In addition to immediate implications for pregnancy complications, increasing evidence implicates maternal obesity as a major determinant of offspring health during childhood and later adult life. ...Observational studies provide evidence for effects of maternal obesity on her offspring's risks of obesity, coronary heart disease, stroke, type 2 diabetes, and asthma. Maternal obesity could also lead to poorer cognitive performance and increased risk of neurodevelopmental disorders, including cerebral palsy. Preliminary evidence suggests potential implications for immune and infectious-disease-related outcomes. Insights from experimental studies support causal effects of maternal obesity on offspring outcomes, which are mediated at least partly through changes in epigenetic processes, such as alterations in DNA methylation, and perhaps through alterations in the gut microbiome. Although the offspring of obese women who lose weight before pregnancy have a reduced risk of obesity, few controlled intervention studies have been done in which maternal obesity is reversed and the consequences for offspring have been examined. Because the long-term effects of maternal obesity could have profound public health implications, there is an urgent need for studies on causality, underlying mechanisms, and effective interventions to reverse the epidemic of obesity in women of childbearing age and to mitigate consequences for offspring.
Parental environmental factors, including diet, body composition, metabolism, and stress, affect the health and chronic disease risk of people throughout their lives, as captured in the Developmental ...Origins of Health and Disease concept. Research across the epidemiological, clinical, and basic science fields has identified the period around conception as being crucial for the processes mediating parental influences on the health of the next generation. During this time, from the maturation of gametes through to early embryonic development, parental lifestyle can adversely influence long-term risks of offspring cardiovascular, metabolic, immune, and neurological morbidities, often termed developmental programming. We review periconceptional induction of disease risk from four broad exposures: maternal overnutrition and obesity; maternal undernutrition; related paternal factors; and the use of assisted reproductive treatment. Studies in both humans and animal models have demonstrated the underlying biological mechanisms, including epigenetic, cellular, physiological, and metabolic processes. We also present a meta-analysis of mouse paternal and maternal protein undernutrition that suggests distinct parental periconceptional contributions to postnatal outcomes. We propose that the evidence for periconceptional effects on lifetime health is now so compelling that it calls for new guidance on parental preparation for pregnancy, beginning before conception, to protect the health of offspring.
Maternal smoking during pregnancy is linked to reduced birth weight but the gestation at onset of this relationship is not certain. We present a systematic review of the literature describing ...associations between maternal smoking during pregnancy and ultrasound measurements of fetal size, together with an accompanying meta-analysis.
Studies were selected from electronic databases (OVID, EMBASE and Google Scholar) that examined associations between maternal smoking or smoke exposure and antenatal fetal ultrasound measurements. Outcome measures were first, second or third trimester fetal measurements.
There were 284 abstracts identified, 16 papers were included in the review and the meta-analysis included data from eight populations. Maternal smoking was associated with reduced second trimester head size (mean reduction 0.09 standard deviation (SD) 95% CI 0.01, 0.16) and femur length (0.06 0.01, 0.10) and reduced third trimester head size (0.18 SD 0.13, 0.23), femur length (0.27 SD 0.21, 0.32) and estimated fetal weight (0.18 SD 0.11, 0.24). Higher maternal cigarette consumption was associated with a lower z score for head size in the second (mean difference 0.09 SD 0, 0.19) and third (0.15 SD 0.03, 0.26) trimesters compared to lower consumption. Fetal measurements were not reduced for those whose mothers quit before or after becoming pregnant compared to mothers who had never smoked.
Maternal smoking during pregnancy is associated with reduced fetal measurements after the first trimester, particularly reduced head size and femur length. These effects may be attenuated if mothers quit or reduce cigarette consumption during pregnancy.
Recent evidence demonstrates important maternal effects on an offspring's risk of developing metabolic disease. These effects extend across the full range of maternal environments and partly involve ...epigenetic mechanisms. The maternal effects can be explained in evolutionary terms, and there is some evidence for their transmission into succeeding generations. Unbalanced maternal diet or body composition, ranging from poor to rich environments, adversely influences the offspring's response to later challenges such as an obesogenic diet or physical inactivity, increasing the risk of disease. Adopting a life course approach that takes into account intergenerational effects has important implications for prevention of non-communicable diseases, particularly in populations undergoing rapid economic transition.
The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, ...which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD
levels through perturbed NAD
biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.
In preterm infants, poor postnatal growth is associated with adverse neurocognitive outcomes; conversely, rapid postnatal growth is supposedly harmful for future development of metabolic diseases.
...Conclusion
In this systematic review, observational studies reported consistent positive associations between postnatal weight or head growth and neurocognitive outcomes; however, there was limited evidence from the few intervention studies. Evidence linking postnatal weight gain to later adiposity and other cardiovascular disease risk factors in preterm infants was also limited.
Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce ...the incidence of gestational diabetes and large-for-gestational-age infants.
The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15–18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m2). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing.
Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m2 (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79–1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83–1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups.
A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants.
National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.
We found that the relatively simple microbiota of young infants shifts predictably to a more mature anaerobic microbiota during infancy and the dynamics of this shift are influenced by environmental ...factors. In this longitudinal study of 75 infants, we demonstrate high interindividual variability within the normal range of birth outcomes, especially in the rate of microbiota progression. Most had acquired a microbiota profile high in Bifidobacterium and Collinsella by 6 months of age, but the time point of this acquisition was later in infants delivered by caesarean section and those born after a shorter duration of gestation. Independently of the delivery mode and gestation duration, infants who acquired a profile high in Bifidobacterium and Collinsella at a later age had lower adiposity at 18 months of age.
This study shows that the acquisition of the early microbiota is strongly influenced by environmental factors such as the delivery mode and duration of gestation, even in healthy neonates. The composition of the early microbiota has been linked with long-lasting effects on health and disease. Here we show that the rate of acquisition of certain microbiota predicts adiposity at 18 months of age and so potentially the risk of later obesity.
Analyze the relation of gestational diabetes and maternal blood glucose levels to early cognitive functions in the first two years of life.
In a prospective Singaporean birth cohort study, pregnant ...women were screened for gestational diabetes at 26-28 weeks gestation using a 75-g oral glucose tolerance test. Four hundred and seventy three children (n = 74 and n = 399 born to mothers with and without gestational diabetes respectively) underwent neurocognitive assessments at 6, 18, and/or 24 month, including electrophysiology during an attentional task and behavioral measures of attention, memory and cognition.
Gestational diabetes is related to left hemisphere EPmax amplitude differences (oddball versus standard) at both six (P = 0.039) and eighteen months (P = 0.039), with mean amplitudes suggesting offspring of mothers with gestational diabetes exhibit greater neuronal activity to standard stimuli and less to oddball stimuli. Associations between 2-hour maternal glucose levels and the difference in EPmax amplitude were marginal at 6 months adjusted β = -0.19 (95% CI: -0.42 to +0.04) μV, P = 0.100 and significant at 18 months adjusted β = -0.27 (95% CI: -0.49 to -0.06) μV, P = 0.014, and the EPmax amplitude difference (oddball-standard) associated with the Bayley Scales of Infant and toddler Development-III cognitive score at 24 months β = 0.598 (95% CI: 0.158 to 1.038), P = 0.008.
Gestational diabetes and maternal blood glucose levels are associated with offspring neuronal activity during an attentional task at both six and eighteen months. Such electrophysiological differences are likely functionally important, having been previously linked to attention problems later in life.
The extent of interpregnancy weight change and its association with subsequent pregnancy outcomes among Asians remain unclear. We examined changes in maternal body mass index (BMI) between the first ...two deliveries and outcomes in the second delivery. Medical records of women with their first two consecutive deliveries between 2015 and 2020 at KK Women's and Children's Hospital, Singapore were retrieved. Gestational-age-adjusted BMI was determined by standardising to 12 weeks gestation and interpregnancy BMI change was calculated as the difference between both pregnancies. Pregnancy outcomes were analysed using modified Poisson regression models. Of 6264 included women with a median interpregnancy interval of 1.44 years, 40.7% had a stable BMI change within ± 1 kg/m
, 10.3% lost > 1 kg/m
, 34.3% gained 1-3 kg/m
and 14.8% gained ≥ 3 kg/m
. Compared to women with stable BMI change, those with > 1 kg/m
loss had higher risk of low birthweight (adjusted risk ratio RR 1.36; 95% confidence interval 1.02-1.80), while those with 1-3 kg/m
gain had higher risks of large-for-gestational-age birth (1.16; 1.03-1.31), gestational diabetes (1.25; 1.06-1.49) and emergency Caesarean delivery (1.16; 1.03-1.31); these risks were higher in those with ≥ 3 kg/m
gain. Our study strengthens the case for interpregnancy weight management to improve subsequent pregnancy outcomes.
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