List the events that take place in the first 4 weeks of gestation
1st week - sperm + ovum = fertilisation - morula - blastocyst - implantation 2nd week - bilaminar germ disc, epiblast/hypoblast (clinical gestation week 4) 3rd week - gastrulation - ectoderm/mesoderm/endoderm - neurulation - by end of 4th week
What structures are formed form the following:
- ectoderm
- mesoderm
- endoderm
Ectoderm - skin - neural tissue - pigment cells Mesoderm - cardiac muscle - skeletal muscle - tubule cell of kidney - red blood cells - smooth muscle Endoderm - alveolar cell - thyroid cell - pancreatic cell
Describe the folding of the embryonic disc
- flat trilaminar disc –> cylindrical embryo
- cephalo-caudal folding
- lateral folding
When and what events occur during:
- the embryonic period
- the foetal period
Embryonic period
- organogenesis
- establishment of main organ systems
- post-fertilisation weeks 3-8 (clinical gestation weeks 5-10)
Foetal period
- maturation and growth of tissues and organs
- post-fertilisation week 9-38 (clinical gestation 11-40 weeks)
What are birth defects?
What are the three types?
Birth defects = developmental disorders present at birth, not only physical defects Types: - structural = congenital anomaly - function = organ dysfunction - metabolic = enzyme/cellular defect
What are the causes of birth defects?
Genetic
Environmental
Multi-factorial inheritance - interaction between genetic constitution and environmental factors
Describe the following congenital anomalies:
- Malformation
- Disruption
- Deformation
Malformation
- incomplete or abnormal formation of structure
- complete or partial absence of a structure
- alteration of its normal configuration
Disruption
- morphological alterations of already formed structure
- destructive process e.g amniotic bands
Deformation
- mechanical factors e.g. positional talipes w
Describe the chromosomal/genetic causes of birth defects
Decribe Syndromes, Associations and Sequence
- multiorgan involvement
- usually lethal/significant defects
Syndromes - a group anomalies with a known specific cause
- e.g. Down’s syndrome
Association - abnormalities which tend to occur together but the cause is not determined e.g. CHARGE
Sequence - when a defect leads to a cascade of further abnormalities e.g. Potters sequence (kidneys don’t form, then no urine, no amniotic fluid, no lungs, other physical changes)
What are the clinics features of Down’s syndrome?
- craniofacial appearance = flat nasal bridge, upslanted palpebral fissures, epicanthic folds, brush field spots)
- single palmar creases
- hypotonia
- congenital heart defects
- duodenal atresia
- variable learning difficulties
- Alzheimer’s/malignancy
What are the two major causes of Down’s syndrome/
Maternal non-disjunction
Robertsonian translocation
Define teratogens
What are the determining factors of teratogenic effect?
- agents that can cause predispose to a birth defect
- single or few systems involved
Determining factors - timing
- dosage
- genetic constitution of the embryo
What are the types of teratogen?
Drugs - include alcohol, cocaine, thalidomide, anticonsulsants, antipsychotics, ACE inhibitors, warfarin Environmental chemicals - e.g. organic mercury, lead Infectious agents - e.g rubella, CMV, zika Radiation - high levels of ionising radiation Maternal factors - SLE, poorly controlled pre-existing DM Mechanical factors - e.g. malformed uterus, oligohyrdramnios, amniotic band
What are the different effects of timing and insult during foetal life?
Prior to post-fertilisation week 2
- either miscarriage or no effect
Organogenesis period (week 3-8)
- period of greatest sensitivity to malformation
- different organ systems have different periods of peak sensitivity
- leading to birth defects
Fetogenesis period (week 9-38)
- main effect on growth and functional maturation
- usually not leading to birth defect
What are the classifications of spina bifida?
Occulta
Meningocoele
Myelomeningocoele
Draw neural tube formation
see lecture
What are the ultrasound features of spina bifida?
Lemon sign - tethering of spine –> frontal bone scallopping
Banana sign - cerebellum sucked back and looks bent
What is the prognosis of spina bifida?
Level of lesion is critical
- cognitive outcome
- ambulation
- spinal deformity
- continence
- sexual function
What prevents spina bifida and is recommended to women?
folic acid
Describe craniofacial formation and malformation
Face made up of 5 prominences
- frontonasal, lateral nasal, medial nasal, maxillary, mandibular
- sulci where they should join
- if malunion –> cleft lip/palate
Give 2 examples of abdominal wall defects
Omphalocoele
- transparent sac of amnion attached to umbilical ring containing herniated viscera
- persistence of embryonic midgut herniation
- 60% associated with other abnormalities
- 20% associated with chromosomal disorders e.g. Edward’s
Gastroschisis
- evisceration of foetal intestine through a paraumbilical wall defect
- possible origins include: involution of right umbilical vein or right vitelline artery
- abnormal body wall folding
- associated with young mums, smoking and drug use
- good prognosis after surgical correction
What are the options for detection of congenital abnormalities?
Genetic testing
- screening e.g. for Down’s
- PIGD
- Invasive testing and non-invasive testing - single gene disorder, chromosomal abnormalities
Imaging
- detailed foetal anomaly scan for structural anomalies at 20 weeks
What are the screening options for Down Syndrome?
Which is routinely offered?
Triple test = AFP, hCG, uE3
Quadruple test = AFT, hCG, uE3, Inhibin A
Nuchal translucency on ultrasound
Combined = NT, PAPP-A, hCG
What is non-invasive prenatal testing?
- foetal genome pieced together from free DNA in maternal blood
- will soon be a national programme
- step before invasive testing
- can pick up XS chromosome 21 for example
What are the techniques available for prenatal diagnosis and therapy?
- amniocentesis
- fetoscopy
- foetal blood sampling
- chorionic villous sampling
- pre-implantation genetic diagnosis
- non invasive genetic diagnosis (maternal blood)
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HPG Axis41
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Adrenal 227
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Testicular Function39
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Ovarian Function27
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Fertilisation33
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Endocrine Disorders Affecting Reproduction35
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Contraception and HRT42
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Infertility42
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Assisted Reproduction16
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Stem Cells0
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Placenta50
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Endocrinology of Pregnancy and Parturition23
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Foetal Growth32
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Foetal Development28
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Clinical Genetics0
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Clinical Management of Pregnancy and Parturition17
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Neonatal Physiology26
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Childhood Growth44
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Sexual Differentiation and Puberty38
