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Pregnant Pause
For expectant moms coping with illnesses ranging from depression to diabetes, uncertainty about the safety of medical treatment looms ominously. Many at Hopkins are pushing to fill the knowledge gap.

By Joanne Cavanaugh Simpson
Illustration by William Cigliano

"People pause today during pregnancy before they take a tablet, before they smoke, before they take a drink, knowing that it could possibly affect the fetus. Nobody knew that before us."
--Randy Warren, one of 5,000 people with birth defects caused by the drug thalidomide.

Ruth Faden was pregnant and flying cross country when she started feeling pains in her calves. She had thrombosis, serious blood clots that sometimes accompany pregnancy. A doctor prescribed heparin injections, a treatment that likely saved her life. But Faden, who is one of Hopkins's leading bioethicists, worried that the drug might have harmed her baby. "I remember obsessing about it 20 times a day," she says. "I wanted my physician to tell me heparin is OK, it's OK for the baby. These are the concerns that plague women."

Faden's anxiety proved unfounded. Her child, now 26, was born healthy.

Yet for decades the question of drug safety in pregnancy has remained a nearly taboo area of science. And every day, scores of pregnant women who need medical treatment, and their doctors, face the same dilemma. "With the majority of drugs, people don't know," says F. J. Montz, Hopkins professor of gynecology and obstetrics. "One has to fly by the seat of the pants."

Early in Claire Ricci's second pregnancy, she was coughing so much her rib cage felt bruised and she couldn't sleep. She also was caring for her 2-year-old. Yet her doctors had little advice. They told her to take Robitussin cough syrup but couldn't say how much. One doctor said it was OK to do a chest X-ray; another refused because Ricci was pregnant. A few months into her pregnancy she ended up in the hospital one day when she found she couldn't breathe. "I was afraid that my baby wasn't getting oxygen," she says. They told her it was a cough, and there wasn't much they could do.

"The doctors were reluctant to give their gut feeling or advice," she says. "It was just, 'Here is what the reference book says: There have been a couple of studies in animals, no studies in women. It's up to you.' It would be fine if I went to medical school. But here I am paying $200 a visit and they say, 'Here is some information. Help yourself.'"

Because of ethical and legal concerns, pregnant women are rarely included in clinical drug trials. Doctors are reluctant to prescribe many medications because of the lack of data. And when they do, there's almost no information to help them determine the best dosage to use during pregnancy, which changes a woman's physiology. The knowledge gap, critics say, threatens the health of women and their babies. It is a situation some call "therapeutic nihilism."

Research involving pregnant women was mostly banned by federal health agencies after the tragedy of thalidomide, the sedative that caused more than 10,000 babies worldwide to be born in the early 1960s with flipper-like limbs, heart defects, and other malformations. Women who took even one 10-cent tablet early in pregnancy gave birth to deformed babies. The lingering images--and subsequent lawsuits related to other drugs and birth defects--have made pharmaceutical firms even more wary. Many simply prefer to label most drugs: Safety in pregnancy not known. Only about 30 drugs are known to cause birth defects.

Yet a whole array of medications with sketchy safety data are used by pregnant women, including ibuprofen and Prozac. That's because millions of pregnant women suffer from chronic diseases--epilepsy, cancer, diabetes, schizophrenia, depression--while others encounter illnesses related to pregnancy, such as blood clots, severe morning sickness, or gestational diabetes. Some of the illnesses themselves affect the fetus, so the issue is often one of balancing risk. Is a drug for epilepsy more dangerous than the seizures? Only well-controlled studies, comparing an adequate number of women who take a test drug to a control group of women given another treatment, or a placebo, can offer definitive answers. But how many pregnant women want to be guinea pigs, subjecting their babies to possibly toxic drugs or themselves to a placebo that offers no treatment?

"There's the feeling that women should muscle through the nine months," says Kass. "But for some conditions, waiting is not an option." Meanwhile, half of the 3 million pregnancies in the United States each year are unplanned, so millions of women take over-the-counter medications or consume a few glasses of wine before they learn they're pregnant. Others who become pregnant encounter commonplace yet sometimes debilitating health problems such as insomnia, allergies, or the flu. Shouldn't science know by now which drugs are safe for such common ailments? Yet look up nearly any drug in the Physicians' Desk Reference and you could find a few scary side effects that might be linked to that drug: club foot, respiratory distress, drug dependence--even stillbirth. Certainly in most situations, the child is born healthy, but the lack of information could prove most damaging of all. In some cases, doctors have advised women to abort the fetus "just to be safe," Hopkins researchers say.

The AIDS epidemic has pressed the issue. Until the mid-1990s, doctors were reluctant to treat pregnant women who tested positive for HIV because of concerns about how the antiretroviral drug zidovudine, or AZT, would affect the fetus. Today, thanks to clinical trials involving pregnant women, doctors know that AZT and the drug cocktails that reduce viral loads help prevent transmission of the virus to the fetus. Such drugs are now prescribed regularly during pregnancy. Yet the delay meant that babies were born with HIV, and women suffered. "It was very frustrating because the government was totally ignoring the women," says Jean Anderson, director of the Hopkins Women's HIV Health Program, and co-author of a recent article on the issue. "The guidelines were that they couldn't take AZT because of the baby. But if you don't have a mother, you don't have a baby."

Today, ethicists, researchers, physicians, drug manufacturers, and others are looking harder at the use of clinical studies during pregnancy--as well as alternate ways to gather data. The U.S. Food and Drug Administration (FDA) has discussed expanding access to such trials. "It is very understandable that no one wants to do harm," says Sandra Kweder, acting director of the Office of Review Management at the FDA's Center for Drug Evaluation and Research. But Kweder, who says such research should be approached with great caution, notes that the release of almost any new drug on the market means that pregnant women might eventually use it. As a society, she says, "we are willing to accept that every pregnant woman is her own experiment. Instead of carefully studying a few women, we subject each one to a new test. That is what some say is unethical."

The question touches one of the most emotional debates of our time: the right of a woman to make her own health care decisions vs. views that a fetus has rights and is vulnerable because it can't give consent to experimental treatment. As part of that larger political controversy, the Bush administration recently delayed a Clinton-era policy meant to liberalize the inclusion of pregnant women in scientific research.

To Faden, executive director of Hopkins's Bioethics Institute, the need for more research is clear. "There is no justification for providing a therapeutic space for drugs in everyone else except pregnant women," she says. "Women suffer from manic depression, chronic diabetes, lupus, arthritis, epilepsy--I could go down the line of illnesses that do not magically disappear when women become pregnant.

"Any way you slice it," Faden says, "pregnant women are entitled to the same standard of evidence-guided pharmaceutical therapies as everybody else."

Beset by a bad cough during her pregnancy, Claire Ricci (with son Anthony) couldn't get clear counsel on what to do.
Photo by Mike Ciesielski
Roslynn Howard-Moss prayed. In December 1990, Howard-Moss was just a few weeks pregnant when she learned she was HIV positive. A medical technician in an AIDS hospice facility, she heard about a clinical trial in which women were given AZT. Her dilemma: Take a drug that doctors couldn't tell her was safe for her fetus, or take the risk that her baby would later test positive for HIV.

"I prayed, and it came back to me that if it would help, the study was something worth doing," she says, adding that the prospect of her child battling AIDS was much worse. "If AZT didn't help me, maybe they would know not to do it to anyone else."

Howard-Moss was enrolled in the AIDS Clinical Trial Group 076, the first national systematic trial of AIDS drugs in pregnancy. She was in the group given a placebo, something she didn't learn until her daughter, Sequoia, was nearly 4 years old. Partly because Howard-Moss's viral loads were low, Sequoia tested negative and has remained so. She is now 10 years old.

Howard-Moss, who today works as a counselor in the Hopkins Women's HIV Health Program, also agreed to appear in a film produced by an AIDS funding agency a few years ago. "One day, my daughter was watching it and said, 'Ma, why did you do it?' She asked if I wondered what would happen to her if I took the drug.

"I told her I wondered even harder what would happen if I didn't do it," Howard-Moss remembers. "About a year ago, she said she thought I was brave."

In an article published last year in the American Journal of Obstetrics and Gynecology, Nancy Kass, an ethicist at Hopkins's Bloomberg School of Public Health; Holly Taylor, an assistant research professor at Public Health; and Anderson described a shift in medical attitudes toward HIV treatment during pregnancy--from concern solely for fetal protection to guidelines that emphasize the health of the mother, and in turn the fetus.

That shift, the researchers argued, could be a model for approaches to drug therapy in other diseases involving pregnant women.

During the first 15 years of the AIDS epidemic, in addition to the reluctance to prescribe AZT to pregnant women, preventive treatment was delayed for pneumonia, one of the leading causes of death in AIDS patients. In 1989, the Centers for Disease Control and Prevention released guidelines stating that it was "inadvisable to provide" drugs during pregnancy as a prophylactic to pneumonia. It was not until 1995, six years and tens of thousands of pregnancies later, that the CDC recommended that pregnant women receive drugs to prevent pneumonia, the researchers noted. In these and other cases, the seemingly cautious approach is to avoid giving a treatment until clinical experience shows it's safe. The authors write, "What may be ignored with a wait-and-see approach, however, is that significant harm to the child may result from not providing treatments."

Pregnant women who suffer from chronic disease but who are told to forgo drug therapy because it's not fully understood--or do so because of social pressure--could in the end threaten their own lives. "It has become an issue of morality," say Kass, associate professor of health policy and management. "There's the feeling that women should muscle through the nine months. That makes it seem like a question of women just feeling a little better. For some conditions, waiting is not an option." Kass, Anderson, Faden, and other advocates aren't arguing that possibly toxic drugs be given cavalierly to healthy pregnant women just to test side effects. The dilemma of testing and using drug therapies during pregnancy, they argue, is simply part of the standard medical balancing act of risk vs. benefit. Is the remedy more damaging, or is the disease?

In the case of epilepsy, for example, medications that control maternal seizures have known teratogenic effects in animals--"teratogen" refers to agents that cause birth defects. Such anticonvulsants also have been shown to greatly increase the risk of congenital abnormalities in human infants. Yet without medication, women remain at risk from seizures, which can lead to intrauterine growth restrictions and neonatal death.

Hopkins gynecologic oncologist F.J. Montz: "With the majority of drugs, people just don't know.
Photo by Mike Ciesielski
Doctors in such cases do have resources to analyze drug treatment protocols, but there are caveats: There's the generally accepted clinical experience, the sort of word-of-mouth wisdom that shows, for example, that the anti-allergy drug Benadryl appears to be safe during pregnancy. But such safety has not been proved. Studies of new drugs in pregnant animals are conducted, yet humans and animals process drugs differently so what is safe for rabbits might be toxic for expectant human mothers. There are assorted pregnancy registries, maintained by researchers or drug manufacturers, that identify women who have taken a drug, then track pregnancy outcomes. Hospitals, private health groups, and the CDC also run birth defect monitoring programs. Yet in many cases such efforts are not centralized. And some drug manufacturers avoid keeping registries, which can be costly. (Drug makers do have to report known adverse effects of a drug to the FDA. Any experimental use of a drug also requires an Investigational New Drug application, in which study procedures must meet FDA approval.)

A small number of clinical studies, meanwhile, have been approved by the FDA for certain drugs, primarily those considered critical because the drugs are related to pregnancy, such as drugs to induce labor. For commonly used drugs, such as the antidepressant Prozac (fluoxetine), safety has been tested in a variety of ways, including surveillance studies of women already taking the drug and accidental exposure cases reported to the manufacturer's worldwide registry. Available data show the drug does not appear to cause any malformations or developmental problems, though in various studies the incidence of spontaneous abortions was reported to be slightly higher, according to Drugs in Pregnancy and Lactation (5th ed., 1998, Williams and Wilkins).

Pregnant women who suffer from depression and other illnesses often feel they should stop taking medication to be safe. That decision could prove deadly. Gideon Koren directs Motherisk, one of the world's most extensive information clearinghouses for drug safety during pregnancy (see the resource guide below). The Motherisk hotline gets as many as 200 calls a day from women and physicians, and its database includes outcomes for 200,000 mother-child pairs. "I counsel pregnant women who try to commit suicide after they stop Prozac. And we know of some women who have committed suicide," says Koren, whose program is based at the Hospital for Sick Children in Toronto. "The risk of dying is a true risk. It's not enough to tell them, 'We don't know. Just quit cold turkey.' It's not humane or ethical."

For some dangerous diseases common to pregnancy, drug treatment protocols are further along. Diabetes, which can show up for the first time during pregnancy as gestational diabetes, can wreak havoc on a fetus, causing low birth weights, congenital malformations, spina bifida, and heart defects. Women who have vascular complications from diabetes and don't get treatment also can suffer from kidney and heart disorders. Studies of women who took insulin while pregnant show it does not appear to pass through the placenta, so insulin is prescribed. Now, there's a new development: A study published in the October 19, 2000, issue of the New England Journal of Medicine indicates that one oral hypoglycemic drug, glyburide, appears to be safe for the fetus. Yet doctors remain cautious. "We are slow to automatically say you can use this now," says Edith Gurewitsch, Hopkins assistant professor of gynecology and obstetrics in the Division of Maternal Fetal Medicine.

Sometimes women are faced with even tougher choices, and the dearth of information can leave some doctors rattled and more likely to advise the "safest route"--abortion. Tara Casagrande found out she was pregnant with her second child earlier this year and then got the results of a routine Pap smear. Adenocarcinoma was present in her cervix. Most treatments, including hysterectomy or chemotherapy, would likely kill the fetus. Some drugs, such as Taxol, can be taken later in pregnancy in some cancer cases, but likely would not be effective for her. Casagrande could find little information about the safety of anti-cancer therapies during pregnancy. Still, she wanted to continue the pregnancy.

After one doctor advised her to abort and undergo the hysterectomy, she came to Hopkins's Montz--the first doctor to prioritize her wanted pregnancy. "The big issue we are wrestling with is one of delaying a therapy that is very likely to be curative," says Montz, director of Hopkins's Kelly Gynecologic Oncology Service. An MRI, which some hospitals refuse to do on pregnant women, had shown that the cancer seemed to be contained.

In such cases, says Montz, the issue becomes: Can we hold off on cancer-fighting therapies until the risk of neonatal complications is low and the fetus viable?

Casagrande has decided to wait it out. Her hope is to deliver early, at 36 weeks. "I learned a lot about motherhood, about myself," she says of her decision. "I realized this is a choice no one else could make other than myself. I have a 2-year-old son and a husband, all these people I want to be there for. I don't know what will happen."

Says Montz: "It is very thorny and highly emotionally charged."

"I counsel pregnant women who try to commit suicide after they stop Prozac. It's not enough to tell them, 'We don't know. Just quit cold turkey,'" says Koren. "Europe's deformed baby crop seen at 7,000"

"Sleeping pill deforms unborn child"

"Deformity drug's toll not final"

So read the headlines across the United States in summer 1962. Nearly 40 years later, no discussion on the safety of drugs during pregnancy can escape comparisons to thalidomide. The drug's tragic consequences were simply too searing.

Of the more than 10,000 infants who suffered thalidomide-caused malformations--deformed internal organs, or missing legs or arms--many were born in Germany, where the drug was developed. Others showed up in maternity wards in England, Canada, and 40 other countries. Nearly half the children died soon after birth; others never made it to term. The drug, which was not approved in the United States, was given out as samples by doctors, and 17 thalidomide babies were born here. The late Helen Taussig, Hopkins professor and founder of pediatric cardiology, played a pivotal role in alerting Americans to the drug disaster.

On Christmas Day 1956, the daughter of an employee of the drug's manufacturer was born with no ears--though her parents didn't then understand the cause. The baby girl would later be known as the first thalidomide birth. The company, Chemie Grunenthal, had given free samples to its workers, but did not follow up.

In fact, for the next five years, under a number of brand names, thalidomide was aggressively marketed as "completely safe." There had been only limited toxicology studies in humans, and none involving pregnant women, though such studies were standard practice for drug manufacturers at the time. The drug's German developers, one of whom had been a medical scientist in the army of the Third Reich, were simply impressed they couldn't find a dose high enough to kill lab rats. Thalidomide became one of the best-selling sedatives in the world and was prescribed for morning sickness, insomnia, colds, cough, flu, anxiety, asthma, and headaches.

Meanwhile, a birth defect so rare that formerly it had affected 1 in 4 million infants had begun to appear by the dozens--phocomelia, from the Greek for "seal's limb." (Thalidomide only caused such malformations if taken during a few weeks in the first trimester, when the fetus's limbs are being formed.) Yet for years, no one linked the drug with the defect, partly because a belief born in the Middle Ages was still prevalent among doctors of the nuclear age: the assurance that the placenta acted as a barrier between mother and child. The idea of a drug that was not toxic to adults nonetheless harming the fetus was especially novel. Even the effects of alcohol on the fetus were thought to be an old wives' tale.

In the 1950s, with the discovery of a polio vaccine and other major advances, drugs were hailed as powerful new tools in mankind's health arsenal. Against this backdrop, an American drug manufacturer, Richardson-Merrell, began pressuring the FDA to approve thalidomide. By 1961, 10 million pills were waiting to flood the U.S. market. A wary FDA examiner, Frances Kelsey, reviewed the application and found it wanting. Among other concerns, her earlier research on anti-malarial quinine in pregnant rabbits had alerted her to the fact that drugs could pass through the placental barrier. The FDA put the approval on hold to await more toxicology results.

Then, in late 1961, doctors in Germany and Australia finally made the connection and published their findings. America was not yet fully aware. Soon after New Year's Day in 1962, Hopkins's Taussig was visited by a former student, by then a doctor in Germany. Over dinner at her home, he told her of the "epidemic of infant monsterism" in Europe. Taussig flew to Germany and England, touring hospitals to examine and photograph the infants. She later wrote in a widely publicized article in Scientific American: "The one-third who are so deformed that they die may be the luckier ones."

Once back in the United States, Taussig discovered to her horror that American mothers had not been spared. While awaiting FDA approval, Richardson-Merrell had sent out 2.5 million thalidomide "samples" to physicians in the United States. As many as 20,000 patients--including 207 pregnant women--took the drug. There was little follow-up between patients and their doctors and the drug company. Patients also gave no informed consent, as was required by the Nuremberg Code drafted after the post-World War II trials of the Nazi doctors--but not by the FDA.

Taussig and physicians from the FDA set out to track down doctors who had handed out thalidomide tablets, and, when possible, to find and inform their patients. If they found women who were pregnant, Taussig suggested X-rays to determine whether the fetus was deformed, according to Dark Remedy, by Trent Stephens and Rock Brynner (Perseus Publishing, 2001). Taussig also suggested therapeutic abortions, which were allowed in limited cases before the 1973 U.S. Supreme Court abortion rights decision, Roe v. Wade.

Thalidomide, which became a catalyst in the subsequent movement to legalize abortion, would also be the spark of reformation for the FDA, setting up the drug approval process we have today. A law passed by Congress in 1962 required stricter limits on the testing and distribution of new drugs, including proof of efficacy, informed consent from patients, and strict federal guidelines for clinical trials.

The thalidomide story also helped create today's dilemma. The new concern for fetal protection and reproductive safety led the federal government to generally prohibit women of child-bearing age from enrolling in most research studies. Such blanket restrictions were lifted by federal research agencies by the 1990s. But the National Institutes of Health (NIH) and hospital review boards continue to bar most pregnant women from research by holding to a 1975 regulation of the U.S. Department of Health and Human Services (HHS); the regulation asserts that for a study to be allowed, the "fetus will be placed at risk only to the minimum necessary." Minimal risk is a vague limit. Should a pregnant woman meet the criteria to enroll, she must first gain permission from the father of the fetus, among other barriers.

Informed consent is in fact a moral and medical sticking point. "A fetus can't make decisions for itself," says Gurewitsch, of Hopkins's Maternal Fetal Medicine. "It's the same with children [in clinical studies]. There's a greater potential for abuse."

Resource Guide

Some drugs on the market can cause severe birth defects if taken during pregnancy. Accutane (isotretinoin), used to treat severe acne, is highly teratogenic and has caused infants to be born with heart abnormalities, cortical and cerebellar defects, cleft palate, and other problems. With most over-the-counter medicines and other drugs taken in pregnancy--sometimes by women who don't yet know they're pregnant--outcomes are usually less clear. The anti-inflammatory ibuprofen, taken late in pregnancy, has in some cases caused pulmonary hypertension in newborns and has inhibited labor. (Ibuprofen also can interfere with conception.) Regular alcohol consumption, usually a few glasses daily or more, has been shown to cause mental retardation and birth defects.
   Women with questions about medicines or other substances, including vitamins and herbs, should consult their physicians. There are also other resources, including:

Drugs in Pregnancy & Lactation: A Reference Guide to Fetal and Neonatal Risk (1998, eds. Roger K. Freeman et al., Williams and Wilkins.)

PDR: Physicians' Desk Reference (2001, Medical Economics)

Organization of Teratology Information Services State-by-state listing:

Motherisk, Hospital for Sick Children, Toronto, Canada 416-813-6780,

The physician's Hippocratic oath has its flaws. Most doctors remember the warning: First do no harm. So then, what if doing no harm causes harm?

For much of human history, women with lupus could rarely bear children. The autoimmune disorder, which today affects as many as 500,000 Americans, can cause premature birth and miscarriage. And the sometimes fatal disease often flares up in pregnancy, threatening the woman's health.

Yet partly because of drug research conducted on pregnant women, including long-term observational studies in the U.S. and a recent clinical drug trial conducted in Brazil, there's a success story to be told.

Today, an estimated 90 percent of women with lupus can bear their own children. But only if drugs are prescribed, and the pregnancy monitored. "It's really important that women understand that staying on medicine is their best chance of having a successful pregnancy," says Michelle Petri, Hopkins professor of medicine.

This has meant a revolution. "There was a big shift at Hopkins," says Petri, who 16 years ago helped found the Lupus Pregnancy Center, which she also directs. "At that time, there had been no successful pregnancies here. Since then, there have been over 250."

Researchers, clinicians, and ethicists are pressing HHS and other agencies to reconsider guidelines discouraging the inclusion of pregnant women in research. "We don't have a moral conflict here, we have a dicey medical problem," says Hopkins's Faden. "It's not who is more important, the baby or the mom. We want to maximize outcomes for the baby and the mother."

Yet any issue at the ideological crossroads of women's reproductive rights and fetal research inevitably raises the abortion debate. And the Bush administration, wary of research involving fetuses, has delayed and could block a Clinton revision to the HHS rule. That revision, set to go into effect this past March, would help foster the "presumed inclusion" of pregnant women in research partly by eliminating the need for the father's permission. Such consent is not required for an abortion. "A woman could have a serious disease, but because she is pregnant, the father of the baby gets to decide if she can undergo an experimental trial," says Ellen Wright Clayton, a law professor at Vanderbilt University and a pediatrician who has spoken before the FDA on clinical research.

Pharmaceutical companies--which do the majority of clinical trials related to new medicines--wouldn't appear likely to test drugs during pregnancy. "Companies are scared stupid of doing clinical trials in pregnant women. The overwhelming concern is that they will end up with endless liability," Clayton says.

Physician Maria Palmisano '85, who is director of clinical pharmacology-experimental medicine at Bristol-Myers Squibb, notes, "At present, trials [involving pregnant women] are undertaken on a very limited basis." But she predicts a gradual increase in such studies among pharmaceutical companies. The increase, she says, will be "influenced by regulatory authorities and by market forces--what consumers are requesting in terms of information." Says Palmisano, "On the whole, what the industry is looking for is that the drug has been shown to be safe in application in the general population before proceeding."

An everlasting irony, Clayton and others point out, is that a lack of adequate clinical studies about drug safety in pregnancy led to the thalidomide disaster--in the end exposing far more people to risk. Four decades later, women and their doctors still can't assume that drugs that have been around for years are safe, even if there's been no news to the contrary.

In December 2000, the FDA and the National Institute of Child Health and Human Development, part of NIH, held a workshop focused on clinical pharmacology in pregnancy, the possible expansion of clinical trials, and ways to improve the labeling of medicines. "Even after a drug has been on the market, the clinical experience we do have with pregnant women never makes it to labeling," says Kweder, also co-chair of the FDA's Pregnancy Labeling Task Force. "There is a huge disconnect between the knowledge available and what's in labeling."

Doctors also are demanding data on how best to prescribe certain antibiotics and other medicines commonly used during pregnancy, when a woman's altered physiological state can affect how drugs function. As Hopkins's Anderson says, "There is a need to know things beside toxicity and birth defects. We need to know if the same dose should be given to pregnant women, and at what frequency."

Some suggestions to bridge the knowledge gap, meanwhile, are being proposed. Anderson, Kass, and others are calling for more in-depth animal studies of drugs during pregnancy, and broader public discussion on the issue. As doctors and pregnant women become more aware of the need for information, they can take part in observational studies and voluntarily report drug effects when a therapy is elected. The data gathered could feed into a centralized pregnancy registry or database accessible to women and physicians, say women's health advocates and FDA officials. In some cases, says Kweder, maybe the answer "would not be large, randomized, controlled trials, but how can we use more of women's real-life experiences to help us do better in the future."

Will enough women be willing to take a personal gamble that could also potentially improve the health of babies and mothers in the future? Clinical studies that are done could be structured without a placebo, as many AIDS studies are now being done, for ethical reasons, in Africa. In the end, of course, there are no guarantees. People who participate in clinical trials put their lives in other people's hands. Even if such studies are conducted, years might pass before long-term effects of a drug are known.

Take the case of diethylstilbestrol (DES), which was given to an estimated 6 million mothers between 1940 and 1971 to prevent miscarriage and premature delivery. The drug, which turned out to be ineffective for these disorders, later caused severe reproductive problems in adult offspring, including cervical cancer and infertility. The effects were not discovered for decades. "This is a really tough issue," says Amy Allina, policy and program director of the National Women's Health Network. "Doing clinical trials that include pregnant women is very difficult to do ethically and safely."

The question may come down to a mother's instinct. Will enough women, like Howard-Moss, be willing to take a personal gamble that could also potentially improve the health of babies and mothers in the future? Some will. "Women who are already taking medicines had to make a hard decision," Kweder says. "Many are very motivated to help other women in their circumstances. They tell their doctors, 'If there is anything I can do so that someone else doesn't have the painful experience I've had, I'd like to do that.'"

Yet as Ricci, whose cough finally went away later in her pregnancy, notes: "It's a quandary. It's not like any pregnant woman I know would say, 'Test this drug on me.'"

Postscript: After much debate, thalidomide was approved by the FDA in 1998 and is being prescribed to treat painful ulcers and cachexia, the severe wasting disease that plagues people with leprosy, tuberculosis, and AIDS. Strict FDA restrictions--including a central source for the drug, agreements to use birth control, and pregnancy tests--are meant to stop another thalidomide baby from being born. But that doesn't guarantee one won't be.

Anderson has had to decide whether to prescribe thalidomide to young women who are HIV positive. "We can't guarantee what a patient will do," she says. "I have to talk to them first. I have to do some soul-searching."

Return to September 2001 Table of Contents

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