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What have epidemiological studies in both the developed and developing worlds shown with regard to birthweight 4; 3-5
Lower birth weight is associated with increased risk in later life of (1) obesity, (2) CVD, and (3) metabolic syndrome (hypertension, insulin resistance, type 2 diabetes, dyslipidemia, and obesity)
(4) Impaired cognitive function
1. Define metabolic syndrome (symptoms - 4, increases risk of 3)
2. How does timing of nutritional constraint during pregnancy impact offspring? Periconceptually vs. later stages of gestation
1. Cluster of conditions - having at least 3 of the 5 following - hypertension, hyperglycemia, excess visceral body fat, high cholesterol, low HDL, that occur together increasing risk of CVD, stroke, and diabetes.
2. Periconceptual/first trimester of of pregnancy exposure - no reduced birth weights but as adults, had increased risk of obesity & CVD.
Later stages of gestation - reduced birth weights and increased incidence of insulin resistance and hypertension
1. What is the association bt overnutrition in pregnant mothers and risk of obesity/metabolic disorders of their offspring later in life?
2. Does this increased susceptibility to obesity later in life?
3. What has a similar impact? Leading to what? (4)
1. Overnutrition in early life can increase susceptibility to future obesity (U or J shaped relationships bt birth weight & obesity/insulin resistance later in life)
3. Maternal gestational diabetes.
(1) altered hypothalamic development (2) increased food intake and weight gain/obesity (3) insulin resistance (4) impaired ability to regulate appetite
1. What type of diet/"nutrition cues" have been shown to alter metabolic phenotypes (2)
2. What are implications of a protein-restricted diet as shown in rats?
3. What does this indicate? ^
1. Protein-restricted diets in mother scan lead to cardio-metabolic disease --> altered metabolic phenotype
(2) Over-rich early nutritional environment "cues" regulation of gene methylation, altering metabolic phenotype of offspring
2. Mothers fed protein-restricted (PR) diet from conception throughout pregnancy (and sometimes in lactation) have shown cardio-metabolic disease
Implications: (1) hypertension (2) increased fat deposition (3) altered feeding behavior (4) impaired glucose homeostasis (5) dyslipidemia (6) vascular dysfunction (7) impaired immunity (8) impaired susceptibility to oxidative stress
3. Even small variations in maternal diet can affect risk of disease in later life
1. What is epigenetics?
2. What is integral about epigenetics?
3. What are the major types of epigenetic proceses? (4)
1. "on top" of "genetics" --> refers to processes that induce heritable changes in gene expression without altering the gene sequence.
2. Determines when and where specific genes are expressed
3. DNA methylation (silencing), histone modification (acetylation; activating), microRNAs (silencing), chromatin remodeling
1. What is DNA methylation?
1.5 What are heritable changes in chromatin?
1.7. Describe histone acetylation & how it affects transcription.
2. Is the evidence strong to support that maternal diabetes increases the risk of type 2 diabetes in their offspring? What is the evidence?
3. What is the confounding variable of the relationship bt maternal diabetes & childhood BMI? (4)
1. Biochemical process that involves addition of a methyl group to the cytosine or adenine DNA nucleotides which silences gene expression
1.5. Heterochromatin - tightly packed, low tx activity; euchromatin - loosely packed --> high tx activity
1.7. Addition of acetyl groups to histone proteins, reducing positive charges that normally attract negatively charged DNA --> results in less tightly packed chromatin.
Deacetylation restores positive charge preventing tx.
2. Yes, Pima women with gestational diabetes had 6fold higher prevalence of type 2 diabetes in their children.
3. Maternal BMI --> frequently retrospective cohorts, no controls, and paternal data is absent.
1. What have animal models shown us the fetal programming of diabetes in offspring? (4)
2. What is the thrifty gene hypothesis?
3. How is the above illustrated by Pima Indians? (4 arrows)
4. What is the estimated contribution of genetics to obesity?
1. Offspring is more likely to be obese - hyperphagic, abnormal beta cell function, hypothalamus malformations
2. Some people are genetically predisposed to obesity (fat-storing genes), which was advantageous in scarce times.
3. Pima Indians were once a very active hunter-gatherer group with limited food source ---> genes adapted to cause them to carry more body fat with less food --> trait is disadvantage now that they are sedentary & food is plentiful --> they're obese .
4. The estimated genetic contribution to obesity is less than 25%
1. What is fetal programming?
2. How does the Dutch Winter Hunger illustrate this concept?
3. What is the thrifty phenotype hypothesis?
4. What is the thrifty genotype hypothesis?
5. What does the Dutch Winter Hunger demonstrate?
6. What is the difference between the thrifty phenotype and genotype hypothesis?
1. In utero is important time for forming epigenetic patterns --> environmental conditions during pregnancy (esp during ontogenic windows) have long-term effects on adult health.
2. Serves as natural epidemiological study to examine effects of maternal undernutrition during different gestational stages.
Supports fetal programming hypothesis in that maternal undernutrition leads to lower birth weight due to restricted intrauterine conditions --> leads to higher risk of chronic conditions in adult life.
3. Conditions during pregnancy will have a long-term effect on adult health.
4. Some people are genetically predisposed to obesity (fat-storing genes), which was advantageous in scarce times.
5. Thrifty phenotype
6. Thrifty genotype refers to evolved trait within the genome. Thrifty phenotype hypothesis works on the individual/epigenetic level and refers to the intrauterine environment.
1. What are the effects of overnutrition in a mother on fetal programming? (7)
2. Describe the proposed mechanisms of how maternal exposure leads to fetal obesity (2)
1. High BW, defective beta cells, increased adiposity, altered hypothalamic development, hypertension, impaired insulin signaling --> fatty liver/skeletal muscle impairments.
- No definitive studies on mechanisms --> instead most focus on developmental changes in hypothalamic circuits regulating body weight.
(1) High fat diets/obesity leads to oxidative stress which leads to impaired placental function OR (2) increased energy leads to increased fetal insulin production which leads to increased adipogenesis.
1. Describe the phenomenon referred to as nutrition transition
2. Why do women in less affluent societies have smaller changes in body composition?
3. Why do women in both affluent and less affluent societies experience only moderate weight loss after pregnancy? (2)
4. In other countries, season appears to have an important effect on birth weight? What are possible mechs for this effect? (2)
1. Shift in country form state of undernourished (high communicable disease prevalence) to overnourished (chronic disease prevalence)
2. They tend to gain much less weight due to available food and energy
3. Tendency for higher dietary intake and less exercise after pregnancy; physiologically reinforced to keep fat for purposes of lactation
4. (1) Larger issue in less affluent societies - time of harvest allows for maternal nutrition/physical activity --> available calories for child; (2) Seasonality also impacts infectious disease
1. How can researchers assess development at 18 months (Oken - maternal fish intake)?
2. What was Oken et al's major finding about the relation bt maternal fish intake and childhood development?
3. What was the relation of longer breastfeeding to child development?
1. Mothers were surveyed about whether child could perform specific tasks
2. Both maternal fish intake & breastfeeding duratino led to higher development scores but factors were DEPENDENT on each other (required both!!!)
3. Longer breastfeeding --> higher development scores
Olsen et al --> exercise in pregnancy
1. What are the weekly exercise guidelines for women published by American College of Obstetricians and Gynecologists?
2. What types of exercises should be avoided any why?
3. Describe physiological changes that occur during pregnancy? (8)
1. 30 min of moderate exercise on mst, if not all, days of the week
2. Activities with high risk of falling/trauma (as well as scuba diving)
3. (1) Heart displacement (2) increased cardiac output for uteroplacental circulation (3) drop in systemic blood BP in 2nd trimester (4) increased blood volume due to increased RBCs (5) increased weight/length of kindeys (6) Displaced bladder (7) relaxed tendons (8) Tissue swelling
1. Describe the typical average weight and loss pattern in pregnancy (3)
2. What makes up the weight gain during pregnancy? 8 What is the largest source?
3. What is the recommended weight gain for underweight <18.5, normal weight, overweight, and obese women?
1. Steady linear increase in body weight until delivery (9 months) ----> rapid decrease in weight due to baby being born --> gradual loss of residual weight during lactation (highly variable)
- 2. Maternal stores (fat; 25%), tissue fluid )10%), blood, uterus/breasts (10%), fetus/placenta/amniotic fluid (45-50%)
1. What is the relationship between maternal weight gain and birth weight? 2
2. Why does birth weight matter? 6. What weight is best?
3. How does maternal weight affect baby mortality?
4. What is LGA? What is SGA? Define. Can a preterm baby be LGA?
1. Birth weight is directly correlated with maternal weight gain AND pre-pregancy weight (increased BMI/weight gain --> increased birth weight)
2. Higher BW reduces newborn mortality (lowest mortality rates are in infants within 4000-4500 g). Protects against hospitalization, respiratory distress, CNS viral infections, bacterial meningitis, diarrhea. Higher IQ at age 7, MODERATE WEIGHT.
3. Although high birth weight is generally protective, obese/overweight mothers also tend to have worse birth weight/mortality outcomes.
4. Large Gestational Age (over 90th percentile), Small Gestational Age (less than 10th percentile) --> yes.
1. Are heavier babies likely to be overweight adults?
2. Does birth weight correlate with weight in childhood?
3. What correlates with each other at birth and childhood?
4. What correlates at birth and adulthood? 2
5. What does increased BW generally do? 4
1. There is a stronger correlation bt higher weight-for-length at 6 months and adult obesity (vs. weight-for-length at birth!)
3. % body fat
4. Higher BW & increased fat-free mass; high BW and least amount visceral body fat
5. Lowers metabolic risk (glucose tolerance, systolic BP, 2-hr insulin levels)
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