Before the Beginning

A formidable force is changing the way prenatal diseases and birth defects are viewed by pioneering ways to help babies before they are born.

by Monika Guttman

The conference room off the cafeteria in the basement of Childrens Hospital Los Angeles does not have the best lighting, but at the moment that does not matter. Every eye is riveted on the image projected at the front of the room. Hollie Jackson, M.D., assistant professor of radiology at the Keck School of Medicine of USC, talks the group of physicians, nurses, social workers and counselors through the hazy gray and black high-resolution MRI image of a 22-week old fetus: Here is where the baby’s spinal cord ends, she notes, pointing her red laser light—and here is where there is an abnormal amount of fluid around the brain.

David Miller, M.D., medical director of the CHLA-USC Institute for Maternal-Fetal Health (IMFH) at Childrens Hospital and associate professor of obstetrics and gynecology and pediatrics at the Keck School, turns to another specialist attending the weekly case management meeting: Istvan Seri, M.D., Ph.D., Keck School professor of pediatrics, chief of the division of neonatal medicine and the Childrens Hospital administrative director of the IMFH. Given this scenario, Miller asks Seri, what is the prognosis for this baby?

If the baby has a chance anywhere, it is here with this team of perinatologists, neonatologists, radiologists, geneticists, surgeons and other pediatric specialists who make up the Institute for Maternal-Fetal Health. These physicians and nurses practice at the frontier of medicine, providing one of the few comprehensive programs nationwide offering concrete help for fetal conditions diagnosed during pregnancy. The program, which is going on its fourth year, is the product of innovative collaboration between the USC Maternal-Fetal Medicine program—one of the first in the country—initiated at LAC+USC Women’s and Children’s Hospital decades ago, and the Childrens Hospital departments of pediatrics and pediatric surgery.

In practice, the IMFH’s advanced, multidisciplinary healthcare approach—treating both mother and baby, bringing specialists in all fields together in one integrated center, continuing care through the pregnancy, birth and neonatal periods—sounds simple. But what the IMFH really does is change the way many prenatal diseases and birth defects are viewed by pioneering ways to help babies before they are born. They are changing the face of perinatal medicine.

“We’re finding many diseases can be prevented or impacted by early interventions from appropriate specialists,” notes T. Murphy Goodwin, M.D., chief of the division of maternal-fetal medicine at USC and USC administrative director of the IMFH. “It’s a revolution, and it’s happening here.”

Take, for example, the fetal surgeries performed by Ramen Chmait, M.D., Keck School assistant professor of obstetrics and gynecology. One of the few perinatologists in the country to offer surgical interventions for a baby in utero, Chmait is saving infants before they are born. In 2006, Chmait performed the first fetal surgery in Los Angeles: an operative fetoscopic laser therapy on a woman 20 weeks pregnant with twins to treat twin-twin transfusion syndrome (TTTS). This life-threatening condition, in which identical twins share a placenta but do not share the blood supply evenly, comes about when the shared placenta contains abnormal blood vessels that connect the umbilical cords and circulations of the twins. TTTS frequently results in the death of at least one, if not both, fetuses.

“When we did the surgery, the recipient twin was already in heart failure,” Chmait says. “If the recipient twin dies, the donor twin has a 30 percent chance of death or brain damage.”

Placing a 3.3-millimeter scope—slightly smaller than a drinking straw—into the uterus through a tiny hole in the skin and the abdominal wall, Chmait used laser energy to remove the connecting blood vessels on the surface of the placenta so that the babies’ blood supply was no longer shared. A few months later, at 36 weeks old, the identical twin boys were born. The first boy weighed in at 4 lbs. 15.6 oz. and the second weighed in at 5 lbs. 13.2 oz., and both were fine.

Since the inception of the minimally invasive fetal surgery program at Childrens Hospital in March 2006, surgeons have performed more than 25 cases. Chmait currently performs about one fetal surgery a week, and has patients referred to him from as far away as Texas, Oregon, Nevada and Hawaii. Among the other fetal operative procedures Chmait performs are an amniopatch, which can seal critical membranes if the amniotic sac breaks too early, as well as placing shunts for urinary tract abnormalities and performing transfusions for severe fetal anemia. “The menu is continuously expanding,” he adds, noting that soon the IMFH team, in collaboration with the division of pediatric cardiology and the departments of cardiothoracic surgery and general pediatric surgery, is planning protocols for fetal heart surgery as well as treatment of congenital diaphragmatic hernias in utero.

Even if the IMFH team is unable to intervene during the pregnancy, the in-depth diagnostics and meetings with specialists before birth mean a top-notch team is assembled to help the newborn during and after birth. That can make the difference between life and death.

In a groundbreaking case, for example, using high-resolution 3D and 4D ultrasound imaging and ultrafast magnetic resonance imaging, physicians at the IMFH realized weeks before that a baby in their care probably would not survive birth because it had an obstructed windpipe.

A team of 30 doctors and nurses was assembled to perform a rare surgery called an ex-utero intrapartum treatment, or EXIT, procedure. Miller performed the first portion of the procedure, a modified cesarean operation, and the baby was delivered. However, instead of clamping and cutting the umbilical cord, as in a standard cesarean section, the umbilical cord was allowed to continue delivering oxygen from the placenta to the baby.

This gave Jeff Koempel, M.D., Keck School assistant professor of otolaryngology, time to perform a laryngoscopy to examine the baby’s airway. Once he determined that the airway was completely blocked due to lack of normal formation of the larynx—commonly known as the voice box—a team of specialists including Koempel and Henri Ford, M.D., Keck School professor of surgery, chair of the Childrens Hospital Department of Pediatric Surgery and surgical director of the IMFH, performed emergency surgery to open the airway. Once the baby’s airway was opened and secured by a tracheostomy, the umbilical cord was cut. The entire procedure, the first of its kind in Southern California, took just over an hour. “If the baby had been delivered normally, it couldn’t take a breath since the whole airway was blocked,” Seri notes.

After birth, newborns benefit from the extraordinary care and expertise provided at the Center for Newborn and Infant Critical Care (CNICC) at Childrens Hospital. It is here that physicians like Seri and Phillipe Friedlich, M.D., Keck School associate professor of pediatrics and medical director of the CNICC, oversee a team that provides cutting-edge care. Besides “micropreemies”—babies born between 23 and 27 weeks gestation with birth weights in the 500 to 1,000 gram range—almost 70 percent of the more than 400 children treated at the CNICC every year undergo surgery just hours after birth. That these babies survive at all is a testament to the enormous progress in neonatal medicine available only in large medical centers in the United States and around the world.

To be sure, technologic advances have helped the IMFH team achieve milestones not possible even a decade ago. In the CNICC, for example, babies with lung or heart trouble benefit from the largest extra corporeal membrane oxygenation (ECMO) program in California. The ECMO unit essentially performs the work of the heart and lungs, boosting survival rates for the babies with certain critical heart and lung conditions from 10 percent to more than 80 percent. Newer medications bolster the flow of oxygen into immature lung cells and incubators are continuously being redesigned to enhance development and comfort. In the surgical arena, “many of the procedures we do now weren’t even possible ten years ago,” notes Chmait. “From the high-resolution ultrasound to the microsurgical equipment we use, none of it was available. And there’s so much more on the horizon.”

What distinguishes the IMFH is that, since it is part of an academic medical institution, all new procedures and developments are conducted under research protocols, all overseen by an Institutional Review Board. “We closely monitor outcomes, advancing our understanding of these complex problems and constantly refine our ability to diagnose and treat them,” Miller says.

here is a growing demand for such carefully researched information: The IMFH held a symposium last spring in Los Angeles that quickly filled to capacity, turning what Miller and the other directors thought might be an occasional conference into an annual event. “When faced with difficult situations, doctors want to be able to provide their patients with the full spectrum of alternatives. We believe the comprehensive, multidisciplinary IMFH team offers unique perspective and experience,” Miller says.

For most of the physicians on the IMFH team, the draw is the ability to offer parents and their developing infants some real alternatives. Chmait initially specialized in obstetrics and perinatology, but became frustrated because “it focused heavily on prenatal diagnosis. So I could diagnose, but I couldn’t do anything about the problems I’d find.”

Chmait says, “Imagine how much hope we can give parents today. Instead of telling them they have to wait until the baby is born, we can potentially ameliorate the issue before the baby is born.”

Fetal surgery, he cautions, is still in its early stages. “When we look back in 20 years, this will seem like the dark ages. But it is important because we’ve unveiled the black box. Pregnancy was the black box, in that we couldn’t deal with the fetus until the baby was born. Now we have the ability to access the intrauterine environment and deal with congenital defects. Potentially we could use that access to treat genetic syndromes, whether cystic fibrosis or Tay Sachs disease or anything else,” he says. “The future is wide open.”