Scientists Discover Exactly How Stress Causes Premature Labor

As premature births and infant deaths increase in world, Chinese team uncovers hormonal cascade that causes birth to start – often too soon.

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Babies in a maternity ward.
Babies in a maternity ward.Credit: Alon Ron
Ruth Schuster
Ruth Schuster

We cannot definitively say we know the causes of premature labor and birth, at least not in all cases. However, among the many potential causes are stress, whether traumatic or chronic. Now a team of scientists has uncovered a physiological feedback loop that boosts the production of one of the stress hormones known to trigger labor under normal conditions – which could be the factor being prematurely activated during preterm labor.

According to the World Health Organization, 15 million children are born preterm every year. , and, says the organization, “the number is rising.” That is at least partly because people are marrying and procreating later in life. The older the parents, not only the mother, the higher the probability of problems in pregnancy and premature birth.

Almost 1 million children die each year due to complications of preterm birth, the WHO says, adding that 12% of infants are born preterm (on average) in the poorer countries, where bad maternal nutrition is a factor, versus 9% in higher-income countries.

Normal human pregnancy lasts about 40 weeks; full-term is considered 39-40 weeks. The earlier babies are born before their due date, the greater the probability of problems. Babies born in weeks 37-38, now commonly called “early term,” face more health risks than do those born at 39 or 40 weeks, for instance. “Premature” is usually defined as birth before the gestational age of 37 weeks. Preventing premature birth matters: Babies born in late-preterm are still considered three times more likely to die in the first year of life than full-term babies are.

Understanding the hormonal mechanism leading to labor could lead to the development of new drugs to prevent or delay premature birth, which has become the leading cause of infant death worldwide, according to a 2014 study.

Stress is just one of countless potential causes for premature birth, but perhaps it can be addressed by more than a pat on the head and Zoloft. The feedback loop now discovered involves cortisol, one of the dozens of hormones at work in our bodies.

Hormones are like signals that travel through our circulatory system, causing a physiological or behavioral effect. A massively oversimplified classic example is that something annoys us, which causes our irked glands to release the hormone adrenaline, which causes us to want to kick that something (or flee).

Cortisol is one of the multiple hormones released (by adrenal glands located on top of our kidneys) under conditions requiring heightened awareness – such as when we wake up, and when we get stressed. Its production also steps up towards the end of normal pregnancy, ahead of normal delivery.

Understanding how cortisol ramps up before regular delivery was the key to understanding its involvement in prematurity.

Studying cells from the inner layer of the placenta, Wangsheng Wang of the Jiao Tong University in Shanghai, China, working with doctors at various Chinese medical institutions, found a positive feedback loop that boosts cortisol production. The release of cortisol triggered a cascade that resulted in the production of another hormone, prostaglandin E2. The E2 in turn activated receptors that created a loop driving yet more production of cortisol and prostaglandin E2. And there you have it.

In supportive evidence, the team also found that women who gave active birth had higher levels of both cortisol and E2 in their blood compared with women who had caesarean delivery before labor actually ensued. The full article, “Phosphorylation of STAT3 mediates the induction of cyclooxygenase-2 by cortisol in the human amnion at parturition,” was published Wednesday in the journal Science Signaling.

In Israel, in 2014 there were 176,427 live births (all sectors, including Jewish, Muslim and Christian), up about 5,000 from the year before, according to the Central Bureau of Statistics.

According to the WHO, in 2010 less than 10% of births in Israel, most of Europe and Russia were premature. The country with the worst prematurity problem was Malawi, where 18% of births were premature. The rate in the United States is 10% to 15% – of the 1.2 million preterm births estimated to occur in high-income regions, more than 42% were in the U.S., says the WHO.

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