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Childhood Matters: Health and Early Childhood Experiences. Michael Gardner MD, MPH Hillcrest Chairman and Professor of Obstetrics and Gynecology School of Community Medicine Jennifer Hays-Grudo, PhD George Kaiser Family Foundation Chair in Community Medicine Professor of Internal Medicine
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Childhood Matters: Health and Early Childhood Experiences Michael Gardner MD, MPH Hillcrest Chairman and Professor of Obstetrics and Gynecology School of Community Medicine Jennifer Hays-Grudo, PhD George Kaiser Family Foundation Chair in Community Medicine Professor of Internal Medicine School of Community Medicine
Developmental Origins of Adult Health and Disease (DOHaD) • Barker hypothesis(Barker & Osmond, 1986; Barker, 1995) • Fetal undernutrition associated with adult obesity, CVD and type II diabetes (Law et al., 1992; Sayer et al., 2004) • Fetal undernutrition + rapid “catch-up growth” (Ong, 2006; Stettler et al., 2003, 2005) • Thrifty phenotype(Hales & Barker, 2001) • Adaptive response for deprived pretnatal environment maladaptive for postnatal environment • Developmental Origins of Adult Health and Disease (DOHaD)(Gluckman et al 2005; Taylor & Poston, 2007) • Fetal environment either nutritionally deprived or over-rich increases risk for child and adult obesity and its sequelae(Catalano, 2003; Oken & Gillman, 2003; Ehrenberg et al., 2004)
Barker Hypothesis Based on medical archives from Preston, Hertfordshire, and Sheffield, England 16,000 men and women born in Hertfordshire, 1911- 1930: ● 2-fold increase in coronary heart disease from largest to smallest BW ● Impaired GT increased from 14% to 40% Barker, et al ClinSci 1998; 115:118
Death Rates From Coronary Artery Disease According to Birthweight
Prevelance of Type II DM and Impaired Glucose Tolerance in Men Age 59-70
The Nurses Health Study ● 121,701 RNs aged 30 - 55 yrs, followed since 1976 ● BW self-reported, validated by birth certificate Rich-Edwards, et al BMJ 1997; 315:396
The Nurses Health Study Rich-Edwards, et al BMJ 1997; 315:396
Thrifty Phenotype Hypothesis During periods of starvation, the fetus reduces insulin secretion, and increases peripheral insulin resistance, thus directing more glucose to the brain and heart, and less to skeletal muscle, etc. Hales and Barker Diabetologica 1992; 35: 595
What happens inside matters outside • Antenatal stress associated with: • Decreased cognitive function • Quebec Ice Storm -1998 - loss of electricity & water for up to 5 weeks • Children had lower MDI scores • Lower language development scores • These held when controlling for Ob complications, birth weight , post partum depression (LaPlante et al, 2004) • Maternal exposure to traumatic events associated with: • Schizophrenia (OR – 1.5 in cohort from Dutch famine) • Depression in adulthood
Chinese FamineRate of Schizophrenia Proportion of familial cases unchanged (17-18%) St. Clair, et al JAMA 2005; 294:557
Childhood behaviors – Mom’s input • In pregnant women in the top 15% of symptoms of anxiety at 32 weeks • Children had double the risk of behavioral problems at age 4 and 7 • Higher risk for ADHD, depression or conduct disorders • Attributable risk may be as high as 15% • If true – economic consequences for special education and even incarceration are stunning • annual societal ‘‘cost of illness’’ for ADHD is estimated to be between $36 and $52 billion – prenatal stress accounting for $5-7 billion per year
How? • Epigenetic modifications represent a potential way that “metabolic programming” occurs • Alteration in the hypothalamic-pituitary-adrenal axis involving: • Mobilizing energy stores • Response to stress • Inhibiting inflammatory responses during stress • Post natal stress is cumulative with prenatal stress leading to increased vulnerability to stressors • Prenatal stress can lead to impaired fetal growth • Attention disorders and increased anxiety observed
Metabolic “Programming” via Genetic Imprinting ● Imprinting turns gene off ● Gene dosage effect- only one gene operational ● Some imprinting reflects gender of transmitting parent ● Many imprinted genes involve metabolism i.e. Igf 2 , Igf 2r, H19
Tulsa - We’re Number 1!! • Statistics published in Newsweek • Tulsa, Oklahoma Smokers: 24.6% Cigarettes per day: 16.2 Tried to quit with gum: 26.9% Tried to quit with patch: 32.8% Tried to quit with support program: 7.4%
Smoking in Pregnancy • Decreased fetal growth • Increase in Preterm Birth • Increase in placental abruption
Children Born with IUGR (< 2.5K): ↓ Nephron number Fewer glomeruli ↓ Renal volumes Adult glomeruli : 1,400,000 / kidney in controls 700,000 / kidney in HTN Rostand NepholDial Transplant 2003; 18:1434
Smoking effects • Children exposed to tobacco prenatally: • Decreased memory skills at age 6 • Deficits in auditory processing • Effects more pronounced then children who were exposed prenatally only to marijuana smoking (those children have decreased “executive function”)
Alcohol Fetal Alcohol Syndrome – associated with 6 or more drinks per day Leads to neurologic impairment Post natal growth restriction Microcephaly
Alcohol – other effects alcohol ingestion during pregnancy represents a risk factor in terms of later alcohol-related problems in offspring hypothesis that low to moderate levels of maternal ethanol intoxication during late pregnancy set the opportunity for fetal learning about ethanol
Meth exposure Meth-exposed children scored lower on measures of visual motor integration, attention, verbal memory and long-term spatial memory children exposed to Meth prenatally exhibit smaller subcortical volumes
Maternal Obesity • Higher rates of macrosomia • Higher rates of pregnancy induced hypertension • Higher rates of Gestational Diabetes (a precursor for Type 2 DM)
DULCE Program • Provides culturally competent group prenatal care for Diabetic mothers • Education emphasizes diet and life style changes (i.e. just a 20 minute walk a day can smooth out blood sugars) • Teaches self reliance in managing DM • Early review of findings shows a decrease in LGA babies in the Group prenatal care as compared to traditional care
SUMMARY ●The intrauterine environment exerts a permanent influence on postnatal metabolism and growth ●The mother’s fetal life can affect the development of her own offspring ●Influential factors include calories, content of diet, micronutrients, stressors
Two complementary theories • Critical periods (latency model) • Barker hypothesis • Organogenesis • Fewer beta cells in pancreas – type 2 diabetes • Fewer nephrons - hypertension • Cumulative experiences (pathways model) • Allostasis and allostatic load • Behavioral responses
Poverty and health Childhood SES Critical periods Adult SES Accumulation of insults Childhood health Adult health Conroy K et al. JDBP 2010;31:154-160
Allostasis and Allostatic Load The stress response and development of allostatic load are illustrated. Perception of stress is influenced by one’s experiences, genetics, and behavior. When the brain perceives an experience as stressful, physiologic and behavioral responses are initiated leading to allostasis and adaptation. Over time, allostatic load can accumulate, and the overexposure to neural, endocrine, and immune stress mediators can have adverse effects on various organ systems, leading to disease. McEwen 1998
Adverse Childhood Experiences (ACE) study • Felitti V, Anda R et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. Am J Prev Med 1998;14:245-258. • 9,508 Kaiser-Permanente adults • 7 categories of childhood exposure • Abuse: psychological, physical, sexual • Dysfunction: substance abuse, mental illness, domestic violence, criminality • 10 health risk factors • Smoking, obesity, inactivity, depressed mood, suicide attempts, alcoholism, drug abuse, parenteral drug abuse, >50 sexual partners, history of STDs. • Disease conditions: • Ischemic heart disease, cancer, stroke, COPD, diabetes, hepatitis, skeletal fractures, general health rating
ACE results • Childhood stressors linked to adult health risk behaviors • Childhood stressors linked to disease conditions (OR) diabetes (1.6), COPD (3.9), fractures (1.6), hepatitis (2.3), self-rated poor health (2.2) • Strong dose-response relationship between number of childhood stressors and each of 10 behavioral RFs (p<.05) and for heart disease, cancer, COPD, hepatitis, fractures, poor self-rated health (not for stroke or diabetes).
More recent follow-up At least 1 ACE was reported by 64% of respondents. For persons with ≥ 4 ACEs, the risk of panic reactions, depressed affect, anxiety, and hallucinations were increased 2.5-, 3.6-, 2.4 and 2.7-fold, respectively The mean number of comorbid outcomes in the study sample was 2.1 (range: 0–14); means are adjusted for age, sex, race, and educational attainment. The trend in the means is significant (P<0.0001); vertical error bars represent 95% confidence intervals Anda et al Eur Arch Psychiatry ClinNeurosci (2006) 256 : 174–186
Implications of ACE Study “Clearly, further research and training are needed to help medical and public health practitioners understand how social, emotional, and medical problems are linked throughout the lifespan. Such research and training would provide physicians with the confidence and skills to inquire and respond to patients who acknowledge these types of childhood exposures. The magnitude of the difficulty of introducing the requisite changes into medical and public health research, education, and practice can be offset only by the magnitude of the implications that these changes have for improving the health of the nation.” Felitti et al.. Am J Prev Med 1998;14:245-258.
Health and stress in Tulsa families Tulsa Educare – 2 sites Yearly parent interviews at • Child’s health • “What happened to you last year” – 18 items 247 parents Interviews conducted by family support specialists Data analyzed for links to child health • Health issues • Allergies • Asthma • Eczema • Obesity (0) • 4 categories of stressors • Financial • Relationship • ACE • Life Changes
Preschool health by demographics *95 of the 105 Hispanic parents selected race as “other”
Family stress and child health 81% of healthy children had at least one stressor (M=2.6 [SD=2.4]) 95% of children with a health problem had at least one stressor (M=3.5 [SD=2.3]) (all p values < 0.05)
Health problem by stress category • Children with asthma, allergies and eczema were more likely to have experienced a family stress in the past year • Children with health problems were more likely to have stressors from multiple categories (2.1) than healthy children (1.5)
Tulsa Children’s Project • Based at Tulsa Educare • Community-based participatory research • Multiple partners • Interdisciplinary design • Highly integrated set of interventions • Funded by George Kaiser Family Foundation http://youtu.be/3AKYdr2VGxo
Caren Calhoun, Vicki Wolfe Master Teachers Jack Shonkoff Bill Beardslee Snow, Yoshikawa Ruth Slocum Elizabeth Miranda Chris King Bob Glover Jennifer Hays-Grudo Jerry Root JuellHomco Julie Miller-Cribbs Natalie O’ReilleyTrishia Pratt Candice Weed Diane Horm, Lisa Monroe TCP Partners Annie Van Hanken Monica Basu
Intervention Model Children prepared to succeed in school (foundation for life-long success) Low-income families Education Children (0-5) enrolled in Tulsa Educare Medical Home Nutrition Physical activity Health Early Childhood Education Healthy Competent Children in Healthy Competent Families Social- Emotional Health Low-opportunity communities EduCareers: Adult Education and Workforce Training Parents actively improving their own & their children’s life circumstances Economic security Reduction in inter-generational poverty Current Situation Short-term outcomes Long-term outcome Intervention
Integrated components • Improve quality of classroom experience • Enhance curriculum and • Professional development for teachers and staff • Provide opportunities for parents • Adult education • Workforce training • Promote physical health • Health promotion for parents and staff • Improved access to care through on-site clinic
Early Childhood Education • Developed and implemented new curriculum – Catherine Snow from Harvard Graduate School of Education • Conducted monthly full or half-day professional development sessions with master teachers and Harvard consultants • Assisted teachers in developing plans for improved outdoor play program Expected long-term outcomes: • improved language skills in children • improved effectiveness in teachers