Death in the neonatal intensive care unit: changing patterns of end of life care over two decades.

BACKGROUND: Death remains a common event in the neonatal intensive care unit, and often involves limitation or withdrawal of life sustaining treatment. OBJECTIVE: To document changes in the causes of death and its management over the last two decades. METHODS: An audit of infants dying in the neonatal intensive care unit was performed during two epochs (1985-1987 and 1999-2001). The principal diagnoses of infants who died were recorded, as well as their apparent prognoses, and any decisions to limit or withdraw medical treatment. RESULTS: In epoch 1, 132 infants died out of 1362 admissions (9.7%), and in epoch 2 there were 111 deaths out of 1776 admissions (6.2%; p<0.001). Approximately three quarters of infants died after withdrawal of life sustaining treatment in both epochs. There was a significant reduction in the proportion of deaths from chromosomal abnormalities, and from neural tube defects in epoch 2. CONCLUSIONS: There have been substantial changes in the illnesses leading to death in the neonatal intensive care unit. These may reflect the combined effects of prenatal diagnosis and changing community and medical attitudes.

Left-lung-collapse bronchial deformation in giant omphalocele.

Five infants with giant omphalocele had persistent collapse of the left lung and required prolonged respiratory support. Narrowing of the left main bronchus, reversible with positive end-expiratory pressure, was identified radiographically in 3 infants, and we postulate that this relates to distortion of the bronchus within the constraints of the elongated, narrow thoracic cavity characteristic of these patients. The lung collapse may be precipitated by manipulation (reduction or attempted reduction) of the omphalocele. J Pediatr Surg 36:846-850.

Surfactant and surfactant inhibitors in meconium aspiration syndrome.

Surfactant indices and inhibitors were measured in lung lavage fluid from 8 infants with meconium aspiration syndrome (MAS) who were receiving mechanical ventilation and 11 healthy control subjects. Surfactant phospholipid and surfactant protein A content in MAS was not different from that of control subjects, but concentrations of total protein, albumin, and membrane-derived phospholipid were elevated. All infants with MAS had hemorrhagic pulmonary edema. These findings reinforce the notion of MAS as a toxic pneumonitis with epithelial disruption and proteinaceous exudation.

Comparison of two methods of diagnostic lung lavage in ventilated infants with lung disease.

The methods of nonbronchoscopic lung lavage used for collection of samples of epithelial lining fluid (ELF) in intubated patients are poorly standardized and incompletely validated. In infants with lung disease requiring ventilatory support, we evaluated two techniques of small volume saline lavage for the collection of a specimen suitable for pulmonary surfactant analysis. We aimed to compare apparent origin of the return fluid obtained by each method, equivalence and agreement of the estimates of measured pulmonary surfactant concentration, and the relative strength of association between surfactant indices and lung dysfunction. Fifty-three contemporaneous paired samples of lung lavage fluid suitable for surfactant analysis were collected from 31 infants using tracheal aspirate (TA, 4 x 0.5 ml saline), and then nonbronchoscopic bronchoalveolar lavage (NB-BAL, 3 x 1 ml/kg). Return fluid from TA had higher mean ELF concentration of total protein and IgA secretory component (SC), and a lower surfactant protein A (SP-A) concentration than NB-BAL, indicating that the TA lavage was sampling ELF more proximally in the tracheobronchial tree (protein: TA 7.7 versus NB-BAL 4.7 mg/ml; SC: 21 versus 1.8 microgram/ml; SP-A: 9.8 versus 19 microgram/ml; all p < 0.01). Mean concentration of surfactant indices in ELF differed only for SP-A, but for all indices, paired values showed poor agreement on Bland-Altman analysis, highlighting the potential imprecision associated with small volume lung lavage. TA return fluid yielded estimates of surfactant indices which were at least equivalent to NB-BAL in prediction of the severity of lung dysfunction. We conclude that NB-BAL return fluid has more distal origin, but analysis of TA fluid may have equal validity in the estimation of indices of pulmonary surfactant. The results of individual estimates of ELF constituents in a single sample of lavage fluid should be interpreted with caution, even when standardized sampling techniques are employed.

Validity of markers of dilution in small volume lung lavage.

Definitive analysis of solute concentrations in lung lavage fluid involves the use of a marker of dilution to correct for variable recovery of epithelial lining fluid (ELF), but the question of the most appropriate dilutional marker remains unresolved. In lavage fluid collected from infants with lung disease and healthy control subjects, we examined ELF concentration of protein, albumin, sphingomyelin (SM), and IgA secretory component (SC), and critically appraised the relative validity of SC and urea as dilutional markers in the context of lung infection and lung injury. Protein, albumin, and SM were found not to be valid dilutional markers, as their ELF concentration varied significantly between the diseased, recovering, and normal lung. Differences in concentration were noted in both tracheal aspirate samples (TA, 4 x 0.5 ml) and nonbronchoscopic bronchoalveolar lavage fluid (NB-BAL, 3 x 1 ml/kg), but were not uniform (e.g., TA-disease versus control: albumin 2.8 versus 0.68 mg/ml, SM 45 versus 16 microgram/ml, both p < 0.05; NB-BAL-disease versus recovery: protein 8.1 versus 4.8 mg/ml, albumin 2.9 versus 1. 4 mg/ml, both p < 0.05). Overall, SC concentrations in ELF were not different between the diseased and normal lung, but in the NB-BAL samples, significantly higher SC concentration was noted in viral bronchiolitis and pneumonia than in noninfective lung diseases. No clear evidence of additional influx of urea into lavage fluid in association with epithelial disruption was found in the diseased lung. Comparative analysis of SC and urea revealed no difference in TA samples, but in NB-BAL specimens, urea best standardized the lavage concentration of surfactant indices to correspond to the degree of lung dysfunction as indicated by oxygenation index. We conclude that SC and urea, but not protein, albumin, or SM, are valid dilutional markers with which to estimate ELF recovery during small volume lung lavage. Urea appears a more appropriate choice in return fluid derived from the distal tracheobronchial tree, and SC should not be used in the context of lung infection.

A maternally transmitted lethal neonatal progeroid syndrome with prominent genitourinary and gastrointestinal features.

Twin brothers and their maternal uncle with a previously undescribed neonatal progeroid syndrome are presented. In addition to progeroid features, they had pseudo-obstruction of the urinary and gastrointestinal tracts, severe leucocytosis, liver dysfunction, and low complex III and IV in muscle but not in liver. Previously described neonatal progeroid syndromes and syndromes featuring pseudo-obstruction are discussed. The two most likely aetiological mechanisms are an X linked single gene disorder or a mitochondrial disorder. The evidence for these possibilities is presented.

Pulmonary surfactant concentration during transition from high frequency oscillation to conventional mechanical ventilation.

OBJECTIVE: To test the hypothesis that conventional mechanical ventilation (CV) provides a greater stimulus to secretion of pulmonary surfactant than high frequency oscillatory ventilation (HFO). METHODOLOGY: Sequential examination of surfactant indices in lung lavage fluid in a group of six infants with severe lung disease (group 1), ventilated with HFO and then converted back to CV as their lung disease recovered. A similar group of 10 infants (group 2) ventilated conventionally throughout the course of their illness were studied for comparison. In groups 1 and 2, two sequential tracheal aspirate samples were taken, the first once lung disease was noted to be improving, and the second 48-72 h later. Group 1 infants had converted from HFO to CV during this time. RESULTS: A marked increase in concentration of total surfactant phospholipid (PL) and disaturated phosphatidylcholine (DSPC) was seen in group 1 after transition from HFO to CV; the magnitude of this increase was significantly greater than that sequentially observed in group II (total PL: 9.4-fold increase in group 1 vs 1.8-fold in group 2, P = 0.006; DSPC: group 1 6.4-fold increase vs. group 2 1.7-fold, P = 0.02). CONCLUSION: These findings suggest that intermittent lung inflation during CV produces more secretion of surfactant phospholipid than continuous alveolar distension on HFO, and raise the possibility that conservation and additional maturation of surfactant elements may occur when the injured lung is ventilated with HFO.

Surfactant abnormalities in infants with severe viral bronchiolitis.

To determine whether abnormalities of pulmonary surfactant occur in infants with acute viral bronchiolitis, surfactant indices were measured in lung lavage fluid from 12 infants with severe bronchiolitis and eight infants without lung disease. Compared with controls, the bronchiolitis group showed deficiency of surfactant protein A (1.02 v 14.4 micrograms/ml) and disaturated phosphatidylcholine (35 v 1060 micrograms/ml) which resolved as the disease improved. Surfactant functional activity was also impaired (minimum surface tension 22 v 17 mN/m). These findings indicate that surfactant abnormalities occur in bronchiolitis, and may represent one of the pathophysiological mechanisms causing airway obstruction.

Does intramuscular vitamin K1 act as an unintended depot preparation?

OBJECTIVE: To propose a hypothesis that the long duration of effect of intramuscular (i.m.) vitamin K1 in preventing late onset haemorrhagic disease results from a depot effect after i.m. injection. METHODOLOGY: Review of scientific literature relating to the pharmacology of vitamin K, and the aetiology of late onset haemorrhagic disease. RESULTS: A single i.m. dose of vitamin K1 is effective for at least 2 months, whereas the duration of effect of a single oral dose is about 3-4 weeks. The known pharmacological properties of vitamin K1 are seemingly at variance with the long duration of effect of an i.m. dose. Menaquinones (vitamins K2) are absent in the newborn liver, but gradually accumulate after birth. This, together with the low concentrations of vitamin K1 in human breast milk, may explain the peak frequency of late onset haemorrhagic disease at 4-8 weeks. We hypothesize that after i.m. injection, vitamin K1 acts as a depot preparation by forming a viscous mass in muscle tissue which is slowly absorbed over many weeks. This hypothesis is supported by reports indicating significantly higher plasma vitamin K1 levels several weeks after i.m., as compared to oral vitamin K1. CONCLUSIONS: The prolonged efficacy of i.m. vitamin K1, compared to oral preparations may be due to a depot effect. New oral preparations of vitamin K1, despite greatly improved bioavailability, may have a shorter duration of effect than i.m. vitamin K1, and therefore be less effective for long-term prophylaxis.

Late onset haemorrhagic disease in premature infants who received intravenous vitamin K1.

The clinical details are reported of two premature infants who developed late onset haemorrhagic disease after receiving their initial doses of vitamin K1 prophylaxis intravenously. Both reported infants had received two doses of intravenous vitamin K1, 0.1 mg, in the 1st week of life, and a further oral dose, 1.0 mg, at 4 weeks. Bleeding due to vitamin K deficiency occurred on days 74 and 84, respectively. Vitamin K deficiency bleeding is rare in low birthweight infants, probably because it has been routine practice to give such infants intramuscular vitamin K1. One of the reported infants had cytomegalovirus hepatitis, the other did not have liver disease. These findings could be explained if intramuscular vitamin K1 were to have a longer duration of effect than intravenous vitamin K1. This may be because intramuscular vitamin K1 acts as a depot preparation. The findings suggest that intravenous vitamin K1 is less effective than intramuscular for long-term prophylaxis against late onset haemorrhagic disease. Intravenous vitamin K1 should not be used for long-term prophylaxis in the prevention of late onset haemorrhagic disease.

High frequency oscillation in newborn infants with respiratory failure.

OBJECTIVE: To report ventilation strategies, survival and complications in 39 outborn infants treated with high frequency oscillatory ventilation (HFOV). METHODOLOGY: Data were collected prospectively between 1 May 1992 and 31 December 1993 on all infants treated with HFOV who had severe respiratory failure despite optimal conventional ventilation. RESULTS: Twenty-eight out of 39 (72%) survived. Of the 15 infants with birthweights < 1500 g, eight survived. Best survival rates were for infants with pulmonary interstitial emphysema with air leak (4/5) and for infants of birthweight > 1500 g with hyaline membrane disease (8/8), and meconium aspiration syndrome (7/7). Three infants deteriorated while on HFOV and required extracorporeal membrane oxygenation. Complications were: (i) development of pulmonary interstitial emphysema (1); (ii) recurrence of pneumothorax (3); (iii) hypotension (2); and (iv) bronchopulmonary dysplasia (9). One of the eight infants weighing < 1500 g who received HFOV in the first week of life developed periventricular haemorrhage. CONCLUSION: The initial results of HFOV for severe failure were encouraging although a learning curve was encountered with its introduction.

Munchausen syndrome by proxy--a cause of preterm delivery.

OBJECTIVE: To present the first case of Munchausen syndrome by proxy involving self-induced preterm delivery. CLINICAL FEATURES: A 27-year-old Caucasian woman induced antepartum haemorrhage and rupture of membranes with a knitting needle at 26 weeks' gestation, leading to delivery of the infant. This "prenatal child abuse" led to a prolonged intensive care stay, extensive treatment and subsequent bronchopulmonary dysplasia. As the child recovered from the effects of extreme prematurity, he became a victim of fabricated illness and recurrent smothering episodes. INTERVENTION AND OUTCOME: After the diagnosis of Munchausen syndrome by proxy was made, the child was removed from the mother and he has since enjoyed good health. CONCLUSION: Self-induction of antepartum haemorrhage can lead to preterm delivery and may be recognisable by certain clinical parameters. The victim of self-induced preterm delivery, if survival ensues, may be subject to further abuse.

Choanal atresia as a feature of ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome.

We report here a father and daughter with digital abnormalities, nasolacrimal duct obstruction, and variable alopecia. The father had a cleft lip and palate and the daughter had choanal atresia. We propose they both have the EEC syndrome and show the variable expressivity of this disorder. Choanal atresia has not been previously reported in this condition.

Inappropriate use of contrast studies prior to referral of neonatal gastrointestinal anomalies and bowel obstruction.

Ten cases of neonatal gastrointestinal anomalies and bowel obstruction are described, in which contrast studies were carried out prior to transfer. Nine of the 10 infants had bile-stained vomiting, indicating the need for immediate surgical referral. The contrast studies resulted in delayed referral, deferment of appropriate resuscitation, and complications associated with the study. In several cases the wrong type of study, or the wrong contrast medium was used. These 10 infants required urgent surgical referral, not a sophisticated radiological procedure in geographic and surgical isolation.

Successful suprapubic aspiration of urine.

When the bladder of neonates requiring suprapubic aspiration of urine was shown to contain urine on ultrasound scanning, suprapubic aspiration was successful on the first attempt in all cases. Without prior scanning only 36% of first attempts at aspiration were successful.