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 r²for 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.

Excessive gestational weight gain (GWG) and postpartum weight retention (PPWR) may predispose women to the development of obesity. The objective of this systematic review was to evaluate the effectiveness of lifestyle interventions in overweight or obese pregnant and/or postpartum women for managing postpartum weight up to 2 years after giving birth. Eighteen randomised controlled trials were included (2559 participants) and divided into three categories according to the timing of the intervention: pregnancy only (n = 3), postpartum only (n = 12) and pregnancy and postpartum (n = 3). The intervention duration varied from 10 weeks to 10 months and included diet only (n = 5) or diet and physical activity (n = 13). Seven postpartum only interventions reported significant improvements in postpartum weight when compared to the control group. Most of these interventions were short and intensive, lasting 10–16 weeks. One pregnancy only and one pregnancy and postpartum intervention reported reduced PPWR at 6 months. Nine trials did not report an effect of the intervention on postpartum weight. However, of these, four reported associations between GWG and PPWR. This review suggests that successful postpartum weight management is achievable with intensive lifestyle interventions starting in the postpartum period; however, there is insufficient evidence to conclude whether interventions starting in pregnancy are effective. Larger trials utilising comparative methodologies in the pregnancy and postpartum periods are required to inform the development of targeted strategies preventing PPWR or reducing postpartum weight.

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.

Obesity in pregnancy may negatively influence maternal and infant iron status. The aim of this study was to examine the association of obesity with inflammatory and iron status in both mother and infant in two prospective studies in pregnancy: UPBEAT and SCOPE. Maternal blood samples from obese (n = 245, BMI ≥ 30 kg/m²) and normal weight (n = 245, BMI < 25 kg/m²) age matched pregnant women collected at approximately 15 weeks’ gestation, and umbilical cord blood samples collected at delivery, were analysed for a range of inflammatory and iron status biomarkers. Concentrations of C- reactive protein and Interleukin-6 in obese women compared to normal weight women were indicative of an inflammatory response. Soluble transferrin receptor (sTfR) concentration [18.37 nmol/L (SD 5.65) vs. 13.15 nmol/L (SD 2.33)] and the ratio of sTfR and serum ferritin [1.03 (SD 0.56) vs. 0.69 (SD 0.23)] were significantly higher in obese women compared to normal weight women (P < 0.001). Women from ethnic minority groups (n = 64) had higher sTfR concentration compared with white women. There was no difference in maternal hepcidin between obese and normal weight women. Iron status determined by cord ferritin was not statistically different in neonates born to obese women compared with neonates born to normal weight women when adjusted for potential confounding variables. Obesity is negatively associated with markers of maternal iron status, with ethnic minority women having poorer iron statuses than white women.

Summary: Background: The relationships between eating habits, behaviours, and the development of obesity in preschool children is not well established.Objective: As children of mothers with obesity are themselves at risk of obesity, we examined these relationships in a cohort of 482 three‐year‐old children of mothers with obesity from the UK Pregnancy Better Eating and Activity Trial (UPBEAT).Method: Dietary patterns were derived using factor analysis of an 85‐item food frequency questionnaire (FFQ). Eating behaviours were assessed using the Children's Eating Behaviour Questionnaire (CEBQ). Measures of body composition included age‐specific BMI cut‐offs, WHO z scores, sum of skinfolds, waist and arm circumferences, and body fat percentage. Using adjusted regression analysis, we examined associations between dietary patterns, eating behaviours, and measures of body composition.Results: Three distinct dietary patterns were defined: “healthy/prudent,” “African/Caribbean,” and “processed/snacking.” The “processed/snacking” pattern was associated with greater odds of obesity; OR 1.53 (95% CI, 1.07‐2.19). The “African/Caribbean” and the “healthy/prudent” patterns were associated with a lower arm circumference (β = −0.23 cm [−0.45 to −0.01]) and sum of skinfolds (β = −1.36 cm [−2.88 to −0.37]), respectively. Lower enjoyment of food and food responsiveness, and greater slowness in eating and satiety, were associated with lower arm and waist circumferences, WHO z scores, and obesity (all P < .05).Conclusion: In children of mothers with obesity, those who had higher scores on a “processed/snacking” dietary pattern had greater odds of obesity. In contrast, slowness in eating was associated with lower measures of body composition. These novel findings highlight modifiable behaviours in high‐risk preschool children which could contribute to public health strategies for prevention of childhood obesity.

Summary: 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.