HtrA1 secreted from fetal syncytiotrophoblasts cleaves A1AT and generates NIP–A1ATM₃₈₃S-CF in fetal blood vessels. NIP–A1ATM₃₈₃S-CF inhibits excess NET formation in neonates just after birth and ameliorates neonatal sepsis. A1AT cleaved by HtrA1 (in the middle of RCL) loses its inhibitory activity against NE. The balance of these 2 opposite mechanisms might regulate inflammation during neonatal sepsis. It is an important issue whether HtrA1 inhibits NET formation in the intervillous space through NIP–A1ATM₃₈₃S-CF and, thereby, is involved in the pathogenesis of PE and IUGR. It is possible that similar mechanisms underlie other HtrA1-related diseases, such as cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), age-related macular degeneration (AMD), osteoarthritis (OA), rheumatoid arthritis (RA), Alzheimer disease (AD), and cancer.