Caroline H.D. Fall's research while affiliated with University of Southampton and other places
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Publications (152)
Sustainable Development Goal 2.2—to end malnutrition by 2030—includes the elimination of child wasting, defined as a weight-for-length z -score that is more than two standard deviations below the median of the World Health Organization standards for child growth ¹ . Prevailing methods to measure wasting rely on cross-sectional surveys that cannot m...
Growth faltering in children (low length for age or low weight for length) during the first 1,000 days of life (from conception to 2 years of age) influences short-term and long-term health and survival 1,2 . Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programm...
Globally, 149 million children under 5 years of age are estimated to be stunted (length more than 2 standard deviations below international growth standards) 1,2 . Stunting, a form of linear growth faltering, increases the risk of illness, impaired cognitive development and mortality. Global stunting estimates rely on cross-sectional surveys, which...
Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigate links between blood DNA methylation and child height in four LMIC cohorts ( n = 1927) and identify a robust association at three CpGs in the suppressor of cyt...
Background
Asian Indians are at higher risk of cardiometabolic disease compared to other ethnic groups, and the age of onset is typically younger. Cardiac structure and function are poorly characterized in this ethnic group. In this study, we describe image-acquisition methods and the reproducibility of measurements and detailed echocardiography ch...
Background:
Gestational diabetes can predispose two generations-a mother and her child-to a higher risk of obesity and type 2 diabetes. Culture-specific strategies to prevent gestational diabetes are required. BANGLES investigated the associations between women's periconceptional diet and gestational diabetes risk.
Methods:
BANGLES was a prospec...
The consequences for adolescent health due to early life exposure to natural disasters combined with war are not known. We collected data from adolescents aged 12-13 years in Sri Lanka whose mothers were pregnant during the Indian Ocean tsunami in 2004 in a tsunami-affected region (n = 22), conflict-affected region (n = 35), conflict-plus-tsunami-a...
Human height is strongly influenced by genetics but the contribution of modifiable epigenetic factors is under-explored, particularly in low and middle-income countries (LMIC). We investigated links between blood DNA methylation and child height in four LMIC cohorts (n=1927) and identified a robust association at three CpGs in the suppressor of cyt...
Changes in brain morphology have been reported during development, ageing and in relation to different pathologies. Brain morphology described by the shape complexity of gyri and sulci can be captured and quantified using fractal dimension (FD). This measure of brain structural complexity, as well as brain volume, are associated with intelligence,...
We analysed DNA methylation data from 30 datasets comprising 3474 individuals, 19 tissues and 8 ethnicities at CpGs covered by the Illumina450K array. We identified 4143 hypervariable CpGs (‘hvCpGs’) with methylation in the top 5% most variable sites across multiple tissues and ethnicities. hvCpG methylation was influenced but not determined by gen...
With type 2 diabetes presenting at younger ages, there is a growing need to identify biomarkers of future glucose intolerance. A high (20%) prevalence of glucose intolerance at 18 years was seen in women from the Pune Maternal Nutrition Study (PMNS) birth cohort. We investigated the potential of circulating microRNAs in risk stratification for futu...
Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital....
Background: Emerging evidence from high income settings indicates that lung function may be an independent determinant of cognitive abilities in late life. Despite a high burden of chronic lung disorders and neurocognitive disorders, there are limited data exploring the relationship between lung and cognitive function in later life in low- and midd...
Background
The prevalence of cardiometabolic disease (CMD) is rising globally, with environmentally induced epigenetic changes suggested to play a role. Few studies have investigated epigenetic associations with CMD risk factors in children from low- and middle-income countries. We sought to identify associations between DNA methylation (DNAm) and...
Background
Maternal nutrition influences fetal development and may permanently alter (‘program’) offspring body composition and metabolism, thereby influencing later risk of diabetes and cardiovascular (cardiometabolic) disease. The prevalence of cardiometabolic disease is rising rapidly in India.
Objectives
To test the hypothesis that supplementi...
We analysed DNA methylation data from 30 datasets comprising 3,474 individuals, 19 tissues and 8 ethnicities at CpGs covered by the Illumina450K array. We identified 4,143 hypervariable CpGs ('hvCpGs') with methylation in the top 5% most variable sites across multiple tissues and ethnicities. hvCpG methylation was influenced but not determined by g...
A high (20%) prevalence of glucose intolerance at 18-years was seen in women from the Pune Maternal Nutrition Study (PMNS) birth cohort. Here, we provide preliminary longitudinal analyses of circulating microRNAs in normal glucose tolerant (NGT@18y, N=10) and glucose intolerant (N=8) women (ADA criteria) at 6-, 12- and 17-years of their age using d...
Background: to examine the associations of total and regional adiposity with metabolic and cardiovascular disease (CVD) risk markers.
Methods: this cross-sectional study included 1,080 (53.8% men, aged 39-44 years) individuals from South India. Anthropometry (height, weight, waist and hip circumference), body composition assessment using dual ener...
Objective:
India is a double world capital of early-life undernutrition and type 2 diabetes. We aimed to characterize life course growth and metabolic trajectories in those developing glucose intolerance as young adults in the Pune Maternal Nutrition Study (PMNS).
Research design and methods:
PMNS is a community-based intergenerational birth coh...
Background: both ethnicity and age are important determinants of musculoskeletal health. We aimed to determine the prevalence of sarcopenia, assess the suitability of current diagnostic guidelines, and explore muscle-bone relationships in adults from India. Methods: 1009 young (20-35years) and 1755 older (>40years) men and women from existing studi...
Aims/hypothesis
The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide in all ethnic groups. Low vitamin B 12 and low/high folate levels may contribute to GDM risk, but there is conflicting evidence. Our aim is to assess the relationships of early pregnancy vitamin B 12 and folate levels with the risk of GDM status at 26–28 w...
Objective: to examine if smaller size at birth, an indicator of growth restriction in utero, is associated with lower cognition in late life, and whether this may be mediated by impaired early life brain development and/or adverse cardiometabolic programming.
Design: longitudinal follow-up of a birth cohort.
Setting: CSI Holdsworth Memorial Hosp...
Background:
A comparison of the anthropometry of children and adolescents with that of their parents at the same age may provide a more precise measure of intergenerational changes in linear growth and body mass index (BMI).
Methods:
New Delhi Birth Cohort participants (F1), born between 1969 and 1972, were followed up for anthropometry at birth...
Introduction
The Healthy Life Trajectories Initiative is an international consortium comprising four harmonised but independently powered trials to evaluate whether an integrated intervention starting preconceptionally will reduce non-communicable disease risk in their children. This paper describes the protocol of the India study.
Methods and ana...
Introduction
India has high mortality rates from cardiovascular disease (CVD). Understanding the trends and identifying modifiable determinants of CVD risk factors will guide preventive strategies and policy making.
Research design and methods
CVD risk factors (obesity, central obesity, and type 2 diabetes (T2D), hypertension, hypercholesterolemia...
Globally, we are living through one of the most serious public health crises in recent history. Apart from the obvious health risks, the COVID-19 pandemic is exposing the damaging impact of inequalities. The risk of contracting SARS-CoV-2 infection and of hospitalization and mortality rates differ greatly among different communities and populations...
Our objective was to investigate associations of body size (birth weight and body mass index (BMI)) and growth in height, body fat (adiposity) and lean mass during childhood and adolescence, with risk markers for diabetes in young South Asian adults. We studied 357 men and women aged 21 years from the Pune Children’s Study birth cohort. Exposures w...
Background:
Maternal nutrition in pregnancy has been linked to offspring health in early and later life, with changes to DNA methylation (DNAm) proposed as a mediating mechanism.
Objective:
We investigated intervention-associated DNAm changes in children whose mothers participated in 2 randomized controlled trials of micronutrient supplementatio...
Background: the aim of this study was to determine whether physical activity volume and intensity in mid-childhood and early adolescence were associated with cardiometabolic risk factors at 13.5 years.
Methods: participants were recruited from the Mysore Parthenon observational birth cohort. At ages 6-10 and 11-13 years, volume and intensity of ph...
Context
Imbalances in maternal one-carbon nutrients (vitamin B12, folate) have been shown to be associated with higher offspring cardiometabolic risk markers in India.
Objective
We examined the hypothesis that low plasma vitamin B12 (B12), and high folate and homocysteine concentrations in the mother are associated with higher hypothalamic-pituita...
Objectives:
To (1) describe micronutrient intakes among women of reproductive age living in Mumbai slums; (2) assess the adequacy of these intakes compared with reference values; (3) identify important dietary sources of micronutrients.
Subjects/methods:
Participants were 6426 non-pregnant women aged 16-39 years, registered in a randomised contr...
Background
Vitamin B-12 deficiency is often considered synonymous with pernicious anemia, a rare condition in which severe malabsorption of the vitamin requires high-dose parenteral treatment. In developing countries such as India, inadequate dietary intake of B-12 due to socio-cultural factors leads to widely prevalent asymptomatic low B-12 status...
Background:
Preeclampsia is a major cause of maternal, fetal and neonatal morbidity and mortality, particularly in developing countries. Considering the burden of preeclampsia and its associated complications, it is important to understand the underlying risk factors and mechanisms involved in its etiology. There is considerable interest in the po...
Introduction
Recent evidence suggests that growth restriction in utero may lead to neurocognitive disorders in late life, either through impaired brain development or adverse metabolic programming.
Methods
Systematic review of literature investigating the relationship between size at birth and cognitive abilities in late life. The search, data ext...
Background:
Diets in rural India are cereal based with low intakes of micronutrient-rich foods. The value chains for nutrition approach aims to study supply and demand of such foods. This may aid in development of interventions to improve diets and livelihoods.
Objectives:
(1) To identify how fruit and vegetables are accessed, (2) to describe an...
Background:
Body mass index (BMI) reaches a nadir in mid-childhood, known as the adiposity rebound (AR). Earlier AR is associated with a higher risk of cardio-vascular diseases in later life. Skinfolds, which are a more direct measure of adiposity, may give better insight into the relationship between childhood adiposity and later obesity and card...
An association of low birth weight with an increased risk of adult cardiovascular disease and diabetes led to the developmental origins of health and disease (DOHaD) hypothesis, which proposes that undernutrition during early development permanently ‘programmes’ organ structure and metabolism, leading to vulnerability to later cardio-metabolic dise...
Background: Micronutrient insufficiencies are a serious public health problem among women of reproductive age in Low and Middle Income Countries including India, adversely affecting maternal health and economic productivity, and child growth and educational outcomes. Fruit and vegetables are important sources of micronutrients and consumption of th...
Background:
Mounting evidence suggests that nutritional exposures during pregnancy influence the fetal epigenome, and that these epigenetic changes can persist postnatally, with implications for disease risk across the life course.
Methods:
We review human intergenerational studies using a three-part search strategy. Search 1 investigates associ...
Background::
Young maternal age is associated with poorer birth outcomes, but the mechanisms are incompletely understood. Using data from a prospective cohort of pregnant women living in Mumbai slums, India, we tested whether lower maternal age was associated with adverse fetal growth.
Methods::
Fetal crown-rump length (CRL) was recorded at a me...
India is facing high and rising rates of mid-and late-life chronic non-communicable diseases (NCDs) such as hypertension, type 2 diabetes and coronary heart disease (CHD). Indian cohort studies have made a major contribution to the global evidence that disease risk is influenced by the nutritional environment experienced during fetal and childhood...
Introduction:
South Asians have high rates of cardiovascular disease (CVD) and its risk factors (hypertension, diabetes, dyslipidaemia and central obesity). Left ventricular (LV) hypertrophy and dysfunction are features of these disorders and important predictors of CVD mortality. Lower birth and infant weight and greater childhood weight gain are...
The nutritional status of both women and men before conception has profound implications for the growth, development, and long-term health of their offspring. Evidence of the effectiveness of preconception interventions for improving outcomes for mothers and babies is scarce. However, given the large potential health return, and relatively low cost...
Background/objective:
Fat distribution is a strong and independent predictor of type 2 diabetes (T2D) and cardiovascular disease (CVD) and is usually determined using conventional anthropometry in epidemiological studies. Dual-energy X-ray absorptiometry (DXA) can measure total and regional adiposity more accurately. Nonetheless, whether DXA provi...
Table S1. Ingredients of the snack at each stage of the trial
Table S2. Mean nutrient composition and mean percentage contribution to nutrient requirements of the snacks at each stage of the triala
Table S3. Comparison of z‐scores for HC, BPD, AC, and FL between male and female fetuses
Table S4. Comparison of baseline characteristics between wom...
Background:
There are limited data on the use of artificial intelligence methods for the diagnosis of dementia in epidemiological studies in low- and middle-income country (LMIC) settings. A culture and education fair battery of cognitive tests was developed and validated for population based studies in low- and middle-income countries including I...
Background:
Animal studies have shown that nutritional exposures during pregnancy can modify epigenetic marks regulating fetal development and susceptibility to later disease, providing a plausible mechanism to explain the developmental origins of health and disease. Human observational studies have shown that maternal peri-conceptional diet predi...
Non-communicable diseases (NCDs), such as cardiovascular disease and osteoporosis, affect individuals in all countries worldwide. Given the very high worldwide prevalence of NCDs across a range of human pathology, it is clear that traditional approaches targeting those at most risk in older adulthood will not efficiently ameliorate this growing bur...
Improving micronutrient intakes of under-nourished mothers in low- and middle-income countries increases birth weight, but there is little data on the nature and timing during gestation of any effects on fetal growth. Ultrasound measures of fetal size were used to determine whether and when a food-based supplement affected fetal growth. Non-pregnan...
We discuss the analysis of data in which, for each subject, size measures, typically height and weight, are combined to form a growth trajectory, and the interest is in how that growth trajectory is associated with an outcome measured at or after the last size measurement. This is a common scenario in studies of the "Developmental Origins of Health...
[This corrects the article DOI: 10.1371/journal.pone.0166281.].
Abstract
Purpose Limited availability of specialist services places a
considerable burden on caregivers of Persons with
Dementia (PwD) in Low- and Middle-Income Countries
(LMICs). There are limited qualitative data on coercive
behavior towards PwD in an LMIC setting.
Aim The aim of this study was to find relevant themes of
the lived experience of r...
PurposeLimited availability of specialist services places a considerable burden on caregivers of Persons with Dementia (PwD) in Low- and Middle-Income Countries (LMICs). There are limited qualitative data on coercive behavior towards PwD in an LMIC setting. AimThe aim of this study was to find relevant themes of the lived experience of relatives as...
Small birth size and rapid postnatal growth have been associated with higher future blood pressure. The timing of these effects, the relative importance of weight gain and linear growth and the role of infant feeding need to be clarified.We assessed how blood pressure relates to birth weight, infant and childhood growth and infant feeding (duration...
Objectives:
To investigate independent relationships of childhood linear growth (height gain) and relative weight gain to adult cardiovascular disease (CVD) risk traits in Asian Indians.
Study design:
Data from 2218 adults from the Vellore Birth Cohort were examined for associations of cross-sectional height and body mass index (BMI) and longitu...
Background
Multiple micronutrient supplementation for pregnant women reduces low birth weight and has been recommended in low- and middle-income countries (LMICs) to improve child survival, growth and health. We aimed to review the evidence from long-term follow-up studies of multiple micronutrient supplementation beginning in the later first or se...
Background & objectives:
Abnormal endothelial function represents a preclinical marker of atherosclerosis. This study was conducted to evaluate associations between anthropometry, cardiometabolic risk factors, and early life factors and adult measures of endothelial function in a young urban Indian cohort free of clinical cardiovascular disease.
M...
Background:
We aimed to determine how linear growth and fat and lean tissue gain during discrete age periods from birth to adolescence are related to adolescent cardiometabolic risk factors and cognitive ability.
Methods:
Adolescents born to mothers with normal glucose tolerance during pregnancy from an Indian birth cohort (N = 486, age 13.5 yea...
Design Non-randomised non-blinded school-based intervention study.
Setting Two schools in the cities of Pune and Nasik, India.
Participants The intervention group comprised children attending a Pune school from 7–10 years until 12–15 years of age. Two control groups comprised children of the same age attending a similar school in Nasik, and childre...
Background: Disturbed one-carbon (1-C) metabolism in the mother is associated with poor fetal growth but causality of this relationship has not been established. Methods: We studied the association between maternal total homocysteine and offspring birthweight in the Pune Maternal Nutrition Study (PMNS, Pune, India) and Parthenon Cohort Study (Mysor...
Both young and advanced maternal age is associated with adverse birth and child outcomes. Few studies have examined these associations in low-income and middle-income countries (LMICs) and none have studied adult outcomes in the offspring. We aimed to examine both child and adult outcomes in five LMICs.
In this prospective study, we pooled data fro...
The Pune Children's Study aimed to test whether glucose and insulin measurements in childhood predict cardiovascular risk factors in young adulthood.
We followed up 357 participants (75% follow-up) at 21 years of age who had undergone detailed measurements at 8 years of age (glucose, insulin, HOMA-IR and other indices). Oral glucose tolerance, anth...
Intakes of micronutrient-rich foods are low among Indian women of reproductive age. We investigated whether consumption of a food-based micronutrient-rich snack increased markers of blood micronutrient concentrations when compared with a control snack. Non-pregnant women (
n
222) aged 14–35 years living in a Mumbai slum were randomised to receive a...
BACKGROUND:
High blood pressure, blood glucose, serum cholesterol, and BMI are risk factors for cardiovascular diseases and some of these factors also increase the risk of chronic kidney disease and diabetes. We estimated mortality from cardiovascular diseases, chronic kidney disease, and diabetes that was attributable to these four cardiometabolic...
