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Editor's note: The following is an excerpt from Origins: How the Nine Months Before Birth Shape the Rest of Our Lives (Free Press, 2010) by science writer Annie Murphy Paul. It chronicles her own pregnancy as well as her quest to find the latest science behind how environment—physical, chemical and biological—can shape a person for decades to come. During the fourth month of her pregnancy, she assesses the growing—but still incomplete—knowledge base about all of the everyday medications that can cross the placental boundary and impact prenatal development.
We are all too aware of the fetus’s vulnerability, in which the placenta seems not an unbreachable barrier but the merest wisp. What is the placenta capable of blocking, I wonder, and what does it allow to pass through? To find out, I call Gideon Koren, professor of pediatrics and pharmacology at the University of Toronto and director of the Motherisk program at Toronto’s Hospital for Sick Children. Motherisk runs the busiest hotline in the world for pregnant women with questions about exposures to drugs, chemicals, and diseases; its operators field hundreds of calls a week.
“During most of pregnancy, the placenta separating mother and fetus is only one cell thick,” Koren tells me. “But it has an array of mechanisms to help it do its job of protecting the fetus.” These subcellular tools, he explains, include tiny pumps that expel toxins before they can do any damage, immune agents that guard the placenta’s perimeter, and placental enzymes that chemically break down intruding molecules.
This armamentarium does an impressive job of blocking bacteria from reaching the fetus, but it lets other substances sail right through. “The criteria that determine whether a molecule crosses the placenta include its size, its electrical charge, and its solubility,” says Koren. “Not, notice, whether it is harmful or not.” Particles that are small, that are neutrally charged, and that easily dissolve in fat will be waved past the placenta’s layers of security, regardless of their potential toxicity.
Once they do cross the placenta, Koren continues, chemicals can affect fetuses more powerfully than adults, for several reasons: first, the fetus is so small that, pound for pound, it receives a higher relative dose of the chemical than would a person who’s fully grown. Second, the fetus’s detoxification and immune systems are still immature, unable to clear drugs and other chemicals from its system as effectively as the body of an adult. And third, the fetus is developing so rapidly that even a small disruption induced by a chemical can have far-reaching effects.
Science is still sifting through the fallout from its belated recognition of the risks posed by thalidomide, DES (Diethylstilbestrol), and alcohol. It is evidence of the evolving state of our knowledge that the mechanisms by which these substances do their damage are not completely clear, even now. Thalidomide seems to wreak its devastation by inhibiting the growth of new blood vessels, preventing fetal limbs and other body parts from growing to their full size. DES appears to impersonate one of the body’s own hormonal messengers, thereby disrupting the proper development of the female fetus’s reproductive tract and making it more vulnerable to cancer later in life. And alcohol may trigger the death of cells in the fetus’s growing brain, producing mental retardation and other neurocognitive deficits along with its distinctive effects on the anatomy.
The name for these substances, I now know, is teratogen: an agent that causes malformation of the developing embryo or fetus. The word is derived from the greek word for monster, and indeed, historians have noted that many of the monsters of ancient Greek mythology, like the two-faced Janus and the one-eyed Cyclops, appear to be based on types of congenital malformations. To this old and primal dread of a defective child I have joined a new, more modern fear: of drugs and what they can do. Before I began my reading this month, I knew little about thalidomide and DES, yet somehow the horror they inspired when their malignity was revealed had seeped into my consciousness and stayed there. My half-aware reaction, once I became pregnant, was to avoid anything like the drugs that led to those dimly remembered disasters.
But this response is not universal, as I learn to my surprise. Dozens of surveys have reached the same conclusion: women swallow all manner of pills while pregnant. A 2005 study of 418 women, published in the American Journal of Perinatology, found that more than three-quarters took at least one medication during pregnancy; one-third took more than one, and 13.6 percent took four or more. Several surveys have found that women take more over-the-counter drugs when they’re pregnant than when they’re not, and that pregnant women are taking more such drugs now than in the recent past. The slone epidemiology Center Birth Defects study, which tracks 7,563 mothers and their children, found that the use during pregnancy of five common nonprescription drugs rose between 1976 and 2004. Pain relievers, cold remedies, and allergy medications are the drugs most often consumed by pregnant women; a study of more than ten thousand pregnant women, published in the American Journal of Obstetrics and Gynecology, found that 65 percent took acetaminophen (the active ingredient in Tylenol); 18 percent took ibuprofen (Advil or Motrin) and 15 percent took pseudoephedrine (sudafed).
Pregnant women are also prescribed drugs by their doctors. A study of the records of eight HMOs, encompassing almost a hundred thousand patients, found that 64 percent of women were prescribed at least one drug during pregnancy; the Food and Drug Administration reports that while pregnant, American women take an average of three to five prescription drugs.
Most of these medications appear to have no effect on the fetus (though ibuprofen, for one, is not recommended for use during pregnancy, because of a very small risk of miscarriage or a fetal heart defect). My fear of taking so much as a Tylenol would seem to be overblown. But some scientists say we don’t know nearly enough about how drugs work during pregnancy, including those commonly regarded as safe. “We’re working without good, definitive information,” says Martha Werler, senior epidemiologist at the Slone Epidemiology Center and professor of epidemiology at the Boston University School of Public health. “Pregnant women should proceed with caution.”
The FDA itself has acknowledged that its approach to labeling drugs for use by pregnant women is flawed. Its current system, devised in 1979, categorizes medications as A, B, C, D, or X, with A indicating little known risk to the fetus and X indicating a high risk. Doctors and patients have complained that the letter grades are confusing and inaccurate, and can’t adequately accommodate emerging data about the drugs’ safety. In spring 2008, the FDA proposed replacing the letters with more detailed information about risks to the fetus, and said it would require some drug manufacturers to fund studies on the use of their products by pregnant women. Such steps are long overdue. A 2000 study published in the medical journal the Lancet reported that 79 percent of pregnant women take at least one drug for which safety data are unavailable; even more troubling, the HMO study mentioned above found that almost one-half of pregnant women were prescribed drugs labeled C, D, or X.