Ischemic placental disease and hospitalization for neurological and psychiatric disorders

Ischemic placental disease, a syndrome that comprises preeclampsia, placental abruption, and fetal growth restriction, is characterized by ischemic, endothelial, and microvascular dysfunction. These processes, in turn, may serve as sentinel markers of maternal brain vulnerability, resulting in structural abnormalities, altered neuronal connectivity, and impaired neurogenesis.

To estimate the burden of postpartum readmissions for neurological and psychiatric disorders (hereafter referred to as brain disorders) in women associated with ischemic placental disease in the same calendar year as the delivery hospitalization.

We designed a population-based retrospective cohort study using the Healthcare Cost and Utilization Project's Nationwide Readmissions Database. The cohort included patients aged 15 to 54 who delivered in a hospital in the United States (2010-2020). Using adjusted Cox proportional hazard models, we examined hospitalizations for neurological disorders (including epilepsy, migraine, stroke, and transient ischemic attack) and psychiatric conditions (including major depression, postpartum depression, anxiety disorder, post-traumatic stress disorder, psychosis/schizophrenia, bipolar disorder, and a suicide attempt) at delivery or in the calendar year of delivery associated with ischemic placental disease. Using quantitative bias analysis, the associations were corrected for outcome misclassification and unmeasured confounding.

Of 17,368,071 hospital deliveries, 10.7% (n=1,856,739) had a recorded diagnosis of ischemic placental disease. The incidence rates of brain disorder hospitalization with and without ischemic placental diseases were 1219 (n=226,768) and 730 (n=1,132,878) per 10,000 hospitalizations, respectively (incidence proportion difference 489, 95% confidence interval [CI] 479 to 499; adjusted hazard ratio [HR] 1.50, 95% CI 1.48-1.51). Compared with those without ischemic placental disease, the HRs of brain disorder hospitalization among those with 1, 2, and all 3 ischemic placental disease conditions were 1.47 (95% CI 1.46-1.49), 1.66 (95% CI 1.63-1.70), and 1.85 (95% CI 1.70-2.01), respectively. Corrections for biases slightly attenuated these effect estimates.

Ischemic placental disease is associated with maternal hospitalizations for brain disorders in this younger reproductive age cohort, within the year following delivery. These findings suggest that the microvascular dysfunction and uteroplacental ischemia characteristic of ischemic placental disease may have consequential implications for maternal brain health at delivery and in the postpartum period, with potentially substantial long-term consequences across the life course. If ischemic placental disease unmasks these risks in the immediate postpartum period, their implications across the life course are likely to remain substantial.