By Jacqueline M. Duda
Special to The Washington Post
Tuesday, February 6, 2007; HE01
The muscles surrounding my pregnant belly were tightening with ominous regularity as I waited for my asthma doctor to check my wheezy lungs. I have a small frame, and it looked like I had stuffed a dinosaur egg under my shirt. Now, at 25 weeks, it looked ready to hatch.
I crossed my legs. Yeah, like that would help.
“Are you having contractions?” the nurse asked.
“I don’t think so,” I said with a bit of hesitation. But I had been there, done this, once before. When pregnant with our third child, I started contracting at 20 weeks. I left my teaching job to endure a marathon 17 weeks of bed rest. Elise made it to 37 weeks — considered full term — and arrived healthy. An optimal outcome despite a troubled pregnancy.
The nurse put her hand on my stomach and looked at her watch. She glanced at my doctor.
“I think she’s in labor.” I fought off panic. This baby — a girl — wasn’t ready. My doctor ordered me promptly to the hospital, intent on buying her more time.
Preterm birth — birth anytime before 37 weeks of gestation — is the nation’s leading cause of infant death, responsible for more than one-third of infant deaths before age 1, according to the Centers for Disease Control and Prevention. That finding, published in October, depicts preterm birth as more dangerous than previously thought. And with the rate of preterm births rising (they accounted for 12.5 percent of all births in 2004, compared with 9.4 percent in 1981), the news is spotlighting efforts to identify women at risk and to intervene in time to make a difference. Specialists are studying the use of drugs (such as progesterone and antibiotics), bed rest, medical monitoring — or a combination of these — as a situation demands.
“The problem of preterm birth is multi-factorial,” says Siva Subramanian, chief of neonatology at Georgetown University Hospital. To have a significant impact, he added, research must address social and cultural as well as medical factors that might affect a woman’s risk of premature delivery.
There is good reason for these efforts. Even when preemies survive at birth, they often need intensive care for respiratory distress, infection, brain hemorrhage or myriad other life-threatening conditions; many suffer multiple problems, says Subramanian.
A report last year from the Institute of Medicine estimated the annual cost of preterm births in the United States at more than $26 billion, or $51,600 per infant. Preemies often face lifelong health problems such as cerebral palsy, as well as behavior and learning problems that take an emotional toll on those caring for them.
At Georgetown’s 44-bed neonatal intensive care unit, preemies, some of them small enough to fit in the palm of a hand, lie in see-through incubators draped by blankets to block the light and mimic a womb environment. Tubes and wires wind their way in and out of tiny bodies covered with translucent, paper-thin skin. Respirators and vital signs monitors beep and hum in the background.
While an infant born at 25 weeks today has a 30 to 50 percent survival rate, the chances of a healthy survival for such a baby can be as low as 10 percent, according to Tonse N.K. Raju, medical officer and program scientist at the Pregnancy and Perinatology Branch at the National Institute of Child Health and Human Development.
Slow Steps
Why the rate of preterm births is rising isn’t entirely clear. But Catherine Spong, chief of the Pregnancy and Perinatology Branch at NICHD, suspects that increased use of fertility drugs and other reproductive technologies and the multiple births often tied to them may be partly responsible.
In his study of about 28,000 infant deaths that occurred in 2002, Bill Callaghan, a senior scientist in the CDC’s maternal and infant health branch, reclassified approximately 5,000 that had been attributed to such causes as respiratory distress syndrome, brain hemorrhage and maternal complications — all preterm-related conditions. To these he added the more than 4,600 (17 percent) attributed to preterm birth, arriving at a new number of nearly 9,600 births (34 percent) classified as preterm.
The NICHD has been investigating causes of preterm birth and possible interventions since 1986. Studies start with a similar group of women who share a similar risk factor.
A 2002 study published in the New England Journal of Medicine, for example, tested the ability of home uterine activity monitors to predict early labor in women who had had spontaneous preterm deliveries. The finding? Home monitoring of contraction rates was a poor predictor of preterm birth.
Another study, published in 2003 in the journal Obstetrics and Gynecology, involved the use of the antibiotic metronidazole to treat asymptomatic pregnant women who tested positive for trichomonas vaginalis or bacterial vaginosis. “We know that these two [vaginal] infections seem to trigger preterm birth,” Spong says.
The antibiotic not only failed to reduce the rate of preterm births, it actually increased the rate in women with trichomonas vaginalis. “Sometimes,” Spong says, “removing one factor may trigger another.”
A randomized, double-blind, placebo-controlled trial involving injection of a form of progesterone called 17 a-hydroxyprogesterone caproate, or 17P, shows more promise, she says.
In the study, published in 2003 in the New England Journal of Medicine, NICHD researchers administered either 17P or a placebo to 463 pregnant women who had previously delivered a preterm infant. Spong says women treated with 17P were 30 percent more likely to carry their babies to term than those treated with the placebo.
Researchers found no evidence that 17P caused birth defects or other problems for the infants — an important consideration. Spong says studies are underway involving other high-risk groups, such as women with short cervixes or multiple gestations. The results of a randomized study of 17P with women carrying twins and triplets are slated to be released this month.
Women known to be at a high risk for preterm birth include those who have had a previous preterm birth, those who are expecting multiples and those who have cervical and uterine abnormalities.
Other possible risk factors include lifestyle or environmental issues such as stress, lack of social support, sporadic or no prenatal care, and health conditions such as vaginal or urinary tract infections, diabetes, high blood pressure and clotting disorders. Women who have never been pregnant may also be considered at risk because there is no pregnancy history to help predict complications or guide treatment should problems arise, Spong notes.
For reasons that are not well understood, premature birthrates tend to be higher for African American women (17.8 percent, compared with 11.5 percent for white women, according to the Institute of Medicine) and for women of lower socioeconomic status, Spong says. Petite women (those who weigh less than 100 pounds) and those who have high-stress occupations or who stand all day also appear to have a higher incidence of preterm labor, according to Gary Hankins, professor and chief of obstetrics and gynecology at the University of Texas Medical Branch at Galveston.
But stress is hard to pin down as a risk factor, he says, because it is difficult to measure and because women respond differently to it.
A Cautious Approach
With previous pregnancies, I booked prenatal appointments as soon as the test stick read positive. After my first preterm labor was followed by four consecutive miscarriages, I sought out Christos Hatjis, a high-risk obstetrician at St. Agnes Hospital in Baltimore. He scheduled exams once a week for the first six weeks and every other week after that, and also prescribed progesterone for the first 12 weeks.
I didn’t smoke, drink or use drugs. I watched my weight, remained physically active and tried to keep my asthma under control with prescribed medications and checkups. When a blood test showed my blood had a tendency to clot too quickly, Hatjis prescribed heparin, a blood thinner that I injected daily. I followed my doctor’s orders to a T.
The problem with this approach is that the treatments don’t get to the root of the problem. “Currently, the treatment of disease in obstetrics is largely based on symptoms and signs, and not in understanding the precise mechanisms of the disease responsible,” says Roberto Romero, chief of the Perinatology Research Branch at NICHD.
Inducing preterm birth can be the only effective treatment to deal with such potentially fatal pregnancy complications as preeclampsia, marked by soaring blood pressure and protein in the urine, or intrauterine growth restriction, where fetal growth becomes dangerously slow. Or, as in my case, preterm birth can be spontaneous. That is, labor begins with no obvious cause.
Was it my age, I wondered? (I was 38.) Or was it because my small body built big babies? My first child weighed nearly 10 pounds at birth; this newcomer, it appeared, was headed in the same direction. Hatjis was inclined to blame a combination of factors: asthma, occupational stress and exhaustion, a urinary tract infection and dehydration.
While I watched the needle on the uterine activity monitor jump at regular intervals, indicating contractions, the hospital medical team began tocolysis, the use of medications to slow or stop uterine contractions. They gave me a shot of terbutaline, a respiratory medication that obstetricians commonly use off label for premature labor (it relaxes smooth muscle, both in the lungs and in the uterus), and an intravenous drip for hydration.
Despite initial hope that tocolytic medications would prevent preterm delivery, 30 years of experience and extensive clinical study show they can buy time but do not reduce the preterm birthrate or the rate of fetal complications, Romero says.
Still, he says, they are among the only tools available.
In my case, the terbutaline slowed — but failed to stop — my contractions. Once they dropped to one every 20 minutes and stayed at that rate for 24 hours, I was sent home with an order of extended bed rest. After 11 weeks of that, combined with terbutaline pills every four hours, twice-weekly medical monitoring and one additional hospitalization when my contractions increased at 33 weeks, Alexis arrived at 36 weeks via Caesarean section. She weighed an amazing 8 pounds 12 ounces. Some minor respiratory issues required intermittent hospital monitoring, and she was jaundiced, possibly from the Caesarean. She left the hospital after six days. Today, she is a healthy, active 6-year-old. Doctors want more stories to have such a happy ending.
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