A new study published in BMC Medicine suggests that the effects of a stressful environment during pregnancy can be passed down to later generations. The research team, led by Gerlinde Metz, Ph.D., of the University of Lethbridge, examined the effects of stress over four generations of rats. They found that stress in previous generations did affect the pregnancies of later generations, sometimes even more than the stress those later generations were currently experiencing. Mystery Often Surrounds Preterm Birth Preterm birth in humans\u2014defined as any birth that comes before the 37th week of a normal 40-week pregnancy\u2014remains puzzling in many cases. One of every nine babies in the U.S. is born preterm, yet research estimates that the causes of more than half of human preterm births are not known. While medical science has made tremendous strides in caring for infants who are born preterm, this population remains at much higher risk of serious illness, birth defects and early death than infants who are born full-term. Researchers hope that by making progress in identifying the causes of preterm births they will have a better idea of how to prevent them. Dr. Metz and her colleagues set out to evaluate the effects of stress during pregnancy on current generations as well as later generations. They wanted to discover whether stress was a factor in preterm births, and possibly other adverse characteristics. Study Finds No Effect on First Generation The researchers stressed a group of pregnant rats in two different ways between the 12th and 18th days of gestation\u2014the equivalent of the third trimester of a human pregnancy. Another group served as the control and was not placed in the same stressful situations. Somewhat surprisingly, the study found no difference in the gestation periods of rats that were stressed compared to rats that were not stressed. Stress that the rats personally experienced did not appear to be a factor in preterm birth. Later Generations Have Shorter Gestation Periods The researchers then proceeded to repeat the experiment on the new generation of rats, and the two following generations. In the later generations, signs of inherited stress began to appear. In the daughters of the first generation of stressed rats as well as the granddaughters of the first generation, gestation periods decreased by an average of seven hours. While this would be insignificant in a human, seven hours represented a statistically significant variation in the comparatively short gestation periods of the rodents in the study. Furthermore, shorter gestation periods were not the only difference seen in the rats whose mothers or grandmothers had been stressed. The study also found higher glucose levels in these rats (a sign of gestational diabetes) and lower weight gain during pregnancy. Low weight gain may not seem like a negative symptom, but a certain amount of weight gain during pregnancy is important for both maternal and fetal health. Perhaps the most interesting results came in the fourth generation of rats. Throughout the generational experiments, the researchers split each generation in order to test the impact of many variables. By the end, they had rats whose ancestors had all been exposed to stress, rats with no stress since the first generation (their great-grandmothers) and rats with other variations of stressed\/un-stressed generations. The study found that the rats with the smallest pups, and pups with more prominent behavioral changes, were rats with no history of stress since their great-grandmothers. Rats whose mothers, grandmothers and great-grandmothers were all stressed showed fewer effects than those whose stress dated back to the fourth generation. Research Poses Many Questions These results suggest that a family history of stressful pregnancies may help to explain previously mysterious preterm births in humans. However, the results also generate many questions. Future studies will attempt to reveal the biological mechanisms that explain this stress inheritance. This may in turn shed light on why this inheritance behaves the way it does over multiple generations.