Fetal Growth and Nutrition Flashcards
Problems small Babies Face (small because they’re preterm or due to growth restrictions)
- 30% neonatal admissions
- Lower IQ (~8 point)
- perinatal morbity
- Inattention, hyperacitvity, behavioural problems
- 20% of adult short stature
- Lower income
- Increased adult non-communicable diseases
How does low fetal growth affect stillbirth?
Suboptimal fetal growth is a major risk factor for still birth
30-50% stillborn babies are small
often not identified before birth in over 85% cases
Because Placental insuffciency plays a key role in both fetal growth restriction and stillbirth
What is term gestation?
Post menstrual weeks (so if it’s IVF add 14 days to that)
Pre-term: before 37 weeks
Term: Is still from 37 weeks
- 37 is no longer the ‘normal’ and the lowest risk for babies was to be born 39-40 weeks. **babies born at 37 weeks have high admission rates for respiratory distress, and this increases due to caserean
- Early Term: 37-38wks
- Full Term: 39 onwards
What are the varying ranges for birth size?
Birth weight and weight for gestation?
Weight:
- Low Birth weight (LBW) <2500g
- Very Low Birth Weight (VLBW) <1500g
- Extremely Low Birth Weight (ELBW) <1000g
- macrosomia >4500g
***lower limit for survival; <450g
Weight for Gestation
- Appropriate for gestational age (AGA) 10-90th centile
- Small for Gestational Age (SGA) <10th centile
- Large for Gestational age (LGA) >90th centile
Whats the issue with using a population reference for birth weight centile?
What are the other/better options?
- Takes all the birthweights ffrom babies born at different gestations.*
- Not that great because preterm centiles are actually too small! Because many, if not all have growth restrictions to some degree.*
Population Standard: doesn’t have enough preterms so not enough info.
Customised Birthweight**: model expected fetal growth velocity due to mum.
What is fetal growth?
An increase in body size and mass from the end of organogenesis (so starts around 8-10 weeks)
- Hyperplasia oG → Hypertrophy fetal growth
- Mean weigth gain 16-17g/kd/day
Continues quite steadily to term, (don’t be confused by artifacts in fetal gowth charts)
Why is this concept of ‘Hyperplasia vs hypertrophy’ so important?
Your most important organs (heart, kidneys, skeletal muscle) have cell numbers that are determined before you are born.
- No more nephrons, cardiac fibres and skeletal muscle fibres have a set number determined by or shortly after birth
- Also Pancreatic Beta Cells have no more increase shortly after birth
- This means that fetal growth determines most of metabolic Capacity!
What determines metabolic capacity someone has?
Mainly fetal growth at beginning of life, determines how your metabolism is going to function for the rest of your life.
If you get disease: depends on the Metabolic load you place on the capacity you’ve created.
Metabolic Load: can be affecte by weight, diet, smoking, exercise/loading → increases metabolic Load → can lead to chronic disease.
Rapid infant growth → exacerbates metabolic load
Poor infant Gorwth → constrains metabolic capacity
What is Fetal Growth Restriction?
What is it usually due to?
What is FGR a key risk factor for?
- When your ‘in-utero’ growth is limited by pathological process
Decreased accretion of fat and lean tissue, as well as skeletal growth if severe enough. (SO in extreme cases they’ll be short)
- Pretty hard to define
- Most cases due to poor placentation
- Key Risk Factor for: stillbirth, neonatal death, asphyxia
What is the difference between FGR and SGA?
Describe the growth journey’s babies A,B,C,D take
They do not mean the same thing!
- Although many SGA babies have growth restrictions, but not all
- There’s more growth restriction then small babies
- You can be growth restricted, but still within a normal Gestational weight
- *A**: Has had significant late growth restriction, and ended up an average size (should’ve be larger)
- *B**: Has a mild insult earlier in pregnancy, gradual slowing of growth, would be hard to spot
- *C**: normal baby with healthy growth
- *D**: poor early growth, then significant insult to growth, then a catch up
What does this graph tell us about.
Babies at term divided into four groups.
- The most severely GR babies are small on both the population and customised data; SGA IG21 and Cust
- 3x risk of having neonatal problems; NN admission, ventilatin, death
- Babies small on IG21 population but not on Cust are actually not at higher risk of neonatal issue
- SGA babies only on cust do have an increased risk
What’s the 10th centile and why do we use it?
- The 10th centile is good at picking up babies who may have problems at birth
FGR is common in pre-term babies (37-38weeks).
Eg; baby D, who had sever growth restrictions, still fell within the normal range, but has a lot of growth issues
Babies with growth restrictions are more likely to be born early.
Shown by birth dates of Preterm babies, there’s a left handed skew showing Preterm babies having more growth restrictions
- Around 1/4 preterm babies are growth restricted.
What are the tree key determinants of Fetal Growth?
- Genetics
- Hormones
- Nutrition: the most important!
What is the embryo’s nutrition before the placenta proper is formed?
- Initially the embryo is supported from endometrial gland secretions
- Rich in Carbohydrates and Lipids
- Growth of the embryo and chorionic sac is consistent and “autonomous”
- Why Dating via US is better/more accurate earlier on
- This is a period of Organogenesis
- when all the organs are formed
Maternal-Placental Circulation is established by _____?
What does this entail?
10-12 weeks (End of 1st Trimester)
- Then you get a sudden rise of Oxygen in the placenta (3-fold rise)
- The chorionic villi regress on one side, forming the chorion laeve > discoid chorion
What is Haemotrophic Nutrition
- Occurs from the 2nd Trimester
- Where Fetal Growth is now entirely from the placenta, via a long supply line
- Maternal Diet influences → Mums metabolic and Endocrine Status
- The Uterine Blood Flow influences → The Transport and metabolism in/to the placenta (through intervillous spaces)
- Umbilical art. Blood Flow influences → Fetal metabolic and Endocrine Status
- At the end of all this is what’s available for fetal Growth!
What is the ‘Fetal Diet’ that they are getting from the placenta?
-
Glucose via facilitated diffusion (GLUT1)
- Key Oxidative fuel (~80%)
- Carbon source for tissue acretion
- Needed as there’s limited fetal gluconeogenesis
-
Amino Acids via Active transport, placenta synthesis (glutamate and glycine) or feto-placental shuttle**
- For metabolic Balance between Oxidation and growth
- Carbon and Nitrogen for tissue accretion
- Nucleotides
-
Lactate via placenta production
- Mostly oxidised
-
Fatty Acids via diffusion gradient down Placenta
- Limited Oxidation
- Energy store
- Cell membranes
What are the 2 main hormones required for fetal growth?
- Insulin-like growth factors
- Insulin
What do the ILGF hormones do and where are they produced?
- Most important for fetal growth
- Widely produced in fetal tissues and placenta
- Potent Mitogens, protein anabolism
- Paracrine and endocrine hormones
- Take Out IGF1 and 2: non-viable fetus (take out one of these leads to major growth restriction)
- In many species the birth size correlates to IGF levels
IGF is regulated by???
Fetal Nutrition
- Starvation → both fetal and maternal IGF drop
- Infuse with glucose → big increase in IGF
- Infuse with AA → smaller increase in IGF
The role of insulin hormone and fetal growth?
When insulin is removed fetal growth will decline; by injecting insulin into the fetus you can bring back to normal.
Upregulates growth when nutrition is plentiful
Insulin Actions:
- Increased glucose uptake (to everywhere but the brain)
- Fat deposition
- Protein anabolism
- May promote placental growth
- In early pregnanacy AA stimulate fetal Insulin secretion
- Also increases IGF hormone the same as glucose can
Growth Hormone in the fetus? Is it that important?
- Circulating concentrations are high
- Deficiency has minimal effect on fetal weight
- Receptors absent in the liver
- Doesn’t regulate IGF like insulin and glucose can
BUT
- Regulation is similar to that seen postnatally
- Deficient Infants are measureably short
- Receptors present in many other tissue
- May alter fetal metabolism
Glucocorticoids and Fetal Growth ?
- Increase hugely around the time of birth due to fetal adrenal activation near term
- Promote cell differentiation and tissue maturation
- Decreased DNA synthesis and cell division
- Have a role in timing of birth for many species; but not in humans; this is good as it means we can give preterm babies steroids
- “turn on” somatrophic axis by inducing expression of growth hormone receptors in the liver →centralised control of growth
Fetal steroids have a potent effect at birth, why don’t maternal steroids do the same?
There’s an 11 BHSD2 enzyme functional barrier in placental, metabolises most of the maternal cortisol!
- Reduced 11 BHSD2 enzyme activity during
- Maternal protein malnutrition
- Ischaemic Placental Disease
- Allows more cortisol to be accessed by the baby, but you don’t want baby to be exposed for too long!!
Genetic Influences on Fetal Growth?
- Race and Sex account for <20% varience in birthweight (small influence)
- Genetics have more influence on lean mass
- Fetal growth normally limited more by Constraint
- Non-genetic/non-pathological factors limiting fetal growth
What are maternal genetic CONSTRAINTS that can affect birth weight?
Maternal Constraint: The ability of the utero-placental unit to supply O2 and nutrients
- Put thoroughbred embryo in pony → small thoroughbred!
- Maternal Size: small mum
- Maternal Age (adolescant pregnancy)
- Parity: primiparous (babies get bigger after 2nd pregnancy)
- Short inter-pregnancy interval
- Macronutrient balance:
What are two constraints during Embryogenesis that can occur?
- Twins: always smaller in weight, and if you get rid of one twin later the remaining twins growth still isn’t as high as a non-twin baby
- Periconceptual undernutrition: even if you supply adequate nutrition later, they are still eventually smaller
Shows that events during early nutrition can affect growth throughout gestation
How common is it to have fetal constraints, and what is considered a ‘normal’ birthweight?
- Fetal growth is usually constrained below optimal for survival
- Optimal fitness at birthweight : 80th to 90th centile, around the upper end
Fetal Growth: normally constrained by maternal environment.
If endocrine status is adequate, growth is regulated by substrate supply
Postnatal Growth: Due to genetic potential.
If nutritional status is adequate, growth is regulated by endocrine status
Main causes of Fetal Undernutrition
- Placental Insufficiency
- Idiopathic unknown
- Vascular Disease Type I and II diabetes
- Maternal Undernutrition (<1500 kcal/day) has to be really severe
Main causes of Fetal Pathology
- Congenital Malformation
- Congenital infection
- Toxins
- Chromosomal disorders
- Specific Genetic Disorders
Genetic disorders affecting Fetal Growth are Imprinted
One of the parents genes are silenced
- Maternally expressed genes suppress growth (mum wnts to limit size to survive)
- Paternally expressed genes promote growth
Beckwith Wiedemann Syndrome
Overexpression of IGF2 (maternal allele normally imprinted)
Usually due to paternal uniparental disomy (2 dad genes → overgrowth)
- Macrosomia, macroglossia
- Hemihypertrophy (24%)
- Transverse Ear Crease
- Omphalocoele liver/intestine outside abdominal wall
- Hypoglycaemia (50%)
- Embryonal tumours
Russell Silver Syndrome
60% Due to underexpression of IGF2
- Hypomethylation of paternal IC1 region 11p15.5
- SGA baby, short with normal head growth
Placental Insufficiency leading to FGR?
- Deficient trophoblast invasion and remodelling of spiral arteries.
- That leads to Maldevelopment of Terminal villi
- Reduced SA, diffusing capacity and uteroplacental/fetoplacental blood flow.
- Placental inflammation, hypoxic/hyperoxic stress, antiangiogenic state, thrombo-occlusive damage
Early sign: fetal resistance in the umbilical artery, with abnormal BF on the doppler ultrasound
STRIDER?
Sildenafil Therapy In Dismal Prognosis Early-onset intrauterine growth Restriction
To increase fetal blood flow and allow for longer gestation time
Long term Health effects of FGR??
Limitation in function units due to decreased Hyperplasia.
Your metabolic load can hugely affect your metabolic capacity.
- Not just at the severe end that these can affect the person, this can ocur up into the normal birthweight range
- Risk are on a spectrum, they don’t work to the centil ranges.
Gestational Diabetes is due to?
- Glucose intolerance developing in pregnancy
- usually develops in the 3rd Trimester
- Intolerance is rising worldwide, up to 15% in USA
- Leads to large babies; birth trauma for mum
- Mum + baby now likely to develop Type II diabetes
Excessive fetal substrate (glucose + FFA) → excess fetal insulin
Excess substrate + Excess insuling → Excess growth
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