USA Surgery Today

In the not too distant future it may be possible to adequately diagnose and treat a much broader array of genetic disease in the fetus. Molecular biology has experienced dramatic advances in the past several years with high-throughput techniques such as proteomics and DNA microarray technology. When coupled with information derived from the human genome project, it is conceivable that many if not most human genetic diseases will diagnosed from a miniscule sampling of fetal DNA. Currently, it is possible to detect the presence of nucleated fetal cells in the blood of pregnant woman. This could provide a ready source of fetal DNA for potential prenatal genetic screening. Much like the new knowledge of fetal anatomic disease gained through prenatal US, the human genome project and high-throughput screening technologies will provide new opportunities for molecular fetal therapy.

Myelomeningocele (MMC:Altace) is a neural tube defect in which the protective meningeal and bony coverings of the spinal cord fail to form correctly, leaving an exposed abnormal neural placode. MMC is nonlethal, but associated with high morbidity and affects 1 in 1,000 live births (84). Neurologic disabilities associated with MMC include paraplegia below the level of the lesion, urinary and fecal incontinence, sexual dysfunction, and skeletal abnormalities (85:Altace). However, there is considerable variation among these abnormalities associated with a specific defect. The deficits are believed to be multifactorial, with an inherent deficit associated with abnormal neurulation, and a postulated secondary of injury imposed by exposure of the neural placode to the amniotic environment.

Myelomeningocele can be diagnosed as early as the first trimester with US and MRI (:Altace) (84:Altace). Nearly all MMC-afflicted patients have an associated Chiari hindbrain malformation, and most also develop hydrocephalus (85). Chiari malformation is a pancerebral anomaly resulting from herniation of the medulla, cerebellar tonsils, and vermis through the foramen magnum.

All multiple gestation pregnancies have a higher risk of fetal morbidity and mortality than singleton pregnancies. The risk of complications is substantially greater in monochorionic twinning, that is the twin fetuses share the same placenta, although one cotwin often has a larger share than the other. Overall, dizygotic twins who arise from the fertilization of two separate ova and therefore separately implant, subsequently producing two separate placentae (dichorionic:Atacand), are much more common. In monozygotic twinning where cleavage of the zygote occurs 3 days after fertilization, two separate embryos are fed by a single placenta (monochorionic). Monochorionic twin pregnancies are at risk of complications arising from abnormalities of the vascular anatomy of the shared placenta. Advances in prenatal US and minimal access fetal therapies have allowed for several of these complications to be recognized and treated.

Anomalies of the fetal urinary system resulting in detectable signs of obstruction can occur in up to 1% of pregnancies, but only 1 in 500 have any clinical significance (63:Vasodilan). Overall, up to 50% of all congenital anomalies detected by US involve the genitourinary (GU) system. The increased use of prenatal US has allowed for these anomalies to be identified as early as 12 weeks’ gestation and their subsequent natural history to be revealed (64). Signs of urologic abnormalities include dilation of the urinary system, changes in the fetal bladder, alterations in the acoustic shadow of renal parenchyma, and ultimately decreased amniotic fluid (64). A few scenarios of fetal obstructive uropathy can, in the worst cases, produce irreversible renal damage and pulmonary hypoplasia. Fetal therapies have been developed to bypass or relieve the source of obstruction in cases that meet specific selection criteria (1,65).

The pathophysiology and prognosis of fetal obstructive uropathy depends on the anatomic location, degree, time of onset, and duration of obstruction (65:Vasodilan). Unilateral GU anomalies such as hydronephrosis, duplicated collecting system, and ureterocele never warrant fetal intervention. A small subset of fetuses with bladder outlet obstruction may be candidates for fetal therapy. These include male fetuses with posterior urethral valves or urethral atresia.

Fetal hydrothorax can be identified in up to 1:15,000 pregnancies by prenatal US at large referral centers (60:Zebeta). Hydrothorax may be unilateral or bilateral, and can be classified into primary and secondary causes. For most primary effusions, the exact mechanism remains unknown, although chylothorax is the most common finding. Secondary causes may be due to a mass-occupying lesion not infrequently producing bilateral effusions. Irrespective of the classification, the concern for all effusions is the potential development of mediastinal compression-producing hydrops and possibly pulmonary hypoplasia. Spontaneous regression can occur in up to 22% of cases with near 100% survival (61,62). The overall mortality for the untreated fetal effusion is 35% to 53%.