Childhood Disadvantage Research Articles

Retrospective reports of socioeconomic disadvantage in childhood and mortality risk: are associations consistent across measures and sex?

Although prior research has established associations between childhood socioeconomic disadvantage and all-cause mortality, there is still limited research investigating (1) the consistency between subjective and objective reports of childhood socioeconomic status, (2) sex differences in the associations between childhood socioeconomic disadvantage and all-cause mortality, and (3) potential mediators within these associations. Drawing on data from the Midlife in the United States (MIDUS) cohort (N = 7425), we examined the associations between three distinct indicators of childhood socioeconomic disadvantage and all-cause mortality risk, and whether these associations differ for males and females. Among males only, lower perceived relative childhood financial status, lower levels of parents' education, and receipt of welfare during childhood were associated with excess mortality risk, adjusted for age and minority status, with adjusted hazard ratios ranging from 1.24 (95% confidence interval (CI): 1.02, 1.51) for perceived childhood financial status to 1.28 (95% CI: 1.11, 1.47) for welfare in childhood. When additionally adjusted for education, substance use, depression, and underlying health conditions, only childhood welfare status maintained an association with mortality (AHR, 1.17; 95% CI, 1.02-1.35). Mediation analyses among males revealed that education, substance use, depression, and underlying health conditions accounted for substantial proportions of these associations, ranging from 31.03 to 57.63%, across indicators of childhood socioeconomic disadvantage. Future research is needed to clarify the developmental mechanisms that lead to sex differences and identify effective strategies to intervene on the relation between childhood socioeconomic position and excess mortality risk among males.

Family disadvantage, gender, and the returns to genetic human capital*

AbstractIn this paper, we investigate the context‐dependence of genetic influences on human capital formation in Denmark. We show that the returns to genetic endowments are smaller for individuals who have experienced childhood disadvantage. We discuss how we can rule out omitted variables or measurement error bias as explanations, because we observe the attenuation effect of childhood disadvantage in both between‐family and within‐family analyses. Our results highlight an important mechanism driving the persistence of disadvantage across generations. We show that children who experience childhood disadvantage are not able to fully realize their educational potential, even in the context of the generous Danish welfare state.

Benzodiazepines and Z-drugs Prescriptions Trends over time among the Aberdeen Children of the 1950s and Associated Characteristics with Chronic prescriptions.

BackgroundThere are ongoing concerns worldwide about prescribing benzodiazepines and Z-drugs (BZDs) due to the risks associated with these medicines. Despite guidance to limit their prescribing, in Scotland, the sustained level of prescribing over the last decade suggests chronic prescribing of BZDs. Although prescribing decisions is a complex process that is influenced by patient-related factors, little is known about the characteristics of those who are on chronic BZDs prescriptions, including childhood and adulthood characteristics. Therefore, this study aims to describe the trend of BZDs prescriptions over seven years and to characterise those who were on chronic/recurrent BZDs prescriptions. MethodsThis is a prospective longitudinal cohort study using data linkage technique, in which a birth cohort was linked to the Prescribing Information System, the Scottish Morbidity Database. Simple descriptive analysis was used to describe the incidence trends. To characterise individuals with chronic/recurrent prescriptions, multivariable Poisson regression models were constructed using a stepwise regression, the calculated risk ratios were reported with a 95% confidence interval. FindingsThe incidence of BZDs prescription declined from 3.4% [3.0-3.7] in 2010 to 2.0% [1.7%-2.3%] in 2015. While, within those receiving any prescriptions, the incidence of chronic/recurrent prescriptions was relatively constant around 7%. The study showed that those who had a history of behavioural disturbance in childhood were at increased risk of chronic/recurrent BZDs prescriptions compared with those who had not (risk ratio: 1.18 [95%CI: 1.03-1.35]). Similarly, those who had an IQ score < 100 were also more likely to be on chronic/recurrent BZDs prescriptions than those >100 (1.09 [0.99-1.21]). Chronic/recurrent BZDs prescriptions were more common among individuals in receipt of psychotropic prescriptions (1.77 [1.55-2.02]) or who had been hospitalised with depression/schizophrenia (1.28 [1.13-1.46]). Multimorbidity was also important: a dose-risk relationship was evident, such that, compared to participants reporting no morbidity, those reporting one, or five or more morbidities, experienced a 116% and 451% increase in risk (2.16 [1.47-3.18] and 5.51 [3.98-7.62], respectively). Finally, those who had taken early retirement (1.65 [1.36-1.99]) and those looking after family (1.35 [1.11-1.65]) were more likely to receive chronic/recurrent BZDs, compared to employed individuals. ConclusionsChronic/recurrent BZDs prescriptions are common. Careful interpretation for the decline in incidence as this is a close cohort where incidence might be diluted after a long follow-up. The need for these drugs might be an indication of an impaired coping system. Childhood is a sensitive age period for individuals’ development. And behavioural disturbance and/or lower IQ score might be a manifestation of a disadvantaged childhood which, in turn, might affect individuals’ ability to cope with life in adulthood. Also, the accumulation of trajectory events such as impact physical and mental health or lacking socioeconomic opportunity could impact individuals’ ability to cope, although, for factors in adulthood, one must be wary of reverse causation.

The Intergenerational Transmission of Mental and Physical Health in Australia: Evidence Using Data From the Household Income and Labor Dynamics of Australia Survey.

Promoting good health across the life course is high on countries agenda. There is a growing evidence base that health is correlated across generations. We examine the persistence of physical and mental health status across generations and explore how different early life factors and adult outcomes impact on this association. In particular, we focus on childhood disadvantage and childhood health, educational attainment, and social mobility measured by household income compared to one's parents. We use data from 19 waves of the Household, Income and Labor Dynamics in Australia (HILDA) Survey. The analysis is restricted to young adults (aged 25–35 years old in 2019) and their parents. We find an intergenerational correlation in health which ranges from 0.19 for physical health to 0.20 for the QALY and 0.21 for mental health. After we include covariates related to childhood disadvantage, childhood health, educational attainment, and social mobility, the intergenerational correlations are reduced to 0.13 for physical health, 0.18 for mental health, and 0.14 for QALYs. We find that early life disadvantage is the only factor influencing the intergenerational correlation for all health measures. Policy focusing on reducing the negative impact of early life disadvantage is likely to have a larger impact on improving health across the life course and reducing intergenerational health inequalities.

Diet quality in preschool children and associations with individual eating behavior and neighborhood socioeconomic disadvantage. The STEPS Study

A good quality diet in childhood is important for optimal growth as well as for long-term health. It is not well established how eating behaviors affect overall diet quality in childhood. Moreover, very few studies have considered the association of diet quality and a neighborhood socioeconomic disadvantage in childhood. Our aim was to investigate how diet quality is associated with eating behaviors and neighborhood disadvantage and their interaction in preschool age children in Finland. The participants were from the Steps to Healthy Development Study at age 2 y (n = 780) and 5 y (n = 653). Diet quality was measured with a short questionnaire on habitual food consumption and eating behavior was assessed with the child eating behavior questionnaire to indicate the child's eating style regarding food approach and food avoidance dimensions. Information on neighborhood socioeconomic disadvantage were obtained from the statistics Finland grid database. We found that diet quality was higher at 5 years compared to 2 years of age (p < 0.001). Food approach subscale, enjoyment of food, was positively associated with the diet quality (p < 0.001 for 2 and 5 y) while subscale desire to drink was negatively associated with the diet quality (p = 0.001 for 2 and 5 y). Food avoidance was negatively associated with the diet quality both at 2 and at 5 years of age (p < 0.001). A higher neighborhood disadvantage was negatively associated with the diet quality at the age of 2 years (p = 0.02), but not at the age of 5 years. Eating behavior had similar associations with diet quality both in affluent and deprived neighborhoods. Our results suggest that both the eating behavior and neighborhood disadvantage are, already in the early age, important factors when considering children's diet quality.

Childhood Disadvantage and Adult Functional Status: Do Early-Life Exposures Jeopardize Healthy Aging?

To examine whether childhood disadvantage is associated with later-life functional status and identify mediating factors. Unique and additive effects of five childhood domains on functional status were assessed at baseline (2006) and over time (2006-2016) in a sample of 13,894 adults from the Health and Retirement Study (>50years). Adult health behaviors and socioeconomic status (SES) were tested as mediators. Respondents exposed to multiple childhood disadvantages (OR = .694) as well as low childhood SES (OR = .615), chronic diseases (OR = .694), impairments (OR = .599), and risky adolescent behaviors (OR = .608) were less likely to be free of functional disability by baseline. Over time, these unique and additive effects of childhood disadvantage increased the hazard odds of eventually developing functional disability (e.g., additive effect: hOR = 1.261). Adult health behaviors and SES mediated some of these effects. Given the enduring effects of childhood disadvantage, policies to promote healthy aging should reduce exposure to childhood disadvantage.

Early-Life Circumstances and Cross-Country Disparities in Cognition Among Older Populations - China, the US, and the EU, 2008-2018.

Many health challenges have emerged due to rapid population aging, including declined cognitive ability among older adults. Childhood circumstances have significant and lasting impacts on cognition in old age. This study compared cognition data from China with both the United States (U.S.) and the European Union (EU) during 2008-2018, finding that childhood circumstances could respectively explain 65.4% [95% confidence interval (CI): 59.4%, 71.4%] (China vs. the U.S.) and 38.2% (95% CI: 35.1%, 41.2%) (China vs. the EU) of the overall differences in cognition among older adults. Family socioeconomic status explained the largest share of differences among all considered childhood circumstances. Large disparities in cognition should be addressed by mitigating childhood disadvantages.

The lasting imprint of childhood disadvantage: cumulative histories of exposure to childhood adversity and trajectories of psychological distress in adulthood.

This study contributes to the literature on the long-term effects of childhood disadvantage on mental health by estimating the association between patterns of cumulative childhood adversity on trajectories of psychological distress in adulthood. There is little research that investigates how compositional variations in the accumulation of childhood adversity may initiate distinct processes of disadvantage and differentially shape trajectories of psychological distress across the adult life course. Using the Panel Study of Income Dynamics' Childhood Retrospective Circumstance Study and latent class analysis, we first identify distinct classes representing varied histories of exposure to childhood adversities using 25 indicators of adversity across multiple childhood domains. Next, the latent classes are included as predictors of trajectories of psychological distress in adulthood. The results demonstrate that patterns of experiences of childhood adversity are associated with higher levels of adult psychological distress that persists, and in some cases worsens, in adulthood, contributing to disparities in mental health across the life course.

Life-course socioeconomic circumstances in acute, chronic and disabling pain among young employees: a double suffering.

Pain is known to be socioeconomically patterned and associated with disability. However, knowledge is scarce concerning life-course socioeconomic circumstances and pain among young adults. Our aim was to examine the associations of childhood and current socioeconomic circumstances with acute pain and chronic pain with low and high disability levels among young Finnish municipal employees. We analysed questionnaire data retrieved from the Young Helsinki Health Study (n=4683) covering 18-39-year-old employees of the City of Helsinki, Finland. We included multiple indicators of childhood and current socioeconomic circumstances and examined their associations with acute pain and with chronic pain with low and high disability levels. The level of chronic pain-related disability was assessed by the chronic pain grade questionnaire. Multinomial logistic regression analyses were conducted with stepwise adjustments for sociodemographic, socioeconomic and health-related covariates. Childhood and current socioeconomic disadvantage were associated with acute and chronic pain, particularly with chronic pain with high disability level. The strongest associations after adjustments for covariates remained between chronic pain with high disability level and low educational level (odds ratio (OR) 3.38, 95% confidence interval (CI) 2.18-5.24), manual occupation (OR 3.75, 95% CI 1.92-7.34) and experiencing frequent economic difficulties (OR 3.07, 95% CI 2.00-4.70). Pain is a common complaint that contributes to disability among young employees, particularly the most socioeconomically vulnerable. There is a socioeconomic gradient in both pain chronicity and the level of chronic pain-related disability. Life-course socioeconomic factors should be considered in pain-preventing strategies and in clinical practice.

Associations Between Life-Course Socioeconomic Conditions and the Pace of Aging.

Socioeconomic disadvantage is a well-established predictor of morbidity and mortality, and is thought to accelerate the aging process. This study examined associations between life-course socioeconomic conditions and the Pace of Aging, a longitudinal measure of age-related physiological decline. Data were drawn from a Swiss population-based cohort of individuals originally recruited between 2003 and 2006, and followed up for 11 years (2 834 women, 2 475 men aged 35-75 years [mean 52]). Pace of Aging was measured using 3 repeated assessments of 12 biomarkers reflecting multiple body systems. Analysis tested associations of socioeconomic conditions with physiological status at baseline and with the Pace of Aging. Participants with more life-course socioeconomic disadvantage were physiologically older at baseline and experienced faster Pace of Aging. Effect sizes (β) for associations of childhood socioeconomic disadvantage with baseline physiological status ranged from 0.1 to 0.2; for adulthood socioeconomic disadvantage, effect sizes ranged from 0.2 to 0.3. Effect sizes were smaller for associations with the Pace of Aging (<0.05 for childhood disadvantage, 0.05-0.1 for adulthood disadvantage). Those who experienced disadvantaged socioeconomic conditions from childhood to adulthood aged 10% faster over the 11 years of follow-up as compared with those who experienced consistently advantaged socioeconomic conditions. Covariate adjustment for health behaviors attenuated associations, but most remained statistically significant. Socioeconomic inequalities contribute to a faster Pace of Aging, partly through differences in health behaviors. Intervention to slow aging in at-risk individuals is needed by midlife, before etiology of aging-related diseases become established.

Childhood Disadvantage and Later-Life Multimorbidity: Demonstrating Robustness Under Imperfect Identification

This study assesses the relationship between indicators of early childhood disadvantage and later-life multimorbidity within a nationally representative sample of Brazilians aged 50 and over (n = 9,412). Data come from the baseline assessment (2015/2016) of the Brazilian Longitudinal Study of Aging (ELSI). We employed survey-weighted Ordinary Least Squares regression to estimate the effects of individual and combined measures of childhood disadvantage on the total number of chronic conditions in later life. Mediation analysis assessed whether adult socioeconomic status (SES) mediated the relationship between childhood disadvantage and chronic conditions. We found that individual and combined measures of childhood disadvantage were associated with the total number of chronic conditions, even after controlling for potential confounders. Mediation analysis suggested that part of the effect of childhood adversity is mediated by higher SES in adulthood (~10%). A formal strategy of sensitivity analysis showed that omitted variable bias is extremely unlikely. To rule out the observed effect, an unobserved hypothetical confounder would need the explanatory power of the residual variance of both the independent and the dependent variables that is at least 30 times larger than that of BMI or 5 times larger than the explanatory power of age. Results should inform efforts to strengthen interventions targeting early childhood development and to improve other key inputs (such as education) to enhance adult SES and lessen the impact of early life stressors on health in older adulthood.

The Long-Term Impact of Childhood Disability on Mental Health in Mid- to Late-Adulthood

For decades, life course and stress process scholars have documented that negative, stressful experiences in childhood have consequences for health across the life course. One aspect of the childhood adversity that deserves more research attention is childhood disability. Children with disabilities experience higher levels of psychological distress compared to their peers and having a disability can negatively impact traditional markers of the transition to adulthood (e.g., education, employment, family status). At present, there is limited evidence regarding the impact of childhood disability on mental health over multiple years of adulthood. This study applies random effects models to nationally representative data from five waves (2008-2016) of the Health and Retirement Study (n=15,380; n=590 with a childhood disability), to examine how experiencing disability before the age of 16 shapes depressive symptoms over multiple years of adulthood. Given known gender differences in mental health, the models are stratified by gender to examine how the association between childhood disability and adult mental health varies by gender. Preliminary results suggest that experiencing a childhood disability is associated with different patterns of depressive symptoms in adulthood. Men who experienced childhood disability report more depressive symptoms in adulthood, net of sociodemographic, adult health, and childhood disadvantage covariates. Women who experienced childhood disability report more depressive symptoms in adulthood, net of all covariates except for childhood depression. Next steps are to conduct age-based growth curve models using Stata’s mixed function to estimate whether childhood disability influences baseline and growth of depressive symptoms in adulthood.

Cost-Effectiveness of Screening Preschool Children for Hearing Loss in Australia.

While all newborns in Australia are tested for congenital hearing loss through universal newborn hearing screening programs, some children will acquire hearing loss in their first five years of life. Delayed diagnosed or undiagnosed hearing loss in children can have substantial immediate- and long-term consequences. It can significantly reduce school readiness, language and communication development, social and emotional development, and mental health. It can also compromise lifetime educational achievements and employment opportunities and future economic contribution to society through lost productivity. The need for a universal hearing screening program for children entering their first year of primary school has been noted in two separate Australian Government hearing inquiries in the last decade. Sound Scouts is a hearing screening application (app) that tests for hearing loss in children using a tablet or mobile device, supervised by parents at home. It tests for sensorineural or permanent conductive hearing loss and central auditory processing disorder in children. In 2018 the Australian Government funded the roll-out of Sound Scouts to allow up to 600,000 children to test their hearing using Sound Scouts. This study estimated the cost-effectiveness of screening 5-year-old children for hearing loss using Sound Scouts at home, compared with no screening. A decision-analytic model was developed to estimate the incremental costs and quality-adjusted life years (QALYs) of administering Sound Scouts over a 20-year time horizon. Testing accuracy was based on comparing Sound Scouts test results to clinical test results while other parameters were based on published data. Costs were estimated from the perspective of the Australian health care system. Univariate and probabilistic sensitivity analyses were undertaken. Sound Scouts is estimated to result in an average incremental cost of A$61.02 and an average incremental increase in QALYs of 0.01. This resulted in an incremental cost-effectiveness ratio of A$5392 per QALY gained, which is likely to be considered cost-effective by Australian decision makers. Screening with Sound Scouts was found to have a 96.2 per cent probability of being cost-effective using a threshold of A$60,000 per QALY gained. Using Sound Scouts to screen five-year-old children for hearing loss (at home) is likely to be cost-effective. Screening children using Sound Scouts will result in early identification and intervention in childhood hearing loss, thereby reducing early childhood disadvantage through cumulative gains in quality of life, education, and economic outcomes over their lifetime.

Impact of urban birth and upbringing on expression of psychosis in a Chinese undergraduate population

BackgroundUrban birth and upbringing show consistent associations with psychotic illness but the key urban exposures remain unknown. Associations with psychotic-like experiences (PEs) are inconsistent. These could be confounded by common mental disorders associated with PEs. Furthermore, associations between PEs and urban exposures may not extrapolate to psychotic disorders such as schizophrenia.MethodsAnnual cross-sectional surveys among first year Chinese undergraduates 2014–2019 (n = 47,004). Self-reported, hierarchical categorisation of psychosis: from psychoticism, paranoid ideation, schizotypal symptoms, nuclear syndrome using SCL-90-R, to clinical diagnosis of schizophrenia. Depressive symptoms using PHQ 9. Dissociative symptoms and posttraumatic stress disorder (PTSD) measured using PCL-C. Etiological factors of family history and childhood disadvantage. We studied effects of urban birth, urban living and critical times of exposure in childhood on psychosis phenotypes.ResultsAssociations with urbanicity were found only after adjustments for depression. Urban birth was associated with paranoia (AOR 1.34, 1.18–1.53), schizotypal symptoms (AOR 1.59, 1.29–1.96), and schizophrenia (AOR 2.07, 1.10–3.87). The same phenotypes showed associations with urban residence > 10 years. Only schizophrenia showed an association with urban exposure birth-3 years (AOR 7.01, 1.90–25.86). Child maltreatment was associated with both psychosis and depression. Urbanicity measured across the total sample did not show any associations with demography, family history of psychosis, or child maltreatment. Sensitivity analysis additionally adjusting for dissociative symptoms and PTSD showed the same pattern of findings.ConclusionsUrban birth and urban living showed a hierarchical pattern of increasing associations from paranoid ideation to schizotypal disorder to schizophrenia, confirming that associations for psychotic experiences could be extrapolated to schizophrenia, but only after adjusting for confounding from depression, dissociative symptoms and PTSD. Several etiological factors were the same for psychosis and depression. Future studies of PEs should adjust for confounding from common mental disorders and dissociative symptoms. Effects of urbanicity on psychosis were not explained by demography, family history of mental disorder, or child maltreatment.

Life course socioeconomic position and DNA methylation age acceleration in mid-life

BackgroundAgeing biomarkers can help us better understand how well-established socioeconomic position (SEP) disparities in ageing occur. A promising new set of DNAm methylation (DNAm)-based ageing biomarkers indicate through their age...

Cumulative Childhood Adversity and Long-Term Educational Outcomes in Individuals with Out-of-Home Care Experience: Do Multiples Matter for a Population Defined by Adversity?

Abstract Previous research has demonstrated a graded relationship between cumulative childhood adversity and adverse later outcomes. Individuals with out-of-home care (OHC) experience constitute a population characterised by both childhood and educational disadvantages. Based on a fifty-year follow-up of a Stockholm cohort born in 1953, the purpose of this study was to examine the associations between cumulative childhood adversity and long-term educational outcomes in this group. The cumulative disadvantage perspective suggests that there would be a negative association, while the disadvantage saturation perspective implies that cumulative adversity would be less consequential for disadvantaged individuals. By means of multigroup path analysis, we furthermore asked whether this association may differ in relation to individuals with child welfare contact (CWC) and to the general population (GP). Adjusting for socioeconomic conditions and cognitive ability, cumulative childhood adversity had a negative influence on midlife educational attainment in the GP. However, it did not seem to influence the educational outcomes of neither OHC experienced individuals nor individuals with other types of CWC. The results of this study thus lend support to the disadvantage saturation perspective. Further studies are needed to explore this relationship.

1444Housing disadvantage in childhood and health: A systematic review

Abstract Background Housing has been recognised as one of the important determinants of health outcomes. However, little is known of the contribution of these pathways to children’s health and wellbeing and their pattern of health throughout life. This review aims to provide a synthesis of longitudinal studies linking experiences of disadvantaged housing in childhood to health outcomes. Methods A literature search was performed on four databases including Medline, EMBASE, PsycINFO, and Web of Science from 2000 to 2020. Peer-reviewed longitudinal studies assessing the association between housing disadvantage in childhood and subsequent physical and mental health were included. The methodological quality of selected studies was appraised using the ROBINS-I tool. A narrative synthesis was developed due to study heterogeneity. Results Forty-five cohort studies were included, and no randomised controlled trial met the inclusion criteria. The majority of the studies was evaluated to have a moderate risk of bias. Across the studies, while many relationships remained mixed, consistent evidence of detrimental impact was identified between: poor housing conditions and mortality; inadequate heating and respiratory illness; frequent residential moves and psychiatric mortality and morbidity. Little evidence is found between overcrowding in childhood and health outcomes. Conclusions Evidence from longitudinal studies indicates that poor housing experience in childhood may impact health later in life. Key messages The findings stressed housing as a key social determinant of child health, and interventions designed to mitigate housing disadvantage may have significant health gains across the life span

Invited Commentary: Is the Long Shadow of Childhood Disadvantage on Lifelong Health Getting Worse Over Time?

Social inequalities in health and their early-life origins have been extensively documented. Although the complex direct and intermediate mechanisms linking early-life disadvantage to later health are not yet fully understood, new findings on biological markers distinctly related with early-life experiences suggest a causal relationship. In this issue, Fuller-Rowell et al. (Am J Epidemiol. 2021:190(11):2284-2293) step back to examine the role of childhood disadvantage in the United States in different periods, observing that the relationship with later health seems to have strengthened over time. The main explanation the authors bring up has to do with increased income segregation and changes in labor market composition that limit opportunities for persons with low educational attainment. In other words, while the rich get richer, the poor get poorer, the middle class shrinks, and there are fewer interactions across different socioeconomic groups and the social ladder is blocked. Other evidence suggests that investments in children, through early education and academic support programs, could help reduce the consequences of childhood disadvantage on long-term health.

Fuller-Rowell et al. Respond to "The Long Shadow of Childhood Disadvantage".

Fuller-Rowell et al. Respond to "The Long Shadow of Childhood Disadvantage".

Growing Old Before Their Time: Measuring Aging.

In this issue of Pediatrics , Raffington et al1 describe an association between early childhood disadvantage and a measure of aging based on DNA methylation. Pediatricians will be intrigued by the concept that a genome-based measure can quantify and perhaps partially explain the well-known link between social equality and remote health effects, including obesity, hypertension, and cardiovascular disease, as well as an easily measured early predictor of whether an initiative to mitigate these morbidities is likely to be successful. Because some of the underlying biological concepts may not be familiar, it will be helpful to discuss DNA methylation and “methylation age.” The genetic code is embedded in the DNA sequence of the 4 canonical nucleobases: adenine, guanine, thymine, and cytosine. This sequence specifies the messenger RNA that codes proteins, several types of functionally active non–messenger RNAs, and diverse control and structural regions. DNA bases are also subject to chemical modification. The most relevant modification for this discussion is methylation of some cytosines (addition of CH3) to form 5-methylcytosine. Methylation of cytosine regulates the rate of RNA transcription and therefore regulates which proteins a cell expresses. During development, patterns of methylation change in a tissue-specific and age-dependent manner.2 … Address correspondence to Daniel A. Notterman, MD, MA, FAAP, Department of Molecular Biology, Princeton University, 219 Lewis Thomas Laboratory, Princeton, NJ 08544. E-mail: dan1{at}princeton.edu