Vitamin D status of pregnant women with obesity in the UK and its association with pregnancy outcomes: a secondary analysis of the UK Pregnancies Better Eating and Activity Trial (UPBEAT) study.

Prenatal vitamin D deficiency is widely reported and may affect perinatal outcomes. In this secondary analysis of the UK Pregnancies Better Eating and Activity Trial, we examined vitamin D status and its relationship with selected pregnancy outcomes in women with obesity (BMI ≥ 30 kg/m2) from multi-ethnic inner-city settings in the UK. Determinants of vitamin D status at a mean of 17 ± 1 weeks' gestation were assessed using multivariable linear regression and reported as percent differences in serum 25-hydroxyvitamin D (25(OH)D). Associations between 25(OH)D and clinical outcomes were examined using logistic regression. Among 1089 participants, 67 % had 25(OH)D < 50 nmol/l and 26 % had concentrations < 25 nmol/l. In fully adjusted models accounting for socio-demographic and anthropometric characteristics, 25(OH)D was lower among women of Black (% difference = -33; 95 % CI: -39, -27), Asian (% difference = -43; 95 % CI: -51, -35) and other non-White (% difference = -26; 95 % CI: -35, -14) ethnicity compared with women of White ethnicity (n 1086; P < 0·001 for all). In unadjusted analysis, risk of gestational diabetes was greater in women with 25(OH)D < 25 nmol/l compared with ≥ 50 nmol/l (OR = 1·58; 95 % CI: 1·09, 2·31), but the magnitude of effect estimates was attenuated in the multivariable model (OR = 1·33; 95 % CI: 0·88, 2·00). There were no associations between 25(OH)D and risk of preeclampsia, preterm birth or small for gestational age or large-for-gestational-age delivery. These findings demonstrate low 25(OH)D among pregnant women with obesity and highlight ethnic disparities in vitamin D status in the UK. However, evidence for a greater risk of adverse perinatal outcomes among women with vitamin D deficiency was limited.

Interventions in preconception and pregnant women at risk of gestational diabetes; a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Women at risk of gestational diabetes mellitus (GDM) need preventative interventions. OBJECTIVE: To evaluate targeted interventions before and during pregnancy for women identified as being at risk of developing GDM. METHODS: Systematic review and meta-analysis conducted following PRISMA guidelines. MEDLINE, EMBASE and the Cochrane Library in addition to reference and citation lists were searched to identify eligible randomised controlled trials (RCTs) utilising risk stratification during the preconception period or in the first/early second trimester. Screening and data extraction were carried out by the authors independently. Quality assessment was conducted based on the Cochrane risk-of-bias tool. Random effects meta-analysis and narrative synthesis were performed. RESULTS: Eighty-four RCTs were included: two during preconception and 82 in pregnancy, with a pooled sample of 22,568 women. Interventions were behavioural (n = 54), dietary supplementation (n = 19) and pharmacological (n = 11). Predictive factors for risk assessment varied; only one study utilised a validated prediction model. Gestational diabetes was reduced in diet and physical activity interventions (risk difference - 0.03, 95% CI 0.06, - 0.01; I2 58.69%), inositol (risk difference - 0.19, 95% CI 0.33, - 0.06; I2 92.19%), and vitamin D supplements (risk difference - 0.16, 95% CI 0.25, - 0.06; I2 32.27%). Subgroup analysis showed that diet and physical activity interventions were beneficial in women with ≥ 2 GDM risk factors (risk difference - 0.16, 95% CI 0.25, - 0.07; I2 11.23%) while inositol supplementation was effective in women with overweight or obesity (risk difference - 0.17, 95% CI 0.22, - 0.11; I2 0.01%). Effectiveness of all other interventions were not statistically significant. CONCLUSIONS: This review provides evidence that interventions targeted at women at risk of GDM may be an effective strategy for prevention. Further studies using validated prediction tools or multiple risk factors to target high-risk women for intervention before and during pregnancy are warranted.

Metabolic Profiling of Pregnant Women with Obesity: An Exploratory Study in Women at Greater Risk of Gestational Diabetes.

Gestational diabetes mellitus (GDM) is one of the most prevalent obstetric conditions, particularly among women with obesity. Pathways to hyperglycaemia remain obscure and a better understanding of the pathophysiology would facilitate early detection and targeted intervention. Among obese women from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), we aimed to compare metabolic profiles early and mid-pregnancy in women identified as high-risk of developing GDM, stratified by GDM diagnosis. Using a GDM prediction model combining maternal age, mid-arm circumference, systolic blood pressure, glucose, triglycerides and HbA1c, 231 women were identified as being at higher-risk, of whom 119 women developed GDM. Analyte data (nuclear magnetic resonance and conventional) were compared between higher-risk women who developed GDM and those who did not at timepoint 1 (15+0−18+6 weeks) and at timepoint 2 (23+2−30+0 weeks). The adjusted regression analyses revealed some differences in the early second trimester between those who developed GDM and those who did not, including lower adiponectin and glutamine concentrations, and higher C-peptide concentrations (FDR-adjusted p < 0.005, < 0.05, < 0.05 respectively). More differences were evident at the time of GDM diagnosis (timepoint 2) including greater impairment in ß-cell function (as assessed by HOMA2-%B), an increase in the glycolysis-intermediate pyruvate (FDR-adjusted p < 0.001, < 0.05 respectively) and differing lipid profiles. The liver function marker γ-glutamyl transferase was higher at both timepoints (FDR-adjusted p < 0.05). This exploratory study underlines the difficulty in early prediction of GDM development in high-risk women but adds to the evidence that among pregnant women with obesity, insulin secretory dysfunction may be an important discriminator for those who develop GDM.

Prevention of gestational diabetes in pregnant women with obesity: protocol for a pilot randomised controlled trial.

BACKGROUND: Obesity in pregnancy increases the risk of gestational diabetes mellitus (GDM) and associated adverse outcomes. Despite metabolic differences, all pregnant women with obesity are considered to have the same risk of developing GDM. Improved risk stratification is required to enable targeted intervention in women with obesity who would benefit the most. The aim of this study is to identify pregnant women with obesity at higher risk of developing GDM and, in a pilot randomised controlled trial (RCT), test feasibility and assess the efficacy of a lifestyle intervention and/or metformin to improve glycaemic control. METHODS: Women aged 18 years or older with a singleton pregnancy and body mass index (BMI) ≥ 30kg/m2 will be recruited from one maternity unit in London, UK. The risk of GDM will be assessed using a multivariable GDM prediction model combining maternal age, mid-arm circumference, systolic blood pressure, glucose, triglycerides and HbA1c. Women identified at a higher risk of developing GDM will be randomly allocated to one of two intervention groups (lifestyle advice with or without metformin) or standard antenatal care. The primary feasibility outcomes are study recruitment, retention rate and intervention adherence and to collect information needed for the sample size calculation for the definitive trial. A process evaluation will assess the acceptability of study processes and procedures to women. Secondary patient-centred outcomes include a reduction in mean glucose/24h of 0.5mmol/l as assessed by continuous glucose monitoring and changes in a targeted maternal metabolome, dietary intake and physical activity. A sample of 60 high-risk women is required. DISCUSSION: Early risk stratification of GDM in pregnant women with obesity and targeted intervention using lifestyle advice with or without metformin could improve glucose tolerance compared to standard antenatal care. The results from this feasibility study will inform a larger adequately powered RCT should the intervention show trends for potential effectiveness. TRIAL REGISTRATION: This study has been approved by the NHS Research Ethics Committee (UK IRAS integrated research application system; reference 18/LO/1500). EudraCT number 2018-000003-16 .

Community Pharmacist-Led Interventions to Improve Preconception and Pregnancy Health: A Systematic Review.

Background: Community pharmacist-led interventions are effective in improving health outcomes; however, their impact in improving preconception and pregnancy health is not clear. This study evaluated the effectiveness of community pharmacist-led interventions which aimed to improve health outcomes of preconception and pregnant women. Methods: A systematic review of the literature, consistent with PRISMA guidelines, was performed. Five electronic databases were searched up to February 2021. Results: Four studies, three in pregnant women and one in preconception women, were identified. The studies focused on improving micronutrient status and smoking cessation. The studies increased knowledge about, and use of, iron supplements, and improved iron status and smoking cessation rates in pregnant women, while improving knowledge regarding, and increasing the use of, preconception folic acid. The studies were ranked as weak to moderate quality. Conclusion: This review provides preliminary evidence for the potential benefit of community pharmacist-led interventions to improve the health of women before and during pregnancy.