The number of conditions for which fetal surgical or medical interventions are available has expanded significantly in the last 4 decades and is frequently impacted by ethical considerations related to the underlying genetic etiology of the fetal condition in need of treatment. Fetal therapy began in the 1960s with intrauterine transfusion for anemia, particularly in the setting of fetal Rh alloimmunization. This was followed by insertion of shunts to drain excess fluid from the fetus into the amniotic cavity. Shunts are still used for some cases of fetal uropathy (e.g., to drain urine when there is bladder outlet obstruction or to drain large pleural effusions). Laser ablation of communicating placental vessels for twin- twin transfusion syndrome started in the 1990s, and laser procedures for this condition have now become standard of care. For some cases of evolving hypoplastic left heart syndrome, aortic valvuloplasty and now balloon septostomy and atrial septostomy are done in expert centers. After a multicenter randomized controlled trial, the Management of Myelomeningocele Study (MOMS) showed improved outcomes after intra uterine surgical repair of fetal myelomeningocele (spina bifida); this option is now available at selected centers. In recent years the approach has transitioned from open to laparoscopic repair. A subset of fetuses with congenital diaphragmatic hernia have improved outcomes after a balloon is placed inside the trachea with the goal to improve growth and expansion of the fetal lungs. The balloon is removed prior to controlled delivery. Finally, investigation is underway to examine the value of serial amnioinfusions to treat early- onset anhydramnios for fetuses with nonfunctioning kidneys.

In addition to these mechanical fetal procedures, a number of in utero medical therapies are being adopted. Fetal arrhythmias are treated with maternally administered antiarrhythmia medications such as digoxin and sotalol. Sirolimus has established efficacy in the treatment of severe cases of fetal rhabdomyomas. In utero stem cell transplantation and gene therapy trials are underway for conditions such as osteogenesis imperfecta and hemoglobinopathies.

The disorders and congenital anomalies for which these fetal interventions can provide benefit can be caused by genetic defects. Therefore multidisciplinary approaches to evaluation and decision making that include prenatal genetic counseling and assessment are recommended prior to any such procedures. Debate remains as to the depths of investigation that should be undertaken, and a fetal karyotype is recommended as the minimum requirement for some procedures, which contrasts with general recommendations for CMA as a primary genetic test for major congenital anomalies. Post-test counseling after genetic test results are available should include multidisciplinary discussion about the risks, benefits, and alternatives of pursuing a fetal procedure.

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مواضيع ذات صلة

Maternal Inheritance of Disorders Caused by Variants in the Mitochondrial Genome

Genetic Screening in Populations

Genetic Counseling for Preconception and Prenatal Diagnosis and Screening

X-Linked Inheritance

Preconception Genetic Screening and Testing

Problems in Prenatal Chromosome Analysis and Gene Sequencing

Introduction to Cytogenetics and Genome Analysis

Methods to Detect Fetal Chromosomal Abnormalities

The Origin and Frequency of Different Types of Mutation

Noninvasive Prenatal Screening by Analysis of Cell- Free Fetal DNA

Screening for Down Syndrome and Other Aneuploidies

Screening for Neural Tube Defects