Known Unknowns

Why no one can say exactly how much is safe to drink while pregnant

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I was waiting in the dining car of an Amtrak train recently when I looked up and saw that old familiar sign:

“According to the Surgeon General, women should not drink alcoholic beverages during pregnancy because of the risk of birth defects.”

One finds this warning everywhere: printed on bottles and menus or posted on placards at restaurants and even train cars barreling through Midwestern farmland in the middle of the night. The warnings are, of course, intended to reduce the number of cases of fetal alcohol syndrome in the United States. To that end, the Centers for Disease Control and Prevention (CDC) and the American Congress of Obstetricians and Gynecologists (ACOG) recommend that women avoid drinking any alcohol throughout their pregnancies.

Here’s how the CDC puts it:

“There is no known safe amount of alcohol to drink while pregnant.”

And here’s ACOG’s statement in 2008:

“. . . ACOG reiterates its long-standing position that no amount of alcohol consumption can be considered safe during pregnancy.”

Did you notice what they did there? These statements don’t actually say that no amount of alcohol is safe during pregnancy. They say that no safe amount is known and that no amount can be considered safe, respectively. Ultimately, these are statements of uncertainty. We don’t know how much is safe to drink, so it’s best if you don’t drink any at all.

Lest you think this is a merely a reflection of America’s puritanical roots, check out the recommendations of the U.K.’s National Health Service. While they make allowances for the fact that some women choose to drink, they still advise pregnant women to avoid alcohol altogether. As they say:

“If women want to avoid all possible alcohol-related risks, they should not drink alcohol during pregnancy because the evidence on this is limited.”

Yet it seems odd that the evidence is so limited. The damaging effects of binge drinking on fetal development were known in the 18th century and the first modern description of fetal alcohol syndrome was published in a French medical journal nearly 50 years ago. Six years later, in 1973, a group of researchers at the University of Washington documented the syndrome in The Lancet. Even then, people knew the cause of fetal alcohol syndrome: alcohol. And in the forty years since, fetal alcohol syndrome has become a well-known and well-studied illness. NIH alone devotes more than $30 million dollars annually to research in the field. So how come no one has answered the most pressing question (at least for pregnant women): How much is safe to drink?

One reason is that fetal alcohol syndrome isn’t like HIV. You can’t diagnose it with a blood test. Doctors rely on a characteristic pattern of facial abnormalities, growth delays and neural or mental problems – often in addition to evidence of prenatal alcohol exposure – to diagnose a child. Yet children exposed to and affected by alcohol during fetal development don’t always show all of these symptoms. Doctors and agencies now define fetal alcohol syndrome as the extreme end of a spectrum of disorders caused by prenatal alcohol exposure. The full spectrum, called fetal alcohol spectrum disorders (FASD), includes milder forms of the illness that involve subtler cognitive or behavioral problems and lack the classic facial features of the full-blown syndrome.

As you might imagine, milder cases of FASD are hard to identify. Pediatricians can miss the signs altogether. And there’s a fundamental difficulty in diagnosing the mildest cases of FASD. To put it crudely, if your child is slow, who’s to say whether the culprit is a little wine during pregnancy, genetics, too much television, too few vegetables, or god-knows-what-else? Unfortunately, identifying and understanding the mildest cases is crucial. These are the cases that worry pregnant women who drink lightly. They lie at the heart of the uncertainty voiced by the CDC, ACOG, and others. Most pregnant women would like to enjoy the occasional merlot or Sam Adams, but not if they thought it would rob their children of IQ points or otherwise limit their abilities – even just a little – down the line.

While it’s hard to pin down the subtlest cases in the clinic, scientists can still detect them by looking for differences between groups of children with different exposures. The most obvious way of testing this would be to randomly assign pregnant women to drink alcohol at different doses, but of course that experiment would be unethical and should never be done. Instead, researchers capitalize on the variability in how much women choose to drink during pregnancy (or at least how much they report that they drank, which may not always be the same thing.) In addition to interviewing moms about their drinking habits, the scientists test their children at different ages and look for correlations between prenatal alcohol exposure and test performance.

While essential, these studies can be messy and hard to interpret. When researchers do find correlations between moderate prenatal alcohol exposure and poor test performance, they can’t definitively claim that the former caused the latter (although it’s suggestive). A mysterious third variable (say, maternal cocaine use) might be responsible for them both. On the flip side, interpreting studies that don’t find correlations is even trickier.  It’s hard to show that one thing doesn’t affect another, particularly when you are interested in very small effects. To establish this with any confidence, scientists must show that it holds with large numbers of people and that they are using the right outcome measure (e.g., IQ score). FASD impairments can span language, movement, math skills, goal-directed behaviors, and social interactions. Any number of measures from wildly different tests might be relevant. If a given study doesn’t find a correlation between prenatal alcohol exposure and outcome measure, it might be because the study didn’t test enough children or didn’t choose the right test to pick up the subtle differences between groups.

When studies in humans get tricky, scientists often turn to animal models. FASD research has been no exception. These animal studies have helped us understand the physiological and biochemical mechanisms behind fetal alcohol syndrome, but they can’t tell us how much alcohol a pregnant woman can safely drink. Alcohol metabolism rates vary quite a bit between species. The sensitivity of developing neurons to alcohol may differ too. One study used computational modeling to predict that the blood alcohol level of a pregnant rat must be 10 times that of a pregnant human to wreak the same neural havoc on the fetus. Yet computational models are far from foolproof. Scientists simply don’t know precisely how a dose in a rat, monkey, or other animal would translate to a human mother and fetus.

And here’s the clincher: alcohol’s prenatal effects also differ between humans. Thanks to genetic differences, people metabolize alcohol at very different rates. The faster a pregnant woman clears alcohol from her system, the lower the exposure to her fetus. Other factors make a difference, too. Prenatal alcohol exposure seems to take a heavier toll on the fetuses of older mothers. The same goes for poor mothers, probably because of confounding factors like nutrition and stress. Taken together, these differences mean that if two pregnant women drink the same amount of alcohol at the same time, their fetuses might experience very different alcohol exposures and have very different outcomes. In short, there is no single limit to how much a pregnant woman can safely drink because every woman and every pregnancy is different.

As organizations like the CDC point out, the surest way to prevent FASD is to avoid alcohol entirely while pregnant. Ultimately, every expecting mother has to make her own decision about drinking based on her own understanding of the risk. She may hear strong opinions from friends, family, the blogosphere and conventional media. Lots of people will seem sure of many things and those are precisely the people that she should ignore.

When making any important decision, it’s best to know as much as you can – even when that means knowing how much remains unknown.

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Photo Credit: Uncalno Tekno on Flickr, used via Creative Commons license

Hurley TD, & Edenberg HJ (2012). Genes encoding enzymes involved in ethanol metabolism. Alcohol research : current reviews, 34 (3), 339-44 PMID: 23134050

Stoler JM, & Holmes LB (1999). Under-recognition of prenatal alcohol effects in infants of known alcohol abusing women. The Journal of Pediatrics, 135 (4), 430-6 PMID: 10518076

The Trouble with (and without) Fish

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This week I’m posting a piece from my archives (August, 2011) that I’ve updated a little. Two things brought this post to mind: 1) the recent EPA report that women have become better informed about mercury and are making better choices at the fish counter and 2) remarkable updates from my scientist friend who is blogging her way through the world’s oceans as she collects water samples to catalog mercury levels around the globe. Both demonstrate that we are making some progress in studying and alerting people to the mercury in our waters and our fish. NB: when I say “now that I’m pregnant,” it’s 2011 me talking.

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Once upon a time in a vast ocean, life evolved. And then, over many millions of years, neurons and spinal cords and eyes developed, nourished all the while in a gentle bath of nutrients and algae.

Our brains and eyes are distant descendants of those early nervous systems formed in the sea. And even though our ancestors eventually sprouted legs and waddled out of the ocean, the neural circuitry of modern humans is still dependent on certain nutrients that their water-logged predecessors had in abundance.

This obscure fact about a distant evolution has recently turned into a major annoyance for me now that I’m pregnant. In fact, whether they know it or not, all pregnant women are trapped in a no-win dilemma over what they put into their stomachs. Take, for instance, a popular guidebook for pregnant women. On one page, it advocates eating lots of seafood while pregnant, explaining that fish contain key nutrients that the developing eyes and brain of the fetus will need. A few pages later, however, the author warns that seafood contains methylmercury, a neurotoxic pollutant, and that fish intake should be strictly curtailed. What is a well-meaning pregnant lady to do?

On a visceral level, nothing sounds worse than poisoning your child, so many women reduce their seafood intake while pregnant. I have spoken with women who cut all seafood out of their diet while pregnant, for fear that a little exposure could prove to be too much. They had good reason to be worried. Extreme methylmercury poisoning episodes in Japan and Iraq in past decades have shown that excessive methylmercury intake during pregnancy can cause developmental delays, deafness, blindness, and seizures in the babies exposed.

But what happens if pregnant women eliminate seafood from their diet altogether? Without careful supplementation of vital nutrients found in marine ecosystems, children face neural setbacks or developmental delays on a massive scale. Consider deficiencies in iodine, a key nutrient readily found in seafood. Its scarcity in the modern land-based diet was causing mental retardation in children – and sparked the creation of iodized salt (salt supplemented with iodine) to ensure that the nutritional need was met.

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Perhaps the hardest nutrient to get without seafood is an omega-3 fatty acid known as DHA. In recent years, scientists have learned that this particular fatty acid is essential for proper brain development and functioning, yet it is almost impossible to get from non-aquatic dietary sources. At the grocery store, you’ll find vegetarian products that claim to fill those needs by supplying the biochemical precursor to DHA (found in flaxseed, walnuts, and soybean oils), but it’s not clear that the precursor will do the trick. Our bodies take a while to synthesize DHA from its precursor. In fact, we may burn much of the precursor for energy before we manage to convert it to DHA.

The best way for pregnant women to meet the needs of their growing babies is to eat food from marine sources. Yet thanks to global practices of burning coal and disposing of industrial and medical waste, any seafood women eat will expose their offspring to some amount of methylmercury. There’s no simple solution to this problem, although studies suggest that child outcomes are best when women consume ample seafood while avoiding species with higher levels of methylmercury (such as shark, tilefish, walleye, pike, and some types of tuna). It also matters where the fish was caught. Mercury levels will be higher in fish from mercury-polluted waters – one of the reasons that it’s important to catalog mercury levels around the globe.

Unless we start cleaning up our oceans, pregnant women will continue to face this awful decision each time they sit down at the dinner table. Far worse, we may face future generations with lower IQs and developmental delays regardless of which choice their mothers make. Thanks to shoddy environmental oversight, we may be saddling our children with brains that don’t work as well as our own. And that is something I truly can’t swallow.

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Photo credits:

Photo 1: by Gideon (malias) on Flickr, used via Creative Commons license

Photo 2: by @Doug88888 on Flickr, used via Creative Commons license

Mother’s Ruin, Moralists, and the Circuitous Path of Science

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Update: Since posting this piece, I’ve come across a paper that questions ancient knowledge about the effects of prenatal alcohol exposure. In particular, the author makes a compelling argument that the biblical story mentioned below has nothing to do with the safety of drinking wine while pregnant. Another paper (sorry, paywall) suggests that the “rhetoric of rediscovery” about the potential harm of alcohol during pregnancy was part of a coordinated attempt by “moral entrepreneurs” to sell a moralist concept to the American public in the late 1970s. All of which goes to show: when science involves controversial topics, its tortuous path just keeps on twisting.

If you ask someone to draw you a roadmap of science, you’re likely to get something linear and orderly: a one-way highway, perhaps, with new ideas and discoveries converging upon it like so many on-ramps. We like to think of science as something that slowly and deliberately moves in the right direction. It doesn’t seem like a proper place for off-ramps, not to mention detours, dead-ends, or roundabouts.

In reality, science is messy and more than a little fickle. As I mentioned in the last post, research is not immune to fads. Ideas fall in and out of fashion based on the political, financial, and social winds of the time. I’m not just talking about wacky ideas either. Even the idea that drinking during pregnancy can harm a developing fetus has had its share of rises and falls.

The belief that drinking while pregnant is harmful has been around since antiquity, popping up among the Ancient Greeks and even appearing in the Old Testament when an angel instructs Samson’s mother to abstain from alcohol while pregnant. Yet the belief was far from universal across different epochs and different peoples. In fact, it took a special kind of disaster for England and, in turn, America to rediscover this idea in the 18th century. The disaster was an epidemic . . . of people drunk on gin.

By the close of the 17th century, bickering between England and France caused the British to restrict the import of French brandy and encourage the local production of gin. Soon gin was cheap and freely available to even the poor and working classes. The Gin Epidemic was underway. Rampant drunkenness became a fact of life in England by 1720 and would persist for several decades after. During this time, gin was particularly popular among the ladies – a fact that earned it the nickname “Mother’s Ruin.”

Soon after the start of the Gin Epidemic, a new constellation of abnormalities became common in newborns. Physicians wondered if heavy prenatal exposure to alcohol disrupted fetal development. In 1726, England’s College of Physicians argued that gin was “a cause of weak, feeble and distempered children.” Other physicians noted the rise in miscarriages, stillbirths, and early infant mortality. And by the end of this gin-drenched era, Britain’s scientific community had little doubt that prenatal alcohol could irreversibly harm a developing fetus.

The notion eventually trickled across the Atlantic Ocean and took hold in America. By the early 19th century, American physicians like Benjamin Rush began to discourage the widespread use of alcohol-based treatments for morning sickness and other pregnancy-related ailments. By the middle of the century, research on the effects of prenatal alcohol exposure had become a talking point for the growing temperance movement. Medical temperance journals sprung up with names like Journal of Inebriety and Scientific Temperance Journal. Soon religious and moralistic figures were using the harmful effects of alcohol on fetal development to bolster their claims that all alcohol is evil and should be banned. They often couched the findings in inflammatory language, full of condemnations and reproach. In the end, their tactics worked. The 18th Amendment to the U.S. Constitution was ratified in 1919, outlawing the production, transportation, and sale of alcohol on American soil.

When the nation finally emerged from Prohibition more than thirteen years later, it had fundamentally changed. People were disillusioned with the temperance movement and wary of the moralistic rhetoric that had once seemed so persuasive. They discounted the old familiar lines from teetotal preachers – including those about the harms of drinking while pregnant. Scientists rejected studies published in medical temperance journals and began to deny that alcohol was harmful during pregnancy. In 1942, the prestigious Journal of the American Medical Association published a response to a reader’s question about drinking during pregnancy which said that even large amounts of alcohol had not been shown to be harmful to the developing human fetus. In 1948, an article in The Practitioner recommended that pregnant women drink alcohol with meals to aid digestion. Science was, in essence, back to square one yet again.

It wasn’t until 1973 that physicians rediscovered and named the constellation of features that characterize infants exposed to alcohol in the womb. The disease, fetal alcohol syndrome, is now an accepted medical phenomenon. Modern doctors and medical journals now caution women to avoid alcohol while pregnant. After a few political and religious detours, we’ve finally made it back to where we were in 1900. That’s the funny thing about science: it isn’t always fast or direct or immune to its cultural milieu. But if we all just have faith and keep driving, we’re bound to get there eventually. I’m almost sure of it.

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Photo Credit: Gin Lane by William Hogarth 1751 (re-engraving by Samuel Davenport circa 1806). Image in public domain and obtained from Wikipedia.

Dreaming of Me

My belly button has all but disappeared. In its place, an odd little pillow of skin lies flush with the rest of my stomach. A dark line – the linea nigra – now runs down the length of my abdomen, dividing me in two. My appendix and intestines, previously at home in my abdominal cavity, have been pushed up and to the sides so that they now form mysterious bulges just below my ribs. Stranger still, I find myself in possession of someone else’s breasts. And then there’s the most noticeable change: the beach ball sized stomach that wholly eclipses my view of my feet.

Of course these changes didn’t come on all at once. I’ve had many months to notice and adjust to them. Still, they’ve happened more rapidly than any other physical changes I’ve experienced in my life. Faster than an adolescent growth spurt, certainly, or any weight gain or loss. My brain has had trouble keeping up. I bump into things with my belly, forgetting its size. I struggle to maintain my balance as my vestibular system tries to adjust to my changing weight distribution. But the lag that has fascinated me most is how I envision myself in my dreams.

Even months into my pregnancy, after my stomach had visibly ballooned, the self I inhabited while dreaming remained as lean as ever. Although thoughts of my pregnancy filled my waking hours, at night I wasn’t the least bit pregnant. In fact, I often dreamt of myself as a high schooler again, wandering the halls without a class schedule or scrambling to find a bus that would deliver me there on time. Why high school? I don’t put much stock in the elaborate interpretation of dream symbols, but I imagine that my dreams of being a lost high school student reflect my waking awareness that parenthood is at my doorstep and I am unprepared. In the face of such a dramatic life change, I can’t help but feel that I’ve lost my lunchbox or forgotten a homework assignment somewhere.

Then, a month or so ago, my dreams began to change. Or rather my dream self changed. My new self often had a swollen midsection and wore maternity clothes (or in one case, a maternity prom dress). She couldn’t drink alcohol and got worn out just walking from the car. The dreams weren’t usually about my pregnancy; my enormous belly was simply present, just like my arm, hands, and feet. Something about my self-image, my internal body schema, had updated. A switch had been flipped and my mind was caught up with my changing body.

I began to wonder about these internal self-schemas that reveal themselves in our dreams. Do other pregnant women experience the same switch and a similar lag? And how long does it take for them to switch back after they’ve delivered their babies? What about other changes to one’s appearance, like growing or shaving off a beard? Or, in a more dramatic example, what happens when someone loses a limb?

I haven’t found much written on baby bumps and beards, but several people have studied whether amputees dream of themselves with intact or amputated bodies. The answer, in short, is it depends. One study found that a majority of surveyed amputees dreamt of themselves with amputated bodies at least some of the time. Among them, 77% made the switch within the first 6 months following their amputations. But the study also showed that a surprising percentage of the surveyed amputees (31%) dreamt exclusively of themselves with intact bodies, even a decade or more after their amputations. Preliminary findings suggest that those who undergo the amputation at a later age, those who regularly use a prosthetic limb, and those who experience phantom sensations from the missing limb may all be more likely to dream with their bodies intact.

It should come as no surprise that the results of the studies are complicated and variable. We can’t expect anything as complex as dreams and internal self-representations to be wholly consistent from person to person or from one dream to another. In my case, I may be pregnant in one dream but not in the next. At times I even dream I’m someone other than myself. Wading into dreams can be a messy business, certainly, but my curiosity is piqued and I’m eager for more data. To all those pregnant or post-pregnant ladies, beard growers, or head shavers out there: please comment and share your experiences! How long did it take for your dream self to catch up with the real thing?

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Photo credit: Sabin Dang

Locked Away

The results are in. The ultrasound was conclusive. And despite my previously described hunch that our growing baby is a boy, she turned out to be a girl. We are, of course, ecstatic. A healthy baby and a girl to boot! As everyone tells us, girls are simply more fun.

As I was reading in my pregnancy book the other day, I came across an interesting bit of trivia about baby girls. At this point in my pregnancy (nearly 6 months in), our baby’s ovaries contain all the eggs she’ll have for her entire life. As I mentioned in a prior post, the fact that a female fetus develops her lifetime supply of eggs in utero represents a remarkable transgenerational link. In essence, half of the genetic material that makes up my growing baby already existed inside my mother when she was pregnant. And now, inside me, exists half of the genetic material that will become all of the grandchildren I will ever have. This is the kind of link that seems to mix science and spirituality, that reminds us that, though we are a mere cluster of cells, there’s a poetry to the language of biology and Life.

But after stumbling upon this factoid about our baby’s eggs, I was also struck by a sense that somewhere someone seemed to have his or her priorities mixed up. If our baby were born today, she would have a slim chance of surviving. Her intestines, cerebral blood vessels, and retinas are immature and not ready for life outside the womb. Worse still, the only shot her lungs would have at functioning is with the aid of extreme medical intervention. The order of it all seems crazy. My baby is equipped with everything she’ll need to reproduce decades in the future, yet she lacks the lung development to make it five minutes in the outside world. What was biology thinking?

Then I remembered two delightful popular science books I’d read recently, The Red Queen by Matt Ridley and Life Ascending by Nick Lane. Both described the Red Queen Hypothesis of the evolution of sex, which states that the reason so much of the animal kingdom reproduces sexually (rather than just making clones of itself) is to ‘outwit’ parasites. In short, if each generation of humans were the same as the next, parasites large and microbial could evolve to overtake us. By mixing up our genetic makeup through sexual reproduction, we make it harder for illnesses to wipe us out. Like the Red Queen from Lewis Carroll’s classic, we keep running in order to stay in the same place (which is one step ahead of parasites and disease).

Just as there are parasitic organisms and bacteria, one might say that there are parasitic genes. For example, mutations in the DNA of our own replicating cells can cause cancer, which is essentially a self-made, genetic parasite. Moreover, retroviruses like HIV are essentially bits of genetic material that invade our bodies and can insert themselves into the DNA of our cells. And the ultimate road to immortality for a parasitic gene would be to hitch a ride on the back of reproduction. Imagine what an easy life that would be! If a retrovirus could invade the eggs in the ovaries, it would be passed on from one generation to the next without doing one iota of work. It’s the holy grail of parasitic invasion – get thee to the ovaries! According to Matt Ridley in another of his books, The Origins of Virtue, the human germ line is segregated from the rest of the growing embryo by 56 days after fertilization. Within two months of conception, the cells that will give rise to all of the embryo’s eggs (or sperm, in males) are already cordoned off. They are kept safe until they are needed many years in the future.

So perhaps my little baby’s development isn’t as backwards as it seemed at first. Yes, lungs are important. But when you’ve got something of value to others, it makes practical sense to hurry up and lock it away.

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