Publications by authors named "Keith M Godfrey"

370 Publications

-inositol - A potential prophylaxis against premature onset of labour and preterm birth.

Nutr Res Rev 2021 Sep 16:1-19. Epub 2021 Sep 16.

Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo-inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo-inositol as a preventive agent. However, the underlying molecular mechanisms by which myo-inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo-inositol in human parturition and explains possible underlying molecular mechanisms by which myo-inositol might modulate the uteroplacental environment and inhibit preterm labour-onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour-onset. A higher uteroplacental inositol level, potentially promoted by maternal myo-inositol supplementation, might affect lipid metabolism, eicosanoid production, and secretion of pro-inflammatory chemocytokines, that overall dampen the pro-labour uteroplacental environment responsible for labour-onset and progress, thus, reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo-inositol supplementation and definitively address the efficacy of myo-inositol prophylaxis against PTB.
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http://dx.doi.org/10.1017/S0954422421000299DOI Listing
September 2021

Human non-CpG methylation patterns display both tissue-specific and inter-individual differences suggestive of underlying function.

Epigenetics 2021 Aug 30:1-12. Epub 2021 Aug 30.

MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.

DNA methylation (DNAm) in mammals is mostly examined within the context of CpG dinucleotides. Non-CpG DNAm is also widespread across the human genome, but the functional relevance, tissue-specific disposition, and inter-individual variability has not been widely studied. Our aim was to examine non-CpG DNAm in the wider methylome across multiple tissues from the same individuals to better understand non-CpG DNAm distribution within different tissues and individuals and in relation to known genomic regulatory features.DNA methylation in umbilical cord and cord blood at birth, and peripheral venous blood at age 12-13 y from 20 individuals from the Southampton Women's Survey cohort was assessed by Agilent SureSelect methyl-seq. Hierarchical cluster analysis (HCA) was performed on CpG and non-CpG sites and stratified by specific cytosine environment. Analysis of tissue and inter-individual variation was then conducted in a second dataset of 12 samples: eight muscle tissues, and four aliquots of cord blood pooled from two individuals.HCA using methylated non-CpG sites showed different clustering patterns specific to the three base-pair triplicate (CNN) sequence. Analysis of CAC sites with non-zero methylation showed that samples clustered first by tissue type, then by individual (as observed for CpG methylation), while analysis using non-zero methylation at CAT sites showed samples grouped predominantly by individual. These clustering patterns were validated in an independent dataset using cord blood and muscle tissue.This research suggests that CAC methylation can have tissue-specific patterns, and that individual effects, either genetic or unmeasured environmental factors, can influence CAT methylation.
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http://dx.doi.org/10.1080/15592294.2021.1950990DOI Listing
August 2021

Increasing nausea and vomiting of pregnancy is associated with sex-dependent differences in early childhood growth: the GUSTO mother-offspring cohort study.

BMC Pregnancy Childbirth 2021 Aug 22;21(1):578. Epub 2021 Aug 22.

Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 12, Singapore, 119228, Singapore.

Background: Nausea and vomiting of pregnancy (NVP) is common and underlying mechanisms are poorly understood. Longer-term offspring outcomes are also not well documented. This study aimed to determine if NVP, even in milder forms, is associated with adverse pregnancy and childhood growth outcomes.

Methods: In the GUSTO prospective mother-offspring cohort, women with singleton pregnancies (n = 1172) recruited in first trimester responded to interviewer-administered questions at 26-28 weeks' gestation about earlier episodes of NVP since becoming pregnant. Pregnancy outcomes were obtained from medical records. Offspring height and weight measured at 15 time-points between birth to 72 months (m) were standardised for age and sex.

Results: 58.5% (n = 686) reported mild-moderate vomiting (mNVP), 10.5% (n = 123) severe vomiting (sNVP) and 5.7% (n = 67) severe vomiting with hospitalisation (shNVP). There was no difference in odds of gestational diabetes, hypertensive disorders of pregnancy, labour induction or caesarean section after adjustment for covariates. sNVP was associated with late preterm delivery [34-36 weeks', adjusted OR = 3.04 (95% CI 1.39,6.68)], without increased odds of neonatal unit admission. Compared with no NVP, boys born to mothers with sNVP were longer at birth [adjusted β = 0.38 standard deviations (SDs) (95% CI 0.02,0.73)], remained taller [0.64 SDs (0.23,1.04) at 72 m] and heavier [0.57 SDs (0.05,1.08) at 60 m] without differences in BMI. Conversely, girls born to mothers with shNVP were lighter from 48 m [- 0.52 SDs (- 1.00, - 0.03)] onwards with lower BMI [- 0.61 SDs (- 1.12,-0.09)]. Conditional growth modelling revealed significant sex-divergence in weight-gain at birth-3 m, 6-9 m and 4-5 years.

Conclusions: Severe NVP was associated with late preterm delivery, and both mild-moderate and severe NVP associated with sex-dependent differences in early childhood growth. Boys whose mothers had NVP were taller and heavier from birth with faster growth in the first year, whereas, girls had poorer weight gain and were lighter by 48 m. As even milder severities of NVP could have long-term impact on offspring growth, further research is needed to determine mechanisms involved and implications on future health.

Trial Registration: Clinicaltrials.gov identifier NCT01174875 .
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http://dx.doi.org/10.1186/s12884-021-04024-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380383PMC
August 2021

Placental C-DHA metabolism and relationship with maternal BMI, glycemia and birthweight.

Mol Med 2021 08 6;27(1):84. Epub 2021 Aug 6.

Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, 1E Kent Ridge Road, NUHS Tower Block, Level 12, Singapore, 119228, Singapore.

Background: Fetal docosahexaenoic acid (DHA) supply relies on preferential transplacental transfer, which is regulated by placental DHA lipid metabolism. Maternal hyperglycemia and obesity associate with higher birthweight and fetal DHA insufficiency but the role of placental DHA metabolism is unclear.

Methods: Explants from 17 term placenta were incubated with C-labeled DHA for 48 h, at 5 or 10 mmol/L glucose treatment, and the production of 17 individual newly synthesized C-DHA labeled lipids quantified by liquid chromatography mass spectrometry.

Results: Maternal BMI positively associated with C-DHA-labeled diacylglycerols, triacylglycerols, lysophospholipids, phosphatidylcholine and phosphatidylethanolamine plasmalogens, while maternal fasting glycemia positively associated with five C-DHA triacylglycerols. In turn, C-DHA-labeled phospholipids and triacylglycerols positively associated with birthweight centile. In-vitro glucose treatment increased most C-DHA-lipids, but decreased C-DHA phosphatidylethanolamine plasmalogens. However, with increasing maternal BMI, the magnitude of the glucose treatment induced increase in C-DHA phosphatidylcholine and C-DHA lysophospholipids was curtailed, with further decline in C-DHA phosphatidylethanolamine plasmalogens. Conversely, with increasing birthweight centile glucose treatment induced increases in C-DHA triacylglycerols were exaggerated, while glucose treatment induced decreases in C-DHA phosphatidylethanolamine plasmalogens were diminished.

Conclusions: Maternal BMI and glycemia increased the production of different placental DHA lipids implying impact on different metabolic pathways. Glucose-induced elevation in placental DHA metabolism is moderated with higher maternal BMI. In turn, findings of associations between many DHA lipids with birthweight suggest that BMI and glycemia promote fetal growth partly through changes in placental DHA metabolism.
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http://dx.doi.org/10.1186/s10020-021-00344-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349043PMC
August 2021

Atopic dermatitis trajectories to age 8 years in the GUSTO cohort.

Clin Exp Allergy 2021 Sep 31;51(9):1195-1206. Epub 2021 Jul 31.

Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

Background: The heterogeneity of childhood atopic dermatitis (AD) underscores the need to understand latent phenotypes that may inform risk stratification and disease prognostication.

Objective: To identify AD trajectories across the first 8 years of life and investigate risk factors associated with each trajectory and their relationships with other comorbidities.

Methods: Data were collected prospectively from 1152 mother-offspring dyads in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort from ages 3 months to 8 years. AD was defined based on parent-reported doctor's diagnosis. An unsupervised machine learning technique was used to determine AD trajectories.

Results: Three AD trajectories were identified as follows: early-onset transient (6.3%), late-onset persistent (6.3%) and early-onset persistent (2.1%), alongside a no AD/reference group (85.2%). Early-onset transient AD was positively associated with male gender, family history of atopy, house dust mite sensitization and some measures of wheezing. Early-onset persistent AD was associated with antenatal/intrapartum antibiotic use, food sensitization and some measures of wheezing. Late-onset persistent AD was associated with a family history of atopy, some measures of house dust mite sensitization and some measures of allergic rhinitis and wheezing.

Conclusion And Clinical Relevance: Three AD trajectories were identified in this birth cohort, with different risk factors and prognostic implications. Further work is needed to understand the molecular and immunological origins of these phenotypes.
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http://dx.doi.org/10.1111/cea.13993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611621PMC
September 2021

Household environmental microbiota influences early-life eczema development.

Environ Microbiol 2021 Jul 26. Epub 2021 Jul 26.

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Exposure to a diverse microbial environment during pregnancy and early postnatal period is important in determining predisposition towards allergy. However, the effect of environmental microbiota exposure during preconception, pregnancy and postnatal life on development of allergy in the child has not been investigated so far. In the S-PRESTO (Singapore PREconception Study of long Term maternal and child Outcomes) cohort, we collected house dust during all three critical window periods and analysed microbial composition using 16S rRNA gene sequencing. At 6 and 18 months, the child was assessed for eczema by clinicians. In the eczema group, household environmental microbiota was characterized by presence of human-associated bacteria Actinomyces, Anaerococcus, Finegoldia, Micrococcus, Prevotella and Propionibacterium at all time points, suggesting their possible contributions to regulating host immunity and increasing the susceptibility to eczema. In the home environment of the control group, putative protective effect of an environmental microbe Planomicrobium (Planococcaceae family) was observed to be significantly higher than that in the eczema group. Network correlation analysis demonstrated inverse relationships between beneficial Planomicrobium and human-associated bacteria (Actinomyces, Anaerococcus, Finegoldia, Micrococcus, Prevotella and Propionibacterium). Exposure to natural environmental microbiota may be beneficial to modulate shed human-associated microbiota in an indoor environment.
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http://dx.doi.org/10.1111/1462-2920.15684DOI Listing
July 2021

Maternal height, gestational diabetes mellitus and pregnancy complications.

Diabetes Res Clin Pract 2021 Aug 23;178:108978. Epub 2021 Jul 23.

Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address:

Aims: To explore the glucose-overload hypothesis of artefactual gestational diabetes (GDM) diagnosis in shorter women during oral glucose tolerance testing (OGTT), by investigating associations between height and maternal glycemia; and GDM and pregnancy complications in height-groups.

Methods: Women from GUSTO (n = 1100, 2009-2010) and NUH (n = 4068, 2017-2018) cohorts underwent a mid-gestation two and three time-point 75 g 2-hour OGTT, respectively. GDM-related complications (hypertensive disorders of pregnancy, preterm delivery, emergency cesarean section, neonatal intensive care unit admission, macrosomia, birthweight) were compared within shorter and taller groups, dichotomized by ethnic-specific median height.

Results: Using WHO-1999 criteria, 18.8% (GUSTO) to 22.9% (NUH) of women were diagnosed with GDM-1999; and by WHO-2013 criteria, 21.9% (NUH) had GDM-2013. Each 5-cm height increment was inversely associated with GDM-1999 (adjusted odds ratio [aOR, 95% CI] = 0.81 [0.76-0.87], 2-h glycemia (adjusted β [aβ, 95% CI] = -0.171 mmol/L [-0.208, -0.135]) and 1-h glycemia (aβ = -0.160 mmol/L [-0.207, -0.112]). The inverse association between height and 2-h glycemia was most marked in "Other" ethnicities (Eurasians/Caucasians/mixed/other Asians) and Indians, followed by Chinese, then Malays. Compared with non-GDM, GDM-1999 was associated with preterm delivery (aOR = 1.76 [1.19-2.61]) and higher birthweight (aβ = 57.16 g [20.95, 93.38]) only among taller but not shorter women.

Conclusions: Only taller women had an increased odds of GDM-related pregnancy complications. An artefactual GDM diagnosis due to glucose-overload among shorter women is plausible.
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http://dx.doi.org/10.1016/j.diabres.2021.108978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611603PMC
August 2021

Bone turnover in pregnancy, measured by urinary C-terminal telopeptide of type I collagen (CTX), is influenced by vitamin D supplementation and is associated with maternal bone health: Findings from the MAVIDOS trial.

Am J Clin Nutr 2021 Jul 23. Epub 2021 Jul 23.

MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.

Background: The pattern of change in maternal bone turnover throughout pregnancy is poorly characterized.

Objective: We investigated changes across pregnancy in a marker of maternal bone resorption, urinary C-terminal telopeptide of type I collagen (CTX), the influence of gestational vitamin D supplementation, and associations between CTX and maternal postnatal bone indices.

Design: The Maternal Vitamin D Osteoporosis Study (MAVIDOS) is a randomized, double-blind, placebo-controlled trial of 1000 IU/day cholecalciferol vs placebo from 14 weeks' gestation to birth. Maternal second void urinary α- and β-CTX were measured (Enzyme Linked Immunosorbent Assay, ELISA) at 14 and 34 weeks' gestation; DXA was performed within 2 weeks post-partum. Mann-Whitney rank sum, Spearman's rank correlation and linear regression were used to compare median CTX values within and between groups from early to late pregnancy, and associations with maternal bone outcomes.

Results: 372 women had CTX and 25(OH)-vitamin D measured in early and late pregnancy. CTX at 14 and 34 weeks' gestation were correlated in both placebo (r = 0.31) and cholecalciferol (r = 0.45) groups (P < 0.0001). Median CTX(μg/mmol creatinine) increased from 14 to 34 weeks' gestation in both groups (n = 372 total) [placebo (n = 188) 223.6 to 449.7; cholecalciferol (n = 184) 222.3 to 419.3; P = 0.03 for placebo vs cholecalciferol difference in CTX at 34 weeks' gestation]. The conditional increase in CTX(SD) from early to late pregnancy was greater in the placebo group (n = 188) than in the cholecalciferol group (n = 184) [placebo, mean(SD) 0.16(0.92); cholecalciferol, -0.16(1.06); p difference < 0.01]. Higher CTX at 34 weeks' gestation was associated, similarly in both groups, with lower maternal total hip and lumbar spine bone mineral content (BMC) and bone mineral density, e.g., lumbar spine BMD [β= -0.02 g/cm2/SD increase in CTX; 95%CI: -0.027, -0.002; P = 0.02, n = 283].

Conclusions: Maternal urinary CTX, a bone resorption marker, rises through pregnancy, though to a lesser degree with gestational cholecalciferol supplementation, and is inversely associated with maternal bone mass post-partum.Clinical Trial Registry number and website: ISRCTN:82927713; EUDRACT:2007-001716-23.
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http://dx.doi.org/10.1093/ajcn/nqab264DOI Listing
July 2021

Evaluation of a child food reward task and its association with maternal feeding practices.

PLoS One 2021 21;16(7):e0254773. Epub 2021 Jul 21.

Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research, Singapore, Singapore.

Food reward is defined as the momentary value of a food to the individual at the time of ingestion and is characterised by two psychological processes-"liking" and "wanting". We aimed to validate an age-appropriate food reward task to quantify implicit wanting of children from the GUSTO cohort (n = 430). At age 5 years, child appetitive traits and maternal feeding practices were reported by mothers via questionnaires. At age 6, a write-for-food task based on the child's preference for food or toy rewards was undertaken in laboratory conditions. Child BMI and skinfold measurements were taken at age 7. Convergent validity of the food reward task was assessed by associating with child appetitive traits, where enjoyment of food/food responsiveness (OR: 1.51; 95% CI: 1.06, 2.15) and emotional overeating (OR: 1.64; 95% CI: 1.09, 2.48) were positively associated with high food reward in children. Criterion validity was tested by associating with child BMI, however no significant relationships were observed. Multivariable logistic regression analysis with maternal feeding practices revealed that children whose mother tend to restrict unhealthy food (OR: 1.37; 95% CI: 1.03, 1.82) and girls whose mothers taught them about nutrition (OR: 2.09; 95% CI: 1.19, 3.67) were more likely to have high food reward. No further significant associations were observed between food reward, other appetitive traits and feeding practices. Despite the lack of association with child weight status, this study demonstrated the value of the write-for-food task to assess food reward in children and presented sex-specific associations with maternal feeding practices.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254773PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294516PMC
July 2021

Influence of Maternal Lifestyle and Diet on Perinatal DNA Methylation Signatures Associated With Childhood Arterial Stiffness at 8 to 9 Years.

Hypertension 2021 Sep 19;78(3):787-800. Epub 2021 Jul 19.

From the School of Human Development and Health, Institute of Developmental Sciences Building, Faculty of Medicine (R.M., N.K., E.A., G.C.B., K.M.G., M.A.H.), University of Southampton, United Kingdom.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8357051PMC
September 2021

Fecundability in reproductive aged women at risk of sexual dysfunction and associated risk factors: a prospective preconception cohort study.

BMC Pregnancy Childbirth 2021 Jun 25;21(1):444. Epub 2021 Jun 25.

Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, 229899, Singapore.

Background: Female sexual dysfunction (FSD) is a prevalent problem, affecting up to 41% of reproductive aged women worldwide. However, the association between female sexual function (FSF) and fecundability in women attempting to conceive remains unclear. We aimed 1) to examine the association between FSF in reproductive-aged preconception Asian women and fecundability, as measured by time-to-pregnancy in menstrual cycles, and 2) to examine lifestyle and behavioral factors associated with FSF.

Methods: From the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) prospective cohort, we evaluated FSF using the 6-item Female Sexual Function Index (FSFI-6) and ascertained time-to-pregnancy within a year of baseline assessment. We estimated fecundability ratio (FR) and 95% confidence interval (CI) using the discrete-time proportional hazards model, accounting for left-truncation and right censoring. We used multivariable logistic and linear regression models to identify potential factors related to FSF.

Results: Among 513 participants, 58.9% had low FSF as defined by a total FSFI-6 score at or below the median value of 22. Compared to women with high FSF, those with low FSF had a 27% reduction in fecundability (FR 0.73; 95% CI 0.54, 0.99), with adjustment for age, ethnicity, education, parity and body mass index. Overall, the FRs generally reduced with decreasing FSFI-6 scores. Physical activity, obesity, absence of probable depression and anxiety were independently associated with reduced odds of low FSF and increased FSFI-6 scores, after adjusting for sociodemographic characteristics.

Conclusions: Low FSF is associated with a longer time-to-pregnancy. Early evaluation and optimization of FSF through increased physical activity and optimal mental health may help to improve female fecundity. The finding of obese women having improved FSF remains uncertain which warrants further investigations on plausibly mechanisms. In general, the current finding highlights the importance of addressing FSF in preconception care service for general women, which is currently lacking as part of the fertility promotion effort in the country.
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http://dx.doi.org/10.1186/s12884-021-03892-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228958PMC
June 2021

Brown adipose tissue, adiposity and metabolic profile in preschool children.

J Clin Endocrinol Metab 2021 Jun 18. Epub 2021 Jun 18.

Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore.

Context: An inverse relationship between brown adipose tissue (BAT) and obesity has previously been reported in older children and adults, but unknown in young children.

Objective: We investigated the influence of BAT in thermoneutral condition on adiposity and metabolic profile in Asian preschool children.

Design, Setting And Participants: A total of 198 children aged 4.5 years from a prospective birth cohort study, Growing Up in Singapore Towards healthy Outcomes (GUSTO) were successfully studied with water-fat magnetic resonance imaging of the supraclavicular-axillary fat depot (FDSA). Regions within FDSA with fat-signal-fraction between 20% and 80% were considered BAT, and percentage BAT (%BAT), (100*BAT volume/ FDSA volume) was calculated.

Main Outcome Measures: Abdominal adipose tissue compartment volumes, ectopic fat in the soleus muscle and liver, fatty liver index, metabolic syndrome scores and markers of insulin sensitivity.

Results: A one percent unit increase in %BAT was associated with lower body mass index, difference (95%CI), -0.08 (-0.10, -0.06) kg/m 2 and smaller abdominal adipose tissue compartment volumes. Ethnicity and sex modified these associations. In addition, each unit increase in %BAT was associated with lower ectopic fat at 4.5 years in the liver, -0.008 (-0.013, -0.003) %, soleus muscle, -0.003 (-0.006, -0.001) % of water-content and lower fatty liver index at 6 years.

Conclusions: Higher %BAT is associated with a more favorable metabolic profile. BAT may thus play a role in the pathophysiology of obesity and related metabolic disorders. The observed ethnic and sex differences imply that the protective effect of BAT may vary among different groups.
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http://dx.doi.org/10.1210/clinem/dgab447DOI Listing
June 2021

The longitudinal association between early-life screen viewing and abdominal adiposity-findings from a multiethnic birth cohort study.

Int J Obes (Lond) 2021 09 9;45(9):1995-2005. Epub 2021 Jun 9.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

Importance: Screen viewing in adults has been associated with greater abdominal adiposity, with the magnitude of associations varying by sex and ethnicity, but the evidence is lacking at younger ages. We aimed to investigate sex- and ethnic-specific associations of screen-viewing time at ages 2 and 3 years with abdominal adiposity measured by magnetic resonance imaging at age 4.5 years.

Methods: The Growing Up in Singapore Towards healthy Outcomes is an ongoing prospective mother-offspring cohort study. Parents/caregivers reported the time their child spent viewing television, handheld devices, and computer screens at ages 2 and 3 years. Superficial and deep subcutaneous and visceral abdominal adipose tissue volumes were quantified from magnetic resonance images acquired at age 4.5 years. Associations between screen-viewing time and abdominal adipose tissue volumes were examined by multivariable linear regression adjusting for confounding factors.

Results: In the overall sample (n = 307), greater total screen-viewing time and handheld device times were associated with higher superficial and deep subcutaneous adipose tissue volumes, but not with visceral adipose tissue volumes. Interactions with child sex were found, with significant associations with superficial and deep subcutaneous and visceral adipose tissue volumes in boys, but not in girls. Among boys, the increases in mean (95% CI) superficial and deep subcutaneous and visceral adipose tissue volumes were 24.3 (9.9, 38.7), 17.6 (7.4, 27.8), and 7.8 (2.1, 13.6) mL per hour increase in daily total screen-viewing time, respectively. Ethnicity-specific analyses showed associations of total screen-viewing time with abdominal adiposity only in Malay children. Television viewing time was not associated with abdominal adiposity.

Conclusion: Greater total screen-viewing time (and in particular, handheld device viewing time) was associated with higher abdominal adiposity in boys and Malay children. Additional studies are necessary to confirm these associations and to examine screen-viewing interventions for preventing excessive abdominal adiposity and its adverse cardiometabolic consequences.
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http://dx.doi.org/10.1038/s41366-021-00864-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611569PMC
September 2021

Risk score to stratify miscarriage risk levels in preconception women.

Sci Rep 2021 Jun 8;11(1):12111. Epub 2021 Jun 8.

Duke-NUS Medical School, Singapore, 169857, Singapore.

Spontaneous miscarriage is one of the most common complications of pregnancy. Even though some risk factors are well documented, there is a paucity of risk scoring tools during preconception. In the S-PRESTO cohort study, Asian women attempting to conceive, aged 18-45 years, were recruited. Multivariable logistic regression model coefficients were used to determine risk estimates for age, ethnicity, history of pregnancy loss, body mass index, smoking status, alcohol intake and dietary supplement intake; from these we derived a risk score ranging from 0 to 17. Miscarriage before 16 weeks of gestation, determined clinically or via ultrasound. Among 465 included women, 59 had miscarriages and 406 had pregnancy ≥ 16 weeks of gestation. Higher rates of miscarriage were observed at higher risk scores (5.3% at score ≤ 3, 17.0% at score 4-6, 40.0% at score 7-8 and 46.2% at score ≥ 9). Women with scores ≤ 3 were defined as low-risk level (< 10% miscarriage); scores 4-6 as intermediate-risk level (10% to < 40% miscarriage); scores ≥ 7 as high-risk level (≥ 40% miscarriage). The risk score yielded an area under the receiver-operating-characteristic curve of 0.74 (95% confidence interval 0.67, 0.81; p < 0.001). This novel scoring tool allows women to self-evaluate their miscarriage risk level, which facilitates lifestyle changes to optimize modifiable risk factors in the preconception period and reduces risk of spontaneous miscarriage.
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http://dx.doi.org/10.1038/s41598-021-91567-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187346PMC
June 2021

Maternal circulating SPINT1 is reduced in small-for-gestational age pregnancies at 26 weeks: Growing up in Singapore towards health outcomes (GUSTO) cohort study.

Placenta 2021 Jul 1;110:24-28. Epub 2021 Jun 1.

The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Victoria, Australia; Singapore Institute of Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Fetal growth restriction arising from placental insufficiency is a leading cause of stillbirth. We recently identified low maternal circulating SPINT1 concentrations as a novel biomarker of poor fetal growth. Here we measured SPINT1 in a prospective cohort in Singapore. Circulating SPINT1 concentrations were significantly lower among 141 pregnant women destined to deliver small-for-gestational age infants (birthweight <10th centile), compared to 772 controls (p < 0.01) at as early as 26 weeks' gestation. There were no correlations between infant body composition and circulating SPINT1 concentrations at 26 weeks. This provides validation that low maternal SPINT1 concentration is associated with poor fetal growth.
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http://dx.doi.org/10.1016/j.placenta.2021.05.007DOI Listing
July 2021

Characterising and monitoring preconception health in England: a review of national population-level indicators and core data sources.

J Dev Orig Health Dis 2021 Jun 4:1-14. Epub 2021 Jun 4.

School of Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, UK.

Initiatives to optimise preconception health are emerging following growing recognition that this may improve the health and well-being of women and men of reproductive age and optimise health in their children. To inform and evaluate such initiatives, guidance is required on indicators that describe and monitor population-level preconception health. We searched relevant databases and websites (March 2021) to identify national and international preconception guidelines, recommendations and policy reports. These were reviewed to identify preconception indicators. Indicators were aligned with a measure describing the prevalence of the indicator as recorded in national population-based data sources in England. From 22 documents reviewed, we identified 66 indicators across 12 domains. Domains included wider (social/economic) determinants of health; health care; reproductive health and family planning; health behaviours; environmental exposures; cervical screening; immunisation and infections; mental health, physical health; medication and genetic risk. Sixty-five of the 66 indicators were reported in at least one national routine health data set, survey or cohort study. A measure of preconception health assessment and care was not identified in any current national data source. Perspectives from three (healthcare) professionals described how indicator assessment and monitoring may influence patient care and inform awareness campaign development. This review forms the foundation for developing a national surveillance system for preconception health in England. The identified indicators can be assessed using national data sources to determine the population's preconception needs, improve patient care, inform and evaluate new campaigns and interventions and enhance accountability from responsible agencies to improve preconception health.
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http://dx.doi.org/10.1017/S2040174421000258DOI Listing
June 2021

Role of maternal tryptophan metabolism in allergic diseases in the offspring.

Clin Exp Allergy 2021 May 25. Epub 2021 May 25.

Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore City, Singapore.

Background: Nicotinamide (vitamin B3) is a metabolite of tryptophan and dietary precursor of enzymes involved in many regulatory processes, which may influence fetal immune development.

Objective: We examined whether maternal plasma concentrations of nicotinamide, tryptophan or nine related tryptophan metabolites during pregnancy were associated with the risk of development of infant eczema, wheeze, rhinitis or allergic sensitization.

Methods: In the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) study, we analysed the associations between maternal plasma levels of nicotinamide, tryptophan and tryptophan metabolites at 26-28 weeks of gestation and allergic outcomes collected through interviewer-administered questionnaires at multiple time-points and skin prick testing to egg, milk, peanut and mites at age 18 months. Multivariate analysis was undertaken adjusting for all metabolites measured and separately adjusting for relevant demographic and environmental exposures. Analyses were also adjusted for multiple comparisons using the false discovery method.

Results: Tryptophan metabolites were evaluated in 976/1247 (78%) women enrolled in GUSTO. In multivariate analysis including all metabolites, maternal plasma 3-hydrokynurenine was associated with increased allergic sensitization at 18 months (AdjRR 2.6, 95% CI 1.3-5.2 for highest quartile) but the association with nicotinamide was not significant (AdjRR 1.8, 95% CI 0.9-3.6). In analysis adjusting for other exposures, both 3-hydrokynurenine and nicotinamide were associated with increased allergic sensitization (AdjRR 2.0, 95% CI 1.1-3.6 for both metabolites). High maternal plasma nicotinamide was associated with increased infant eczema diagnosis by 6 and 12 months, which was not significant when adjusting for all metabolites measured, but was significant when adjusting for relevant environmental and demographic exposures. Other metabolites measured were not associated with allergic sensitization or eczema, and maternal tryptophan metabolites were not associated with offspring rhinitis and wheeze.

Conclusions And Clinical Relevance: Maternal tryptophan metabolism during pregnancy may influence the development of allergic sensitization and eczema in infants.
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http://dx.doi.org/10.1111/cea.13953DOI Listing
May 2021

Placental polar lipid composition is associated with placental gene expression and neonatal body composition.

Biochim Biophys Acta Mol Cell Biol Lipids 2021 09 23;1866(9):158971. Epub 2021 May 23.

MRC Lifecourse Epidemiology Unit, University of Southampton, UK; NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK. Electronic address:

The polar-lipid composition of the placenta reflects its cellular heterogeneity and metabolism. This study explored relationships between placental polar-lipid composition, gene expression and neonatal body composition. Placental tissue and maternal and offspring data were collected in the Southampton Women's Survey. Lipid and RNA were extracted from placental tissue and polar lipids measured by mass spectrometry, while gene expression was assessed using the nCounter analysis platform. Principal component analysis was used to identify patterns within placental lipid composition and these were correlated with neonatal body composition and placental gene expression. In the analysis of placental lipids, the first three principal components explained 19.1%, 12.7% and 8.0% of variation in placental lipid composition, respectively. Principal component 2 was characterised by high principal component scores for acyl-alkyl-glycerophosphatidylcholines and lipid species containing DHA. Principal component 2 was associated with placental weight and neonatal lean mass; this component was associated with gene expression of APOE, PLIN2, FATP2, FABP4, LEP, G0S2, PNPLA2 and SRB1. Principal components 1 and 3 were not related to birth outcomes but they were associated with the gene expression of lipid related genes. Principal component 1 was associated with expression of LEP, APOE, FATP2 and ACAT2. Principal component 3 was associated with expression of PLIN2, PLIN3 and PNPLA2. This study demonstrates that placentas of different sizes have specific differences in polar-lipid composition and related gene expression. These differences in lipid composition were associated with birth weight and neonatal lean mass, suggesting that placental lipid composition may influence prenatal lean mass accretion.
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http://dx.doi.org/10.1016/j.bbalip.2021.158971DOI Listing
September 2021

Trajectories of Systolic Blood Pressure in Children: Risk Factors and Cardiometabolic Correlates.

J Pediatr 2021 Sep 18;236:86-94.e6. Epub 2021 May 18.

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research (A∗STAR), Singapore, Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore.

Objective: To identify systolic blood pressure (SBP) percentile trajectories in children and to describe the early-life risk factors and cardiometabolic correlates of those trajectories.

Study Design: Using age-, sex-, and height-specific SBP percentiles based on the American Academy of Pediatrics reference, we examined SBP trajectories using latent class mixed models from ages 3 to 8 years (n = 844) from the Growing Up in Singapore Towards healthy Outcomes-study, a Singaporean mother-offspring cohort study. We analyzed associations between SBP trajectories and early-life risk factors using multinomial logistic regression and differences across trajectories in cardiometabolic outcomes using multiple linear regression.

Results: Children were classified into 1 of 4 SBP percentile trajectories: "low increasing" (15%), "high stable" (47%), "high decreasing" (20%), and "low stable" (18%). Maternal hypertension during early pregnancy was a predictor of the "high stable" and "low increasing" SBP trajectories. Rapid child weight gain in the first 2 years of life was only associated with the "high stable" trajectory. Compared with children in the "low stable" trajectory, children in the "high stable" SBP trajectory had greater body mass index z scores, sum of skinfold thicknesses, waist circumference from ages 3 to 8 years, and abdominal adipose tissue (milliliters) at 4.5 years (adjusted mean difference [95% CI]: superficial and deep subcutaneous abdominal adipose tissue: 115.2 [48.1-182.3] and 85.5 [35.2-135.8]). Their fat mass (kilograms) (1.3 [0.6-2.0]), triglyceride levels (mmol/L) (0.10 [0.02-0.18]), and homeostasis model assessment of insulin resistance (0.28 [0.11 0.46]) at age 6 years were also greater but not their arterial thickness and stiffness.

Conclusions: Reducing maternal blood pressure during pregnancy and infant weight gain in the first 2 years of life might help to prevent the development of high SBP.
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http://dx.doi.org/10.1016/j.jpeds.2021.05.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611585PMC
September 2021

Quantifying Precision Loss in Targeted Metabolomics Based on Mass Spectrometry and Nonmatching Internal Standards.

Anal Chem 2021 06 20;93(21):7616-7624. Epub 2021 May 20.

Bevital, Laboratoriebygget, 9 etg., Jonas Lies veg 87, 5021 Bergen, Norway.

In mass spectrometry, reliable quantification requires correction for variations in ionization efficiency between samples. The preferred method is the addition of a stable isotope-labeled internal standard (SIL-IS). In targeted metabolomics, a dedicated SIL-IS for each metabolite of interest may not always be realized due to high cost or limited availability. We recently completed the analysis of more than 70 biomarkers, each with a matching SIL-IS, across four mass spectrometry-based platforms (one GC-MS/MS and three LC-MS/MS). Using data from calibrator and quality control samples added to 60 96-well trays (analytical runs), we calculated analytical precision (CV) retrospectively. The use of integrated peak areas for all metabolites and internal standards allowed us to calculate precision for all matching analyte (A)/SIL-IS (IS) pairs as well as for all nonmatching A/IS pairs within each platform (total = 1442). The median between-run precision for matching A/IS across the four platforms was 2.7-5.9%. The median CV for nonmatching A/IS (corresponding to pairing analytes with a non-SIL-IS) was 2.9-10.7 percentage points higher. Across all platforms, CVs for nonmatching A/IS increased with increasing difference in retention time (Spearman's rho of 0.17-0.93). The CV difference for nonmatching vs matching A/IS was often, but not always, smaller when analytes and internal standards were close structural analogs.
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http://dx.doi.org/10.1021/acs.analchem.1c00119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611570PMC
June 2021

Modifiable early life exposures associated with adiposity and obesity in 3-year old children born to mothers with obesity.

Pediatr Obes 2021 May 17:e12801. Epub 2021 May 17.

Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.

Background: Children born to mothers with obesity are at increased risk of obesity. Influences underlying this predisposition include in-utero exposures, genetic predisposition and a shared family environment. Effective intervention strategies are needed to prevent obesity in these high-risk children; this requires evaluation of modifiable pregnancy and early-life risk factors.

Objectives: To assess the individual and cumulative contributions of maternal and early-life modifiable exposures on childhood adiposity and obesity outcomes in 3-year-old children born to women with obesity.

Methods: We used adjusted regression to assess the individual and cumulative contributions of six exposures (early pregnancy BMI, excessive gestational weight gain, mode of infant feeding and three measures of childhood eating habits [food responsiveness, slowness in eating and a processed/snacking dietary pattern score]) on body composition in 495 three-year-old children. Outcomes included BMI z-score, arm circumference and overweight/obesity (BMI≥25.0 kg/m ).

Results: While the UPBEAT intervention did not influence adiposity outcomes in 3-year-old children, the six modifiable exposures combined incrementally to increase childhood adiposity and obesity. For each additional exposure, children had a higher BMI z-score (β = 0.35SD [95% confidence interval: 0.23, 0.47]), arm circumference (β = 0.59 cm [0.40, 0.79]) and risk of overweight/obesity (relative risk 1.49 [1.26, 1.77]). Compared to no exposures, children with four or more exposures had a higher BMI z-score (1.11SD [0.65, 1.58]), arm circumference (2.15 cm [1.41, 2.89]) and risk of overweight/obesity (3.01 [1.67, 5.41]) (all P < 0.001).

Conclusion: Our findings suggest that complex interventions targeting preconception, pregnancy, perinatal and early childhood exposures offer a potential strategy for prevention of pre-school obesity.
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http://dx.doi.org/10.1111/ijpo.12801DOI Listing
May 2021

The influence of body position on bioelectrical impedance spectroscopy measurements in young children.

Sci Rep 2021 May 14;11(1):10346. Epub 2021 May 14.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Bioelectrical impedance techniques are easy to use and portable tools for assessing body composition. While measurements vary according to standing vs supine position in adults, and fasting and bladder voiding have been proposed as additional important influences, these have not been assessed in young children. Therefore, the influence of position, fasting, and voiding on bioimpedance measurements was examined in children. Bioimpedance measurements (ImpediMed SFB7) were made in 50 children (3.38 years). Measurements were made when supine and twice when standing (immediately on standing and after four minutes). Impedance and body composition were compared between positions, and the effect of fasting and voiding was assessed. Impedance varied between positions, but body composition parameters other than fat mass (total body water, intra- and extra-cellular water, fat-free mass) differed by less than 5%. There were no differences according to time of last meal or void. Equations were developed to allow standing measurements of fat mass to be combined with supine measurements. In early childhood, it can be difficult to meet requirements for fasting, voiding, and lying supine prior to measurement. This study provides evidence to enable standing and supine bioimpedance measurements to be combined in cohorts of young children.
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http://dx.doi.org/10.1038/s41598-021-89568-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121940PMC
May 2021

Folate and vitamin B12 status: associations with maternal glucose and neonatal DNA methylation sites related to dysglycaemia, in pregnant women with obesity.

J Dev Orig Health Dis 2021 May 11:1-9. Epub 2021 May 11.

Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.

Recent studies implicate maternal gestational diabetes mellitus (GDM) in differential methylation of infant DNA. Folate and vitamin B12 play a role in DNA methylation, and these vitamins may also influence GDM risk. The aims of this study were to determine folate and vitamin B12 status in obese pregnant women and investigate associations between folate and vitamin B12 status, maternal dysglycaemia and neonatal DNA methylation at cytosine-phosphate-guanine sites previously observed to be associated with dysglycaemia. Obese pregnant women who participated in the UK Pregnancies Better Eating and Activity Trial were included. Serum folate and vitamin B12 were measured at the oral glucose tolerance test (OGTT) visit. Cord blood DNA methylation was assessed using the Infinium MethylationEPIC BeadChip. Regression models with adjustment for confounders were used to examine associations. Of the 951 women included, 356 (37.4%) were vitamin B12 deficient, and 44 (4.6%) were folate deficient. Two-hundred and seventy-one women (28%) developed GDM. Folate and vitamin B12 concentrations were not associated with neonatal DNA methylation. Higher folate was positively associated with 1-h plasma glucose after OGTT (β = 0.031, 95% CI 0.001-0.061, p = 0.045). There was no relationship between vitamin B12 and glucose concentrations post OGTT or between folate or vitamin B12 and GDM. In summary, we found no evidence to link folate and vitamin B12 status with the differential methylation of neonatal DNA previously observed in association with dysglycaemia. We add to the evidence that folate status may be related to maternal glucose homoeostasis although replication in other maternal cohorts is required for validation.
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http://dx.doi.org/10.1017/S2040174421000246DOI Listing
May 2021

The association of maternal gestational hyperglycemia with breastfeeding duration and markers of milk production.

Am J Clin Nutr 2021 Sep;114(3):1219-1228

Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore.

Background: Previous studies focusing on the association between gestational diabetes and breastfeeding duration have been inconclusive.

Objectives: We aimed to determine whether maternal gestational hyperglycemia is associated with the duration of breastfeeding and the concentrations of markers linked to breastmilk production.

Methods: Data from the prospective, multiethnic Growing Up in Singapore Towards Healthy Outcomes study were used to assess the association of fasting plasma glucose (FPG) and 2-h postglucose challenge (2hPG) measured at 26-28 wk of gestation with duration of breastfeeding and concentrations of protein, lactose, citrate, sodium, potassium, and zinc in breastmilk 3 wk postpartum.

Results: Of the 1035 participants, 5.2% and 9.5% had elevated FPG and 2hPG, respectively, consistent with a diagnosis of gestational diabetes mellitus based on International Association of Diabetes and Pregnancy Study Groups criteria. FPG ≥5.1 mmol/L was associated with a crude reduction in median breastfeeding duration of 2.3 mo. In a model adjusted for maternal prepregnancy BMI and intention to breastfeed, FPG ≥5.1 mmol/L predicted earlier termination of any breastfeeding (adjusted HR: 1.47; 95% CI: 1.04, 2.08) but not full breastfeeding (adjusted HR: 1.08; 0.76, 1.55). 2hPG ≥8.5 mmol/L was not significantly associated with the durations of any (adjusted HR: 0.86; 95% CI: 0.62, 1.19) or full (adjusted HR: 0.85; 95% CI: 0.62, 1.18) breastfeeding. Maternal FPG was significantly and positively associated with breastmilk sodium (adjusted coefficient: 1.28; 95% CI: 1.08, 1.51) and sodium-to-potassium ratio (adjusted coefficient: 1.29; 95% CI: 1.08, 1.54) but not with other measured breastmilk components.

Conclusions: Women with FPG ≥5.1 mmol/L during pregnancy breastfeed for a shorter duration. Future work involving measurement of milk production is needed to determine whether low milk production predicts breastfeeding duration among women with elevated FPG. This trial was registered at www.clinicaltrials.gov as NCT01174875.
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http://dx.doi.org/10.1093/ajcn/nqab142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611668PMC
September 2021

A cluster-randomised controlled trial of the LifeLab education intervention to improve health literacy in adolescents.

PLoS One 2021 5;16(5):e0250545. Epub 2021 May 5.

NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.

Adolescence offers a window of opportunity during which improvements in health behaviours could benefit long-term health, and enable preparation for parenthood-albeit a long way off, passing on good health prospects to future children. This study was carried out to evaluate whether an educational intervention, which engages adolescents in science, can improve their health literacy and behaviours. A cluster-randomised controlled trial of 38 secondary schools in England, UK was conducted. The intervention (LifeLab) drew on principles of education, psychology and public health to engage students with science for health literacy, focused on the message "Me, my health and my children's health". The programme comprised: • Professional development for teachers. • A 2-3 week module of work for 13-14-year-olds. • A "hands-on" practical health science day visit to a dedicated facility in a university teaching hospital. Data were collected from 2929 adolescents (aged 13-14 years) at baseline and 2487 (84.9%) at 12-month follow-up. The primary outcome was change in theoretical health literacy from pre- to 12 months post- intervention. This study is registered (ISRCTN71951436) and the trial status is complete. Participation in the LifeLab educational intervention was associated with an increase in the students' standardised total theoretical health literacy score (adjusted difference between groups = 0.27 SDs (95%CI = 0.12, 0.42)) at 12-month follow-up. There was an indication that intervention participants subsequently judged their own lifestyles more critically than controls, with fewer reporting their behaviours as healthy (53.4% vs. 59.5%; adjusted PRR = 0.94 [0.87, 1.01]). We conclude that experiencing LifeLab led to improved health literacy in adolescents and that they demonstrated a move towards a more critical judgement of health behaviour 12 months after the intervention. Further work is needed to examine whether this leads to sustained behaviour change, and whether other activities are needed to support this change.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250545PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099135PMC
May 2021

Dietary patterns of 5-year-old children and their correlates: findings from a multi-ethnic Asian cohort.

Br J Nutr 2021 Apr 29:1-10. Epub 2021 Apr 29.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.

There is limited data on the dietary patterns of 5-year-old children in Asia. The study examined childhood dietary patterns and their maternal and child correlates in a multi-ethnic Asian cohort. Based on caregiver-reported 1-month quantitative FFQ of 777 children from the Growing Up in Singapore Towards healthy Outcomes cohort, cluster analysis identified two mutually exclusive clusters. Children in the 'Unhealthy' cluster (43·9 %) consumed more fries, processed meat, biscuits and ice cream, and less fish, fruits and vegetables compared with those in the 'Healthy' cluster (56·1 %). Children with mothers of lower educational attainment had twice the odds of being assigned to the 'Unhealthy' cluster (adjusted OR (95 % CI) = 2·19 (95 % CI 1·49-3·24)). Children of Malay and Indian ethnicities had higher odds of being assigned to the 'Unhealthy' cluster (adjusted OR = 25·46 (95 % CI 15·40, 42·10) and 4·03 (95 % CI 2·68-6·06), respectively), relative to Chinese ethnicity. In conclusion, this study identified two dietary patterns in children, labelled as the 'Unhealthy' and 'Healthy' clusters. Mothers' educational attainment and ethnicity were two correlates that were associated with the children's assignments to the clusters. These findings can assist in informing health promotion programmes targeted at Asian children.
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http://dx.doi.org/10.1017/S0007114521001434DOI Listing
April 2021

Diagnostic accuracy of loop-mediated isothermal amplification coupled to nanopore sequencing (LamPORE) for the detection of SARS-CoV-2 infection at scale in symptomatic and asymptomatic populations.

Clin Microbiol Infect 2021 Sep 24;27(9):1348.e1-1348.e7. Epub 2021 Apr 24.

MRC Lifecourse Epidemiology Unit, NIHR Southampton Biomedical Research Centre, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, UK.

Objectives: Rapid, high throughput diagnostics are a valuable tool, allowing the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in populations so as to identify and isolate people with asymptomatic and symptomatic infections. Reagent shortages and restricted access to high throughput testing solutions have limited the effectiveness of conventional assays such as quantitative RT-PCR (RT-qPCR), particularly throughout the first months of the coronavirus disease 2019 pandemic. We investigated the use of LamPORE, where loop-mediated isothermal amplification (LAMP) is coupled to nanopore sequencing technology, for the detection of SARS-CoV-2 in symptomatic and asymptomatic populations.

Methods: In an asymptomatic prospective cohort, for 3 weeks in September 2020, health-care workers across four sites (Birmingham, Southampton, Basingstoke and Manchester) self-swabbed with nasopharyngeal swabs weekly and supplied a saliva specimen daily. These samples were tested for SARS-CoV-2 RNA using the Oxford Nanopore LamPORE system and a reference RT-qPCR assay on extracted sample RNA. A second retrospective cohort of 848 patients with influenza-like illness from March 2020 to June 2020 were similarly tested from nasopharyngeal swabs.

Results: In the asymptomatic cohort a total of 1200 participants supplied 23 427 samples (3966 swab, 19 461 saliva) over a 3-week period. The incidence of SARS-CoV-2 detection using LamPORE was 0.95%. Diagnostic sensitivity and specificity of LamPORE was >99.5% (decreasing to approximately 98% when clustered estimation was used) in both swab and saliva asymptomatic samples when compared with the reference RT-qPCR test. In the retrospective symptomatic cohort, the incidence was 13.4% and the sensitivity and specificity were 100%.

Conclusions: LamPORE is a highly accurate methodology for the detection of SARS-CoV-2 in both symptomatic and asymptomatic population settings and can be used as an alternative to RT-qPCR.
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http://dx.doi.org/10.1016/j.cmi.2021.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064897PMC
September 2021

Neonatal amygdala microstructure mediates the relationship between gestational glycemia and offspring adiposity.

BMJ Open Diabetes Res Care 2021 04;9(1)

Department of Biomedical Engineering, National University of Singapore, Singapore

Introduction: To determine if variations in the neonatal amygdala mediate the association between maternal antenatal glycemia and offspring adiposity in early childhood.

Research Design And Methods: 123 non-obese pregnant women with no pregnancy complications aside from gestational diabetes underwent a 75 g 2-hour oral glucose tolerance test at 26-28 weeks' gestation. Volume and fractional anisotropy (FA) of the neonatal amygdala (5-17 days old) were measured by MRI. The Body Mass Index (BMI) z-scores and sum of skinfold thickness (subscapular and triceps) of these children were tracked up to 60 months of age (18, 24, 36, 48, 54 and 60 months).

Results: Maternal fasting glucose levels were positively associated with the offspring's sum of skinfold thickness at age 48 months (β=3.12, 95% CI 0.18 to 6.06 mm) and 60 months (β=4.14, 95% CI 0.46 to 7.82 mm) and BMI z-scores at 48 months (β=0.94, 95% CI 0.03 to 1.85), 54 months (β=0.74, 95% CI 0.12 to 1.36) and 60 months (β=0.74, 95% CI 0.08 to 1.39). Maternal fasting glucose was negatively associated with the offspring's FA of the right amygdala (β=-0.019, 95% CI -0.036 to -0.003). Right amygdala FA was negatively associated with the sum of skinfold thickness in the offspring at age 48 months (β=-56.95, 95% CI -98.43 to -15.47 mm), 54 months (β=-46.18, 95% CI -88.57 to -3.78 mm), and 60 months (β=-53.69, 95% CI -105.74 to -1.64 mm). The effect sizes mediated by right amygdala FA between fasting glucose and sum of skinfolds were estimated at β=5.14 (95% CI 0.74 to 9.53) mm (p=0.022), β=4.40 (95% CI 0.08 to 8.72) (p=0.049) mm and β=4.56 (95% CI -0.17 to 9.29) mm (p=0.059) at 48, 54 and 60 months, respectively.

Conclusions: In the offspring of non-obese mothers, gestational fasting glucose concentration is negatively associated with neonatal right amygdala FA and positively associated with childhood adiposity. Neonatal right amygdala FA may be a potential mediator between maternal glycemia and childhood adiposity.
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http://dx.doi.org/10.1136/bmjdrc-2020-001396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070871PMC
April 2021

Childhood vascular phenotypes have differing associations with prenatal and postnatal growth.

J Hypertens 2021 Sep;39(9):1884-1892

NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton.

Objective: In children aged 8--9 years, we examined the associations of linear and abdominal circumference growth during critical stages of prenatal and postnatal development with six vascular measurements commonly used as early markers of atherosclerosis and later cardiovascular disease (CVD) risk.

Methods: In 724 children from the UK Southampton Women's Survey mother--offspring cohort, offspring length/height and abdominal circumference measurements were collected at 10 ages between 11 weeks' gestation and age 8--9 years. Using residual growth modelling and linear regression, we examined the independent associations between growth and detailed vascular measures made at 8--9 years.

Results: Postnatal linear and abdominal circumference growth were associated with higher childhood SBP and carotid--femoral pulse wave velocity, whereas prenatal growth was not. For example, 1SD faster abdominal circumference gain between ages 3 and 6 years was associated with 2.27 [95% confidence interval (CI): 1.56--2.98] mmHg higher SBP. In contrast, faster abdominal circumference gain before 19 weeks' gestation was associated with greater carotid intima--media thickness [0.009 mm (0.004--0.015) per 1SD larger 19-week abdominal circumference), whereas later growth was not. We found no strong associations between prenatal or postnatal growth and DBP or measures of endothelial function.

Conclusion: Higher postnatal linear growth and adiposity gain are related to higher SBP and carotid--femoral pulse wave velocity in childhood. In contrast, faster growth in early gestation is associated with greater childhood carotid intima--media thickness, perhaps resulting from subtle changes in vascular structure that reflect physiological adaptations rather than subclinical atherosclerosis.
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http://dx.doi.org/10.1097/HJH.0000000000002870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373454PMC
September 2021

-Inositol, Probiotics, and Micronutrient Supplementation From Preconception for Glycemia in Pregnancy: NiPPeR International Multicenter Double-Blind Randomized Controlled Trial.

Diabetes Care 2021 May 29;44(5):1091-1099. Epub 2021 Mar 29.

Liggins Institute, University of Auckland, Auckland, New Zealand.

Objective: Better preconception metabolic and nutritional health are hypothesized to promote gestational normoglycemia and reduce preterm birth, but evidence supporting improved outcomes with nutritional supplementation starting preconception is limited.

Research Design And Methods: This double-blind randomized controlled trial recruited from the community 1,729 U.K., Singapore, and New Zealand women aged 18-38 years planning conception. We investigated whether a nutritional formulation containing -inositol, probiotics, and multiple micronutrients (intervention), compared with a standard micronutrient supplement (control), taken preconception and throughout pregnancy could improve pregnancy outcomes. The primary outcome was combined fasting, 1-h, and 2-h postload glycemia (28 weeks gestation oral glucose tolerance test).

Results: Between 2015 and 2017, participants were randomized to control ( = 859) or intervention ( = 870); 585 conceived within 1 year and completed the primary outcome (295 intervention, 290 control). In an intention-to-treat analysis adjusting for site, ethnicity, and preconception glycemia with prespecified < 0.017 for multiplicity, there were no differences in gestational fasting, 1-h, and 2-h glycemia between groups (β [95% CI] log mmol/L intervention vs. control -0.004 [-0.018 to 0.011], 0.025 [-0.014 to 0.064], 0.040 [0.004-0.077], respectively). Between the intervention and control groups there were no significant differences in gestational diabetes mellitus (24.8% vs. 22.6%, adjusted risk ratio [aRR] 1.22 [0.92-1.62]), birth weight (adjusted β = 0.05 kg [-0.03 to 0.13]), or gestational age at birth (mean 39.3 vs. 39.2 weeks, adjusted β = 0.20 [-0.06 to 0.46]), but there were fewer preterm births (5.8% vs. 9.2%, aRR 0.43 [0.22-0.82]), adjusting for prespecified covariates.

Conclusions: Supplementation with -inositol, probiotics, and micronutrients preconception and in pregnancy did not lower gestational glycemia but did reduce preterm birth.
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http://dx.doi.org/10.2337/dc20-2515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132330PMC
May 2021
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