BACKGROUND: Stroke is a life-threatening condition that causes a major medical burden globally. The currently used methods for the prevention or prediction of stroke have certain limitations. Exposure to tobacco in early life, including smoking during adolescence and maternal smoking during pregnancy, can affect adolescent development and lead to several negative outcomes. However, the association between early-life tobacco exposure and stroke is not known.
METHODS: In this prospective cohort study, for the analyses involving exposure to maternal smoking during pregnancy and age of smoking initiation, we included 304,984 and 342,893 participants, respectively., respectively from the UK Biobank. Cox proportional hazard regression model and subgroup analyses were performed to investigate the association between early-life tobacco exposure and stroke. Mediation analyses were performed to identify the mediating role of biological aging in the association between early tobacco exposure and stroke.
RESULTS: Compared with participants whose mothers did not smoke during pregnancy, participants whose mothers smoked during pregnancy showed an 11% increased risk of stroke (HR: 1.11, 95% CI: 1.05-1.18, P < 0.001). Compared with participants who never smoked, participants who smoked during adulthood, adolescence and childhood showed a 22%, 24%, and 38% increased risk of stroke during their adulthood, respectively. Mediation analysis indicated that early-life tobacco exposure can cause stroke by increasing biological aging.
CONCLUSIONS: This study reveals that exposure to tobacco during early life is associated with an increased risk of experiencing a stroke, and increased biological aging can be the underlying mechanism.

BACKGROUND: The influence of early-life growth pattern and body size on follicular lymphoma (FL) risk and survival is unclear. In this study, we aimed to investigate the association between gestational age, growth during childhood, body size, changes in body shape over time, and FL risk and survival.
METHODS: We conducted a population-based family case-control study and included 706 cases and 490 controls. We ascertained gestational age, growth during childhood, body size and body shape using questionnaires and followed-up cases (median=83 months) using record linkage with national death records. We used a group-based trajectory modeling approach to identify body shape trajectories from ages 5-70. We examined associations with FL risk using unconditional logistic regression and used Cox regression to assess the association between body mass index (BMI) and all-cause and FL-specific mortality among cases.
RESULTS: We found no association between gestational age, childhood height and FL risk. We observed a modest increase in FL risk with being obese 5 years prior to enrolment (OR=1.43, 95 %CI=0.99-2.06; BMI ≥30 kg/m2) and per 5-kg/m2 increase in BMI 5 years prior to enrolment (OR=1.14, 95 %CI=0.99-1.31). The excess risk for obesity 5 years prior to enrolment was higher for ever-smokers (OR=2.00, 95 %CI=1.08-3.69) than never-smokers (OR=1.14, 95 %CI=0.71-1.84). We found no association between FL risk and BMI at enrolment, BMI for heaviest lifetime weight, the highest categories of adult weight or height, trouser size, body shape at different ages or body shape trajectory. We also observed no association between all-cause or FL-specific mortality and excess adiposity at or prior to enrolment.
CONCLUSIONS: We observed a weak association between elevated BMI and FL risk, and no association with all-cause or FL-specific mortality, consistent with previous studies. Future studies incorporating biomarkers are needed to elucidate possible mechanisms underlying the role of body composition in FL etiology.

The Taicang and Wuqiang cohort study (TAWS) was established to examine the association between early-life nutrition and children\'s health, and to explore the potential roles of maternal health, metabolites and microbiota in children\'s health in two different regions of China.
A total of 7041 mother-child pairs were recruited during early pregnancy (n=4035, 57.3%) or delivery phase (n=3006, 42.7%) from health centres or hospitals in Taicang and Wuqiang. Mother-child pairs were followed up three times during pregnancy, once during delivery, and 7-10 times in the 3 years after delivery. Questionnaires were used to collect data on diet, supplementary intake, physical activity, depression scale, disease occurrence, feeding practice and development quotient of children. Anthropometric measurements of mothers and their children were assessed at each visit. Pregnancy outcomes were extracted from medical records. Biospecimens were collected and stored, including venous blood, cord blood, urine, stool, breast milk, cord and placenta.
Data from the TAWS cohort showed different baseline characteristics of participants at the two sites of TAWS. Abnormal metabolism occurred among newborns whose mothers were diagnosed with gestational diabetes mellitus. Maternal serum folic acid above 14.5 ng/mL at early pregnancy was associated with a reduced risk of delivering small-for-gestational-age newborns.
The association between maternal nutrition and the health of offspring will be examined at various follow-up visits. Biomarkers will be analysed to assess the associations between early-life nutrition and child development, immunity and health. Strategic recommendations for optimal infant feeding practices, obesity prevention and routine healthcare items will be developed and proposed based on the findings from the study. Children in this prospective cohort study will be followed up once a year until age 12 years to further examine the relationships between early-life nutrition and children\'s long-term development and health.

Early age at breast development (thelarche) has been associated with increased breast cancer risk. Average age at thelarche has declined over time, but there are few established risk factors for early thelarche. We examined associations between pre- and postnatal exposures and age at thelarche in a US cohort of women born between 1928 and 1974.
Breast cancer-free women ages 35-74 years who had a sister diagnosed with breast cancer were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported information on early-life exposures and age at thelarche, which we categorized as early (≤ 10 years), average (11-13 years), and late (≥ 14 years). For each exposure, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) for early and late thelarche using polytomous logistic regression, adjusted for birth cohort, race/ethnicity and family income level in childhood.
Early thelarche was associated with multiple prenatal exposures: gestational hypertensive disorder (OR = 1.25, 95% CI 1.09-1.43), diethylstilbestrol use (OR = 1.23, 95% CI 1.04-1.45), smoking during pregnancy (OR = 1.20, 95% CI 1.13-1.27), young maternal age (OR 1.30, 95% CI 1.16-1.47 for < 20 vs. 25-29 years), and being firstborn (OR = 1.25, 95% CI 1.17-1.33). Birthweight < 2500 g and soy formula use in infancy were positively associated with both early and late thelarche.
Associations between pre- and postnatal exposures and age at thelarche suggest that the early-life environment influences breast development and therefore may also affect breast cancer risk by altering the timing of pubertal breast development.

The early life period represents the first step in establishing a beneficial microbial ecosystem, which in turn affects both short and longer-term health. Changes during pregnancy influence the neonatal microbiome; through transmission of maternal microbes during childbirth, and beyond, through nutritional programming. However, in-depth exploration of longitudinal maternal-infant cohorts, with sampling of multiple body sites, complemented by clinical and nutritional metadata, and use of cutting-edge experimental systems are limited. The PEARL study will increase our knowledge of; how microbes (including viruses/phages, bacteria, fungi and archaea) change in composition and functional capacity during pregnancy; transmission pathways from mother to infant; the impact of various factors on microbial communities across pregnancy and early life (e.g. diet), and how these microbes interact with other microbes and modulate host processes, including links to disease onset.
PEARL is a longitudinal observational prospective study of 250 pregnant women and their newborns, with stool and blood samples, questionnaires and routine clinical data collected during pregnancy, labour, birth and up to 24 months post birth. Metagenomic sequencing of samples will be used to define microbiome profiles, and allow for genus, species and strain-level taxonomic identification and corresponding functional analysis. A subset of samples will be analysed for host (immune/metabolite) molecules to identify factors that alter the host gut environment. Culturing will be used to identify new strains of health-promoting bacteria, and potential pathogens. Various in vitro and in vivo experiments will probe underlying mechanisms governing microbe-microbe and microbe-host interactions.
Longitudinal studies, like PEARL, are critical if we are to define biomarkers, determine mechanisms underlying microbiome profiles in health and disease, and develop new diet- and microbe-based therapies to be tested in future studies and clinical trials.
This study is registered in the ClinicalTrials.gov Database with ID: NCT03916874 .

We studied the association of early-life environmental and child factors with disruptive behaviors in children with autistic traits around age 7, in the Avon Longitudinal Study of Parents and Children (n = 6,401). Logistic regression with the least absolute shrinkage and selection operator indicated that disruptive behaviors were associated with prenatal smoking, no seafood-consumption during pregnancy, breech presentation at delivery, neonatal feeding problems, low social-economic situation, suboptimal preschool family environment, maternal depression, maternal antisocial behavior, male sex, and difficult child temperament. Compared to controls, male sex, maternal depression, and suboptimal preschool family environment were related to autistic traits without disruptive behaviors. Thus, there may be a difference in early-life factors related to autism spectrum disorder with and without disruptive behaviors.

Light pollution or artificial light at night (ALAN) is increasingly recognised to be an important anthropogenic environmental pressure on wildlife, affecting animal behaviour and physiology. Early life experiences are extremely important for the development, physiological status and health of organisms, and as such, early exposure to artificial light may have detrimental consequences for organism fitness. We experimentally manipulated the light environment of free-living great tit nestlings (Parus major), an important model species in evolutionary and environmental research. Haptoglobin (Hp) and nitric oxide (NOx), as important indicators of immunity, health, and physiological condition, were quantified in nestlings at baseline (13 days after hatching) and after a two night exposure to ALAN. We found that ALAN increased Hp and decreased NOx. ALAN may increase stress and oxidative stress and reduce melatonin which could subsequently lead to increased Hp and decreased NOx. Haptoglobin is part of the immune response and mounting an immune response is costly in energy and resources and, trade-offs are likely to occur with other energetically demanding tasks, such as survival or reproduction. Acute inhibition of NOx may have a cascading effect as it also affects other physiological aspects and may negatively affect immunocompetence. The consequences of the observed effects on Hp and NOx remain to be examined. Our study provides experimental field evidence that ALAN affects nestlings\' physiology during development and early life exposure to ALAN could therefore have long lasting effects throughout adulthood.