11.14 Intrauterine programming of Adult Disease Flashcards
What are the three major complications of pregnancy?
- Preterm Labour
- Pre‐Eclampsia
- Intrauterine Growth Restriction (IUG)
What are some other (less severe but very important) complications of pregnancy?
- bleeding (Important the placenta is delivered intact. Bleeding roughly 500-1000mL in pregnancy)
- anemia; coagulation
- Maternal diseases
- heart & renal disease
- diabetes mellitus (metabolic environment of mother is not ideal impacting nutrition to the foetus)
- convulsions
- breech
- intrauterine fetal death
How is anaemia a complication?
Blood volume increases by about 40% in the mother. Risk of anaemia and the O2 delivery across the placenta is dependent on Hb and O2 carrying capacity
What is the definition of preterm labour?
labour before 37 weeks gestation
What is the incidence and eitiology of preterm labour?
Incidence and Mortality
- 5‐8% deliveries
- 80% perinatal mortality and morbidity
Etiology
- unknown
- role of infection
- premature rupture of membranes
- multiple pregnancy
- polyhydramnios (= Excess amniotic fluid)
What is pre-eclampsia?
The most common serious disorder of pregnancy
- high maternal blood pressure that appears during pregnancy
- proteinuria; generalised edema
- placental dysfunction & intrauterine growth restriction
- common in first pregnancy
- may progress to eclampsia
- Can lead to seizures, convulsions and major organ system failure in mothers
What is the incidence and mortality of pre-eclampsia?
What is the eitiology?
Mild: 5‐10%; severe: 1‐2%
- 15% direct maternal mortality
- 10% perinatal mortality
Eitiolgy:
- unknown
- pregnancy specific
- dependent on trophoblast (placenta)
- genetic basis ?
What is the treatment for pre-eclampsia?
Irrespective of stage of pregnancy ‐ delivery
The only treatment is to remove the trophoblast/placenta and thus delivery of baby
What is interuterine growth restriction?
- Low birth weight (<2500g)
- 2% of term babies
- Small‐for‐gestational age (IUGR) – <2SD below population mean
- 10% of babies
- Placental insufficiency: major cause (placenta not functioning adequately leading to lack of nutritional and O2 delivery)
- Predisposition to adult diseases
Describe the incidence/mortality of interuterine growth restrictino.
Describe the eitiology
Incidence and Mortality
- 2‐10% of babies
- 2‐3 times normal perinatal mortality
Eitiology:
- Unknown
- Multiple pregnancy
- Malformations; Oligohydramnios
- Fetal infection
- Maternal diseases; Pre‐eclampsia
- Exercise; Oxygen deprivation
- Maternal smoking
- Malnutrition
- Placental insufficiency
What controls foetal growth?
- Genome
- Enviroment
- Hormonal factors
Placental and maternal
What parts of genetics impacts on foetal growth?
- About 15% of size of birth is dependent on genotype
- 2% depends on sex (Males are slightly larger than females)
What are the hormonal factors that impact on foetal growth?
- Growth of the human fetus is not particularly GH‐ dependent
- IGFs, thyroid hormones and insulin promote fetal growth
- Glucocorticoids inhibit fetal growth
What are the environmental factors that impact on foetal growth?
- High altitude / hypoxia / oxygen deprivation
- Hyperthermia - Core body temperature rises, the body is able to thermoregulate and largely protect the foetus but not at the extremes
- Maternal exercise
- Substance abuse / alcohol / drugs / smoking / toxins
- Maternal disease / pre‐eclampsia
- Oligohydramnios / multiple pregnancy / malformations - low amniotic fluid volume eg. fetal kidney not expelling enough of lungs not producing enough. Leads to reduced fetal movement and reduced fetal growth
- Stress / hormones / fetal & maternal infection
- Maternal undernutrition
- Fetal undernutrition / uteroplacental insufficiency
- Unknown
How do socioeconomic factors impact foetal growth?
Western Society
- Placental insufficiency
vs. Third World - Maternal undernutrition
- Severe malnutrition during pregnancy may result in low birth weight babies
- Eg. Dutch Famine 1944/45 ‐ trimester specific effects
What is the difference between low birth weight to premature birth?
Being born early is not the same as being born the right size (growth restricted)
What is meant by fetal programming?
Babies born small (<10th centile) have an increased risk (not causative) of developing adult diseases
- This is because adaptations are forced to be made to help the fetus to survive in the short term to make it to being delivered
- Leads to increased disease susceptibility
Is fetal programming a universal concept?
Associations between being born small and adult diseases was found in …
- Many populations
- Different ages, sexes, ethnic origins
- Independent of current level of obesity or exercise
- Although male feotuses born with low birth weight had higher risk than female
What are some of the adult diseases that are increased in risk due to intrauterine growth restriction?
What are the critical programming periods?
- periconception / preimplantation
- implantation / placental development organogenesis / maximum fetal growth prepartum maturation
- suckling / postnatal / infancy
- after weaning / childhood
- after puberty / adolescence
It is also important when exposure happened, how long growth was slowed and the nature of the insult.
What is accelerated post-natal growth?
- 90% of small babies have some accelerated growth in first 6 months
- Accelerated growth independently associated with increased risk of adult diseases
What are the critical periods for accelerated growth?
- lactation / postnatal /infancy
- after weaning / childhood
- after puberty / adolescence
Read this
Interpret this study
What is the second hit in terms of development of the diseases that had higher risks?
