Plasma guanosine 3',5'-cyclic monophosphate and severity of peri/intraventricular haemorrhage in the preterm newborn

Abstract

A poorly controlled cerebral circulation, caused by excessive production of nitric oxide, has been suggested as predisposing to peri/intraventricular haemorrhage (PIVH) in the immature neonate. It is hypothesized that a relation exists between plasma cyclic GMP (cGMP) as an effector of endogenous vasodilatory nitric oxide production and severity of PIVH. In 83 consecutively admitted preterm neonates, nitric oxide production was assessed by measuring plasma cGMP at 0, 24, 48, 72 and 168 h of age. Simultaneously, cranial ultrasound investigations were performed and haemodynamic parameters registered. The investigations showed that 60 neonates (72%) had no PIVH; 18 neonates (22%) had mild to moderate PIVH; and 5 neonates (6%) had severe PIVH. At 48 and 72 h of age, cGMP levels of infants with severe PIVH were significantly higher than those of infants with no or only mild PIVH, whereas at 72 and at 168 h, infants with moderate PIVHs had significantly higher cyclic cGMP levels than infants without PIVH. Finally, at 168 h of age infants with mild PIVH also had higher cyclic cGMP values than those of infants without PIVH. Maximal cGMP values preceded the final extension of PIVH in moderate and severe PIVHs. Blood pressure support was necessary significantly more often in infants with moderate and severe PIVH. A logistic regression model revealed that cGMP was significantly associated with PIVH, irrespective of gestational age, mean arterial pressure or severity of infant respiratory distress syndrome.

Conclusion: Increased cGMP levels are associated with the development of PIVH. It is suggested that vasodilatory nitric oxide-induced impairment of cerebral autoregulation plays a role here.