Fetal therapy

A therapeutic intervention for the purpose of correcting or treating a fetal anomaly or condition
is called fetal therapy.

Personals required for Fetal therapy

 Obstetrician
 Pediatrician
 Anesthetists
 Ultrasonologist
 Neurosurgeon
 Social worker etc.

Tools required for Fetal therapy

 Ultrasound machine
 MRI
 Fetoscope
 laser machine etc.

Types
a) Pharmacological fetal therapy (non invasive)
 Preventive pharmacotherapy
 Therapeutic pharmacotherapy
b) Surgical fetal therapy - (Invasive)

PREVENTIVE PHARMACOTHERAPY

1. Neural tube defects (NTD);

All the women planning a pregnancy should be given folic acid in dose 0.4mg/day for at least one
month.Women with a prior child with NTD, should receive folic acid 4 mg/day for at least one month
preconceptually and three months after the pregnancy.
2. Prevention of hyaline membrane disease (HMD)
The high risk pregnancy associated with risk of preterm delivery should be given steroid at least 48
hours before delivery so as to accelerate lung maturity as well as renal maturity.
Dose: Betamethasone 12 mg twice at 24 hours interval or Dexona 6 mg at 12 hours interval , for total 4
doses are given. This will reduce need of surfactant and ventilatory therapy to baby.
 THERAPEUTIC PHARMACOTHERAPY

1. CARDIAC
 Cardiac arrhythmia, PSVT, atrial flutter, atrial fibrillation and ventricular tachy-cardia can be treated by
giving anti-arrhythmic drugs to mother orally or by trans-placental route.
 PSVT; atrial flutter & fibrillation: Digoxin : Oral – if fetus is normal. If fetus have feature of
hydrops, Digoxin is given either parenteral or transplacental, 0.5- 1 mg, Adenosine : per umbilical 0.05 to
0.2mg, Flecanide : oral 200- 300mg, Amiodarone : parenteral 600-800mg, Sotatlol : oral; 80-320 mg
 Complete A-V Block (CAVB)
Prevalence: 1/15,000- 1/22,000 live birth.
At the time of diagnosis of heart block in fetus, maternal dexamethasone (4 or 8 mg/d for 2 weeks, then 4
mg/day should be initiated, maintained for the duration of the pregnancy, tapering at times (2 mg/d) in the
third trimester. If the average heart rate declined below 55 bpm, a ß-sympathomimetic agent should be
given - salbutamol 40mg/ day for 2 weeks.
In the presence of maternal anti-Ro/La antibodies : There are no known markers that will predict which
fetus will develop an AV conduction defect. Little evidence suggests that the administration of steroids,
immunoglobulins or plasmapheresis in the mother can reverse third-degree AV block. However, these
therapies are helpful if given in early to treat first-degree and second-degree heart block.
Treatment for complete fetal A-V block:
 Delivary at tetriary care center
 Uneventful fetal course - LSCS at 37 wks
 If fetus develop hydrops- Paracentesis, LSCS
 Low CO out - Immediate Pacing, Isoprenline
 Features of SLE - oral prednisolone
 Endocardial fibroelastosis – IV IgG
 Fetus with isolated Complete A –V block
Prevalence: The fetal mortality rate of isolated CAVB may be as much as 30 - 50%. Patients diagnosed and
treated in the neonatal period have a survival rate of 94%, and patients who are diagnosed and treated in
childhood have a survival rate of 100%.
• HR > 55/min with normal LV function; Treatment - Dexamethasone - orally to mother
• HR < 55/min with abnormal LV function; Rx - Dexamethasone - orally with β agonist weekly follow up
by obstetrician with fetal echocardiography
 Premature ventricular contraction in fetus: A benign condition either resolve spontaneously before
birth or after birth of baby. If number of PVC is more, and fetus develop Hydrops: - then β blocker can be
used orally.
 Ventricular tachycardia: Fetal therapy for VT is administration of β – blocker; Flecanide = 200-
300mg/day orally and Amiodarone = 600-800mg/day I.V. to mother.
2. FETAL THYROID GOITER
 Fetal cord blood for thyroid status TSH,T3,T4.
 If hyperthyrodism Rx - carbimazole methimazole
 If hypothyroidism –Levothyroxin 250-500 mg weekly intra amniotic between 29-37 weeks. This will
result in regression of thyroid goiter.

3. CONGENITAL ADRENAL HYPERPLASIA

Congenital adrenal hyperplasia (CAH) is a family disorder caused by reduced activity of enzymes required
for cortisol biosynthesis in the adrenal cortex. The most common defect is 21-hydroxylase (21-OH)
deficiency, which accounts for >90% of all cases of CAH. Classic 21-hydroxylase deficiency is found in
about 1:12 000 to 1:15 000 births. The frequency of non classic deficiency is unknown, although it may
occur in up to 3% of individuals in certain groups.
Clinical consequences of 21-OH deficiency arise primarily from overproduction and accumulation of
precursors proximal to the blocked enzymatic step. These precursors are shunted into the androgen
biosynthesis pathway, producing virilization in the female fetus or infant and rapid postnatal growth with
accelerated skeletal maturation, precocious puberty, and short adult stature in both males and females
Treatment should begin as early as the 4th to 6th week of pregnancy.
 The dose of dexamethasone usually ranged between 0.5 and 2 mg/d or O.3 to o.7 mg/sq m in 1 to 4
divided doses.
 CVS 11-12 wks & amniocentesis at 15 wks for DNA analysis for CYP21B,C4 & HLA class I & II
genes. Then treatment is continued to term in female positive for genes and stoped in male after
confirmation of diagnosis by CVS or Amniocentesis.
 At birth, the external genitalia is normal in the infant whose mother was given dexamethasone and
minimally virilized in the infant whose mother received hydrocortisone.

4. FETUS WITH MATERNAL SLE

If mother is suffering from SLE, then fetus is at risk to develop complete heart block because of damage to
AV node. This can be prevented by giving Tab Dexamethasone 4 mg per day during pregnancy because it
cannot be metabolized by placenta and is available to the fetus in an active form.
 

INVASIVE FETAL THERAPY

1. INTRA UTERINE BLOOD TRANSFUSION

The fetal anemia now can be predicted by doing middle cerebral artery doppler flow study and intra
uterine transfusion (IUT) is done with gamma Irradiated blood.
Volume of blood to be given to fetus is calculated by
Fetoplacental volume X (desired Ht – Fetal Ht)
= ------------------------------------------------------------
Donor hematocrit
Feto placental volume = USG estimated weight of fetus X 0.14
The amount of blood given in intra uterine blood transfusion to fetus is 20,30,40 and 50 ml to the fetus at
22,26,30 and 35 weeks of gestational age respectively.

2. FETAL VISUALIZATION ;
EMBRYOSCOPY
Embryoscopy is performed in the first trimester of pregnancy (up to 12 weeks’ gestation). In this
technique, a rigid endoscope is inserted via the cervix in the space between the amnion and the chorion,
under sterile conditions and ultrasound guidance, to visualize the embryo for the diagnosis of structural
malformations.
FETOSCOPY
Fetoscopy is performed during the second trimester (after 16 weeks’ gestation). In this technique, a
fine-caliber endoscope is inserted into the amniotic cavity through a small maternal abdominal incision,
under sterile conditions and ultrasound guidance, for the visualization of the embryo to detect the presence
of subtle structural abnormalities. An injection will be given in the lower abdomen to numb the skin where
the fetoscope will be inserted. An ultrasound will be used to determine the position of both the fetus and
the placenta.A camera is attached to the fetoscope to take pictures. The fetus is seen through a small
incision made in the belly, and a fetal ultrasound guides the placement of the fetoscope.

3. LASER COAGULATION OF  ARTERIOVENOUS  ANASTOMOSES

Laser coagulation of A –V malformation in case of twin to twin transfusion in monochorionic twin
Rx Indomethacin

4.  CONGENITAL DIAPHRAGMATIC HERNIA

Rx Initial approach to treat CDH was - tracheal occlusion by clips on the trachea. It is now performed with
intra-tracheal inflatable balloon. The balloon is inserted at 26 to 28 weeks and removed at 34 weeks.

5. PLEURAL EFFUSION:
One option in the management of fetuses with pleural effusion is thoracocentesis and drainage of the
effusions. However, in the majority of cases the fluid reaccumulates within 24-48 hours requiring repeated
procedures and it is therefore preferable to achieve chronic drainage by the insertion of pleural- amniotic
shunts.

6. GENE THERAPY
Gene therapy 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.
In most gene therapy a normal gene is inserted into genome to replace an abnormal, disease causing gene.
A carrier molecule called a vector (virus- lenti virus) must be used to deliver the therapeutic gene to the
patient’s target cells.
 There have been several modes of gene delivery used in experimental efforts at fetal gene transfer. These
include intratracheal, intravascular, intraventricular, intracardiac, intraperitoneal, intraplacental,
intramuscular and intra-amniotic injection.
Intra-amniotic gene transfer (IAGT) has been used to target organs exposed to amniotic fluid, that is, the
skin, amniotic membranes and the respiratory and digestive systems

7. FETAL IMAGE GUIDED PROCEDURES.

FETENDO - Fetal Endoscopic Surgery for termination of pregnancy
EXIT procedure - Ex-Utero intrapartum treatment procedure.