Hypertensive Disorders of Pregnancy and Fetal Growth Restriction: Clinical Characteristics and Placental Lesions and Possible Preventive Nutritional Targets

Abstract

Background: The purpose of this study was to describe the placental lesions in pregnancies complicated by hypertensive disorders (HDP) and/or fetal growth restriction (FGR) and in uneventful control pregnancies. Methods: This is a case control study that included singleton pregnancies with HDP and normally grown fetus (HDP-AGA fetus), with HDP and FGR, early FGR, late FGR, and uneventful pregnancies. Feto-placental Doppler velocimetry and sFlt-1/PlGF ratio were performed. Placental histology was evaluated blinded according to the Amsterdam Consensus criteria. Results: Placental lesions with maternal vascular malperfusion (MVM) were significantly more frequent in HDP-FGR and early FGR (92% and 83%). MVM were significantly associated with abnormal feto-placental Doppler parameters, especially in early FGR. Delayed villous maturation (DVM) was associated with late FGR (83%). HDP-AGA fetus cases presented a heterogeneous pattern of placental lesions, including 60% of cases with MVM, but were not associated with abnormal Doppler feto-placental velocimetry. Conclusions: We found a prevalence of placental maternal vascular malperfusion in HDP-FGR and early FGR groups. These lesions were also associated with abnormal, anti-, and angiogenic markers. Conversely HDP-AGA fetus and late FGR presented more heterogeneous placental lesions not severe enough to cause feto-placental Doppler anomalies. These conditions are likely associated with different etiologies, such as maternal pre-pregnancy risk factors for metabolic syndrome. These findings suggest a possible preventive nutritional approach in addition to low-dose aspirin in pregnant women with predisposing factors for HDP-AGA fetuses and late FGR.

Maternal Hemodynamics from Preconception to Delivery: Research and Potential Diagnostic and Therapeutic Implications: Position Statement by Italian Association of Pre-Eclampsia and Italian Society of Perinatal Medicine

“…101,102 Mediterranean diet, intake of micronutrients (folic acid) and other factors (gut microbiome) 15,16,17 could prevent HPD related to metabolic syndrome. [103][104][105] As for pre-pregnancy therapy in chronic hypertensive patients, preliminary data suggest a role of Calcium Channel Blockers, ACE inhibitors, and Angiotensin Receptor Blockers as protective factors for complications in pregnancy. 4 This protective influence might be due to their action on the cardiovascular profile and cardiac structure in those patients taking these medications at least 1 year prior to pregnancy, which probably leads a more favorable cardiac geometry and cardiovascular hemodynamics right before pregnancy.…”

“…101,102 Mediterranean diet, intake of micronutrients (folic acid), and other factors (gut microbiome) [15][16][17] could prevent HDP related to metabolic syndrome. [103][104][105] As for prepregnancy therapy in chronic hypertensive patients, preliminary data suggest a role of calcium channel blockers, ACE inhibitors, and angiotensin receptor blockers as protective factors for complications in pregnancy. 4 This protective influence might be due to their action on the…”

Construction of prediction model for fetal growth restriction during first trimester in an Asian population

“…The basic clinical characteristics of pregnant women included in our model were smoking or passive smoking, gravidity and history of hypertension. These factors may impair the function of trophoblast cells to varying degrees, and affect blood vessel generation and remodeling, thereby influencing the establishment and maintenance of a stable fetal supply of nutrition and oxygen through the placenta [25][26][27] . However, clinical characteristics alone exhibited a relatively poor predictive performance for FGR.…”

Ca2+ signals in human umbilical endothelial cells derived from pregnancy with fetal growth restriction associated with hypertensive disorder

“…However, one of the most common contributing factors is placental insufficiency ( 4 ), a condition that also serves a role in the pathogenesis of hypertensive disorders of pregnancy (HDP), including preeclampsia ( 5 ). In a recent study, it was demonstrated that FGR-HDP, a condition with significant obstetric morbidity and mortality, exhibits maternal vascular malperfusion of the placental bed, abnormal feto-placental Doppler parameters and signs of oxidative stress of the syncytiotrophoblast ( 6 ). Other recent studies show that extracellular vesicles derived from placental tissue influence endothelial cell function, explaining the relationship between placental insufficiency and hypertensive disorder ( 7 , 8 ).…”