Prenatal betamethasone exposure and psychopathology risk in extremely low birth weight survivors in the third and fourth decades of life

Psychoneuroendocrinology. 2016 Dec:74:278-285. doi: 10.1016/j.psyneuen.2016.09.021. Epub 2016 Sep 28.


Background: Mortality rates among extremely low birthweight (ELBW) infants have declined since the advent of antenatal glucocorticoid use. However, the long term neuropsychiatric effects of exposure are not well understood. We utilized the world's oldest longitudinally followed cohort of ELBW survivors to compare psychopathology over two decades in adulthood in those exposed to prenatal betamethasone and those who were not.

Methods: ELBW survivors (n=179) and matched normal birth weight (NBW) controls (n=145) completed the Young Adult Self-Report questionnaire at 22-26 and 29-36 years, and the Beck Depression and Anxiety Inventories at 29-36 years. Symptom levels and rates of clinically significant psychiatric problems were compared in ELBW survivors whose mothers were administered steroids during pregnancy (ELBW-S n=63), ELBW participants who were not (ELBW-NS, n=79), and NBW controls.

Results: At 22-26, ELBW-S had higher levels of anxiety, depressive, and avoidant personality symptoms, and a 3 to 5-fold increase in the odds of clinically significant levels of these problems compared to NBW controls, whereas ELBW-NS did not. These associations were maintained at 29-36, when ELBW-S participants exhibited a 3 to 10-fold increase in the odds of clinically significant anxiety and avoidant personality problems compared to NBW controls. At both time points, the odds of clinically significant anxiety problems were more than 3 times higher among ELBW-S than in ELBW-NS.

Conclusion: ELBW adults exposed to prenatal betamethasone manifest higher levels of anxiety and depression than those who were not, and may represent a group of preterm survivors at particularly high psychiatric risk.

Keywords: Anxiety; Depression; Developmental; Extremely low birth weight; Mood; Prenatal steroids.

MeSH terms

  • Adult
  • Anxiety / etiology*
  • Betamethasone / adverse effects*
  • Depression / etiology*
  • Female
  • Glucocorticoids / adverse effects*
  • Humans
  • Infant, Extremely Low Birth Weight*
  • Longitudinal Studies
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Young Adult


  • Glucocorticoids
  • Betamethasone