Our objective is to determine perinatal factors contributing to the development of pulmonary hypertension (PH) in patients with isolated giant omphaloceles (GO). All cases of omphaloceles that underwent prenatal and postnatal care at the University Hospital of Lille between 1996 and 2021 were reviewed. We included all infants with isolated GO, including at least a part of the liver, who were treated by delayed surgical closure. Prenatal and postnatal data were recorded and correlated with postnatal morbidities. We compared outcomes between a group of infants with GO who developed PH and infants with GO with no PH. We identified 120 infants with omphalocele. Fifty isolated GO cases fulfilled the inclusion criteria of our study. The incidence of PH was 30%. We highlighted a prolonged inflammatory state, defined as a CRP superior to 15 mg/L, platelets higher than 500 G/L, and white blood cells higher than 15 G/l for more than 14 days in patients who developed PH. This event occurred in 73% of patients with PH versus 21% of patients without PH (p < 0.05). Late-onset infection was not different between the two groups. We speculate that prolonged inflammatory syndrome promotes PH in infants with GO treated with delayed surgical closure.