Effects of inhaled oxygen (up to 40%) on periodic breathing and apnea in preterm infants.

To discover whether increases in inhaled O2 fraction (FIO2; up to 40%) decrease apnea via an increase in minute ventilation (VE) or a change in respiratory pattern, 15 preterm infants (birth weight 1,300 +/- 354 g, gestational age 29 +/- 2 wk, postnatal age 20 +/- 9 days) breathed 21, 25, 30, 35, and 40% O2 for 10 min in quiet sleep. A nosepiece and a flow-through system were used to measure ventilation. Alveolar PCO2, transcutaneous PO2, and sleep states were also assessed. All infants had periodic breathing with apneas greater than or equal to 3 s. With an increase in FIO2 breathing became more regular and apneas decreased (P less than 0.001). This regularization in breathing was not associated with significant changes in VE. However, the variability of VE, tidal volume, and expiratory and inspiratory times decreased significantly. The results indicate that the more regular breathing observed with small increases in FIO2 was not associated with significant changes in ventilation. The findings suggest that the increased oxygenation decreases apnea and periodicity in preterm infants, not via an increase in ventilation, but through a decrease in breath-to-breath variability of VE.

A respiratory sensory reflex in response to CO2 inhibits breathing in preterm infants.

Traditionally, the increase in ventilation occurring after approximately 4 s of CO2 inhalation in preterm infants has been attributed to an action at the peripheral chemoreceptors. However, on a few occasions, we have observed a short apnea (2-3 s) in response to 3-5% CO2 in these infants. To test the hypothesis that this apnea reflects a respiratory sensory reflex to CO2, we gave nine preterm infants [birth wt 1.5 +/- 0.1 (SE) kg, gestational age 31 +/- 1 wk] 7-8% CO2 while they breathed 21% O2. To study the dose-response relationship, we also gave 2, 4, 6, and 8% CO2 to another group of seven preterm infants (birth wt 1.5 +/- 0.1 kg, gestational age 31 +/- 1 wk). In the first group of infants, minute ventilation during 21% O2 breathing (0.232 +/- 0.022 l.min-1.kg-1) decreased after CO2 administration (0.140 +/- 0.022, P < 0.01) and increased with CO2 removal (0.380 +/- 0.054, P < 0.05). This decrease in ventilation was related to an apnea (12 +/- 2.6 s) occurring 7.7 +/- 0.8 s after the beginning of CO2 inhalation. There was no significant change in tidal volume. In the second group of infants, minute ventilation increased during administration of 2, 4, and 6% CO2 but decreased during 8% CO2 because of the presence of an apnea. These findings suggest that inhalation of a high concentration of CO2 (> 6%) inhibits breathing through a respiratory sensory reflex, as described in adult cats (H. A. Boushey and P. S. Richardson. J. Physiol. Lond. 228: 181-191, 1973).(ABSTRACT TRUNCATED AT 250 WORDS)

Bedside demonstration of the absence of the right pulmonary artery in a premature baby.

Bedside demonstration of the absence of the right pulmonary artery was made in a premature baby in the neonatal intensive care unit. Antegrade venous and retrograde aortic injections of contrast material excluded the possibility of the anomalous origin of the right pulmonary artery from the aorta, and suggested the above-mentioned diagnosis, with the addition of a ventricular septal defect and a right-to-left shunt.

Effect of maternal tocolysis on the incidence of severe periventricular/intraventricular haemorrhage in very low birthweight infants.

AIM: To examine the relation between grade III-IV periventricular/intraventricular haemorrhage (PVH/IVH) and antenatal exposure to tocolytic treatment in very low birthweight (VLBW) premature infants. STUDY DESIGN: The study population consisted of 2794 infants from the Israel National VLBW Infant Database, of gestational age 24-32 weeks, who had a cranial ultrasound examination during the first 28 days of life. Infants of mothers with pregnancy induced hypertension or those exposed to more than one tocolytic drug were excluded. Of the 2794 infants, 2013 (72%) had not been exposed to tocolysis and 781 (28%) had been exposed to a single tocolytic agent. To evaluate the effect of tocolysis and confounding variables on grade III-IV PVH/IVH, the chi(2) test, univariate analysis, and a logistic regression model were used. RESULTS: Of the 781 infants (28%) exposed to tocolysis, 341 (12.2%) were exposed to magnesium sulphate, 263 (9.4%) to ritodrine, and 177 (6.3%) to indomethacin. The overall incidence of grade III-IV PVH/IVH was 13.4%. In the multivariate logistic regression analysis, the following factors were related significantly and independently to grade III-IV PVH/IVH: no prenatal steroid treatment, low gestational age, one minute Apgar score 0-3, respiratory distress syndrome, patent ductus arteriosus, mechanical ventilation, and pneumothorax. Infants exposed to ritodrine tocolysis (but not to the other tocolytic drugs) were at significantly lower risk of grade III-IV PVH/IVH after adjustment for other variables (odds ratio = 0.3; 95% confidence interval 0.2 to 0.6). CONCLUSION: This study suggests that antenatal exposure of VLBW infants to ritodrine tocolysis, in contrast with tocolysis induced by magnesium sulphate or indomethacin, was associated with a lower incidence of grade III-IV PVH/IVH.

Neonatologists are using much less dexamethasone.

Two historical cohorts (1993-1994 and 2001) of preterm infants ventilated for respiratory distress syndrome were compared. Dexamethasone administration fell from 22% to 6%. Chronic lung disease in survivors rose slightly from 13% to 17%, and mortality fell from 21% to 15% (other causes). The effect of restriction of dexamethasone use on chronic lung disease and mortality remains to be seen.

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy.

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.

Successful resolution of unilateral pulmonary interstitial emphysema in a premature infant by selective bronchial balloon catheterization.

Pulmonary interstitial emphysema (PIE) is a common complication in premature infants with respiratory distress syndrome. The development of pulmonary interstitial emphysema leads to marked respiratory embarrassment in an already compromised infant. Although usually bilateral, PIE may be unilateral. Various forms of treatment for unilateral PIE in the premature infant have been described, including selective bronchial intubation, unilateral pneumonectomy, visceral pleurotomy, pure oxygen administration, and high-frequency low-pressure ventilation. A recently reported conservative regimen consisting of downward lateral positioning of the affected lung for several days may not be successful. We describe a premature infant with progressive worsening of unilateral PIE, which was successfully treated by selective bronchial balloon catheterization after failure of conservative management. In this manner, we avoided selective bronchial intubation or other aggressive forms of treatment.

A new method for selective left main bronchus intubation in premature infants.

Unilateral massive pulmonary atelectasis, and pulmonary interstitial emphysema (PIE) are problems that frequently occur in ventilated premature infants. Selective main bronchus intubation (SBI) of the atelectatic lung, or the contralateral lung in unilateral PIE, is an accepted procedure. However, whereas right SBI is usually easily performed, left SBI is frequently difficult. We have developed a method for left SBI using a regular portex endotracheal tube in which an elliptical hole 1 cm in length has been cut through half the circumference 0.5 cm above the tip of the oblique distal end. With the elliptical side hole directed to the left lung, left SBI can easily, and repeatedly be accomplished. This method may prove life saving in certain cases of unilateral atelectasis or PIE.

In vitro fertilisation and use of ovulation enhancers may both influence childhood height in very low birthweight infants.

CONTEXT: Term-born children conceived by in vitro fertilisation (IVF) are reportedly taller than naturally conceived (NC) children. High levels of growth promoting hormones and epigenetic imprinting have been suggested as pathogenetic mechanisms. HYPOTHESIS: Tall stature in prematurely born IVF-conceived (IVF-C) children suggests pre- or early implantation imprinting rather than a postnatal effect. METHODS: We studied 334 very low birthweight (VLBW: birth weight <1500 g) children born prematurely during 1995-1999 and obtained their anthropometric measures at 6-10 years of age. Perinatal and neonatal data were obtained from the Israeli VLBW database. We compared IVF-C, ovulating agents conceived (OA-C) and naturally conceived (NC) groups of children with respect to their and their parents' anthropometry and their perinatal/neonatal variables. RESULTS: Childhood height standard deviation scores (SDSs) were greatest in IVF-C (-0.12 (SD 1.25); p<0.022) and insignificantly greater in OA-C (-0.37 (SD 1.02)) as compared to NC (-0.58 (SD 1.36)) children. The IVF-C and NC groups were significantly different regarding 17 parental and perinatal variables; however, multiple regression analysis including these variables showed that, as compared with NC, IVF-C children had significantly older mothers at birth with earlier follow-up during pregnancy and more multi-fetal pregnancies. CONCLUSIONS: IVF-C and to a lesser extent OA-C prematurely born children are taller than otherwise NC children. After ruling out postnatal and parental causes, we speculate that pre- or early implantation factors might have contributed to the taller stature of IVF-C children.

The effect on prolonged inhalation of crocidolite asbestos on macrophage-lymphocyte interaction.

The effect of prolonged inhalation of crocidolite asbestos on the physical interactions between alveolar macrophages and the T-lymphocyte population was investigated. When macrophages from dusted rats (dusted macrophages) were cultured with lymphocytes, a prolonged physical interaction occurred followed by lymphocyte proliferation. It was demonstrated that dusted macrophages could bind lymphocytes nonspecifically due to the presence of aldehyde-like groups on the membrane. Dusted macrophages could also, as a consequence of antigen-like molecules appearing in the membrane, give rise to specifically sensitized lymphocytes.

Neonatal diuretic therapy may not alter Children's preference for salt taste.

Human neonates are occasionally treated with diuretics, and we investigated whether this causes a long-term enhancement of salt preference. Salt preference was examined in children aged 4-11 years. Twenty one of the children had received furosemide therapy as preterm neonates, and 24 were preterm neonates from the same ward that had no furosemide therapy. No differences were found between the two groups in preferred concentration of NaCl in soup, in consumption of salty items, and in blood and urine sodium and creatinine. However, in a tested subsample, fractional excretion of sodium (FENa) was higher in the neonatally treated children, suggesting increased salt intake. Reported severity of morning sickness in the mother when pregnant with the child, the child's history of diarrhoea and vomiting and degree of dietary salt exposure were obtained by questionnaire. These variables also did not influence salt preference, or blood and urine sodium and creatinine, except for a correlation between dietary salt exposure and blood sodium concentration. We conclude that while the physiological evidence suggests increased salt intake in children treated neonatally with furosemide, more sensitive tests of salt preference at this age are required to reveal any influence early mineralofluid loss may have on salt preference in childhood.

Liver findings in infantile cytomegalovirus infection: similarity to extrahepatic biliary obstruction.

The histological findings in the liver in four fatal cases of infantile cytomegalovirus (CMV) infection are presented, three occurred in premature infants, and all died at the ages of 2-4 months. Most previously reported cases showed various degrees of hepatitis with giant cell transformation. In three of our four cases, however, the main feature was cholestasis, portal fibrosis and bile duct proliferation, not unlike the findings seen in extrahepatic biliary obstruction. In one case, massive hepatic necrosis was found, a finding not previously reported in this disease. The diversity of liver findings in infantile CMV infection is stressed.

Urinary and blood levels of adenosine 3',5'-monophosphate, phosphorus and calcium in infants.

The changes during the first year of life in urinary and nephrogenous cAMP levels were determined in 152 normal, full-term infants using spot urine samples. The use of spot tests simplifies considerably the logistics of the cAMP determination which can be used for the investigation of parathyroid function. Levels of urinary and nephrogenous cAMP (expressed both as a function of creatinine excretion as well as glomerular filtration rate) rose from birth to 1 year of age, whereas plasma cAMP levels did not change significantly. Levels of cAMP (both urinary and nephrogenous) were significantly correlated with age, length, weight, and urinary phosphorus concentrations of the infants. No significant correlation could be observed, however, between serum phosphorus or serum and urinary calcium on the one hand, and urinary or nephrogenous cAMP on the other.

Atrial natriuretic peptide and endothelin concentrations in human milk during postpartum lactation.

Milk samples from lactating women (n = 24) were examined for atrial natriuretic peptide (ANP) and endothelin-1 (ET-1) content throughout the first 3 months postpartum. Samples were collected at the beginning (foremilk) and towards the end (hindmilk) of nursing. ANP was detected in the milk samples. A value of 9.4 +/- 1.8 pmol/l (mean +/- SEM) was observed on the third day postpartum. No significant variations in concentrations were observed during the 3 months examined. Foremilk and hindmilk ANP concentrations were also similar. ET-1, as previously reported, is present in the milk of lactating women. According to our observations, the concentration of ET-1 varies during the first 3 postpartum months. The highest concentrations were observed on the third day (10.2 +/- 1.8 pmol/l) of lactation, decreasing to 4.5 +/- 0.8 pmol/l after 1 week (p < 0.05) and to 2.0 +/- 0.3 pmol/l, at 1 month postpartum (p < 0.05), this level being maintained for up to 3 months postpartum. Foremilk samples on the third day postpartum contained significantly higher concentrations of ET-1, compared to hindmilk samples (10.2 +/- 1.8 vs 7.7 +/- 1.2 pmol/l, p < 0.05). The stable levels of ANP and the initial high and subsequently decreasing levels of ET-1 in human milk, during the first 3 months postpartum, suggest that these peptides might be of importance either in the lactating mammary gland or in the suckling newborn.