Just decades ago, most fetal anomalies developed invisibly in the womb, presenting only at birth as a medical emergency for unsuspecting obstetricians and as a psychosocial emergency for traumatized parents and families.
With sonographic advances came perspicuity, offering for the first time a prenatal glimpse of obstructive uropathy, congenital cystic adenomatoid malformations (CCAM), and myelomeningocele lesions.
Prenatal diagnosis evolved, and with it so did a highly specialized response to life-threatening malformations. Lessons were learned about ways to provide optimal care for women who carried these high-risk fetuses. Close supervision and sequential ultrasounds preceded delivery at tertiary centers, with surgical teams standing by to perform immediate postnatal procedures. Families could be counseled and prepared.
But these new windows into the womb also offered conundrums.
Overall morbidity and mortality remained dismally high, because most fetuses with evident anomalies suffered so much damage by birth that surgical interventions were of little benefit.
Meanwhile, families demanded information from obstetricians and perinatologists, who lacked answers about the basic biology, pathophysiology, and potential outcomes of the defects mapped so clearly on the sonographer's screen.
On many fronts, decades of meticulous preclinical research and epidemiology have given us answers. Today, we can tell a woman whose fetus has a lung lesion a great deal about the lesion's cause and probable course, as well as her baby's chances for survival.
The most promising advance of all has been the ability, in highly selected cases, to intervene with fetal surgery, thus preventing problems from becoming catastrophes and--in many cases--saving fetuses that otherwise would have been doomed.
When Dr. Michael Harrison and I first proposed that we might be able to fix some defects before birth, colleagues and outsiders alike thought we were dreaming. A tremendous amount of work on fetal animals, plus considerable study of the natural history of prenatal anomalies, allowed us to cautiously apply fetal surgical interventions on the very worst cases. We made mistakes, but we learned from these experiences.
Today, approximately 500 open fetal procedures have been performed in the United States, primarily at Vanderbilt University in Nashville, Tenn.; at the University of California, San Francisco; at the University of North Carolina, Chapel Hill; and at my own institution, Children's Hospital of Philadelphia.
Many more fetoscopic procedures and shunt placements have been successfully accomplished at major medical centers throughout the country.
It is a mark of progress that two major prospective randomized trials funded by the National Institutes of Health are underway:
* The Management of Myelomeningocele Study (MOMS), a head-to-head comparison of midtrimester prenatal vs. postnatal repair of myelomeningoceles with Arnold-Chiari II malformation and lesions at the S1-level or higher.
* The Twin-Twin Transfusion Trial, comparing selective fetoscopic laser photocoagulation (SFLP) with amnioreduction.
Consumer magazines have tended to view fetal surgery as a miracle cure. Community obstetricians and gynecologists have tended to take the opposite tack, underestimating the capabilities of our refined fetal surgical techniques.
Fetal surgery remains a rare solution for rare conditions. In the past 9 years, my institution has handled 5,000 prenatal referrals from every state and 40 countries. Fewer than 10% of malformations undergo fetal intervention. Yet the evidence is building that these procedures can repair anomalies that infants would not have survived or that would have been associated with severe disabilities not too long ago. Most notably, we have made significant advances in the following situations:
Resection of enlarging CCAM not amenable to thoracoamniotic shunting.
These benign lung lesions are usually confined to one lobe, and may regress during fetal development. Fetal hydrops, which is often seen during an ultrasound examination that has been prompted by polyhydramnios, is an indication for fetal surgery. Triggered by compression of the great vessels and cardiac compression from large tumors, it is a strong predictor of fetal death and may lead to "maternal mirror syndrome," a potentially devastating complication in which the mother develops the same symptoms as her critically ill fetus. Symptoms of severe preeclampsia associated with this syndrome may develop quickly and may be irreversible, so definitive management is ideally timed soon after diagnosis.
Having treated approximately 600 cases of fetal lung lesions, we have concluded that the absence of hydrops justifies conservative management. These infants generally survive to birth and may be treated neonatally. Planned delivery should be performed at a center that is capable of immediate postnatal evaluation and has extracorporeal membrane oxygenation capability.
Hydropic fetuses should be considered candidates for early delivery if the condition is discovered at 32 weeks' gestation or later, although ex utero resection is generally associated with poor outcomes. The ex utero intrapartum procedure (EXIT), originally designed to improve cardiorespiratory stability via uteroplacental bypass for treatment of tracheal occlusion during delivery, may improve the outlook for these infants.
Before 32 weeks' gestation, thoracoamniotic shunting may suffice for large predominant cysts that do not have a significant solid component.
Multicystic and predominantly solid CCAM lesions may require fetal lobectomy. Our experience with 30 fetal lobectomies at 21-31 weeks' gestation has been mixed, although the natural predicted course for these fetuses would be grim. We have followed 16 healthy survivors for 1-11 years. There were 14 fetal deaths, some from bradycardia secondary to massive hydrops or uncontrolled intraoperative uterine contractions. We have modified our procedure in response to apparent hemodynamic collapse and reactive bradycardia following removal of the lung mass, and now pretreat with atropine and balance the fluid volume after abrupt relief of cardiac compression while monitoring with sterile intraoperative fetal echocardiography.
Resection of sacrococcygeal teratoma (SCT) in fetuses with nonimmune hydrops.
Newborns diagnosed with SCT generally do well after early surgical resection. SCT diagnosed in utero holds a graver prognosis, with a 30%-50% mortality rate associated with rapid tumor growth leading to placentomegaly and hydrops. Risks include maternal mirror syndrome, premature delivery, and dystocia associated with traumatic tumor rupture and hemorrhage.
Open fetal surgery should be considered before 32 weeks' gestation in the face of high-output cardiac failure presaged by the tumor's "vascular steal" from the fetus and placenta. At our center, three out of four such fetuses with hydrops survived after resections were performed at 20-26 weeks' gestation, suggesting that there is room for hope in some of these desperate cases.
Fetal myelomeningocele (MMC) repair.
Although devastating, spina bifida is not associated with the uniformly fatal outcomes common to several other indications for fetal surgery. Yet almost one-fourth of spina bifida pregnancies are electively terminated, and 14% of affected neonates do not survive to age 6, despite aggressive management. Mortality rises to 35% in children with brainstem dysfunction secondary to the Arnold-Chiari II malformation. Survivors often require lifetime medical care and special help for learning disabilities.
We began undertaking in utero repair of MMC in fetuses with an Arnold-Chiari II malformation and a lesion at the S-1 level or higher, once 200 fetal surgeries for life-threatening causes and extensive animal research demonstrated the safety and appropriateness of this approach. Of 50 fetuses that underwent MMC closure from 1998 to 2002 in our institution, 3 died after premature delivery. Preterm labor complicated three other cases, and 11 patients demonstrated chorioamniotic membrane separations that eventually led to premature rupture of membranes. Five infants were delivered at or before 30 weeks; 40 of 47 survivors were delivered at 32 weeks or later.
All 47 surviving fetuses demonstrated reversal of hindbrain herniation, ascent of the cerebellum, and reestablishment of cerebrospinal fluid within the posterior fossa. The resulting arrest or slowing of progressive ventriculomegaly appears to have led to a substantially reduced need for ventriculoperitoneal shunts, which were required in only about half as many infants as predicted, according to studies of historical controls.
Moreover, more than half of surviving infants with thoracic or lumbar-level defects had better-than-predicted leg function, while 7 of 42 had worse-than-predicted leg function on postnatal neurologic examination.
In utero surgery for MMC remains a challenge, with the threat of membrane separation and its sequelae continuing to place these women at very high risk. However, close supervision (including obstetric monitoring of these pregnant patients who stay in the nearby Ronald McDonald house after discharge) has fostered prolongation of most pregnancies to beyond 32 weeks.
The MOMS study will extend the knowledge of our collective experience with in utero MMC repair by randomizing 200 mothers to prenatal or postnatal surgery. The three participating centers in this study are the Children's Hospital of Philadelphia; the University of California, San Francisco; and Vanderbilt University, with data coordination being conducted at George Washington University in Washington.
I strongly encourage the referral of mothers who are carrying fetuses with MMC to this trial. They will receive state-of-the-art care prenatally, postnatally, and during comprehensive neurodevelopmental follow-up assessments. For more information about the study, go to www.spinabifidamoms.com.
BY N. SCOTT ADZICK, M.D.
COPYRIGHT 2004 International Medical News Group
COPYRIGHT 2004 Gale Group
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