National Institute for Health Research and Medical Research Council.

Purpose To evaluate oxygen-enhanced and blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging parameters in normal pregnancies and those complicated by fetal growth restriction (FGR). Materials and Methods This case-control study was approved by the local research ethics committee. Informed consent was obtained from all subjects. From October 2010 to October 2015, 28 women with uncomplicated pregnancies (individualized birthweight ratio [IBR] >20th percentile and delivery >37 weeks) and 23 with pregnancies complicated by FGR (IBR <5th percentile and abnormal Doppler ultrasonography [US] studies) underwent MR imaging. Differences in placental longitudinal R1 (1/T1) and transverse R2* (1/T2*) were quantified, with subjects breathing either air or oxygen. The difference in R1 (ΔR1) after hyperoxia was converted to change in partial pressure of oxygen (ΔPo). Data were acquired prospectively, with retrospective interpretation of group differences (unpaired t tests). Diagnostic models were developed by using logistic regression analysis with gestational age as a covariate. Results The mean baseline R1 and R2* for normal pregnancies (R1: 0.59 sec, 95% confidence interval [CI]: 0.58 sec, 0.60 sec; R2*: 17 sec, 95% CI: 14 sec, 20 sec) were significantly different from those of pregnancies complicated by FGR (R1: 0.63 sec, 95% CI: 0.62 sec, 0.65 sec; R2*: 26 sec, 95% CI: 22 sec, 32 sec) (P < .0001). The ΔR1 showed a significant negative association with gestational age (P < .0001) in the combined cohort, with the FGR group having a ΔR1 that was generally 61.5% lower than that in the normal pregnancy group (P = .003). The area under the receiver operating characteristic curve for the differentiation between pregnancy complicated by FGR and normal pregnancy by using ΔPo, baseline R1, and baseline R2* was 0.91 (95% CI: 0.82, 0.99). Conclusion R1, R2*, and ΔPo were significantly different between normal pregnancies and those complicated by severe FGR. MR imaging parameters have the potential to help identify placental dysfunction associated with FGR and may have clinical utility in correctly identifying FGR among fetuses that are small for gestational age. A larger prospective study is needed to assess the incremental benefit beyond that offered by US. RSNA, 2017.

Preterm birth is linked to intellectual disability and there is evidence to suggest post-term birth may also incur risk. However, these associations have not yet been investigated in the absence of common genetic causes of intellectual disability, where risk associated with late delivery may be preventable. We therefore aimed to examine risk of intellectual disability without a common genetic cause across the entire range of gestation, using a matched-sibling design to account for unmeasured confounding by shared familial factors. We conducted a population-based retrospective study using data from the Stockholm Youth Cohort (n = 499,621) and examined associations in a nested cohort of matched outcome-discordant siblings (n = 8034). Risk of intellectual disability was greatest among those born extremely early (adjusted OR24 weeks = 14.54 [95% CI 11.46–18.44]), lessening with advancing gestational age toward term (aOR32 weeks = 3.59 [3.22–4.01]; aOR37 weeks = 1.50 [1.38–1.63]); aOR38 weeks = 1.26 [1.16–1.37]; aOR39 weeks = 1.10 [1.04–1.17]) and increasing with advancing gestational age post-term (aOR42 weeks = 1.16 [1.08–1.25]; aOR43 weeks = 1.41 [1.21–1.64]; aOR44 weeks = 1.71 [1.34–2.18]; aOR45 weeks = 2.07 [1.47–2.92]). Associations persisted in a cohort of matched siblings suggesting they were robust against confounding by shared familial traits. Risk of intellectual disability was greatest among children showing evidence of fetal growth restriction, especially when birth occurred before or after term. Birth at non-optimal gestational duration may be linked causally with greater risk of intellectual disability. The mechanisms underlying these associations need to be elucidated as they are relevant to clinical practice concerning elective delivery around term and mitigation of risk in post-term children.Electronic supplementary materialThe online version of this article (10.1007/s10654-017-0340-1) contains supplementary material, which is available to authorized users.

Chronic hypertension in pregnancy is associated with significant adverse pregnancy outcomes, increasing the risk of pre-eclampsia, fetal growth restriction and preterm birth. Dietary nitrate, abundant in green leafy vegetables and beetroot, is reduced in vivo to nitrite and subsequently nitric oxide, and has been demonstrated to lower blood pressure, improve vascular compliance and enhance blood flow in non-pregnant humans and animals. The primary aims of this study were to determine the acceptability and efficacy of dietary nitrate supplementation, in the form of beetroot juice, to lower blood pressure in hypertensive pregnant women. In this double-blind, placebo-controlled feasibility trial, 40 pregnant women received either daily nitrate supplementation (70 mL beetroot juice, n = 20) or placebo (70 mL nitrate-depleted beetroot juice, n = 20) for 8 days. Blood pressure, cardiovascular function and uteroplacental blood flow was assessed at baseline and following acute (3 h) and prolonged (8 days) supplementation. Plasma and salivary samples were collected for analysis of nitrate and nitrite concentrations and acceptability of this dietary intervention was assessed based on questionnaire feedback. Dietary nitrate significantly increased plasma and salivary nitrate/nitrite concentrations compared with placebo juice (p < 0.001), with marked variation between women. Compared with placebo, there was no overall reduction in blood pressure in the nitrate-treated group; however there was a highly significant correlation between changes in plasma nitrite concentrations and changes in diastolic blood pressure in the nitrate-treated arm only (r = -0.6481; p = 0.0042). Beetroot juice supplementation was an acceptable dietary intervention to 97% of women. This trial confirms acceptability and potential efficacy of dietary nitrate supplementation in pregnant women. Conversion of nitrate to nitrite critically involves oral bacterial nitrate reductase activities. We speculate that differences in efficacy of nitrate supplementation relate to differences in the oral microbiome, which will be investigated in future studies.

Experimental methods that allow examination of the intact vascular network of large organs, such as the human placenta are limited, preventing adequate comparison of normal and abnormal vascular development in pregnancy disease. Our aims were (i) to devise an effective technique for three-dimensional analyses of human placental vessels; (ii) demonstrate the utility of the technique in the comparison of placental vessel networks in normal and fetal growth restriction (FGR) complicated pregnancies. Radiopaque plastic vessel networks of normal and FGR placentas (n = 12/group) were created by filling the vessels with resin and corroding the surrounding tissues. Subsequently, each model was scanned in a microCT scanner, reconstructed into three-dimensional virtual objects and analysed in visualisation programmes. MicroCT imaging of the models defined vessel anatomy to our analyses threshold of 100 µm diameter. Median vessel length density was significantly shorter in arterial but longer in venous FGR networks compared to normals. No significant differences were demonstrable in arterial or venous tortuosity, diameter or branch density. This study demonstrates the potential effectiveness of microCT for ex-vivo examination of human placental vessel morphology. Our findings show significant discrepancies in vessel length density in FGR placentas. The effects on fetoplacental blood flow, and hence nutrient transfer to the fetus, are unknown.

Objective Magnetic resonance imaging (MRI) of placental invasion has been part of clinical practice for many years. The possibility of being better able to assess placental vascularization and function using MRI has multiple potential applications. This review summarises up‐to‐date research on placental function using different MRI modalities. Method We discuss how combinations of these MRI techniques have much to contribute to fetal conditions amenable for therapy such as singletons at high risk for fetal growth restriction (FGR) and monochorionic twin pregnancies for planning surgery and counselling for selective growth restriction and transfusion conditions. Results The whole placenta can easily be visualized on MRI, with a clear boundary against the amniotic fluid, and a less clear placental‐uterine boundary. Contrasts such as diffusion weighted imaging, relaxometry, blood oxygenation level dependent MRI and flow and metabolite measurement by dynamic contrast enhanced MRI, arterial spin labeling, or spectroscopic techniques are contributing to our wider understanding of placental function. Conclusion The future of placental MRI is exciting, with the increasing availability of multiple contrasts and new models that will boost the capability of MRI to measure oxygen saturation and placental exchange, enabling examination of placental function in complicated pregnancies.

Background Information on the factors influencing parents’ decision-making process following a lethal, life-limiting or severely debilitating prenatal diagnosis remains deficient. A comprehensive systematic review and meta-synthesis was conducted to explore the influencing factors for parents considering termination or continuation of pregnancy following identification of lethal, life-limiting or severely debilitating fetal abnormalities. Methods Electronic searches of 13 databases were conducted. These searches were supplemented by hand-searching Google Scholar and bibliographies and citation tracing. Thomas and Harden’s (2008) thematic synthesis method was used to synthesise data from identified studies. Results Twenty-four papers were identified and reviewed, but two papers were removed following quality assessment. Three main themes were identified through systematic synthesis. Theme 1, entitled ‘all life is precious’, described parents’ perception of the importance of the fetus’ life, a fatalistic view of their situation alongside moral implications as well as the implications decisions would have on their own life, in consideration of previous life experiences. Theme 2 (‘hope for a positive outcome’) contained two sub-themes which considered the parent’s own imagined future and the influence of other people’s experiences. Finally, Theme 3 (‘a life worth living’) presented three sub-themes which may influence their parental decision-making: These described parental consideration of the quality of life for their unborn child, the possibility of waiting to try for another pregnancy, and their own responsibilities and commitments. Conclusion The first review to fully explore parental decision-making process following lethal, life-limiting, or severely debilitating prenatal diagnosis provided novel findings and insight into which factors influenced parents’ decision-making process. This comprehensive and systematic review provides greater understanding of the factors influential on decision-making, such as hope, morality and potential implications on their own and other’s quality of life, will enable professionals to facilitate supported decision-making, including greater knowledge of the variables likely to influence parental choices.

Placental amino acid transfer is essential for fetal development and its impairment is associated with poor fetal growth. Amino acid transfer is mediated by a broad array of specific plasma membrane transporters with overlapping substrate specificity. However, it is not fully understood how these different transporters work together to mediate net flux across the placenta. Therefore the aim of this study was to develop a new computational model to describe how human placental amino acid transfer functions as an integrated system. Amino acid transfer from mother to fetus requires transport across the two plasma membranes of the placental syncytiotrophoblast, each of which contains a distinct complement of transporter proteins. A compartmental modelling approach was combined with a carrier based modelling framework to represent the kinetics of the individual accumulative, exchange and facilitative classes of transporters on each plasma membrane. The model successfully captured the principal features of transplacental transfer. Modelling results clearly demonstrate how modulating transporter activity and conditions such as phenylketonuria, can increase the transfer of certain groups of amino acids, but that this comes at the cost of decreasing the transfer of others, which has implications for developing clinical treatment options in the placenta and other transporting epithelia.