From Womb to Womb

Worldwide, women suffer an estimated 2.65 million stillbirths each year. Despite those huge numbers, we only understand some of the factors that are responsible. In low- and middle-income countries (where most of the world’s stillbirths occur), diseases like malaria can put pregnant women at risk of stillbirths. In wealthier countries, the biggest risks include smoking and obesity. But these factors only go partway to explaining why some women have stillbirths, leaving many cases unaccounted for. The benefits that would come from that knowledge could be enormous.

One way to learn about reproductive health is to observe how our primate cousins have babies. And a new study on marmosets offers some hints about the causes of stillbirth. It suggests that a mother’s health during pregnant may not be the whole story. In fact, some of the risk factors may arise before mothers are even born.

The first thing that one notices about the white-tufted ear marmoset (Callithrix jacchus) is its wildly adorable face–a tiny visage framed by shocks of white fur. Marmosets are interesting to scientists not because they’re cute, but because of their intriguing way of having kids. While most primate females have a single offspring at a time, marmoset  typically have twins. Some marmoset mothers even have triplets.

This is a tricky strategy for passing on marmoset genes. Marmoset babies can weigh between a fifth and a quarter of their mother’s weight. Imagine a 135-pound woman giving birth to two 16 pound babies–and then nursing them. The strategy only works because marmosets live in groups. A breeding female and male marmoset are attended to by helpers–usually related females that suppress their own ability to have babies while they assist the breeding female. They take turns carrying the babies and getting food. The father even helps out, too.

Despite all the help, however, female marmosets sometimes have stillbirths. Recently, Julienne Rutherford, a biological anthropologist at in Department of Women, Children, and Family Health Science at the University of Illinois at Chicago, went on a search for the factors that put a marmoset at greatest risk of having one.

She and her colleagues studied a marmoset colony at the Southwest National Primate Research Center in San Antonio, Texas. The center keeps detailed records for all the marmosets, from birth to death. Rutherford and her colleagues analyzed the reproductive history of 79 female marmosets since 1994. And when they were done with the analysis, one factor in particular jumped out of the data. Females that were born in sets of triplets are three times more likely to lose a fetus than females born as twins.

The scientists looked at the other data to figure out what was happening. The risk of stillbirth wasn’t just part of an overall problem with fertility. Triplet females were just as likely to get pregnant as twin females. It’s just that they were less likely to carry their pregnancies to a successful term.

Perhaps the result was just a shadow of a much bigger pattern. Scientists have long known that women who were low weight at birth end up at greater risk of stillbirths when they get pregnant. The same goes for other female primates. It was therefore possible that triplet female marmosets were at greater risk of stillbirths simply because triplet marmosets are smaller at birth than twins. Rutherford and her colleagues looked over the records to see if that was the case.

It wasn’t. Triplet females are born at a range of weights, and extra size offer them no protection against stillbirths. The big triplet females are also at risk of having stillbirths when they grow up.

Something must be happening in the marmoset womb that is leaving an invisible mark on triplet females for their entire life. As a female primate embryo develops, it grows the ovaries and uterus it will eventually use to bear its own young. The development of those organs is normally choreographed by the hormones that swirl around the embryo’s body. Sharing a uterus with two other embryos may disrupt that choreography. Most triplet females are born along with at least one brother, for example. It’s possible that the male hormones produced by their brothers  interfered with their own development.

Since women typically only have one baby at a time, there isn’t a simple lesson in Rutherford’s research for medicine.  But it may encourage scientists to to widen their search for the cause of stillbirths. Yes, the health of a woman while she’s pregnant is enormously important to a successful pregnancy. But her reproductive health may be altered before she’s even born.

Scientists have done very little research on this possibility in humans. One of the few studies looked at the legacy of the so-called “Dutch Hunger.” In the winter of 1944/45, the Netherlands suffered a famine. Many women who were pregnant at the time suffered from malnutrition. Scientists have followed their children ever since to see what effect the famine had on them before they were born. In 1997, researchers found that the women were just as fertile as women from well-fed mothers. But their children were at greater risk of stillbirth or of dying just after birth [pdf].

Given how long people live, tracing the effects of pregnancy on stillbirths is going to be slow work. Female marmosets, on the other hand, can start having babies before they’re two years old. Rutherford and her colleagues are taking advantage of the fast life of marmosets by following a number of females from birth to first pregnancy. The scientists are using ultrasound to take pictures of the marmosets’ developing reproductive systems, and measuring their hormone levels along the way.

This new research may allow Rutherford to pinpoint the reason that it’s so risky to be a triplet mother. And it may let her offer some ideas about how to make human childbirth healthier, too.