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.

Longitudinal dietary trajectories from pregnancy to 3 years post delivery in women with obesity: relationships with adiposity.

OBJECTIVE: The study aim was to examine the relationships between longitudinal dietary trajectories from early pregnancy to 3 years post delivery and adiposity measures in women with obesity. METHODS: The diets of 1208 women with obesity in the UPBEAT (UK Pregnancy Better Eating and Activity Trial) study were assessed using a food frequency questionnaire (FFQ) at 15+0 to 18+6 weeks' gestation (baseline), 27+0 to 28+6 weeks' gestation, and 34+0 to 36+0 weeks' gestation, as well as 6 months and 3 years post delivery. Using factor analysis of the baseline FFQ data, four dietary patterns were identified: fruit & vegetable, African/Caribbean, processed, and snacking. The baseline scoring system was applied to the FFQ data at the four subsequent time points. Group-based trajectory modeling was used to extract longitudinal dietary pattern trajectories. Using adjusted regression, associations between dietary trajectories and log-transformed/standardized adiposity measures (BMI and waist and mid-upper arm circumferences) at 3 years post delivery were examined. RESULTS: Two trajectories were found to best describe the data for the four individual dietary patterns; these were characterized as high and low adherence. A high adherence to the processed pattern was associated with a higher BMI (ß = 0.38 [95% CI: 0.06-0.69]) and higher waist (ß = 0.35 [0.03-0.67]) and mid-upper arm circumferences (ß = 0.36 [0.04-0.67]) at 3 years post delivery. CONCLUSIONS: In women with obesity, a processed dietary pattern across pregnancy and 3 years post delivery is associated with higher adiposity.

Ethnic disparities in pregnancy-related acute kidney injury in a United Kingdom population.

BACKGROUND: The incidence of acute kidney injury in pregnancy (P-AKI) is rising and is associated with detrimental maternal and foetal outcomes. Ethnic disparities in pregnancy outcomes are well recognized, with females who identify as Black or Asian being more likely to die during pregnancy compared to females who identify as White ethnicity. METHODS: This study reports rates of P-AKI and associated risk factors in pregnant females of different ethnicities. All pregnancies were recorded between 2016 and 2020. AKI episodes were identified using electronic alerts. Ethnicity, AKI stage (1-3), obstetric outcomes and risk factors for P-AKI (chronic hypertension, pregnancy-induced hypertension and pre-eclampsia, and haemorrhage) were assessed. RESULTS: There were 649 P-AKI episodes from 16,943 deliveries (3.8%). Black females were more likely to have P-AKI (5.72%) compared to those who were White (3.12%), Asian (3.74%), mixed ethnicity (2.89%) and Other/Not Stated (3.10%). Black females, compared to White females, were at greater risk of developing P-AKI if they had haemorrhage requiring blood transfusion (OR 2.44, 95% CI 1.31,4.54; p < 0.001) or pregnancy-induced hypertension (OR 1.79, 95% CI 1.12, 2.86; p < 0.001). After adjusting for risk factors, Black females had increased risk of developing P-AKI (OR 1.52, 95% CI 1.22, 1.80; p < 0.001) compared to White females. Black females were at increased risk of developing P-AKI compared to White females. Mode of delivery, pregnancy-induced hypertension and haemorrhage are likely to have contributed. The increased risk persists despite accounting for these variables, suggesting that other factors such as socioeconomic disparities need to be considered. CONCLUSIONS: The incidence of P-AKI is likely higher than previously stated in the literature. However, caution must be exercised, particularly with AKI stage 1, as the KDIGO system is not validated in pregnancy and gestational changes in renal physiology need to be considered. Pregnancy-specific AKI definitions are needed.

Micronutrient supplementation interventions in preconception and pregnant women at increased risk of developing pre-eclampsia: a systematic review and meta-analysis.

BACKGROUND: Pre-eclampsia can lead to maternal and neonatal complications and is a common cause of maternal mortality worldwide. This review has examined the effect of micronutrient supplementation interventions in women identified as having a greater risk of developing pre-eclampsia. METHODS: A systematic review was performed using the PRISMA guidelines. The electronic databases MEDLINE, EMBASE and the Cochrane Central Register of Controlled trials were searched for relevant literature and eligible studies identified according to a pre-specified criteria. A meta-analysis of randomised controlled trials (RCTs) was conducted to examine the effect of micronutrient supplementation on pre-eclampsia in high-risk women. RESULTS: Twenty RCTs were identified and supplementation included vitamin C and E (n = 7), calcium (n = 5), vitamin D (n = 3), folic acid (n = 2), magnesium (n = 1) and multiple micronutrients (n = 2). Sample size and recruitment time point varied across studies and a variety of predictive factors were used to identify participants, with a previous history of pre-eclampsia being the most common. No studies utilised a validated prediction model. There was a reduction in pre-eclampsia with calcium (risk difference, -0.15 (-0.27, -0.03, I2 = 83.4%)), and vitamin D (risk difference, -0.09 (-0.17, -0.02, I2 = 0.0%)) supplementation. CONCLUSION: Our findings show a lower rate of pre-eclampsia with calcium and vitamin D, however, conclusions were limited by small sample sizes, methodological variability and heterogeneity between studies. Further higher quality, large-scale RCTs of calcium and vitamin D are warranted. Exploration of interventions at different time points before and during pregnancy as well as those which utilise prediction modelling methodology, would provide greater insight into the efficacy of micronutrient supplementation intervention in the prevention of pre-eclampsia in high-risk women.

Evaluation and interpretation of latent class modelling strategies to characterise dietary trajectories across early life: a longitudinal study from the Southampton Women's Survey.

There is increasing interest in modelling longitudinal dietary data and classifying individuals into subgroups (latent classes) who follow similar trajectories over time. These trajectories could identify population groups and time points amenable to dietary interventions. This paper aimed to provide a comparison and overview of two latent class methods: group-based trajectory modelling (GBTM) and growth mixture modelling (GMM). Data from 2963 mother-child dyads from the longitudinal Southampton Women's Survey were analysed. Continuous diet quality indices (DQI) were derived using principal component analysis from interviewer-administered FFQ collected in mothers pre-pregnancy, at 11- and 34-week gestation, and in offspring at 6 and 12 months and 3, 6-7 and 8-9 years. A forward modelling approach from 1 to 6 classes was used to identify the optimal number of DQI latent classes. Models were assessed using the Akaike and Bayesian information criteria, probability of class assignment, ratio of the odds of correct classification, group membership and entropy. Both methods suggested that five classes were optimal, with a strong correlation (Spearman's = 0·98) between class assignment for the two methods. The dietary trajectories were categorised as stable with horizontal lines and were defined as poor (GMM = 4 % and GBTM = 5 %), poor-medium (23 %, 23 %), medium (39 %, 39 %), medium-better (27 %, 28 %) and best (7 %, 6 %). Both GBTM and GMM are suitable for identifying dietary trajectories. GBTM is recommended as it is computationally less intensive, but results could be confirmed using GMM. The stability of the diet quality trajectories from pre-pregnancy underlines the importance of promotion of dietary improvements from preconception onwards.

Changing epidemiology of acute kidney injury in critically ill patients with COVID-19: a prospective cohort.

BACKGROUND: Acute kidney injury (AKI) is common in critically ill patients with coronavirus disease-19 (COVID-19). We aimed to explore the changes in AKI epidemiology between the first and the second COVID wave in the United Kingdom (UK). METHODS: This was an observational study of critically ill adult patients with COVID-19 in an expanded tertiary care intensive care unit (ICU) in London, UK. Baseline characteristics, organ support, COVID-19 treatments, and patient and kidney outcomes up to 90 days after discharge from hospital were compared. RESULTS: A total of 772 patients were included in the final analysis (68% male, mean age 56 ± 13.6). Compared with wave 1, patients in wave 2 were older, had higher body mass index and clinical frailty score, but lower baseline serum creatinine and C-reactive protein (CRP). The proportion of patients receiving invasive mechanical ventilation (MV) on ICU admission was lower in wave 2 (61% vs 80%; p < 0.001). AKI incidence within 14 days of ICU admission was 76% in wave 1 and 51% in wave 2 (p < 0.001); in wave 1, 32% received KRT compared with 13% in wave 2 (p < 0.001). Patients in wave 2 had significantly lower daily cumulative fluid balance (FB) than in wave 1. Fewer patients were dialysis dependent at 90 days in wave 2 (1% vs. 4%; p < 0.001). CONCLUSIONS: In critically ill adult patients admitted to ICU with COVID-19, the risk of AKI and receipt of KRT significantly declined in the second wave. The trend was associated with less MV, lower PEEP and lower cumulative FB. TRIAL REGISTRATION: NCT04445259.

Lifestyle intervention in obese pregnancy and cardiac remodelling in 3-year olds: children of the UPBEAT RCT.

BACKGROUND/OBJECTIVES: Obesity in pregnancy has been associated with increased childhood cardiometabolic risk and reduced life expectancy. The UK UPBEAT multicentre randomised control trial was a lifestyle intervention of diet and physical activity in pregnant women with obesity. We hypothesised that the 3-year-old children of women with obesity would have heightened cardiovascular risk compared to children of normal BMI women, and that the UPBEAT intervention would mitigate this risk. SUBJECTS/METHODS: Children were recruited from one UPBEAT trial centre. Cardiovascular measures included blood pressure, echocardiographic assessment of cardiac function and dimensions, carotid intima-media thickness and heart rate variability (HRV) by electrocardiogram. RESULTS: Compared to offspring of normal BMI women (n = 51), children of women with obesity from the trial standard care arm (n = 39) had evidence of cardiac remodelling including increased interventricular septum (IVS; mean difference 0.04 cm; 95% CI: 0.018 to 0.067), posterior wall (PW; 0.03 cm; 0.006 to 0.062) and relative wall thicknesses (RWT; 0.03 cm; 0.01 to 0.05) following adjustment. Randomisation of women with obesity to the intervention arm (n = 31) prevented this cardiac remodelling (intervention effect; mean difference IVS -0.03 cm (-0.05 to -0.008); PW -0.03 cm (-0.05 to -0.01); RWT -0.02 cm (-0.04 to -0.005)). Children of women with obesity (standard care arm) compared to women of normal BMI also had elevated minimum heart rate (7 bpm; 1.41 to 13.34) evidence of early diastolic dysfunction (e prime) and increased sympathetic nerve activity index by HRV analysis. CONCLUSIONS: Maternal obesity was associated with left ventricular concentric remodelling in 3-year-old offspring. Absence of remodelling following the maternal intervention infers in utero origins of cardiac remodelling. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The UPBEAT trial is registered with Current Controlled Trials, ISRCTN89971375.

Preventing and treating childhood overweight and obesity in children up to 5 years old: A systematic review by intervention setting.

The prevalence of childhood obesity is increasing worldwide with long-term health consequences. Effective strategies to stem the rising childhood obesity rates are needed but systematic reviews of interventions have reported inconsistent effects. Evaluation of interventions could provide more practically relevant information when considered in the context of the setting in which the intervention was delivered. This systematic review has evaluated diet and physical activity interventions aimed at reducing obesity in children, from birth to 5 years old, by intervention setting. A systematic review of the literature, consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, was performed. Three electronic databases were searched from 2010 up to December 2020 for randomised controlled trials aiming to prevent or treat childhood obesity in children up to 5 years old. The studies were stratified according to the setting in which the intervention was conducted. Twenty-eight studies were identified and included interventions in childcare/school (n = 11), home (n = 5), community (n = 5), hospital (n = 4), e-health (n = 2) and mixed (n = 1) settings. Thirteen (46%) interventions led to improvements in childhood obesity measures, including body mass index z-score and body fat percentage, 12 of which included both parental/family-based interventions in conjunction with modifying the child's diet and physical activity behaviours. Home-based interventions were identified as the most effective setting as four out of five studies reported significant changes in the child's weight outcomes. Interventions conducted in the home setting and those which included parents/families were effective in preventing childhood obesity. These findings should be considered when developing optimal strategies for the prevention of childhood obesity.

Maternal weight and gestational diabetes impacts on child health.

PURPOSE OF REVIEW: To review recent evidence linking maternal body mass index and gestational diabetes mellitus (GDM) with offspring health outcomes. RECENT FINDINGS: It is now established that the rising prevalences of maternal obesity and GDM are both making substantial contributions to the growing burden of childhood obesity and associated disorders. Strengthening evidence also links maternal obesity with increased offspring risks of cardiovascular disease, nonalcoholic fatty liver disease, lower respiratory tract infections during infancy, wheezing illnesses, asthma and attention deficit hyperactivity disorder during childhood, and with higher risks of psychiatric disorders and colorectal cancer in adulthood. GDM has been associated with increased offspring risks of cardiovascular disease, childhood wheeze/asthma (but not allergic sensitization), and with high refractive error, attention deficit hyperactivity and psychiatric disorders from childhood onwards. SUMMARY: The long-term consequences of maternal obesity and GDM for the offspring in childhood and later adult life present major challenges for public health across the life course and for future generations. Tackling these challenges requires a systems-based approach to support achieving a healthy weight in young people prior to conception, alongside new insights into population based preventive measures against gestational diabetes.

Folate and vitamin B12 status: associations with maternal glucose and neonatal DNA methylation sites related to dysglycaemia, in pregnant women with obesity.

Recent studies implicate maternal gestational diabetes mellitus (GDM) in differential methylation of infant DNA. Folate and vitamin B12 play a role in DNA methylation, and these vitamins may also influence GDM risk. The aims of this study were to determine folate and vitamin B12 status in obese pregnant women and investigate associations between folate and vitamin B12 status, maternal dysglycaemia and neonatal DNA methylation at cytosine-phosphate-guanine sites previously observed to be associated with dysglycaemia. Obese pregnant women who participated in the UK Pregnancies Better Eating and Activity Trial were included. Serum folate and vitamin B12 were measured at the oral glucose tolerance test (OGTT) visit. Cord blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. Regression models with adjustment for confounders were used to examine associations. Of the 951 women included, 356 (37.4%) were vitamin B12 deficient, and 44 (4.6%) were folate deficient. Two-hundred and seventy-one women (28%) developed GDM. Folate and vitamin B12 concentrations were not associated with neonatal DNA methylation. Higher folate was positively associated with 1-h plasma glucose after OGTT (ß = 0.031, 95% CI 0.001-0.061, p = 0.045). There was no relationship between vitamin B12 and glucose concentrations post OGTT or between folate or vitamin B12 and GDM. In summary, we found no evidence to link folate and vitamin B12 status with the differential methylation of neonatal DNA previously observed in association with dysglycaemia. We add to the evidence that folate status may be related to maternal glucose homoeostasis although replication in other maternal cohorts is required for validation.

Longitudinal dietary trajectories from preconception to mid-childhood in women and children in the Southampton Women's Survey and their relation to offspring adiposity: a group-based trajectory modelling approach.

BACKGROUND: Rates of childhood obesity are increasing globally, with poor dietary quality an important contributory factor. Evaluation of longitudinal diet quality across early life could identify timepoints and subgroups for nutritional interventions as part of effective public health strategies. OBJECTIVE: This research aimed to: (1) define latent classes of mother-offspring diet quality trajectories from pre-pregnancy to child age 8-9 years, (2) identify early life factors associated with these trajectories, and (3) describe the association between the trajectories and childhood adiposity outcomes. DESIGN: Dietary data from 2963 UK Southampton Women's Survey mother-offspring dyads were analysed using group-based trajectory modelling of a diet quality index (DQI). Maternal diet was assessed pre-pregnancy and at 11- and 34-weeks' gestation, and offspring diet at ages 6 and 12 months, 3, 6-7- and 8-9-years using interviewer-administered food frequency questionnaires. At each timepoint, a standardised DQI was derived using principal component analysis. Adiposity age 8-9 years was assessed using dual-energy X-ray absorptiometry (DXA) and BMI z-scores. RESULTS: A five-trajectory group model was identified as optimal. The diet quality trajectories were characterised as stable, horizontal lines and were categorised as poor (n = 142), poor-medium (n = 667), medium (n = 1146), medium-better (n = 818) and best (n = 163). A poorer dietary trajectory was associated with higher maternal pre-pregnancy BMI, smoking, multiparity, lower maternal age and lower educational attainment. Using linear regression adjusted for confounders, a 1-category decrease in the dietary trajectory was associated with higher DXA percentage body fat (0.08 SD (95% confidence interval 0.01, 0.15) and BMI z-score (0.08 SD (0.00, 0.16) in the 1216 children followed up at age 8-9 years. CONCLUSION: Mother-offspring dietary trajectories are stable across early life, with poorer diet quality associated with maternal socio-demographic and other factors and childhood adiposity. The preconception period may be an important window to promote positive maternal dietary changes in order to improve childhood outcomes.

Regulatory T Cells in Pregnancy Adverse Outcomes: A Systematic Review and Meta-Analysis.

Background: Several studies report the role of Regulatory T-cells (Tregs) in the pathophysiology of pregnancy adverse outcomes. Objective: The aim of this systematic review and meta-analysis was to determine whether there is an association between regulatory T cell levels and pregnancy adverse outcomes (PAOs), including pre-eclampsia and preterm birth (PTB). Method: Literature searches were conducted in PubMed/MEDLINE, Embase, and Cochrane CENTRAL databases. Inclusion criteria were original articles (clinical trials, case-control studies and cohort studies) comparing Tregs, sampled from the decidua or maternal blood, in healthy pregnant women versus women with pre-eclampsia or PTB. The outcome was standardised mean difference (SMD) in Treg numbers. The tau-squared (Tau²), inconsistency index (I²), and chi-squared (χ²) test quantified heterogeneity among different studies. Analyses were performed in RevMan software V.5.4.0 for Mac using a random-effects model with outcome data reported with 95% confidence intervals (CI). This study was prospectively registered with PROSPERO (CRD42020205469). PRISMA guidelines were followed. Results: From 4,085 unique studies identified, 36 were included in qualitative synthesis, and 34 were included in quantitative synthesis (meta-analysis). In total, there were 1,783 participants in these studies: healthy controls=964, pre-eclampsia=759, PTB=60. Thirty-two studies compared Tregs in healthy pregnant women and women with pre-eclampsia, and 30 of these sampled Tregs from peripheral blood showing significantly higher Treg numbers in healthy pregnancies (SMD; 1.46; 95% CI, 1.03-1.88; I²=92%). Four studies sampled Tregs from the maternal decidua showing higher Tregs in healthy pregnancies (SMD, 0.76; 95% CI, -0.13-1.65; I²=84%). No difference was found in the number of Tregs between early versus late pre-eclampsia (SMD,-1.17; 95% CI, -2.79-0.44; I²=94%). For PTB, two studies compared Tregs sampled from the peripheral blood with a tendency for higher Tregs in healthy pregnancies but this did not reach significance (SMD, 2.18; 95% CI, -1.34-5.70; I²=96%). Subcohort analysis using Treg analysis (flow cytometry vs. qPCR vs. immunofluorescence tissue staining) showed similar associations. Conclusion: Lower Tregs in pregnancy, sampled from the maternal peripheral blood, are associated with pre-eclampsia. There is a need for further studies to confirm a relationship between low Tregs and PTB. As the precise mechanisms by which Tregs may mediate pre-eclampsia and PTB remain unclear, further fundamental research is necessary to elucidate the underlying processes and highlight the causative link. Systematic Review Registration: PROSPERO, identifier CRD42020205469.

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.

Modifiable Determinants of Postpartum Weight Loss in Women with Obesity: A Secondary Analysis of the UPBEAT Trial.

Pregnancy can alter a woman's weight gain trajectory across the life course and contribute to the development of obesity through retention of weight gained during pregnancy. This study aimed to identify modifiable determinants associated with postpartum weight retention (PPWR; calculated by the difference in pre-pregnancy and 6 month postpartum weight) in 667 women with obesity from the UPBEAT study. We examined the relationship between PPWR and reported glycaemic load, energy intake, and smoking status in pregnancy, excessive gestational weight gain (GWG), mode of delivery, self-reported postpartum physical activity (low, moderate, and high), and mode of infant feeding (breast, formula, and mixed). At the 6 month visit, 48% (n = 320) of women were at or above pre-pregnancy weight. Overall, PPWR was negative (-0.06 kg (-42.0, 40.4)). Breastfeeding for ≥4 months, moderate or high levels of physical activity, and GWG ≤9 kg were associated with negative PPWR. These three determinants were combined to provide a modifiable factor score (range 0-3); for each added variable, a further reduction in PPWR of 3.0 kg (95% confidence interval 3.76, 2.25) occurred compared to women with no modifiable factors. This study identified three additive determinants of PPWR loss. These provide modifiable targets during pregnancy and the postnatal period to enable women with obesity to return to their pre-pregnancy weight.

Diet, Physical Activity and Gestational Weight Gain Patterns among Pregnant Women Living with Obesity in the North East of England: The GLOWING Pilot Trial.

Maternal diet, physical activity (PA) behaviours, and gestational weight gain (GWG) are important for optimum health of women and their babies. This secondary analysis of the GLOWING pilot cluster trial explored these among women living with obesity in high deprivation. Pregnant women completed food frequency, PA and psychosocial questionnaires. Weights were retrieved from medical records and measured during routine appointments with midwives. Descriptive and regression analyses were stratified by obesity class. A total of 163 women were recruited; 54.0% had class 1 obesity, 25.8% class 2, 20.2% class 3, and 76.1% lived in the two most deprived quintiles. Women had suboptimal dietary intake, particularly for oily fish, fruit and vegetables. PA was predominantly light intensity, from household, care and occupational activities. Most women gained weight outside of Institute of Medicine (IOM) guideline recommendations (87.8%); women in class 3 obesity were most likely to have inadequate GWG below IOM recommendations (58.3%, p < 0.01) and reduced odds of excessive GWG compared with class 1 (AOR 0.13, 95% 0.04-0.45). Deprived women with obesity have a double inequality as both increase pregnancy risks. This population requires support to meet guideline recommendations for diet, PA and GWG. Further research exploring obesity classes would inform policies and care to achieve the best pregnancy outcomes.

Modifiable early life exposures associated with adiposity and obesity in 3-year old children born to mothers with obesity.

BACKGROUND: Children born to mothers with obesity are at increased risk of obesity. Influences underlying this predisposition include in-utero exposures, genetic predisposition and a shared family environment. Effective intervention strategies are needed to prevent obesity in these high-risk children; this requires evaluation of modifiable pregnancy and early-life risk factors. OBJECTIVES: To assess the individual and cumulative contributions of maternal and early-life modifiable exposures on childhood adiposity and obesity outcomes in 3-year-old children born to women with obesity. METHODS: We used adjusted regression to assess the individual and cumulative contributions of six exposures (early pregnancy BMI, excessive gestational weight gain, mode of infant feeding and three measures of childhood eating habits [food responsiveness, slowness in eating and a processed/snacking dietary pattern score]) on body composition in 495 three-year-old children. Outcomes included BMI z-score, arm circumference and overweight/obesity (BMI≥25.0 kg/m2 ). RESULTS: While the UPBEAT intervention did not influence adiposity outcomes in 3-year-old children, the six modifiable exposures combined incrementally to increase childhood adiposity and obesity. For each additional exposure, children had a higher BMI z-score (ß = 0.35SD [95% confidence interval: 0.23, 0.47]), arm circumference (ß = 0.59 cm [0.40, 0.79]) and risk of overweight/obesity (relative risk 1.49 [1.26, 1.77]). Compared to no exposures, children with four or more exposures had a higher BMI z-score (1.11SD [0.65, 1.58]), arm circumference (2.15 cm [1.41, 2.89]) and risk of overweight/obesity (3.01 [1.67, 5.41]) (all P < 0.001). CONCLUSION: Our findings suggest that complex interventions targeting preconception, pregnancy, perinatal and early childhood exposures offer a potential strategy for prevention of pre-school obesity.

Adiposity and cardiovascular outcomes in three-year-old children of participants in UPBEAT, an RCT of a complex intervention in pregnant women with obesity.

BACKGROUND: Maternal obesity is associated with offspring cardiometabolic risk. UPBEAT was a randomised controlled trial of an antenatal diet and physical activity intervention in 1555 women with obesity. The intervention was associated with lower gestational weight gain, healthier diet and metabolic profile in pregnancy, and reduced infant adiposity at six months. OBJECTIVE: We have investigated whether the UPBEAT intervention influenced childhood cardiometabolic outcomes or was associated with sustained improvements in maternal lifestyle 3-years after delivery. METHODS: In UPBEAT mother-child dyads at the 3-year follow-up, we assessed childhood blood pressure, resting pulse rate, and adiposity (body mass index, skinfold thicknesses, body fat, waist and arm circumferences) and maternal diet, physical activity, and anthropometry. RESULTS: 514 three-year-old children attended the appointment (49% intervention, 51% standard care). There was no difference in the main outcome of interest, subscapular skinfold thickness, between the trial arms (-0.30 mm, 95% confidence interval: -0.92, 0.31). However, the intervention was associated with a lower resting pulse rate (-5 bpm [-8.41, -1.07]). There was also a non-significant lower odds of overweight/obesity (OR 0.73; 0.50, 1.08). Maternal dietary improvements observed in the UPBEAT trial, including glycaemic load and saturated fat were maintained 3-years postpartum. CONCLUSION: This study has demonstrated that an antenatal dietary and physical activity intervention in women with obesity is associated with lower offspring pulse rate and sustained improvement in maternal diet. Whilst larger than previous cohorts, there remains potential for bias from attrition and these findings require validation in future cohorts.

Iodine status of pregnant women with obesity from inner city populations in the United Kingdom.

BACKGROUND/OBJECTIVES: Iodine is essential for foetal neurodevelopment and growth. Requirements increase in pregnancy to support increased thyroid hormone synthesis for maternal and foetal requirements, and for foetal transfer. Iodine deficiency in pregnancy is widely reported, and obesity has been associated with sub-optimal thyroid function. We evaluated iodine status and its relation with birthweight in a secondary analysis of pregnant women with obesity from multi-ethnic inner-city settings who participated in the UK Pregnancies Better Eating and Activity trial (UPBEAT). SUBJECTS/METHODS: Iodine and creatinine concentrations were evaluated in spot urine samples in the second (15+0-18+6 weeks, n = 954) trimester of pregnancy. We assessed iodine status as urinary iodine concentration (UIC) and urinary iodine-to-creatinine ratio (UI/Cr) and applied WHO/UNICEF/IGN population threshold of median UIC > 150 µg/L for iodine sufficiency. Relationships between iodine status and birthweight were determined using linear and logistic regression with appropriate adjustment, including for maternal BMI and gestational age. RESULTS: Median (IQR) UIC and UI/Cr in the second trimester of pregnancy were 147 µg/L (99-257) and 97 µg/g (59-165), respectively. An UI/Cr <150 µg/g was observed in 70% of women. Compared to women with UI/Cr >150 µg/g, there was a trend for women with UI/Cr <150 µg/g to deliver infants with a lower birthweight (ß = -60.0 g; 95% CI -120.9 to -1.01, P = 0.05). CONCLUSIONS: Iodine status of pregnant women with obesity from this cohort of UK women was suboptimal. Lower iodine status was associated with lower birthweight.

Maternal dysglycaemia, changes in the infant's epigenome modified with a diet and physical activity intervention in pregnancy: Secondary analysis of a randomised control trial.

BACKGROUND: Higher maternal plasma glucose (PG) concentrations, even below gestational diabetes mellitus (GDM) thresholds, are associated with adverse offspring outcomes, with DNA methylation proposed as a mediating mechanism. Here, we examined the relationships between maternal dysglycaemia at 24 to 28 weeks' gestation and DNA methylation in neonates and whether a dietary and physical activity intervention in pregnant women with obesity modified the methylation signatures associated with maternal dysglycaemia. METHODS AND FINDINGS: We investigated 557 women, recruited between 2009 and 2014 from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), a randomised controlled trial (RCT), of a lifestyle intervention (low glycaemic index (GI) diet plus physical activity) in pregnant women with obesity (294 contol, 263 intervention). Between 27 and 28 weeks of pregnancy, participants had an oral glucose (75 g) tolerance test (OGTT), and GDM diagnosis was based on diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), with 159 women having a diagnosis of GDM. Cord blood DNA samples from the infants were interrogated for genome-wide DNA methylation levels using the Infinium Human MethylationEPIC BeadChip array. Robust regression was carried out, adjusting for maternal age, smoking, parity, ethnicity, neonate sex, and predicted cell-type composition. Maternal GDM, fasting glucose, 1-h, and 2-h glucose concentrations following an OGTT were associated with 242, 1, 592, and 17 differentially methylated cytosine-phosphate-guanine (dmCpG) sites (false discovery rate (FDR) ≤ 0.05), respectively, in the infant's cord blood DNA. The most significantly GDM-associated CpG was cg03566881 located within the leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) (FDR = 0.0002). Moreover, we show that the GDM and 1-h glucose-associated methylation signatures in the cord blood of the infant appeared to be attenuated by the dietary and physical activity intervention during pregnancy; in the intervention arm, there were no GDM and two 1-h glucose-associated dmCpGs, whereas in the standard care arm, there were 41 GDM and 160 1-h glucose-associated dmCpGs. A total of 87% of the GDM and 77% of the 1-h glucose-associated dmCpGs had smaller effect sizes in the intervention compared to the standard care arm; the adjusted r2 for the association of LGR6 cg03566881 with GDM was 0.317 (95% confidence interval (CI) 0.012, 0.022) in the standard care and 0.240 (95% CI 0.001, 0.015) in the intervention arm. Limitations included measurement of DNA methylation in cord blood, where the functional significance of such changes are unclear, and because of the strong collinearity between treatment modality and severity of hyperglycaemia, we cannot exclude that treatment-related differences are potential confounders. CONCLUSIONS: Maternal dysglycaemia was associated with significant changes in the epigenome of the infants. Moreover, we found that the epigenetic impact of a dysglycaemic prenatal maternal environment appeared to be modified by a lifestyle intervention in pregnancy. Further research will be needed to investigate possible medical implications of the findings. TRIAL REGISTRATION: ISRCTN89971375.