Relationship of uric acid concentrations and severe intraventricular hemorrhage/leukomalacia in the premature infant.

The purine metabolite hypoxanthine accumulates with hypoxia ischemia and with reperfusion is converted to uric acid (UA). We hypothesized that elevated UA concentration is a marker of previous hypoxia ischemia and would identify infants at greatest risk for having subsequent intraventricular hemorrhage (IVH)/periventricular leukomalacia (PVL). We determined the relationship between UA concentrations in the first postnatal day and the development of severe IVH, PVL, or both in 58 infants of birth weight 865 +/- 177 gm and gestational age 27 +/- 2 weeks. Severe IVH developed in 10 (17%) infants and PVL in 3 (5.1%) infants. UA concentrations on day 1 (obtained at 16 +/- 4 hours) were 7.9 +/- 2.8 mg/dl and increased to 9.5 +/- 2.58 mg/dl on day 2. UA concentrations on day 1 were higher in infants with severe IVH/PVL versus those in infants with neither condition: 10.2 vs 7.3 mg/dl (p = 0.005). Infants with hyperkalemia on the second postnatal day had higher UA concentrations on the first day versus infants with normal potassium levels: 11.7 +/- 2 mg/dl versus 6.8 +/- 1.8 mg/dl (p < 0.0005). Infants with severe IVH/PVL had higher potassium levels on day 2 versus infants with neither condition: 11.9 vs 6.9 mg/dl (p < 0.048). By univariate analysis UA concentrations were significantly related to gestational age (p = 0.005) and birth weight (p = 0.03). Only UA concentration (p = 0.004) and gestational age (p = 0.02) were related to IVH/PVL. By multivariate analysis UA remained significantly related to IVH/PVL even when adjusted for other clinical variables, with an odds ratio estimate of 1.63 (95% confidence interval 1.16 to 2.31). In conclusion, higher UA concentrations on the first postnatal day were associated with the subsequent development of severe IVH/PVL and with subsequent hyperkalemia. Elevated UA concentrations in the first postnatal day may help to identify a subset of premature infants at greatest risk for having subsequent hemorrhagic ischemic injury.

Apnea after immunization of preterm infants.

OBJECTIVE: To determine the frequency of adverse reactions, particularly the occurrence of apnea, among preterm infants after immunization with diphtheria and tetanus toxoids and whole cell pertussis vaccine adsorbed (DTP) and Haemophilus influenzae type b conjugate (HibC) vaccine in the neonatal intensive care unit. STUDY DESIGN: After the occurrence of apnea in two preterm infants following immunization with DTP and HibC, a prospective surveillance of 97 preterm infants younger than 37 weeks of gestation who were immunized with DTP (94 also received HibC at the same time) in the neonatal intensive care unit was performed to assess the frequency of adverse reactions and in particular, the occurrence of apnea. For each infant, data were recorded for a 3-day period before and after receipt of the immunization. RESULTS: The majority of preterm infants tolerated immunizations with DTP and HibC without ill effects. However, 12 (12%) infants experienced a recurrence of apnea, and 11 (11%) had at least a 50% increase in the number of apneic and bradycardic episodes in the 72 hours after immunization. This occurred primarily among smaller preterm infants who were immunized at a lower weight (p = 0.01), had experienced more severe apnea of prematurity (p = 0.01), and had chronic lung disease (p = 0.03). CONCLUSION: The temporal association observed between immunization of preterm infants and a transient increase or recurrence of apnea after vaccination merits further study. Cardiorespiratory monitoring of these infants after immunization may be advisable.

Renal injury in the asphyxiated newborn infant: relationship to neurologic outcome.

The relationship of renal and central nervous system injury was prospectively evaluated in 120 asphyxiated infants. Renal evaluation findings were considered abnormal if there was oliguria (urine output less than 1 ml/kg/hr), which was designated transient if present in the first 24 hours only and persistent if present for at least 36 hours, or if the urinary beta 2-microglobulin concentration from first-void urine was elevated: (1) Thirteen infants had persistent oliguria; the urinary beta 2-microglobulin level was elevated in all. The six term infants had clinical signs consistent with hypoxic-ischemic encephalopathy (HIE); all six had ultrasonographic abnormalities. The outcome was poor (i.e., death or long-term neurologic deficits) in five of six infants. The seven preterm infants with persistent oliguria had clinical evidence of HIE, and three infants had intraventricular hemorrhage; all seven infants died. (2) Fifteen infants had transient oliguria (beta 2-microglobulin level was elevated in eight infants). Two of the eight term infants had evidence for HIE; the cranial ultrasound scan was normal in all. At follow-up, seven term infants are normal and one is abnormal. Six of the seven preterm infants with transient oliguria had clinical evidence of HIE; three infants had intraventricular hemorrhage. Three infants died, and the four survivors are normal at follow-up. (3) Ninety-two infants had normal urine output. Of the 22 term infants, two developed signs of HIE, and the ultrasound scan was abnormal in three infants. Of the 70 preterm infants, eight (11%) had clinical signs consistent with HIE, the ultrasound scan was abnormal in 20 of 64 (31%) infants scanned, and 14 (20%) infants died. Most of the followed infants are normal. Thus oliguria was significantly associated with clinical signs of HIE, including seizures, death (specifically in the premature infant), and long-term neurologic deficits. These data suggest that oliguria in the perinatal period is a sensitive indicator of infants at risk for long-term neurologic deficits.

Renal failure in sick hypertensive premature infants receiving captopril therapy.

A retrospective study of nine sick premature infants with chronic lung disease who received captopril for control of systemic hypertension (systolic blood pressure (BP) greater than 113 mm Hg) was carried out to determine efficacy of therapy and associated complications. All nine infants had markedly elevated peripheral renin values, 134.3 +/- 128.1 ng/mL/hr (mean +/- SD). Five infants had abnormal renal sonographic and perfusion scans with evidence of renal artery thrombosis, parenchymal disease, or both. Captopril therapy (0.3 mg/kg) was instituted at a postnatal age of 123 +/- 108 days. After the initial dose, the systolic BP decreased significantly in all infants, the decrease ranging from 21% to 58% of the pretreatment value. Dosage was subsequently halved in all infants. Seventeen episodes of unpredictable decreases in BP more than 40% from baseline occurred during the reduced maintenance therapy. Four infants had a total of seven episodes during which the BP decreased by 57 +/- 10% from baseline; this decrease persisted for 17 +/- 6 hours and was unresponsive to volume reexpansion and inotropic therapy. All seven episodes were accompanied by oliguria (urine output less than 1 mL/kg/hr) that persisted for 18 +/- 12 hours. These episodes were accompanied by neurologic signs (subtle seizures, lethargy, and/or apnea) within 18 +/- 6 hours after the onset of oliguria. The remaining five infants had a total of 13 episodes of decreased BP of 50 +/- 8% of baseline, which were of significantly shorter duration and responded to volume reexpanders, inotropic therapy, or both and were unaccompanied by oliguria. These data suggest the need for close observation of BP in infants receiving maintenance captopril therapy.

Seizures in the preterm infant: effects on cerebral blood flow velocity, intracranial pressure, and arterial blood pressure.

The relationship of neonatal seizures to changes in the cerebral circulation was studied in 12 premature newborn infants. The objectives of the study were to determine whether important alterations in cerebral hemodynamics occur with neonatal seizures and whether such alterations relate to systemic hemodynamic events. Blood flow velocity in the anterior cerebral arteries was measured by a transcutaneous Doppler technique. A marked increase in cerebral blood flow velocity was documented with seizures in every patient. The prominent changes in the cerebral circulation occurred despite the fact that 10 of the 12 infants had only subtle seizures and all 12 were receiving mechanical ventilation at the time of the seizures. Accompanying the increase in cerebral flow velocity was a marked increase in intracranial pressure. The cerebral hemodynamic changes appeared to reflect directly changes in systemic hemodynamic events, that is, a marked increase in blood pressure at the time of seizures. The increase in cerebral blood flow velocity with seizures, an apparent adaptive physiologic response in older individuals, may be maladaptive in the newborn infant with certain vulnerable capillary beds, such as the germinal matrix in the premature infant or the margins of an infarct in the asphyxiated infant.

Cerebral blood flow velocity in relation to intraventricular hemorrhage in the premature newborn infant.

The relation of IVH to blood flow velocity in the anterior cerebral arteries has been studied in the premature newborn infant. The objectives of the study were to determine the effect of IVH on cerebral blood flow velocity, measured by a noninvasive Doppler technique, and to assess the reliability of this technique in the diagnosis of the hemorrhage. Thirty-two premature newborn infants with IVH were identified by real-time ultrasound scanning: IVH was present in the first 24 hours of life in approximately 50%, progressed postnatally in approximately 20%, and was severe in approximately 50%. Cerebral blood flow velocity, determined daily in the first five days of life, was compared to the time of occurrence of IVH and to simultaneous measurements of systemic blood pressure and blood gases. No consistent relationship between timing or severity of IVH and cerebral blood flow velocity could be discerned. We conclude that cerebral blood flow velocity in the anterior cerebral arteries is not likely to be affected by IVH and that the noninvasive Doppler technique for measurement of this velocity is not reliable for diagnosis of the lesion.

The effect of patent ductus arteriosus on flow velocity in the anterior cerebral arteries: ductal steal in the premature newborn infant.

Marked changes in blood flow velocity in the anterior cerebral arteries, measured by a Doppler technique, have been related to PDA in premature infants. Thus, 55 premature infants of birth weight less than 2,000 gm were studied. Ten developed PDA between days three and ten of life. A sharp decrease in diastolic flow velocity and an increase in pulse amplitude in the ACA was observed with the occurrence of PDA. Return of these values to normal occurred promptly following closure of the lesion. These changes in flow velocity and pulse amplitude in the ACA appear to be determined principally by changes in systemic diastolic pressure which accompany PDA. There was no consistent relationship between the changes in flow velocity and arterial PCO2 values. These data suggest that PDA may be involved in the genesis of ischemic and hemorrhagic cerebral injury in the premature newborn infant. Thus, the decrease in flow velocity appears to represent a "steal" of blood from the cerebral arteries, analogous to other documented steal phenomena observed in older patients. Major fluctuations of blood flow velocity in the ACA, with opening and closure of the PDA, and the increase in amplitude of each pulse with PDA may, in the presence of disturbed autoregulation, cause rupture of the capillaries of the germinal matrix and thus, IVH.