James S. Rawlings

Estimated blood volumes in polycythemic neonates as a function of birth weight

This prospective study was designed to test the correlation of blood volume per kilogram of body weight with birthweight in polycythemic neonates. One hundred and sixty-four neonates with venous hematocrits of 65% or greater were treated with partial exchange transfusion. Follow-up venous hematocrits were obtained, and BV/kg was estimated for each infant based on the exchange volume used and the observed change in hematocrit. Birth weight ranged from 1,210 to 5,080 gm. Individual blood volume estimates ranged from 44 to 176 ml/kg, with a mean of 88.4 +/- 23.5 ml/kg. There was a highly significant negative linear correlation of BV/kg with birth weight (P less than 0.001), the regression line intersecting 100 ml/kg at 2,000 gm and 70 ml/kg at 4,500 gm. This correlation has clinical application in the management of polycythemic neonates with partial exchange transfusion. A nomogram is provided for estimating BV/kg in polycythemic neonates based on birth weight.

391 GENTAMICIN THERAPY IN PREMATURE NEONATES: DOSAGE INTERVAL (DI) BASED ON GESTATIONAL AGE (GA)

Peak gentamicin serum concentrations (GSC) of 4-12 mcg/ml and trough concentrations < 2 mcg/ml are recommended for effective therapy without toxicity. Currently recommended gentamicin dosage regimens for premature neonates within the first week of life have a significant incidence of toxic or subtherapeutic GSC. In a previous study by the authors using a standard regimen with fixed DI, an inverse linear correlation was found between peak and trough GSC and GA. A new gentamicin dosage regimen was formulated based on this correlation using a one-compartment pharmacokinetic model. This regimen consists of a 3.5 mg/kg dose given at a DI which is inversely related to GA: DI = 50.5 - 0.76 GA. This regimen is designed to yield peak and trough GSC of 8.0 mcg/ml and 1.5 mcg/ml, respectively, in premature infants, irrespective of GA. To test this new regimen, 32 premature neonates were studied within the first week of life. Mean GA was 31.4 weeks (range 25-36); mean birth weight was 1675 grams (range 570-2900). Mean peak and trough GSC (± SD) were 7.0 ± 1.17 mcg/ml and 1.1 ± 0.26 mcg/ml, respectively. All GSC were within the recommended range. This is the lowest incidence of inappropriate GSC in any series reported in the literature. Serial peak and trough GSC did not vary significantly in individual patients during the first 4 days of therapy. The previously observed correlation between GSC and GA was lost with this regimen. We conclude that relating DI to GA in this fashion is a simple and effective way of achieving optimal peak and trough GSC in premature infants of various GAs.

1494 NEONATAL POLYCYTHEMIA AND THE DURATION OF LABOR

Elevated intrauterine hydrostatic pressures occurring during labor may redistribute blood within the feto-placental unit in the direction of the fetus. The induction of fetal intravascular hypervolemia is a recognized precursor of neonatal polycythemia. Prolonged labor might thus occur more commonly in association with neonatal polycythemia. To investigate this hypothesis, data from neonatal and obstetric records relating to the births of 30 polycythemic neonates were compared to analogous data from records relating to the births of 100 randomly selected normocythemic neonates. Infants in the two groups were similar for gestational age, gender, birth weight, Apgar scores, and mode of delivery. The umbilical cord was clamped immediately after the delivery of each infant in both groups. Mothers in the two groups were similar for age, gravidity, parity, and obstetric complications. Mothers in the polycythemic group had a greater incidence of hypertension (23% vs. 11%); however, the difference was not highly significant. Mean duration of labor (±SD) in the polycythemic group was 9.0 ± 5.8 hours with a range of 1 to 26 hours. Duration of labor in the normocythemic group was 8.9 ± 6.1 hours with a range of 0 to 30 hours. There was no significant difference in the two groups in the duration of labor or in the duration of ruptured fetal membranes prior to delivery. There was no correlation of calculated neonatal blood volumes per kilogram birth weight with duration of labor in the polycythemic group. Prolonged labor is unlikely to be an important factor in the pathophyslology of neonatal polycythemia.

FAILURE OF FUROSEMIDE TO AFFECT THE CLINICAL COURSE OF TRANSIENT OF THE NEWBORN

Transient Tachypnea of the Newborn (TTN) prolongs neonatal hospitalization and occasionally results in serious complications. The most widely accepted theory of the etiology of TTN is a delay in the absorption of fetal lung fluid. Furosemide has been shown to affect fluid dynamics in the lung. We hypothesized that a pharmacologically-induced diuresis of body water may reverse the mechanism of TTN and shorten the course of the illness. We designed a controlled, prospective trial of oral furosemide in infants with TTN. 50 consecutive infants presenting with the clinical and radiographic findings of TTN were randomly assigned to two groups. Infants in the treatment group received 2 mg/kg of oral furosemide at the time of diagnosis followed by a 1 mg/kg dose 12 hours later if the tachypnea (RR> 60) persisted. Infants in the control group received an equal volume of placebo. There were no significant differences in the prenatal and perinatal courses, nor in the demographic characteristics between the two groups. Although mean weight loss at discharge was similar in the two groups, the furosemide-treated group lost significantly more weight in the first 24 hours after birth (p<0.001). Compared to infants in the control group, the furosemide-treated infants demonstrated no statistically significant difference in the duration and severity of symptoms, nor in the duration of hospitalization. We conclude that oral furosemide, at the doses used in this study, does not alter the clinical course of TTN.

PRENATAL CARE AND PREMATURITY

The value of frequent routine prenatal clinic visits in seemingly uncomplicated pregnancies has been questioned. To determine whether routine outpatient care significantly influences the incidence of premature delivery, we analyzed prenatal care compliance among low-risk patients who delivered over a one-year period. Prenatal care records of 50 patients who delivered prematurely were compared to those of 175 randomly selected patients who delivered at term. There were no demographic differences between the two groups. Rates of clinic attendance were significantly lower (p < 0.01) among patients who delivered severely premature infants (Table). Mortality among premature infants with a history of poor prenatal care was 23% in contrast to 2% among prematures with adequate prenatal care (p < 0.001). We conclude that seemingly low-risk obstetric patients who demonstrate poor early prenatal care compliance are at high risk for premature delivery and neonatal demise. Routine prenatal care may be an important factor in limiting both the incidence and degree of prematurity.

GENTAMICIN IN PREMATURE NEONATES: A DOSAGE REGIMEN BASED ON MATURITY

Gentamicin toxicity and efficacy studies have indicated desired peak and trough serum concentrations of 4-12 mcg/ml and less than 2 mcg/ml, respectively. Choosing an appropriate dose and dosage interval for premature infants is complicated by decreasing glomerular function with decreasing gestational age. We tested a regimen in which 24 infants less than 7 days of age,who were born between 26 and 36 weeks of gestation, received 2.5 mg/kg of gentamicin intravascularly every 18 hours. Trough serum gentamicin concentrations exceeded 2 mcg/ml in 33%; peak serum concentrations exceeded 12 mcg/ml in none but were less than 4 mcg/ml in 12.5%. Regression analysis of the data revealed inverse linear correlations between peak and trough serum gentamicin concentrations and gestational age (p<0.01 and p<0.05, respectively). Using these relationships a mathematical model was derived for calculating optimal gentamicin dose and dosage interval based on gestational age (G, in weeks):Initial dose (mg/kg) ė 4.2 + 0.038 GSubsequent doses (mg/kg) ė 3.4 + 0.031 GDosage interval (hours) ė 50 − 0.76 GThis regimen is designed to yield peak and trough serum concentrations of 8 mcg/ml and 1.5 mcg/ml, respectively. We conclude that the observed variations in gentamicin serum concentrations in premature neonates warrants the use of dosage regimens based on estimated gestational age. Additional clinical experience is needed to confirm the validity of these dosage recommendations.