Antenatal Depression and Adverse Pregnancy Outcomes (ADAPT)

Major depression is one of the most common complications of pregnancy.1,2 Not only does depression incur serious maternal risks, but it has been associated with adverse perinatal outcomes, including fetal growth restriction (FGR) 3-6 and preterm birth (PTB). 4,6,7 These perinatal complications are responsible for the majority of neonatal morbidity and mortality and are an enormous economic burden to the health care system. Emerging evidence suggests that inflammatory cytokines (IL-1β, IL-6, TNFα, IL-23, and IL-33) are associated with depressive and anxiety symptomatology outside of pregnancy.8-13 Furthermore, evidence of causality includes the observation that treatment of hepatitis or cancer with inflammatory cytokines leads to major depressive disorder in the majority of recipients.14-17 In addition, treatment with infliximab (an immunosuppressant) is an effective treatment for treatment-refractory depression in a subset of patients with evidence of increased inflammation.18 Pregnancy is characterized by profound alterations in the maternal immune system that facilitate trophoblastic implantation and prevent fetal rejection. Aberrations of these alterations may predispose pregnant women to the increased risk of mood disorders during and after pregnancy.1 Indeed, maternal immune hyperactivation has been associated with depressive and anxiety symptomatology.19-23 Furthermore, as these same inflammatory cytokines are associated with FGR and PTB, increases in their levels could explain the adverse pregnancy outcomes seen in association with antenatal depression.3,4,24 Finally, animal research has demonstrated that placental inflammation associated with prenatal stress can be ameliorated by treatment with anti-inflammatory agents.25