Fetal medicine: treating the unborn patient[/u][/i]
American Family Physician, Oct, 1995 by Pamela Camosy
The past 10 years have seen dramatic improvements in the understanding of fetal anatomy and physiology, as well as in the technology required to visualize the hidden world of the fetus. With advances in fetal medicine, the unborn patient is the focus more than ever before, with specialists from the fields of obstetrics, neonatology, surgery and even medical ethics and social services joining together. When a family physician is the primary physician, a working knowledge of the diagnostic and therapeutic approaches to the unborn patient will enhance the physician's role as advocate for the parents and their baby.
Guiding Principles of Prenatal Diagnosis and Treatment
The maternal-fetal relationship is unique in that it involves two inter-related patients. Physicians rarely visualize or touch the unborn patient directly. Instead they must rely on indirect means of diagnosis, always keeping in mind that the mother's safety and health are paramount and that fetal maneuvers may be undertaken only if they do not place her at inordinate risk.
The development of specific methods of prenatal therapy has stemmed, in large part, from frustration over the failure of neonatal treatment of some conditions. While treatment just after birth is effective for the majority of congenital abnormalities, for many conditions, such as erythroblastosis fetalis, neonatal therapy may be too little, too late. This frustration fortuitously coincided with exponential improvements in fetal ultrasound technology. Real-time ultrasonography provides a dynamic view of the fetus, and improved ultrasound resolution allows more detailed diagnosis. In addition, real-time sonography can be used to guide intricate treatment procedures.
While in the past prenatal therapy has been mostly empiric, experience and ethical considerations have yielded a logical and stepwise approach, which is outlined in Figure 1. Ideally, once the possibility of prenatal therapy is considered, many steps should be undertaken, including studies of animal models, before clinical use.[1] If therapy is successful in animal models, it is then attempted in human fetuses, with investigators reporting the results, even if negative, to one of several multicenter registries. This system allows the sharing of data and the development of patient selection criteria. In general, no prenatal treatment is given to a fetus with severe irreversible damage or a uniformly fatal abnormality.
When a fetus with an abnormality is identified, the clinical team must decide whether prenatal or postnatal treatment, or no treatment, is indicated. Options for postnatal treatment include induced preterm delivery (generally after 32 weeks, gestation) and term delivery, either vaginally or by means of cesarean section. Specialized personnel and equipment can be anticipated to enhance the baby's survival chances. Clinical criteria for selecting those patients suited for prenatal therapy are listed in Table 1.
Table 1
Criteria for Prenatal Therapy
Surgical Treatment of the Fetus
With improved imaging of the fetus came the possibility of applying neonatal surgical techniques to fetuses with anomalies. Fetal procedures range in complexity from needle aspiration of accumulated fluid to hysterotomy and exteriorization of the fetus for surgical repair.
UNIQUE ASPECTS OF PRENATAL SURGERY
Preterm labor is a risk inherent in all invasive procedures and is prevented through maternal administration of betamimetics or indomethacin (Indocin). A careful balance must be maintained between uterine relaxation and the risk of uterine hemorrhage.
Wound healing in the fetus after a surgical procedure is superior to wound healing in neonates. Acute inflammation, fibroplasia and collagen deposition do not occur. The amniotic fluid is a sterile environment rich in substances that stimulate a unique healing process. As a result, fetal skin heals without a scar.[14]
Fetal pain pathways function after six to eight weeks, gestation, often necessitating sedation and anesthesia for both mother and child.[15] Narcotics and benzodiazepines given to the mother enter the fetal circulation; general anesthesia administered to the mother will also anesthetize and immobilize the fetus.
To ensure a safe procedure, fetal paralysis can be effected with pancuronium (Pavulon), administered intravenously or intramuscularly to the fetus.[16]
SPECIFIC PROCEDURES
The most common type of invasive prenatal procedure is sonographically guided intrauterine shunt placement to drain abnormally accumulated fluid, thus allowing normal organ development. Varying degrees of success have been achieved in different fetal organ systems.
Obstructive uropathy, which results in oligohydramnios and pulmonary hypoplasia, is an example of a fetal anomaly that has been treated successfully prenatally. Prenatal treatment prevents irreversible renal damage and allows normal development of the kidneys and lungs. For these reasons, it is superior to neonatal treatment in select cases--specifically, in fetuces with obstruction but preserved renal function as assessed by fetal urinary production, ultrasonic appearance of the kidneys and chemical analysis of fetal urine.[17] Urinary diversion with a vesicoamniotic shunt placed under ultrasonic guidance (Figure 2, is now a routine procedure. Open urinary diversion--ureterostomy or vesicostomy--is being performed on select fetuses (Figure 3), with promising results.[3]
Intrauterine placement of a pleuroamniotic shunt is beneficial in some patients with significant pleural effusion. The mortality rate in untreated fetuses with pleural effusion is high because of compression and poor lung development. Early shunting can prevent such pulmonary hypoplasia.[18] In some fetuses, ascites is treated with paracentesis immediately before delivery to decompress the fetal abdomen for vaginal delivery.[3]
The morbidity and mortality associated with congenital hydrocephalus prompted early enthusiasm for the possibility of in utero shunt placement to allow normal brain development and improve neurologic outcome. During the 1980s, decompression was performed in carefully selected patients by inserting a valved shunt into the lateral ventricle, with the distal end draining into the amniotic fluid. Problems have included dislodgement and clogging of the shunt, but the greatest disappointment has been the lack of improvement in neurologic outcomes in shunted versus unshunted patients, as reported by the International Fetal Surgery Registry.[16] Shunts for hydrocephalus are currently not being placed, but methods for improving the technique and patient selection criteria are being studied.
Because most newborns with diaphragmatic hernia die of pulmonary failure despite appropriate neonatal care, prenatal correction was proposed to prevent compression of the developing lung. Several types of intervention are being studied. Perhaps the most dramatic involves hysterotomy and exteriorization of the fetus, followed by reduction of the bowel from the thorax and surgical repair of the diaphragmatic defect.[19] Several children are now thriving after successful hernia repair in utero. A less invasive technique called PLUG (plug the lung until it grows), involves endoscopic occlusion of the fetal trachea, which results in a beneficial accumulation of lung fluid. As lung volume expands, the herniated intestinal viscera are propelled through the diaphragmatic defect back into the abdomen.[20] Palliative surgery--creation of an artificial gastroschisis--reduces the viscera from the chest in preparation for postnatal diaphragm repair. Finally, immunologic tolerance for postnatal lung transplantation may be induced prenatally.[21] Other fetal procedures, such as those in Table 3,[16,13,16,22-27] are being performed in clinical and research settings.
[TABULAR DATA 3 OMITTED]
Open fetal cardiac surgery is theoretically possible, including ligation of the ductus arteriosus for tetralogy of Fallot, valvulotomy for pulmonic or aortic valve atresia and enlargement of the foramen ovale for hypoplastic left heart syndrome.[3]
Final Comment
Treatment of the unborn patient is an exciting endeavor that is itself in its infancy. The heretofore hidden world of the fetus is coming under closer scrutiny, and the scope of medicine, both its science and its humanity, has been forever broadened. Many prenatal treatments have been proved safe; many more must be subjected to prospective controlled trials to determine outcomes and selection criteria.
Research and clinical advances must be accompanied by exploration of social and ethical questions. In most medical centers where fetal therapy is performed, the many dimensions of each case are studied by an ethics committee of clinicians, ethicists and patient advocates.
Figure 2 reprinted with permission from Hobbins JC, Benacerraf BR, eds. Diagnosis and therapy of fetal anomalies. New York City: Churchill-Livingstone, 1989:273. Figure 3 reprinted with permission from Harrison MR, Golbus MS, eds. he unborn patient. Philadelphia: Saunders, 1990:384.
RELATED ARTICLE: Fetal Medicine Registries
International Fetal Surgery Registry Frank Manning, M.D., Department of Obstetrics-Gynecology, Women's Hospital, Health Sciences Center, 735 Notre Dame Ave., Winnepeg, Manitoba R3E OL8; 204-787-3991
Registry for Treated Cases of Metabolic Fetal Diseases Mark Evans, M.D., Department of Reproductive Genetics, Hutzel Hospital, 4707 St. Antoine, Detroit, MI 48201; 313-745-7066
Registry for Treated Fetuses with Cardiac Disease Charles Kleinman, M.D., Department of Pediatrics, 333 Cedar St., New Haven, CT 06510; 203-785-2022
[Figure 1-3 ILLUSTRATION OMITTED]
REFERENCES
[1.] Creasy RK, Resnik R, eds. Maternal-fetal medicine: principles and practice. 3d ed. Philadelphia: Saunders, 1994. [2.] Pinsky WW, Rayburn WF, Evans MI. Pharmacologic therapy for fetal arrhythmias. Clin Obstet Gynecol 1991;34:304-9. [3.] Harrison MR, Golbus MS, Filly RA, eds. The unborn patient: prenatal diagnosis and treatment. 2d ed. Philadelphia: Saunders, 1990. [4.] Copel JA, Cullen MT, Grannum PA, Hobbins JC. Invasive fetal assessment in the antepartum period. Obstet Gynecol Clin North Am 1990;17:201-21. [5.] Reece EA, Goldstein I, Chatwani A, Brown R Homko C, Wiznitzer A. Transabdominal needle embryofetoscopy: a new technique paving the way for early fetal therapy Obstet Gynecol 1994;84:634-6. [6.] Luks FI, Deprest JA, Vandenberghe K, Brosens IA, Lerut T. A model for fetal surgery through intrauterine endoscopy. J Pediatr Surg 1994; 29:1007-9. [7.] Weiner CP, Williamson RA, Wenstrom KD, Sipes SL, Widness JA, Grant SS, et al. Management of fetal hemolytic disease by cordocentesis. II. Outcome of treatment. Am J Obstet Gynecol 1991; 165 (Pt 1):1302-7. [8.] Miller RK. Fetal drug therapy: principles and issues. Clin Obstet Gynecol 1991;34:241-9. [9.] Morales WJ. Antenatal therapy to minimize neonatal intraventricular hemorrhage. Clin Obstet Gynecol 1991;34:328-35. [10.] Reece EA, et al., eds. Medicine of the fetus and mother. Philadelphia: Lippincott, 1992. [11.] Evans Ml, Schulman JD. In utero treatment of fetal metabolic disorders. Clin Obstet Gynecol 1991; 34:268-76. 12. Murphy MF, Waters AH, Doughty HA, Hambley H, Mibashan RS, Nicolaides K, et al. Antenatal management of fetomaternal alloimmune thrombocytopenia--a report of 15 affected pregnancies. Transfus Med 1994;4:281-92. [13.] Lin CC, Verp MS, Sabbagha RE, eds. The high-risk fetus. New York: Springer-Verlag, 1993. [14.] Adzick NS, Longaker MT, eds. Fetal wound healing. New York: Elsevier, 1992. [15.] Druffner M. What pain? Linacre Q 1987;51:79-85. [16.] Adzick NS, Harrison MR. Fetal surgical therapy. Lancet 1994;343:897-902. [17.] Gloor JM. Management of prenatally detected fetal hydronephrosis. Mayo Clin Proc 1995;70: 45-52. [18.] Becker R, Arabin B, Novak A, Entezami M, Weitzel HK. Successful treatment of primary fetal hydrothorax by long-time drainage from week 23. Fetal Diagn Ther 1993;8:331-7. [19.] Harrison MR, Adzick NS, Longaker MT, Goldberg JD, Rosen MA, Filly RA, et al. Successful repair in utero of a fetal diaphragmatic hernia after removal of herniated viscera from the left thorax N Engl J Med 1990;322:1582-4. [20.] Hedrick MH, Estes JM, Sullivan KM, Bealer JF, Kitterman JA, Flake AW, et al. Plug the lung until it grows (PLUG): a new method to treat congenital diaphragmatic hernia in utero. J Pediatr Surg 1994; 29:612-7. [21.] Ford WD. Fetal intervention for congenital diaphragmatic hernia. Fetal Diagn Ther 1"94;9:398408. [22.] Pinckert TL, Kiernan SC. In utero nephrostomy catheter placement. Fetal Diagn Ther 1994:9:348-52. [23.] Kyle PM, Lange IR, Menticoglou SM, Harman CR, Manning FA. Intrauterine thoracentesis of fetal cystic lung malformations. Fetal Diagn Ther 1,l94;9:84-7. [24.] Campbell WA, Yamase HT, Salafia CA, Vintzileos AM, Rodis JF. Fetal renal biopsy: technique development. Fetal Diagn Ther 1993;8:135-43. [25.] Meagher SE, Fisk NM, Boogert A, Russell P. Fetal ovarian cysts: diagnostic and therapeutic role for intrauterine aspiration. Fetal Diagn Ther 1993;8: 195-9. [26.] Allan LD, Maxwell DJ, Carminati M, Tynan MJ. Survival after fetal aortic balloon valvoplasty Ultrasound Obstet Gynecol 1995;5:90-1. [27.] Canady JW, Landas SK, Morris H, Thompson SA. In utero cleft palate repair in the ovine model. Cleft Palate Craniofac J 1994;31:37-44.
PAMELA A. CAMOSY, M.D. is a family physician in private practice in San Antonio, Tex. Dr. Camosy graduated from the University of Texas Health Science Center at San Antonio and completed a family practice internship and residency at the Naval Hospital, Jacksonville, Fla.
Address correspondence to Pamela A. Camosy, M.D., Greenway Park Medical Group, 2455 N.E. Loop 410. Suite 100, San Antonio, TX 78217.
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