Dietary Intakes of Folate, Vitamin D and Iodine during the First Trimester of Pregnancy and the Association between Supplement Use and Demographic Characteristics amongst White Caucasian Women Living with Obesity in the UK.

Folate, vitamin D and iodine are key micronutrients in pregnancy, with deficiency associated with poor maternal and infant outcomes. For folate and vitamin D especially, deficiency is more common amongst women with obesity and recommended intakes and guidance on supplementation varies worldwide. The present study aims to investigate dietary and supplementary intakes of these micronutrients amongst a population of pregnant women with obesity in the United Kingdom, alongside key maternal demographic characteristics. Expectant women (n = 75) with a body mass index ≥ 30 kg/m2 at first antenatal appointment were recruited at 12 weeks gestation. Participants were asked about their supplement use preconception and during trimester one in a baseline questionnaire which also asked about demographic characteristics. Women also completed a four day diet diary from which dietary and supplemental intakes of micronutrients intakes were estimated. Folic acid was taken by 96% of women at any point in trimester 1, whilst only 26% of women took the higher 5 mg dose recommended for women with obesity in the UK. For vitamin D and iodine, 56% and 44% of women met the UK RNI, respectively. Maternal age was positively associated with taking supplements of any kind and the 5 mg folic acid supplement, whilst parity was inversely associated with both outcomes. This study strengthens the rationale for further work to be done raising awareness of the need for women with obesity to supplement both with a higher dose of folic acid and vitamin D and to be aware of the role of iodine during pregnancy.

The relationship between gestational weight gain, maternal upper-body subcutaneous fat changes and infant birth size: A pilot observational study amongst women with obesity.

BACKGROUND: It is widely acknowledged that maternal obesity and excessive gestational weight gain (GWG) are associated with increased risk of fetal macrosomia and recent studies have suggested a role for the timing and composition of GWG. AIMS: To examine the effect of the rate of change in GWG and maternal upper-body subcutaneous fat on neonatal anthropometric outcomes in a pilot observational study amongst women with obesity. STUDY DESIGN: Expectant women with a body mass index (BMI) > 30 kg/m2 at first antenatal appointment were recruited at 12 weeks gestation. Maternal height, weight and skinfold thickness (SFT) measurements were collected at baseline and repeated at 28 and 36 weeks gestation. Following delivery, World Health Organisation (WHO)-UK infant birthweight z-scores were calculated, and infant anthropometric measurements were obtained. RESULTS: The sum of upper body SFT measurements increased in mid-pregnancy (0.08 ± 0.71 mm/week) and decreased in late pregnancy (-0.04 ± 1.17 mm/week). After adjustment for maternal age, BMI and parity, mid- but not late- pregnancy GWG was positively associated with infant birthweight z-score (p<0.05), while mid- but not late-pregnancy changes in the sum of SFT were inversely associated with infant birthweight z-score (p<0.01). CONCLUSIONS: The present study suggests that mid- rather than late-pregnancy changes in weight and upper-body subcutaneous fat are associated with infant birthweight. Further research is required in larger, more diverse populations to explore whether pregnancy interventions aiming to improve maternal and offspring health can be personalised beyond BMI and GWG.

Objectively measured sleep duration and plasma glucose values following an oral glucose tolerance test amongst pregnant women with obesity in the UK.

BACKGROUND/OBJECTIVES: Short sleep duration has been linked to maternal hyperglycaemia following a 1-h 50 g oral glucose tolerance test (OGTT) in observational studies conducted primarily in the USA. Our objective was to examine the relationship between objectively measured sleep duration and plasma glucose values following the 2-h 75 g OGTT routinely used in the UK amongst women with obesity. METHODS: Sleep and OGTT data were available for 49 pregnant women who wore wrist actigraphs for at least two nights, and took a 2-h 75 g OGTT at the end of their second trimester. Multivariable regression was used to evaluate associations between sleep duration and OGTT results. RESULTS: Higher 2-h plasma glucose values were significantly associated with shorter sleep duration and higher maternal age and BMI, with no association observed between wake after sleep onset (WASO) and 2-h plasma glucose values. No associations were observed between fasting plasma glucose values and any sleep parameters. CONCLUSIONS: We found that shorter sleep duration, as measured using actigraphy, is associated with higher 2-h plasma glucose values following a 2-h 75 g OGTT in the UK. These findings are in keeping with those observed elsewhere in the world, employing alternative OGTT protocols. Future studies should investigate sleep extension as a potential candidate for inclusion in future RCTs aiming to improve glucose tolerance and prevent GDM amongst those at risk.

TRPV6 compound heterozygous variants result in impaired placental calcium transport and severe undermineralization and dysplasia of the fetal skeleton.

Transient receptor potential vanilloid 6 (TRPV6) functions in tetramer form for calcium transport. Until now, TRPV6 has not been linked with skeletal development disorders. An infant with antenatal onset thoracic insufficiency required significant ventilatory support. Skeletal survey showed generalized marked undermineralization, hypoplastic fractured ribs, metaphyseal fractures, and extensive periosteal reaction along femoral, tibial, and humeral diaphyses. Parathyroid hormone (PTH) elevation (53.4-101 pmol/L) initially suggested PTH signaling disorders. Progressively, biochemical normalization with radiological mineralization suggested recovery from in utero pathophysiology. Genomic testing was undertaken and in silico protein modeling of variants. No abnormalities in antenatal CGH array or UPD14 testing. Postnatal molecular genetic analysis found no causative variants in CASR, GNA11, APS21, or a 336 gene skeletal dysplasia panel investigated by whole exome sequencing. Trio exome analysis identified compound heterozygous TRPV6 likely pathogenic variants: novel maternally inherited missense variant, c.1978G > C p.(Gly660Arg), and paternally inherited nonsense variant, c.1528C > T p.(Arg510Ter), confirming recessive inheritance. p.(Gly660Arg) generates a large side chain protruding from the C-terminal hook into the interface with the adjacent TRPV6 subunit. In silico protein modeling suggests steric clashes between interface residues, decreased C-terminal hook, and TRPV6 tetramer stability. The p.(Gly660Arg) variant is predicted to result in profound loss of TRPV6 activity. This first case of a novel dysplasia features severe but improving perinatal abnormalities. The TRPV6 compound heterozygous variants appear likely to interfere with fetoplacental calcium transfer crucial for in utero skeletal development. Astute clinical interpretation of evolving perinatal abnormalities remains valuable in complex calcium and bone pathophysiology and informs exome sequencing interpretation.

Design and preliminary evaluation of a self-steering, pneumatically driven colonoscopy robot.

Colonoscopy is a diagnostic procedure to detect pre-cancerous polyps and tumours in the colon, and is performed by inserting a long tube equipped with a camera and biopsy tools. Despite the medical benefits, patients undergoing this procedure often complain about the associated pain and discomfort. This discomfort is mostly due to the rough handling of the tube and the creation of loops during the insertion. The overall goal of this work is to minimise the invasiveness of traditional colonoscopy. In pursuit of this goal, this work presents the development of a semi-autonomous colonoscopic robot with minimally invasive locomotion. The proposed robotic approach allows physicians to concentrate mainly on the diagnosis rather than the mechanics of the procedure. In this paper, an innovative locomotion approach for robotic colonoscopy is addressed. Our locomotion approach takes advantage of longitudinal expansion of a latex tube to propel the robot's tip along the colon. This soft and compliant propulsion mechanism, in contrast to minimally invasive mechanisms used in, for example, inchworm-like robots, has shown promising potential. In the preliminary ex vivo experiments, the robot successfully advanced 1.5 metres inside an excised curvilinear porcine colon with average speed of 28 mm/s, and was capable of traversing bends up to 150 degrees. The robot creates less than 6 N of normal force at its tip when it is pressurised with 90 kPa. This maximum force generates pressure of 44.17 mmHg at the tip, which is significantly lower than safe intraluminal human colonic pressure of 80 mmHg. The robot design inherently prevents loop formation in the colon, which is recognised as the main cause of post procedural pain in patients. Overall, the robot has shown great promise in an ex vivo experimental setup. The design of an autonomous control system and in vivo experiments are left as future work.

Fetal Sex and RHD Genotyping with Digital PCR Demonstrates Greater Sensitivity than Real-time PCR.

BACKGROUND: Noninvasive genotyping of fetal RHD (Rh blood group, D antigen) can prevent the unnecessary administration of prophylactic anti-D to women carrying RHD-negative fetuses. We evaluated laboratory methods for such genotyping. METHODS: Blood samples were collected in EDTA tubes and Streck® Cell-Free DNA™ blood collection tubes (Streck BCTs) from RHD-negative women (n = 46). Using Y-specific and RHD-specific targets, we investigated variation in the cell-free fetal DNA (cffDNA) fraction and determined the sensitivity achieved for optimal and suboptimal samples with a novel Droplet Digital™ PCR (ddPCR) platform compared with real-time quantitative PCR (qPCR). RESULTS: The cffDNA fraction was significantly larger for samples collected in Streck BCTs compared with samples collected in EDTA tubes (P < 0.001). In samples expressing optimal cffDNA fractions (≥4%), both qPCR and digital PCR (dPCR) showed 100% sensitivity for the TSPY1 (testis-specific protein, Y-linked 1) and RHD7 (RHD exon 7) assays. Although dPCR also had 100% sensitivity for RHD5 (RHD exon 5), qPCR had reduced sensitivity (83%) for this target. For samples expressing suboptimal cffDNA fractions (<2%), dPCR achieved 100% sensitivity for all assays, whereas qPCR achieved 100% sensitivity only for the TSPY1 (multicopy target) assay. CONCLUSIONS: qPCR was not found to be an effective tool for RHD genotyping in suboptimal samples (<2% cffDNA). However, when testing the same suboptimal samples on the same day by dPCR, 100% sensitivity was achieved for both fetal sex determination and RHD genotyping. Use of dPCR for identification of fetal specific markers can reduce the occurrence of false-negative and inconclusive results, particularly when samples express high levels of background maternal cell-free DNA.