Life in Womb Holds Secrets To Developing Diabetes Later In Life

According to Jill Goldstein, PhD, of Brigham and Women's Hospital in Boston, women in their late 40s whose fetal growth was restricted and whose mother developed preeclampsia were significantly more likely than their male counterparts to have both major depression and signs of cardiac dysfunction (RR 1.38, P<0.01),

In addition, women exposed to these two risk factors in the womb had deficits in the regions of the brain associated with stress response, mood, and cardiac function -- the hypothalamic-pituitary-adrenal axis..

Goldstein and colleagues hypothesized that, .It has been known that women carry a higher risk than men for the combination of major depression and cardiovascular disease, and the effects of a stressful fetal environment on the development of the stress response circuitry in the brain -- which develops and functions differently in men and women -- might provide a reason why.

"By understanding the early signs and pathways, we hope to intervene early and to lessen disability and to eventually prevent the illnesses," said Goldstein, who noted that the co-occurrence of major depression and cardiovascular disease is expected to be the main cause of disability worldwide by 2020. "We need to approach this through the lens of understanding sex differences in diseases in order to develop treatments or prevention strategies that are sex-specific."

Goldstein and her colleagues have been following the adult offspring of mothers who participated in a cohort study starting in 1959 to 1966. The study was originally designed to follow the offspring for seven years to answer developmental questions. But for the past 20 years, the researchers have re-recruited the adult offspring -- now mostly in their late 40s -- for further studies. The current analysis included 295 participants.

The researchers performed physical examinations and studied brain responses in the hypothalamic-pituitary-adrenal axis to various stimuli using fMRI.

Participants who had been exposed to preeclampsia and fetal growth restriction in the womb were significantly more likely to have both depression and cardiovascular disease -- as shown by autonomic nervous system dysregulation. The finding was stronger in women.

Goldstein stated that, women exposed to those two risk factors were also significantly more likely to have deficits in various parts of the hypothalamic-pituitary-adrenal axis, which co-occurred with hormonal abnormalities.

Practice Pearls:

• Tthis study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Factors that occur during fetal development may help identify offspring -- particularly females -- who are susceptible to the co-occurrence of major depression and cardiovascular disease in mid-life.
• Women exposed to preeclampsia and fetal growth restriction in the womb had deficits in the regions of the brain associated with stress response, mood, and cardiac function -- the hypothalamic-pituitary-adrenal axis.

Goldstein J, et al "Fetal programming of sex differences in stress response circuitry, endocrine, and ANS deficits in adulthood: implications for understanding sex differences in comorbidity of depression and CVD risk" ACNP 2011.