SM_188b: Fetal Origins of Disease Flashcards
Developmental Origins of Health and Disease Paradigm (DOHaD) includes ___, ___, ___, and ___
Developmental Origins of Health and Disease Paradigm (DOHaD) includes fetail origins of adult disease, thrifty phenotype, fuel-mediated teratogenesis, and developmental overnutrition
Low birth weight is associated with ____ and ____
Low birth weight is associated with increased death rate from coronary artery disease and increased risk of HTN and T2DM
- Early life events determine, in part, later disease development and mortality
Prenatal factors such as ____, ____, and ____ affect postnatal onset of cardiovascular diseases, neurological diseases, and metabolic diseases
Prenatal factors such as maternal fuels, maternal stress, and obstetric diseases affect postnatal onset of cardiovascular diseases, neurological diseases, and metabolic diseases
- Maternal fuels: glucose, lipids, amino acids
Epigenetics is ___
Epigenetics is study of changes in gene function without changes to DNA sequence
- Identical twins: same genome yet epigenomes vary due to differental environmental exposures while in the womb
- Variance in susceptibility to adult diseases
Undernutrition leads to ____
Undernutrition leads to nutrient-mediated teratogenesis
Overnutrition leads to ____
Overnutrition leads to fuel-mediated teratogenesis
Teratogenesis is ___
Teratogenesis is developmental disruption (harm to fetus)
- Ex: fetal alcohol syndrome, drugs, infections
Developmental plasticity is ____
Developmental plasticity is developmental adaptation
(biological programming may induce a survival advantage)
Describe fetal alcohol syndrome
Fetal alcohol syndrome
- Dose-reponse effect
- Few gyri
- 1st trimester: birth defects, malformations
- 3rd trimester: CNS abnormalities (cognitive and behavioral)
Fetal alcohol syndrome in the 1st trimester presents with ____ and ____
Fetal alcohol syndrome in the 1st trimester presents with birth defects and malformations
Fetal alcohol syndrome in the 3rd trimester presents with ____
Fetal alcohol syndrome in the 3rd trimester presents with CNS abnormalities (cognitive and behavioral)
Fetal alcohol syndrome brain has ___ gyri
Fetal alcohol syndrome brain has few gyri
- Folding of gyri in fetal brain occurs late in gestation
- Lack of folding is a mechanism underlying developmental delays, behavioral and cognitive impairments
Plasticity is ___
Plasticity is developmental adaptation
(abnormal body composition -> small baby)
Describe utero-placental insufficiency
Utero-placental insufficiency
- Placental blood flow is the only source of nutrition to the fetus
- Multiple causes: placental defects (2-vessel cord), maternal cord
- Pathophysiology: uterine ligation, protein restriction, total caloric restriction
Describe intrauterine growth restriction
Intrauterine growth restriction
- Intrauterine growth restriction
- Developmental programming of glucose and insulin metabolism: adaptations to adverse intrauterine conditions
- Increased adult risk for diabetes, cardiovascular disease, obesity
Describe the thrifty phenotype hypothesis
Thrifty phenotype hypothesis
- Maternal or placental abnormalities
- Fetal malnutrition (especially amino acids)
- Decrease beta cell mass or islet function
- Decreased fetal growth
- Infant malnutrition
- Decreased adult beta cell function
- Non-insulin dependent diabetes
- Metabolic syndrome
Thrifty phenotype occurs due to ___
Thrifty phenotype occurs due to mismatch between uterine environment (maternal undernutrition) and childhood environment
- Famine exposure
- Timing of maternal exposure is important
Intrauterine growth restriction can occur in the setting of infection, preeclampsia, pregnancy-induced hypertension, smoking, and multiples (twins, triplets). The common mechanism of these conditions leading to intrauterine growth restriction is ____
Intrauterine growth restriction can occur in the setting of infection, preeclampsia, pregnancy-induced hypertension, smoking, and multiples (twins, triplets). The common mechanism of these conditions leading to intrauterine growth restriction is placental insufficiency
Diabetes in pregnancy causes ___ and ___
Diabetes in pregnancy causes fuel-mediated teratogenesis and developmental overnutrition
Describe the pathophysiology of diabetes in pregnancy
Pathophysiology of diabetes in pregnancy
- Mother: decreased insulin
- Mother: increased plasma glucose, amino acids, lipids
- Placenta
- Fetus neonate: mixed nutrients
- Fetus neonate: increased insukin
- Macrosmia and hypoglycemia (fetus neonate) and obesity and impaired glucose tolerance (child)
- Diabetes mellitus
Insulin production starts to ramp up before ___
Insulin production starts to ramp up before delivery
(gestational diabetes: less insulin)
Describe diabetes in pregnancy
Diabetes in pregnancy
- Type 1 diabetes = hyperglycemia in 1st trimester
- Impaired organesis
- Congenital abnormalities
- 3% develop congenital cardiac anomalies
- Other anomalies: TE fistula, duodenal atresia, renal agenesis, NTDs
Type 1 diabetes is associated with ____
Type 1 diabetes is associated with hyperglycemia in 1st trimester
Gestational diabetes mellitus results in ___
Gestational diabetes mellitus results in developmental overnutrition
- Poorly controlled diabetes -> worse outcomes
Describe risk factors for gestational diabetes
Risk factors for gestational diabetes
- Maternal age > 35
- Overweight / obese maternal BMI
- FMHx of diabetes
- Parity of 2 or more
- Asian ethnic groups
Gestational diabetes can lead to ____ or ____
Gestational diabetes can lead to fetal demise or jaundice of the baby
____, ____, and ____ are maternal fuels that cross the placenta to the developing fetus
Glucose, amino acids, and lipids are maternal fuels that cross the placenta to the developing fetus
(insulin does NOT)
Insulin is a ___
Insulin is a growth factor
Fetal hyperinsulinemia involves ____, leading to ____ and ____
Fetal hyperinsulinemia involves insulin binding IGF-1 receptor with as much affinity as insulin receptor in utero, leading to fetal growth / macrosmia and large for gestational age
Describe phenotype of offspring of gestational diabetes mother
Phenotype of offspring of gestational diabetes mother
- Large for gestational age / macrosmia = birthweight > 4 kg
- Higher amounts of adipose tissue at birth
- Long-term follow-up studies
Infants exposed to diabetes in utero have ____ BMI
Infants exposed to diabetes in utero have higher BMI
Describe T2DM in children
T2DM in children
- More severe, more rapid beta cell deterioration
- Less insulin sensitive, even post0puberty
- Earlier disease complications
- Poor treatment options
Describe large birth weight
Large birth weight
- Risk factor for obesity in childhood
- Fatness at birth prediposes to fatness throughout life
- Mechanism: fetal hypothalamus / neuroendocrine systems, energy balance / satiety
Mechanism underlying excessive fetal growth in pregnancies complicated by gestational diabetes mellitus is ___
Mechanism underlying excessive fetal growth in pregnancies complicated by gestational diabetes mellitus is fetal insulin binds IGF-1 receptors with high affinity
Describe obesity in pregnancy
Obesity in pregnancy
- Common
- Pregnancy complications: HTN, hyperglycemia, insulin resistance, risk of operative delivery
- Large for gestational age neonates
- Increases adiposity at birth and childhood
- Increased risk of childhood obesity
Developmental origins of disease affects ____, ____, and ____
Developmental origins of disease affects lung development, endocrine-disrupting chemicals, and fetal neurodevelopment
- Allergy / asthma / atopy: environmental exposures in utero influence development of respiratory and immune systems, abnormal lung / immune system development, asthma risk
- Endocrine-disrupting chemicals: exposures linked to metabolic disease, sensitive period (conception to birth = cellular replication and differentiation)
- Fetal neurodevelopment: perinatal anxiety / depression / stress, increased inattentiveness / hyperactivity in boys, autism-like traits
