Fetal therapy

FETAL THERAPY

ByMagdy abdelrahman mohamed

2015

DEFINITION

Therapeutic intervention for the purpose of correcting or treating a fetal abnormalities.

TYPES Non invasive (pharmacological).

› Preventive.› Therapeutic.

Invasive.

PREVENTIVE FETAL THERAPY

Peri-conceptional folic acid supplementation.

Antenatal steriod to enhance fetal lung maturity.

Anti D immunoglobulin.

Congenital adrenal hyperplasia.› Dexamethazone 20 ug/kg in three divided

doses, started less than 9w.› Stopped when proved male fetus or

unaffected female.

Fetus with maternal SLE. Fetus at risk to develop Complete

heart block because of damage to AV bundle.

This can be prevented by giving Dexamethasone 4 mg per day during pregnancy.

THERAPEUTIC PHARMACOTHERAPY

Cardiac arrhythmias can be managed by digoxin and/or amiodarone.

Fetal thyroid goitre ….. fetal cord blood for thyroid status then treated by either carbimazol or levothyroxin.

INVASIVE FETAL THERAPY

Termination of pregnancy. Fetal Image Guided procedures. Fetal Endoscopic Surgery (FETENDO). EXIT procedure (Ex-Utero Intrapartum

Treatment Procedure). Open fetal surgery. High intensity focused ultrasound

(HIFU). Gene therapy & stem cell.

HISTORICAL BACKGROUND

1961.› In utero transfusion (liley).

1970s› Embryoscopy / Fetoscopy was introduced

to visualized malformations.› High resolution U/S take their diagnostic

role.

1984.› 1st successful resection of congenital cystic

adenomatous malformation. 1992

› 1st successful resection of sacrococcygeal teratoma.



Treatment Procedure). Open fetal surgery. High intensity focused ultrasound (HIFU). Gene therapy & stem cell.

FETAL IMAGE GUIDED PROCEDURES.

Ultrasound image guided procedure

Needle or a Trocar-Canula -Shunt introduced.

ADVANTAGES Least invasive.

Least risk of amniotic fluid leak.

Least risk of preterm labour.

Fetal Image Guided procedures.

Amniocentesis. Amnioinfusion. Septostomy. Selective Fetal reducion. Intrauterine transfusion.

Acardiac twins ( twins reversed arterial perfusion).› Bipolar diathermy or radiofrequency

ablation of umblical cord. Balloon Dilatation of Aortic Stenosis. Vesico-amniotic shunt. Pleuro-amniotic shunt.


Termination of pregnancy. Fetal Image Guided procedures. Fetal Endoscopic Surgery

(FETENDO). EXIT procedure (Ex-Utero Intrapartum


FETAL ENDOSCOPIC SURGERY

Fetoscopic access to the Fetus. The fetal visualisation is a combination

of endoscopic and sonographic on two different screens.

CDH (Congenital Diaphragmatic Hernia)-Balloon Occlusion of trachea

TTTS (Twin to Twin Transfusion Syndrome)- Laser coagulation of vessels

Laser ablation of umblical cord in cases of acardiac Twins

Amniotic bands division Posterior uretheral valve laser ablation.

Twin to Twin Transfusion Syndrome

Determine Chorionicity.

DIAGNOSIS

Amniotic Fluid Discordance Recipient

› Maximum vertical pocket greater than or equal to 8.0 cm

Donor› Maximum vertical pocket less than or

equal to 2.0 cm

Quintero Staging System› I. Amniotic Fluid Discordance› II. Donor Bladder Not Visible› III. Abnormal Dopplers› IV. Fetal Hydrops› V. Fetal Demise


Termination of pregnancy. Fetal Image Guided procedures. Fetal Endoscopic Surgery (FETENDO). EXIT procedure (Ex-Utero

Intrapartum Treatment Procedure). Open fetal surgery. High intensity focused ultrasound (HIFU). Gene therapy & stem cell.

EXIT (Ex-utero Intrapartum treatment procedure)

It is the intervention that occurs at the time of delivery.

It is primarily used in cases where baby’s airway requires surgical intervention as:› CHAOS (Congenital High Airway Obstruction

Syndrome)

› Removal of balloon after treatment of diaphragmatic hernia.




OPEN FETAL SURGERIES Congenital cystic adenomatous

malformation.› Progressive increase in the size.› Mediastinal shift.› Hydrops.› Polyhydramnios.

Sacrococcygeal teratoma.› Fetal Hydrops due to vascular shunts. ( high

output heart failure) Open spina bifida ???

Dr.Michael Harrison (California)

Father of open fetal surgery

CHALLENGES Ethical dilemma.

Maternal & Fetal anaesthesia.

Risks both to mother and fetus.

Post surgical tocolysis.

Ethical dilemma Not all procedures are performed regularly.

The results are not guaranteed.

Research in Fetal Surgery is ethically controversial as it poses a risk to both the fetus and the mother.

Surgical Animal models do not always replicate in human beings.

Maternal risks Tocolytic therapy can cause pulmonary

edema. Subsequent delivery by LSCS. Intraoperative blood loss. Intra uterine infection. Deep anaesthesia can cause maternal

myocardial depression.

Fetal risks

Prematurity & PROM. Intra Uterine Infection. Fetal vascular embolic events.

› Intestinal atresia.› Renal agenesis.

Fetal risks Fetal circulating volume is low, hence

little intra-operative bleeding can cause hypovolemia.

During prolonged surgery, fetus may be transfused Oneg blood

Premature closure of Ductus Arteriosus CNS injuries due to maternal hypoxia

or fetal circulatory disturbance.

Pre-operative preparation Assessment of the mother for fitness

for anaesthesia & cross matched blood. Assessment of the fetus

› Detailed U/S to exclude other malformations.

› O neg blood for fetus kept ready.› Detailed Fetal Echocardiography.› Localization of placenta.› Fetal MRI.

Intra-operative measures

Mother given GA with intubation as the uterus has to be relaxed to allow manipulation of the uterus.

Intra operative U/S to localise placenta and to assess the surface anatomy of the fetus

Incision to be taken close to the area of interest

Uterine Stapler to reduce blood loss

The fetus is monitored with › Fetal

Echocardiography› Pulse Oxymetry

Continous Infusion of warmed Ringer Lactate to replace amniotic fluid



Treatment Procedure). Open fetal surgery. High intensity focused ultrasound

(HIFU). Gene therapy & stem cell.

HIGH INTENSITY FOCUSED ULTRASOUND (HIFU).

(HIFU) is a non-invasive alternative method of vessel occlusion which may avoid complications inherent to surgery.

Still under research in animal study for treating TTTs, A cardiac twin & sacrococcygeal teratoma.

Only one case report in human. It was used to occlude umblical cord vessel in A cardiac twin (Okai T, et al., 2013)




GENE THERAPY It means replacement of missing gene by

introduction of foreign Nucleic acid sequence.

It is divided into two categories, classic gene therapy and stem cell gene therapy.

A carrier molecule called a vector (virus-lentivirus) must be used to deliver the therapeutic gene to the patient’s target cells.

Stem cell Hematopoeitic stem cells can give rise to

complete blood system. Potential for treatment or even cure of many

hematopoeitic diseases. Theoretically, rejection should not be a

problem of “fetal tolerance”. Fetus remains in a sterile environment, so

post- transfusion isolation after transplant is automatic.

Health & Medicine

Fetal therapy