Background/Aims: Patent ductus arteriosus (PDA) is common in preterm infants and is inversely related to gestational age. The incidence is 40–55% in infants of 23–28 weeks gestation but drops to 0.1% for full term infants. PDA management appears to be variable; from conservative waiting to pharmacotherapy and surgery. We undertook a national survey among neonatologists to determine if there was any consensus regarding the management of PDAs. Methods: We surveyed all 133 active neonatologists working in level 2 or 3 centres with 29 questions regarding the diagnosis and management of PDA. The results were reviewed with a descriptive analysis. Results: Out of the 79%(105/133) who responded, 75% of neonatologists wanted echocardiographic confirmation before initiating treatment. 71% waited until the PDA became a clinical problem before initiating treatment. Prior to initiating pharmacotherapy, 78% of neonatologists assessed creatinine levels and 94% assessed platelet counts. 68% decreased fluid intake and 52% stopped feeding. Medical treatment is the first line of treatment for everyone. Indomethacin was the drug of choice with only 5% using ibuprofen. Only 31% of neonatologists used indomethacin prophylacticly. The dosage for indomethacin varied widely. Surgery is primarily done when medical treatment was contraindicated and/or after medical treatment had failed. Surgical ligation was performed by pediatric cardiac surgeons in 64% of centres and by pediatric general surgeons in 26% of centres. Conclusion: Management of PDA varied across Canada. Echocardiographic conformation was sought before treatment. Similarly, the majority waited until the PDA became a clinical problem before intervention. Indomethacin was the first line of treatment. Creatinine and platelets were measured and fluid was restricted prior to treatment. Prophylactic indomethacin use was rare. Surgical ligations were done by pediatric surgeons. These findings suggest that a systematic approach to the management of PDA appears to be necessary so that treatment effects can be assessed.

Objective To evaluate the added nutritional value of the two commercially available human breast milk fortifiers: Similac Natural Care (NC) and Enfamil Powder (EP).Design A randomized controlled evaluation in healthy preterm neonates.Setting Neonatal Intensive Care Unit, Royal University Hospital, Saskatoon, Saskatchewan, and Neonatal Intensive Care Unit, Jewish General Hospital, Montreal, Quebec, Canada.Subjects Healthy preterm infants admitted to and cared for in the aforementioned neonatal intensive care units.Interventions Healthy preterm neonates who were receiving expressed breast milk from their own mothers were supplemented with human milk fortifiers (NC and EP) per manufacturer's recommendations.Main outcome measures Gestational age and birth weight, gender, and race. At entry to and exit from the study. serum concentrations of albumin, protein, calcium, phosphorus, and alkaline phosphatase. The age at which the supplements were added and the number of days the infant remained in the hospital. Daily weight gain, head circumference, length, and height were also measured.Statistical analyses performed Student's t test was used to test the differences between the groups and within the groups at entry to and exit from the study. Fisher's exact test was used to determine differences in race, size, and gestational age in each group. When necessary, a chi(2) test was used to analyze the preponderance of either sex in each group. A Wilcoxon rank test was applied to the true exit date to determine whether the bias was comparable in each group.Results The mean (+/- standard error) gestational age and birth weight were similar in both groups: 30+/-0.3 weeks and 1,314+/-40 g, respectively, for NC vs 29.6+/-0.35 weeks and 1,262+/-45 g, respectively, for EP. At entry to the study, values for the NC group (N=29) were albumin 31+/-1.2, g/L, serum protein 48+/-1.4 g/L, calcium 2.4+/-0.03 mmol/L, phosphorus 1.85+/-0.08 mmol/L, alkaline phosphatase 347+/-27 IU/L. The values for the EF group (N=30) were albumin 32+/-0.9 g/L, serum protein 49+/-1.4 g/L, calcium 2.4+/-0.4 mmol/L, phosphorus 1.9+/-0.1 mmol/L, alkaline phosphatase 420+/-34 IU/L. At the study exit, the values for the NC group were albumin 30+/-0.7 g/L, serum protein 45+/-0.9 g/L, calcium 2.4+/-0.3 mmol/L, phosphorus 1.96+/-0.07 mmol/L, and alkaline phosphatase 371+/-23 IU/L. The values for the EP group were albumin 32+/-1.0 g/L, serum protein 46.0+/-1.4 g/L, calcium 2.5+/-0.03 mmol/L, serum phosphorus 2.2+/-0.1, and alkaline phosphatase 367+/-27 IU/L.No significant differences were observed between groups at entry to and exit from the study. However, in the EP group the alkaline phosphatase decreased significantly (P=.02) from entry to exit and calcium increased significantly during the same period compared with the NC group (P=.003). The mean daily weight gain was 33+/-0.7 g for the NC group and 31+/-1 g for the EP group. The weekly gain in head circumference and body length were also similar in both groups: approximately 1 cm/week. Both groups tolerated the fortifiers well.Applications/conclusions These findings suggest that both products provide the additional nutritional support necessary for optimal overall postnatal growth in healthy preterm infants. The differences in calcium and alkaline phosphatase may be due to the differences in vitamin D content in fortifiers 88 IU/100 mL in mixed NC vs 270 IU/100 mL in mixed EP. This observation calls for careful monitoring of calcium and alkaline phosphatase values and possible adjustments of vitamin D intake when fortifiers are used for extended periods.

Prolonged interdelivery periods in preterm twin and triplet gestations have resulted in a good outcome for the fetus(es) remaining in utero. This is the second reported case of delayed delivery intervals in quadruplets who were born on 3 separate days. We report on a set of quadruplets following gonadotropin induction of ovulation, in which preterm delivery of the first infant occurred at 26 weeks' gestation. Active uterine contractions ceased and ultrasonography confirmed the remaining triplets to be in separate amniotic sacs with satisfactory heart rate tracings. With bed rest and tocolysis, the delivery of the second infant did not occur until 8 days later. After a further 36-h delay, placental abruption prompted cesarean delivery of the remaining twins. The first infant died of sequelae of prematurity at 7 months, while the remaining triplets survived and are neuro-developmentally normal 1 year after delivery. This report demonstrates the feasibility of prolonging the delivery interval of the fetus(es) in higher order multiple gestations, using tocolysis and watchful expectancy, after the preterm birth of one or more fetuses.

Apnea of prematurity is a common problem in neonatal intensive care nurseries. Xanthines are used to treat apnea, but their mechanism of action is not clearly understood. To determine whether xanthines stimulated beta-endorphin (beta-ED) release in preterm infants, plasma beta-ED concentrations were measured in 27 infants with apnea of prematurity. These infants had a mean (+/-SD) birthweight of 1560 +/- 487 g, gestational age 31 +/- 2.5 weeks, and a postnatal age of 7.3 +/- 4.6 d. Twenty-five of the infants were treated with I.V. aminophylline 2.5 mg/kg/dose 4 times daily and 2 were treated orally with caffeine (10 mg/kg). Blood samples were collected prior to and 30 min after treatment with xanthines. Apneic spells greater than 15 sec were recorded and reviewed every 24 h using a Hewlett-Packard Merlin Monitor (Waltham, MA.) system. Infants were then stratified into responders (Group 1, n = 14) and nonresponders (Group 2, n = 13), with responders defined as showing more than 50% decrease in the frequency of apneic spells in the first 24 h of treatment. Beta-ED were measured as previously described using a radioimmunoassay technique. In group 1, plasma beta-ED concentration increased significantly, (p = 0.0496) from pre-xanthine (24.4 +/- 12 pg/ml) to post xanthine (34.6 +/- 24 pg/ml) treatment, whereas in Group 2 the concentrations remained the same (23.3 +/- 5 pg/ml) and (22.6 +/- 4 pg/ml). Birthweight, gestational age, postnatal age, and diagnoses in both groups were compared and no significant differences were observed. Interestingly, xanthine treatment caused increased plasma beta-ED release when apneas decreased.

Although the metabolism and pharmacokinetics of chloral hydrate (CH) have been reported, there have been no attempts to correlate CH or its metabolite, trichloroethanol (TCE) with the sedative or hypnotic effects. In order to determine whether plasma concentrations of CH or TCE reflect the sedative/hypnotic effects, a sedation/agitation scale was developed. Based on the results of the present study, the sedative/hypnotic effects of TCE cannot be ruled out completely. However, in the neonate, the parent drug CH seems to have a more important role than has been previously suggested from human research.

Although the metabolism and pharmacokinetics of chloral hydrate (CH) have been studied in healthy adults, no comprehensive studies have been done in neonates and young infants. Major physiological differences between these groups could greatly affect drug disposition. In this study the patient population (22 patients) was divided into three groups according to postconceptual age: group 1 = preterm infants (31-37 weeks), group 2 = fullterm infants (38-42 weeks) and group 3 = toddler-child patients (57-708 weeks). After receiving one 50 mg/kg oral dose of CH, the parent drug and its metabolites were determined by gas chromatography utilizing an electron capture detector. CH, contrary to what has been reported in the adult, was detectable for several hours after oral administration to patients in all three groups. A highly significant negative correlation was observed amongst the three groups for the half-life (t1/2) and area-under-the-curve for 0 to infinity values for trichloroethanol (TCE), the active metabolite responsible for the sedation effect. The t1/2 value for TCE in group 3 (9.67 h) was similar to that reported for the adult population, but in the less mature subjects it was approximately three (group 2: 27.8 h) to four times (group 1: 39.8 h) greater. Trichloroacetic acid had a remarkably long residence time in the study population after a single dose of CH. The concentration of this metabolite failed to decline even 6 days after dose. These issues should be carefully considered when CH administration is contemplated for clinical use in neonates, infants and children.

Chloral hydrate has been used clinically for over 100 years. There is significant paucity of information regarding chloral hydrate metabolism in neonates and infants. Chloral hydrate and its various metabolites were quantitated in 12 neonates and 2 infants at prescribed time intervals. The analysis of the data indicates accumulation of trichloroacetic acid and trichloroethanol in tissue of compromised infants. There is indirect evidence of competition for hepatic glucuronidation for bilirubin with trichloroethanol in ill preterm infants. Multiple dosing of chloral hydrate in preterm infants should be used with caution and frequent monitoring of serum bilirubin concentrations is indicated in such cases. The mechanism of chloral hydrate metabolism is discussed in detail.

A simple, rapid and sensitive electron-capture gas chromatographic method has been developed for the simultaneous determination of chloral hydrate, trichloroethanol and trichloroacetic acid in biological fluids. The described method is applicable to single-dose pharmacokinetic studies of chloral hydrate in the adult. The method also meets the important requirement of using very small sample volumes and is sufficiently sensitive and reliable for disposition studies in the neonate.

Life-threatening events such as prolonged apnea and severe bradycardia are uncommon in infants. When such events occur in a family, however, the results may be disastrous. Over a period of 3 years ending June 1986, we have looked after 111 such infants aged 4 weeks to 40 weeks with a mean age of 14 weeks (male-female ratio 1.26:1). Of these infants, 33 had an identifiable cause and were treated according to the diagnoses. A structural approach to this problem yielded good results. Only 10 infants were treated with a home monitor (4 prescribed by physician and 6 by parental request). Sleep and pneumogram (polysomnogram) studies showed fewer apneic episodes with advancing age (P less than .01). Giving theophylline seemed to abolish pneumogram abnormalities. No infants died.

We examined the records of 14 patients aged 7 months to 10 1/4 years who were treated for bacterial tracheitis from May 1982 to December 1987; the management protocol for 13 of the patients included the use of nasotracheal intubation. The infection was caused by Staphylococcus aureus in seven, Haemophilus influenzae in three, Branhamella catarrhalis in one and Streptococcus pneumoniae in one. Both H. influenzae and B. catarrhalis were isolated in another patient, and no organism was found in the remaining patient. In addition to the bacteria, viruses were cultured from the tracheal secretions of two patients. The mean duration of intubation was 7.6 days and of hospital stay 9.2 days. Twelve of the cases occurred during the cold months of the year (October to March). Of the three deaths only one occurred in the pediatric intensive care unit and was due to severe bronchospasm and an air leak that caused bilateral pneumothorax and pneumomediastinum. In one patient subglottic stenosis developed that necessitated tracheostomy. Healing began 5 to 9 days after the onset of symptoms, as demonstrated with the use of repeated fibreoptic bronchoscopy. We found that the airway could be safely managed with the use of a nasotracheal tube. Bronchoscopy helped to confirm the diagnosis, to remove adherent secretions and to monitor the course of the disease. The ventilation tube can be removed after the patient's temperature returns to normal, if there is an air leak around the tube, if the quantity and viscosity of the secretions decrease and if healing is observed at bronchoscopy.

To determine whether a diurnal rhythm exists in neonates admitted to neonatal intensive care units where there is continuous artificial lighting and periodic nursing and medical care, plasma cortisol, adrenocorticotropin (ACTH), and beta-endorphin concentrations were measured in two groups of infants and in adult human volunteers. As expected, a diurnal rhythm was seen in adults. A diurnal rhythm was also found for cortisol and endorphin levels in neonates (3 to 4 days postnatally) with minimal stress and in infants who were clinically severely stressed. There was not a significant difference between the morning and afternoon concentrations of ACTH in these infants, but the afternoon concentrations were lower than the morning's, as would be expected. We found that a diurnal rhythm does exist in neonates within the first few days of postnatal life and that the continuous lighting and medical and nursing interventions do not interfere with this rhythm.

A two-year-old child dying of pulmonary hypertension and cor pulmonale secondary to bronchopulmonary dysplasia, was demonstrated to have reactive pulmonary hypertension in response to 100% oxygen and isoproterenol infusion. In an attempt to find an oral medication to maintain pulmonary vasodilatation, experimental trials were done using hydralazine, salbutamol, nifedipine and diltiazem. Cardiac index, pulmonary and systemic vascular resistances and intrapulmonary shunts were monitored during the trials. Hydralazine, salbutamol and nifedipine were ineffective. Diltiazem 2.0 mg given every 6 h resulted in a profound and sustained decrease in pulmonary pressures and resistance, and a reversal of the cor pulmonale.

To determine whether a diurnal rhythm exists in neonates admitted to neonatal intensive care units (NICU) where there is continuous artificial lighting and periodic nursing and medical care exists, Plasma cortisol, ACTH and β-endorphin (BED) concentrations were measured in two groups of infants and another group of adult human volunteers. As expected, a diurnal rhythm is seen in adults. Plasma concentrations found during morning and (afternoon) hours were: cortisol - 475.0 ± 204.2 (255.0 ± 75.2) nmoles /L; ACTH - 10.9 ± 3.4 (13.0 ± 4.6) pg/mL; β-ED -22.l ± 9.5 (16.8 ± 7.2) pg/mL. A diurnal rhythm was also observed for ACTH and cortisol in neonates (3-4 days postnatally) :cortisol - 340 ± 194.5 (228.8 ± 101.0) nmoles/L; ACTH - 6.3 ± 4.2 (8.8 ± 5.5)pg/mL. Although there was not a statistically significant difference between morning and afternoon β -ED levels in this group, the afternoon levels like the adults were lower: 24.2 ± 13.0 (19 ± 9.8) pg/mL. There was no significant difference between the concentrations of any of the three substances in infants who were severely stressed clinically: cortisol - 320 ± 230.6 (406.4 ± 227.4) nmoles/L; ACTH - 7.0 ± 3.1 (8.0 ± 4.7) pg/mL; β- ED -37.1 ± 19.4 (45.6 ± 35.7) pg/mL. It would appear that a diurnal rhythm exists in neonates within the first few days of postnatal life and that the continuous lighting, medical and nursing interventions do not seem to interfere with this rhythm. Severe stress seems to override this rhythm.

Aminoglycoside antibiotics are frequently used for the treatment of suspected and confirmed sepsis in the newborn patient. In an attempt to evaluate gentamicin dosing based on serum creatinine concentrations, two groups of neonates were studied (infants less than 34 weeks n = 8 and greater than 34 weeks n = 14). The dosing interval was adjusted per protocol depending on the serum creatinine concentrations. Analysis of the results indicate reasonable therapeutic serum gentamicin trough and peak concentrations in most infants.