Risk factors for postpartum relapse in women at risk of postpartum psychosis

Several predictors for postpartum psychosis (PP)--the most severe psychiatric disorder linked to childbirth—are known. These include a history of bipolar disorder, schizoaffective disorder, and/or previous episodes of PP. While biological stress, measured through hormones like cortisol and genes related to the immune system, has been linked to the development of psychosis unrelated to childbirth, its role in the onset of PP has remained mostly unknown. This 2021 study, a part of the greater Psychiatry Research and Motherhood (PRAM) Study, investigated stress as both a predictor of PP and as an indicator of PP relapse.


The study was composed of 112 total pregnant people: 61 were healthy with no past or current psychiatric diagnoses, and 51 were at risk for PP due to a DSM-IV diagnosis of bipolar disorder, a DSM-IV diagnosis of schizoaffective disorder, or a previous PP diagnosis. It is important to note that most women at risk or with a history of PP took medication to manage PP symptoms or to prevent PP onset throughout the postpartum period. All participants were followed by researchers from their third trimester of pregnancy through 4 weeks postpartum to monitor whether they experienced a psychiatric episode in the postpartum period. Sociodemographic information, medical history, stress experiences (severe childhood maltreatment, stressful life events, and intimate partner violence), and biological measures of stress were assessed at 6 days and 8 weeks postpartum. Study participants were also assessed for current psychiatric disorders (per DSM-IV) at baseline and at eight weeks postpartum.


At four-weeks postpartum, people deemed at risk for PP who experienced an episode within the first four weeks postpartum (22) were considered “AR-unwell,” and people who were at risk for PP who did not experience a relapse within the first 4 weeks postpartum (29) were considered “AR-well.” Psychiatric relapses were recorded if participants met a DSM-IV diagnosis for psychotic, manic, hypomanic, depressive, or mixed episodes. A psychiatric relapse was also recorded if they had a combination of DSM-IV symptoms that impacted their daily functioning to a point of changing their ability to take care of their baby or themselves regardless of whether they met the DSM-IV criteria. Severe psychiatric relapses were noted if participants experienced psychotic, manic, mixed symptoms, and/or a psychiatric hospitalization up until four weeks after giving birth.


Researchers compared the baseline stress levels of participants in both subgroups of the at-risk group: those who experienced psychiatric episodes and those who remained well. Both “psychological stress,” measured by the presence of severe childhood maltreatment and stressful events in participants’ lives, and “biological stress,” measured by testing cortisol levels and inflammatory biomarkers, were accounted for in the study. Researchers also quantitatively measured traumatic life events and intimate partner violence in participants.


Out of the at-risk group who did go on to experience psychiatric symptom relapse in the postpartum period, 9 (40.9%) experienced depression or depression and anxiety, 8 (36.4%) had manic or hypomanic symptoms, 4 (18.2%) had psychotic symptoms, and 1 (4.5%) had mixed symptoms. Out of those who met the study’s definition of “relapse,” nearly 60% had symptoms that met DSM-IV criteria, and the remainder had symptoms that impacted their daily functioning but did not meet the DSM-IV criteria for a psychiatric diagnosis.


By analyzing both psychological and biological stress in the AR-well and AR-unwell groups, researchers found severe childhood maltreatment and elevated daily cortisol levels during the third trimester of pregnancy predicted psychiatric relapses in the first 4 weeks postpartum among women already at risk of PP. However, inflammatory markers in the third trimester of pregnancy and a history of stressful life events were not found to predict a psychiatric relapse in the postpartum. Additionally, researchers found that psychiatric episodes during pregnancy were associated with postpartum relapses across all groups.


This study was one of the first longitudinal studies to follow participants throughout pregnancy and up to eight weeks postpartum in order to provide a comprehensive analysis of stress as it relates to PP. Despite this strength, the study’s sample size was still relatively small and participant engagement with the study was varied. For example, some participants did not consistently attend visits or follow through with the check-ins. Additionally, because the participants deemed to be ‘at-risk’ for PP were recruited from a specialist perinatal mental health service, it is possible that the number of psychotic episodes reported in the postpartum period may not be representative of all people in this ‘at-risk’ population due to the fact that these individuals were already receiving quality mental healthcare.


The findings of this study continue to support the existing notion that certain facets of the psychosocial and biological stress systems predict postpartum relapse in women who are already at risk for PP.


Written by Hannah Dineen, Clinical Research Intern


Hazelgrove K, Biaggi A, Waites F, et al. Risk factors for postpartum relapse in women at risk of postpartum psychosis: The role of psychosocial stress and the biological stress system. Psychoneuroendocrinology. Jun 2021;128:105218. doi:10.1016/j.psyneuen.2021.105218