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Abstract Body mass results from a complex interplay between genetics and environment. Previous studies of the genetic contribution to body mass have excluded repetitive regions due to the technical limitations of platforms used for population scale studies. Here we apply genome-wide approaches, identifying an association between adult body mass and the copy number (CN) of 47S-ribosomal DNA (rDNA). rDNA codes for the 18 S, 5.8 S and 28 S ribosomal RNA (rRNA) components of the ribosome. In mammals, there are hundreds of copies of these genes. Inter-individual variation in the rDNA CN has not previously been associated with a mammalian phenotype. Here, we show that rDNA CN variation associates with post-pubertal growth rate in rats and body mass index in adult humans. rDNA CN is not associated with rRNA transcription rates in adult tissues, suggesting the mechanistic link occurs earlier in development. This aligns with the observation that the association emerges by early adulthood.

IntroductionCounseling, together with iron and folic acid supplements, can improve hemoglobin levels in pregnant women, but few interventions have tested a virtual method of delivering counseling. We hypothesized that a virtual counseling intervention delivered via a mobile device (mHealth) would prevent and treat anemia, compared with routine antenatal care (ANC).MethodsVirtual antenatal intervention for improved diet and iron intake (VALID) was a non-blinded parallel group two-arm, individually randomized superiority trial (1:1 allocation). Participants were pregnant women who were married, aged 13–49 years, able to answer questions, 12–28 weeks’ gestation and living in Kapilvastu district, Nepal. Women were randomized to receive routine ANC (control arm), or ANC plus a virtual antenatal intervention of two problem-solving counseling sessions via video call. The primary outcome was iron folic acid (IFA) tablet compliance (consumption on 12 or more days of the previous 14 days). Secondary outcomes were dietary diversity, promoted food consumption, iron bioavailability enhancement, and knowledge of iron-rich foods. Primary logistic regression analysis was by intention-to-treat, adjusting for baseline values.ResultsWe enrolled 319 pregnant women (161 control, 158 intervention) from 23 January 2022 to 6 May 2022 and analyzed outcomes in 144 control and 127 intervention women. Compliance with IFA increased in both arms. In the intervention arm, compliance increased by 29.7 percentage points (pp) (49.0–78.7%) and 19.8 pp. in the control arm (53.8–73.6%). Despite the more significant increase in the intervention arm, we found no intervention effect upon IFA compliance (adjusted odds ratio [aOR] 1.33; 95% confidence interval [CI]: 0.75, 2.35; p = 0.334), dietary diversity, or ANC visits. The intervention increased knowledge of iron-rich foods (coefficient 0.96; 95% CI: 0.50, 1.41; p

BackgroundThe Maternal Mortality Rate (MMR) in Tanzania is 78 times higher than that of the UK. Obstetric haemorrhage accounts for two-thirds of these deaths in Mbeya, Tanzania. A lack of healthcare providers' (HCPs') competencies has been the key attribute. This study measured the impact on HCP's competencies from a blended training programme on obstetric haemorrhage.MethodsA “before and after” cohort study was undertaken with HCPs in 4 hospitals in the Mbeya region of Tanzania between August 2021 and April 2022. A multidisciplinary cohort of 34 HCPs (doctors, nurses, midwives, anaesthetists and radiologists) were enrolled on a blended face-to-face and virtual training course. The training was delivered by a multidisciplinary team (MDT) from London, UK, assisted by local multidisciplinary trainers from Mbeya, Tanzania and covered anaesthetic, obstetrics, haematology and sonographic use.ResultsThere were 33 HCP in the cohort of trainees where 30/33 (90.9%) of HCPs improved their Anaesthesia skills with a mean score improvement of 26% i.e., 0.26 (−0.009 −0.50), 23 HCPs (69.7%) improved obstetric skills 18% i.e., 0.18 (−0.16 to 0.50), 19 (57.6%), (57.6%) improved competences in Haematology 15%.i.e., 0.15 (−0.33 to 0.87), 20 out of 29 HCPs with ultrasound access (68.8%) improved Sonographic skills 13%.i.e., 0.13 (−0.31 to 0.54). All 33 HCPs (100%) presented a combined change with the mean score improvement of difference of 25% i.e., 0.25 (0.05–0.66). The deaths attributed to obstetric haemorrhage, the mortality rate declined from 76/100,000 to 21/100,000 live births. Actual number of deaths due to obstetric haemorrhage declined from 8 before training to 3 after the completion of the training.ConclusionThis comprehensive blended training on anaesthetic surgical, haematological, and sonographic management of obstetric haemorrhage delivers a significant positive impact on the detection, management and outcomes of obstetric haemorrhage.

Fetal growth restriction (FGR) is a leading cause of perinatal morbidity and mortality. Altered placental formation and functional capacity are major contributors to FGR pathogenesis. Relating placental structure to function across the placenta in healthy and FGR pregnancies remains largely unexplored but could improve understanding of placental diseases. We investigated integration of these parameters spatially in the term human placenta using predictive modelling. Systematic sampling was able to overcome heterogeneity in placental morphological and molecular features. Defects in villous development, elevated fibrosis, and reduced expression of growth and functional marker genes (IGF2, VEGA, SLC38A1, and SLC2A3) were seen in age-matched term FGR versus healthy control placentas. Characteristic histopathological changes with specific accompanying molecular signatures could be integrated through computational modelling to predict if the placenta came from a healthy or FGR pregnancy. Our findings yield new insights into the spatial relationship between placental structure and function and the etiology of FGR.

Pathological low birth weight due to fetal growth restriction (FGR) is an important predictor of adverse obstetric and neonatal outcomes. It is more common amongst native lowlanders when gestating in the hypoxic environment of high altitude, whilst populations who have resided at high altitude for many generations are relatively protected. Genetic study of pregnant populations at high altitude permits exploration of the role of hypoxia in FGR pathogenesis, and perhaps of FGR pathogenesis more broadly. We studied the umbilical cord blood DNA of 316 neonates born to pregnant women managed at the Sonam Norboo Memorial Hospital, Ladakh (altitude 3540m) between February 2017 and January 2019. Principal component, admixture and genome wide association studies (GWAS) were applied to dense single nucleotide polymorphism (SNP) genetic data, to explore ancestry and genetic predictors of low birth weight. Our findings support Tibetan ancestry in the Ladakhi population, with subsequent admixture with neighboring Indo-Aryan populations. Fetal growth protection was evident in Ladakhi neonates. Although no variants achieved genome wide significance, we observed nominal association of seven variants across genes (ZBTB38, ZFP36L2, HMGA2, CDKAL1, PLCG1) previously associated with birthweight.

Background: The London borough of Camden has long been home for many refugees, asylum seekers, and undocumented migrants (RASUs). Over time, it has witnessed an increase in the population of these migrant groups, accompanied by notable changes in the obstacles they encounter when seeking health services, particularly maternity care. We explore how the ‘hostile environment’ policies affect access to and delivery of quality maternity services for RASUs. Methods: This study was conducted over eight months (November 2021–July 2022) both remotely and face-to-face, in various locations in Camden and in the Maternity Department at University College London Hospital, UK. Healthcare professionals (HCPs) and community organisations (COs) were identified as two major stakeholders involved in the care provision for RASUs. 33 semi-structured interviews were conducted (with 22 HCPs and 11 COs) to understand their experiences of delivering care to this population. Results: There was consensus among HCPs and COs that the current immigration policies undermined their duty of care, personal morals, and the principles of the NHS. These policies have created a restrictive environment, making it increasingly difficult for migrants to navigate the healthcare system and creating an atmosphere of distrust, propagating fears of being charged. This has led to HCPs and COs going beyond their remits to ensure that RASUs are accessing and engaging with maternity care, regardless of an individual's status and despite any potential repercussions for themselves. Conclusion: In the face of an intensifying hostile environment under the UK government, supporting RASUs cannot be solely reliant on political measures. We need to advocate for healthcare navigator roles, health justice partnerships, specialist teams, and comprehensive training for service providers. HCPs and COs should be adequately supported in their endeavours to ensure RASUs have access to standardised, high-quality maternity care.