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

Emerging concepts of shear stress in placental development and function.

Blood flow, and the force it generates, is critical to placental development and function throughout pregnancy. This mechanical stimulation of cells by the friction generated from flow is called shear stress (SS) and is a fundamental determinant of vascular homeostasis, regulating remodelling and vasomotor tone. This review describes how SS is fundamental to the establishment and regulation of the blood flow through the uteroplacental and fetoplacental circulations. Amongst the most recent findings is that alongside the endothelium, embryonic stem cells and the villous trophoblast are mechanically sensitive. A complex balance of forces is required to enable effective establishment of the uteroplacental circulation, whilst protecting the embryo and placental villi. SS also generates flow-mediated vasodilatation through the release of endothelial nitric oxide, a process vital for adequate placental blood flow. The identification of SS sensors and the mechanisms governing how the force is converted into biochemical signals is a fast-paced area of research, with multiple cellular components under investigation. For example, the Piezo1 ion channel is mechanosensitive in a variety of tissues including the fetoplacental endothelium. Enhanced Piezo1 activity has been demonstrated in response to the Yoda1 agonist molecule, suggesting the possibility for developing tools to manipulate these channels. Whether such agents might progress to novel therapeutics to improve blood flow through the placenta requires further consideration and research

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

The relationship between dietary supplement use in late pregnancy and birth outcomes: a cohort study

Objective To examine the relationship between dietary supplement use during pregnancy and birth outcomes. Design A prospective birth cohort. Setting Leeds, UK. Sample One thousand two hundred and seventy-four pregnant women aged 18-45 years. Methods Dietary supplement intake was ascertained using three questionnaires for the first, second and third trimesters. Dietary intake was reported in a 24-hour dietary recall administered by a research midwife at 8-12 weeks of gestation. Information on delivery details and antenatal pregnancy complications was obtained from the hospital maternity records. Main outcome measures Birthweight, birth centile and preterm birth. Results Reported dietary supplement use declined from 82% of women in the first trimester of pregnancy to 22% in the second trimester and 33% in the third trimester. Folic acid was the most commonly reported supplement taken. Taking any type of daily supplement during any trimester was not significantly associated with size at birth taking into account known relevant confounders. Women taking multivitaminmineral supplements in the third trimester were more likely to experience preterm birth (adjusted OR = 3.4, 95% CI 1.2, 9.6, P = 0.02). Conclusions Regular multivitamin-mineral supplement use during pregnancy, in a developed country setting, is not associated with size at birth. However, it appears to be associated with preterm birth if taken daily in the third trimester. The mechanism for this is unclear and our study&apos;s findings need confirming by other cohorts and/or trials in developed countries

Variants in the fetal genome near FLT1 are associated with risk of preeclampsia.

: Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613; P = 5.4 × 10(-11)) in 4,380 cases and 310,238 controls. This locus is near the FLT1 gene encoding Fms-like tyrosine kinase 1, providing biological support, as a placental isoform of this protein (sFlt-1) is implicated in the pathology of preeclampsia. The association was strongest in offspring from pregnancies in which preeclampsia developed during late gestation and offspring birth weights exceeded the tenth centile. An additional nearby variant, rs12050029, associated with preeclampsia independently of rs4769613. The newly discovered locus may enhance understanding of the pathophysiology of preeclampsia and its subtypes.<br/

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

Diffusion Tensor Imaging determines three-dimensional architecture of human cervix: a cross sectional study

Objective To determine the microarchitecture of the cervix using high-resolution diffusion tensor (DT) magnetic resonance imaging (MRI). Design Cross-sectional study. Setting Leeds, UK. Sample Women undergoing hysterectomy for benign pathology. Methods Ex-vivo DT-MRI measurements were obtained using a 9.4-T Bruker nuclear magnetic resonance (NMR) spectrometer on seven fixed human cervices obtained at hysterectomy. A deterministic fibre-tracking algorithm was used to indirectly visualise underlying fibre organisation. Inter-regional differences in tissue structure were sought using quantitative measurements of diffusion. Main outcome measure The identification of an occlusive structure in the region corresponding to the internal cervical os. Results Fibre tracking demonstrated two regions: an outer circular and inner longitudinal layer. The total circumferential tract volume (TV) was greatest in the proximal region of the cervix (TV: proximal, 271 ± 198 mm3; middle, 186 ± 119 mm3; distal, 38 ± 36 mm3). Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) measurements were significantly different between regions in all samples (P < 0.0005), indicating greater tract density and organisation towards the internal os. Conclusion Fibre tracking infers a system of dense, well-defined, encircling fibres in the proximal region of the cervix, corresponding to the location of the internal os. These findings may provide evidence of specific anatomic microarchitecture within the cervix able to resist intrauterine forces associated with pregnancy

Maternal marijuana use has independent effects on risk for spontaneous preterm birth but not other common late pregnancy complications

Widespread legalisation of marijuana raises safety concerns for its use in pregnancy. This study investigated the association of marijuana use prior to and during pregnancy with pregnancy outcomes in a prospective cohort of 5588 nulliparous women from the international SCOPE study. Women were assessed at 15 ± 1 and 20 ± 1 weeks’ gestation. Cases [278 Preeclampsia, 470 gestational hypertension, 633 small-for-gestational-age, 236 spontaneous preterm births (SPTB), 143 gestational diabetes] were compared separately with 4114 non-cases. Although the numbers are small, continued maternal marijuana use at 20 weeks’ gestation was associated with SPTB independent of cigarette smoking status [adj OR 2.28 (95% CI:1.45–3.59)] and socioeconomic index (SEI) [adj OR 2.17 (95% CI:1.41–3.34)]. When adjusted for maternal age, cigarette smoking, alcohol and SEI, continued maternal marijuana use at 20 weeks’ gestation had a greater effect size [adj OR 5.44 (95% CI 2.44–12.11)]. Our data indicate that increasing use of marijuana among young women of reproductive age is a major public health concern

Piezo1 channels are mechanosensors in human fetoplacental endothelial cells

Study question: Does the shear stress sensing ion channel subunit Piezo1 have an important mechanotransduction role in human fetoplacental endothelium? Summary answer: Piezo1 is present and functionally active in human fetoplacental endothelial cells, and disruption of Piezo1 prevents the normal response to shear stress. What is known already: Shear stress is an important stimulus for maturation and function of placental vasculature but the molecular mechanisms by which the force is detected and transduced are unclear. Piezo1 channels are Ca2+-permeable non-selective cationic channels which are critical for shear stress sensing and maturation of murine embryonic vasculature. Study design, samples/materials, methods: We investigated the relevance of Piezo1 to placental vasculature by studying human fetoplacental endothelial cells (FpECs) from healthy pregnancies. Endothelial cells were isolated from placental cotyledons and cultured, for the study of tube formation and cell alignment to shear stress. In addition, human placental arterial endothelial cells were isolated and studied immediately by patch-clamp electrophysiology. Main results and the role of chance: The synthetic Piezo1 channel agonist Yoda1 caused strong elevation of the intracellular Ca2+ concentration with a 50% effect occurring at about 5.4 μM. Knockdown of Piezo1 by RNA interference suppressed the Yoda1 response, consistent with it being mediated by Piezo1 channels. Alignment of cells to the direction of shear stress was also suppressed by Piezo1 knockdown without loss of cell viability. Patch-clamp recordings from freshly isolated endothelium showed shear stress-activated single channels which were characteristic of Piezo1. Limitations, reasons for caution: The in vitro nature of fetoplacental endothelial cell isolation and subsequent culture may affect FpEC characteristics and PIEZO1 expression. In addition to Piezo1, alternative shear stress sensing mechanisms have been suggested in other systems and might also contribute in the placenta. Wider implications of the findings: These data suggest that Piezo1 is an important molecular determinant of blood flow sensitivity in the placenta. Establishing and manipulating the molecular mechanisms regulating shear stress sensing could lead to novel therapeutic strategies to improve blood flow in the placenta. Large-scale data: Not applicable. Study funding/competing interest(s): LCM was funded by a Clinical Research Training Fellowship from the Medical Research Council and by the Royal College of Obstetricians and Gynaecologists, and has received support from a Wellcome Trust Institutional Strategic Support Fund. JS was supported by the Wellcome Trust and a BHF Intermediate Research Fellowship. HJG, CW, AJH and PJW were supported by PhD Studentships from BHF, BBSRC and the Leeds Teaching Hospitals Charitable Foundation respectively. All authors declare no conflict of interest

Implementing natural capital credit risk assessment in agricultural lending

Agriculture has critical impacts and dependencies on natural capital, and agriculturallenders are therefore exposed to natural capital credit risk through their loans tofarmers. Currently, however, lenders lack any detailed guidance for assessing naturalcapital credit risk in agriculture and are challenged by the fact that the relevant material risks vary considerably by agricultural sector and geography. This paper developsa natural capital credit risk assessment framework based on a bottom‐up review ofthe material risks associated with natural capital impacts and dependencies forAustralian beef production. It demonstrates that implementing natural capital creditrisk assessment is feasible in agricultural lending, using a combination of quantitativeand qualitative inputs. Implementation challenges include the complexity and interconnectedness of natural capital processes, data availability and cost, spatial data analytical capacity, and the need for transformational change, both within lendingorganisations and across the banking sector