Demographic and intrapartum characteristics of term pregnancies with early-onset neonatal seizures.

OBJECTIVE: To compare the demographic and intrapartum factors of term pregnancies in which early-onset neonatal seizures developed with the characteristics of a large, unselected control population. STUDY DESIGN: Pregnancies delivered at term (gestational age > or = 37 weeks) in one birthing unit between 1984 and 1995 with a discharge diagnosis of neonatal seizures were identified. Maternal and neonatal charts of these patients were reviewed to confirm the diagnosis of early-onset seizure (EOS) which was defined as a clinical or EEG-diagnosed seizure within 72 hours of life. Demographic and intrapartum factors were compared between these EOS cases and all singleton term pregnancies delivered over the same time period in which there was no EOS. A regression model was then developed to determine factors predictive of EOS. RESULTS: Of 80,561 total deliveries during the 11-year study period, there were 64,340 control and 62 EOS (0.1%) deliveries. Regression modeling identified NICU admission, depressed 1- and 5-minute Apgar scores, and neonatal intubation as predictors of EOS, but not operative vaginal, vaginal breech, or cesarean delivery. CONCLUSION: Depressed condition at birth and/or the requirement for NICU care was the most important risk associated with early seizures in term infants.

Plasma immunoreactive endothelin-1 concentrations in infants with persistent pulmonary hypertension of the newborn.

Plasma concentrations of endothelin-1 (ET-1) have been reported to be elevated in children and adults with pulmonary hypertension. We hypothesized that infants with persistent pulmonary hypertension of the newborn (PPHN) have elevated plasma concentrations of ET-1. Plasma concentrations of immunoreactive-endothelin-1 (ir-ET-1) were measured using a radioimmunoassay in 20 infants with PPHN and 20 normal term infants. Mean birthweight and gestational age of the infants were comparable in the two groups. The mean plasma ir-ET-1 concentrations were significantly elevated in neonates with PPHN compared to those of normal term infants (2.04 +/- 0.30 versus 1.04 +/- 0.29 pg/mL, p = 0.02). A linear regression analysis demonstrated a significant relationship between ir-ET-1 concentrations and alveolar-arterial oxygen gradient (r = 0.49, p = 0.02) and mean airway pressure (r = 0.49, p = 0.02). There was also a significant correlation between ir-ET-1 concentrations and duration of extracorporeal membrane oxygenation among infants with PPHN (r = 0.44, p = 0.05). We conclude that plasma ir-ET-1 concentrations are elevated in infants with PPHN. The presence of elevated ir-ET-1 concentrations and their positive correlation with disease severity suggests that ET-1 may serve as a marker of the disease severity in these infants. However, further studies are needed to elucidate the role of ET-1 in the pathophysiology of PPHN.

Adenosine infusion improves oxygenation in term infants with respiratory failure.

OBJECTIVES: Adenosine infusion causes selective pulmonary vasodilation in fetal and neonatal lambs with pulmonary hypertension. We investigated the effects of a continuous infusion of adenosine on oxygenation in term infants with persistent pulmonary hypertension of newborn (PPHN). DESIGN: A randomized, placebo-controlled, masked trial comparing the efficacy of intravenous infusion of adenosine to normal saline infusion over a 24-hour period. SETTING: Inborn and outborn level III neonatal intensive care units at a university medical center. PARTICIPANTS: Eighteen term infants with PPHN and arterial postductal PO2 of 60 to 100 Torr on inspired O2 concentration of 100% and optimal hyperventilation (PaCO2 <30 Torr) were enrolled into the study. Study infants were randomly assigned to receive a placebo infusion of normal saline, or adenosine infusion in doses of 25 to 50 microg/kg/min over a 24-hour period. PARTICIPANTS: Eighteen term infants with PPHN and arterial postductal PO2 of 60 to 100 Torr on inspired O2 concentration of 100% and optimal hyperventilation (PaCO2 <30 Torr) were enrolled into the study. Study infants were randomly assigned to receive a placebo infusion of normal saline, or adenosine infusion in doses of 25 to 50 microg/kg/min over a 24-hour period. RESULTS: Nine infants each received adenosine or placebo. The two groups did not differ in birth weight, gestational age, or blood gases and ventilaator requirements at the time of entry into the study. Four of nine infants in the adenosine group and none of the placebo group had a significant improvement in oxygenation, defined as an increase in postductal PaO2 of > or =20 Torr from preinfusion baseline. The mean PaO2 in the adenosine group increased from 69 +/- 19 at baseline to 94 +/- 15 during 50 microg/kg/min infusion rate of adenossine and did not change significantly in the placebo group. Arterial blood pressure and heart rate did not change during the study in either group. The need for extracorporeal membrane oxygenation, incidence of bronchopulmonary dysplasia, and mortality were not different in the two groups. CONCLUSION: Data from this pilot study indicate that adenosine infusion at a dose of 50 microg/kg/min improves PaO2 in infants with PPHN without causing hypotension or tachycardia. Larger trials are needed to determine its effects on mortality and/or need for extracorporeal membrane oxygenation in infants with PPHN.

Plasma immunoreactive endothelin-1 concentration in cord blood of normal term neonates.

Plasma immunoreactive endothelin-1 (ir-ET-1) concentrations in cord blood of 20 term infants were measured by radioimmunoassay. The mean (+/- SEM) ir-ET-1 concentration was 1.04 +/- 0.29 pg/mL. There was no relationship between ir-ET-1 concentrations and race, sex, mode of delivery, and prenatal characteristics, such as cocaine exposure. The current methodologies were reviewed in an effort to explain the differences in ET-1 concentrations reported in various studies.

Prenatal diagnosis of congenital diaphragmatic hernia not amenable to prenatal or neonatal repair: Brachmann-de Lange syndrome.

Brachmann-de Lange syndrome (BDLS) is a variable multiple congenital anomaly syndrome that occasionally includes congenital diaphragmatic hernia (CDH). CDH per se is commonly diagnosed antenatally and has been corrected with increasing success in utero and by neonatal repair with extracorporeal membrane oxygenation (ECMO). In utero repair requires normal karyotype as well as the absence of other lethal anomalies. Postnatal repair in combination with ECMO has resulted in improved neonatal outcome and has been recommended in all cases not having in utero repair. We describe a fetus diagnosed with a diaphragmatic hernia at 18 weeks of gestation in a woman whose only other pregnancy has been a 16 week abortus diagnosed with Fryns syndrome (FS). FS is a lethal, variable congenital anomaly syndrome that includes CDH, which is thought to contribute to the lethality of the syndrome. In utero repair was considered, but rejected because of the position of the liver and suspected FS. The patient elected to carry the pregnancy to term. Postnatal repair with ECMO was considered; however, the infant died at several hours of age because of severe pulmonary hypoplasia, being considered ineligible for ECMO. The diagnosis of BDLS was made at autopsy and suggests that the first case may, in fact, have been BDLS. In spite of recent success in the repair of CDH both in et ex utero, CDH in association with BDLS is likely lethal, and women with fetuses diagnosed antenatally with CDH and BDLS should be counseled as such.

Effects of thiazide diuretics on the lipid profile of infants with bronchopulmonary dysplasia.

Hyperlipidemia has been reported in some infants with bronchopulmonary dysplasia (BPD) who received thiazides for extended periods. In this prospective, controlled trial, we studied 17 infants with BPD who received diuretic therapy and 26 control infants who did not receive diuretics. Plasma triglycerides, total cholesterol and high-density lipoprotein (HDL) cholesterol were measured enzymatically prior to onset of diuretic therapy in the study group of infants and on the day of recruitment into the study in control infants, and every 2 weeks thereafter. Plasma low-density lipoprotein cholesterol concentrations were calculated. At the end of 4 weeks, plasma lipid concentrations were comparable in both groups of infants except for significantly higher plasma HDL cholesterol concentrations observed in infants who received chlorothiazide (39 +/- 15 vs. 30 +/- 6 mg/dl, p less than 0.05). Short-term administration of chlorothiazide to infants with BPD is not associated with clinically significant changes in plasma lipid concentrations.

Dexamethasone effects on the hospital course of infants with bronchopulmonary dysplasia who are dependent on artificial ventilation.

A randomized double-blind placebo-controlled trial was conducted to evaluate the effects of enterally administered dexamethasone on the hospital course of infants with bronchopulmonary dysplasia. A total of 23 infants with a birth weight less than 1500 g who were dependent on artificial ventilation 3 to 4 weeks of age received dexamethasone (n = 12) or saline placebo (n = 11). Dexamethasone (0.5 mg/kg per day) was given in tapering doses for 7 days followed by hydrocortisone (8 mg/kg per day) which was progressively reduced for a total of 17 days of therapy. Infants who received dexamethasone required less oxygen on days 8 and 17 (P less than .05) and were more likely to extubate 8 days after therapy than infants in the control group (respectively 8/12 vs 3/11 infants, P less than .05; P = .12 after Yates correction). The use of dexamethasone significantly shortened median duration of mechanical ventilation (4 vs 22 days, P less than .05) but had no effect on length of oxygen therapy, hospitalization, home oxygen therapy, occurrence and severity of retinopathy of prematurity, rate of growth, and mortality. No significant complications resulted from dexamethasone therapy. Measurements of plasma dexamethasone levels confirmed the absorption of drug from the gastrointestinal tract (23.7 ng/mL in dexamethasone vs 4.6 ng/mL in the control group, P less than .05). Dexamethasone administration resulted in short-term improvements in pulmonary function but did not ameliorate the hospital course of infants with bronchopulmonary dysplasia.

Effect of extracorporeal membrane oxygenation on body water content and distribution in lambs.

Water content of the various body compartments were estimated immediately after beginning extracorporeal membrane oxygenation (ECMO), and daily thereafter for 3 days, in seven healthy 2-month-old lambs. Total body water, extracellular water, and plasma volume were estimated simultaneously by 18O, bromide, and T-1824 dilution, respectively. Volumes of intracellular water, interstitial water, blood, and red cells were calculated from the experimental estimates. No statistically significant changes occurred in the water content of the various body compartments in relation to duration of ECMO. The data suggest that water retention, clinically noted in human neonates treated with ECMO for persistent pulmonary hypertension, may be related to the primary disease process and/or its medical management, rather than to ECMO.

Placental transfer of vitamin K1 in preterm pregnancy.

Seventy-eight women at earlier than 35 weeks' gestation with premature rupture of membranes and/or preterm labor were randomly assigned to receive either 10 mg vitamin K1 intramuscularly (IM) or no treatment. If delivery did not occur within 4 days, the dose of vitamin K1 was repeated. Women whose pregnancies continued beyond 8 days received 20 mg of vitamin K1 orally every day until the end of the 34th week or until delivery, whichever occurred earlier. The median maternal plasma vitamin K1 level was significantly higher in treated than in untreated subjects (11.592 versus 0.102 ng/mL; P less than .001). The median cord plasma levels were 0.024 ng/mL in the treated group and 0.010 ng/mL in the controls, a significant difference (P = .046). Median plasma vitamin K1 levels were comparable in mothers receiving the drug by the IM route only and by both the IM and oral routes (10.533 versus 11.928 ng/mL; P = .460). The infants of the latter group, however, had significantly higher median cord plasma levels (0.42 versus 0.017 ng/mL; P less than .001). There was no correlation between cord plasma vitamin K1 levels and gestational age or duration of maternal supplementation with vitamin K1. We conclude that, in preterm pregnancies, vitamin K1 crosses the placenta slowly and to a limited degree.

Simultaneous estimation of neonatal total body water by antipyrine and H2(18)O dilution.

Total body water was estimated simultaneously by dilution of antipyrine (antipyrine space; APS) and H2(18)O (18O-space; 18OS) in 5 baboon neonates and 2 two-month-old lambs (total of 14 studies). Calculations of 18OS were made either from a single plasma delta 18O measured 4 h after injection of the marker (18OS4) or by extrapolation to time zero of several plasma delta 18O obtained at precisely timed interval (18OS0). Mean (+/- SD) 18OS4 was on the average 23% lower than mean 18OS0 (796 +/- 70 ml/kg vs. 650 +/- 67 ml/kg, p less than 0.001). Mean APS was not statistically different from mean 18OS0 (664 +/- 127 ml/kg vs. 658 +/- 57 ml/kg), but APS ranged from 41% lower to 30% higher than 18OS0. These data and information from the literature suggest that antipyrine is of doubtful reliability and should be abandoned as a marker for total body water.

Maternal administration of vitamin K does not improve the coagulation profile of preterm infants.

The effect of maternal administration of vitamin K1 on cord blood prothrombin time, activated partial thromboplastin time, activity of factors II, VII, and X, and antigen levels of factors II and X in infants less than 35 weeks' gestation was evaluated. Pregnant women in preterm labor were randomly assigned to receive 10 mg of vitamin K1 intramuscularly or no injection. If delivery did not occur in 4 days, the dose of vitamin K1 was repeated. Women who continued their pregnancy 4 days beyond the second dose received 20 mg of vitamin K1 orally daily until the end of the 34th week of gestation. The birth weights of infants ranged from 370 to 2550 g and gestational age ranged from 22 to 34 weeks. The prothrombin time, activated partial thromboplastin time, factors II, VII, and X activity, and factors II and X antigen levels were not statistically different in either group of infants. Intraventricular hemorrhage occurred in 25 of 51 control infants and 25 of 47 vitamin K-treated infants. More control infants had grade III intraventricular hemorrhage on day 1 (P = .032), but on day 3 and 14 of life, the severity of intraventricular hemorrhage was comparable in both groups. Infants in whom an intraventricular hemorrhage developed were significantly smaller, younger, and more critically ill than infants without intraventricular hemorrhage. Administration of vitamin K1 to pregnant women at less than 35 weeks' gestation does not improve the hemostatic defects nor does it reduce the incidence or severity of intraventricular hemorrhage in their infants.

Fetal hepatoblastoma presenting as nonimmune hydrops.

The list of conditions associated with nonimmune hydrops fetalis has been steadily increasing. We describe a liveborn neonate with fetal hepatoblastoma presenting as nonimmune hydrops. The hepatic tumor was diagnosed on prenatal ultrasound. The infant survived for 2 days. The pathophysiology of nonimmune hydrops in this case is also described.

Fatal echovirus type 7 in a premature infant.

Echovirus 7 infections have not been previously recognized as fatal in neonates. A premature male member of a twin gestation developed an echovirus 7 infection at 5 days of age and succumbed to it. The clinical manifestations were similar to an echovirus 11 infection described in neonates. The second twin was free of illness as well as of virus shedding.

Neonatal complications following in utero exposure to intravenous ritodrine.

Intravenous administration of ritodrine for tocolysis has been associated with maternal cardiovascular and metabolic changes. Studies with other tocolytic agents, such as isoxsuprine, have shown an increased neonatal morbidity among infants born soon after failure of such therapy. We examined the potential side effects of maternal intravenous ritodrine therapy in 58 neonates born within 12 h following discontinuation of maternal medication. 'Low dextrostix' was significantly greater in the ritodrine exposed neonates (p less than 0.05) than in the controls. It occurred within a mean 1.0 +/- 0.5 h following birth. The mean 1 min and 5 min Apgar scores, neonatal pH, bicarbonate levels, hypotension and neonatal mortality were comparable in the ritodrine-exposed and control groups of neonates. The occurrence of any of the neonatal morbidity variables, including 'low dextrostix' was not related either to the total dose of ritodrine used or to the interval between drug discontinuation and delivery. Administration of ritodrine by the standard protocol to stop preterm labor is not associated with any significant increase in neonatal morbidity.

Maternal and fetal plasma concentrations of ritodrine.

Previous studies using other beta-adrenergic drugs for tocolysis suggest that if treatment fails and the patient delivers shortly after the therapy is discontinued, there is a direct correlation between neonatal drug concentration and major neonatal complications. In the present study, the disposition of ritodrine was studied in 28 maternal-infant pairs in whom intravenous ritodrine had been administered for clinical indications. The fetal to maternal ratio of ritodrine was 1.17 +/- 0.48. The concentration of ritodrine in both maternal and umbilical vein was found to vary inversely with the length of time the drug was discontinued before delivery. A stepwise multilinear regression revealed that the maternal ritodrine dose in the 24 hours before delivery and the drug discontinuance to delivery interval were both independently related to umbilical vein ritodrine concentrations. When combined, the two variables explained 52% of the variance in umbilical vein ritodrine levels. The frequency of respiratory distress syndrome was increased in the neonates in whom umbilical vein ritodrine was greater than 10 ng/mL, compared with the groups with umbilical vein levels ranging from 3.0 to 10.0 ng/mL. However, neonates with the highest ritodrine concentration were also of lower gestational age (29.4 versus 33.5 weeks, P less than .05) and thus, had greater inherent risk of prematurity-related complications.

When is an amniocentesis for fetal maturity unnecessary in nondiabetic pregnancies at risk?

For several years standard obstetric practice has been to perform an amniocentesis for evaluation of fetal maturity. In order to provide a more definitive answer as to which pregnancies need an amniocentesis, a group of 294 nondiabetic pregnant women in whom an amniocentesis for the evaluation of fetal maturity had been performed for clinical indications were evaluated. Three predictors of fetal maturity--obstetric estimate of gestational age, fetal biparietal diameter, and ultrasonic determination of placental maturation--were evaluated for their ability to predict three outcomes of fetal maturity, including positive amniotic fluid phosphatidylglycerol, pediatric estimate of gestational age greater than or equal to 38 weeks, and absence of hyaline membrane disease. A fetal biparietal diameter of greater than or equal to 90 mm was present in 36% of the total population and was associated with 97% term delivery, 87% positive amniotic fluid phosphatidylglycerol, and 0% hyaline membrane disease. The results associated with an obstetric estimate of gestational age of greater than or equal to 38 weeks were similar. In the present data set over one third of clinically indicated amniocenteses could potentially be avoided without losing any predictive capability for fetal maturity.

The relationship of placental grade, fetal lung maturity, and neonatal outcome in normal and complicated pregnancies.

Ultrasonically diagnosed maturity changes in the placenta, Grades 0 to III, have been previously shown to correlate with fetal lung maturity. In a prospective study of 230 term and preterm complicated pregnancies, we compared the relationship between sonographic placental grading, amniotic fluid phospholipids, and neonatal outcome. The frequencies of gestational age less than 38 weeks, lecithin/sphingomyelin (L/S) ratio less than 2.0, negative phosphatidylglycerol, and neonatal hyaline membrane disease were found to decrease as placental grade advanced from 0 to III. Patients were divided into subgroups on the basis of maternal complications. In patients with Grade III placentas, the frequencies of gestational age less than 38 weeks and L/S ratio less than 2.0 were significantly increased when the subgroup of patients with chronic hypertension was compared individually to both of the subgroups, repeat cesarean section deliveries, and Classes A, B, and C diabetes mellitus (both with p less than 0.05) All three infants who developed hyaline membrane disease in association with Grade III placentas were from pregnancies of less than 38 weeks complicated by chronic hypertension. These findings suggest that the presence of a Grade III placenta is affected by both gestational age and pregnancy complications. Hence, when an elective cesarean section delivery is being planned near term gestation, a Grade III placenta is a reliable predictor of lung maturity. In preterm complicated pregnancies, an ultrasound-diagnosed Grade III placenta may still be associated with hyaline membrane disease.

Detection of intrauterine growth retardation: a new use for sonographic placental grading.

Intrauterine growth retardation (IUGR) is a major source of perinatal death and long-term neurobehavioral morbidity, but its diagnosis antenatally remains difficult. Advanced placental maturity (Grade III), as determined on ultrasound examination, has previously been reported to be a marker of term gestation. In this study of 109 pregnancies which resulted in the birth of infants weighing less than or equal to 2,700 gm, the hypothesis that a Grade III placenta, according to Grannum's classification, can differentiate small-for-gestational age (SGA) infants from small non-SGA infants was tested. Of the study patients, 44 had Grade III placentas and 65 had non-Grade III (0, I, II) placentas within 1 week of delivery. The presence of a Grade III placenta was followed by the delivery of a SGA infant 59% of the time, and 62% of the SGA infants could be correctly identified (p less than 0.001). The association of a Grade III placenta and SGA birth was maintained in patients at less than or equal to 34 weeks of gestation--Grade III placenta was significantly related to the delivery of SGA infants with a true positive rate of 62% and a sensitivity of 66% (p less than 0.008). These results were consistent with the concept that for small fetuses documentation of "maturity" can be used to discriminate those with IUGR from those without this problem. Furthermore, placental "maturation," as detected sonographically, appears to be accelerated in association with IUGR, consistent with the anatomic concept of premature placental senescence. Thus, in situations in which the fetus is known to be small, sonographic grading of the placenta may be helpful in detecting IUGR.