Fetal therapy

D R AN K I T G U P TA
M M D P E D I AT R I C S
K I M S , K AR AD
FETAL THERAPY

 FETAL THERAPY
 A branch of fetal medicine
 Focused on the health of the baby even before birth
 Includes a series of interventions on the ‘sick’ fetus with the
aim of achieving fetal well being
 Interventions may be
 Medical
 Surgical
 Team work
 Obstetricians, pediatricians, geneticists, endocrinologists and
surgeons working together for early diagnosis and management

HIGH RISK PREGNANCIES
 Primary selection
 Maternal under nutrition
 Presence of chronic illness like DM, hypothyroidism and
thyrotoxicosis
 Bad obstetric history
 Rh negative blood group
 Secondary selection
 Maternal infections, APH, anemia,
 Multiple pregnancy
 PROM, Poly or Oligohydraminos
 Rh isoimmunization, PIH, early onset of labor

MALFORMATION
 DEFINITION
 A structural defect in the body due to abnormal embryonic or
fetal development
 For ex – cleft lip and cleft palate
 Zygote
 Fertilization of sperm and ova
 Embryo
 Upto 8 weeks of gestation
 Fetus
 9th week till birth

PATTRENS OF MALFORMATION
 SYNDROME
 Group of anomalies due to single or similar etiologies. For ex –
Down syndrome due to trisomy 21
 Associations
 Clusters of malformations that occur together . For ex
VACTERL association
 Disruption
 Extrinsic event during normal development. For ex –
amputation of digits or limbs
 Deformation
 Physical force act upon previously formed structure. For ex –
club feet

IDENTIFICATION OF ANAMOLIES
 Early diagnosis may reduce the birth of abnormal
babies
 Hope in future to achieve normal growth with the aid
of genetic engineering
 Fetus with life threatening defects are managed with
therapeutic abortion

 Prerequisites for prenatal diagnosis and termination
of pregnancy
 Treatment of disorder not available or expensive
 Termination of pregnancy acceptable to couples
 Risk of genetic disorder higher than the diagnostic procedure (
Trisomies, neural tube defects )
 Accurate prenatal diagnostic tests available

ULTRASONOGRAPHY
 Non invasive non-ionozing method
 Replaced radiographic techniques for antenatal
diagnosis and assessment and fetal maturity, growth
and malformations
 Pregnancy can be diagnosed and timed accurately
before the appearance of a positive conventional
pregnancy test
 Fetal sex can be identified as early as 8-10 weeks

 ADVANTAGES
 Widely available and no known adverse effects
 Newer techniques, including high resolution multiplanar
imaging, 3D imaging, and doppler imaging have improve its
yield
 DISADVANTAGES
 Poor images with an engaged fetal or oligohydraminos
 Success is operator dependent

FETOSCOPY
 Fetoscopy
 Endoscopic procedure
during pregnancy to allow
access to the fetus, the
amniotic cavity, the
umbilical cord, and the
fetal side of the placenta
 Fetoscopy allows medical
interventions such as
a biopsy or a laser
occlusion of abnormal
blood vessels or the
treatment of spina bifida

ASSESSMENT OF FETAL WELL BEING
 FETAL ACTIVITY RECORD
 Simple method
 Counting the no. of movements or ‘quickening’ made by baby
during third trimester of pregnancy
 NON STRESS MONITORING
 Simultaneous record of FHR, uterine contractions and fetal
movements provide useful information
 Fetus is considered ‘reactive’ and without distress if
 Demonstrate acceleration of heart beats by 15 or more for 15 sec
in association with fetal movements at least twice in a 20 minute
period
 For demonstration of fetal hypoxia

 OXYTOCIN CHALLENGE TEST (OCT)
 Useful test to assess integrity of uteroplacental unit
 Uterine contractions are induced with oxytocin and their effects
on fetal heart rate is monitored
 Positive OCT indicative of fetal hypoxia
 Negative OCT indicator of adequacy of utero-placental unit
 If OCT shows permanent late deceleration, baby should be
delivered if L/S ratio indicates fetal maturity

 FETAL BIOPHYSICAL PROFILE
 Most accurate and non-invasive method to assess fetal well
being and assessed by real time USG
 Based on five parameters as shown in table
 Acc to score interventions are taken
 Score 8 - 10 – Normal fetus
 Score 6 – Indicative of chronic asphyxia
 Score 4 – Compromised fetus
 Score 0-2 – Severe degree of chronic asphyxia

MANNING SCORE
VARIABLE NORMAL ABNORMAL
Posture Flexed Extended
Fetal breathing
movements
At least 1 episode of FBM of
at least 30 sec duration in
30 min
Absent FBM or < 30 sec
Gross body
movements
At least 3 body/limb
movements in 30 min
2 or less
Reactive FHR At least 2 episodes of FHR
acceleration of 15 bpm of at
least 15 sec duration in a
period of 30 min
Less than 2 episodes
Amniotic fluid
volume
At least 1 pocket of AF
measuring 1 cm or more
No AF pocket or < 1 cm

 DOPPLER VELOCIMETRY STUDIES
 Reliable to assess the adequacy of utero-placental circulation
to fetus
 Normal flow is from mother to fetus
 Absence of umbilical artery end diastolic flow (AEDF) or
reversal of umbilical artery end diastolic flow (REDF) are
ominous
 FETAL SCALP BLOOD SAMPLING
 Good correlation between fetal scalp pH of 7.15 and severe
birth asphyxia at birth
 If scalp pH less than 7.10, baby should be delivered

BIOCHEMICAL SCREENING
 ALPHA-FETO PROTEIN( AFP )
 Glycoprotein produced by yolk sac and fetal liver during
second month
 Peak levels achieved around 14 weeks of gestation and then
production wanes off gradually

 MATERNAL SERUM ALPHA-FETO PROTEIN
(MSAFP)
 A useful non invasive test to monitor high risk pregnancies
 Fetal AFP transferred to mother through placenta and amniotic
membranes
 Median level around 25ng/ml at 16 weeks and incerases till 30
weeks
 Maintained for next 5-6 weeks and then falls rapidly
 Optimum time for screening is 16-20 weeks of gestation
 If high or low should be repeated with USG to confirm
diagnosis

 Elevated MSFAP
 Fetal causes
 Open neural tube defects: anencephaly, open meningomyelocele
 Multiple pregnancy
 Missed or threatened abortion or fetal death
 Fetal infections
 Turner syndrome
 Extrophy bladder
 Exomphalos and gastrochisis
 Underestimated gestation

 Maternal causes
 Below average maternal weight
 Low MSAFP levels
 Fetal autosomal aneuploidy (Down syndrome, trisomy 18)
 Molar pregnancy
 Diabetes mellitus
 Over estimated gestation
 Above average maternal weight

 HUMAN CHORIONIC GONADOTROPHIN
 Produced during pregnancy and helps in maintenance of
corpus luteum
 Initially produced by trophoblast, later by placental
synchitiotrophoblast
 During Normal pregnancy
 Increase in hCG levels till 8th week followed by gradual decline
 In Molar pregnancy
 Continue to rise beyond 8th week
 Also elevated in Down’s syndrome

 UNCONJUGATED ESTRIOL (UE3)
 Produced by fetal adrenal gland is handled by placenta and
conjugated by fetal liver
 Lower in pregnancies with Down’s syndrome
 TRIPLE TEST
 Evaluation of three maternal serum factors namely AFP, hCG
and UE3 for evaluation for Down’s syndrome
 In Down’s syndrome
 AFP and UE3 decreased
 hCG levels increased

TRIPLE TEST
DISOREDRS MSAFP UE3 Beta hCG INHIBIN A
Open NTD Increased No change No change No change
Down’s
syndrome
Decreased Decreased Increased Increased
Trisomy 18 Decreased Decreased No change No change

PRENATAL CYTOGENETICS
 Chromosomal aneuploidies and chromosomal
abnormalities (deletion, translocation) can be
diagnosed prenatally
 Indications are
 Advanced maternal age
 Previous child with aneuploidy
 Parental chromosomal abnormalities
 Fetal abnormalities detected on USG
Cells used are
 Chorionic villus sampling (CVS)

 Amniocytes obtained by amniocentesis
 Fetal blood by cordocentesis
 Result is available
 Within 72 hours with CVS and cordocentesis
 2 to 3 weeks with amniotic fluid

AMNIOCENTESIS
 Diagnostic
 Detection of chromosomal abnormalities.
 Downs syndrome
 Trisomy 18, 13.
 Inborn errors of metabolism.
 Sex linked disorder – Turners, klinefelters, fragile x syndrome.
 NTD – by AFAFP levels
 Fetal lung maturity by measuring ratio of Lecithin and
sphingomycelin in later pregnancy.
 Spectrometric analysis of AF determination of degree of fetal
hemolysis in Rh neg mother.
 Therapeutic
 Decompression of polyhydroamnios.

•STEPS OF AMNIOCENTESIS-
1. Under all aseptic precautions a 20 or
22-G needle is used, under USG
guidance needle is inserted in two rapid
steps.
2. Once in amniotic cavity fluid is
aspirated 1st ml of fluid is discarded
because of possible contamination.
3. Total of 20ml of fluid is aspirated and
used for fetal karyotyping and for AFP
levels.
4. At end of procedure puncture site is
observed with help of USG for any
bleeding and fetal cardiac activity is
documented at end of procedure.
5. Bloody tap is discarded as it
overestimate the AFP levels

CHORIONIC VILLUS SAMPLING
 CVS, a biopsy of the developing placenta is
performed at 10 to 13 weeks of gestation for
indications similar to Amniocentesis.
 Advantages over Amniocentesis are
 Performed earlier in gestation.
 Early diagnosis and patient can have option of 1st trimester
abortion. (more safer then 2nd trimester.)
 Two commonly used approaches
 1) Transcervical
 2) Transabdominal.
 Sample consist of placental tissue (~20 mg).

CORDOCENTESIS
 Direct fetal blood is obtained from the umblical
vessel with USG guidance
 Diagnostic tests
 Direct karyotyping
 DNA studies
 Diagnosis of hematologic problems. For ex – thalassemia,
hemophillia
 Diagnosis of fetal infections
 Complications may be fetal loss, preterm labor,
chorioamnionitis

PROCEDURES FOR ANTENATAL DIAGNOSIS
PROCEDURE TIMING RISKS INDICATIONS
CVS 9-12 weeks
(transcervical)
>12 weeks
(transabdominal)
Fetal loss 3-5%,
feto-maternal
hemorrhage and
limb defects
Molecular,
cytogenetic and
biochemical
studies
Amniocentesis 16-18 weeks Fetal loss 0.5-1%,
feto-maternal
hemorrhage and
respiratory
problems
Molecular,
cytogenetic and
biochemical
studies
Cordocentesis > 18 weeks Fetal loss 1-5% Hematological,
infections and
cytogenetic studies

MATERNAL MEDICATION
 Developing fetus is immature both structurally and
functionally
 Drug safe for mother may be harmful and damaging
to fetus
 Women are exposed to various potential
reproductive toxins without being aware of as
 Occupational, environmental and household chemicals e.g.
solvents, pesticides, and hair products

 Timing of intake of drugs have the most influence on
the effect
 For instance ‘Periconceptional period’ is most vulnerable as
women do not realize they are pregnant until they miss the
period
 So, married woman should avoid unnecessary medications
two weeks preceding menstruation
 During first trimester results in miscarriage or
congenital malformations
 During later period effects mostly neonate rather
than the fetus

 Effect of drug may be evident even during later life
 For eg diethylstilbestrol resulted in adenocarcinoma in the
female offspring during 2nd or 3rd decade of life
 Therefore pediatrician should always be alert to
recognize and manage a baby who show effects of
in-utero medication

TERATOGENS
 Any agent that can disturb the
development of an embryo or
fetus
 May include radiation, maternal
infections, chemicals and drugs
 Teratogens are usually discovered after
an increased prevalence of a particular
birth defect
 Harm depends on a range of factors
including:
 the type of drug
 the size of the dose
 how often it’s taken
 the stage of fetal development
(gestational age) at the time of drug
exposure

HUMAN TERATOGENS
DRUGS FETAL EFFECT
RETINOIC ACID CNS DEFECTS, VSD, ASD, TOF
LITHIUM EBSTEIN ANAMOLY
PROPYLTHIOURACIL HYPOTHYRODISM
WARFARIN SKELETAL ANAMOLIES, NASAL
HYPLASIA
ALCOHOL FETAL ALCOHOL SYNDROME
THALIODOMIDE LIMB REDUCTION DEFECTS
VALPROIC ACID NEURAL TUBE DEFECTS
PHENYTOIN DYSMORPHIC FEATURES, CLEFT LIP
AND PALATE
MISOPROSTOL LIMB MALFORMATIONS
METHOTREXATE GROWTH RESTRICTION,
SYNDACTYLY, SKELETAL DEFECTS

MATERNAL CONDITIONS FETAL EFFECT
DIABETES NEURAL TUBE DEFECTS, SACRAL
AGENESIS, CHD, RENAL ANAMOLIES
SYSTEMIC LUPUS
ERYTHEMATOSUS
CARDIAC CONDUCTION
ABNORMALITIES
MATERNAL PHENYKETONURIA MICROCEPHALY
MYSTHENIA GRAVIS NEONATAL MYSTHENIA
EXPOSURE TYPE FETAL EFFECT
RADIATION MISCARRIAGE
PROLONGED HEAT EXPOSURE MICROCEPHALY
SMOKING GROWTH RESTRICTION
LEAD LOW BIRTH WEIGHT
MERCURY CNS ANAMOLIES

INFECTIONS FETAL EFFECT
CYTOMEGALOVIRUS MICROCEPHALY, CHORIORETINITIS
TOXOPLASMOSIS HYDROCEPHALUS,
CHORIORETINITIS, VISUAL
IMPAIRMENT
RUBELLA CATRACTS, MICRO-OPTHALMIA,
GLAUCOMA, CHORIORETINITIS,
CHD
SYPHILLIS MENIGIOENCEPHALITIS, SNUFFLES,
PERIOSTITIS

RADIATION
 Large doses of radiation (20-50 rad) may cause
 Fetal death ( 3rd to 4th post conception week )
 Microcephaly, severe mental retardation, and growth
retardation ( 4th to 15th week )
 Higher incidence of leukemia and cancer to the
children born
 Women may be unaware of the hazard she is
exposed to at the time of conception. So it is
recommended
 Radiological studies restricted to 2 weeks post-menstruation
period
 No pelvic X–ray during first trimester

 X-ray(0.1 rad) and CT scan(5 rad) should be avoided
as much possible
 Available data suggest no harmful effect on fetus of
diagnostic MRI or USG

FETAL THERAPY
 MEDICAL
 LUNG MATURITY INDUCTION
 INFECTIONS
 Rh ISOIMMUNIZATION
 THROMBOCYTOPENIA
 CAH
 THYROID DISORDERS
 NEURAL TUBE DEFECTS
 FETAL HEMATOPOIETIC STEM CELL TRANSPLANTATION
 FETAL ARRUTHMIAS, SUPRAVENTRICULAR
TEACHYCARDIA AND CONGENTIAL COMPLETE HEART
BLOCK

 SURGICAL
 OBSTRUCTIVE UROPATHY
 HYDROCEPHALUS
 TWIN TO TWIN TRANSFUSION
 CONGENITAL DIAPHRAGMATIC HERNIA

MEDICAL
 ACCELERATION OF FETAL MATURATION
 HYALINE MEMBRANE DISEASE (HMD) OR RESPIRATORY
DISTRESS SYNDROME (RDS)
 Commonest cause of neonatal mortality in preterm babies
 Lack of surfactant due to immaturity of lungs is main abnormality
 Pulmonary maturity assesed by results of Lecithin/Spingomyelin
ratio or Phosphatidyl glycerol
 When induction of premature labor unavoidable,
 Betamethasone 12mg IM OD for 2 doses
 Dexamethasone 6 mg IM BD for 4 doses
 Betamethasone preffered, and should be given 24hours to 7 days
before delievery

FETAL INFECTIONS
 EARLY ONSET GROUP B STREPTOCOCCAL
INFECTIONS (GBS)
 Rare in INDIA compared to WEST
 Early infections leads to respiratory distress indistinguishable
from HMD while late cause meningitis
 Predisposing factors
 Prolonged rupture of membrane
 Peripatal febrile maternal illness
 Prematurity
 Intrapartum prophylaxis with antibitoics is administered

DIFFERENCE BETWEEN RDS AND GBS
CRITERIA HYALINE MEMBRANE
DISEASE
GROUP B
STREPTOCCOCAL
INFECTION
PROM > 12 HOURS RARE COMMON
PERIPATAL FEBRILE
ILNESS
RARE COMMON
GESTATIONAL MATURITY INVARIABLY PRETERM MOSTLY PRETERM
ONSET FIRST 6 HOURS ALWAYS AFTER 3
HOURS
COURSE OF ILLNESS VARIABLE SHORT AND
FULMINANT
XRAY CHEST GROUND GLASS INCREASED LUNG
MARKING
GASTRIC ASPIRATE NORMAL POLYMORPHS

TORCH
 STANDS FOR
 T for Toxoplasmosis
 O for others (syphillis, gonococcal ophthalmia, malaria,
tuberculosis, varicella, hepatitis B, parvovirus B19, HIV)
 R for Rubella
 C for Cytomegalovirus
 H for Herpes simplex
 Acronym have become obsolete, VERTICALLY
TRANSMITTED INFECTIONS

CLINICAL FINDINGS IN TORCH
INFECTION IUGR HEPATOSPLE
NOMEGALY
AND
JAUNDICE
OPHTHALMIC NEUROLOGI
CAL AND
OTHERS
CYTOMEGA
LOVIRUS
60-70% TWO-THIRD COTTAGE
CHESSE
WITH
KETCHUP
TYPE OF
CHORIORETI
NITIS
MICROCEP
HALY,
PERIVENTRI
CULAR
CALCIFICATI
ON
RUBELLA 60-70% 50-60%
JAUNDICE
UNCOMMON
CATARACTS,
MICROOPHT
HALMIA, SALT
AND PEPPER
TYPE OF
CHORIORETI
NITIS
MENINGOE
NCEPHALITI
S, CHD
NAMELY –
PDA,
PULMONAR
Y STENOSIS

INFECTION IUGR HEPATOSP
LENOMEG
ALY AND
JAUNDICE
OPHTHALMIC NEUROLOGI
CAL AND
OTHERS
TOXOPLASM
OSIS
20-30% 40-50% CENTRAL
DESTRUCTIVE
CHORIORETINI
TTIS
HYDROCEPH
ALY,
CEREBRAL
CALCIFICATI
ON
SYPHILIS UNCOMMON 30-40% KERATITIS SNUFFLES,
PERIOSTITIS,
CHINDRITIS,
DEAFNESS

SCREENING
 Widespread practice of one time screening of
pregnant women for TORCH infection
 But routine screening not recommended as
 Difficult to differentiate between primary and reinfection
 Sensitivity and specificity of tests of doubtful value
 Created unncessary confusion , NOT COST EFFECTIVE
 So only mother showing symptoms of any disease
should be screened
 If any evidence of active infection, USG and
cordocentesis to confirm fetal diagnosis

DIAGNOSIS
 To screen pregnant women and newborns for
antibodies to the infectious diseases
 Results are either positive or negative
 Presence of IgM antibodies indicate current infection
 In mother
 IgM – CURRENT INFECTION
 IgG – PAST INFECTION
 In baby
 IgM – ACTIVE INFECTION
 IgG – PASSIVE TRANSFER OF ANTIBODIES FROM
MOTHER

 If IgM positive in baby active infection present
 If IgG positive in baby titre to be compared with
mothers titre ( 10 fold rise )
 Also increasing IgG titre in baby suggestive of active
infection

PREVENTION
 TOXOPLASMOSIS
 Spiramycin 2gm/day throughout pregnancy
 After 20 weeks add sulfadiazine and pyrimethamine
 Folinic acid 5mg twice a week along with pyrimethamine
 CYTOMEGALOVIRUS
 Avoidance of unnecessary blood transfusions and use of CMV
negative or leukocyte depleted blood
 Avoid use of donor breast milk
 HERPES SIMPLEX
 10 days course of acyclovir
 In genital herpes, elective cesarean section

 Mother to be treated with appropriate therapeutic
agents
 Family needs to be counseled and option for MTP if
fetus severely affected

 VERTICAL TRANSMISSON OF HIV
 25 – 35% risk of mother to child transmission (MTCT) of HIV
during perinatal period
 30% occur during pregnancy while 70% during labor and
delivery
 Through breast milk – 10 – 15%
 Risk can be reduced to < 2% by
 Prophylaxis given to mother during pregnancy and labor
 To infant during first week of life
 Elective cesarean delivery
 Complete avoidance of breast feeding

 Breastfeeding
 Important modality of transmission of HIV infection
 Controversial whether to be given or not
 Factors that increase the risk of transmission
 Detectable levels of HIV in breast milk
 Presence of mastitis
 Low maternal CD4+ T cell count
 Exclusive breast feeding rather than mixed feeding
 Current UN recommendation
 If replacement feeding is acceptable, feasible, affordable,
sustainable, and safe, (AFASS) breastfeed to be avoided
 ‘Early and abrupt’ cessation of breastfeeding

NEURAL TUBE DEFECTS
 Most common congenital malformation affecting the
brain and spinal cord
 Due to failure of closure of neural tube
 Predisposing factors
 Folic acid deficiency
 Antiepileptic drugs (valproate)
 Folic acid antagonists
 Maternal fever and irradiation
 Recurrence rate
 If one pregnancy affected – 2-3%
 If two pregnancy affected – 10%

 DIAGNOSIS
INVESTIGATION FINDINGS
MATERNAL SERUM RAISED AFP
AMNIOTIC FLUID RAISED AFP AND ACETYL
CHOLINESTERASE
USG
TRANSVAGINAL
TRANSABDOMINAL
SKULL VESSEL ABSENT IN
ANCEPHALY
SPINA BIFIDA – SPLAYING OF SPINE
EVIDENCES OF HYDROCEPHALUS,
LEMON SIGN, BANANA SIGN AND
LOWER LIMB DEFECTS
CHROMOSOMAL STUDIES IF NTD ASSOCIATED WITH
CHROMOSOMAL DISORDER

 Prevention
 Folate 0.4mg daily in normal pregnancy
 Folate 4mg daily in high risk or previously NTD affected
pregnancy
 Fortification of staple foods with folic acid

RHESUS ISO-IMMUNIZATION
 ANTI-D IMMUNOGLOBULIN
 Destroy the Rh positive RBC of the fetus which seeps into the
maternal circulation before they initiate the antibody-antigen
response and prevent the sensitization
 All unsensitized Rh negative mother should receive
prophylactic injection of anti – D when
 After birth of each Rh positive baby
 After abortion of Rh positive conception
 Situations with increased risk of feto-maternal hemorrhage
 Injection of anti-D immunoglobulin(300mcg) should
be given within 72 hours of delivery

 Occasional failures may occur due to
 Prior sensitization
 Feto-maternal leak in early pregnancy
 Large amount of hemorrhage

 IMMUNE HYDROPS
 Hemolytic disease of the fetus
 Condition of fetal anemia caused by Rh isoimmunization
 Antibody screen – to detect presence and titer of maternal
antibodies
 Serial amniocentesis for measurement of bilirubin or serial
codocentesis for direct measurement of hemotocrit, reticulocyte
count and bilirubin are done
 Intrauterine blood transfusion
 Intraperitoneal or intravascular
 Intravascular by codocentesis have replaced intraperitoneal
transfusion

 Combination achieves a more stable Hct and delays time for next
transfusion
 Aim of transfusion to raise hematocrit to 45-50%
 Hct falls at rate of approx. 1% per day so repeated transfusion
requires every 15-20 days till pulmonary maturity or
gestational age of 35 weeks
 O negative, CMV negative allogenic or maternal blood tested
for infection, washed, packed, filtered, irradiated with 2500 Gy
and then transfused
 Baby born with adult O negative blood

INTRA UTERINE BLOOD TRANSFUSION

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
 Clinical consequences of 21-OH deficiency arise primarily from
over production 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

 Following birth of a child with CAH, subsequent
pregnancy should be monitored by CVS at 8-9
weeks
 If fetus affected
 Mother should receive oral dexamethasone 1 mg daily
throughout pregnancy to prevent musculization of female fetus
 Therapy to be continued if fetus is to be found to be
female, otherwise stopped

THROMBOCYTOPENIA
 Mothers with active ITP should receive corticosteroid
therapy during last 2 weeks of pregnancy
 In iso-immune type of fetal thrombocytopenia ( as
evidenced by platelet antigen PLA and history of
previous sibling affected)
 Transfusion of maternal platelets and immunoglobulin through
the umbilical vessels by cordocentesis
 If cordocentesis not feasible
 High doses of iv IVIG 1gm/kg to the mother can prevent fetal
thrombocytopenia

SYSTEMIC LUPUS ERYTHOMATOSUS
 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 4mg per day during pregnancy
because it cannot be metabolized by placenta and is
available to the fetus in an active form.

DIABETES MELLITUS
 Commonest endocrinal disorder during pregnancy
 Duration and severity of maternal diabetes and quality of
its control determine the outcome of the offspring
 Infant of diabetic mother
 Macrosomia
 Susceptible to birth injuries
 Metabolic imbalance
 Greater risk to develop HMD
 Polycythemia
 Increased incidence of congenital malformations

 Management
 Diabetes to be effectively controlled with insulin
 Oral hypoglycemic agents contraindicated due to risk of
teratogenesis and intractable hypoglycemia in newborn
 Strict maintenance of normoglycemia significantly reduce
neonatal morbidity and mortality
 Pulmonary maturity to be assessed
 L/S ratio > 3.5 and SPC > 1000 mcg/dl
 Large baby to be delivered by CS

THYROID DISORDERS
 MATERNAL HYPOTHYROIDISM
 Associated with early fetal deaths
 Placental transfer of thyroid blocking immunoglobulin may cause
fetal hypothyroidism
 Can be prevented by increasing dose of thyroxine to mother
 MATERNAL THYROTOXICOSIS
 High doses of anti thyroid drugs during later pregnancy may cause
fetal goiter and hypothyroidism because they readily cross placental
barrier
 Propylthiouracil drug of choice due to reduced passage across
placenta and excretion in the breast milk
 After initial stabilization with anti thyroid drugs, sub-total
thyroidectomy is the treatment of choice

STEM CELL TRANSPLANTATION
 Hematopoietic stem cell (HSC) transplantation an
attractive theoretical option
 No graft versus host disease
 Prior to 14 weeks, bone marrow has not developed sites for
hematopoiesis
 Thymic processing of self antigens not started
 Foreign HSC should engraft without inducing an immune
rejection
 Bone marrow can be transplanted postnatally from same
donor

 DISADVANTAGES
 Fetal and maternal risk
 Technical expertise
 Expense
 Diseases amenable
 Sickle cell disease and thalassemias
 Immune deficiency diseases
 Inborn errors of metabolism

SUPRAVENTRICULAR TACHYCARDIA
 Must be treated if
 Are sustained and associated with hydrops
 Impending congestive heart failure
 Maternal treatment started after 12-24 hours of fetal
cardiac monitoring
 Digoxin is the first line drug
 Determination of electrolyte, BUN, and creatinine
prior to digoxin loading
 Propranolol, procainamide and quinidine have also
been used

COMPLETE HEART BLOCK
 Prevalence:1/15,000-1/22,000 live birth
 HR > 55/min with normal LV function
 Rx 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

SURGICAL
 Three approaches
 Ultrasonography guided
 Inadequate function, migration, iatrogenic gastrochisis
 Fetoscopic techniques
 Risk of bleeding, rupture of membranes and chorioamnionitis
 Open fetal surgery
 Chorioamnionitis, bleeding, direct trauma

OBSTRUCTIVE UROPATHY
 Fetoscopic techniques can be used for fulguration of
posterior urethral valve, placement of vesicoamniotic
shunts, and vesicostomy
 In severely affected fetus with bladder neck
obstruction
 Marsupialization of the urinary bladder with vesicoamniotic
shunt have been performed with variable results
 In cases with oligohydraminos, outcome poor due to
hypoplastic lungs
 Open surgery have a high mortality rate of 45%

HYDROCEPHALUS
 Ventriculoamniotic shunts
 Used for decompression of obstructive hydrocephalus have
had poor outcome
 Thus their use not indicated
 Fetal surgical procedure
 Both open and endoscopic, have been used to repair
myelomenigocele in utero
 Open procedure is performed at 24-30 weeks and is shown
 To reduce both hindbrain herniation and
 Requirement of shunt posnatally

DIAPHRAGMATIC HERNIA (CDH)
 Intrauterine therapy indicated in fetuses with poor
prognosis
 Those with liver in the chest
 Those with a low lung to head ratio (<1.0) on USG
 Current fetal surgery is tracheal occlusion
 Causes enlargement of the lungs and pushing abdominal
viscera into the abdomen
 Trachea occluded by external metal clips
 Survival rate of 33% compared to 10% with conventional
postnatal therapy

TWIN TO TWIN TRANSFUSION
 May lead to syndrome of acardia due to large arterial
anastmoses
 Umbilical cord ligation is done in the acardiac twin
 Other procedures
 Serial amniocentesis to reduce polyhydraminos
 Occlusion of vascular anastomosis by YAG laser
photocoagulation

GENE THERAPY
 Means replacement of missing gene by introduction
of foreign
 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-lentivirus) must be
used to deliver the therapeutic gene to the patient’s target cells
 Research shows that gene transfer to the developing fetus
targets rapidly expanding populations of stem cells, which are
inaccessible after birth, and indicates that the use of
integrating vector systems results in permanent gene transfer

 For clinicians and parents, fetal gene therapy would
give a third choice following prenatal diagnosis of
inherited disease, where termination of pregnancy or
acceptance of an affected child are currently the only
options
 MAY BE HELPFUL IN
 HEMOPHILLIA B
 ALPHA THALESSEMIA

Fetal therapy

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Fetal therapy