Tuesday, July 31st 2012

SciAm Beginnings: When a Beginning is Not a Beginning

Thursday 26th July saw the launch of SciLogs.com, a new English language science blog network. SciLogs.com, the brand-new home for Nature Network bloggers, forms part of the SciLogs international collection of blogs which already exist in German, Spanish and Dutch. To celebrate this addition to the NPG science blogging family, some of the NPG blogs are publishing posts focusing on “Beginnings”.

Participating in this cross-network blogging festival is nature.com’s Soapbox Science blog, Scitable’s Student Voices blog and bloggers from SciLogs.com, SciLogs.de, Scitable and Scientific American’s Blog Network. Join us as we explore the diverse interpretations of beginnings – from scientific examples such as stem cells to first time experiences such as publishing your first paper. You can also follow and contribute to the conversations on social media by using the #BeginScights hashtag.

Over the course of my training to become a biological anthropologist with a specialty in women’s reproductive ecology and life history theory, or ladybusiness expert , I have learned a lot about miscarriage. Only it wasn’t miscarriage, it was spontaneous abortion. Except that some didn’t like the term spontaneous abortion and used intrauterine mortality (Wood, 1994). Or fetal loss. Fetal loss is probably the most common.

There is also pregnancy loss (Holman and Wood, 2001). You can use that term, too. Oh, or a-conceptions (a for abortion), compared to l-conceptions (l for live birth) (Wood, 1994).

A large number of these fetal losses are before or close to the time of implantation. For many of those, unless the mother is measuring her hCG levels via a pregnancy test because she’s trying (or not) to get pregnant, she is at most going to notice a day or two longer cycle, maybe a slightly longer but lighter period. Most women with very early fetal loss will never even know they were pregnant.

So fetal loss, while important to my research, never seemed like a big deal to me from a cultural or emotional perspective. And there are a lot of ways to talk about it, plenty of terms to choose from.

They’re all inadequate.

* * *

The first time I talked to someone about her miscarriage was only a week or two after she told me she was pregnant. “I know the convention is to wait twelve weeks, but it seems silly to keep it a secret that long.” I was maybe twenty five, still uninterested in children enough to be perplexed that she wanted one, but thrilled for her. We hugged over the stick shift of her car.

Then, later, she shares that the fetus hadn’t grown since the last ultrasound, and almost certainly was dead. We hug again, and I don’t know what to say. I never found out if she had to get a D&C or whether she miscarried on her own. A few days later, we’re in an important meeting in a local cafe. She hasn’t gotten some key things done. I don’t know what to do: is the right thing to do to push her and act like nothing’s happened, or give her time to grieve? Asshole that I was, I ask her about her piece of the work.

She pauses. “I just feel… lost.”

And she begins to cry.

The third person in our meeting, our boss and friend, says, “We are not pushing a woman who just had a miscarriage.” And so the three of us just sat in that cafe, in the uncomfortable semi-silence of trying to hold back tears. And none of us knew what to do next.

* * *

A few years later, I found myself a very different person, no longer remotely perplexed by the idea of wanting a child. I loved the smell and feel of babies. I wanted to carry a baby in my belly. And thankfully, after a little help, I was pregnant.

Shortly after implantation, I had about a week of almost continuous menstrual cramps. I felt as though I would get my period at any moment, and spent almost every day semi-working from home, in a panic that I was about to miscarry. In a follow-up call with my nurse, she told me the cramping was actually normal in a healthy pregnancy and that my hCG concentrations – that’s the signal the fetus sends to the mother to let her know it’s there – were quite high. For about the millionth time that week, I sobbed like a baby.

For the rest of that first trimester I was so nauseous that I could barely eat. I lost six pounds, unheard of for a big eater like me. Yet as awful as I felt, I relished every second of that nausea, because I knew it meant the fetus was most likely alive and thriving.

As far as I know, I have never miscarried.

Miscarriage still terrifies me.

* * *

There was the woman who was having twins, until one stopped growing. There was the one who didn’t tell anyone until she was twenty weeks into her next pregnancy for fear of jinxing the one that seemed to be sticking. There are the ones where the woman shrugs it off, where tears prick at the corners of her eyes, where the shoulders slump even as she tries to smile.

The beginning of pregnancy, which if you want to be pregnant is a joyous moment, is also fraught with tension. Most of the advice newly pregnant women receive is about denial: no caffeine, no alcohol, no raw fish or raw milk or tuna or swordfish or deli meat or unwashed fruits or vegetables. No cleaning kitty litter. Don’t let your heart rate get too high. No heavy lifting. Don’t gain too much weight, or too little.

And don’t stress out, of course. It can hurt the baby.

The majority of factors that influence fetal loss are likely out of the mother’s control, meaning they have little to do with any of the above factors. Genetic abnormalities comprise the majority of very early fetal losses, as far as we can tell. These are embryos that probably would not develop properly into fetuses. When this happens, the body can reject an ill-formed embryo, or the embryo itself simply fails to grow. But this is a mechanism we know very little about.

Maternal age also matters, as the risk for fetal loss increases with age (more so after thirty-five years). There are at least three factors contributing to this: the eggs, the ovaries, and the endometrium. Aging eggs probably contribute to the genetic abnormality issue. And aging ovaries and an aging endometrium could have an increasingly hard time supporting a fetus, and so lower hormones or a thinner or less-nourished endometrium could help explain some fetal losses (there’s a lot more I could say on this, so let’s just assume I’ll elaborate in a future post). For instance, low progesterone concentrations, which is the hormone the ovary and then placenta secretes to maintain pregnancy, is associated with miscarriage risk (Arck et al., 2008). After thirty, progesterone concentrations begin to decline, but are still in the peak range through about thirty five years of age (Ellison et al., 1993; O’Rourke et al., 1996). Another study found that maternal age decreases the chance of conception, but donor’s age increased the risk of miscarriage in women undergoing IVF (Levran et al., 1991). These are women who are undergoing progesterone supplementation, so my best guess is that their endometria become less responsive to hormonal control as they age (Clancy, 2009). Yet, a mother cannot control her own age and can only partially control her chances of getting pregnant.

Figure 1. The straight line represents the increase in the number of fetal losses over a woman's lifetime, the curved line her ovarian hormone concentrations.

The controllable factors still probably have little to do with all the things a pregnant woman is supposed to avoid during pregnancy. Across a few clinical samples, researchers have found that spontaneously conceiving, underweight women are at a greater risk for miscarriage (Arck et al., 2008), overweight and obese women are not (Turner et al., 2010), but obese women with recurrent (three or more) miscarriages are (Metwally et al., 2010) and overweight women conceiving with IVF are as well (Dokras et al., 2006). There is a sweet spot that reduces risk the most in terms of maternal weight. Yet weight is a potent mix of genetics, socioeconomic status, and nutritional status that rests on top of the supposed biggest culprit of willpower.

Of all the things a pregnant woman is supposed to avoid, stress is the one with a growing body of evidence in its favor. One prospective study – meaning they began to study participants before they were pregnant – found that women from a rural Mayan sample who experienced very early fetal loss had higher cortisol concentrations (Nepomnaschy et al., 2006, who happens to be a collaborator on a different project). Cortisol is often mistakenly called a “stress hormone” in our popular interpretation of psychological stress. But cortisol is a signal of physiological, or constitutional stress. It indicates that our hypothalamic-pituitary-adrenal axis has been activated, which means the body is at minimum trying to allocate towards maintenance effort or the stress response. So this study – one of the first of its kind and, I think, performed to a high technical standard – shows us that freeliving women who happen to have miscarriages also happen to have an elevated stress response. Whether that is causal is unclear.

Fig. 2. From Nepomnaschy et al 2006.

In efforts to get at stress from a different angle, some researchers have explored inflammation, which I review in a chapter in Building Babies, out in September (Clancy, 2012). Systemic inflammation, often measured via C-reactive protein (CRP), is correlated with psychological stress (Danese et al., 2009; Miller et al., 2005; Miller et al., 2002). And there are indicators that both systemic and local inflammation impact pregnancy. But here’s the funny thing: you actually need some inflammation to support pregnancy. So very high and very low concentrations of CRP are both correlated with an increased risk of early fetal loss (Sacks et al., 2004). There’s that sweet spot again.

To make it all extra confusing, many of these studies employ different methods to understand fetal loss. Prospective or retrospective study designs, different ways of determining pregnancy, different cutoffs for what constitutes early fetal loss, very early fetal loss, and so on. So actual estimates of how much these factors influence fetal loss varies. The safest overall estimate for any given pregnancy is probably about 30%, though one study, even with conservative estimates of pregnancy and fetal loss puts it at 60% (Holman and Wood, 2001). This means, though, that for every two live births a woman has, she’ll have at least one miscarriage. And that’s not because she’s done anything in particular to deserve it.

The randomness, the lack of control, the fact that it can even happen a few times in a row in a woman and just be poor luck, that is the terror of miscarriage. Trying to give it a different name, or restricting women’s intake or movements, these are just ways to try and establish control in something largely uncontrollable.

So, beginnings are wonderful. But beginnings can be brutal, too. And there are no words I can say that will make the experience of miscarriage less raw or inexplicable.


Arck PC, Rücke M, Rose M, Szekeres-Bartho J, Douglas AJ, Pritsch M, Blois SM, Pincus MK, Bärenstrauch N, Dudenhausen JW. 2008. Early risk factors for miscarriage: a prospective cohort study in pregnant women. Reproductive biomedicine online 17(1):101-113.
Clancy KB. 2012. Inflammation, reproduction, and the Goldilocks Principle. In: Clancy KB, Hinde K, Rutherford JR, editors. Building Babies: Primate Development in Proximate and Ultimate Perspective. New York: Springer.
Clancy KBH. 2009. Reproductive ecology and the endometrium: physiology, variation, and new hypotheses. Yearbook of Physical Anthropology 52:137-154.
Danese A, Moffitt TE, Harrington H, Milne BJ, Polanczyk G, Pariante CM, Poulton R, Caspi A. 2009. Adverse Childhood Experiences and Adult Risk Factors for Age-Related Disease: Depression, Inflammation, and Clustering of Metabolic Risk Markers. Arch Pediatr Adolesc Med 163(12):1135-1143.
Dokras A, Baredziak L, Blaine J, Syrop C, VanVoorhis BJ, Sparks A. 2006. Obstetric outcomes after in vitro fertilization in obese and morbidly obese women. Obstetrics & Gynecology 108(1):61.
Ellison PT, Panter-Brick C, Lipson SF, O’Rourke MT. 1993. The ecological context of human ovarian function. Human Reproduction 8(12):2248-2258.
Holman D, Wood J. 2001. Pregnancy loss and fecundability in women. In: Ellison P, editor. Reproductive Ecology and Human Evolution. New York: Aldine de Gruyter.
Levran D, Ben-Shlomo I, Dor J, Ben-Rafael Z, Nebel L, Mashiach S. 1991. Aging of endometrium and oocytes: observations on conception and abortion rates in an egg donation model. Fertil Steril 56(6):1091-1094.
Metwally M, Saravelos SH, Ledger WL, Li TC. 2010. Body mass index and risk of miscarriage in women with recurrent miscarriage. Fertility and Sterility 94(1):290-295.
Miller GE, Rohleder N, Stetler C, Kirschbaum C. 2005. Clinical depression and regulation of the inflammatory response during acute stress. Psychosomatic medicine 67(5):679-687.
Miller GE, Stetler CA, Carney RM, Freedland KE, Banks WA. 2002. Clinical depression and inflammatory risk markers for coronary heart disease. The American Journal of Cardiology 90(12):1279-1283.
Nepomnaschy P, Welch K, McConnell D, Low B, Strassmann B, England B. 2006. Cortisol levels and very early pregnancy loss in humans. Proceedings of the National Academy of Sciences 103(10):3938-3942.
O’Rourke MT, Lipson SF, Ellison PT. 1996. Ovarian function in the latter half of the reproductive lifespan. American Journal of Human Biology 8(6):751-759.
Sacks GP, Seyani L, Lavery S, Trew G. 2004. Maternal C-reactive protein levels are raised at 4 weeks gestation. Hum Reprod 19(4):1025-1030.
Turner MJ, Fattah C, O’Connor N, Farah N, Kennelly M, Stuart B. 2010. Body Mass Index and spontaneous miscarriage. Eur J Obstet Gynecol Reprod Biol 151(2):168-170.
Wood JW. 1994. Dynamics of Human Reproduction: Biology, Biometry, Demography. Hrdy SB, editor. Hawthorne, NY: Aldine de Gruyter.

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