Infant arterial stiffness and maternal iron status in pregnancy: A UK birth cohort (Baby VIP study)

Background In animal studies, iron deficiency during pregnancy has been linked to increased offspring cardiovascular risk. No previous population studies have measured arterial stiffness early in life to examine its association with maternal iron status. Objective This study aimed to examine the association between maternal iron status in early pregnancy with infant brachio-femoral pulse wave velocity (PWV). Methods The Baby VIP (Baby’s Vascular health and Iron in Pregnancy) study is a UK-based birth cohort which recruited 362 women after delivery from the Leeds Teaching Hospitals postnatal wards. Ferritin and transferrin receptor levels were measured in maternal serum samples previously obtained in the first trimester. Infant brachio-femoral PWV was measured during a home visit at 2-6 weeks. Results Iron depletion (ferritin <15 ug/L) was detected in 79 (23%) women in early pregnancy. Infant PWV (m=6.7 m/s, sd=1.3, n=284) was not associated with maternal ferritin (adjusted change per 10 ug/L= 0.02, 95% CI -0.01, 0.1), nor with iron depletion (adjusted change = -0.2, 95% CI -0.6, 0.2). No evidence of association was observed between maternal serum transferrin receptor level or its ratio to ferritin with infant PWV. Maternal anaemia (<11 g/dL) at ≤20 weeks gestation was associated with a 1.0 m/s increase in infant PWV (adjusted 95% CI 0.1, 1.9). Conclusion This is the largest study to-date which assessed peripheral PWV as a measure of arterial stiffness in infants. There was no evidence of an association between markers of maternal iron status early in pregnancy and infant PWV

Relationship of the Frequency, Distribution, and Content of Meals/Snacks to Glycaemic Control in Gestational Diabetes: The myfood24 GDM Pilot Study

This study examines nutritional intakes in Gestational diabetes mellitus piloting the myfood24 tool, to explore frequency of meals/snacks, and daily distribution of calories and carbohydrates in relation to glycaemic control. A total of 200 women aged 20–43 years were recruited into this prospective observational study between February 2015 and February 2016. Diet was assessed using myfood24, a novel online 24-h dietary recall tool. Out of 200 women 102 completed both ≥1 dietary recalls and all blood glucose measurements. Blood glucose was self-measured as part of usual care. Differences between groups meeting and exceeding glucose targets in relation to frequency of meal/snack consumption and nutrients were assessed using chi-squared and Mann–Whitney tests. Women achieving a fasting glucose target <5.3 mmol/L, compared to those exceeding it, consumed three meals (92% vs. 78%: p = 0.04) and three snacks (10% vs. 4%: p = 0.06) per day, compared with two or less; and in relation to evening snacks, consumed a higher percentage of daily energy (6% vs. 5%: p = 0.03) and carbohydrates (8% vs. 6%: p = 0.01). Achieving glycaemic control throughout the day was positively associated with snacking (p = 0.008). Achieving glucose targets was associated with having more snacks across the day, and may be associated with frequency and distribution of meals and nutrients. A larger study is required to confirm this

Maternal Fatty Fish Intake Prior to and during Pregnancy and Risks of Adverse Birth Outcomes: Findings from a British Cohort

Fish is an important source of the essential fatty acids contributing to foetal growth and development, but the evidence linking maternal fatty fish consumption with birth outcomes is inconsistent. In the UK, pregnant women are recommended to consume no more than two 140 g portions of fatty fish per week. This study aimed to investigate the association between fatty fish consumption before and during pregnancy with preterm birth and size at birth in a prospective birth cohort. Dietary intake data were acquired from a cohort of 1208 pregnant women in Leeds, UK (CARE Study) to assess preconception and trimester-specific fatty fish consumption using questionnaires. Multiple 24-h recalls during pregnancy were used to estimate an average fatty fish portion size. Intake was classified as ≤2, >2 portions/week and no fish categories. Following the exclusion of women taking cod liver oil and/or omega-3 supplements, the associations between fatty fish intake with size at birth and preterm delivery (<37 weeks gestation) were examined in multivariable regression models adjusting for confounders including salivary cotinine as a biomarker of smoking status.. The proportion of women reporting any fatty fish intake decreased throughout pregnancy, with the lowest proportion observed in trimester 3 (43%). Mean intakes amongst consumers were considerably lower than that recommended, with the lowest intake amongst consumers observed in the 1st trimester (106 g/week, 95% CI: 99, 113). This was partly due to small portion sizes when consumed, with the mean portion size of fatty fish being 101 g. After adjusting for confounders, no association was observed between fatty fish intake before or during pregnancy with size at birth and preterm delivery

Is infant arterial stiffness associated with maternal blood pressure in pregnancy? Findings from a UK birth cohort (Baby VIP study)

Background: In adults, arterial stiffness measured by pulse wave velocity (PWV) is regarded as a predictor of cardiovascular disease. Infant vascular development depends on factors related to pregnancy, including maternal blood pressure (BP). This study assessed the association between maternal BP in pregnancy and infant brachio-femoral PWV at age 2–6 weeks. Methods: The Baby Vascular health and Iron in Pregnancy (Baby VIP) study is a birth cohort which measured PWV and heart rate (HR) in 284 babies in Leeds, UK, at 2–6 weeks after birth. Maternal BP measurements at 12 and 36 weeks gestation was collected from antenatal clinical records. Multivariable linear regression models assessed associations between maternal systolic and diastolic BPs, and BP change from booking to 36 weeks, with infant PWV adjusting for covariables at both mother and baby level. Results: There was no evidence of an association between infant PWV and maternal systolic BP at booking (adjusted regression coefficient -0.01 m/s per 10mmHg, 95% CI -0.11, 0.14, p = 0.84) or at 36 weeks (adjusted regression coefficient 0.00 m/s per 10mmHg, 95% CI -0.12, 0.11, p = 0.95). Change between 12 and 36 weeks gestation of more than 30 mmHg in systolic BP or 15 mmHg in diastolic BP was also not associated with infant PWV. There was an inverse relationship between infant HR and infant PWV (regression coefficient -0.14 m/s per 10 bpm, 95% CI -0.22, -0.05, p<0.01). Conclusions: This study has shown no evidence of association between infant PWV at 2–6 weeks of age and maternal BP in early or late pregnancy. Infant HR was inversely associated with infant PWV. Further studies are required to determine the predictors of infant PWV as well as the importance and long term implications of PWV measurements in infants

Agreement between an online dietary assessment tool (myfood24) and interviewer-administered 24-h dietary recall in British adolescents aged 11-18 years

myfood24 is an online 24hour dietary assessment tool developed for use among British adolescents and adults. Limited information is available regarding the validity of using new technology in assessing nutritional intake among adolescents. Thus, a relative validation of myfood24 against a face-to-face interviewer-administered 24hour multiple-pass recall (MPR) was conducted among 75 British adolescents aged 11-18 years old. Participants were asked to complete myfood24 and an interviewer-administered MPR on the same day for two non-consecutive days at school. Total energy intake (EI) and nutrients recorded by the two methods were compared using intraclass correlation coefficients (ICC), Bland-Altman plots (using between and within-individual information) and weighted Kappa to assess the agreement. Energy, macronutrients and other reported nutrients from myfood24 demonstrated strong agreement with the interview MPR data and ICC ranged from 0.46 for sodium to 0.88 for EI. There was no significant bias between the two methods for EI, macronutrients and most reported nutrients. The mean difference between myfood24 and the interviewer-administered MPR for EI was -55 kcal (-230kJ) (95% CI: -117, 7 kcal, (-490 to 30 kJ); P=0.4) with limits of agreement ranging between 39% (-797kcal (3336kJ)) lower and 34% (687 kcal (2874kJ)) higher than the interviewer-administered MPR. There was good agreement in terms of classifying adolescents into tertiles of EI (κ=0.64). The agreement between day1 and day2 was as good for myfood24 as for the interviewer-administered MPR reflecting the reliability of myfood24. myfood24 has the potential to collect dietary data of comparable quality to that of an interviewer-administered MPR

Prenatal and Postpartum Maternal Iodide Intake from Diet and Supplements, Urinary Iodine and Thyroid Hormone Concentrations in a Region of the United Kingdom with Mild-to-Moderate Iodine Deficiency

Iodine is essential for normal thyroid function, supporting healthy fetal and child development. Io-dine requirements increase in pregnancy, but many women in regions without salt iodisation have insufficient intakes. We explored associations between iodide intake and urinary iodine concentra-tion (UIC), urinary iodine:creatinine ratio (I:Cr), thyroid stimulating hormone, thyroglobulin, free triiodothyronine, free thyroxine and palpable goiter in a region of mild-to-moderate iodine insufficiency. 246 pregnant women aged 18-40 in Bradford, UK, joined the Health and Iodine in Babies (Hiba) study. They provided detailed information on diet and supplement use, urine and serum samples and were assessed for goiter, at around 12, 26 and 36 weeks gestation, and 6, 18 and 30 weeks postpartum. Dietary iodide intake from food and drink was estimated using six 24-hour re-calls. During pregnancy, median (IQR) dietary iodide intake was 101µg/day (54, 142), with 42% from dairy and 9% white fish. Including supplements, intake was 143µg/day (94, 196), with 49% < UK reference nutrient intake (140µg/day). Women with Pakistani heritage had 129µg/day (87, 190) median total intake. Total intake during pregnancy was associated with 4% (95% CI: 1%, 7%) high-er UIC, 5% (3%, 7%) higher I:Cr, 4% (2%, 6%) lower thyroglobulin and 21% (9%, 32%) lower odds of palpable goiter per 50µg/day. This cohort consumed less iodide in pregnancy than UK and World Health Organization dietary recommendations. UIC, I:Cr and thyroglobulin were associated with intake. Higher intake was associated with fewer goiters. Because dairy was the dominant source of iodide, women following plant-based or low-dairy diets may be at particular risk of iodine insufficiency

Maternal iodine status in a multi‐ethnic UK birth cohort: Associations with child cognitive and educational development

Background: Maternal iodine requirements increase during pregnancy to supply thyroid hormones critical for fetal neurodevelopment. Iodine insufficiency may result in poorer cognitive or child educational outcomes but current evidence is sparse and inconsistent. Objectives: To quantify the association between maternal iodine status and child educational outcomes. Methods: Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6971 mothers at 26‐28 weeks' gestation participating in the Born in Bradford cohort. Maternal iodine status was examined in relation to child school achievement (early years foundation stage (EYFS), phonics, and Key Stage 1 (KS1)), other learning outcomes, social and behavioural difficulties, and sensorimotor control in 5745 children aged 4‐7 years. Results: Median (interquartile range) UIC was 76 µg/L (46, 120), and I:Cr was 83 µg/g (59, 121). Overall, there was no strong or consistent evidence to support associations between UIC or I:Cr and neurodevelopmental outcomes. For instance, predicted EYFS and phonics scores (primary outcomes) at the 25th vs 75th I:Cr percentiles (99% confidence intervals) were similar, with no evidence of associations: EYFS scores were 32 (99% CI 31, 33) and 33 (99% CI 32, 34), and phonics scores were 34 (99% CI 33, 35) and 35 (99% CI 34, 36), respectively. Conclusions: In the largest single study of its kind, there was little evidence of detrimental neurodevelopmental outcomes in children born to pregnant women with iodine insufficiency as defined by World Health Organization–outlined thresholds. Alternative functional biomarkers for iodine status in pregnancy and focused assessment of other health outcomes may provide additional insight

A systematic review of reviews identifying UK validated dietary assessment tools for inclusion on an interactive guided website for researchers: www.nutritools.org

Background: Health researchers may struggle to choose suitable validated dietary assessment tools (DATs) for their target population. The aim of this review was to identify and collate information on validated UK DATs and validation studies for inclusion on a website to support researchers to choose appropriate DATs. Design: a systematic review of reviews of DATs was undertaken, DATs validated in UK populations were extracted from the studies identified . A searchable website was designed to display this data. Additionally, mean differences and limits of agreement between test and comparison methods were summarised by method, weighting by sample size. Results: Over 900 validation results covering 5 life-stages, 18 nutrients, 6 dietary assessment methods and 9 validation method types were extracted from 63 validated DATs which were identified from 68 reviews. These were incorporated into www.nutritools.org. Limits of Agreement were determined for about half of validations. 34 DATs were FFQs. Only 17 DATs were validated against biomarkers, and only 19 DATs were validated in infant/children/adolescents. Conclusions: The interactive www.nutritools.org website holds extensive validation data identified from this review and can be used to guide researchers to critically compare and choose a suitable DAT for their research question, leading to improvement of nutritional epidemiology research

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care