Gateway drug

From the LA Times....

http://www.latimes.com/news/nationworld/nation/la-sci-premature30jun30,0,7239244.story?coll=la-home-nation


Birth drug leaves some moms feeling worse
A drug commonly used for preterm labor has more serious side effects than alternatives and may even harm newborns, researchers say.
By Thomas H. Maugh II
Times Staff Writer

June 30, 2007

The drug most commonly used to delay preterm labor in women has more — and more serious — side effects than alternatives, without being any more effective, Stanford researchers reported Friday. The drug may even harm infants, they concluded.

Although labor generally cannot be stopped completely, physicians try to delay it for at least 48 hours to allow transfer of the mother to a specialized hospital and to maximize the effectiveness of steroids used to help the fetus' lungs mature.

The drug most commonly used is magnesium sulfate, but nifedipine and others are occasionally used.

"There is no free lunch with any of these drugs," collectively called tocolytic agents, said Dr. Deirdre Lyell of Stanford University's Lucille Packard Children's Hospital. "But magnesium sulfate has some particularly unpleasant side effects, including vomiting, lethargy and blurry vision. The alternative, nifedipine, often leaves women feeling better."

Despite obstetric advances, preterm delivery — births before 37 weeks' gestation — remains a major problem. In the U.S., 12.3% of births are preterm, for reasons largely unknown. Prematurity is the cause of 30% of infant deaths and of a variety of developmental problems.

Lyell, Dr. Yasser El-Sayed of Stanford and their colleagues studied 192 women in preterm labor at Packard Children's and Santa Clara Valley Medical Center. Half were randomly assigned to receive infusions of magnesium sulfate, and half oral nifedipine.

In the journal Obstetrics & Gynecology, the team reported that though magnesium sulfate quieted contractions more effectively than nifedipine, there were no differences in how long delivery was delayed, in the gestational age of the newborn or in the birth weight of the infants.

Meanwhile, two-thirds of the women who received magnesium sulfate experienced mild to severe side effects during treatment, including shortness of breath and fluid buildup in the lungs. Only a third of the women receiving nifedipine experienced side effects, such as headaches.

Infants born to the mothers who received magnesium sulfate, moreover, were more likely to be admitted to the neonatal intensive care unit and to stay there longer — a median of 8.8 days, compared with 4.2 days for the babies whose mothers received nifedipine.

Dr. Victoria Camerini, a neonatologist at Childrens Hospital Los Angeles who was not involved in the study, pointed out that magnesium can cause respiratory depression and bowel dysfunction in infants and that the mother's body has a mechanism to transport the drug across the placenta.

"If an obstetrician asked me which drug I would prefer," she said, "I would say nifedipine."

The researchers emphasized that magnesium sulfate was still an appropriate treatment for preterm labor. Many physicians continue to use it at the two hospitals where the study was conducted.

But perhaps it is time for physicians to give more weight to side effects when considering what to try first, Lyell said. "It has been my experience that women who have had magnesium sulfate remember it," she said. "They don't like it."

The findings are "probably a strong call to come up with more effective … agents with fewer side effects," said Dr. Michael C. Lu of UCLA's David Geffen School of Medicine, who was not involved in the research. "We also need to rethink our strategy in terms of preventing preterm births. Giving tocolytic therapy may be too little, too late."


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thomas.maugh@latimes.com