Search

This report describes six cases of achondroplasia, four of whom died unexpectedly in early childhood. Clinical details and pathological findings are reported. Unexpected death seems to be a feature of children with achondroplasia, and appears to be related to brain-stem lesions secondary to deformities of the foramen magnum and posterior fossa.

Measurement of pressure-volume relations is a commonly used technique to elucidate small intestinal stiffness. There is a lack of data on the relation between stiffness and history-dependent mechanical properties of the gastrointestinal tract. We aimed to distinguish between passive properties of the tissue that depend on the time-history of load (viscoelastic effects) versus those that depend on the maximum previous load (strain softening effects). Ten repeated pressure-volume relations were measured at each peak pressure level in six isolated, passive guinea-pig jejuni in vitro during balloon inflation and deflation cycles. With inflation to a new higher peak pressure (ranging from 3 to 15 mm Hg), the pressure-volume relation became less stiff, particularly in the low pressure range, without a significant change in unloaded jejunal volume. We computed the jejunal normalized volume change as a function of the integrated volume-time history and maximum volume. Analysis of covariance revealed significant dependence of the normalized volume change on the volume-time history (P0.001) and the maximum volume history (P0.001). Multiple linear regression analysis showed that approximately 90% of the history dependence could be attributed to the maximum volume. Most softening (loss of stiffness) happens in the low pressure range of the curve (0-3 mm Hg). We adopted the Johnson and Beatty strain softening theory and computed the volume amplification factor. This factor was shown to be a linear function of the normalized peak volume (r20.999). Since strain softening effects were significantly greater than viscoelastic effects, we conclude that history-dependent changes in jejunal stiffness are more likely to involve alterations to elastic rather than viscous structures in the tissue. These effects must be taken into account when performing balloon distension studies in the gastrointestinal tract for studying physiological and pathophysiological problems in which loading conditions are altered, e.g., mechanoreceptor studies in normal intestine and in acute and chronic obstruction, in order to have an accurate description of the biomechanics.

Overstretching the intact ventricle increases global compliance as a function of maximum previously experienced load and may have an important role in the diseased heart, but the corresponding changes in local myocardial mechanics and structure are unknown. Therefore, we measured two-dimensional strain on the left ventricular (LV) epicardium in isolated arrested rat hearts sequentially inflated to increasing cavity pressures of 10, 30, and 120 mmHg. Strains at matched LV pressures increased significantly (P < 0.002) as the maximum pressure previously experienced by the LV (Pmax) increased. Compared with Pmax = 10 mmHg, relative increases in fiber strain for Pmax = 30 and 120 mmHg (100 and 149%, respectively) were significantly greater (P < 0.001) than the corresponding increases in cross-fiber (51 and 78%, respectively) and fiber shear (57 and 86%, respectively) strains. Using an optimized prolate spheroidal finite-element model of the rat LV that reliably reproduced experimental strains, we estimated progressive decreases in epicardial biaxial wall stiffness up to 87% with increasing Pmax that were not different in the fiber and cross-fiber directions. Thus, although passive ventricular overloading causes direction-dependent increases in epicardial strain, these changes are the consequence of local myocardial softening that is actually independent of direction.

Some assume that, when there are 2 or 3 unexpected and unexplained infant deaths in a family, they are likelier to be unnatural than natural. The chance of a second infant death being natural or unnatural was examined inthe context of the Care of Next Infant (CONI) program in the United Kingdom, which supports parents who previously had an unexplained infant death. The study group included 6373 infants from 5229 families who completed the CONI program. Approximately one fifth of infants were siblings of an earlier CONI infant. The previous death and the CONI death were assessed by a family interview, an autopsy review, and a case discussion. The 57 CONI infants who died within the first year of life represent an incidence of 8.9 per 1000. Nine of these deaths were inevitable, whereas 48 were unexpected. Two families lost 2 children each. Forty of the 46 first CONI deaths were natural. Six were classified as probably homicides, 5 of which were committed by 1 or both parents. Two families probably had covert double homicides. The odds ratio that 2 unexpected deaths were natural rather than unnatural was 6.7 (95% confidence interval [CI], 2.8-19.4), Eighteen families had 2 sudden infant death syndrome (SIDS) deaths; the relative risk of SIDS recurring was 5.9 (95% CI, 4.1-8.1). The ratio of the rate of natural sudden unexpected infant deaths among CONI infants to that in the general population was at least 5.71 (95% CI, 4.1-7.7). The investigators conclude that, in most cases, a second or third sudden unexpected infant death within a family is the result of natural causes.

Alteration of hemodynamic preload leads to ventricular growth and remodeling, but the specific diastolic mechanical factors, such as myocardial stress or strain, that regulate the hypertrophic response remain unclear. To assess the relative importance of these factors in a model of volume-overload hypertrophy, we measured passive pressure-strain relationships by using ultrasonic crystals in the left ventricle (LV) midwall of rats at 1, 2, 4, and 6 wk after an arteriovenous fistula (AVF). Compared with baseline, mean strain in the muscle fiber direction (Eff) at an end-diastolic (ED) pressure corresponding to the acute elevation in hemodynamic load with AVF increased by 96% from 0.056 +/- 0.028 to 0.110 +/- 0.044 (P < 0.05). Eff returned to normal levels after 6 wk of remodeling (0.045 +/- 0.029). Fiber stress at ED pressure, computed from an optimized prolate spheroidal finite-element model for each group, increased by 82% in the acute response, rose to 5.8 times normal level at 1 wk, and remained substantially elevated (5.2 times) at 6 wk. Concurrently, stiffness in both fiber and cross-fiber directions was increased in all groups and reached a maximum of 10 times normal values by 6 wk. Collagen area fraction, as measured in picrosirius-stained sections of the LV free wall, was not different between 6 wk and control. Thus we conclude that ED strain, rather than stress, is normalized during volume hypertrophy through changes in ventricular geometry and wall stiffness that appear unrelated to changes in collagen content.

We investigated whether strain softening (or the Mullins effect) may explain the reduced left ventricular stiffness previously associated with the strain-history-dependent preconditioning phenomenon. Passive pressure–volume relations were measured in the isolated, arrested rat heart during LV balloon inflation and deflation cycles. With inflation to a new higher maximum pressure, the pressure–volume relation became less stiff, particularly in the low (diastolic) pressure range, without a significant change in unloaded ventricular volume. In five different loading protocols in which the maximum passive cycle pressure ranged from 10 to 120 mmHg, we measured increases at 10 mmHg in LV volume up to 350 percent of unloaded volume that depended significantly on the history (p < 0.05) and magnitude (p < 0.01) of maximum previous pressure. Although a quasi-linear viscoelastic model based on the pressure-relaxation response could produce a nonlinear pressure–volume relation with hysteresis, it was unable to show any significant change in ventricular stiffness with new maximum pressure. We incorporated a strain softening theory proposed by Johnson and Beatty (1992) into the model by modifying the elastic response with a volume-amplification factor that depended on the maximum previous pressure. This model more accurately reproduced the experimentally observed behavior. Thus, the preconditioning behavior of the myocardium is better explained by strain softening rather than viscoelasticity and may be due to damage to elastic components, rather than the effects of viscous tissue components.

The conclusions of confidential inquiries into 115 registered unexpected infant deaths over a period of nine years were reviewed. Deaths were classified based on the total information available into group A: poor prognosis (n = 7), group B: treatable disease (n = 45), group C: minor disease (n = 32), group D: no disease (n = 19), group E: probably accidental (n = 4), and group F: probably filicide (n = 8). Less than 20% of deaths corresponded to the classic definition of sudden infant death syndrome (SIDS). Babies who died during the course of potentially treatable disease had more adverse family and social factors: the parents were less likely to be owner occupiers, or own a car or telephone, their mothers were more likely to be young, to smoke, and to present late in pregnancy. Babies who died of minor disease tended to come from similar backgrounds, their families had greater levels of stress and the deaths appeared to be due to more than one factor. Babies who died with no terminal disease were younger, and more likely to be boys. Their families appeared to be demographically similar to those of a control group and to the general population.

Information on whether mothers intended to breast feed and whether they actually did so one month after delivery has been recorded for all mothers in Sheffield during the last 15 years, and changes in the last 10 years have been reported. There was a steady increase in the percentage of mothers intending to breast feed and in those who did so in the 1970s. From 1984-8, however, there has been a rapid and progressive decline, despite an increase in mean maternal age and a reduction in the number of non-white births. The decline in the percentage of mothers who intend to breast feed has been greatest among those whose education did not extend beyond the age of 18, and among Asian mothers.

Editor—Green's article is obviously intended to stir up the cot death establishment.1 When cot death was introduced as a registerable cause of death, largely under the influence of forensic pathologists Bernard Knight of Cardiff and Francis Camps of London, some of us working in paediatric pathology were not in favour of this as we knew that it had many different causes. We have known from the outset that a proportion of the deaths were technically filicide. In the early 1980s, when we publicly gave the figure of 10%, our findings were fiercely contested, but they were confirmed recently.2 The recent studies by Meadows and Southall et al showing parents deliberately and calculatingly harming their infants apply to only a small proportion of the group of cot deaths that could be classified as infanticide.3,4 In our experience of hundreds of confidential inquiries into sudden unexpected deaths the most usual scenario for filicide is for the baby to have been suffocated by an exhausted parent (usually the mother) while trying to quieten his or her crying. These parents usually barely knew what they were doing and did not intend or want to kill their child. We need to prevent these deaths, not victimise the parents. Green's advice to “think dirty” needs to be considered against our experience with the care of next infant (CONI) programme. This programme, funded by the Foundation for the Study of Infant Deaths, provides support for families with children born after a cot death. Of 5000 babies from 4182 families in the programme, 44 died (8.8 per 1000 live births), 35 unexpectedly.5 After confidential inquiries 20 were considered to be natural deaths, of which 12 were classified as inevitable because of congenital anomaly or specific diseases and eight as unexplained because there was minimal or no disease. Fourteen were classified as non-natural deaths, including four attributed to overlaying. Ten deaths were not fully investigated (in seven cases the family declined investigation, in two cases no histology was done, and in the last the mother could not be traced). Thus at least 20 of the second deaths in these families were due to natural causes. We found that before the death that led to enrolment the 4182 families had had 6406 infants, of whom 112 died (17.5 per 1000 live births). The difference between the earlier mortality and that on the programme cannot be explained simply by falling infant mortality over the period. What is needed are deeper non-critical confidential inquiries into all unexpected deaths that include interested paediatric pathologists and are followed by systematic support. We do not need to create a pool of parents to which a label of unproved homicide is publicly attached.

The reported association of cot death and sleeping prone could be due to rebreathing of expired gases. A mechanical model simulating the respiratory system of an infant, exhaling warm humidified air with an end tidal carbon dioxide of 5%, has been used to investigate this. Some commonly used bedding materials caused an accumulation of carbon dioxide of 7% to over 10% with the model lying face down. This phenomenon persisted even with the head inclined at 45 degrees, but only on very soft materials, and could be a cause of cot death in a baby unresponsive to asphyxial blood gas changes. A coir fibre mattress allowed complete dispersal of exhalate as did a rubber sheet between any mattress and the covering sheet.

A detailed pathological and psychosocial study was made of all postperinatal (8 days-2 years) deaths in Sheffield during a 2-year period. The cause of death was classified from the point of view of possible prevention. Of the total of 65 deaths, 35 were unpreventable after the perinatal period, but 9 might have been preventable before birth. Of the 30 other deaths, 20 had evidence of possible treatable disease, and for the majority of these adverse social factors could be identified. Proved non-accidental injury occurred in 2 children and in 3 others there was a high degree of suspicion of 'gentle battering'. Only in 4 children was death unexplained and this apparently represents the local true unexplained cot death rate of 0.16/1000 births.

At least a quarter of the babies dying as unexpected home 'cot deaths' do so from recognizable diseases. A study of the background of such children, compared with age and admission controls, suggests that the disease symptomatology in this group of children differs in no way from children who are successfully treated. The factors leading to the death of these children appear to lie in the general lack of ability of some parents to recognize the importance of symptoms, their negative attitude and inability to avail themselves of health services, and the amount of drive and persistence required to obtain general medical practice services in some areas. There is also the failure of some practitioners to recognize severely ill children.

A randomised control trial was carried out on support measures given to parents with a subsequent child after previously suffering a cot death. Apnoea monitors were used in one group and weighing scales in the other. General support measures given to both groups included the keeping of symptom charts and weekly visits by health visitors. Many alarms occurred which were presumed to be false. Eleven per cent fewer symptoms were reported by parents of children on monitors than parents of children being weighed daily. Both systems were acceptable and gave parents confidence. Sixty per cent of parents were reluctant to give up using the monitor compared with 26% of parents using scales. Virtually all parents commented on the great value of the weekly home visit of the health visitor and the symptom diary.

A quantitative morphological assessment was carried out of the cellularity and staining properties of the cells of the layers of the human cerebellar cortex, both in the normal child and in 41 children suffering from a series of disorders including mental retardation. A computerized image analyser and highly standardized procedures were used. All of the cases of mental retardation and some cases with congenital cardiac anomalies showed abnormal cell concentrations and staining properties. 3 cases of 'cot death' also showed abnormal results. These findings are presented as a new measurable aspect of brain disease, and as a indication for further study.

Histological sections of the common carotid arteries from 259 children who were stillborn or died under 16 years of age were examined for intimal thickening, lamellar irregularities and ruptures, foam cells, and fat. Lesions were present at birth in approximately half the children examined, and the incidence increased rapidly in the first two months after birth. All the children had the early features of the prodroma of atheroma by 8 months of age. Compared with the findings of previous studies of the coronary arteries and aorta the histological findings appeared in the carotid arteries at an earlier age. The prevalence of intimal lesions in infant cot deaths, chronic diseases, and congenital heart disease was compared with that in all other children in the study. There was no difference in the cot death group, but in children under 2 years in both the chronic disease and heart deformity group there was a lower incidence of intimal thickening and visible fat.

The presence of fat-laden cells in the cerebrospinal fluid is usually associated with a fatty change found particularly in the area of the tapetum in the postnatal infant. In a series of 307 child deaths the presence of fatty change in this area of the brain was age-related, decreased with age, and was rarely present over the age of 4 years. It was particularly common in stillborns and in children dying with respiratory distress, but was rare in children dying from acute surgical conditions or from acute infections. It was found in one-half of a series of 41 infants found unexpectedly dead and in whom no adequate cause of death was found. The most likely cause of this fatty change is thought to be chronic hypoxia.

SummaryThe pathological significance of giant cells, inspissitated bile plugs and hepatic fibrosis in the liver of infants is critically reviewed. Evidence is presented suggesting that a wide variety of pathological change in the paediatric liver results from the interaction of the effects of growth, metabolic maturity, genetic metabolic variability and infection. Understanding of the bile retention syndromes might increase if the diagnosis of ‘Neonatal Hepatitis’ and ‘biliary atresia’ as finite conditions, were to cease and their pathogenesis considered in such a multifactorial way.

Families with congenital heart deformities appear to have more difficulties and stress than those with other deformities. Some problems are intrinsic to the deformity but others are largely related to communication difficulties between the groups doing home support and those in supraregional centres.

A comparison was made of pillows of various designs and their effects on the flow of air through the respiratory tract of six children who had been found dead in their cots. The effects of alterations in posture and of soaking the pillow with milk were also studied. There was a wide variation in the obstruction to air flow in pillows of different design. A firm pillow which allows air and fluid to pass through it is best, and is probably superior to a mattress covered with a mackintosh and a sheet. External obstruction to respiration could be a contributory factor in some cases of cot death.

172 liver samples from infants were analysed chemically for iron concentration, and histochemically for the presence of iron staining. A closer correlation was found between the amount of iron estimated chemically, and the presence of diffuse cytoplasmic staining than with the presence of granular staining. At levels of less than 5 mg/100 gm there was neither granular nor cytoplasmic staining present. Cytoplasmic staining was found in all sections from livers with an iron concentration of more than 30 mg/100 gm. Granular staining was not always seen above a level of 30 mg/100 gm, and some sections from livers with iron concentrations as high as 41 and 58 mg/100 gm, showed only cytoplasmic staining.

A random sample of 500 infant thyroids in which post-mortem changes were, as far as possible, eliminated was studied histologically. In the great majority of neonatal thyroids there are distinct changes which suggest the occurrence of an acute `perinatal thyroid discharge' probably due to over stimulation, and which are confined to the immediate perinatal period. These changes are characterized by (i) reduction and loss of colloid (often complete), (ii) vacuolation and detachment of cells, (iii) irregular and pyknotic nuclei, and (iv) the presence of nuclear knots. The thyroid changes are probably physiological and labour-related. The only clinical symptom found to be related to neonatal thyroid discharge was sclerema neonatorum, when there appeared to be an absence of thyroid reaction.

A study of 250 post-perinatal deaths in Sheffield during the past 8 years has shown an increased rate of unexpected infant death. This increase appears to be mainly caused by deaths in children with minor disease in families where the father is either absent or unemployed. The number of children who die during the course of more serious disease continues to fall. The number of infant deaths from other causes is unchanged.

A quantitative study was carried out of the fat cells of the hilar pannicle of the adrenal in 150 infants comprising 60 hospital deaths, 2 accidental deaths, and 88 cot deaths. The cells were rated in categories of fat vacuolation. For a period of up to 8 weeks after birth there is an apparent depletion in the number and size of overt fat vacuoles in the cell and from this time on there is a progressive change to monolocular fat cells. The postnatal discharge of fat from the cell in the pannicle seems to be reduced in some children presenting as unexpectec death in infancy.

A girl aged 1 year died of acute haemorrhagic pancreatitis while taking sodium valproate. Necropsy showed widespread vascular disease that may have contributed to the onset of pancreatitis. Previous reports of pancreatitis in children receiving valproic acid are reviewed and although the association is rare, a causal relation between pancreatitis and valproic acid seems to have been established.

The birth rates for all neural tube defects and the mortality rates from spina bifida and encephalocele have been obtained for Sheffield children by examining the congenital anomalies register and death certificates during the period from 1963-1978. The introduction of atenatal alpha foetoprotein screening of all pregnant women in 1977 is associated in time with a sharp fall in the birth rate of neural tube defects. The mortality rate for spina bifida with encephalocele rose gradually from 1967 to 1976, apparently unaffected by the introduction of clinical selection prior to surgery in 1971. The antenatal screening of previously affected families (since 1973) did not affect the mortality rate, but screening the total pregnant population since 1977 has been associated with a sharp reduction in the mortality rate. The mortality rate curve for spina bifida with encephalocele is markedly different from the birth rate curve which makes the common practice of inferring birth rates from mortality rates invalid. There was a gradual increase from 1967 to 1978 in the proportion of children born with spina bifida in any given year who died before their second birthday. This increase appears to have been uninfluenced by the introduction of selection or antenatal screening. The changes in mortality rate and survival may be as much due to unknown factors as to changes in medical management.

A diet which is marginally deficient in the vitamin biotin may cause sudden unexpected death of young broiler chickens when they are exposed to stress. Chickens affected with this disorder have low levels of biotin in their livers. In conditions of biotin insufficiency, we postulate that a similar disorder, triggered by mild stress, may occur in the human infant. We have now used a radiochemical technique to measure the biotin content of 204 livers obtained from infants at autopsy. The levels of biotin in the livers of infants who had died of sudden infant death syndrom (SIDS; cot death) were significantly lower than those in livers of infants of similar age, who had died of explicable causes. These findings support an association of biotin with SIDS.