Medical conditions with a postpartum flare pattern – including postpartum thyroiditis, multiple sclerosis and rheumatoid arthritis – have an etiology related to immune system dysregulation. Some have also speculated that some cases of postpartum psychosis may be immune-mediated.
It turns out that preeclampsia is also immune-mediated and, like postpartum psychosis, is strongly linked to first pregnancies. This overlap between the two has led some to wonder if preeclampsia may be associated with a higher risk of severe postpartum psychiatric illness.
Using data from the Danish population registry, Bergink and colleagues explored whether preeclampsia is a risk factor for first-onset postpartum psychiatric illness. A total of 400,717 primiparous women with a singleton delivery between 1995 and 2011 were assessed. Primiparous women were at particularly high risk of first-onset psychiatric illness during the first month postpartum, with an incidence rate ratio or IRR of 2.93 (95% CI 2.53-3.40). In first-time mothers with preeclampsia, the risk was even higher (IRR 4.21, 95% CI 2.89-6.13). Having both preeclampsia and a medical comorbidity resulted in the highest risk of psychiatric episodes during the 3-month period after childbirth (IRR 4.81, 95% CI 2.72-8.50).
There are several possible ways to understand these findings. One explanation for this finding is that both postpartum psychiatric illness and pre-eclampsia are immune-mediated events and may occur together when there is dysregulation of the immune system. In addition, the authors hypothesize that the vascular inflammation observed in preeclampsia could modulate neurobiological vulnerability to psychiatric illness.
Another possible explanation is that the psychological impact of a serious medical condition may increase a woman’s vulnerability to postpartum psychiatric illness. Preeclampsia is associated with significant perinatal complications, including preterm delivery and poor neonatal outcome. It is plausible that these adverse events trigger stress and grief, making women more vulnerable to psychiatric episodes after delivery.
A systematic review and meta-analysis from Caropreso and colleagues looked at the association between preeclampsia and perinatal psychiatric illness. They analyzed data from a total of 13 studies. Eight of the 13 studies demonstrated an association between preeclampsia and depression. Most of these studies were smaller than the Bergink study and, while they demonstrated an association between preeclampsia and postpartum psychiatric illness, the magnitude of the association tended to be smaller than that observed in the Bergink study.
Only two of the studies examined the association between preeclampsia and postpartum psychosis. In a cross-sectional study of 130 women with preeclampsia, Cetin and colleagues (2017) observed that severe preeclampsia was associated with psychotic features. In contrast, Meltzer-Brody and colleagues (2017) found no association between preeclampsia and postpartum psychosis in a population-based cohort study which included 1155 women. However, the number of women with preeclampsia and psychosis in this study was very small (n = 8).
Most, but not all, studies show an association between preeclampsia and increased risk for postpartum psychiatric illness. Given the rarity of postpartum psychosis, we are not able to determine if preeclampsia increases risk for postpartum psychosis. Further research will help us to better understand the link between preeclampsia and postpartum psychiatric illness. In the meantime, we should be aware that women who have experienced preeclampsia, especially women with associated medical illness, carry a significantly increased risk of postpartum psychiatric illness and may benefit from closer monitoring after delivery.
Ruta Nonacs, MD PhD
Bergink V, Laursen TM, Johannsen BM, Kushner SA, Meltzer-Brody S, Munk-Olsen T. Pre-eclampsia and first-onset postpartum psychiatric episodes: a Danish population-based cohort study. Psychol Med. 2015 Dec;45(16):3481-9.
Caropreso L, de Azevedo Cardoso T, Eltayeb Ani M, Frey BN. Preeclampsia as a risk factor for postpartum depression and psychosis: a systematic review and meta-analysis. Arch Womens Ment Health. 2020 Aug; 23(4):493-505