Hypoxic ventilatory defence in very preterm infants: attenuation after long term oxygen treatment.

The activity of peripheral chemoreceptors was studied in 19 preterm very low birthweight infants at the postconceptional age of 36 and 40 weeks using the hyperoxic test. The infants were in a healthy condition and did not receive any extra oxygen or medication when tested. The inhalation of pure oxygen caused a decrease in mean (SE) ventilation by 16.1 (2.6)% and 15.1 (2.1)% at the 36th and 40th gestational week respectively. At the 36th gestational week the ventilatory response was significantly slower than at 40 weeks (10.9 (6) and 7.3 (3) sec). Six infants who had been on supplemental oxygen for more than 21 days (from 21 to 56 days) responded with significantly lower response to hyperoxia at the 36th gestational week (-7.9 (3.6)%) than those receiving oxygen treatment for a shorter period of time, 0 to 16 days (-19.9 (3.2)%). The 'low responding' group included three infants who had suffered from chronic lung disease. Those infants showed the lowest hyperoxic response (-4.3 (3.9)%). There was no difference in the response among healthy preterm infants (eight infants) and infants with respiratory distress syndrome. At the 40th gestational week the differences, even though showing the same characteristics, were not statistically significant. No statistically significant relationship was found between the strength of the ventilatory response to oxygen versus gestational, postnatal age, nor the time interval between the termination of supplemental oxygen treatment and the test. No relationship was found between the number of apnoeic/bradycardic spells and the strength of the ventilatory depression caused by hyperoxia. In conclusion we found that the very preterm infants, with the exception of those who received long periods of oxygen treatment, have stronger peripheral chemoreceptor responses than those reported for 2-4 day old full term infants. However, infants who had suffered from chronic lung disease show a depressed hyperoxic response.     

Decreased lung surfactant disaturated phosphatidylcholine in sudden infant death syndrome

The lipid composition of lung surfactant obtained by lung lavage at autopsy in 40 infants dying from the sudden infant death syndrome (SIDS), was compared to that obtained from 12 infants dying from other causes (control group). Analysis of the lipids from the two groups showed no major difference in the proportions of the various phospholipid classes particularly the predominant component, phosphatidylcholine (PC), which was present at 60.7 +/- 0.9% (mean +/- S.E.) of the total phospholipids in the SIDS group and 57.9 +/- 2.9% in the control group. However the proportion of the PC present as the disaturated form (DSPC), was significantly (P less than 0.01) reduced in the SIDS group (65.8 +/- 1.6%) in comparison to the control group (77.4 +/- 3.5%). The proportion of DSPC present in the PC fraction of SIDS infants in the high-risk age range of 1-26 weeks (63.9 +/- 1.9%) was also significantly reduced (P less than 0.01) in comparison to the total control group of infants. For infants older than 26 weeks, significant differences in the proportion of DSPC in PC were not observed between SIDS and control groups. A functional consequence of the observed reduction in the DSPC content of lung surfactant of SIDS infants could be a greater degree of fluidity of the surfactant, particularly at exhalation. Such a biophysical change in surfactant properties could have a profound influence on lung function and be a causative factor in sudden infant death.     

Decreased lung surfactant disaturated phosphatidylcholine in sudden infant death syndrome

The lipid composition of lung surfactant obtained by lung lavage at autopsy in 40 infants dying from the sudden infant death syndrome (SIDS), was compared to that obtained from 12 infants dying from other causes (control group). Analysis of the lipids from the two groups showed no major difference in the proportions of the various phospholipid classes particularly the predominant component, phosphatidylcholine (PC), which was present at 60.7 ± 0.9% (mean ± S.E.) of the total phospholipids in the SIDS group and 57.9 ± 2.9% in the control group. However the proportion of the PC present as the disaturated form (DSPC), was significantly (P < 0.01) reduced in the SIDS group (65.8 ± 1.6%) in comparison to the control group (77.4 ± 3.5%). The proportion of DSPC present in the PC fraction of SIDS infants in the high-risk age range of 1–26 weeks (63.9 ± 1.9%) was also significantly reduced (P < 0.01) in comparison to the total control group of infants. For infants older than 26 weeks, significant differences in the proportion of DSPC in PC were not observed between SIDS and control groups. A functional consequence of the observed reduction in the DSPC content of lung surfactant of SIDS infants could be a greater degree of fluidity of the surfactant, particularly at exhalation. Such a biophysical change in surfactant properties could have a profound influence on lung function and be a causative factor in sudden infant death.     

Sudden infant death syndrome and small airway occlusion: facts and a hypothesis

Respiratory failure is almost certainly the cause of death in the majority of cases of sudden infant death syndrome (SIDS), but the mechanisms leading to it have not been elucidated. SIDS shares many environmental and socioeconomic risk factors with severe forms of bronchiolitis, and the age distribution of incident cases is similar. Present knowledge of lung and airway development during infancy, determinants of peripheral airway patency, changes in lung surface activity in infants with SIDS, and fluid film dynamics in small airways are reviewed. It is hypothesized that many cases of SIDS may be due to a final episode of progressive peripheral bronchial occlusion in infants with preceding critically diminished conductance of the smaller airways.     

Ultrastructure of carotid bodies in sudden infant death syndrome

Recent studies have implicated an abnormality in carotid body structure and function in the pathogenesis of sudden infant death syndrome (SIDS). In the present investigation, the light and electron microscopic findings in carotid bodies from ten victims of SIDS were compared with those in six control infants and five infants dying of congenital heart disease. The cross-sectional area of carotid body chemoreceptor cells and the frequency, distribution, and size of neurosecretory granules were assessed morphometrically. The area of carotid body occupied by chemoreceptor cells (the functional area) was comparable in SIDS victims, control infants, and infants with congenital heart disease. By electron microscopy, the carotid body chief cells from all groups contained numerous electron-dense neurosecretory granules. Distribution, frequency, and size of neurosecretory granules in SIDS victims and control infants did not differ significantly. Morphology of carotid bodies from SIDS victims was found to be normal. The presence of neurosecretory granules in chemoreceptor cells of SIDS victims suggests that the cellular mechanism of neurotransmitter synthesis and storage is not altered.     

Cytological changes in endotracheal aspirates associated with chronic lung disease

Endotracheal aspirates taken serially from mechanically ventilated premature infants born at <28 weeks gestation between March 1992 and August 1993 were studied to determine whether early cytological changes would be a good predictor of lung damage in infants who develop chronic lung disease (CLD). CLD was diagnosed if the infant required supplemental oxygen at 36 weeks corrected gestational age. Fifty-five infants were enrolled in the study, five died and of the 50 infants remaining, 17 (34%) developed CLD. The infants with CLD had a significantly lower gestation (25.5±1.8 (mean±1 SD) versus 26.2±0.9 weeks, p<0.05), significantly more required surfactant (14/17 vs. 16/33, p<0.05) and were ventilated for a significantly longer period (43.3±26.6 vs. 19.3±12.8 days, p<0.0001). Endotracheal aspirate cytology showed that infants with CLD had significantly more degenerated columnar epithelial cells on day 3 (p=0.001), and more neutrophils on day 10 (p=0.007). Though not predictive of CLD, cytological changes consistent with bronchial epithelial and pulmonary damage followed by an inflammatory response were found in the tracheal aspirates of a group of infants clinically diagnosed with CLD.     

Respiratory control in infants at increased risk for sudden infant death syndrome.

There is much debate relating to possible abnormalities in respiratory control mechanisms in infants considered at increased risk for sudden infant death syndrome (SIDS). The P0.1 occlusion technique was used to assess the central respiratory response to hyperoxic hypercapnia during quiet sleep in 21 normal infants, 13 siblings of SIDS victims, and 17 infants with apparent life threatening events. The slope of P0.1 plotted against carbon dioxide concentration increased exponentially with age, independent of body weight in each group. Birth weight has a significant effect on slope with a lower weight predisposing to a lower slope. Siblings as a group had a significantly lower slope at any given age than normal infants, whereas the infants who had had apparent life threatening events were not significantly different from the controls. As intragroup variation in both siblings and control groups greatly exceeded the significant intergroup differences observed, the technique cannot identify individual infants as belonging to one or other group.     

Effect of chronic lung disease on blood pressure levels at follow up

Thirteen preterm infants (median gestational age 28 weeks) who had developed neonatal chronic lung disease (CLD) and 13 gender- and gestational agematched controls (without CLD) were prospectively followed. The infants were seen at monthly intervals for 6 months. At each attendance the infants were examined and their blood pressure (BP) measured using a noninvasive Doppler technique. No infant developed symptoms related to hypertension and there were no significant differences in their BP levels at follow up. Our results suggests significant BP elevation is uncommon following neonatal CLD.     

Motility and arousal in near miss sudden infant death syndrome

Developmental sleep patterns were compared in infants at known risk for "near-miss" sudden infant death syndrome and age-matched normal infants. Near-miss SIDS infants had significant differences suggestive of a temporary developmental delay. They retained rapid eye movement (REM) sleep at neonatal proportions, and stage 2 non-REM sleep appeared later. They also had a significantly increased apnea index. Twenty-four-hour recordings of sleep and respiratory patterns in near-miss SIDS infants from 3 weeks through 6 months of age showed a significant reduction in number of body movements in REM, non-REM, and total sleep time and in percentage of movement time at 3 weeks through 3 months of age. These findings can be used to address the role of arousal threshold in infants at risk for SIDS.     

Dexamethasone and hypertension in preterm infants

The magnitude and duration of the effect of dexamethasone on systolic blood pressure has been examined in 13 very preterm infants (median gestational age 25 weeks). All had chronic lung disease (CLD). To exclude any effect of CLD on blood pressure each infant acted as his or her own control. Systolic blood pressure increased in all infants (P<0.01) and remained elevated for at least 48h following cessation of therapy. The median maximum increase in blood pressure was 24 mm Hg (range 13–49 mmHg) and occurred on day 4 (median, range 2–10) of treatment. One infant developed hypertensive encephalopathy. These results demonstrate the need to monitor infants with CLD throughout steroid therapy and preferably for some days after it has ceased.     

Brainstem auditory evoked responses in very low birthweight infants with chronic lung disease.

Very low birthweight (VLBW) infants who had prolonged oxygen dependence due to chronic respiratory problems, typically neonatal chronic lung disease (CLD), are at high risk of neurodevelopmental impairment. To assess the effect of CLD on neonatal auditory function we studied brainstem auditory evoked response (BAER) in VLBW infants who suffered CLD but no other major perinatal complications or problems. At 37-42 week postconceptional age, the latencies of waves I, III and V in CLD infants were all significantly longer than in normal term infants (all p<0.001). The differences between CLD infants and the term controls were greater for the later waves than for the earlier waves. Abnormally prolonged wave latency (>2.5 SD of the mean measurement) was seen in 7 (21.2%) CLD infants for wave I, suggesting peripheral auditory impairment, 8 (24.2%) for wave III and 14 (42.4%) for wave V. I-V interval in CLD infants was significantly longer than in the term controls (p<0.001). Seven (21.2%) infants had abnormally prolonged I-V interval, suggesting brainstem or central auditory impairment. Of these infants, 2 had both prolonged wave latencies and prolonged I-V interval, suggesting both peripheral and central auditory impairment. Similar abnormalities were found in CLD infants when compared with the BAER in birthweight- and age-matched healthy VLBW infants without CLD. CONCLUSION: Neonatal auditory function is impaired, both peripherally and centrally, at term age in VLBW infants who suffer neonatal CLD.     

Polysomnographic studies of infants who subsequently died of sudden infant death syndrome

The polygraphic findings from 11 future victims of sudden infant death syndrome (SIDS) are reported and compared with those of matched pairs of control infants. The recordings had been done to alleviate parental anxiety about sleep apnea. Four infants had siblings who were victims of SIDS. Two infants were studied 3.5 to 9.5 weeks before their deaths because of an unexplained apparent life-threatening event that had occurred during sleep. For each victim of SIDS, two control infants were selected from the 2,000 infants who had been tested in the same hospitals. They were matched for sex, gestational age, postnatal age, and weight at birth with the SIDS victims. Their polygraphic recordings had been performed within similar conditions. Each record was allocated a random code number and was analyzed without knowledge of the patient's identity by two independent scorers. Most sleep and cardiorespiratory variables studied did not differentiate SIDS victims from control infants. Only four variables significantly characterized the future SIDS victims: the maximal duration of central apneas, the number of sighs followed by a central apnea, the presence of obstructive apneas, and the presence of mixed apneas. Central apneas were longer during all sleep states in the SIDS victims compared with their matched controls, but none exceeded 14 seconds. Sighs immediately followed by an apnea were significantly less frequent in the future SIDS group. Obstructive and mixed sleep apneas were seen in eight of 11 SIDS victims and in only three of 22 control infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prediction of early outcome in resolving chronic lung disease of prematurity after discharge from hospital.

In an attempt to identify those infants with resolving chronic lung disease of prematurity (CLD) at greatest risk of sudden infant death syndrome or acute life threatening event (SIDS/ALTE), or readmission to hospital following discharge, recordings of arterial oxygen saturation were made on 35 infants. Recordings were collected while the infants were breathing room air. Movement artefact was excluded and the data analysed to provide the mean individual arterial oxygen saturation (MSaO2), and the variability of the mean individual oxygen saturation (delta MSaO2). These data were related to clinical outcome recorded over the three months following investigation. A MSaO2 less than 90% on discharge predicted hospital admission within three months with a sensitivity of 1 and a specificity of 0.76, and SIDS/ALTE with a sensitivity of 1 and a specificity of 0.75. A delta MSaO2 greater than 6% predicted SIDS/ALTE with a sensitivity 0.88 and specificity of 1. Infants with resolving chronic lung disease of prematurity who are at risk of increased morbidity and mortality can be assessed by accurate measurement of mean arterial saturation.     

Surfactant abnormality and the sudden infant death syndrome--a primary or secondary phenomenon?

A prospective study of 46 infant deaths occurring between 3 and 100 weeks of age was performed and comprised a structured necropsy followed by collection of lung washings for surfactant phospholipid analysis and samples for microbiological examination. Of the 46 infants studied, 23 died from sudden infant death syndrome (SIDS) alone; SIDS was the cause of death in a further 12 but there were additional clinical or pathological findings insufficient in themselves to account for the death (''SIDS-plus''). In 11 there were other causes of death (''non-SIDS''). The lung washings from infants dying from SIDS had significantly lower concentrations of phosphatidylcholine and a significantly lower palmitate content in the phosphatidylcholine. There was no association between surfactant phospholipid abnormality and the presence of recognised pathogens, histological evidence of pulmonary inflammation, aspiration of stomach contents, age at death, sex, and death-postmortem interval. There were, however, lower concentrations of phosphatidylcholine and phosphatidylcholine palmitate content in infants colonised by organisms with reported phospholipase A2 activity.     

Home monitoring for central apnoea.

Between July 1978 and December 1981, 64 infants thought to be at increased risk from sudden infant death syndrome (SIDS) were monitored at home for central apnoea. Twenty four of the infants had had a ''near miss'' episode at age, median (range), 6 (1 to 33) weeks, and of these infants 22 had had 335 alarms for apnoea by age 6 months. Stimulation by shaking was carried out on 38 occasions and bag and mask resuscitation on one. The remaining 40 infants were siblings of SIDS victims and of these, 35 were monitored from age 1 week (usually after discharge home). Thirty four of the SIDS siblings had had 573 alarms for apnoea by age 6 months: stimulation by shaking was carried out on 32 occasions and bag and mask resuscitation on one. The duration of home monitoring was, median (range), 34 (8 to 87) weeks for ''near miss'' infants and 45 (12 to 70) weeks for SIDS siblings. All infants survived. As part of an over all support system monitors were accepted and greatly appreciated by most parents, especially those with previous experience of SIDS. Home monitoring was practicable but the commitment in time and expertise was great and objective benefits to the infant remain unproved.     

Obstructive sleep apnea in infants: relation to family history of sudden infant death syndrome, apparent life-threatening events, and obstructive sleep apnea

OBJECTIVES: Familial aggregation of obstructive sleep apnea (OSA) has been shown to be associated with sudden infant death syndrome (SIDS) and apparent life-threatening events (ALTE) in infants. We wanted to determine the incidence of OSA in infants with siblings with ALTE and SIDS referred to our sleep clinic and to ascertain whether OSA was more common in infants who have family histories of SIDS, ALTE, and OSA. STUDY DESIGN: We studied 125 infants (mean age, 11.5 +/- 0.6 weeks) who were separated into 2 groups on the basis of their family history; polysomnographic studies were performed on each infant. RESULTS: Twenty infants had a multiple family history of SIDS, ALTE, or OSA (group 1), whereas the other 105 infants (group 2) had only one case of SIDS or ALTE within the family and no known history of OSA. We found that 19 of 20 infants in group 1 had OSA, whereas only 31 of 105 infants in group 2 had OSA (chi-squared analysis, P <.05). The OSA recorded was more frequent in infants of group 1 than in those of group 2. Follow-up studies in some infants with OSA demonstrated a progressive decrease in OSA, which resolved between 6 and 12 months of age. CONCLUSION: We conclude that infants of families with multiple histories of SIDS, ALTE, and OSA are more likely to have OSA than infants of families with only one case of SIDS or ALTE.     

Chronic lung disease of prematurity and respiratory outcome at eight years of age

AIM: The study aimed to determine the respiratory outcome of children who had chronic lung disease of prematurity (CLD) compared with a preterm control group of children at school age. METHODS: Fifty-two preterm infants with CLD born between 26 and 33 weeks gestation were assessed regarding respiratory illness with 47 having lung function testing. Information regarding respiratory illness was obtained from 52 children in the birthweight-matched control group of whom 45 had lung function testing. The results were compared between the CLD and control groups. RESULTS: There was no difference in respiratory symptomatology between CLD groups and control preterm infants. On lung function testing, a significantly lower mean forced expiratory flow at 25-75% of vital capacity was identified compared with the preterm controls (P=0.024). This significant difference did not persist after bronchodilator therapy. There was no evidence of increased air trapping or bronchial hyper-reactivity in the CLD children compared with the controls. CONCLUSION: Lung function in CLD children is largely normal in comparison with preterm controls, apart from some evidence of reversible small airway obstruction. Respiratory symptomatology is not increased in chronic disease children in comparison with control preterm children.     

Postnatal depression and SIDS: A prospective study

Abstract This study was carried out in response to reports from nurses to a post-neonatal mortality review committee that a number of mothers of infants dying from sudden infant death syndrome (SIDS) appeared to be depressed before the child's death. The New Zealand Cot Death Study was a 3 year multicentre case-control study for SIDS. There were 485 SIDS cases in the post-neonatal age group in the study regions, and these were compared with 1800 control infants. Infants of mothers with either a self-reported use of medication for psychiatric disorders, a history of hospitalization for psychiatric illness or a family history of postnatal depression had a significantly increased risk of SIDS compared with infants of mothers who were either not using medication (odds ratio (OR) = 1.45; 95% confidence interval (Cl) = 1.03, 2.04) or were without a history of hospitalization for psychiatric illness (OR = 1.80; 95% Cl = 1.03, 3.11) or a family history of postnatal depression (OR = 1.61; 95% Cl = 1.06, 2.43). All mothers of infants born in the study areas over a 1 year period were eligible to complete a questionnaire measuring maternal depression when the infant was 4 weeks of age. Thirty-three infants subsequently died from SIDS, and they were compared with 174 controls. Fifteen (45.5%) of the mothers of cases were depressed, compared with 28 (16.1%) of the mothers of controls. This prospective study found that the infants of those mothers that were depressed were more likely to die from SIDS than those of the non-depressed mothers (OR = 4.35; 95% Cl = 1.82, 10.37) and postnatal depression as a risk factor for SIDS was still significant after controlling for possible confounding variables (OR = 3.37; 95% Cl = 1.24, 9.12). We conclude that postnatal depression is a risk factor for SIDS.     

Medial Smooth Muscle Thickness in Small Pulmonary Arteries in Sudden Infant Death Syndrome Revisited

Increased relative medial thickness (RMT) of smooth muscle in small pulmonary arteries, peripheral extension of smooth muscle into the alveolar wall arteries, and right ventricular hypertrophy (RVH), in response to purported prolonged hypoxia, have been reported in sudden infant death syndrome (SIDS). Prone sleep position, an important risk factor for SIDS, predisposes infants to hypoxia from airway obstruction or rebreathing. Since publication of the earlier pulmonary artery studies, the SIDS definition has been expanded, and sudden infant death investigational protocols have been implemented. Our aims in this study were to (1) compare RMT in preacinar arteries (PA), intra-acinar arteries accompanying small airways (SIA), and alveolar wall arteries (AW) in SIDS infants and controls; (2) correlate RMT with postmortem variables; (3) determine if peripheral extension occurred more often in SIDS infants than in controls; and (4) determine if RVH occurred in SIDS. Movat-stained sections from standardized tissue blocks taken prospectively from the apex of the right upper lobe from 88 SIDS cases and 17 controls were evaluated using a computer-assisted digitizing system with images obtained from a microscope with an attached video camera. When adjusted for age, the RMT values for the SIA arteries were significantly greater in controls, while the PA and AW arteries were not statistically different between the SIDS cases and controls. Peripheral medial smooth muscle extension did not differ between the groups, and RVH was not seen in SIDS cases. Given the recent identification of brain stem abnormalities interfering with protective cardiorespiratory responses against acute life-threatening hypoxia perhaps precipitated by prone sleeping, our data suggest that SIDS is an acute event not preceded by recurrent or prolonged apnea and hypoxia.