Evaluation of the Fetal Fornix and Hippocampus in Pregnant Women With Early-Onset Preeclampsia

Hypertensive disorders complicate approximately 5-10% of all pregnancies and account for nearly 16% of maternal mortality. Preeclampsia (PE) occurs in 4-5% of pregnancies, and in the United States, preeclampsia or eclampsia contributed to 7.4% of the 2,009 pregnancy-related maternal deaths reported between 2011 and 2013. Preeclampsia is defined by new-onset hypertension and proteinuria, or new-onset hypertension with or without proteinuria, accompanied by evidence of significant end-organ dysfunction. It is a progressive, multisystem disorder that generally develops after 20 weeks of gestation or during the postpartum period.

Preeclampsia is also considered a pregnancy-specific syndrome capable of affecting every organ system. Because of its significant maternal and perinatal morbidity and mortality, PE represents a major public health concern. The condition is commonly described as a two-stage disease. Stage 1 (placental syndrome) is characterized by early placental ischemia/reperfusion, oxidative stress, and the release of toxic factors, primarily due to abnormal endovascular trophoblastic remodeling, primigravidity, trophoblast load, genetic predisposition, and maternal immunologic maladaptation. Stage 2 (maternal syndrome) represents the clinical phase, driven by an exaggerated maternal systemic inflammatory response and endothelial dysfunction. Maternal genetic susceptibility and underlying vascular disease may further contribute.

Overall, the etiopathogenesis of PE involves abnormal trophoblastic invasion, maternal-fetal immunologic incompatibility, maladaptation to normal cardiovascular and inflammatory changes of pregnancy, systemic vascular dysfunction, genetic influences, and epigenetic mechanisms. Approximately 90% of preeclampsia cases occur in the late-preterm (34-37 weeks), term, or postpartum period and generally have more favorable outcomes. However, severe morbidity and mortality may still occur. The remaining 10% of cases present as early-onset preeclampsia (EOPE, <34 weeks), in which abnormal placentation and defective trophoblastic invasion are more pronounced and closely correlate with disease severity. EOPE carries a markedly higher risk of serious perinatal complications, largely due to its strong association with preterm delivery. Consequently, the study of EOPE remains clinically important.

The hippocampus is a seahorse-shaped structure located within the medial temporal lobe, protruding laterally toward the temporal horn of the lateral ventricle. It plays essential roles in memory processing (dorsal hippocampus) and regulation of stress responses (ventral hippocampus). Fetal hippocampal development involves progressive inward folding of the dentate gyrus, cornu ammonis, subiculum, and parahippocampal gyrus around the shrinking hippocampal sulcus.

Experimental studies have demonstrated that adverse maternal conditions may affect hippocampal development. In rodent models, uncontrolled maternal diabetes reduces hippocampal volume and neuronal density during early postnatal life, leading to delayed development and motor, behavioral, and cognitive deficits in offspring. In an experimental preeclampsia model induced with a cholesterol-based diet, hippocampal arteriolar vasoreactivity to neurovascular coupling mediators was impaired, resulting in deficits in long-term-but not spatial-memory. These findings may parallel long-term cardiovascular and neurocognitive outcomes observed in women with a history of preeclampsia and eclampsia. Persistent endothelial and vascular smooth muscle dysfunction in hippocampal vessels may contribute to disrupted hippocampal networks and early cognitive impairment.