Ophthalmological morbidity in very-low-birthweight infants with bronchopulmonary dysplasia.

This study was undertaken to determine the relationship between retinopathy of prematurity, ocular sequelae of retinopathy, and bronchopulmonary dysplasia in infants weighing < 1250 g at birth prior to the introduction of steroid therapy for chronic lung disease. Ophthalmological data from 67 infants (22 with severe bronchopulmonary dysplasia and 45 controls) who were enrolled prospectively in an early intervention program were analyzed. The infants had two or more eye examinations prior to discharge and a follow-up examination at 12 to 18 months postconceptual age. The incidence of any retinopathy of prematurity was 33%, and severe retinopathy was 25%. Infants with severe bronchopulmonary dysplasia were 1.7 times more likely to develop any retinopathy and 1.8 times more likely to develop severe retinopathy than controls. The incidence of ocular sequelae, was 45%. Infants with any retinopathy had a 2.3 odds of developing sequelae, and infants with severe retinopathy had a 2.64 odds ratio. When adjusted for bronchopulmonary dysplasia, the odds ratio for developing sequelae was 1.36 in infants with any retinopathy and 1.27 in those with severe retinopathy. The predictors of retinopathy were lower birthweight and gestational age, acidosis, and hypoxemia. Bronchopulmonary dysplasia per se has an adverse effect on ophthalmologic morbidity. Evaluation of the adverse effect of any therapy for chronic lung disease on retinopathy of prematurity should make adjustments for the underlying lung disease.

Maternal and neonatal outcome of pregnancies complicated with maternal HELLP syndrome.

UNLABELLED: Preeclampsia complicated by the HELLP syndrome is associated with poor maternal outcome; there is scant information on neonatal outcome. OBJECTIVE: To evaluate the outcome of infants born to mothers with HELLP syndrome. STUDY DESIGN: Chart review comparing perinatal variables and the clinical course of 23 infants born to mothers whose pregnancy was complicated with HELLP syndrome (H) with 23 infants of mothers with uncomplicated preeclampsia (P). RESULTS: Infants in the H group, when compared with those in the P group, had a higher incidence of low Apgar scores (52% vs 18%, p < 0.01), lower admission systolic blood pressure (45 +/- 7 vs 32 +/- 11, p < 0.01), and more frequent need for assisted ventilation (61% vs 30%, p < 0.05). There were no differences between the two groups of infants in hematocrit, leukocyte and platelet count, or duration of ventilation and hospitalization. CONCLUSIONS: These findings suggest that infants born to preeclamptic mothers who develop HELLP syndrome have an increased need for resuscitation at delivery and a higher incidence of postnatal cardiopulmonary instability. Thus mothers with HELLP syndrome should be identified promptly and delivered in level II or III centers with appropriate facilities for management of these newborn infants at risk for perinatal asphyxia and a potential for long-term neurologic sequelae.

A crossover comparison of the efficacy and safety of lovastatin and gemfibrozil in the treatment of hyperlipidemic organ transplant recipients.

Hypercholesterolemia is associated with accelerated atherosclerosis in transplant recipients. It has been notoriously difficult to treat pharmacologically due to the complex interactions that occur with lipid-lowering drugs and immunosuppressive therapies. The purpose of the current study was to compare the efficacy and safety of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (lovastatin, 20 mg/d) with a fibric acid derivative (gemfibrozil, 600 mg twice a day). We used a randomized, crossover design in 18 solid organ transplant recipients who followed the National Cholesterol Education Program Adult Treatment Guidelines diet for 8 weeks and had persistent elevations of total cholesterol (>240 mg/dL). Each patient received each therapy for a minimum of 8 weeks (mean 14.2 +/- 2.4, range 8-20 weeks). The participants had stable allograft function and were treated with a standard immunosuppressive regimen containing cyclosporine, prednisone, and azathioprine. Lovastatin therapy reduced the mean total cholesterol by 15.5% (271.9 mg/dL to 229.9 mg/dL; p = 0.02) and the mean low-density lipoprotein (LDL) cholesterol by 22.7% (178.2 mg/dL to 137.8 mg/dL; p = 0.07). There were no significant changes in high-density lipoprotein (HDL) cholesterol or triglycerides. Conversely, when these same patients were treated with gemfibrozil, the mean total cholesterol decreased by 7.9% (271.9 mg/dL to 250.5 mg/dL; p = NS) and the LDL cholesterol decreased by 5.1% (178.2 mg/dL to 169.1 mg/dL; p = NS). In addition, the mean triglyceride concentration decreased significantly by 46.1% (234.0 mg/dL to 126.3 mg/dL; p = 0.002) and the mean HDL cholesterol increased 15.4% (48.8 mg/dL to 56.3 mg/dL; p = 0.09). In all patients, the serum creatinine, hepatocellular enzymes, and creatinine phosphokinase remained stable. Lovastatin was discontinued in three patients for myalgias, one patient with unexplained anemia, and one patient with parasthesias. These results suggest that lovastatin and gemfibrozil are both safe and efficacious in transplant patients. However, neither therapy alone completely corrects abnormalities of high LDL cholesterol and low HDL cholesterol in transplant recipients.

Congenital cutaneous candidiasis: case report and review.

This report describes a preterm infant with congenital cutaneous candidiasis associated with paronychia, dystrophy of the nail plates, and marked, transient leukocytosis.

Renal failure in the neonate associated with in utero exposure to non-steroidal anti-inflammatory agents.

In utero exposure to non-steroidal anti-inflammatory agents (NSAIAs) can produce combinations of oligohydramnios, a bleeding diathesis, ileal perforation, premature closure of the ductus, and acute or chronic renal injury. NSAIAs induce renal dysgenesis in fetal monkeys and renal structural abnormalities in the developing human fetus. We report oligohydramnios and renal failure associated with in utero exposure to early, prolonged, high-dose indomethacin in four neonates, and to ibuprofen in one neonate. Four of the affected neonates were one of twins. In each set of twins, only one of the pair was affected. One set of twins was proven to be identical, whereas the other three sets seemed to be identical. It is possible that the histopathological findings of uncertain or incomplete tubular differentiation may be the result of a direct effect of NSAIAs on developing or "immature" tubules. Therefore, the advantages of NSAIAs as tocolytics need to be weighed against the complication of severe renal injury.

Neonatal group B streptococcal cellulitis-adenitis.

A 38-day-old prematurely born infant developed rapidly progressive facial cellulitis in association with ipsilateral submandibular lymphadenopathy and pulmonary consolidation. Group B streptococci (GBS) were isolated from blood, endotracheal, and lesion cultures. Prompt recognition of GBS cellulitis-adenitis and institution of parenteral, synergistic antibiotic therapy are important.

Chest physiotherapy in preterm infants with RDS in the first 24 hours of life.

To evaluate if chest physiotherapy is beneficial to premature infants with respiratory distress syndrome (RDS) during the first 24 hours of life, 20 infants were randomly assigned to two groups; 10 infants in Group I received routine chest physiotherapy and suction, and 10 infants in Group II received suction only. The birth weight, gestational age, postnatal age, Apgar scores, blood gases, acid-base status, and ventilatory requirements prior to study were comparable between the two groups. There were no significant differences between the groups in the amount of endotracheal secretions removed, the PO2/FIO2 ratio, blood gases, and pH during the study. The incidence of patent ductus arteriosus (PDA), bronchopulmonary dysplasia (BPD), Grade I and II intraventricular hemorrhage (IVH), and mortality was comparable. However, five of 10 Group I and zero of 10 Group II infants developed Grade III or IV IVH (P less than 0.05).

Renal response to frusemide in preterm infants with respiratory distress syndrome during the first three postnatal days.

The renal effects of frusemide treatment in infants with respiratory distress syndrome shortly after birth and during the first three postnatal days were evaluated. Eighty five infants were randomly assigned to two groups. Forty two received three doses of intravenous frusemide (1 mg/kg) starting at age, mean (SD) 7.5 (4.1) hours and given at approximately 24 hour intervals. Forty three control infants were treated similarly but were not given frusemide. The groups were comparable in birthweight, gestational age, and Apgar score and in pulmonary status, blood gases, serum electrolytes, and postnatal age. Infants who received frusemide had significantly higher fractional excretion of sodium and chloride at 12 to 24, 24 to 48, and 48 to 72 hours, and higher calcium excretion at 24 to 48 and 48 to 72 hours after entry into the study than control infants. The study group had a significantly higher urine output and greater weight loss than the control group at 48 to 72 hours after entry into the study. There was no significant difference between groups in serum sodium, potassium, and calcium and in fractional excretion of potassium and the glomerular filtration rate. Infants with an Apgar score of more than 3 had higher urine output and had a better diuretic response to frusemide than those with a lower score. The results suggest that perinatal hypoxia may play an important role in renal function and in diuretic response to frusemide shortly after birth and early in the postnatal life of infants with respiratory distress syndrome.

Early furosemide therapy in premature infants (less than or equal to 2000 gm) with respiratory distress syndrome: a randomized controlled trial.

Pulmonary edema has been demonstrated in the early stages of respiratory distress syndrome in premature infants. To evaluate whether early furosemide therapy (0 to 8 hours after birth) would affect the electrolyte balance, pulmonary status, and outcome, 57 infants (less than or equal to 2000 gm) with respiratory distress syndrome who required mechanical ventilation shortly after birth were randomized into two groups: 29 given furosemide (1 mg/kg/day intravenously for three doses) and 27 control. The clinical, biochemical, and laboratory characteristics of the groups were comparable before entry into the study. Administration of furosemide significantly enhanced the urinary excretion of Na and Cl at 0 to 24, 24 to 48 and 48 to 72 hours and of Ca at 24 to 48 and 48 to 72 hours after drug administration. There was no significant difference between the groups in urinary excretion of K and in serum Na, Cl, K, and Ca values. A spontaneous increase in urine output occurred in the control group at 48 to 72 hours after the initiation of the study (mean +/- SD 7.0 +/- 3.5 hours postnatal age), along with a decrease in mean airway pressure for mechanical ventilation. The use of furosemide (7.3 +/- 3.5 hours postnatal age) enhanced urine output at 24 to 48 and 48 to 72 hours after medication, resulting in further decrease in mean airway pressure and facilitating extubation. There was, however, no significant difference between the groups with respect to incidence of patent ductus arteriosus, morbidity from bronchopulmonary dysplasia, and mortality.

Indomethacin treatment in small versus large premature infants with ductus arteriosus. Comparison of plasma indomethacin concentration and clinical response.

An analysis of clinical response and plasma indomethacin concentration was performed on 10 small (less than or equal to 1000 g) and 12 large (greater than 1000 g) premature infants who had symptomatic ductus arteriosus and required intravenous indomethacin therapy (0.3 mg/kg per day). The postnatal age, daily fluid intake, and cardiopulmonary status of the two groups at time of study were comparable, The small premature infants had a significantly lower peak plasma indomethacin concentration and lower concentration in the first four hours after infusion, and lower plasma concentration X time integral than that of the larger premature infants. There was a significant difference between the groups in proportion of response (2/10 vs 9/12) after one dose of indomethacin; this difference was not seen after two to three doses. The results of the study suggest that small premature infants do respond to indomethacin treatment, but compared to the larger infants may require repeated doses.

Penicillin in infants weighing two kilograms or less with early-onset Group B streptococcal disease.

We studied the effect of penicillin on early-onset Group B streptococcal disease over a 52-month period in neonates who were at high risk of infection. Shortly after birth, 1187 neonates weighing 2000 g or less had blood samples taken for cultures and were randomized into an early-treatment group (given intramuscular penicillin G within 60 minutes of birth) or a control group. The incidence of early-onset disease was 20 per 1000 live births (24 of 1187); the number of infants in the early-treatment group who had disease (10 of 589) was similar to that in the control group (14 of 598). The fatality rates were similar in both groups (6 of 10 vs. 8 of 14). Cultures from blood obtained with one hour of birth were positive in 21 of the 24 infants with disease; 22 of the 24 were symptomatic within four hours of birth. Thus, infection was well established before the first hour of postnatal life. At autopsy, gram-positive cocci were seen in lung sections of four infants in whom cultures of blood obtained after treatment had been sterile; this indicates that giving routine antibiotic therapy before culture samples are obtained can obscure bacteriologic diagnosis. We conclude that penicillin given at birth to neonates weighing 2000 g or less does not prevent early-onset streptococcal disease or reduce excess mortality associated with disease.

Retinopathy of prematurity (ROP) and indomethacin therapy in premature infants with patent ductus arteriosus (PDA).

Recent studies suggested that prostaglandins (PGs) may play a role in the pathogenesis of retinopathy of prematurity (ROP). To evaluate if PGs inhibitor, indomethacin, would affect the incidence or severity of the ROP, an analysis was performed on 47 infants who participated in a double-blind controlled study of indomethacin for the closure of PDA. Twenty-three were in the control group and 24 in the indomethacin group. Indirect ophthalmoscopic examinations were performed from about 4 weeks of postnatal age and onward as needed. There was no significant difference between the groups with respect to birth weight, gestational age, postnatal age, Apgar score, and cardiopulmonary status shortly after birth and at the time of study. Six in the control and 2 in the indomethacin group (p = 0.58) developed active ROP; one in each group developed cicatricial ROP. It appears that with current doses of therapy, indomethacin does not increase the incidence or severity of ROP.

Decreased plasma glucose following indomethacin therapy in premature infants with patent ductus arteriosus.

In the course of a double-blind controlled trial of intravenous indomethacin therapy in premature infants with patent ductus arteriosus, plasma glucose was evaluated in 47 infants before and at 24, 48, and 72 hours following the medication. Twenty-two infants were assigned to the control group and 25 were in the indomethacin group. Significantly lower plasma glucose was noted at 24 (P less than 0.01) and 48 (P less than 0.05) hours in the indomethacin group as compared to the control group. There was a significant inverse correlation between the plasma glucose and the corresponding plasma indomethacin concentration (P less than 0.05) and between the plasma glucose and the corresponding plasma indomethacin concentration-time integral (P less than 0.01) at 24, 48, and 72 hours after drug administration, suggesting that the decreased plasma glucose may be related to indomethacin therapy. The results of this study indicate that endogenous prostaglandin may play a role in glucose homeostasis in premature infants.

Clinical evaluation of premature infants with patent ductus arteriosus: a scoring system with echocardiogram, acid-base, and blood gas correlations.

To provide a clinical assessment of cardiovascular dysfunction (CVD) in premature infants with patent ductus arteriosus (PDA), a scoring system (CVD score) was devised and correlated with blood gases, acid-base balance, and echocardiogram. The score consisted of evaluation of heart rate, quality of peripheral arterial pulsation, degree of precordial pulsation, duration of murmur and cardiothoracic ratio on chest roentgenogram. There were 116 observations made on 55 premature infants who had PDA and required medical or surgical treatment. Significant positive correlations were seen for CVD score with left atrial (LA)/aortic (Ao) ratio (p less than 0.001), left ventricular and diastolic dimension (DD) (p less than 0.001), blood pH (p less than 0.01), and blood PCO2 (p less than 0.01). The scoring system may by used as a clinical guide when echocardiogram or angiogram is not available.

Intravenous indomethacin therapy in premature infants with persistent ductus arteriosus--a double-blind controlled study.

A double-blind controlled trial of intravenous indomethacin therapy was performed using a group of 55 premature infants (27 placebo, 28 indomethacin) with a significant persistent ductus arteriosus. Indomethacin administration at a mean postnatal age of 8.9 days was followed by a significant effect on PDA in 89%; 75% of successes were attributable to indomethacin and 25% to spontaneous effects, an improvement by indomethacin of 86% in infants not undergoing spontaneous improvement. The short-term side effects of indomethacin were transient; urinary output and serum sodium concentration decreased and serum potassium concentration increased. Indomethacin administration was associated with a decreased need for assisted ventilation and a decreased need for surgical closure of PDA. There was no significant difference between the placebo and indomethacin groups in mortality and bronchopulmonary dysplasia morbidity. The infants who developed BPD had higher RDS scores and lower PO2 values, requiring higher FIO2s within four hours of birth than those who did not develop BPD, indicating a more severe underlying pulmonary disability present birth.

Pharmacokinetics of intravenously administered indomethacin in premature infants.

We studied the pharmacokinetics of indomethacin (0.3 mg/kg) given intravenously in 17 premature infants to promote closure of persistent ductus arteriosus. The decay of indomethacin generally showed an initial rapid distribution (alpha) phase followed by a slower elimination (beta) phase. The mean half-life of elimination (20.7 +/- 8 hours) was three times longer, and the mean clearance rate (13 +/0 9.5 ml/kg/hour) was seven times less than that reported in adults. The indomethacin clearance rate was linearly correlated with postnatal age (r = 0.71, P < 0.01). There was strong evidence of later re-entry of indomethacin into the plasma, suggesting that enterohepatic recirculation may be common in premature infants and may contribute to the relatively long half-life of elimination. Our data do not clarify the question of target concentration or minimal exposure time above which permanent closure may occur, but the group of infants who had permanent PDA closure after only one dose (8/17) had a significantly higher plasma indomethacin concentration time integral than the group (9/17) who needed more than one dose (P < 0.01). A 24-hour dosage interval was often sufficient when an iv indomethacin bolus of 0.3 mg/kg was used but, below the age of nonresponsiveness to indomethacin, a shorter interval may be preferable as postnatal age increases.