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During pregnancy, changes occur to influence the maternal gut microbiome, and potentially the fetal microbiome. Diet has been shown to impact the gut microbiome. Little research has been conducted examining diet during pregnancy with respect to the gut microbiome. To meet inclusion criteria, dietary analyses must have been conducted as part of the primary aim. The primary outcome was the composition of the gut microbiome (infant or maternal), as assessed using culture-independent sequencing techniques. This review identified seven studies for inclusion, five examining the maternal gut microbiome and two examining the fetal gut microbiome. Microbial data were attained through analysis of stool samples by 16S rRNA gene-based microbiota assessment. Studies found an association between the maternal diet and gut microbiome. High-fat diets (% fat of total energy), fat-soluble vitamins (mg/day) and fibre (g/day) were the most significant nutrients associated with the gut microbiota composition of both neonates and mothers. High-fat diets were significantly associated with a reduction in microbial diversity. High-fat diets may reduce microbial diversity, while fibre intake may be positively associated with microbial diversity. The results of this review must be interpreted with caution. The number of studies was low, and the risk of observational bias and heterogeneity across the studies must be considered. However, these results show promise for dietary intervention and microbial manipulation in order to favour an increase of health-associated taxa in the gut of the mother and her offspring.

OBJECTIVE: To examine the association between maternal metabolic parameters in pregnancy and growth trajectories up to 5 years of age. METHODS: Data from mother-child pairs who participated in the ROLO study, a randomized trial examining the impact of a low glycaemic index diet on the recurrence of macrosomia, were analysed. Fetal and child growth trajectories were developed from longitudinal measurements from 20 weeks gestation up to 5 years of age. We examined associations between maternal fasting glucose, insulin, HOMA-IR and leptin, taken in early pregnancy (14-16 weeks) and late pregnancy (28 weeks), and weight (kg) and abdominal circumference (cm) trajectories using linear spline multilevel models. RESULTS: We found no strong evidence of associations between any maternal metabolic parameters and fetal to childhood weight and abdominal circumference trajectories from 20 weeks gestation to 5 years. CONCLUSION: In a cohort of women with obesity with infants at risk of macrosomia, maternal metabolic markers were not strongly associated with trajectories of weight or abdominal circumference from 20 weeks gestation to 5 years of age.

BACKGROUND/OBJECTIVES: Women with gestational diabetes (GDM) are advised to adapt a low glycaemic index (GI) diet, which may impact consumption of low-calorie sweeteners (LCS). LCS are increasingly popular as they add sweetness without contributing calories. This study aims to investigate the reported intakes of LCS-containing foods in women during pregnancy. SUBJECTS/METHODS: Pregnant women recruited for the ROLO study were included in this analysis (n = 571). Women were randomised to receive either an intervention of low-GI dietary advice or usual antenatal care. Women completed a 3-day food diary in each trimester. Nine LCS-containing food groups were identified, and the quantity (g/day) consumed was calculated. RESULTS: One-third of all pregnant women consumed LCS across each trimester of pregnancy. Of those in the intervention group who were LCS consumers in trimester 1, 71.6% were consumers in trimester 2, and 54.1% remained consumers in trimester 3. In the control group, less women remained consumers in trimester 2 and 3 at 58.1% and 41.9%, respectively. In trimester 2, following the dietary intervention, the proportion of LCS consumers in the intervention group was significantly higher than the proportion of consumers who were in the control group (p < 0.001). The most commonly consumed food groups were low-calorie fruit drinks, diet-cola drinks, and low-calorie yoghurts. CONCLUSIONS: One-third of pregnant women consumed LCS. The proportion of LCS consumers increased in the intervention group compared to the control group. Further research is needed to determine exposure levels to individual LCS, and the effect of prenatal exposure to LCS on maternal and child health outcomes.

BACKGROUND: Individual differences in children eating behaviours have been linked with childhood overweight and obesity. The determinants of childhood eating behaviours are influenced by a complex combination of hereditary and ecological factors. This study examines if key ecological predictors of childhood overweight; maternal socio-economic status (SES), children's screen time, and childcare arrangements, are associated with eating behaviours in children aged 5-years-old. METHODS: This is secondary, cross-sectional analysis of the ROLO (Randomized COntrol Trial of LOw glycemic diet in pregnancy) study, using data from the 5-year follow-up (n = 306). Weight, height, and body mass index (BMI) were obtained from mothers and children at the 5-year follow-up. Children's BMI z-scores were calculated. SES was determined using maternal education level and neighborhood deprivation score. Information on children's screen time and childcare arrangements were collected using lifestyle questionnaires. Children's eating behaviours were measured using the Children's Eating Behaviour Questionnaire (CEBQ). Multiple linear regression, adjusted for potential confounders, assessed associations between maternal SES, screen time and children's eating behaviours. One-way ANOVA, independent sample t-tests and Spearman's correlation examined childcare exposure and children's eating behaviour. RESULTS: Mothers in the lowest SES group had higher BMI and were younger than those in the highest SES group (p = < 0.001, p = 0.03 respectively). In adjusted analysis, the lowest SES group was associated with a 0.463-point higher mean score for 'Desire to Drink' (95% CI = 0.054,0.870, p = 0.027) and higher 'Slowness to Eat' (B = 0.388, 95% CI = 0.044,0.733, p = 0.027) when compared with the highest SES group. Screen time (hours) was associated with higher 'Food Fussiness' (B = 0.032, 95% CI = 0.014,0.051, p = 0.001). Those who attended childcare had higher scores for 'Desire to Drink'(p = 0.046). N

Engaging women with obesity in health-related studies during preconception is challenging. Limited data exists relating to their participation. The aim of this study is to explore the experiences and opinions of women participating in a weight-related, preconception trial. This is an explanatory sequential (quan-QUAL) mixed-methods Study Within A Trial, embedded in the GetGutsy randomized controlled trial (ISRCTN11295995). Screened participants completed an online survey of eight questions (single or multiple choice and Likert scale) on recruitment, motivations and opinions on study activities. Participants with abdominal obesity (waist circumference ≥ 80 cm) were invited to a subsequent semi-structured, online focus group (n = 2, 9 participants) that was transcribed and analyzed using inductive thematic analysis, with a pragmatic epistemological approach. The survey (n = 102) showed the main research participation motivations were supporting health research (n = 38, 37.3%) and wanting health screening (n = 30, 29.4%). Most participants were recruited via email (n = 35, 34.7%) or social media (n = 15, 14.7%). In the FGs, participants valued flexibility, convenience and. research methods that aligned with their lifestyles. Participants had an expanded view of health that considered emotional well-being and balance alongside more traditional medical assessments. Clinical trialists should consider well-being, addressing the interconnectedness of health and incorporate a variety of research activities to engage women of reproductive age with obesity.

The present paper outlines current issues in the nutritional care of women during pregnancy and potential resources to address them. Globally, overnutrition, undernutrition and nutritional imbalances are widespread among women of reproductive age; increasing the risk of pregnancy complications and non-communicable diseases in both mothers and their children. Most women do not meet dietary guidelines for pregnancy. The World Health Organisation (WHO) recommends nutrition and weight counselling during pregnancy for all women. However, clinical practices focusing on nutrition vary and there is no consensus on which outcomes are most important for pregnancy nutrition interventions, with little consideration for the ‘patient voice’. The International Federation of Gynaecology and Obstetrics (FIGO) nutrition checklist is a clinical practice tool that is available for healthcare professionals that will address this issue. The pregnancy nutrition core outcome set will also support advancement of antenatal nutrition by identifying the most critical nutrition-related outcomes from the perspective of healthcare professionals, researchers and women with experience of pregnancy. While poor nutrition can result in adverse outcomes across women of all weight categories, those with obesity may require specialist care to reduce their risk. Obesity is a chronic, progressive, relapsing disease that has high individual variability in its prognosis. The use of obesity staging systems, which consider mental, physical and functional health, can stratify individuals into risk categories and aid in treatment prioritisation in pregnancy. As the prevalence of obesity continues to rise, an obesity staging approach may support clinicians, especially those in limited resource settings.

INTRODUCTION: Childhood obesity remains a significant global health concern. Early intervention through maternal diet during pregnancy represents a possible mode of improving childhood adiposity. AIM: To examine the impact of a low glycaemic index diet during pregnancy on offspring anthropometry at 5 years of age. METHODS: This is a secondary analysis of 387 children from the ROLO pregnancy study 5 years' post-intervention. At the follow-up, BMI, circumferences and skinfold thickness were obtained. A subgroup of 103 children had a DXA scan completed. Statistical analyses included Independent sample t tests, Mann Whitney-U tests and chi-square tests to compare the intervention and control groups. Adjusted analysis using linear regression controlled for significant confounders between participants who returned at follow-up and those that did not. RESULTS: There were no significant differences in BMI (16.05 kg/m2 vs 16.16 kg/m2 , P = 0.403), general adiposity (36.60 mm vs 36.00 mm, P = 0.920), central adiposity (0.61 mm vs 0.60 mm, P = 0.540), total fat mass (4.91 kg vs 4.71 kg, P = 0.377) or total lean mass (14.29 kg vs 14.56 kg, P = 0.386) between the intervention and control groups, respectively. No associations were observed in 5-year outcomes in adjusted analyses when controlling for maternal age at delivery, maternal early pregnancy BMI, maternal education and gestational age. CONCLUSION: Our study found no evidence that a low glycaemic index diet in pregnancy impacts offspring anthropometry 5 years' post-intervention. Therefore, modulating maternal carbohydrate quality in pregnancy may not be an appropriate approach to improving weight status in childhood. Future research should investigate the impact of other dietary practices in pregnancy on child health.

BACKGROUND: Child eating behaviours can negatively contribute to the development of childhood obesity. This study investigated associations between breastfeeding habits, maternal eating behaviours and child eating behaviours, in 5-year-old children. METHODS: Secundigravida women were recruited to the ROLO dietary randomised controlled trial (Dublin, Ireland) and were followed up with their children to 5 years of age. Breastfeeding exposure and duration were obtained at postnatal and infant follow-up at 2 and 6 months and 2 and 5 years. At 5 years, maternal and child eating behaviours were measured using the Three Factor Eating Questionnaire and the Child Eating Behaviour Questionnaire, respectively. Regression determined associations between breastfeeding habits and maternal eating behaviours with child eating behaviours, controlling for RCT group, maternal education level, maternal BMI at 5 years, childcare exposure and child BMI centile at 5-year follow-up. RESULTS: There were 230 mother and child pairs analysed. One hundred and fifty-eight mothers had initiated breastfeeding. Median breastfeeding duration was 22 (IQR 33) weeks. Children who were never breastfed were more likely to express a desire to drink (B = -1.01, p = 0.022). Longer breastfeeding duration was associated with lower food responsiveness (B = -1.71, p = 0.003). Maternal uncontrolled eating was positively associated with child food responsiveness, emotional overeating and emotional undereating (B = 0.21, p < 0.001; B = 0.14, p = 0.005; B = 0.14, p = 0.005, respectively). Maternal emotional eating was associated with child emotional overeating and undereating (B = 0.27, p < 0.001, B = 0.29, p = 0.004, respectively). CONCLUSION: Not breastfeeding and short breastfeeding duration may contribute to the development of obesogenic eating behaviours in children, alongside maternal eating behaviours including uncontrolled and emotional eating. These 'food approach' eating behaviours may increase risk of ov

BACKGROUND: Gestational diabetes (GDM) impacts 8-18% of pregnancies and greatly increases both maternal and child risk of developing non-communicable diseases such as type 2 diabetes and obesity. Whilst lifestyle interventions in pregnancy and postpartum reduce this risk, a research translation gap remains around delivering implementable interventions with adequate population penetration and participation. Impact Diabetes Bump2Baby is an implementation project of an evidence-based system of care for the prevention of overweight and obesity. Bump2Baby and Me is the multicentre randomised controlled trial investigating the effectiveness of a mHealth coaching programme in pregnancy and postpartum for women at high risk of developing GDM. METHODS: Eight hundred women will be recruited in early pregnancy from 4 clinical sites within Ireland, the UK, Spain, and Australia. Women will be screened for eligibility using the validated Monash GDM screening tool. Participants will be enrolled from 12 to 24 weeks' gestation and randomised on a 1:1 basis into the intervention or control arm. Alongside usual care, the intervention involves mHealth coaching via a smartphone application, which uses a combination of synchronous and asynchronous video and text messaging, and allows for personalised support and goal setting with a trained health coach. The control arm receives usual care. All women and their children will be followed from early pregnancy until 12 months postpartum. The primary outcome will be a difference in maternal body mass index (BMI) of 0.8 kg/m2 at 12 months postpartum. Secondary maternal and infant outcomes include the development of GDM, gestational weight gain, pregnancy outcomes, improvements in diet, physical activity, sleep, and neonatal weight and infant growth patterns. The 5-year project is funded by the EU Commission Horizon 2020 and the Australian National Health and Medical Research Council. Ethical approval has been received. DISCUSSION: Previous inte

BACKGROUND: Adverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes. METHODS AND FINDINGS: We harmonized and pooled individual participant data (IPD) from up to 24,861 mother-child pairs in 7 European mother-offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal hei

BACKGROUND: Mounting evidence suggests that maternal diet influences pregnancy and birth outcomes, but its contribution to the global epidemic of childhood obesity has not as yet been definitively characterized. We investigated whether maternal whole diet quality and inflammatory potential influence childhood adiposity. METHODS: We harmonized and pooled individual participant data from 16,295 mother-child pairs in seven European birth cohorts. Maternal pre-, early-, late-, and whole-pregnancy (any time during pregnancy) dietary quality and inflammatory potential assessed with the Dietary Approaches to Stop Hypertension (DASH) score and the energy-adjusted Dietary Inflammatory Index (E-DII™) score, respectively. Primary outcome was childhood overweight and obesity (OWOB) (age-and-sex-specific BMI z-score > 85th percentile). Secondary outcomes were sum of skinfold thickness (SST), fat mass index (FMI) and fat-free mass index (FFMI). We used multivariable regression analyses (adjusting for maternal lifestyle and sociodemographic factors) to assess the associations of maternal DASH and E-DII scores with offspring adiposity outcomes in cohort-specific analyses, with subsequent random-effect meta-analyses. RESULTS: The study mothers had a mean (SD) age of 30.2 (4.6) years and a mean BMI of 23.4 (4.2) kg/m2. Higher early-pregnancy E-DII scores (more pro-inflammatory diet) tended to be associated with a higher odds of late-childhood [10.6 (1.2) years] OWOB [OR (95% CI) 1.09 (1.00, 1.19) per 1-SD E-DII score increase], whereas an inverse association was observed for late-pregnancy E-DII score and early-childhood [2.8 (0.3) years] OWOB [0.91 (0.83, 1.00)]. Higher maternal whole pregnancy DASH score (higher dietary quality) was associated with a lower odds of late-childhood OWOB [OR (95% CI) 0.92 (0.87, 0.98) per 1-SD DASH score increase]; associations were of similar magnitude for early and late-pregnancy [0.86 (0.72, 1.04) and 0.91 (0.85, 0.98), respectively]. These associat

Background: Mounting evidence suggests that maternal diet influences pregnancy and birth outcomes, but its contribution to the global epidemic of childhood obesity has not as yet been definitively characterized. We investigated whether maternal whole diet quality and inflammatory potential influence childhood adiposity. Methods: We harmonized and pooled individual participant data from 16,295 mother-child pairs in seven European birth cohorts. Maternal pre-, early-, late-, and whole-pregnancy (any time during pregnancy) dietary quality and inflammatory potential assessed with the Dietary Approaches to Stop Hypertension (DASH) score and the energy-adjusted Dietary Inflammatory Index (E-DII™) score, respectively. Primary outcome was childhood overweight and obesity (OWOB) (age-and-sex-specific BMI z-score > 85th percentile). Secondary outcomes were sum of skinfold thickness (SST), fat mass index (FMI) and fat-free mass index (FFMI). We used multivariable regression analyses (adjusting for maternal lifestyle and sociodemographic factors) to assess the associations of maternal DASH and E-DII scores with offspring adiposity outcomes in cohort-specific analyses, with subsequent random-effect meta-analyses. Results: The study mothers had a mean (SD) age of 30.2 (4.6) years and a mean BMI of 23.4 (4.2) kg/m2. Higher early-pregnancy E-DII scores (more pro-inflammatory diet) tended to be associated with a higher odds of late-childhood [10.6 (1.2) years] OWOB [OR (95% CI) 1.09 (1.00, 1.19) per 1-SD E-DII score increase], whereas an inverse association was observed for late-pregnancy E-DII score and early-childhood [2.8 (0.3) years] OWOB [0.91 (0.83, 1.00)]. Higher maternal whole pregnancy DASH score (higher dietary quality) was associated with a lower odds of late-childhood OWOB [OR (95% CI) 0.92 (0.87, 0.98) per 1-SD DASH score increase]; associations were of similar magnitude for early and late-pregnancy [0.86 (0.72, 1.04) and 0.91 (0.85, 0.98), respectively

Background Adverse birth outcomes are major causes of morbidity and mortality during childhood and associate with a higher risk of noncommunicable diseases in adult life. Maternal periconception and antenatal nutrition, mostly focusing on single nutrients or foods, has been shown to influence infant birth outcomes. However, evidence on whole diet that considers complex nutrient and food interaction is rare and conflicting. We aim to elucidate the influence of whole-diet maternal dietary inflammatory potential and quality during periconceptional and antenatal periods on birth outcomes. Methods and findings We harmonized and pooled individual participant data (IPD) from up to 24,861 mother-child pairs in 7 European mother-offspring cohorts [cohort name, country (recruitment dates): ALSPAC, UK (1 April 1991 to 31 December 1992); EDEN, France (27 January 2003 to 6 March 2006); Generation R, the Netherlands (1 April 2002 to 31 January 2006); Lifeways, Ireland (2 October 2001 to 4 April 2003); REPRO_PL, Poland (18 September 2007 to 16 December 2011); ROLO, Ireland (1 January 2007 to 1 January 2011); SWS, United Kingdom (6 April 1998 to 17 December 2002)]. Maternal diets were assessed preconceptionally (n = 2 cohorts) and antenatally (n = 7 cohorts). Maternal dietary inflammatory potential and quality were ranked using the energy-adjusted Dietary Inflammatory Index (E-DII) and Dietary Approaches to Stop Hypertension (DASH) index, respectively. Primary outcomes were birth weight and gestational age at birth. Adverse birth outcomes, i.e., low birth weight (LBW), macrosomia, small-for-gestational-age (SGA), large-for-gestational-age (LGA), preterm and postterm births were defined according to standard clinical cutoffs. Associations of maternal E-DII and DASH scores with infant birth outcomes were assessed using cohort-specific multivariable regression analyses (adjusted for confounders including maternal education, ethnicity, prepregnancy body mass index (BMI), maternal he

An association between the vaginal microbiota and preterm birth (PTB) has been reported in several research studies. Population shifts from high proportions of lactobacilli to mixed species communities, as seen with bacterial vaginosis, have been linked to a twofold increased risk of PTB. Despite the increasing number of studies using next-generation sequencing technologies, primarily involving 16S rRNA-based approaches, to investigate the vaginal microbiota during pregnancy, no distinct microbial signature has been associated with PTB. Shotgun metagenomic sequencing offers a powerful tool to reveal community structures and their gene functions at a far greater resolution than amplicon sequencing. In this study, we employ shotgun metagenomic sequencing to compare the vaginal microbiota of women at high risk of preterm birth (n = 35) vs. a low-risk control group (n = 14). Although microbial diversity and richness did not differ between groups, there were significant differences in terms of individual species. In particular, Lactobacillus crispatus was associated with samples from a full-term pregnancy, whereas one community state-type was associated with samples from preterm pregnancies. Furthermore, by predicting gene functions, the functional potential of the preterm microbiota was different from that of full-term equivalent. Taken together, we observed a discrete structural and functional difference in the microbial composition of the vagina in women who deliver preterm. Importance: with an estimated 15 million cases annually, spontaneous preterm birth (PTB) is the leading cause of death in infants under the age of five years. The ability to accurately identify pregnancies at risk of spontaneous PTB is therefore of utmost importance. However, no single cause is attributable. Microbial infection is a known risk factor, yet the role of vaginal microbes is poorly understood. Using high-resolution DNA-sequencing techniques, we investigate the microbial communities pre

Shotgun metagenomic sequencing is a valuable tool for the taxonomic and functional profiling of microbial communities. However, this approach is challenging in samples, such as milk, where a low microbial abundance, combined with high levels of host DNA, result in inefficient and uneconomical sequencing. Here we evaluate approaches to deplete host DNA or enrich microbial DNA prior to sequencing using three commercially available kits. We compared the percentage of microbial reads obtained from each kit after shotgun metagenomic sequencing. Using bovine and human milk samples, we determined that host depletion with the MolYsis complete5 kit significantly improved microbial sequencing depth compared to other approaches tested. Importantly, no biases were introduced. Additionally, the increased microbial sequencing depth allowed for further characterization of the microbiome through the generation of metagenome-assembled genomes (MAGs). Furthermore, with the use of a mock community, we compared three common classifiers and determined that Kraken2 was the optimal classifier for these samples. This evaluation shows that microbiome analysis can be performed on both bovine and human milk samples at a much greater resolution without the need for more expensive deep-sequencing approaches.

BACKGROUND: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. METHODS: IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. RESULTS: Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model's calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions

BACKGROUND: The ROLO Study (Randomised cOntrol trial of a Low glycaemic index diet in pregnancy to prevent macrosomia) was a randomised control trial conducted between 2007 and 2011 to examine if a low glycaemic index (GI) diet could reduce the incidence of macrosomia. The ROLO Family Advisory Committee is a self-selected group of parents who are involved in the longitudinal follow-up of the ROLO Study. The committee was established in 2017 and the goal is to achieve a partnership between ROLO families and researchers, leading to improved research quality, relevance, and outcomes. This research method is termed "Public and patient involvement (PPI)" and describes how researchers collaborate and engage with the public in order to make research more relevant to them. METHODS: The ROLO study mothers and children have been prospectively followed-up at multiple time points post-pregnancy. In October 2017, all women were invited to join the ROLO Family Advisory Committee via email or via advertisement on the ROLO Study Facebook page. Fathers and other guardians of the study children were also invited to join. Two annual meetings with the research team and parents were held in 2018 and 2019. The meetings were recorded, transcribed verbatim by researchers, and thematically analysed. RESULTS: Parents provided opinions on the areas they felt should be explored within the ROLO study using information that was collected up to the current follow-up point. They also shared views on research interests which were of importance to them. These topics included; child mental health, fussy eating in childhood and healthy eating policies in schools. Mothers were much more concerned about factors which influenced their child's health rather than their own. Incorporating an element of PPI to this study was found to be a positive learning experience for participants and researchers. CONCLUSION: The involvement of parents has enriched the research agenda at the UCD Perinatal Research Centre.

BACKGROUND: The growth of the fetus is a complex process influenced by multiple factors. Studies have highlighted the important role of biochemical growth markers such as leptin and adiponectin on fetal growth. OBJECTIVE: To compare fetal growth trajectories with biochemical growth markers from maternal blood samples at 28 weeks' gestation, cord blood samples at birth, and in child blood samples at 5 years of age from mother-infant pairs who were part of the longitudinal ROLO study. METHODS: 781 mother-infant pairs from the ROLO and ROLO Kids study were included. Ultrasound measurements and birth weight were used to develop fetal growth trajectory groups for estimated abdominal circumference and estimated weight. Blood serum levels of leptin, adiponectin, insulin, TNF-alpha, and IL-6 from maternal, cord, and 5-year child samples were recorded. ANOVA and chi-square tests were applied to test the associations between fetal growth trajectory membership and maternal and child biochemical growth indicators. The influence of child sex was also investigated. RESULTS: Male sex was associated with a faster weight trajectory compared to females (p=0.001). At 28 weeks' gestation, maternal leptin levels were significantly higher in mothers with a fetus on a slower estimated abdominal circumference trajectory compared to fast (25616 [IQR: 11656.0 to 35341.0] vs. 14753.8 [IQR: 8565.4 to 24308.1], p < 0.001) and maternal adiponectin levels were lower in fetuses on a slower estimated abdominal circumference trajectory compared to a fast trajectory (22.4 [IQR: 13.6 to 35.9] vs. 27.6 [IQR: 17.6 to 46.3], p=0.027). No associations were noted with inflammatory markers. No associations were identified between fetal growth trajectories and growth markers at 5 years of age. CONCLUSIONS: This study shows that male sex is associated with an accelerated estimated weight trajectory. Furthermore, high leptin and low adiponectin in maternal serum in late gestation are associated with a slower f

INTRODUCTION: The establishment of the neonatal gut microbiome is a crucial step that may have lifelong health implications. We aimed to systematically review evidence on maternal probiotic supplementation during pregnancy and vertical transfer of the corresponding strain to the infant gut. MATERIAL AND METHODS: Medline, CINAHL, Embase, Web of Science, and OVID were searched from inception to September 2018. Studies of maternal probiotic supplementation for a minimum duration of 2 weeks and analyses of neonatal stool samples were included. The primary outcome was presence of the specific probiotic strain in the infant stool. Electronic databases were searched for relevant studies and references were cross-checked. Risk of bias among included studies was assessed and data were extracted independently by two authors. RESULTS: Three studies were included in the review. Only one study was identified involving prenatal maternal probiotic supplementation alone. Neonatal colonization with the maternally administered probiotic was not demonstrated but supplementation with the probiotic influenced levels of a bacterial strain other than that found in the probiotic product. The other two studies identified included both prenatal and postnatal supplementation of either mother or infant. All three studies reported employing strain-specific isolation methodology to isolate the supplemented bacterial strain in infant stool but none used whole metagenome shotgun sequencing. CONCLUSIONS: Few studies investigating transfer of a specific probiotic bacterial strain from mother to infant were identified, showing inconclusive evidence of vertical transfer.

A range of in utero and early-life factors can influence offspring epigenetics, particularly DNA methylation patterns. This study aimed to investigate the influence of a dietary intervention and factors in pregnancy on offspring epigenetic profile at five years of age. We also explored associations between body composition and methylation profile in a cross-sectional analysis. Sixty-three five-year-olds were selected from the ROLO Kids Study, a Randomized controlled trial Of a LOw glycemic index dietary intervention from the second trimester of pregnancy. DNA methylation was investigated in 780,501 CpG sites in DNA isolated from saliva. Principal component analysis identified no association between maternal age, weight, or body mass index (BMI) during pregnancy and offspring DNA methylation (p > 0.01). There was no association with the dietary intervention during pregnancy, however, gene pathway analysis identified functional clusters involved in insulin secretion and resistance that differed between the intervention and control. There were no associations with child weight or adiposity at five years of age; however, change in weight from six months was associated with variation in methylation. We identified no evidence of long-lasting influences of maternal diet or factors on DNA methylation at age five years. However, changes in child weight were associated with the methylome in childhood.

Bone health is extremely important in early childhood because children with low bone mineral density (BMD) are at a greater risk of bone fractures. While physical activity and intake of both calcium and vitamin D benefit BMD in older children, there is limited research on the determinants of good bone health in early childhood. The aim of this cross-sectional study was to investigate the impact of diet, physical activity, and body composition on BMD at five years of age. Dietary intakes and physical activity levels were measured through questionnaires. Whole body BMD was measured by dual-energy X-ray absorptiometry in 102 children. Child weight, height, circumferences, skinfolds and serum 25-hydroxyvitamin D (25OHD) concentrations were assessed. There was no association between BMD and dietary calcium, dietary vitamin D, 25OHD, physical activity, or sedentary behaviour. Several measures of body composition were significantly positively associated with BMD; however, neither fat mass nor lean body mass was associated with BMD.Conclusion: Although we found no association between self-reported dietary and lifestyle factors and bone health in early years, increased body size was linked with higher BMD. These findings are important as identifying modifiable factors that can improve bone health at a young age is of utmost importance.What is Known:• Bone health is extremely important in early childhood, as children with low bone mineral density (BMD) are at greater risk of bone fractures.• Physical activity has been found to be beneficial for bone health in adolescents, and body composition has also been associated with BMD in teenage years.• Limited research on the determinants of good bone health in early childhood.What is New:• No association between self-reported lifestyle and dietary factors with bone health in early childhood.• Increased body size was associated with higher BMD at five years of age.

BACKGROUND: High blood pressure (BP) in pregnancy is associated with significant adverse outcomes. In nonpregnant populations, the DASH (Dietary Approaches to Stop Hypertension) diet is associated with reductions in blood pressure. The present study investigated the relationship between the DASH dietary pattern and maternal BP in pregnancy. METHODS: This is an observational study of 511 women who participated in the ROLO study (Randomized cOntrol trial of LOw glycaemic index diet for the prevention of recurrence of macrosomia), 2007-2011, Dublin, Ireland. Auscultatory blood pressure, systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were taken. Mean arterial pressure (MAP) was calculated. Dietary intakes were recorded using 3-day food diaries in each trimester. DASH scoring criteria were used to score and rank participants from low to high intakes of foods recommended in the DASH diet. Statistical analysis using analysis of variance and multiple linear regression were used to determine the relationship between maternal BP and DASH scores. RESULTS: Dietary intake more closely resembling the DASH dietary recommendations throughout pregnancy was associated with a lower DBP (mmHg) in trimesters 1 [B: -0.70; 95% confidence interval (CI) = -1.21 to -0.18] and 3 (B: -0.68; 95% CI = -1.19 to -0.17), as well as lower MAP (mmHg) in trimesters 1 (B: -0.78; 95% CI = -1.33 to -0.25) and 3 (B: -0.54; 95% CI = -1.04 to -0.04), controlling for body mass index, age, education, energy intake and intervention grouping. CONCLUSIONS: The DASH dietary pattern was associated with lower maternal BP in pregnancy among healthy women without hypertensive disorders of pregnancy. Despite the observational nature of these findings, the results demonstrate the potential for healthcare professionals to intervene to promote cardiovascular health in pregnancy.

BACKGROUND: Elevated post-prandial blood glucose during pregnancy has been associated with adverse pregnancy and offspring outcomes, such as maternal gestational diabetes and excessive foetal growth. The ROLO Study is a randomized controlled trial (RCT) investigating the effect of a low glycaemic index (GI) diet in pregnancy to prevent foetal macrosomia (birth weight > 4000 g). We described the impact of a low-GI diet on the maternal and feto-placental unit metabolism by studying how the ROLO intervention affected maternal and cord blood metabolomes. METHODS: Fasting maternal plasma samples pre- and post-intervention of 51 pregnant women and 132 cord blood samples were measured with a targeted metabolomics approach using liquid-chromatography coupled to tandem mass spectrometry. The differences between RCT groups were explored via multivariate models with covariates correction. Significance was set at Bonferroni-corrected level of 0.05. RESULTS: A total of 262 metabolites species, sums and ratios were investigated. While no metabolite reached statistical significance after Bonferroni correction, many maternal phospholipids and acylcarnitines were elevated in the intervention group at uncorrected 0.05 alpha level. Most species contained saturated and monounsaturated fatty acid chains with 16 or 18 carbon atoms. In cord blood, no differences were identified between RCT groups. CONCLUSIONS: A low-GI diet in pregnancy was associated with a trend to modest but consistent changes in maternal lipid and fatty acid metabolism. The intervention seemed not to affect foetal metabolism. Our exploratory findings may be used to direct further investigations about low GI diets before and during pregnancy, to improve patient care for pre-conceptional and pregnant women with lipid dysregulations and potentially modulate the offspring's risk for future metabolic diseases. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54392969.

The physiology of how prelabour caesarean section (PCS) and induction of labour (IOL) in comparison to spontaneous vaginal delivery (SVD) has not been fully clarified yet. We measured 201 cord blood (CB) phospholipids and energy metabolites via LC/MS-MS in 109 newborns from the ROLO Kids study; metabolites were compared across the three parturition groups via linear mixed models with correction for multiple testing. In comparison to SVD, PCS babies had lower non-esterified fatty acids (NEFA), including sum of NEFA (p < 0.001), and trends for lower acylcarnitines. The lack of hormonal stimuli, especially catecholamines and cortisol, may underlie the metabolic changes involving gluconeogenesis from fatty acid oxidation (FAO) in PCS born infants. IOL and SVD infants showed no significant differences in metabolites, but ratios estimating carnitine palmitoyltrasferase 1 activity (precursor for FAO) were slightly higher in IOL than in SVD. Thus, IOL does not induce metabolic disadvantage when compared to SVD, though post-natal gluconeogenesis might start earlier due to the artificial solicitation in IOL. These data shed light on the physiology of parturition and may contribute to understand how mode of delivery might modulate future metabolic risks.

OBJECTIVE: To investigate whether maternal blood pressure (BP) below the diagnostic criteria of hypertensive disorders of pregnancy (HDP) is associated with maternal BP 5 years later. DESIGN: Prospective, observational study. SETTING: Dublin, Ireland (2007-2011). SAMPLE: Three hundred twenty-nine women from the ROLO study (Randomized cOntrol trial of LOw glycaemic index diet to prevent the recurrence of macrosomia). METHODS: Maternal BP measurements were taken during pregnancy (13, 28 and 34 weeks' gestation and day 1 postpartum) and at the 5-year follow-up. Systolic BP (SBP) and diastolic BP (DBP) were categorized as normal (SBP < 120 and DBP < 80 mm Hg), elevated (SBP 120-129 and DBP < 80 mm Hg), HTN stage 1 (SBP 130-139 or DBP 80-89 mm Hg) or HTN stage 2 (SBP ≥ 140 or DBP ≥ 90 mm Hg) at each timepoint. MAIN OUTCOME MEASURES: Maternal blood pressure at the 5-year follow-up. RESULTS: Women with elevated BP at 28 and 34 weeks' gestation had 2.68 (95% CI: 1.36-5.26) and 2.45-fold (95% CI: 1.22-4.95) increased odds of HTN stage 1 respectively, at the 5-year follow-up, compared to those with normal BP in pregnancy. CONCLUSION: Elevated BP at 28 and 34 weeks' gestation was associated with an increased risk of HTN stage 1 at 5 years later. Thus, raised BP, below the diagnostic criteria of HDP, could be flagged for follow-up postpartum.

BACKGROUND: Vitamin D status and season are intrinsically linked, and both have been proposed to be associated with glucose homeostasis in pregnancy, with conflicting results. We aimed to determine if exposure to winter and low maternal 25 hydroxyvitamin D (25OHD) in early pregnancy were associated with maternal glucose metabolism. METHODS: This is a secondary data analysis of 334 pregnant women enrolled in the ROLO study, Dublin. Serum 25OHD, fasting glucose, insulin and insulin resistance (HOMA-IR) were measured in early (12 weeks' gestation) and late pregnancy (28 weeks' gestation). Season of first antenatal visit was categorised as extended winter (November-April) or extended summer (May-October). Multiple linear regression models, adjusted for confounders, were used for analysis. RESULTS: Those who attended their first antenatal visit in extended winter had lower 25OHD compared to extended summer (32.9 nmol/L vs. 44.1 nmol/L, P < 0.001). Compared to those who attended their first antenatal visit during extended summer, extended winter was associated with increased HOMA-IR in early-pregnancy (46.7%) and late pregnancy (53.7%), independent of 25OHD <30 nmol/L and confounders. Early pregnancy 25OHD <30 nmol/L and extended winter were independently associated with significantly higher fasting glucose in late pregnancy (B = 0.15 and 0.13, respectively). CONCLUSIONS: Women who attended their first antenatal visit during the months of extended winter were more likely to have raised insulin resistance in early pregnancy, which had a lasting association to 28 weeks, and was independent of 25OHD. Our novel findings imply that seasonal variation in insulin resistance may not be fully explained by differences in vitamin D status. This could reflect circannual rhythm or seasonal lifestyle behaviours, and requires further exploration. TRIAL REGISTRATION: ISRCTN registry, ISRCTN54392969, date of registration: 22/04/2009, retrospectively registered.

BACKGROUND: Pregnancy is a time of altered metabolic functioning and maternal blood lipid profiles change to accommodate the developing fetus. While these changes are physiologically necessary, blood lipids concentrations have been associated with adverse pregnancy outcomes such as gestational diabetes, pregnancy-induced hypertension and high birth weight. As blood lipids are not routinely measured during pregnancy, there is limited information on what is considered normal during pregnancy and in fetal blood. METHODS: Data from 327 mother-child pairs from the ROLO longitudinal birth cohort study were analysed. Fasting total cholesterol and triglycerides were measured in early and late pregnancy and fetal cord blood. Intervals were calculated using the 2.5th, 50th and 97.5th centile. Data was stratified based on maternal body mass index (BMI) measured during early pregnancy. Differences in blood lipids between BMI categories were explored using ANOVA and infant outcomes of macrosomia and large-for-gestational-age (LGA) were explored using independent student T-tests and binary logistic regression. RESULTS: All maternal blood lipid concentrations increased significantly from early to late pregnancy. In early pregnancy, women with a BMI < 25 kg/m2 had lower concentrations of total cholesterol compared to women with a BMI of 25-29.9 kg/m2 (P = 0.02). With triglycerides, women in the obese category (BMI > 30 kg/m2) had higher concentrations than both women in the normal-weight and overweight category in early and late pregnancy (P < 0.001 and P = 0.03, respectively). In late pregnancy, triglyceride concentrations remained elevated in women in the obese category compared to women in the normal-weight category (P = 0.01). Triglyceride concentrations were also elevated in late pregnancy in mothers that then gave birth to infants with macrosomia and LGA (P = 0.01 and P = 0.03, respectively). CONCLUSION: Blood lipid concentrations increase during pregnancy and differ by mater

BACKGROUND: The in-utero environment affects fetal development; it is vital to understand how maternal diet during pregnancy influences childhood body composition. While research indicates that triglycerides in hyperglycaemic women may increase birth weight, little is known about this relationship in euglycemic women. This study examines the relationship between maternal blood lipid status and infant adiposity up to 2 years of age. METHODS: Data from 331 mother-child pairs from the ROLO longitudinal birth cohort study was analysed. Maternal dietary intakes were recorded and fasting blood lipids, leptin and HOMA were measured in early and late pregnancy and cord blood. Infant anthropometric measurements and skin-fold thicknesses were recorded at birth, 6 months and 2 years. Correlation and regression analyses were used to explore associations between maternal blood lipid status and infant adiposity. RESULTS: All maternal blood lipids increased significantly during pregnancy. Maternal dietary fat intake was positively associated with total cholesterol levels in early pregnancy. Late pregnancy triglycerides were positively associated with birth weight (P = 0.03) while cord blood triglycerides were negatively associated with birth weight (P = 0.01). Cord HDL-C was negatively associated with infant weight at 6 months (P = 0.005). No other maternal blood lipids were associated with infant weight or adiposity up to 2 years of age. CONCLUSION: Maternal and fetal triglycerides were associated with birth weight and cord HDL-C with weight at 6 months. Thus, maternal lipid concentrations may exert in-utero influences on infant body composition. There may be potential to modulate infant body composition through alteration of maternal diet during pregnancy.