How Much Does Prenatal Influence Matter?

Dear Annie,

Thanks for your terrific response. You write that you have come to see the notion of fetal origins—the idea that very early influences and exposures affect our health later on—as “beautiful, even wondrous.” And this reminds me: During my stint in medical school, when I dissected the cadaver of a man who’d died in old age, I remember marveling at a small mark, like a thumbprint, in his heart. Before this man was born, before he’d ever taken a breath, he had a small opening (as normal fetuses do) between the top two chambers of his heart. This opening reroutes blood away from the fragile lungs as they develop—at a point when the fetus gets its oxygen from the mother.

This tiny passage within the heart closes after birth. But I saw the mark as a visible trace of an earlier fetal life. When I was pregnant, this image came back to me as a touchstone for the profound entwining of mother and child. Along similar lines, I’ve written about how maternal cells cross the placenta and take up residence in the fetus’s body, where they may help to make its budding immune system more tolerant, partly of the mother’s own cells. I still find this possibility alluring, both as medical research and as metaphor.

At the same time, for every gem of fetal origins research there is a lump of coal. This is true, of course, of any emerging science. But you point out that this work faces particular challenges. It’s hard to assign women to study groups. Complex confounding variables, like genetics and experience after birth, can loom large. And the effects we care about, like later health or behavior or cognitive development, tend to play out over many years. Partly as a result, many studies don’t adhere to the highest standards of evidence, and preliminary claims can linger for a long time before they are effectively confirmed or debunked. So, to what extent should we give early work the benefit of the doubt? To what extent should we grade it on a curve?

For the most part, you incline toward tolerance yourself, writing with a lyrical, light touch. You search out studies on the “positive proactive steps pregnant women can take” to improve the later health of their fetuses—even though, as we seem to agree, these tend not to be the best-supported work in the field. Of course, the positive steps you mention, like physical exercise and psychotherapy, are clearly good for pregnant women’s own health, too. So what’s the harm in playing up additional benefits they might confer on the fetus if this can serve as a coping strategy for dealing with anxiety, as you say it did for you? Maybe there is none. But at the risk of sounding ungenerous, I’ll point out that the paper on maternal exercise and fetal heart rate you cite appears to include just six participants. The same researcher has since done a follow-up pilot, but the sample size remains small, the work is still not well-controlled or randomized, and a significant number of women missed follow-up assessments, which is no good for data collection. For a mental pick-me-up, I’d go instead with a Philip Larkin poem.

The stakes get higher for some of the more controversial claims. You describe research on how the ratio of male to female births seems to vary depending on environmental conditions. Some studies have found that fewer male babies are born in stressful times, like in the wake of a large earthquake in Kobe, Japan, or the collapse of the Berlin wall. One evolutionary explanation you discuss begins with the assumption (I don’t know if it’s well-founded) that under tough conditions, weak males are relatively less likely than weak females to survive and reproduce. So in stressful times, weak male fetuses are more likely to be miscarried, leaving a woman free to get pregnant again with a female (or a stronger male). This theory, championed by Berkeley public health professor Ralph Catalano, predicts that the males born during tougher times should be relatively stronger, on average, than males born in other periods. In one study, Catalano considered Swedish population data on births from 1751 to 1912 and found that males born in years when the male-to-female birth ratio was lower (implying environmental stress) tended to have longer lifespans.

But I’m curious: How seriously do you take this theory? I haven’t done the legwork on sex ratios or fetal gender and miscarriage, and I have no idea whether Catalano’s assumptions are valid. But his overall take sounds a little fringe, and what strikes me is that his perspective is at odds with other fetal origins researchers—including David Barker, who serves as a hero of your story. Barker’s research suggests that fetuses that undergo privation in utero should be relatively less healthy later in life, with higher rates of heart disease and other problems. Catalano predicts the opposite. In your book, you don’t challenge or criticize them, but what do you make of this contradiction?

Also at stake in the interplay between Barker and Catalano are competing visions of pregnancy itself. To Barker (and others), gestation is largely a time of training, in which signals from the outside environment, transmitted through the mother, help to prepare the fetus for the world it will soon enter. You write passionately about this perspective. To Catalano, however, gestation is largely a time of natural selection, in which weak fetuses are “culled”—and this is the key mechanism ensuring that babies are “fit” for the conditions they enter. Of course, these two theories need not be mutually exclusive. You could have natural selection in utero and then training for the fetuses that make it. But to some degree, they are in tension. Do you think Catalano’s view of the womb as a Darwinian proving ground has merit?

Another, broader question: Your book is, ultimately, an expansive, big-tent appreciation of fetal origins research. And as such, it focuses on how exposures in utero might matter later on; other key variables like genetics or later environmental influences get less attention. This is understandable—you weren’t writing an encyclopedia! But if you take a step back, how much do you think prenatal influences matter relative to these other factors? I’m particularly curious about how you’d weigh their relative importance when it comes to later mental health and cognitive development, given what we know about brain plasticity.

I ask especially because of the public-policy implications. If we imagine trade-offs between money spent to address problems prenatally and postnatally, I wonder which ought to get priority, in particular cases, based on the evidence available today. For example, you argue, based on the findings of the Ice Storm Project, which tracks the cognitive progress of children who were in utero during a severe storm in Canada, that more resources should go to helping pregnant women during emergencies. I’m certainly not against giving blankets to pregnant women deprived of heat in the middle of winter. But if you only had $1 million to put toward kids’ cognitive development, how much would go for the pregnant women and how much for education for at-risk kids? In a world of scarce resources, do we know enough to justify diverting funds toward prenatal needs and away from programs with a more established track record?

My point, I suppose, is that the hype about fetal origins research means we should be extra sure to put it in perspective. You cite the inventor of medical ultrasound (he of the water-balloon condoms), as saying: “The first forty weeks of existence may well prove to be far more important medically than the next forty years.” I can see why you frame this quote as a “prescient insight.” But isn’t it also a wee bit much? Isn’t there a downside to overstating the promise, even of a promising field?

Looking forward to your thoughts,

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