Identification and reproducibility of dietary patterns assessed with a FFQ among women planning pregnancy.

OBJECTIVE: To identify a posteriori dietary patterns among women planning pregnancy and assess the reproducibility of these patterns in a subsample using two dietary assessment methods. DESIGN: A semi-quantitative FFQ was administered to women enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes study. Dietary patterns from the FFQ were identified using exploratory factor analysis (EFA). In a subsample of women (n 289), 3-d food diaries (3DFD) were also completed and analysed. Reproducibility of the identified patterns was assessed using confirmatory factor analysis (CFA) in the subsample, and goodness of fit of the CFA models was examined using several fit indices. Subsequently, EFA was conducted in the subsample and dietary patterns of the FFQ and the 3DFD were compared. SETTING: Singapore. PARTICIPANTS: 1007 women planning pregnancy (18-45 years). RESULTS: Three dietary patterns were identified from the FFQ: the 'Fish, Poultry/Meat and Noodles' pattern was characterised by higher intakes of fish, poultry/meat and noodles in soup; 'Fast Food and Sweetened Beverages' pattern was characterised by higher intakes of fast food, sweetened beverages and fried snacks; 'Bread, Legumes and Dairy' pattern was characterised by higher intakes of buns/ethnic breads, nuts/legumes and dairy products. The comparative fit indices from the CFA models were 0·79 and 0·34 for the FFQ and 3DFD of the subsample, respectively. In the subsample, three similar patterns were identified in the FFQ while only two for the 3DFD. CONCLUSIONS: Dietary patterns from the FFQ are reproducible within this cohort, providing a basis for future investigations on diet and health outcomes.

Long-Term Fate of Human Fetal Liver Progenitor Cells Transplanted in Injured Mouse Livers.

Liver progenitor cells have the potential to repair and regenerate a diseased liver. The success of any translational efforts, however, hinges on thorough understanding of the fate of these cells after transplant, especially in terms of long-term safety and efficacy. Here, we report transplantation of a liver progenitor population isolated from human fetal livers into immune-permissive mice with follow-up up to 36 weeks after transplant. We found that human progenitor cells engraft and differentiate into functional human hepatocytes in the mouse, producing albumin, alpha-1-antitrypsin, and glycogen. They create tight junctions with mouse hepatocytes, with no evidence of cell fusion. Interestingly, they also differentiate into functional endothelial cell and bile duct cells. Transplantation of progenitor cells abrogated carbon tetrachloride-induced fibrosis in recipient mice, with downregulation of procollagen and anti-smooth muscle actin. Paradoxically, the degree of engraftment of human hepatocytes correlated negatively with the anti-fibrotic effect. Progenitor cell expansion was most prominent in cirrhotic animals, and correlated with transcript levels of pro-fibrotic genes. Animals that had resolution of fibrosis had quiescent native progenitor cells in their livers. No evidence of neoplasia was observed, even up to 9 months after transplantation. Human fetal liver progenitor cells successfully attenuate liver fibrosis in mice. They are activated in the setting of liver injury, but become quiescent when injury resolves, mimicking the behavior of de novo progenitor cells. Our data suggest that liver progenitor cells transplanted into injured livers maintain a functional role in the repair and regeneration of the liver. Stem Cells 2018;36:103-113.

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.

Longitudinal characterization of determinants associated with obesogenic growth patterns in early childhood.

BACKGROUND: Longitudinal assessment of the determinants of obesogenic growth trajectories in childhood can suggest appropriate developmental windows for intervention. METHODS: Latent class growth mixture modelling was used to identify body mass index (BMI) z-score trajectories from birth to age 6 years in 994 children from a prospective mother-offspring cohort (Chinese, Indian and Malay ethnicities) based in Singapore. We evaluated the early-life determinants of the trajectories as well as their associations with cardiometabolic risk markers at age 6 years. RESULTS: Five BMI z-score trajectory patterns were identified, three within the healthy weight range, alongside early-acceleration and late-acceleration obesogenic trajectories. The early-acceleration pattern was characterized by elevated fetal abdominal circumference growth velocity, BMI acceleration immediately after birth and crossing of the obesity threshold by age 2 years. The late-acceleration pattern had normal fetal growth and BMI acceleration after infancy, and approached the obesity threshold by age 6 years. Abdominal fat, liver fat, insulin resistance and odds of pre-hypertension/hypertension were elevated in both groups. Indian ethnicity, high pre-pregnancy BMI, high polygenic risk scores for obesity and shorter breastfeeding duration were common risk factors for both groups. Malay ethnicity and low maternal educational attainment were uniquely associated with early BMI acceleration, whereas nulliparity and obesogenic eating behaviours in early childhood were uniquely associated with late BMI acceleration. CONCLUSION: BMI acceleration starting immediately after birth or after infancy were both linked to early cardiometabolic alterations. The determinants of these trajectories may be useful for developing early risk stratification and intervention approaches to counteract metabolic adversities linked to childhood obesity.

Ovarian biomarkers predict controlled ovarian stimulation for in vitro fertilisation treatment in Singapore.

INTRODUCTION: Ovarian biomarkers have been shown to predict responses to controlled ovarian hyperstimulation (COH) during in vitro fertilisation (IVF) in predominantly Caucasian populations, with limited studies performed in Southeast Asian women in Singapore. METHODS: We evaluated the performance of serum anti-Müllerian hormone (AMH), follicle-stimulating hormone and oestradiol levels, antral follicle count (AFC), body mass index, ovarian volume, and age to establish thresholds for the prediction of poor (< 4 oocytes retrieved) and excessive responses (> 19 oocytes retrieved) in 263 women undergoing COH. Univariate and multivariate logistic regression analysis and receiver operating characteristic curves were used to calculate probabilities for poor and excessive responders to COH. RESULTS: 36 (13.7%) and 50 (19.0%) women had poor and excessive response to COH, respectively. An AMH value of 0.69 ng/mL predicted poor ovarian response with positive likelihood ratio (LR) of 2.94, compared to an AFC of ≤ 5 when the positive LR is 2.36. Conversely, an AMH value of ≥ 3.06 ng/mL predicted excessive ovarian response with positive LR of 2.24, compared to an AFC cut-off of ≥ 12 with positive LR of 1.93. CONCLUSION: AMH levels and AFC are equivalent in the prediction of both poor and excessive ovarian response in women undergoing IVF. Our study highlights the importance of establishing population-specific cut-off biomarker values so that protocols can be tailored to optimise IVF treatment.

Pregnancy Outcomes in COVID-19: A Prospective Cohort Study in Singapore.

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION: The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.

Immunological observations and transcriptomic analysis of trimester-specific full-term placentas from three Zika virus-infected women.

OBJECTIVES: Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear. METHODS: Full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. RESULTS: In this study, each woman exhibited a unique immune response with raised IL-1RA, IP-10, EGF and RANTES expression and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localised to placental Hofbauer cells, the placentas showed no anatomic defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centred on differential eIF2 signalling, mitochondrial dysfunction and oxidative phosphorylation. Despite these, the babies were delivered without any congenital anomalies. CONCLUSION: These findings should translate to improve clinical prenatal screening procedures for virus-infected pregnant patients.

Comparison between Single and Double Cleavage-Stage Embryo Transfers, Single and Double Blastocyst Transfers in a South East Asian In Vitro Fertilisation Centre.

INTRODUCTION: This study investigated the differences in clinical pregnancy rate (CPR), live birth rate (LBR) and multiple pregnancy rate (MPR) between double cleavage-stage embryo transfers compared to single and double blastocysts stage embryo transfers in a single academic medical centre. MATERIALS AND METHODS: This was a retrospective cohort study performed at the KK Women's and Children's Hospital In Vitro Fertilisation (KKIVF) Centre of all women who underwent fresh-cycle in vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI) cycles over a 5-year period. The outcome measures were CPR, LBR and MPR. The study included 5294 cycles, of which 539 patients underwent single embryo transfer (SET); 4533 patients underwent double embryo transfer (DET); 84 patients underwent double blastocyst embryo transfer (DBT); and 65 patients underwent single blastocyst embryo transfer (SBT). RESULTS: The mean age of patients undergoing single blastocysts stage embryo transfer was lower than the other 2 groups. The DET, single and double blastocysts stage embryo transfer groups achieved similar LBR (33.9%, 38.7%, 35.4%, P >0.05) and CPR (42.4%, 46.2%, 46.9%). CONCLUSION: We found that single blastocysts stage embryo transfer is associated with similar LBR and CPR compared to double blastocysts stage embryo transfer and DET, with lower MPRs, and should be offered as standard practice, where possible.

Rapid Assessment Zika Virus Knowledge Among Clinical Specialists in Singapore: A Cross-sectional Survey.

INTRODUCTION: We report the results of a rapid assessment of Zika virus awareness among key clinical specialties in Singapore. METHODS: Between June 6 and June 19, 2016 we conducted an online survey of doctors working in obstetrics and gynaecology, neonatology and paediatrics in Singapore. The survey included 15 multiple choice questions to measure respondents' knowledge of Zika virus in four domains covering clinical and public health. RESULTS: A total of 110 survey responses (15% response rate) were obtained, 82% of respondents worked in the public sector. Overall, the median respondent score was 9.4 (Max score=15), with substantial variation (range: 3.5 - 14.7). Microcephaly and Guillain-Barré syndrome were recognised as causal complications of Zika virus infection by 99% and 50% of respondents respectively.  Clinical features which could help differentiate Zika from Dengue were less well understood with 50% and 68% correctly identifying conjunctivitis and low grade fever respectively. Worryingly, 14% favoured non-steroidal anti-inflammatory drugs as part of treatment, without first excluding dengue as a diagnosis. Also, only 36% of respondents were aware of the current recommendation for preventing sexual transmission of Zika virus. Fewer than 50% were aware of the need for ophthalmological evaluation as part of congenital Zika virus infection. DISCUSSION: Our assessment demonstrates that there is good awareness of the clinical manifestation of Zika virus disease among key specialty doctors, but confusion with Dengue disease remains. It also highlights knowledge gaps in the prevention of sexually-transmitted Zika virus infection and the clinical management of congenital Zika virus infection in newborns. Our study identified strategic areas to improve communication to front-line doctors during public health response to the Zika epidemic.

Stem cell tracking with optically active nanoparticles.

Stem-cell-based therapies hold promise and potential to address many unmet clinical needs. Cell tracking with modern imaging modalities offers insight into the underlying biological process of the stem-cell-based therapies, with the goal to reveal cell survival, migration, homing, engraftment, differentiation, and functions. Adaptability, sensitivity, resolution, and non-invasiveness have contributed to the longstanding use of optical imaging for stem cell tracking and analysis. To identify transplanted stem cells from the host tissue, optically active probes are usually used to label stem cells before the administration. In comparison to the traditional fluorescent probes like fluorescent proteins and dyes, nanoparticle-based probes are advantageous in terms of the photo-stabilities and minimal changes to the cell phenotype. The main focus here is to overview the recent development of optically active nanoparticles for stem cells tracking. The related optical imaging modalities include fluorescence imaging, photoacoustic imaging, Raman and surface enhanced Raman spectroscopy imaging.