Fetal Programming In Humans Flashcards
Definition in developmental programming?
The process through which a stimulus or insult establishes a permanent response
Exposure during a critical period in development may influence later metabolic or physiological functions in adult life
What does low birth weight predict in later life?
Hypertension
coronary heart disease and stroke
insulin resistance
adult obesity
dyslipidaemia
Asthma
Immune dysfunction
Chronic renal failure
Raised cholesterol, cortisol and fibronectin
Neurological disease
Osteoporosis
•studies showed low BW displayed lower stiffness index in adults.
Barker hypothesis of impaired feral growth?
Adverse in utero environment
Impaired—>
Fetal Growth (critical periods)—>
Structural Change within Organs—>
Both poor childhood growth (catch up growth) and Metabolic and endocrine dysfunction—>
All leading to disease in later life.
How did the Dutch famine affect gestation?
Daily rations cut to 400-800kcal (Dec-April)
Exposure to famine in mid or late gestation=
• impaired glucose tolerance
Exposure to famine in early gestation=
• atherogenic lipid profile
• obesity
• increased risk of CHD
What is the thrifty phenotype hypothesis?
The ‘thrifty phenotype hypothesis’ suggests that growth restriction/malnutrition in utero leads to fetal adaptations which favour post natal survival in a similarly deprived environment, and that disease ensues when the diet is ‘richer’ than that anticipated.
Benefits of breast feeding?
WHO estimates 22% reduction in overweight
Beneficial effect of breastfeeding may be due to:
- Reduced intake compared to bottle-fed babies
- Slower weight gain in breast-fed babies
- Milk-borne hormones may be protective (leptin/insulin)
- Composition of formula (high protein) affects growth
- Formulations with lower protein content are now more common and may reduce the estimated benefit of breast milk
High intake of protein postnatal is bad because?
High plasma and tissue levels of insulin oceanic amino acids—>
Enhanced secretion of insulin and IGF1—>
Weight gain up to 2 years and adipose is activity—>
Long term risk of obesity and associated disorders.
Inheritance of obesity?
Estimates of heritability from twin studies= up to 50%
Common ‘Obesity’ - polygenic disorder with no observable simple Mendelian genetics
Childhood obesity – susceptibility is dependent on gene- environment interactions e.g. nutrition
Common variants of the FTO gene (Fat Mass and Obesity- associated gene) and genetic variants in LEPR, MC4R and MC3R involved in satiety
Currently known common genetic variants fail to predict childhood obesity in birth cohorts
What is trans generational acceleration of obesity?
Maternal obesity—>
Increased glucose, insulin, lepton, lipids and inflammatory response—>
Feral macrosomia. Persistently altered energy balance—>
Childhood and adulthood obesity—>
CYCLE REPEATS and accelerates.
Risks associated with maternal obesity?
Hypertensive disorders
Gestational diabetes mellitus (GDM)
Obesity
Thromboembolic events
Caesarean section
Evidence for persistent metabolic and cardiovascular effects on the offspring.
Interventions in prenatal to reduce offspring obesity?
Reducing low birthweight -refractory to nutritional intervention.
Reducing post-natal weight gain- more amenable to intervention?=
• Promotion of breast feeding versus formula.
• New International Child Growth standards (WHO 2006)- adopts the breast fed child as the normative - alerting health professionals to early weight gain.
Formula feed composition=
At 2 years infants on the lower protein had lower BMI- not different from breast fed babies
Interventions in obese pregnant woman?
No random controlled test has randomized women to either weight loss or normal care prior to or during pregnancy- to study effects on childhood obesity.
Some evidence for benefits of weight loss prior to pregnancy:
• obese women undergoing bariatric surgery for weight loss
• 3 fold reduction in prevalence of obesity compared to siblings born prior to weight loss
• in utero environment rather than a genetic influence on offspring obesity risk.
Affects in children born after maternal weight loss surgery?
- Greater insulin sensitivity
- Improved lipid profile
- Lower C reactive protein
- Increased ghrelin
Why use animal models to study mechanisms of Developmental Programming?
- Mice, rats, and humans share all but 1% of each other’s genes
- Reduce possible genetic influence
- Relatively quick life cycle
- Environment can be tightly controlled
- Enable different diets to be tested
- Investigate critical periods in development
Leptin in development?
Exogenous leptin rescues arcuate nucleus development in neonatal but not adult ob/ob (leptin deficient) mice.
Leptin is a satiety factor released from adipocytes, this maintains metabolic activity.
High weight gain in pregnancy and lactation can lead to feral hyperleptinaemia, leading to selective leptin resistance—>
This will lower metabolic action leading to hyperphagia and obesity.
It will also increases SNS activity and cause hypertension.
