NTDs & Foetal Surgery Flashcards
What is neurulation?
What are the major stages in this process that lead to neural tube formation?
- The process by which the neural plate forms the neural tube*
- the neural plate lengthens and its lateral edges elevate to form neural folds
- the depressed midregion forms the neural groove
- the neural folds elevate and approach the midline
- the neural folds fuse in the midline at the cervical region, and fusion continues both cranially and caudally to form the neural tube
- this leaves only the anterior and posterior neuropores open to the external environment
How is open foetal surgery performed?
When during the pregnancy is this performed and why?
- it involves a potentially large hysterectomy to expose the foetus
- the contents of the uterus are removed for a small period of time before being returned
- it occurs around 20 weeks (halfway through development)
- the later the foetal surgery is left, the greater the risk to the mother
- but the foetus has to be developed to a certain extent before surgery can be performed
What is it important not to do during open foetal surgery?
When is this method typically used?
- it is important not to rupture any placental membranes during the procedure as this can result in preterm birth
- it is often performed for prenatal repair of myelomeningocele
How is foetoscopy performed?
For which conditions is this an appropriate method of surgery?
- it is performed using endoscopes and requires a much smaller hysterectomy
- it can be used in:
- urinary tract obstruction
- congenital diaphragmatic hernia repair (poor outcomes)
- TTTs and TRAP
- experimental use in amniotic band syndrome
How is foetal surgery planned?
What is the associated risk?
- CT and MRI can be used to plan treatment
- there is no incidence of a radiating scan leading to a congenital malformation, but there is a well-established link between radiation and chromosomal abnormalities
How can foetoscopy be used in TTTS and TRAP?
Are the outcomes good?
Twin-to-twin transfusion syndrome (TTTS):
- the twins share a placenta and abnormal anastomoses between blood vessels leads to one receiving a greater blood supply than the other
- foetoscopy is used to ablate larger vessels and leave an equal distribution of maternal blood
Twin reverse arterial perfusion (TRAP):
- one foetus is pumping oxygenated blood over towards the other one
- TRAP has poor outcomes regardless of surgical intervention
What medication is given prior to open foetal surgery and how does it work?
Tocolytics
- given to prevent premature labour
- typically involves giving a calcium channel blocker, such as nifedipine
- calcium channel blockers will also relax the uterus
- procedure is performed under general anaesthetic
How is open foetal surgery performed?
What must be pumped into the uterine cavity and why?
- hysterectomy is performed to expose the foetus
- this involves an incision of the anterior abdominal wall and removal of the contents of the uterus
- fluid is continually pumped into the uterine cavity to maintain the pressure and prevent placental separation
- the fluid is similar to saline but has different sodium levels as it is important not to modify the pH of the amniotic sac/fluid
- this can cause problems with development later on
What is the importance of medical imaging during open foetal surgery?
- medical imaging is used to assess the position of the placenta to ensure it is avoided during incision
- if the placental linings attached to the walls of the uterus are accidentally incised, this can lead to placental separation and preterm birth
What injection can be given during open foetal surgery?
How is the surgery concluded and what precaution must be taken in the future?
- a foetal narcotic injection can be given for pain relief
- the defect is repaired and amniotic fluid is replaced before closing the surgical site
- following open surgery, all babies must be born via C-section
What are the limitations on when open foetal surgery can be performed?
Why must all future pregnancies be delivered by C-section?
- it can only be performed after 18 weeks due to the size and fragility of the foetus
- it is usually performed at 20 weeks
- this pregnancy and all future ones must be delivered via C-section to avoid uterine rupture at the scar site
What are the complications associated with open foetal surgery?
- uterine rupture
- maternal bleeding
- premature delivery
- respiratory distress syndrome (RDS)
- foetal death
What is myelomeningocele and why does it occur?
- it is the most severe form of spina bifida
- failure of the posterior neuropore to close leads to protrusion of the meninges and neural tissue through the vertebral arch
- it is not a defect of neurulation as the neural tube has formed
- it occurs due to splitting of the vertebral arches
When do the edges of the neural plate begin to elevate?
What are the processes that occur following this?
- the edges of the neural plate elevate to form neural folds on day 23
- the neural folds fuse in the midline to form the neural tube
- the neural tube separates from the surface ectoderm
- the surface ectoderm will form the epidermis of the skin
- a subset of cells from the neural folds (NCCs) will go on to migrate all around the body
Why do neural tube defects occur?
- NTDs result when neural tube closure fails to occur
What is craniorachischisis and why does it occur?
- there is a completely open brain and spinal cord
- it is a combination of anencephaly (absence of brain & cranial vault) with a continguous bony defect of the spine (rachisisis - no meninges covering neural tissue)
- occurs due to failure of the neural folds to fuse
- the surface ectoderm becomes continuous with part of the nervous system
- it is rachischisis if it only involves the spinal cord
What is anencephaly and why does it occur?
- there is an open brain and lack of skull vault** due to **failure of the anterior neuropore to close
- after a certain point in development, amniotic fluid becomes damaging to the nervous tissue
- if the anterior neuropore does not close, the amniotic fluid damages the cranial structures and prevents development of the brain
- only the brainstem can develop and death occurs in utero or shortly after birth
What is encephalocele and why does it occur?
- there is herniation of the meninges (and brain) through an opening in the skull
- it occurs due to incomplete closure of the neural tube
- any area of the skull can be affected and the protruding sac can be covered with skin or just a thin membrane
What is meant by iniencephaly?
- this describes occipital skull and spine defects with extreme retroflexion of the head
- the neural tube is not always involved
- extreme retroflexion is often combined with occipital encephalocele and rachischisis of the cervical or thoracic spine
- often results in stillbirth and live birth is rare
Why does spina bifida occur?
- it results from failure / abnormal formation of the vertebral arches
- the neural tube and spinal cord form normally, but there is protrusion through an incomplete vertebral arch
What is meant by spina bifida occulta and how can it be recognised?
What symptoms does it present with and why is intervention needed?
- it is the least severe form of spina bifida and is often asymptomatic
-
some of the vertebrae are not completely closed
- it usually affects the caudal region of the spinal cord
- it is called “blind” as it cannot be seen except for a tuft of hair being present on the overlying skin
- intervention is needed as the only thing covering and protecting the spinal cord is subcutaneous fat
What is meant by meningocele?
- there is protrusion of the meninges through a defect in the skull or spine
- as the meninges are filled with CSF, this produces a CSF-filled cyst
- there is no neural tissue protruding through the spinal cord
What is meant by myelomeningocele?
What may this be accompanied by?
- this occurs when both the meninges and neural tissue protrude through a defect in the skull or spine
- the spinal cord is open to the external environment and at risk of damage
- it can be accompanied by severe neurological defects
How can spina bifida be detected prenatally?
Why is it important to recognise this condition?
- both myelomeningocele and meningocele can be detected in utero via USS as part of the foetal anomaly scan
- both of these conditons require closure of the defect
- plans are made for foetal surgery or C-section as you do not want to disturb exposed nervous tissue by squeezing it through the vaginal canal
What are the 4 primary functional deficits associated with myelomeningocele?
- paralysis and sensory loss of the lower limb
- frequent UTIs
- bladder / bowel dysfunction (due to compression of pudendal nerve)
- cognitive dysfunction & hydrocephalus
- in lumbosacral lesions, only 3-15% retain the ability to walk
What is the most common way to repair a myelomeningocele?
- it is detected on prenatal scans and in utero foetal surgery can be performed, but postnatal repair is more common
- closure occurs in the first few hours / days of life after a planned C-section
- a C-section is required to prevent compression of nervous tissue through a vaginal birth
What are the possible complications associated with postnatal repair of a myelomeningocele?
- blood loss
- infection
- leakage of CSF
- problems with wound healing
- hydrocephalus
- tethered spinal cord
- all of these complications lead to functional deficits
- 15-20% will develop a tethered spinal cord at some point in their lifetime as a result of adhesions following surgery
- this will require further surgery to repair
What structure often herniates alongside myelomeningocele and why?
- herniation of the cerebellum into the spinal cord can occur alongside myelomeningocele
- CSF leaks into the defect and reduces the hydrostatic pressure
- this draws the hindbrain through the foramen magnum
What is the benefit of performing in utero surgery for myelomeningocele?
- operating as early as possible in development leads to better outcomes in terms of functional deficits
- there is more time for the nervous system to develop and repair itself, reducing the severity of functional deficits
How did a study using rats look at the use of stem cell therapy to repair congenital defects (including NTDs)?
- mesenchymal stem cells were derived from the amniotic fluid of rat foetuses and concentrated
- NTDs induced in pregnant rats by giving retinoic acid
- concentrated stem cells injected into the amniotic cavities of some mothers, whilst controls were given saline injections
- NTDs were partially or fully covered by skin in the group receiving stem cells
Why is food impregnated with folic acid?
- to ensure that effective neurulation** occurs and to **reduce the incidence of NTDs
- folic acid is important in neurulation
- a mother needs sufficient levels of folic acid 4-6 weeks before fertilisation and 50% of pregnancies are unplanned
What is congenital diaphragmatic hernia?
Who is more commonly affected and how can it be detected?
- there is herniation of the gut / gut structures into the thorax
- it more commonly affects the left side (unknown why)
- it affects 2x more males than females
- it can be detected via prenatal screening but is sometimes missed, resulting in the baby going into respiratory compromise immediately after birth
What other malformations is congenital diaphragmatic hernia associated with?
- NTDs are present in 50% of cases
- trisomy 18
- various other syndromes
What is the septum transversum and what is it derived from?
- a thick plate of mesodermal tissue occupying the space between the thoracic cavity and stalk of the yolk sac
- it is derived from splanchnic mesoderm surrounding the heart
- it assumes its position between the primitive thoracic and abdominal cavities when the cranial end of the embryo grows and curves into the foetal position
How does the septum transversum separate the primitive thoracic and abdominal cavities?
- the septum transversum does NOT fully separate the thoracic and abdominal cavities
- it leaves large openings on either side of the foregut - the pericardioperitoneal canals
How is the connection between the pleural cavities and peritoneal cavity sealed off during development?
- the pleural cavities are in open communication with the peritoneal cavity via the pericardioperitoneal canals
- the opening between the prospective pleural and peritoneal cavities is sealed off by crescent-shaped pleuroperitoneal folds
- by week 7 the pleuroperitoneal folds have fused with the septum transversum and the mesentery of the oesophagus to separate the peritoneal and pleural cavities
Why does congenital diaphragmatic hernia occur?
- it results from failure of one or both of the pleuroperitoneal membranes to close the pericardioperitoneal canals
- this leads to the pleural and peritoneal cavities being continuous with each other at the posterior body wall
Why does failure of the pleuroperitoneal membranes to close the pericardioperitoneal canals result in CDH?
- the pleuroperitoneal folds come towards the midline and fuse with the septum transversum to form the diaphragm
- the septum transversum forms the central part of the muscular diaphragm
- the pleuroperitoneal membranes form the domes of the diaphragm
- if the pleuroperitoneal membranes fail to form sufficiently in size or fail to fuse with the septum transversum, there is a space in the diaphragm
- abdominal contents protrude through the opening in the diaphragm as the pressure in the abdomen is higher than in the thorax
How can CDH affect the developing lungs?
- as the abdominal contents occupy the space of the developing lungs, this results in hypoplasia of one of the lungs
What are the signs and symptoms of congenital diaphragmatic hernia?
- respiratory distress
- difficult resuscitation at birth
- cyanosis
- bowel sounds over one hemithorax (usually left)
- displaced heart sounds
Why are there displaced heart sounds in CDH?
- the presence of the intestines within the thorax leads to mediastinal shift
- the heart is pushed over to the opposite side of the thorax (usually right)
What 2 types of tubes must be inserted immediately after birth in CDH?
- an endotracheal tube is inserted for mechanical ventilation
- a nasogastric tube is inserted and an X-ray taken to confirm correct placement
- the tube is seen passing through the oesophagus and curling back into the thorax as the stomach is situated within the thorax
How can the lungs be affected by CDH?
- a defect in the diaphragm results in herniation of bowel loops into the left (usually) side of the thorax
- this results in hypoplasia of the left lung as it lacks space to develop properly
- sometimes the right lung can become larger to compensate and protrude onto the left side (better prognosis)
What are the 2 aims of prenatal foetal surgery for CDH?
- restore the gastrointestinal tract to the abdomen
- promote normal lung development
How is prenatal foetal surgery performed in CDH?
FETO - foetal endoscopic tracheal occlusion
- the intestinal contents are returned to the abdomen
- a balloon is inserted towards the left bronchus and inflated
- this causes fluid and pressure to build up within the left lung, forcing tissue to expand and promoting development of the hypoplastic lung
What happens in twin-twin transfusion syndrome (TTTS)?
- there is development of abnormal blood vessels between twins that share a placenta
- this results in one twin receiving a greater share of the circulation compared to the other
What problems can occur in the 2 twins involved in TTTS?
- the twin receiving the larger share of the circulation is the “recipient twin”
they become overloaded, resulting in oedema** and **heart failure
- the twin that is deprived of the circulation is the “donor twin”
they become dehydrated, resulting in renal failure
- in the majority of cases, the prognosis is poor for both twins and neither will survive
How can in utero foetal surgery be performed for TTTS?
- laser ablation of vessels is associated with a good chance of survival for at least one twin
- it is minimally invasive and requires only a small incision to insert a scope into the uterus
- this allows for visualisation of abnormal vessels, which can be targeted with a laser
