Lecture 14: Fetal growth and Nutrition Flashcards
What are some porblems that are faced by smaller babies
<2.5kg
6x increase in prenatal mortality and morbidity
Average IQ 8 points lower
Inattention, hyeractivity, behavioural problems
20% adult short stature
What are some problems faced by larger babies
1) Birth trauma
2) Increased neonatal admissions
3) Increased adult non-communicable disease
What is a “full term” baby?
39 weeks
What is considered Low, very low, extremely low and macrosomia birthweight?
What is featl growth?
Change in body size
Growth in organs
Mean weight gain : 16-17kg/day
Fetal growth is essential to functioning of _______________ as an adult
Organ
What is fetal growth restriction?
In utereo, growth potential limited by patholgoical processes
Decreased accretion (growth or increase by the gradual accumulation of additional layers or matter) of fat & lean tissue and gain/loss in skeletal growth
Most cases due to poor placenta
Key risk factors for stillbirth, neonatal death, asphyxia
Is Fetal growth restricted = small gestation age?
No.
Intrauterine growth restriction (IUGR) refers to poor growth of a fetus while in the mother’s womb during pregnancy.
Intrauterine growth restriction can result in a baby being Small for Gestational Age (SGA), which is most commonly defined as a weight below the 10th percentile for the gestational age.[
Intrauterine growth restriction (IUGR) refers to a condition in which a fetus is unable to achieve its genetically determined potential size. This definition intentionally excludes of fetuses that are small for gestational age (SGA) but are not pathologically small. SGA is defined as growth at the 10th or less percentile for weight of all fetuses at that gestational age. Not all fetuses that are SGA are pathologically growth restricted and, in fact, may be constitutionally small. Similarly, not all fetuses that have not met their genetic growth potential are in less than the 10th percentile for estimated fetal weight (EFW).
Being small and growth restricted is super dangerous
THese 4 fetuses were born in the normal range
Only baby C is the only “normal” baby
A and B have late growth restriction.
D has early growth restriction
How do we determine birthweight centiles?
1) Population reference (actual birhtweight of actual babies at actual gestation)
-But preterm babies are born preterm. They will appear larger than they will actually be if they stayed in utero
2) Population standard
- Actual birthweights in optimal pregnancy conditions
- Problem: bad for preterm babies because not many will be in the sample
3) Fetal growth curves
- Serial ultrasound biometry of healthy fetuses born at term
- Problem: we don’t have large samples
4) Customised birthweight
- Models that incorporate maternal size, ethnicity, parity, fetal grwoth velocity
- How do we expect this baby in this mother to be in optimal conditions
If you use 1 centile, you may miss babies that are small
Is it okay using the 10th centile?
Customised centiles in pregnancies with risk factors for FGR
Studies show that 10% is a relatively good predictor of babies that need neonatla care or a caesarian
_____ is common in preterm babies
Fetal Growth Restriction
(25%)
(10% are small for gestational age)
What are SGA babies?
Small for gestational age (SGA) newborns are those who are smaller in size than normal for the gestational age.
SGA is most commonly defined as a weight below the 10th percentile for the gestational age.
What are the determinants of fetal growth?
1) Nutrition that the fetus receives
2) Hormones
3) Genetics
Describe the Embryo: histiotrophic nutrition
- Period of organogenesis (organ is being laid down)
- Embryo supported directly by secretions from endometrial glands
- Growth of embryo and chorionic sac relatively consistent and autonomous
- Maternal placental circulation is estabilised at the end of first trimester
- 3-fold rise in intra-placental oxygen
- Chorionic villous regression and formation of discoid placenta
Term used to describe in e_arly placenta development_ the intital transfer of nutrition from maternal to embryo (histiotrophic nutrition) compared to later blood-borne nutrition (hemotrophic nutrition).
Histotroph is the nutritional material accumulated in s_paces between the maternal and fetal tissue_s, derived from the maternal endometrium and the uterine glands.
In later placental development nutrition is by the exchange of blood-borne materials between the maternal and fetal circulations, hemotrophic nutrition. During the embryonic period uterine glands secrete at least 2 glycoproteins (mucin MUC-1 and glycodelin A) that are taken up by the syncytiotrophoblast cells.
Describe the Fetus: haemotrophic nutrition
- Placenta- proper
- Talk about the fetal supply line
- What gets across the placenta determines fetal growth
- But lots of things can go wrong in the fetal supply line
- Most of the issues occur at the placental level
In later placental development nutrition is by the exchange of _blood-borne materials between t_he maternal and fetal circulations, hemotrophic nutrition. During the embryonic period uterine glands secrete at least 2 glycoproteins (mucin MUC-1 and glycodelin A) that are taken up by the syncytiotrophoblast cells.
What makes up the “fetal diet”?
Name the substrate
Placental transport
Role
1) Glucose
- Facilitated diffusion
- Main form of energy, carbon source for tissue
2) Amino Acids
- Active transport, some are synthesised by placenta, feto-placental shuttle (placenta may scagenge back from the fetus)
- Key role in metbaolic balance between oxidation vs grwoth
3) Lactate
- Produced by placenta
- Mostly oxidised for energy
4) Fatty acids
- Readily cross placenta by diffusion
- Cell membranes, energy store, limited oxidation
What hormones does the fetus produce that is important in fetal growth?
1) Insuin-like growth factors
- IGF2
- IGF1
2) Insulin
3) Growth hormone
4) Corticosteroids
Describe the role of IGF
IGF are the major growth hormones in the fetus
IGF2:
- Embryonic and placental growth
- Main circulating fetal IGF
- Constitutive/background drive for growth
- Tissue differentiation in late gestation (IGF levels drop)
IGF1:
- Match fetal growth to nutrient supply (indicate to the fetus how fast to growth based on nurtition supply)
- Not regulated by grwoth hormone in fetus
Describe the role of Fetal Insulin
1) Increased glucose uptake
2) Fat deposition
3) Protein anabolism
4) May promote placental growth
5) Insulin stimulates fetal IGF1
Tissue accretion (growth or increase by the gradual accumulation) and Fuel storage
In early pregnancy, amino acids stimulate fetal insulin secretion
In later pregnancy, primarily controlled by placental uptake of glucose and FFA
Describe Growth hormones in the fetus
- Circulating concentrations are high
- Receptors are absent in liver but present in other tissues
- Does no regulate IGF-1
- Deficiency has minimal effect on fetal weight
- Deficient infants are measureably short
- May alter fetal metabolism
Describe Glucocorticoids and its effect on fetal growth
- Fetal adrenal activation near term (featl adrenal activation determines timing of labour)
- “turn on” somatotrophic axis by inducing expression of growth hormone receptors in liver
- Promote cell differentiation and tissue maturation
- Decreased DNA synthesis and cell diviision
- Role in parturition in some species
Why does the maternal cortisol not affect the fetus?
placental barrier to maternal cortisol
In some patholgoical conditions, the enzymes that metabolised corticol does not function properly
Describe the genetic influences on fetal growth
Race and Sex accounts for <20% variance in birthweight
Genetic factors have more influence on lean mass
Fetal growth is normally limited by constraint (non-genetic/non-pathological factors that limit fetal growth)
-Maternal constraint. The major constraining factor is the ability of the utero-placental unit to s_upply oxygen_ and nutrients
Describe some constraints on fetal growth
Fetal growth is normally limited by constraint (non-genetic/non-pathological factors that limit fetal growth)
The fetus always wants to grow larger, but the maternal constraints keep it in check (for evolutionary and for the survival of the mother)
-Maternal constraint.
- The major constraining factor is the ability of the u_tero-placental unit_ to supply oxygen and nutrients
- Meternal size (size of the uterus)
- Maternal age- adolescent prengnacy
- Parity - primiparous (how many children the mother had previously)
- Short inter-pregnancy inteval
-Embryonic contraints
- Twins
Fetal growth is….normally/abnormally constrained
Normally
The fetal growth is constrained below optimal for survival
Comapre fetal vs Postnatal growth
Fetal
- Is normally constrained by the maternal environment
- If endocrine status is adequate, growth is normally regulated by substrate supply from placenta
Postnatal
- Is normally to g_enetic potential_
- If nutritional status is adeqate, growth is normally regulated by endocrine status (Growth hormone regulating liver production of IGF1)
What are some causes of fetal growth restriction?
-
Fetal undernutrition
- Placental insufficiency
- Indiopathic
- Vascular disease
- Maternal undernutrition
- Placental insufficiency
-
Fetal pathology
- Congenital malformation
- Congenital infection
- Toxins
- Chromosommal disorders
- Specific genetic disorders
Genetic disorders affecting fetal growth
Maternally expressed genes _______ growth
Paternally expressed genes _______ growth
Maternally expressed genes Supress growth
Paternally expressed genes Promote growth
e.g. Beckwith Wiedemann Syndrome
Overexpression of IGF2 (Maternal allele normally imprinted)
e.g. Russel Silver Snydrome
SGA, short, normal head growth
Describe Beckwith Wiedemann Syndrome
Overexpression of IGF2 (Maternal allele normally imprinted)
Usually due to paternal uniparental disomy
The term “fetal macrosomia” is used to describe a newborn who’s significantly larger than average.
Macroglossia is the medical term for an unusually large tongue.
Describe Russel Silver Snydrome
SGA, short, normal head growth
60% due to reduced expression of IGF2 (paternal gene)
What are some long-term health effects of FGR?
Fetal growth restriction
1) Thrifty phenotype
2) Heatlh risks
If you have delayed growth early in life then normal growth later in life what is often seen?
Coronary diseases
Fetal growth is determined by_____
Subtstrate supply via the placenta
Growth restriction is due primarily to _____
Poor placentation
Maternal metabolic disease is an increasing problem causing ______
Fetal over-growth (insulin resistance)
Fetal under- and over-growth contribute to _____
Adult non-communicable disease
What is Virulisation?
Virilization is a condition in which a female develops _characteristics associated with male hormones (_androgens), or when a newborn has characteristics of male hormone exposure at birth.
- Virilization may be caused by:
- Excess testosterone production
- Use of anabolic steroids
- In newborn boys or girls, the condition may be caused by:
- Certain medicines taken by the mother during pregnancy
- Congenital adrenal hyperplasia in the baby or the mother
- Other medical conditions in the mother (such as tumors of the ovaries or adrenal glands that release male hormones)
- In girls who are going through puberty, the condition may be caused by:
- Polycystic ovary syndrome
- Certain medicines, or anabolic steroids
- Congenital adrenal hyperplasia
- Tumors of the ovaries, or adrenal glands that release male hormones (androgens)
- In adult women, the condition may be caused by:
- Certain medicines, or anabolic steroids
- Tumors of the ovaries or adrenal glands that release male hormones
Describe the Tanner Scale
The Tanner scale is a scale of physical development in children, adolescents and adults.
The scale defines physical measurements of development based on external primary and secondary sex characteristics, such as the size of the breasts, genitals, testicular volume and development of pubic hair.
Describe the growth pattern of these babies
THese 4 fetuses were born in the normal range
- Only baby C is the only “normal” baby
- A and B have late growth restriction.
- D has early growth restriction
What would you observe in fetuses with low GH?
Deficiency has minimal effect on fetal weight
Deficient infants are measureably short
May alter fetal metabolism
What are somatotrophs?
Somatotropes (from the Greek sōmat meaning “body” and tropikós meaning “of or pertaining to a turn or change”) are cells in the anterior pituitary that produce growth hormone.
While in the uterus,
Fetal grwoth iss normally constrained by _________
If _______ is adequate, growth is normally regulated by ______________________
Fetal
Is normally constrained by the maternal environment
If endocrine status is adequate, growth is normally regulated by substrate supply from placenta
Postnatally, infants grow to ____________
If ____________ adeqate, growth is normally regulated by ______________________
Postnatal
Is normally to g_enetic potential_
If n_utritional status_ is adeqate, growth is normally regulated by endocrine status (Growth hormone regulating liver production of IGF1)
In early pregnancy, __________s stimulate fetal insulin secretion
In later pregnancy, primarily controlled by ____________
In early pregnancy, _amino acid_s stimulate fetal insulin secretion
In later pregnancy, primarily controlled by placental uptake of glucose and FFA
Fetal growth is normally limited by _____
Fetal growth is normally limited by constraint
The major constraining factor is ___________________
The major constraining factor is the ability of the utero-placental unit to supply oxygen and nutrients
