Emerging models of human and non-human primate placental development - Centre for Trophoblast Research 17th annual meeting 2024.

The 17th annual meeting of the Centre for Trophoblast Research (CTR) took place at the University of Cambridge, UK, on 1-2 July 2024. This year's meeting provided an opportunity to reflect on the significant advancements made recently in modelling the human placenta in vitro. The meeting featured 12 invited speakers and attracted 260 participants from 25 countries.

Weight gain during nutritional rehabilitation post-childhood malnutrition may influence the associations between adulthood desaturases activity and anthro-cardiometabolic risk factors.

Backgrounds & Aims: Childhood malnutrition is a major global health problem with long-term sequelae, including non-communicable diseases (NCDs). Mechanisms are unknown but may involve metabolic programming, resulting from "short-term" solutions to optimise survival by compromising non-priority organs. As key players in lipid metabolism, desaturases have been shown to be predictive of NCDs.

Physiologically relevant culture medium Plasmax improves human placental trophoblast stem cell function.

Human trophoblast cultures provide powerful tools to model key processes of placental development. In vitro trophoblast studies to date have relied on commercial media that contains nonphysiological levels of nutrients, and the impact of these conditions on trophoblast metabolism and function is unknown. Here, we show that the physiological medium (Plasmax) with nutrient and metabolite concentrations recapitulating human plasma improves human trophoblast stem cell (hTSC) proliferation and differentiation compared with standard medium (DMEM-F12).

Butyrate in Human Milk: Associations with Milk Microbiota, Milk Intake Volume, and Infant Growth.

Butyrate in human milk (HM) has been suggested to reduce excessive weight and adipo-sity gains during infancy. However, HM butyrate's origins, determinants, and its influencing mechanism on weight gain are not completely understood. These were studied in the prospective longitudinal Cambridge Baby Growth and Breastfeeding Study (CBGS-BF), in which infants ( = 59) were exclusively breastfed for at least 6 weeks.

Associations between breast milk intake volume, macronutrient intake and infant growth in a longitudinal birth cohort: the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF).

Growth patterns of breastfed infants show substantial inter-individual differences, partly influenced by breast milk (BM) nutritional composition. However, BM nutritional composition does not accurately indicate BM nutrient intakes. This study aimed to examine the associations between both BM intake volumes and macronutrient intakes with infant growth.

Lipid profiling analyses from mouse models and human infants.

This protocol outlines a translational lipidomic approach to discover lipid biomarkers that could predict morphometric body and histological organ measurements (e.g., weight and adiposity gains) during specific stages of life (e.

Glucose and oxygen in the early intrauterine environment and their role in developmental abnormalities.

The early life environment can have profound impacts on the developing conceptus in terms of both growth and morphogenesis. These impacts can manifest in a variety of ways, including congenital fetal anomalies, placental dysfunction with subsequent effects on fetal growth, and adverse perinatal outcomes, or via effects on long-term health outcomes that may not be detected until later childhood or adulthood. Two key examples of environmental influences on early development are explored: maternal hyperglycaemia and gestational hypoxia.

"Post-GDM support would be really good for mothers": A qualitative interview study exploring how to support a healthy diet and physical activity after gestational diabetes.

Background: Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes mellitus (T2DM). They are therefore recommended to follow a healthy diet and be physically active in order to reduce that risk. However, achieving and maintaining these behaviours in the postpartum period is challenging.

'Oh, I've got an appointment': A qualitative interview study exploring how to support attendance at diabetes screening after gestational diabetes.

Aims: To explore the views of women with a history of gestational diabetes mellitus (GDM) on suggested practical approaches to support diabetes screening attendance after GDM, which is recommended but poorly attended.

Methods: We conducted semi-structured interviews with 20 participants in Cambridgeshire, UK who had been diagnosed with GDM and were 3-48 months postpartum. Interviews covered whether participants had been screened and why, plans for future screening and their views on potential interventions to facilitate attendance (at the first postpartum test and annual testing).

Temporal variations in maternal treatment requirements and early neonatal outcomes in patients with gestational diabetes.

Aims: There is seasonal variation in the incidence of gestational diabetes (GDM) and delivery outcomes of affected patients. We assessed whether there was also evidence of temporal variation in maternal treatment requirements and early neonatal outcomes.

Methods: We performed a retrospective analysis of women diagnosed with GDM (75 g oral glucose tolerance test, 0 h ≥ 5.

Fetal umbilical artery Doppler as a tool for universal third trimester screening: A systematic review and meta-analysis of diagnostic test accuracy.

The objective of this study was to investigate the accuracy of universal third trimester umbilical artery (UA) Doppler to predict adverse pregnancy outcome at term. We searched Medline, EMBASE, the Cochrane library and ClinicalTrials.gov from inception to October 2020 and we also analyzed previously unpublished data from a prospective cohort study of nulliparous women, the Pregnancy Outcome Prediction (POP) study.

Exploring Telomere Dynamics in Aging Male Rat Tissues: Can Tissue-Specific Differences Contribute to Age-Associated Pathologies?

Introduction: Due to increasing lifespan, global aging rates are rising rapidly and age-associated diseases are increasing. To ensure that health span is concomitant with life span, a greater understanding of cellular mechanisms of aging is important.

Methods: Telomere length analysis from a wide range of tissues from weaning, young adult, and middle-aged (3, 12 and 52 week) male Wistar rats were conducted using Southern blotting.

Lipid ratios representing SCD1, FADS1, and FADS2 activities as candidate biomarkers of early growth and adiposity.

Background: Altered lipid metabolism in early life has been associated with subsequent weight gain and predicting this could aid in obesity prevention and risk management. Here, a lipidomic approach was used to identify circulating markers for future obesity risk in translational murine models and validate in a human infant cohort.

Methods: Lipidomics was performed on the plasma of APOE*3 Leiden, Ldlr-/-.

Universal third-trimester ultrasonic screening using fetal macrosomia in the prediction of adverse perinatal outcome: A systematic review and meta-analysis of diagnostic test accuracy.

Background: The effectiveness of screening for macrosomia is not well established. One of the critical elements of an effective screening program is the diagnostic accuracy of a test at predicting the condition. The objective of this study is to investigate the diagnostic effectiveness of universal ultrasonic fetal biometry in predicting the delivery of a macrosomic infant, shoulder dystocia, and associated neonatal morbidity in low- and mixed-risk populations.

Decision-to-delivery interval of emergency cesarean section in Uganda: a retrospective cohort study.

Background: In many low and medium human development index countries, the rate of maternal and neonatal morbidity and mortality is high. One factor which may influence this is the decision-to-delivery interval of emergency cesarean section. We aimed to investigate the maternal risk factors, indications and decision-to-delivery interval of emergency cesarean section in a large, under-resourced obstetric setting in Uganda.

Comparative impact of pharmacological treatments for gestational diabetes on neonatal anthropometry independent of maternal glycaemic control: A systematic review and meta-analysis.

Background: Fetal growth in gestational diabetes mellitus (GDM) is directly linked to maternal glycaemic control; however, this relationship may be altered by oral anti-hyperglycaemic agents. Unlike insulin, such drugs cross the placenta and may thus have independent effects on fetal or placental tissues. We investigated the association between GDM treatment and fetal, neonatal, and childhood growth.

UK stillbirth trends in over 11 million births provide no evidence to support effectiveness of Growth Assessment Protocol program.

Objective: Use of the Growth Assessment Protocol (GAP) has increased internationally under the assumption that it reduces the stillbirth rate. The evidence for this is limited and based largely on an ecological time-trend study. Discordance in the uptake of the GAP program between Scotland and England/Wales enabled us to assess the assertion that implementation of GAP leads to a reduced stillbirth rate.

Barriers to completing oral glucose tolerance testing in women at risk of gestational diabetes.

Aim: Complications of gestational diabetes (GDM) can be mitigated if the diagnosis is recognized. However, some at-risk women do not complete antenatal diagnostic oral glucose tolerance testing (OGTT). We aimed to understand reasons contributing to non-completion, particularly to identify modifiable factors.

Effect of interpregnancy weight change on perinatal outcomes: systematic review and meta-analysis.

Background: Although obesity is a well-known risk factor for adverse pregnancy outcomes, evidence is sparse about the effects of interpregnancy weight change on the risk of adverse perinatal complications in a subsequent pregnancy. The current study aims to assess the effect of interpregnancy weight change on the risk of developing gestational diabetes, pre-eclampsia, pregnancy induced hypertension, preterm birth, or delivering a large- or small-for-gestational age neonate.

Methods: Pubmed, Ovid Embase, ClinicalTrial.

Neonatal, infant, and childhood growth following metformin versus insulin treatment for gestational diabetes: A systematic review and meta-analysis.

Background: Metformin is increasingly offered as an acceptable and economic alternative to insulin for treatment of gestational diabetes mellitus (GDM) in many countries. However, the impact of maternal metformin treatment on the trajectory of fetal, infant, and childhood growth is unknown.

Methods And Findings: PubMed, Ovid Embase, Medline, Web of Science, ClinicalTrials.

Could masking gestational age estimation during scanning improve detection of small-for-gestational-age fetuses? A controlled pre-post evaluation.

Background: Antenatal detection of small-for-gestational-age fetuses improves outcomes and reduces perinatal mortality rates. However, ultrasonographic estimation of fetal weight is subject to several potential sources of error. One potential source of error is subconscious operator bias towards "normal" measurement values for gestational age (observer-expectancy bias).

Human Milk Short-Chain Fatty Acid Composition is Associated with Adiposity Outcomes in Infants.

Background: Presumed benefits of human milk (HM) in avoiding rapid infancy weight gain and later obesity could relate to its nutrient composition. However, data on breast milk composition and its relation with growth are sparse.

Objective: We investigated whether short-chain fatty acids (SCFAs), known to be present in HM and linked to energy metabolism, are associated with infancy anthropometrics.

Screening for breech presentation using universal late-pregnancy ultrasonography: A prospective cohort study and cost effectiveness analysis.

Background: Despite the relative ease with which breech presentation can be identified through ultrasound screening, the assessment of foetal presentation at term is often based on clinical examination only. Due to limitations in this approach, many women present in labour with an undiagnosed breech presentation, with increased risk of foetal morbidity and mortality. This study sought to determine the cost effectiveness of universal ultrasound scanning for breech presentation near term (36 weeks of gestational age [wkGA]) in nulliparous women.

Early life environment influences the trajectory of post-partum weight loss in adult female rats.

Research Question: The physiological processes of pregnancy and lactation require profound changes in maternal metabolism and energy balance. The timescale of metabolic reversion after pregnancy, in particular post-partum weight loss, is highly variable between individuals. Currently, mechanisms influencing post-partum metabolic recovery are not well understood.