, DURATION: Using a cross-sectional study design, 20 overweight and 20 lean PCOS (Rotterdam criteria), 14 overweight and 19 lean body mass index (BMI)-matched control non-PCOS women underwent clinical measures of IR after a 3-month withdrawal of insulin sensitizers and the oral contraceptive pill. MATERIALS, SETTING, METHODS: In an academic clinic setting, glucose infusion rate (GIR) on euglycaemic-hyperinsulinaemic clamp was investigated as a marker of insulin sensitivity. MAIN RESULTS AND THE ROLE OF CHANCE: PCOS women were more IR than BMI-matched controls (main effect for BMI and PCOS; P < 0.001). IR was present in 75% of lean PCOS, 62% of overweight controls and 95% of overweight PCOS. Lean controls (mean ± SD; GIR 339 ± 76 mg min⁻¹ m⁻²) were less IR than lean PCOS (270 ± 66 mg min⁻¹ m⁻²), overweight controls (264 ± 66 mg min⁻¹ m⁻²) and overweight PCOS (175 ± 96 mg min⁻¹ m⁻²). The negative relationship between BMI and IR reflected by GIR was more marked in PCOS (y = 445.1 - 7.7x, R² = 0.42 (P < 0.0001) than controls (y = 435.5 - 4.6x, R² = 0.04 (P < 0.01)). LIMITATIONS, REASONS FOR CAUTION: The study did not use glucose tracer techniques to completely characterize the IR, as well as the lack of matching for body composition and age. WIDER IMPLICATIONS OF THE FINDINGS: IR is exacerbated by increased BMI, supporting intrinsic IR in PCOS. BMI impact on IR is greater in PCOS, than in controls, irrespective of visceral fat, prioritizing lifestyle intervention and the need for effective therapeutic interventions to address intrinsic IR and prevent diabetes in this high-risk population. STUDY FUNDING/COMPETING INTEREST(S): This investigator-initiated trial was supported by grants from the National Health & Medical Research Council (NHMRC) Grant number 606553 (H.J.T., N.K.S. and S.K.H.) as well as Monash University and The Jean Hailes Foundation. H.J.T. is an NHMRC Research Fellow. N.K.S. is supported through the Australian Government's Collaborative Research Networks (CRN) programme. A.E.J. is a Jean Hailes and NHMRC scholarship holder. The authors declare that there is no conflict of interest associated with this manuscript.

Enhanced cell-surface stability of rescued DeltaF508 cystic fibrosis transmembrane conductance regulator (CFTR) by pharmacological chaperones.

Misfolded proteins destined for the cell surface are recognized and degraded by the ERAD [ER (endoplasmic reticulum) associated degradation] pathway. TS (temperature-sensitive) mutants at the permissive temperature escape ERAD and reach the cell surface. In this present paper, we examined a TS mutant of the CFTR [CF (cystic fibrosis) transmembrane conductance regulator], CFTR DeltaF508, and analysed its cell-surface trafficking after rescue [rDeltaF508 (rescued DeltaF508) CFTR]. We show that rDeltaF508 CFTR endocytosis is 6-fold more rapid (approximately 30% per 2.5 min) than WT (wild-type, approximately 5% per 2.5 min) CFTR at 37 degrees C in polarized airway epithelial cells (CFBE41o-). We also investigated rDeltaF508 CFTR endocytosis under two further conditions: in culture at the permissive temperature (27 degrees C) and following treatment with pharmacological chaperones. At low temperature, rDeltaF508 CFTR endocytosis slowed to WT rates (20% per 10 min), indicating that the cell-surface trafficking defect of rDeltaF508 CFTR is TS. Furthermore, rDeltaF508 CFTR is stabilized at the lower temperature; its half-life increases from <2 h at 37 degrees C to >8 h at 27 degrees C. Pharmacological chaperone treatment at 37 degrees C corrected the rDeltaF508 CFTR internalization defect, slowing endocytosis from approximately 30% per 2.5 min to approximately 5% per 2.5 min, and doubled DeltaF508 surface half-life from 2 to 4 h. These effects are DeltaF508 CFTR-specific, as pharmacological chaperones did not affect WT CFTR or transferrin receptor internalization rates. The results indicate that small molecular correctors may reproduce the effect of incubation at the permissive temperature, not only by rescuing DeltaF508 CFTR from ERAD, but also by enhancing its cell-surface stability.

VCP/p97 AAA-ATPase does not interact with the endogenous wild-type cystic fibrosis transmembrane conductance regulator.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is defective in cystic fibrosis. The most common mutation, DeltaF508 CFTR, is retained in the endoplasmic reticulum, retrotranslocated into the cytosol, and degraded by the proteasome. In a proteomics screen to identify DeltaF508 CFTR interacting proteins, we found that valosin-containing protein (VCP)/p97, a Type II AAA ATPase that is a component of the retrotranslocation machinery, binds DeltaF508 CFTR, and this interaction is stabilized by proteasomal inhibition. Since wild-type (WT) CFTR has been reported to be inefficiently processed during biogenesis with as much as 75% of the newly synthesized protein degraded by the proteasome, we examined the VCP interaction in Calu-3, T-84, and 16HBE, three epithelial cell lines that endogenously express WT CFTR. The results indicate that when WT CFTR processing is efficient, as demonstrated in Calu-3 cells, VCP does not interact. Interestingly, overexpression of recombinant WT CFTR in Calu-3 cells results in inefficient processing and VCP interaction, demonstrating that CFTR processing efficiency and the VCP interaction are tightly coupled. Furthermore, induction of ER stress and activation of the unfolded protein response result in inefficient processing of WT CFTR in Calu-3 cells and promote the WT CFTR-VCP interaction. The results support the hypothesis that components of the retrotranslocation machinery such as VCP do not interact with CFTR in epithelial cells that endogenously express WT CFTR, since under normal conditions the processing of the WT protein is efficient.