Nestor B. Ilagan

Antenatal phenobarbital for the prevention of neonatal intracerebral hemorrhage

Forty-six pregnant women less than 35 weeks of gestation were enrolled in a prospective randomized controlled study evaluating the effects of antenatal phenobarbital on neonatal intracerebral hemorrhage. The women were randomly assigned to control (n = 22) or treatment (n = 24) groups; the treatment group received 500 mg of phenobarbital intravenously. The time interval between the dose of phenobarbital and delivery was 5.5 +/- 4.8 hours (mean +/- SD). The infants in the control group (n = 23) and those in the phenobarbital-treated group (n = 25) were comparable regarding birth weight, gestational age, and other obstetric and neonatal risk factors associated with intracerebral hemorrhage. The incidence of intracerebral hemorrhage was 56.5% (13 of 23 infants) in the control group and 32% (eight of 25 infants) in the phenobarbital-treated group (p = 0.08). Moderate or severe hemorrhage was diagnosed in six of 13 control infants and in none of the phenobarbital-treated infants (p less than 0.01). The mortality rate was significantly lower in the phenobarbital-treated group (two of 25 infants) than in the control group (eight of 23 infants; p less than 0.05). Our study suggests that antenatal phenobarbital administration results in a decrease in mortality and in the severity of intracerebral hemorrhage in the preterm neonate.

Mineral excretion following furosemide compared with bumetanide therapy in premature infants.

Mineral excretion following single doses of furosemide were compared with bumetanide in a random cross-over trial in 17 premature infants. The mean birth-weight and gestational age were 889±85 g and 27±2 weeks. Following furosemide therapy, significantly higher chloride losses and urine volumes were noted in the first 8-h period compared with the second or third 8-h periods. Following bumetanide therapy, sodium, calcium, and chloride losses and urine volumes were significantly higher in the first 8 h compared with the second or third 8-h periods. Hourly sodium and chloride losses were significantly lower following bumetanide than furosemide during the first two 8-h periods. During the final 8-h period sodium, potassium, chloride, and calcium losses were significantly lower following bumetanide than following furosemide. Sodium loss per urine volume was lower with bumetanide than furosemide but calcium loss tended to be higher. Hence, bumetanide does not appear to be a calciumsparing diuretic following single-dose therapy.

Subcapsular Hemorrhage of the Liver in the Very Low Birthweight Neonate

ABSTRACT. Between 1974 and 1989, 15 neonates were found, at autopsy, to have subcapsular hematoma of the liver in a retrospective clinicopathologic study of 644 neonates. The majority (75 %) of the neonates were < 28 weeks gestation, male gender, and were delivered by the vaginal route following a complicated pregnancy and labor including malpresentation. The clinical course included resuscitation at birth, ventilatory support and hypovolemic shock with death occurring within 24 hours in 11 neonates. Other clinical events included air leak (n=4 infants) and infection (n=4). Intracranial hemorrhage was suspected in all but was found at autopsy in 8 neonates. The subcapsular hematoma was intact in 7 and ruptured in 8 neonates. Hence, subcapsular hemorrhage of the liver should be considered in the differential diagnosis of hypovolemic shock in very low birthweight infants.

Perinatal and Neonatal Significance of Bacteria‐Related Placental Villous Edema

In a study of 82 cases of clinical chorioamnionitis in which no antibiotics were administered antenatally, significant villous edema was observed in 51 placentas (62%). Polymorphonuclear leukocyte invasion of the placental plate was found in 53 placentas (65%). the presence of SVE was significantly associated with placental bacterial recovery, occurrence of prolonged rupture of membranes, lower one minute Apgar score, the need for resuscitation and significant neonatal respiratory problems. Findings suggest that bacteria‐related placental villous edema can lead to significant perinatal and neonatal morbidities.

Congenital Syphilitic Skeletal Manifestations in a Premature Infant Revisited

Increasing rates of congenital syphilis have been reported in recent years despite the availability of adequate therapy. In our perinatal-neonatal center, approximately 1.5 % of newborns have reactive serologic tests for syphilis.1 Untreated or partly treated maternal syphilis can adversely affect neonatal outcome since the treponeme can cross the placenta at any time during pregnancy. 2 As a result of hematogenous placental transmission, neonatal manifestations are usually systemic and similar to the secondary stage of syphilis, and include hepatosplenomegaly, jaundice, neuro-syphilis, and skeletal changes. A case of early congenital syphilis in an extremely premature infant with primary skeletal involvement is presented.

1519 ANTENATAL PHENOBARBITAL FOR PREVENTION OF NEONATAL IANTRAVENTRICULAR HEMORRHAGE

A prospective randomized controlled study was performed evaluating the effects of antenatal phenobarbital (PB) on neonatal intraventricular hemorrhage (IVH). Forty-six pregnant women in labor <35 wks gestation were assigned to control (n=22) or treatment groups (n=24); the treatment group received 500 mg PB by slow intravenous infusion prior to delivery. Echoencephalograms were performed on all infants. The time between dose of PB and delivery was 5.6 ± 4.6 hrs (all values mean ± SD). Maternal PB levels at delivery were 8.72 ± 2.01 μg/mL and cord serum PB levels were 8.85 ± 1.57 μg/mL. The infants in the control group and those in the PB treated group did not differ regarding delivery route, presentation, Apgar scores, ventilatory support, episodes of acidosis, hypoxemia, hypercarbia, hypotension and fluid therapy in the first 3 days. The results indicate a significant decrease in mortality and occurrence of moderate and severe IVH in the PB treated group as compared to the control group.

ANTENATAL PHENOBARBITAL FOR PREVENTION OF NEONATAL INTRAVENTRICULAR HEMORRHAGE: PRELIMINARY OBSERVATIONS

Eighteen mothers in premature labor <35 week gestation were enrolled in a study to evaluate the effect of antenatal phenobarbital(PB) in preventing neonatal intraventricular hemorrhage.Mothers were randomly assigned to treatment or control groups; the treatment group received 500 mg PB administered intravenously.Maternal and cord blood PB levels were measured at delivery. Echoencephalograms were performed on days 3 and 14 and hemorrhage graded as mild, moderate and severe.Nine mothers(including one multiple pregnancy) received antenatal PB. Mean time between administration of PB and delivery was 2.9±2.7 hours. Maternal PB levels at delivery were 9.2±2.3 μg/ml. Cord blood PB levels were 9.8±2.1 μg/ml. The PB and control groups were comparable regarding maternal age,duration of rupture of membranes, route of delivery, presentation, birth weight,gestational age,Apgar scores and incidence of pneumothoraces, hypotension,acidosis, hypoxemia,hypercarbia or amount of fluid intake or bicarbonate therapy during the first 3 days. Seven of 10 infants in the PB group had no hemorrhage while 1 had a mild and 2 had severe hemorrhages. Five of 9 infants in the control group had no hemorrhage while 2 had moderate and 2 had severe hemorrhages. When comparing mild or no hemorrhage vs moderate and severe hemorrhage in the 2 groups no significant difference has been found thus far (p = .21).

VANCOMYCIN PHARMACOKINETICS IN LOW BIRTH WEIGHT PRETERM NEONATES ON THERAPEUTIC DOSES OF THEOPHYLLINE. 430

We performed Vancomycin pharmacokinetic studies on low birth weight preterm infants receiving therapeutic doses of Theophylline for apnea of prematurity. Four of the five neonates were female and all were free of hepatic or renal impairments. The neonates had a mean gestational age of 24.7 ± 1.1 weeks, mean weight of 1.1 ± 0.3 kilograms, mean Theophylline level of 6.6 ± 0.9 mg/L and a mean chronologic age of 62.2 ± 26.1 days. The use of Vancomycin was indicated for suspected sepsis.

414 PHARMACOKINETIC BASIS FOR ANTENATAL DOSING OF PHENOBARBITAL FOR THE PREVENTION OF NEONATAL INTRACERE BRRL HEMORRHAGE

Transplacental and elimination pharmacokinetics of phenobarbital (PB) were analyzed in pregnant women and their neonates with the aim of determining the dose to be administered to pregnant women to achieve levels in the neonate for prevention of neonatal intracerebral hemorrhage (ICH). A single PB dose of 500 mg was selected to achieve a serum concentration of 10 μg/mL in the women according to the equation: dose (mg/Kg) = serum cone (μg/ mL) x Vd (L/Kg); assuming average weight to be 50 Kg and Vd =1.0 L/Kg. Twenty-five women in premature labor <35 wks gestation received 500 mg PB administered intravenously over 30 min. Average weight of the women was 69.1 ± 13.5 Kg (all values mean ± SD); the actual mean dose of PB therefore was 7.5 ± 1.4 mg/Kg. The mean time from PB administration to delivery was 5.6 ± 4.6 hrs (range 16 min. to 17 hrs). The maternal serum PB level at delivery was 8.8 ± 1.2 ug/mL and the cord serum level was 9.0 ± 1.8 μg/mL. There was no correlation between the time from PB administration to delivery and the cord:maternal serum concentration ratio. This indicated transplacental equilibration within 16 min. of maternal dosing. Mean apparent th of PB estimated in 11 infants was 175.5 ± 45.6 hrs; this is comparable with th in neonates receiving PB postnatally. Based on this study, we recommend a 10 mg/Kg dose of PB for the pregnant woman to achieve a level of 10 pg/ml. This level has been found to be protective against ICH (Shankaran et al, Ann Neurol Abstr #14, 1984).