6-ketoprostaglandin-f1-alpha and Infant--Premature--Diseases

For an investigation of the clinical sequelae of parenteral lipid infusions during the first week of life, 42 neonates (less than 1750 gm birth weight) were randomly assigned to receive parenteral alimentation with (IL) (Vitrum) or without a parenteral lipid infusion (NL) for 5 days. Follow-up clinical status was monitored and compared, and plasma prostaglandin levels were analyzed. Chronic lung disease was increased in duration and tended to be more severe after lipid administration. The number of days of mechanical ventilation (37 +/- 35 vs 21 +/- 18) and supplemental oxygen therapy (51 +/- 39 vs 28 +/- 23) was significantly increased in the IL group. Five IL infants developed stage 3 bronchopulmonary dysplasia, in comparison with none of the NL infants. Seven IL infants were discharged on a regimen of supplemental oxygen therapy versus none of the NL infants. Thromboxane B2 levels were significantly increased in the babies receiving Vitrum. We conclude that early administration of Vitrum in the premature neonate is associated with increased respiratory difficulty in the ensuing weeks of life.

Topics: 6-Ketoprostaglandin F1 alpha; Clinical Trials as Topic; Double-Blind Method; Fat Emulsions, Intravenous; Hemodynamics; Humans; Infant, Newborn; Infant, Premature, Diseases; Oxygen; Parenteral Nutrition, Total; Prognosis; Prostaglandins; Random Allocation; Thromboxane B2

Indomethacin (0.2 mg/kg) or saline was given intravenously during the first 24 hours to 50 preterm infants in a double blind controlled trial. Eight of the control group later required treatment with indomethacin for clinical signs of left to right shunt, but only one in the treatment group (p = 0.03). Treatment with indomethacin prolonged bleeding time, raised serum creatinine concentrations, and was associated with gastrointestinal haemorrhage in seven infants. Five of these had a serum indomethacin concentration greater than 1.0 microgram/ml. There was a significant reduction of the stable metabolite of prostacyclin, 6-ketoprostaglandin F1 alpha, commencing six hours after treatment and lasting for four days. There was no significant difference in the incidence of intraventricular haemorrhage, days of treatment with oxygen or ventilation, or mortality between the two groups.

Topics: 6-Ketoprostaglandin F1 alpha; Clinical Trials as Topic; Double-Blind Method; Drug Administration Schedule; Ductus Arteriosus, Patent; Female; Humans; Indomethacin; Infant, Newborn; Infant, Premature, Diseases; Male

We admitted 48 preterm neonates (600 to 1250 gm birth weight, normal 6-hour echoencephalograms) to a randomized prospective indomethacin or placebo trial for the prevention of neonatal intraventricular hemorrhage. Beginning at 6 postnatal hours, indomethacin or placebo was administered intravenously every 12 hours for a total of five doses. Cardiac ultrasound studies to assess the status of the ductus arteriosus were performed at 6 postnatal hours and on day 5. Urinary output, serum electrolytes, and renal and clotting functions were monitored. No differences in birth weight, gestational age, Apgar scores, or ventilatory needs were noted between the two groups. Six infants given indomethacin had intraventricular hemorrhage, compared to 14 control infants (P = 0.02). The indomethacin-treated group had significant decreases in serum prostaglandin values 30 hours after the initiation of therapy. The overall incidence of patent ductus arteriosus was 82% at 6 postnatal hours; 84% of the indomethacin-treated infants experienced closure of the ductus, compared to 60% of the placebo-treated patients. Closure of the ductus was not related to incidence of intraventricular hemorrhage. We speculate that indomethacin may provide some protection against neonatal intraventricular hemorrhage by acting on the cerebral microvasculature.

Topics: 6-Ketoprostaglandin F1 alpha; Cerebral Hemorrhage; Clinical Trials as Topic; Ductus Arteriosus, Patent; Echocardiography; Humans; Indomethacin; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Prospective Studies; Random Allocation; Thromboxane B2

The cerebrospinal fluid (CSF) of 11 premature infants suffering from posthemorrhagic hydrocephalus was examined by radioimmunoassay for prostaglandin (PG) E2, PGF2 alpha, PGD2, 6-keto PGF1 alpha, thromboxane B2 (TxB2) and peptidoleukotrienes (LTC4/LTD4). The LTs were detected in the CSF of more of these patients (70%) than any of the other eicosanoids, and usually in the highest concentration. Among the 11 posthemorrhagic patients CSF eicosanoid levels were highest when determined soon after injury. Moreover, the variety of eicosanoids present, as well as concentrations, in these infants decreased with time. The types of eicosanoids most evident in the CSF of patients who required shunting were TxB2 and LTs, being present together in 5 of 6 (83%) of these infants. In contrast, 1 of 5 (20%) of the patients who did not require this neurosurgical intervention contained both TxB2 and LTs, the remaining having only one or neither eicosanoid. The highest average concentration for each eicosanoid studied was (pg/ml): PGE2, 628; PGF2 alpha, 985; PGD2, 1410; 6-keto PGF1 alpha, 544; TxB2, 486 and LTs, 1229. This study is the first to demonstrate that the CSF of preterm infants may contain a wide variety of eicosanoids and indicates that these lipids are a manifestation of neurological assault.

Topics: 6-Ketoprostaglandin F1 alpha; Cerebral Hemorrhage; Dinoprost; Dinoprostone; Eicosanoids; Humans; Hydrocephalus; Infant, Newborn; Infant, Premature, Diseases; Leukotrienes; Prostaglandin D2; Thromboxane B2

Measurement of 6-ketoprostaglandin F1-alpha by radioimmunoassay was made during the first three days of life in a group of 48 preterm neonates at risk of intraventricular haemorrhage. The babies who developed haemorrhage had significantly higher levels than those who did not, and failed to show the falling levels seen over the first three days of life in the nonhaemorrhage group. It is suggested that high levels of prostacyclin in low birthweight babies may be one factor which contributes to the alterations of cerebral blood flow and capillary bleeding time which predispose to intraventricular haemorrhage.

Topics: 6-Ketoprostaglandin F1 alpha; Cerebral Hemorrhage; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Radioimmunoassay; Risk

Prostaglandin (PG) levels and M-mode echocardiography were used to evaluate the severity of patent ductus arteriosus (PDA) in 19 premature infants. Mean 6-keto-PGF1 alpha levels in infants with more severe left-to-right shunting were significantly higher than those in infants with a moderate level of shunting (1335 +/- 763 vs. 504 +/- 348 pg/ml, respectively). Furthermore, there was a significant correlation between this elevation and a decrease in the left ventricular systolic time interval, suggesting that both reflect the severity of ductal shunting. Although other echocardiographic measurements of cardiovascular function generally showed some tendency to vary with 6-keto-PGF1 alpha levels, none was as closely correlated with the extent of PG elevation. Levels of PGE2 also seemed to vary with PDA severity; however, this correlation was not as significant.

Topics: 6-Ketoprostaglandin F1 alpha; Dinoprostone; Ductus Arteriosus, Patent; Echocardiography; Electrocardiography; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Prostaglandins E; Respiratory Distress Syndrome, Newborn; Stroke Volume; Time Factors

Urinary excretion of prostacyclin and thromboxane metabolites (2,3-dinor-6-ketoprostaglandin F1 alpha, thromboxane B2, and 2,3-dinor-thromboxane B2) as indices of systemic biosynthesis was prospectively determined in nine premature infants during the first 10 days of life, by gas chromatography-mass spectrometry. The patients ranged in gestational age from 27 to 29 weeks and in birth weight from 720 to 980 gm. Four infants developed symptomatic patent ductus arteriosus (PDA). Excretion of all metabolites exceeded adult values on the basis of body surface area at birth, reached a maximum on the fourth day of life, was related to urine output, and did not distinguish patients with and without symptomatic PDA. We conclude that neither circulating prostacyclin nor thromboxane A2 contribute significantly to the pathophysiology of symptomatic PDA in very low birth weight infants.

Topics: 6-Ketoprostaglandin F1 alpha; Ductus Arteriosus, Patent; Epoprostenol; Gas Chromatography-Mass Spectrometry; Gestational Age; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature, Diseases; Prospective Studies; Thromboxane B2

To determine if vascular abnormalities in preterm neonates might be related to vasoactive prostaglandins, stable prostacyclin (6-KPGF1 alpha) and thromboxane A2 (T X B2) metabolites in arterial blood were measured at less than or equal to 6 hours after birth and at 24, 48, and 72 hours using a radioimmunoassay. Neonates of less than 32 weeks gestation (N = 26) were diagnosed as having either the idiopathic respiratory distress syndrome (IRDS, N = 15) or pulmonary edema (PE, N = 11), and were also grouped according to the presence or absence of intracranial hemorrhage (ICH, N = 11) or patent ductus arteriosus (PDA, N = 10). Initial plasma 6-KPGF1 alpha was greater in neonates with ICH (0.23 +/- 0.04 ng/ml, mean +/- SE) than without ICH (0.11 +/- 0.04, p less than 0.05). Neonates with both ICH and IRDS (N = 8) had significantly elevated T X B2 at all sampling times compared to neonates with IRDS and no ICH (N = 7). Both T X B2 and 6-KPGF1 alpha increased with time in those with major ICH. Among neonates without ICH, 7 with IRDS had higher initial 6-KPGF1 alpha (0.19 +/- 0.07 ng/ml) and lower T X B2 (0.15 +/- 0.04 ng/ml) than 8 with PE (0.04 +/- 0.01 and 0.37 +/- 0.09 ng/ml, respectively). The initial 6-KPGF1 alpha (0.024 + 0.003 ng/ml), measured in neonates with PE and without PDA or ICH (N = 6), was significantly less than the corresponding value in the other neonates (0.201 +/- 0.036 ng/ml) (N = 20).

Topics: 6-Ketoprostaglandin F1 alpha; Cerebral Hemorrhage; Ductus Arteriosus, Patent; Humans; Infant, Newborn; Infant, Premature, Diseases; Pulmonary Edema; Respiratory Distress Syndrome, Newborn; Thromboxane B2; Thromboxanes

Previous studies have suggested that spontaneous diuresis may be important to the recovery from respiratory distress syndrome in preterm infants. Daily quantification of fluid intake (1) and urine output (O) were recorded, and O/I and alveolar-arterial oxygen gradients (AaDO2) were determined for sequential eight-hour periods in 10 inborn premature infants with RDS. Sequential timed-urine-plasma collections were obtained during the first four days of life to evaluate the role of hormonal and vasoactive factors in the acute phase of RDS. Diuresis (O/I greater than 0.80) occurred at 25 to 32 hours, preceded any significant improvement in AaDO2 (which occurred at 57 to 64 hours), and was associated with a 6.2 +/- 1.4% decrease in body weight. Although there was no significant change in glomerular filtration rate, plasma AVP concentrations, or urinary excretion of AVP in the infants, there were significant decreases in both plasma concentrations and urinary excretion of 6-keto-PGF1 alpha (stable metabolite of prostacyclin) in sequential studies. These results suggest that changes in renal function or AVP may not be of primary importance in the diuresis associated with RDS, and that decreasing levels of prostacyclin, a prostaglandin that increases vascular permeability and lowers blood pressure, may have an important physiologic role.

Topics: 6-Ketoprostaglandin F1 alpha; Arginine Vasopressin; Diuresis; Humans; Infant, Newborn; Infant, Premature, Diseases; Kidney; Prostaglandins E; Respiratory Distress Syndrome, Newborn