Early changes in respiratory compliance and resistance during the development of bronchopulmonary dysplasia in the era of surfactant therapy.

Despite the availability of surfactant treatment, extremely low birth weight (ELBW) infants continue to be at high risk of developing bronchopulmonray dysplasia (BPD). Evidence suggests that pathologic changes occur within the first few days of life. We hypothesized that the changes in early respiratory system compliance and resistance in ELBW infants with or without hyaline membrane disease (HMD) would correlate with BPD severity and aid in its prediction. Respiratory system compliance (Crs) and resistance (Rrs) were measured at the end of weeks 1, 2, 3, and 4 in 46 infants weighing 1,000 g or less at birth, using the single breath airway occlusion method. Twenty-four infants had HMD and 22 did not. Fifteen infants with and 10 infants without HMD developed BPD with radiological changes and oxygen needs at 28 days. Twelve BPD infants required supplemental oxygen beyond 36 weeks, defined as chronic lung disease (CLD). Irrespective of whether the infant initially had HMD, the week 1 results showed that infants who subsequently developed BPD had a significantly higher respiratory system resistance than those who did not (P = 0.0014). Though week 1 compliance was lower, it was not statistical significant. Multiple logistic models consisting of simple neonatal variables and week 1 respiratory mechanics showed that Rrs was independently associated with subsequent BPD (P = 0.026) and CLD (P = 0.016), while compliance was not. Prediction of CLD improved with the inclusion of Rrs results as compared to prediction using clinical variables alone. Throughout the 4-week study period, Rrs was significantly higher in BPD infants than in those without BPD, and resistance was particularly abnormal in those who had CLD or subsequently required corticosteroid treatment. These observations provide rationale for interventions to prevent BPD within the first week of life. Respiratory mechanics measurements could be useful in the assessment of therapeutics in the current surfactant era.

Neonatal hypoglycaemia in infants of diabetic mothers.

OBJECTIVE: To determine whether umbilical cord blood glucose correlates with subsequent hypoglycaemia after birth in infants of well-controlled diabetic mothers. METHODOLOGY: Thirty-eight term infants of well-controlled diabetic mothers were enrolled. Five mothers had pre-existing diabetes. Of the 33 gestational diabetic mothers, 16 were managed on insulin and 17 on diet. Maternal blood glucose was maintained between 4 and 8 mmol/L during labour and delivery. Infants' plasma glucose levels were measured from venous cord blood and serially, at less than 30 min, 1 h and 2 h of life by glucose hexokinase method. Blood glucose levels were further monitored by bedside Dextrostix for 24 h. RESULTS: Eighteen (47%) infants developed hypoglycaemia (blood glucose level less than 2 mmol/L) during the first 2 h of life. There was no difference in the cord blood glucose levels between infants with or without hypoglycaemia (3.7 +/- 1.1 vs 4.5 +/- 1.1 mmol/L, respectively). Infants of mothers with diabetes diagnosed prior to 28 weeks gestation were at a higher risk of developing hypoglycaemia (8 of 10 vs 10 of 28, OR 7.2, 95%CI 1.3-40.7). Hypoglycaemic infants were of significantly higher birthweight, and were more likely to be born to Caucasian mothers and by Caesarean section. Raised maternal fructosamine blood level, the need for insulin treatment or the infant's haematocrit were not different between infants with or without hypoglycaemia. CONCLUSIONS: In well-controlled diabetic mothers, the incidence of early hypoglycaemia in infants is still high, particularly in those mothers who had a longer duration of diabetes. Cord blood glucose level did not identify the infants with hypoglycaemia.

Vitamin K in preterm breastmilk with maternal supplementation.

Six healthy lactating mothers who gave birth to preterm infants at a median post conceptional age of 29.5 (range 26-30) weeks were given 2.5 mg phylloquinone (vitamin K1) orally daily for 2 weeks beginning at a median postconceptional age of 31.5 (range 28-32) weeks. Phylloquinone was measured in the breastmilk daily for 14 d. Trough plasma phylloquinone concentrations were also determined on four occasions. Phylloquinone levels in the breastmilk increased from a baseline of 3 +/- 2.3 ng ml(-1) to 22.6 +/- 16.3 ng ml(-1) (mean +/- SD) after the first dose (p < 0.05); a gradual increase was noted until phylloquinone levels reached a plateau of 64.2 +/- 31.4 ng ml(-1) after the sixth daily dose.

Neonatal plasma vitamin K1 levels following oral and intramuscular administration of vitamin K1.

Vitamin K1 levels were measured by high performance liquid chromatography in cord blood (n = 33) and at the age of 97-120 h after administration of 2 mg of vitamin K1 orally (n = 88) or 1 mg of vitamin K1 by im injection (n = 88). Vitamin K1 levels were less than 0.05 micrograms/l in cord blood. The mean (range), SEM, mode and median values (micrograms/l) for the infants given oral vitamin K1 were 17.99 (1-56), 1.25, 8 and 15.5 and those for the infants given im vitamin K1 15.83 (2-57), 1.01, 11 and 14, respectively. The t-test showed no significant difference in the mean values (p = 0.09) in the infants given oral or im vitamin K.

Breath hydrogen excretion in healthy premature infants.

Breath hydrogen excretion during the neonatal period was studied on 84 occasions in 44 well premature infants of 27-37 weeks gestational age who all received lactose-containing feeds. Only one of 15 infants studied during the first 24 h excreted hydrogen. Thereafter, the proportion of infants excreting hydrogen increased daily. From day 5 onwards all the infants studied were found to be excreting hydrogen. The concentration and the volume of hydrogen exhaled by infants ranged from 10-230 parts/10(6) and 2.6-107 microL/min, respectively. Breath hydrogen excretion was variable and showed no relationship to birthweight, gestation period, volume of feed or the time of last feed through there was an increase with the age of the infant. Breath hydrogen excretion appears to be a normal phenomenon in premature infants and is probably related to gut colonization with lactose fermenting organisms.

Peripheral artery cannulation in newborns.

This report outlines our experience (retrospectively over a 3-year period) with peripheral artery cannulation for blood gas monitoring in 170 newborn infants. The technique for radial artery cannulation is described in detail. Recorded sites of cannulation were radial (138), posterior tibial (34), dorsalis pedis (2) and temporal (1). Only minor complications occurred which were transient ischaemia (19 cases), accidental blood loss (4 cases) and superficial abscesses (2 cases). Three other cases were suspected to have systemic infection but these were not proven. Cannulae had to be removed in 52% of cases because no blood could be withdrawn for sampling. It is concluded that peripheral artery cannulation in the newborn is a safer and more convenient procedure than umbilical artery catheterisation.

Volumetric diffusive respirator use in neonatal respiratory failure.

Six very low birthweight neonates with terminal respiratory failure due to severe hyaline membrane disease who failed to respond to conventional ventilation were offered a trial of high frequency jet ventilation using the volumetric diffusive respirator (VDR). All neonates showed improvement in pulmonary function. Two neonates were weaned successfully from high frequency ventilation. The results of this initial trial suggest that the volumetric diffusive respirator is a safe and effective method of ventilation in neonates with respiratory failure and that the survival rate in such neonates might be enhanced if treatment is introduced earlier in the disease.

Suprasellar arachnoid cysts: management by cyst wall resection.

Five children with ventricular dilatation (4 boys, 1 girl) had features seen on computer tomographic scan that were consistent with suprasellar arachnoid cysts. All children were investigated with a CT ventriculogram and/or CT cisternogram, and no communication with the cyst was demonstrated. Three children were seen in the 1st year of life and the remaining 2 children were between 1 and 5 years of age. Hydrocephalus and developmental delay were the most common presenting features, followed by visual disturbance, squint, or ataxia. Direct surgical decompression was performed in all 5 patients to avoid long-term placement of a ventriculoperitoneal shunt. A temporary shunt was placed in 2 children because of high intracranial pressure. Direct partial excision of the cyst wall to allow long-term drainage into the basal cisterns or ventricular system was successful in all children. The presence of subdural collections postoperatively required temporary shunting in 2 children. After follow-up for between 10 and 22 months no clinical endocrinological sequelae have been detected, but 2 children have raised serum prolactin levels. Three children are developmentally delayed; one of these has regained some skills since surgery. Direct surgical decompression of suprasellar arachnoid cysts to avoid long-term shunt placement is the preferred method of surgical treatment for this condition.

Urinary sodium excretion in young infants: role of gestational and postnatal ages.

Fractional urinary sodium excretion (FENa) and urinary sodium excretion (UNaE) were determined 88 times in 42 healthy, appropriate weight-for-gestational age infants. Gestational ages (GA) were 28-41 weeks; birthweights were 930-4135 g. Nineteen preterm infants were studied serially a total of 59 times between 1 and 55 days after birth. During the first 4 days after birth, multiple hierarchical regression analyses showed that FENa and UNaE were inversely related to GA (P less than 0.001). Postnatal age (PN) was not significantly related to FENa or UNaE. However the effect of GA on FENa and UNaE was not significantly greater than the effect due to postnatal age (PA) (P = 0.31 and P = 0.80, respectively). UNaE (1.6 +/- 0.2 mmol/kg per day) was significantly greater than sodium intake (1.1 +/- 0.2 mmol/kg per day) at 2.6 +/- 0.2 days (P less than 0.05). Longitudinal studies extending beyond 4 days indicated that GA and PA had interactive effects on FENa and UNaE; hence the contribution for a given GA was dependent on PA (and vice versa). Sodium intake remained stable (average 1.8 mmol/kg per day) beyond 7 days after birth and was consistently greater than UNAE (P less than 0.01). It is suggested that in healthy preterm infants beyond 2 weeks PA, a sodium intake of 2-3 mol/kg per day may be adequate to meet the renal sodium losses.

Breast milk sodium.

Sodium content was analysed from 360 breast milk samples of 45 mothers who delivered at term and from 206 samples of 22 mothers who delivered preterm in the first 4 weeks postpartum. The sodium content was consistently higher in the milk from mothers of preterm infants. In both groups, the sodium content of the breast milk decreased rapidly for the first 3 days, and then more slowly. After the first week, the daily variation of sodium concentration in the breast milk was minimal. There was no significant statistical difference in the sodium content of breast milk before compared with after feeding nor was there any difference in sodium content from either breast.

Skeletal changes in preterm infants.

The skeletal changes in 19 very low birthweight infants (less than 1500 g) were observed from birth to 10 weeks, by means of clinical, biochemical, and radiological techniques. All infants were receiving a supplement of 800 IU vitamin D a day from age 2 weeks. None of the infants showed any specific physical sign of rickets during the period of study. Six infants showed radiological evidence of skeletal demineralisation; 1 of these had severe changes of rickets and 1 had both rickets and fractures. These 6 infants were of shorter gestational periods and lower birthweights than the infants not showing radiological changes. They tended to have more clinical problems and to reach a predetermined volume of feeds (160 ml/kg a day) later than the unaffected infants. Serum alkaline phosphatase values were significantly higher at 5 weeks in the infants with abnormal radiographs than in those without. There were no significant differences between the two groups in relation to serum calcium, inorganic phosphate, 25 hydroxyvitamin D, and immunoreactive parathyroid hormone. The pathogenesis of the skeletal lesions of very low birthweight infants remains unknown.

Measurement of "lamellar body phospholipid" in amniotic fluid as a method for assessing fetal lung maturity.

A simple, rapid micro-method, suitable for use in a routine clinical laboratory, is described for isolating a surfactant fraction from 0.1 mL of human amniotic fluid and measuring its phospholipid content. We determined the phospholipid content of this fraction, referred to as "lamellar body phospholipid," in 451 samples of amniotic fluid collected within two days of delivery and related the data to the respiratory performance of the newborn in every case; 112 of the infants were delivered at 28-37 weeks gestation. The incidence of hyaline membrane disease was inversely related to the concentration of lamellar body phospholipid in the amniotic fluid. Eleven of 12 infants with lamellar body phospholipid values less than 25 mg/L and four of 44 infants with lamellar phospholipid values between 25 and 50 mg/L developed hyaline membrane disease or other serious respiratory problems possibly related to lung immaturity, whereas all of 395 infants with lamellar body phospholipid values of 50 mg/L or more were free from respiratory problems of this nature. The incidence of transient tachypnea was greatest when the lamellar body phospholipid value was between 25 and 50 mg/L, suggesting that this condition may be related to a degree of lung maturity.

Lamellar body phospholipid content of amniotic fluid and L/S ratio compared in assessing fetal lung maturity.

A micro-method has been devised for isolating a lung-derived membranous fraction from human amniotic fluid. The phospholipid content of this fraction, known as lamellar body phospholipid, provides an indication of fetal lung maturity (Ann. Clin. Biochem 16: 191, 1979). This method has now been applied to 479 samples of amniotic fluid from 330 pregnancies. The lecithin/sphingomyelin ratio has also been determined for each of the samples by the routine method currently in use in the hospitals providing the samples. Hyaline membrane disease was associated with a low concentration of lamellar body phospholipid (less than 35 mg/L) in all eight cases encountered in this study. In contrast, in 182 of the 185 cases where the lamellar body content of the amniotic fluid, collected within two days of delivery, exceeded 35 mg/L, the infants were free from serious respiratory problems. Data are presented which suggests that the lecithin/sphingomyelin ratio falsely indicated lung immaturity in many cases, amounting to 44% or more of all values indicating immaturity that were reported.

Thrombus formation on catheters in new born lambs.

Catheters were inserted into the aorta and inferior vena cava of newborn lambs by cutdown on the femoral vessels and directly into the umbilical vein. The lambs were killed after six days and the amounts of thrombus surrounding the cathethers were measured. Most catheters inserted into the umbilical vein looped within the liver and only a few passed directly into the portal vein or through the ductus venosus into the vena cava. On different types of catheters inserted via the femoral artery or femoral vein, there were significant differences both in the proportion with thrombus and the amount of thrombus. There were also significant differences in renal infarctions caused by different types of catheters.

Very low birthweight infants: a follow-up study.

This study was undertaken to determine the outcome of infants delivered at the Royal Hospital for Women during the years 1971 to 1975 who weighed 1500 g or less at birth and who survived the first 28 days of life. Of the 104 neonatal survivors, 79 were seen by one of the writers, nine were seen by other medical practitioners, four had died after the neonatal period, the parents of two children could not be induced to bring their child to be examined, and the remaining ten could not be traced. Abnormalities were found in 15 of the 88 children examined. Three had major physical handicaps (problems causing a restriction of normal lifestyle), 11 had minor handicaps (problems which did not restrict normal lifestyle), and eight had evidence of developmental delay. Infants who were small for gestational age tended to be below the 10th percentile for height or weight at follow-up more often than infants of the appropriate weight for gestational age.