Holistic preconception care: Providing real-time guidance via a mobile app to optimise maternal and child health.

Introduction: Preconception is a critical period to optimise gamete function and early placental development, essential for successful conception and long-term maternal-child health. However, there is a lack of preconception services and consequently, global fertility rates continue to fall and mothers embark on their pregnancy journey in poor health. There is an urgent need to implement a holistic community-level preconception care programme to optimise risk factors for poor fecundability and improve long-term maternal-child health. Method: We reviewed current evidence on fecundability lifestyle risk factors, the efficacy of existing preconception interventions and the use of digital platforms for health optimisation, to create a new digital-based preconception intervention model that will be implemented via an app. We present the theory, content and mode of delivery of this holistic model targeting couples planning for pregnancy. Results: We propose a new model featuring a user-friendly mobile app, which enables couples to self-assess fecundability risks through a personalised risk score that drives a tailored management plan. This tiered management provides anticipatory guidance supported by evidence-based recommen-dations, and promotes ongoing engagement for behavioural optimisation and specialist referrals as required. Based on the health belief model, this new model delivered with a mobile app seeks to shift couples' perceptions about their susceptibility and severity of subfertility, benefits of making a change and barriers to change. Conclusion: Our proposed digital-based intervention model via a mobile app stands to enhance preconcep-tion care by providing personalised risk assessments, real-time feedback and tiered management to optimise preconception reproductive health of couples. This model forms a reference content framework for future preconception care intervention delivery.

Fetal liver CD34+ contain human immune and endothelial progenitors and mediate solid tumor rejection in NOG mice.

BACKGROUND: Transplantation of CD34+ hematopoietic stem and progenitor cells (HSPC) into immunodeficient mice is an established method to generate humanized mice harbouring a human immune system. Different sources and methods for CD34+ isolation have been employed by various research groups, resulting in customized models that are difficult to compare. A more detailed characterization of CD34+ isolates is needed for a better understanding of engraftable hematopoietic and potentially non-hematopoietic cells. Here we have performed a direct comparison of CD34+ isolated from cord blood (CB-CD34+) or fetal liver (FL-CD34+ and FL-CD34+CD14-) and their engraftment into immunocompromised NOD/Shi-scid Il2rgnull (NOG) mice. METHODS: NOG mice were transplanted with either CB-CD34+, FL-CD34+ or FL-CD34+CD14- to generate CB-NOG, FL-NOG and FL-CD14--NOG, respectively. After 15-20 weeks, the mice were sacrificed and human immune cell reconstitution was assessed in blood and several organs. Liver sections were pathologically assessed upon Haematoxylin and Eosin staining. To assess the capability of allogenic tumor rejection in CB- vs. FL-reconstituted mice, animals were subcutaneously engrafted with an HLA-mismatched melanoma cell line. Tumor growth was assessed by calliper measurements and a Luminex-based assay was used to compare the cytokine/chemokine profiles. RESULTS: We show that CB-CD34+ are a uniform population of HSPC that reconstitute NOG mice more rapidly than FL-CD34+ due to faster B cell development. However, upon long-term engraftment, FL-NOG display increased numbers of neutrophils, dendritic cells and macrophages in multiple tissues. In addition to HSPC, FL-CD34+ isolates contain non-hematopoietic CD14+ endothelial cells that enhance the engraftment of the human immune system in FL-NOG mice. We demonstrate that these CD14+CD34+ cells are capable of reconstituting Factor VIII-producing liver sinusoidal endothelial cells (LSEC) in FL-NOG. However, CD14+CD34+ also contribute to hepatic sinusoidal dilatation and immune cell infiltration, which may culminate in a graft-versus-host disease (GVHD) pathology upon long-term engraftment. Finally, using an HLA-A mismatched CDX melanoma model, we show that FL-NOG, but not CB-NOG, can mount a graft-versus-tumor (GVT) response resulting in tumor rejection. CONCLUSION: Our results highlight important phenotypical and functional differences between CB- and FL-NOG and reveal FL-NOG as a potential model to study hepatic sinusoidal dilatation and mechanisms of GVT.

Association of acylcarnitines with maternal cardiometabolic risk factors is defined by chain length: the S-PRESTO study.

CONTEXT: Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers. OBJECTIVE: To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors. METHODS: LC-MS/MS-based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26-28 weeks' pregnancy, and three months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. RESULTS: Plasma concentrations of free carnitine and acylcarnitines decreased coupled with increased renal clearance in pregnancy compared to preconception and postpartum. Renal clearance of carnitine increased with an increase in pre-pregnancy body mass index (ppBMI) and gestational weight gain. Plasma short-chain acylcarnitines were positively associated with ppBMI, irrespective of the physiological state, while medium- and long-chain acylcarnitines were negatively associated with ppBMI at preconception and postpartum but showed a positive association in pregnancy. Similarly, plasma short-chain acylcarnitines were positively associated with HOMA-IR whereas medium- and long-chain acylcarnitines were negatively associated with HOMA-IR at preconception and in pregnancy. Mothers who developed gestational diabetes mellitus during pregnancy had ∼10% higher plasma propionylcarnitine concentration and ∼18% higher urine tiglylcarnitine concentration compared to mothers with normal glucose metabolism at preconception. CONCLUSIONS: This study provides the metabolic and physiological basis of maternal carnitine homeostasis, which can be used in assessment of maternal cardiometabolic health at preconception to improve pregnancy outcomes.

Relation of preconception eating behaviours to dietary pattern trajectories and gestational weight gain from preconception to late pregnancy.

Studies examining preconception eating behaviours with longitudinal dietary patterns from preconception to late pregnancy as well as gestational weight gain (GWG) are limited. We derived dietary pattern trajectories from preconception to late-pregnancy, and related preconception eating behaviours to these trajectories and GWG. Preconception eating behaviours were assessed using the Three-Factor Eating Questionnaire measuring cognitive restraint (CR) - conscious restriction of food intake, emotional eating (EE) - overeating in response to negative emotions, and uncontrolled eating (UE) - overeating with a feeling of lack of control. Dietary intakes were measured at preconception, 20-21 and 34-36 weeks' gestation with food frequency questionnaires. Dietary patterns were determined using factor analysis, and trajectories derived using group-based trajectory modelling. Inadequate and excessive GWG were defined according to Institute of Medicine guidelines based on weights at preconception and the last antenatal visit (median: 38 weeks' gestation). Two dietary patterns were derived: 'Fast Food, Fried Snacks and Desserts (FFD)' and 'Soup, Fish and Vegetables (SFV)'. Adherence trajectories from preconception to late-pregnancy were characterised as consistently high ("stable-high") and low ("stable-low"). Women with higher UE scores had higher odds of being in the "stable-high" trajectory (n = 34) of the FFD pattern [Odds Ratio (OR): 1.25, 95% Confidence Interval (CI): 1.03, 1.51], compared to "stable-low" (n = 260). Percentages of women with inadequate, adequate or excessive GWG were 21.7% (n = 70), 25.8% (n = 83), and 52.5% (n = 169), respectively; women with higher EE scores had a higher likelihood of excessive GWG [Relative Risk Ratio (RRR): 1.35, 95% CI: 1.02, 1.80], but this association was attenuated after adjusting for preconception body mass index. Eating behaviour interventions to improve dietary patterns among pregnant women may need to start as early as preconception, incorporating strategies to manage UE.

Functional and immunological mapping of domains of the reticulocyte binding protein, Plasmodium vivax PvRBP2a.

We previously described a novel Plasmodium vivax invasion mechanism into human reticulocytes via the PvRBP2a-CD98 receptor-ligand pair. We assessed the PvRBP2a epitopes involved in CD98 binding and recognised by antibodies from infected patients using linear epitope mapping. We identified two epitope clusters mediating PvRBP2a-CD98 interaction. One cluster named cluster B (PvRBP2a431-448, TAALKEKGKLLANLYNKL) was the target of antibody responses in P. vivax-infected humans. Peptides from each cluster were able to prevent live parasite invasion of human reticulocytes. These results provide new insights for development of a malaria blood stage vaccine against P. vivax.

Neonatal Nucleus Accumbens Microstructure Modulates Individual Susceptibility to Preconception Maternal Stress in Relation to Externalizing Behaviors.

OBJECTIVE: Maternal stress influences in utero brain development and is a modifiable risk factor for offspring psychopathologies. Reward circuitry dysfunction underlies various internalizing and externalizing psychopathologies. This study examined (1) the association between maternal stress and microstructural characteristics of the neonatal nucleus accumbens (NAcc), a major node of the reward circuitry, and (2) whether neonatal NAcc microstructure modulates individual susceptibility to maternal stress in relation to childhood behavioral problems. METHOD: K-means longitudinal cluster analysis was performed to determine trajectories of maternal stress measures (Perceived Stress Scale [PSS], hair cortisol) from preconception to the third trimester. Neonatal NAcc microstructural measures (orientation density index [ODI] and intracellular volume fraction [ICVF]) were compared across trajectories. We then examined the interaction between maternal stress and neonatal NAcc microstructure on child internalizing and externalizing behaviors, assessed between ages 3 and 4 years. RESULTS: Two trajectories of maternal stress magnitude ("low"/"high") were identified for both PSS (n = 287) and hair cortisol (n = 336). Right neonatal NAcc ODI (rNAcc-ODI) was significantly lower in "low" relative to "high" PSS trajectories (n = 77, p = .04). PSS at preconception had the strongest association with rNAcc-ODI (r = 0.293, p = .029). No differences in NAcc microstructure were found between hair cortisol trajectories. A significant interaction between preconception PSS and rNAcc-ODI on externalizing behavior was observed (n = 47, p = .047). CONCLUSION: Our study showed that the preconception period contributes to in utero NAcc development, and that NAcc microstructure modulates individual susceptibility to preconception maternal stress in relation to externalizing problems.

Clinical Outcomes of 111 Patients with Early Onset Idiopathic Scoliosis (EOIS) Receiving Brace Treatment: A Longitudinal Retrospective Cohort Study.

Introduction: Bracing is one of the first-line treatment for early-onset idiopathic scoliosis (EOIS) to control curves from progression. This study aimed to explore the determinants that govern bracing effectiveness in EOIS. Methods: One hundred and eleven patients with EOIS (mean age of 8.6 ± 1.25 at diagnosis) received bracing treatment and had a final follow-up beyond skeletal maturity were identified from records between 1988 and 2021. Demographic data and clinical features of spinal curvature were obtained for correlation analyses to determine the associations between curve outcomes and clinical features. Results: Most patients were female (85.6%) and had a major curve on the left side (67%). The mean baseline Cobb angle of major curves was 21.73 ± 7.92°, with a mean Cobb angle progression of 18.05 ± 19.11°. The average bracing duration was 5.3 ± 1.9 years. Only 26 (23.4%) of them underwent surgery. The final Cobb angle and curve progression at the final follow-up with a Cobb angle of ≥50° were positively correlated with the initial Cobb angle (r = 0.206 and r = 0.313, respectively) and negatively correlated with maturity parameters. The lumbar curve type was found to correlate with a smaller final Cobb angle. Conclusions: The majority of patients had a final Cobb angle < 50°, which was considered a successful bracing outcome. The final Cobb angle correlated with the initial Cobb angle and curve types observed in EOIS.

A randomised controlled pilot study of a Nintendo Ring Fit Adventure™ balance and strengthening exercise program in community-dwelling older adults with a history of falls.

OBJECTIVES: This pilot study examined the feasibility, acceptability, and effects of a Nintendo Ring Fit Adventure™-based balance and muscle strengthening exercise program in community-dwelling older adults with a history of falls. METHODS: Older adults who have had at least one fall in the past year were randomly assigned to an experimental (n = 21) or control group (n = 21). The experimental group performed 16 exercise sessions in total, lasting 60 min each, twice a week for 8 weeks, whereas the control group received usual care. Feasibility was evaluated based on the scores of participants in the exercises. Acceptance was evaluated using a customised questionnaire examining participants' self-perceived enjoyment, feasibility and improvements. Clinical outcomes including balance (Mini-BESTest), lower limb muscle strength (Five-Time Sit-to-Stand test), mobility (Timed-Up and Go test), dual-task ability (Timed-Up and Go test-Dual Task), fear of falling (Icon-FES) and executive function (Color Trails Test) were evaluated at baseline and 8 weeks. RESULTS: Thirty-one participants (74%) finished the 8-week assessment. The experimental group significantly improved their scores in six out of eight exercises (all p < .031). The mean scores of the self-perceived enjoyment, feasibility and improvement domains of the acceptability questionnaire were 3.46 ± .53, 3.08 ± .59, and 3.47 ± .57 respectively. A significant improvement in the anticipatory subscore of the Mini-BESTest was found in the experimental group compared to the control group (p = .02; Partial eta squared = .14). CONCLUSIONS: The Nintendo Ring Fit Adventure™-based exercise program was feasible, acceptable, and potentially effective in community-dwelling older adults with a history of falls.

Preliminary assessment of the Healthy Early Life Moments (HELMS) webinars in empowering Developmental Origins of Health and Disease (DOHaD) concept among healthcare professionals - a pragmatic serial cross-sectional study.

OBJECTIVES: The Developmental Origins of Health and Disease (DOHaD) concept has gained prominence in maternal and child health (MCH), emphasizing how early-life factors impact later-life non-communicable diseases. However, a knowledge-practice gap exists in applying DOHaD principles among healthcare professionals. Healthy Early Life Moments in Singapore (HELMS) introduced webinars to bridge this gap and empower healthcare professionals. We aimed to conduct a preliminary assessment to gain early insights into the outreach and effectiveness of the educational initiative offered with the HELMS webinars. METHODS: We employed a pragmatic serial cross-sectional study approach and targeted healthcare professionals involved in MCH care. We also collected and analyzed data on webinar registration and attendance, participants' profession and organizational affiliations, and post-webinar survey responses. RESULTS: The median webinar attendance rate was 59.6 % (25th-75th percentile: 58.4-60.8 %). Nurses represented 68.6 % of attendees (n=2,589 out of 3,774). Post-webinar surveys revealed over 75 % of the participants providing positive responses to 14 out of 15 survey questions concerning content, delivery, applicability to work, and organization. CONCLUSIONS: Assessment of the HELMS webinars provided insight into the outreach and early effectiveness in enhancing healthcare professionals' knowledge and confidence in delivering DOHaD education. Bridging the knowledge-practice gap remains a crucial goal.

A machine-learning exploration of the exposome from preconception in early childhood atopic eczema, rhinitis and wheeze development.

BACKGROUND: Most previous research on the environmental epidemiology of childhood atopic eczema, rhinitis and wheeze is limited in the scope of risk factors studied. Our study adopted a machine learning approach to explore the role of the exposome starting already in the preconception phase. METHODS: We performed a combined analysis of two multi-ethnic Asian birth cohorts, the Growing Up in Singapore Towards healthy Outcomes (GUSTO) and the Singapore PREconception Study of long Term maternal and child Outcomes (S-PRESTO) cohorts. Interviewer-administered questionnaires were used to collect information on demography, lifestyle and childhood atopic eczema, rhinitis and wheeze development. Data training was performed using XGBoost, genetic algorithm and logistic regression models, and the top variables with the highest importance were identified. Additive explanation values were identified and inputted into a final multiple logistic regression model. Generalised structural equation modelling with maternal and child blood micronutrients, metabolites and cytokines was performed to explain possible mechanisms. RESULTS: The final study population included 1151 mother-child pairs. Our findings suggest that these childhood diseases are likely programmed in utero by the preconception and pregnancy exposomes through inflammatory pathways. We identified preconception alcohol consumption and maternal depressive symptoms during pregnancy as key modifiable maternal environmental exposures that increased eczema and rhinitis risk. Our mechanistic model suggested that higher maternal blood neopterin and child blood dimethylglycine protected against early childhood wheeze. After birth, early infection was a key driver of atopic eczema and rhinitis development. CONCLUSION: Preconception and antenatal exposomes can programme atopic eczema, rhinitis and wheeze development in utero. Reducing maternal alcohol consumption during preconception and supporting maternal mental health during pregnancy may prevent atopic eczema and rhinitis by promoting an optimal antenatal environment. Our findings suggest a need to include preconception environmental exposures in future research to counter the earliest precursors of disease development in children.

Presence of onco-fetal neighborhoods in hepatocellular carcinoma is associated with relapse and response to immunotherapy.

Onco-fetal reprogramming of the tumor ecosystem induces fetal developmental signatures in the tumor microenvironment, leading to immunosuppressive features. Here, we employed single-cell RNA sequencing, spatial transcriptomics and bulk RNA sequencing to delineate specific cell subsets involved in hepatocellular carcinoma (HCC) relapse and response to immunotherapy. We identified POSTN+ extracellular matrix cancer-associated fibroblasts (EM CAFs) as a prominent onco-fetal interacting hub, promoting tumor progression. Cell-cell communication and spatial transcriptomics analysis revealed crosstalk and co-localization of onco-fetal cells, including POSTN+ CAFs, FOLR2+ macrophages and PLVAP+ endothelial cells. Further analyses suggest an association between onco-fetal reprogramming and epithelial-mesenchymal transition (EMT), tumor cell proliferation and recruitment of Treg cells, ultimately influencing early relapse and response to immunotherapy. In summary, our study identifies POSTN+ CAFs as part of the HCC onco-fetal niche and highlights its potential influence in EMT, relapse and immunotherapy response, paving the way for the use of onco-fetal signatures for therapeutic stratification.

Joint modelling of mental health markers through pregnancy: a Bayesian semi-parametric approach.

Maternal depression and anxiety through pregnancy have lasting societal impacts. It is thus crucial to understand the trajectories of its progression from preconception to postnatal period, and the risk factors associated with it. Within the Bayesian framework, we propose to jointly model seven outcomes, of which two are physiological and five non-physiological indicators of maternal depression and anxiety over time. We model the former two by a Gaussian process and the latter by an autoregressive model, while imposing a multidimensional Dirichlet process prior on the subject-specific random effects to account for subject heterogeneity and induce clustering. The model allows for the inclusion of covariates through a regression term. Our findings reveal four distinct clusters of trajectories of the seven health outcomes, characterising women's mental health progression from before to after pregnancy. Importantly, our results caution against the loose use of hair corticosteroids as a biomarker, or even a causal factor, for pregnancy mental health progression. Additionally, the regression analysis reveals a range of preconception determinants and risk factors for depressive and anxiety symptoms during pregnancy.

Fetal gene therapy.

Fetal gene therapy was first proposed toward the end of the 1990s when the field of gene therapy was, to quote the Gartner hype cycle, at its "peak of inflated expectations." Gene therapy was still an immature field but over the ensuing decade, it matured and is now a clinical and market reality. The trajectory of treatment for several genetic diseases is toward earlier intervention. The ability, capacity, and the will to diagnose genetic disease early-in utero-improves day by day. A confluence of clinical trials now signposts a trajectory toward fetal gene therapy. In this review, we recount the history of fetal gene therapy in the context of the broader field, discuss advances in fetal surgery and diagnosis, and explore the full ambit of preclinical gene therapy for inherited metabolic disease.

Preconception maternal retinal arteriolar narrowing and fetal growth throughout pregnancy: A prospective cohort study.

OBJECTIVE: To investigate the association between preconception maternal retinal arteriolar calibre and fetal growth. DESIGN, SETTING AND POPULATION: A hospital-based, prospective preconception cohort including 369 women with a singleton live birth. METHODS: We collected detailed information on sociodemographic status, pregnancy history and lifestyle, and performed retinal imaging at the preconception visit. MAIN OUTCOME MEASURES: We retrieved medical records documenting fetal growth biometrics (e.g., abdominal circumference [AC], head circumference [HC], femur length [FL]) at 11-13, 18-21, 24-28, and 32-34 weeks throughout pregnancy. We then computed the z scores for all fetal growth biometrics from 14 weeks of gestation where data were available, referencing the INTERGROWTH-21st fetal growth chart. We used a linear mixed model to estimate the association between maternal preconception retinal arteriolar calibre and fetal growth biometrics z scores throughout pregnancy, with random intercept accounting for repeated measures within individuals. We then performed a multivariable linear regression of maternal preconception retinal arteriolar calibre and z score changes for all fetal growth biometrics between 24-28 weeks and 32-34 weeks of gestation, after full adjustment. RESULTS: Maternal preconception generalised retinal arteriolar narrowing was consistently associated with a reduction in fetal AC z scores (-0.34; 95% CI -0.66 to -0.03) throughout pregnancy. In addition, women with preconception generalised retinal arteriolar narrowing tended to have significantly reduced z score changes in AC (-0.41; 95% CI -0.90 to -0.001) and fetal FL (-0.55; 95% CI -1.00 to -0.10) between 24-28 weeks and 32-34 weeks of gestation, respectively. CONCLUSIONS: Our findings suggest that women with narrower preconception retinal arterioles had smaller fetuses, evidenced by reductions in AC and FL z score throughout pregnancy.

Feasibility, safety, and effects of a Nintendo Ring Fit Adventure™ balance and strengthening exercise program in community-dwelling older adults with a history of falls: A feasibility randomized controlled trial.

AIM: This pilot study examined the feasibility, safety, and effects of a Nintendo Ring Fit Adventure™-based exercise program to enhance balance and lower limb muscle strength in community-dwelling older adults with a history of falls. METHODS: In total, 42 older adults who experienced at least one fall in the past year were randomly assigned to an experimental or control group. Participants in the experimental group performed 60-min sessions of the exercise program twice per week for 8 weeks. The control group received usual care. We assessed the feasibility (retention and adherence to the exercise program), safety (number of adverse events), and clinical outcomes: (1) balance (Mini-BESTest); (2) functional lower limb muscle strength (Five-Time Sit-to-Stand test); (3) mobility (Timed-Up and Go test); (4) dual-task ability (Timed-Up and Go test - Dual Task); (5) fear of falling (Icon-FES); and (6) executive function (Color Trails Test). RESULTS: Thirty-one participants (74%) completed the 8-week assessment. No adverse event associated with the exercise program was reported. There was a significant interaction in the anticipatory domain score of the Mini-BESTest between the experimental and control groups over the 8 weeks (P = 0.019). CONCLUSIONS: The Nintendo Ring Fit Adventure™-based exercise program was feasible, safe, and potentially effective in improving anticipatory balance in community-dwelling older fallers. Geriatr Gerontol Int 2024; 24: 334-341.

Preconception maternal retinal venular widening and steeper resistance increments in the utero-fetoplacental circulation in pregnancy.

We investigated the relationship of preconception maternal retinal vasculature and utero-fetoplacental circulation in ensuing pregnancy. Embedded in a hospital-based, prospective preconception cohort, 396 women with a singleton live birth were included for analysis. We assessed retinal vascular caliber during preconception phase and retrieved ultrasonogram results documenting utero-fetoplacental circulatory indices using Doppler ultrasonography and documented them at 18-21 weeks, 24-28 weeks, and 32-34 weeks where available. We performed a modified Poisson regression to estimate the relative risk of utero-fetoplacental abnormalities, adjusting for major confounders including pre-pregnancy and blood pressure. Per 10 µm increment in maternal preconception retinal venules was associated with over two-fold risks in developing notching (Relative risk [RR]: 2.84; 95% confidence interval [CI]: 1.79, 4.81) and ≥95th percentile umbilical artery pulsatility index (2.36; 1.72, 3.23) during mid-to-late pregnancy, respectively. Women with preconception retinal venular widening tended to demonstrate steeper resistance increments in both maternal uterine arteries and fetal umbilical arteries during mid-to-late pregnancy.

Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes.

Pathological placental inflammation increases the risk for several adult disorders, but these mediators are also expressed under homeostatic conditions, where their contribution to adult health outcomes is unknown. Here we define an inflammation-related expression signature, primarily expressed in Hofbauer cells of the term placenta and use expression quantitative trait loci to create a polygenic score (PGS) predictive of its expression. Using this PGS in the UK Biobank we conduct a phenome-wide association study, followed by Mendelian randomization and identify protective, sex-dependent effects of the placental module on cardiovascular and depressive outcomes. Genes differentially regulated by intra-amniotic infection and preterm birth are over-represented within the module. We also identify aspirin as a putative modulator of this inflammation-related signature. Our data support a model where disruption of placental Hofbauer cell function, due to preterm birth or prenatal infection, contributes to the increased risk of depression and cardiovascular disease observed in these individuals.

A fully convolutional neural network for comprehensive compartmentalization of abdominal adipose tissue compartments in MRI.

BACKGROUND: Existing literature has highlighted structural, physiological, and pathological disparities among abdominal adipose tissue (AAT) sub-depots. Accurate separation and quantification of these sub-depots are crucial for advancing our understanding of obesity and its comorbidities. However, the absence of clear boundaries between the sub-depots in medical imaging data has challenged their separation, particularly for internal adipose tissue (IAT) sub-depots. To date, the quantification of AAT sub-depots remains challenging, marked by a time-consuming, costly, and complex process. PURPOSE: To implement and evaluate a convolutional neural network to enable granular assessment of AAT by compartmentalization of subcutaneous adipose tissue (SAT) into superficial subcutaneous (SSAT) and deep subcutaneous (DSAT) adipose tissue, and IAT into intraperitoneal (IPAT), retroperitoneal (RPAT), and paraspinal (PSAT) adipose tissue. MATERIAL AND METHODS: MRI datasets were retrospectively collected from Singapore Preconception Study for Long-Term Maternal and Child Outcomes (S-PRESTO: 389 women aged 31.4 ± 3.9 years) and Singapore Adult Metabolism Study (SAMS: 50 men aged 28.7 ± 5.7 years). For all datasets, ground truth segmentation masks were created through manual segmentation. A Res-Net based 3D-UNet was trained and evaluated via 5-fold cross-validation on S-PRESTO data (N = 300). The model's final performance was assessed on a hold-out (N = 89) and an external test set (N = 50, SAMS). RESULTS: The proposed method enabled reliable segmentation of individual AAT sub-depots in 3D MRI volumes with high mean Dice similarity scores of 98.3%, 97.2%, 96.5%, 96.3%, and 95.9% for SSAT, DSAT, IPAT, RPAT, and PSAT respectively. CONCLUSION: Convolutional neural networks can accurately sub-divide abdominal SAT into SSAT and DSAT, and abdominal IAT into IPAT, RPAT, and PSAT with high accuracy. The presented method has the potential to significantly contribute to advancements in the field of obesity imaging and precision medicine.

Associations of predominant night-eating with plasma glycemic status and continuous glucose monitoring measures among pregnant women.

BACKGROUND & AIMS: To examine whether predominant night-eating, defined as more than 50% of total daily energy intake consumed between 1900 and 0659 h, is associated with glycemic outcomes in pregnancy. METHODS: This was a prospective cohort study of 277 healthy pregnant women with complete 4-day dietary intake records at 18-24 weeks gestation, recruited from KK Women's and Children's Hospital, Singapore. Primary outcomes were fasting, 1-h, and 2-h plasma glucose after a 75-g oral glucose tolerance test at 24-28 weeks gestation. Secondary outcomes were gestational diabetes mellitus (GDM), fasting insulin, homeostasis model assessment of insulin resistance (HOMA2-IR), ß-cell function (HOMA2-%B), and continuous glucose monitoring (CGM) measures. Glucose variables in continuous form were loge-transformed before analyses. RESULTS: Predominant night-eating (11.6%) was associated with higher fasting glucose (geometric mean ratio (95% confidence interval) 1.05 (1.01, 1.08)) and 1-h glucose (1.11 (1.01, 1.21)), but not with 2-h glucose or GDM risk. Predominant night-eating women had lower fasting insulin (0.77 (0.63, 0.95)), lower HOMA2-IR (0.78 (0.64, 0.97)), and lower HOMA2-%B (0.77 (0.67, 0.89)) than their predominant day-eating counterparts. For CGM measures, predominant night-eating was associated with higher mean glucose (1.07 (1.00, 1.15)), higher glucose management indicator (1.05 (1.00, 1.10)), and higher overall glucose levels throughout 24 h (1.10 (1.02, 1.19)). All these associations were adjusted for socio-demographic, lifestyle factors, and diet composition. CONCLUSION: Predominant night-eating was mainly associated with less desirable glycemic outcomes during pregnancy. Future studies should explore dietary interventions aimed at reducing consumption of relatively more calories at night than day during pregnancy.

Perinatal Plasma Carotenoids and Vitamin E Concentrations with Glycemia and Insulin Resistance in Women during and after Pregnancy.

We examined the associations of perinatal plasma carotenoids and E vitamers concentrations with glycemia, insulin resistance, and gestational and type 2 diabetes mellitus during pregnancy and post-pregnancy in GUSTO women. Plasma carotenoid and E vitamer concentrations were measured at delivery, and principal component analysis was used to derive the patterns of their concentrations. Fasting and 2 h glucose levels and fasting insulin were measured at 26-28 weeks gestation and 4-6 years post-pregnancy, with the derivation of homeostatic model assessment for insulin resistance (HOMA-IR). In 678 women, two carotenoid patterns (CP1: α- and ß-carotene and lutein; CP2: zeaxanthin, lycopene, and ß-cryptoxanthin) and one E vitamer pattern (VE: γ-, δ-, and α-tocopherols) were derived. A higher CP1 score (1-SD) was associated with lower gestational fasting glucose (ß (95%CI): -0.06 (-0.10, -0.02) mmol/L) and lower gestational (-0.17 (-0.82, 0.01) mmol/L, p = 0.06) and post-pregnancy HOMA-IR (-0.11 (-0.15, -0.08) mmol/L). A higher VE score (1 SD) was associated with higher gestational and post-pregnancy fasting and 2 h glucose (gestational: 0.05 (0.01, 0.08) and 0.08 (0.01, 0.16); post-pregnancy: 0.19 (0.07, 0.31) and 0.24 (0.06, 0.42) mmol/L). Higher α- and ß-carotene and lutein may be beneficial for gestational fasting glycemia, but higher vitamin E may increase gestational and post-pregnancy glycemia, although these findings require confirmation in cohorts with prospective longitudinal measurements of these vitamins.