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

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

Identification and functional characterisation of DNA methylation differences between East- and West-originating Finns

Eastern and Western Finns show a striking difference in coronary heart disease-related mortality; genetics is a known contributor for this discrepancy. Here, we discuss the potential role of DNA methylation in mediating the discrepancy in cardiometabolic disease-risk phenotypes between the sub-populations. We used data from the Young Finns Study (n = 969) to compare the genome-wide DNA methylation levels of East- and West-originating Finns. We identified 21 differentially methylated loci (FDR 2.5%) and 7 regions (smoothed FDR < 0.05; CpGs ≥ 5). Methylation at all loci and regions associates with genetic variants (p < 5 × 10−8). Independently of genetics, methylation at 11 loci and 4 regions associates with transcript expression, including genes encoding zinc finger proteins. Similarly, methylation at 5 loci and 4 regions associates with cardiometabolic disease-risk phenotypes including triglycerides, glucose, cholesterol, as well as insulin treatment. This analysis was also performed in LURIC (n = 2371), a German cardiovascular patient cohort, and results replicated for the association of methylation at cg26740318 and DMR_11p15 with diabetes-related phenotypes and methylation at DMR_22q13 with triglyceride levels. Our results indicate that DNA methylation differences between East and West Finns may have a functional role in mediating the cardiometabolic disease discrepancy between the sub-populations.Peer reviewe

Metabolite Cross-Feeding Enhances Virulence in a Model Polymicrobial Infection

Microbes within polymicrobial infections often display synergistic interactions resulting in enhanced pathogenesis; however, the molecular mechanisms governing these interactions are not well understood. Development of model systems that allow detailed mechanistic studies of polymicrobial synergy is a critical step towards a comprehensive understanding of these infections in vivo. In this study, we used a model polymicrobial infection including the opportunistic pathogen Aggregatibacter actinomycetemcomitans and the commensal Streptococcus gordonii to examine the importance of metabolite cross-feeding for establishing co-culture infections. Our results reveal that co-culture with S. gordonii enhances the pathogenesis of A. actinomycetemcomitans in a murine abscess model of infection. Interestingly, the ability of A. actinomycetemcomitans to utilize L-lactate as an energy source is essential for these co-culture benefits. Surprisingly, inactivation of L-lactate catabolism had no impact on mono-culture growth in vitro and in vivo suggesting that A. actinomycetemcomitans L-lactate catabolism is only critical for establishing co-culture infections. These results demonstrate that metabolite cross-feeding is critical for A. actinomycetemcomitans to persist in a polymicrobial infection with S. gordonii supporting the idea that the metabolic properties of commensal bacteria alter the course of pathogenesis in polymicrobial communities

The relationship between birthweight and brachio-femoral pulse wave velocity in early infancy: findings from a British birth cohort (Baby VIP study).

BACKGROUND: In adults, pulse wave velocity (PWV) is regarded as a predictor of cardiovascular disease.(1) However, associations in infants are not well established. One study has linked neonatal aortic PWV, at 1-3 days, with birthweight and maternal blood pressure.(2) AIM: To examine the relationship between infant brachio-femoral PWV and size at birth. METHODS: Baby VIP study recruited 362 newborn babies from the Leeds Teaching Hospitals Trust, including 64 small for gestational age (SGA) (18%). PWV was measured non-invasively from each baby at a follow-up home visit 2-6 weeks after recruitment, using the Vicorder kit. Birthweight and other covariables were collected from the delivery and antenatal medical notes. Individualised birthweight centiles were calculated using the GROW-Centile calculator taking into account maternal weight, height, parity, ethnicity, gestational age and baby's sex.(3) RESULTS: Mean birthweight was 3329 g (standard deviation [sd] 632). Mean infant PWV was 6.7 m/s (sd 1.3). In univariable analysis, SGA babies had, on average, lower PWV by 0.4 m/s (95% confidence interval 0.0, 0.9, P = 0.04). This association persisted after adjusting for pregnancy factors including maternal smoking, pre-eclampsia, gestational diabetes, blood pressure at booking and 36 weeks, and infant factors including type of feeding, baby's age, position and whether asleep or awake at the time of measurement (0.5 m/s lower, 0.1, 0.9, P = 0.02). CONCLUSION: This study has demonstrated the feasibility and acceptability of measuring PWV in early infancy. SGA was associated with a lower PWV. These findings support the evidence linking SGA with cardiovascular indicators, even very early in life