Nutrition in adolescent growth and development.

During adolescence, growth and development are transformative and have profound consequences on an individual's health in later life, as well as the health of any potential children. The current generation of adolescents is growing up at a time of unprecedented change in food environments, whereby nutritional problems of micronutrient deficiency and food insecurity persist, and overweight and obesity are burgeoning. In a context of pervasive policy neglect, research on nutrition during adolescence specifically has been underinvested, compared with such research in other age groups, which has inhibited the development of adolescent-responsive nutritional policies. One consequence has been the absence of an integrated perspective on adolescent growth and development, and the role that nutrition plays. Through late childhood and early adolescence, nutrition has a formative role in the timing and pattern of puberty, with consequences for adult height, muscle, and fat mass accrual, as well as risk of non-communicable diseases in later life. Nutritional effects in adolescent development extend beyond musculoskeletal growth, to cardiorespiratory fitness, neurodevelopment, and immunity. High rates of early adolescent pregnancy in many countries continue to jeopardise the growth and nutrition of female adolescents, with consequences that extend to the next generation. Adolescence is a nutrition-sensitive phase for growth, in which the benefits of good nutrition extend to many other physiological systems.

Comparison of physical examination and laboratory data between a clinical study and electronic health records.

Research based on secondary analysis of data stored in electronic health records (EHR) has gained popularity, but whether the data are consistent with those collected under a study setting is unknown. The objective is to assess the agreement between data obtained in a prospective study and routine-care data extracted retrospectively from the EHR. We compared the data collected in a longitudinal lifestyle intervention study with those recorded in the EHR system over 5 years. A total of 225 working adults were recruited at an academic institution between 2008-2012, whose EHR data were also available during the same time period. After aligning the participants' study visit dates with their hospital encounter dates, data on blood pressure, body mass index (BMI), and laboratory measurements (including high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, and total cholesterol) were compared via a paired t-test for equivalence with pre-specified margins. Summary statistics were used to compare smoking status and medication prescriptions. Overall, data were consistent between the two sources (i.e., BMI, smoking status, medication prescriptions), whereas some differences were found in cholesterol measurements (i.e., HDL and total cholesterol), possibly due to different lab assays and subject's fasting status. In conclusion, some EHR data are fairly consistent with those collected in a clinical study, whereas others may require further examination. Researchers should evaluate the consistency and quality of EHR data and compare them with other sources of data when possible.

Advancing human health in the decade ahead: pregnancy as a key window for discovery: A Burroughs Wellcome Fund Pregnancy Think Tank.

Recent revolutionary advances at the intersection of medicine, omics, data sciences, computing, epidemiology, and related technologies inspire us to ponder their impact on health. Their potential impact is particularly germane to the biology of pregnancy and perinatal medicine, where limited improvement in health outcomes for women and children has remained a global challenge. We assembled a group of experts to establish a Pregnancy Think Tank to discuss a broad spectrum of major gestational disorders and adverse pregnancy outcomes that affect maternal-infant lifelong health and should serve as targets for leveraging the many recent advances. This report reflects avenues for future effects that hold great potential in 3 major areas: developmental genomics, including the application of methodologies designed to bridge genotypes, physiology, and diseases, addressing vexing questions in early human development; gestational physiology, from immune tolerance to growth and the timing of parturition; and personalized and population medicine, focusing on amalgamating health record data and deep phenotypes to create broad knowledge that can be integrated into healthcare systems and drive discovery to address pregnancy-related disease and promote general health. We propose a series of questions reflecting development, systems biology, diseases, clinical approaches and tools, and population health, and a call for scientific action. Clearly, transdisciplinary science must advance and accelerate to address adverse pregnancy outcomes. Disciplines not traditionally involved in the reproductive sciences, such as computer science, engineering, mathematics, and pharmacology, should be engaged at the study design phase to optimize the information gathered and to identify and further evaluate potentially actionable therapeutic targets. Information sources should include noninvasive personalized sensors and monitors, alongside instructive "liquid biopsies" for noninvasive pregnancy assessment. Future research should also address the diversity of human cohorts in terms of geography, racial and ethnic distributions, and social and health disparities. Modern technologies, for both data-gathering and data-analyzing, make this possible at a scale that was previously unachievable. Finally, the psychosocial and economic environment in which pregnancy takes place must be considered to promote the health and wellness of communities worldwide.

Implications of Growth as a Time-Specific Event.

Nutritional influences on human growth are commonly assessed as weight or length/height outcomes, and adequacy is determined by reference to population-based growth charts. These approaches estimate gross effects only and are insensitive proxies for the dynamic processes by which nutritional components affect tissue accrual. Weight provides information about calorie balance and/or hydration status, while offering little insight into functional physiology. Height is often attributed meaning in accordance with growth charts, a static group level statistical summary unrelated to individual skeletal dynamics. Evidence accumulates that the lifelong health consequences of early growth necessitate a better understanding of individual-level body composition and its developmental determinants. Empirical evidence documents that children's skeletal and head circumference growth occurs in time-specific saltations separated by intervals of no growth. These saltation events are accompanied by discrete increases and decreases in subcutaneous fat implying pulsatile metabolic changes that may or may not be reflected in weight. The mechanisms determining the timing of these saltatory growth events to emerge from stasis, as well as the required energy and chemical building blocks to fuel and support them, remain to be clarified. Their occurrence suggests that the present understanding of nutritional needs for growth is incomplete.

How long bones grow children: Mechanistic paths to variation in human height growth.

OBJECTIVES: Eveleth and Tanner's descriptive documentation of worldwide variability in human growth provided evidence of the interaction between genetics and environment during development that has been foundational to the science of human growth. There remains a need, however, to describe the mechanistic foundations of variability in human height growth patterns. METHODS: A review of research documenting cellular activities at the endochondral growth plate aims to show how the unique microenvironment and cell functions during the sequential phases of the chondrocyte lifecycle affect long bone elongation, a fundamental source of height growth. RESULTS: There are critical junctures within the chondrocytic differentiation cascade at which environmental influences are integrated and have the ability to influence progression to the hypertrophic chondrocyte phase, the primary driver of long bone elongation. Phenotypic differences in height growth patterns reflect variability in amplitude and frequency of discretely timed hypertrophic cellular expansion events, the cellular basis of saltation and stasis growth biology. CONCLUSIONS: Final height is a summary of the dynamic processes carried out by the growth plate cellular machinery. As these cell-level mechanisms unfold in an individual, time-specific manner, there are many critical points at which a genetic growth program can be enhanced or perturbed. Recognizing both the complexity and fluidity of this adaptive system questions the likelihood of a single, optimal growth pattern and instead identifies a larger bandwidth of saltatory frequencies for "normal" growth. Further inquiry into mechanistic sources of variability acting at critical organizational points of chondrogenesis can provide new opportunities for growth interventions.

Promoting Healthy Growth or Feeding Obesity? The Need for Evidence-Based Oversight of Infant Nutritional Supplement Claims.

The Developmental Origins of Health and Disease (DOHaD) model recognizes growth in infancy and childhood as a fundamental determinant of lifespan health. Evidence of long-term health risks among small neonates who subsequently grow rapidly poses a challenge for interventions aiming to support healthy growth, not merely drive weight gain. Defining healthy growth beyond "getting bigger" is essential as infant and young child feeding industries expand. Liquid-based nutritional supplements, originally formulated for undernourished children, are increasingly marketed for and consumed by children generally. Clarifying the nature of the evidentiary base on which structure/function claims promoting "healthy growth" are constructed is important to curb invalid generalizations. Evidence points to changing social beliefs and cultural practices surrounding supplementary feeding, raising specific concerns about the long-term health consequences of an associated altered feeding culture, including reduced dietary variety and weight gain. Reassessing the evidence for and relevance of dietary supplements' "promoting healthy growth" claims for otherwise healthy children is both needed in a time of global obesity and an opportunity to refine intervention approaches among small children for whom rapid subsequent growth in early life augments risk for chronic disease. Scientific and health care partnerships are needed to consider current governmental oversight shortfalls in protecting vulnerable populations from overconsumption. This is important because we may be doing more harm than good.

Effects of a Health-Partner Intervention on Cardiovascular Risk.

BACKGROUND: Lifestyle modifications are first-line measures for cardiovascular disease prevention. Whether lifestyle intervention also preserves cardiovascular health is less clear. Our study examined the role of a Health Partner-administered lifestyle intervention on metrics of ideal cardiovascular health. METHODS AND RESULTS: A total of 711 university employees (48±11 years; 66% women, 72% Caucasian/22.5% African Americans) enrolled in a program that promoted healthier lifestyles at Emory University (Atlanta, GA). Anthropometric, laboratory, and physical activity measurements were performed at baseline and at 6 months, 1 year, and 2 years of follow-up. Results were utilized by the Health Partner to generate a personalized plan aimed at meeting ideal health metrics. Compared to baseline, at each of the 6-month, 1-year, and 2-year follow-up visits, systolic blood pressure was lower by 3.6, 4.6, and 3.3 mm Hg (P<0.001), total cholesterol decreased by 5.3, 6.5, and 6.4 mg/dL (P<0.001), body mass index declined by 0.33, 0.45, and 0.38 kg/m2 (P<0.001), and the percentage of smokers decreased by 1.3%, 3.5%, and 3.5% (P<0.01), respectively. Changes were greater in those with greater abnormalities at baseline. Finally, the American Heart Association "Life's Simple 7" ideal cardiovascular health score increased by 0.28, 0.40, and 0.33 at 6 month, 1 year, and 2 years, respectively, compared to baseline visit. CONCLUSIONS: A personalized, goal-directed Health Partner intervention significantly improved the cardiometabolic risk profile and metrics of cardiovascular health. These effects were evident at 6 months following enrollment and were sustained for 2 years. Whether the Health Partner intervention improves long-term morbidity and mortality and is cost-effective needs further investigation.

Milk- and solid-feeding practices and daycare attendance are associated with differences in bacterial diversity, predominant communities, and metabolic and immune function of the infant gut microbiome.

The development of the infant intestinal microbiome in response to dietary and other exposures may shape long-term metabolic and immune function. We examined differences in the community structure and function of the intestinal microbiome between four feeding groups, exclusively breastfed infants before introduction of solid foods (EBF), non-exclusively breastfed infants before introduction of solid foods (non-EBF), EBF infants after introduction of solid foods (EBF+S), and non-EBF infants after introduction of solid foods (non-EBF+S), and tested whether out-of-home daycare attendance was associated with differences in relative abundance of gut bacteria. Bacterial 16S rRNA amplicon sequencing was performed on 49 stool samples collected longitudinally from a cohort of 9 infants (5 male, 4 female). PICRUSt metabolic inference analysis was used to identify metabolic impacts of feeding practices on the infant gut microbiome. Sequencing data identified significant differences across groups defined by feeding and daycare attendance. Non-EBF and daycare-attending infants had higher diversity and species richness than EBF and non-daycare attending infants. The gut microbiome of EBF infants showed increased proportions of Bifidobacterium and lower abundance of Bacteroidetes and Clostridiales than non-EBF infants. PICRUSt analysis indicated that introduction of solid foods had a marginal impact on the microbiome of EBF infants (24 enzymes overrepresented in EBF+S infants). In contrast, over 200 bacterial gene categories were overrepresented in non-EBF+S compared to non-EBF infants including several bacterial methyl-accepting chemotaxis proteins (MCP) involved in signal transduction. The identified differences between EBF and non-EBF infants suggest that breast milk may provide the gut microbiome with a greater plasticity (despite having a lower phylogenetic diversity) that eases the transition into solid foods.

Historical approaches to human growth studies limit the present understanding of growth biology.

BACKGROUND/AIMS: Measurements of children's size have (1) provided a biosensor of health and well-being in their environment; (2) provided references for clinical assessment, and (3) informed public health efforts to ameliorate living conditions. Size-for-age measurements offer no information about the growth trajectories by which children achieve size, and growth trajectories offer no information on proximal mechanisms underlying growth biology. Increasing attention to the biological processes themselves, only estimated by anthropometric parameters and statistically based growth proxies, is needed. METHODS: A literature overview of human growth measurement interpretations. RESULTS: Aspects of study design, analysis and reliance on common conventions contribute to limitations in growth biology knowledge. Examples include conflating both the concepts of size and growth and incremental gains in either weight or length as manifestations of growth; nonuniformity in the use of growth trajectory-derived clinical categories, and conventional approaches to data collection and analysis. CONCLUSIONS: Intensive studies of individuals hold promise for expanding normal growth biology knowledge. Focusing on growth (not merely size), length (not weight alone) and individual growth patterns (not growth chart phenotypes) are important tactics. Benefits include clarification of mechanisms by which nutrition and metabolism influence growth, new solutions to abnormal growth states and improvements in long-term health consequences.

Prenatal and postnatal energetic conditions and sex steroids levels across the first year of life.

OBJECTIVES: Human biologists have documented variability in reproductive maturation, fertility, and cancer risk related to developmental conditions. Yet no previous studies have directly examined the impact of prenatal and postnatal energetic environments on sex steroids in infancy, a critical period for hypothalamic-pituitary-gonadal axis development. Thus, we examined the impact of maternal characteristics, birth size, and feeding practices on fecal sex steroid production in a longitudinal sample of 31 American infants followed from 2 weeks to 12 months of age. METHODS: Maternal characteristics and birth size were collected at study enrollment, infant diet was assessed through weekly 24-h food diaries, and anthropometrics were measured weekly. Fecal estradiol and testosterone levels were assessed weekly using validated microassay RIA techniques. Mixed models were used to test for associations between maternal and birth characteristics, feeding practices, and sex steroids across the first year of life. Formal mediation analysis examined whether the relationship between infant feeding and hormone levels was mediated by infant size. RESULTS: Maternal and birth characteristics had persistent effects on fecal sex steroid levels, with taller maternal height and larger birth size associated with lower estradiol levels in girls and higher testosterone levels in boys. Infant diet was also associated with sex steroid levels independently of infant size. Formula feeding was associated with higher estradiol levels in boys and girls and with higher testosterone in girls. CONCLUSION: These results suggest that markers of early energy availability influence sex hormone levels with potential long-term consequences for reproductive development and function.

Markers of biological fitness as predictors of all-cause mortality.

INTRODUCTION: Within the Helsinki Birth Cohort, men who were tall when they were 7 years old lived for 5 years longer than men who were short. In the present analyses we examined two other influences known to be associated with lifespan: having children and educational attainment. We hypothesized that tall stature, the ability to have children, and high educational attainment reflect three aspects of biological fitness that are acquired during development. METHODS: We examined all-cause mortality in 6975 men and 6370 women born in Helsinki during 1934-1944, whose childhood growth, number of children, and educational attainment were recorded. RESULTS: In contrast to men, tall stature in childhood was not associated with longer lifespan among women. Men and women who had children lived for longer than those who had no children. Among women, having children was only associated with increased lifespan among those whose body mass index increased between 2 and 11 years. High educational attainment was associated with longer lifespan in both sexes. The trends of lower all-cause mortality with higher educational attainment were present in each socio-economic group. The men and women who had children, and attained upper tertiary education, lived for 16 years longer than those who had no children and only basic education. CONCLUSION: We suggest that the associations between having children, educational attainment, and lifespan reflect two different aspects of biological fitness that are acquired during early development.

Engaging young adults in proactive health behaviors: a goal-setting process.

The Human Health Program at Emory University, Atlanta, Georgia, is an undergraduate curriculum that focuses on health in its broadest context, exploring novel strategies that educate, engage, empower, and encourage college students to develop and sustain healthy lifestyle behaviors. In the program, students take part in a onesemester experience that is a blend of academic health education and wellness coaching, where the group class supports a self-directed health goal process.

Perspectives on modelling human growth: mathematical models and growth biology.

CONTEXT: James Tanner had a foundational role in promoting the modelling of growth data as an important step in further understanding the science of human growth. OBJECTIVE: A perspective on how growth models have determined the questions researchers ask and the methods used to analyse data is historically informative. Alternatively, it is useful to review that mathematical models are representations of growth as a function of time and carry assumptions that require consideration in terms of the goals of a research inquiry. METHODS: An overview of the history of the study of human growth models and modelling is summarized with reference to the important roles that these have played in the perceptions of the human growth process. RESULTS: Growth models are important descriptive summaries, embody empirical evidence and provide the opportunity for hypotheses-testing that aides the understanding, explanation and prediction of growth processes and systems. These models are modified as novel data emerge. More frequent sampling protocols and the development of mathematical models has advanced mechanistic investigations of the human growth process. CONCLUSIONS: Technical advances in science are important to investigate potential underlying mechanisms of growth and develop interventions based on a more accurate model of growth biology.

Ethnic differences in the accumulation of fat and lean mass in late gestation.

OBJECTIVES: Lower birth weight within the normal range predicts adult chronic diseases, but the same birth weight in different ethnic groups may reflect different patterns of tissue development. Neonatal body composition was investigated among non-Hispanic Caucasians and African Americans, taking advantage of variability in gestational duration to understand growth during late gestation. METHODS: Air displacement plethysmography assessed fat and lean body mass among 220 non-Hispanic Caucasian and 93 non-Hispanic African American neonates. The two ethnic groups were compared using linear regression. RESULTS: At 36 weeks of gestation, the average lean mass of Caucasian neonates was 2,515 g vs. that of 2,319 g of African American neonates (difference, P = 0.02). The corresponding figures for fat mass were 231 and 278 g, respectively (difference, P = 0.24). At 41 weeks, the Caucasians were 319 g heavier in lean body mass (P < 0.001) but were also 123 g heavier in fat mass (P = 0.001). The slopes for lean mass vs. gestational week were similar, but the slope of fat mass was 5.8 times greater (P = 0.009) for Caucasian (41.0 g/week) than for African American neonates (7.0 g/week). CONCLUSIONS: By 36 weeks of gestation, the African American fetus developed similar fat mass and less lean mass compared with the Caucasian fetus. Thereafter, changes in lean mass among the African American fetus with increasing gestational age at birth were similar to the Caucasian fetus, but fat accumulated more slowly. We hypothesize that different ethnic fetal growth strategies involving body composition may contribute to ethnic health disparities in later life.

Measurement of testosterone in infant fecal samples.

OBJECTIVES: This study reports the validation of a noninvasive method for repeated assessment of testosterone from infant fecal samples. METHODS: Fecal samples were collected from cotton diaper liners, subjected to methanol extraction, and assayed using a modified commercial testosterone RIA kit. RESULTS: Method validity was supported by a recovery near 100%, a sensitivity of 1.23 pg/ml, and inter- and intra-assay coefficients of variations less than 10 and 15%, respectively. Testosterone was detected in all samples from male and female infants aged 2 weeks to 15 months. CONCLUSIONS: Fecal assessment is supported as a novel, non-invasive tool for studying testosterone during early human development.