Perinatal and infant autopsy.

OBJECTIVES: To measure perinatal and infant autopsy rate in Wales over a 10-year period and study factors influencing the decision to perform an autopsy. DESIGN: Retrospective cohort analysis of data from the All Wales Perinatal Survey. METHODS: Autopsy rates were calculated over a 10-year period (1994-2003), and reasons for not performing an autopsy were noted. Two time periods, 1994-1996 and 2001-2003 were compared, to study changing autopsy patterns. RESULTS: Over the 10-year period, there were 4393 perinatal and infant deaths, with data available for 4306 (98%) cases. Consent for autopsy was requested in 89% of cases and granted in 68%. When compared, the 3-year cumulative autopsy rate fell from 67.5% (95% confidence interval (CI) 65% to 69%) in 1994-1996, to 52.7% (CI 49% to 55%) in 2001-2003. The difference in the proportion of autopsies performed between the two time periods was 14.8% (CI 11% to 18%). Parental consent was granted in 76.2% (CI 73% to 78%) of cases in 1994-1996 and 60% (CI 57% to 63%) of cases in 2001-2003. The difference in proportion in consent for autopsy in the two time periods was 16% (CI 12% to 20%). CONCLUSIONS: A decrease in perinatal and infant autopsy rates has been found in Wales over the past 10 years. Parental refusal has been the main cause of this decline.

Improving the quality of perinatal and infant necropsy examinations: a follow up study.

AIM: To compare the quality of perinatal and infant necropsy examinations in 1996 with those performed in 1993. METHODS: Cohort analysis, with data from the All Wales Perinatal Survey, of 1027 deaths (540 in 1993; 487 in 1996) of babies between 20 weeks' gestation and one year of age. The quality of the necropsy was assessed by scoring aspects identified as being part of the investigation. RESULTS: Necropsy was performed in 335 cases (62%) in 1993 and in 320 cases (66%) in 1996. The proportion done in a regional centre increased significantly from 39% (131/335) in 1993 to 76% (243/320) in 1996 (p < 0.0001). The quality of necropsy was above the minimum standard in 54% of cases in 1993 (171/314) compared with 93% in 1996 (289/312) (p < 0.0001). Improvement occurred in all categories. For stillbirths, 35% (46/133) were above the minimum standard in 1993 compared with 90% (104/116) in 1996 (p < 0.0001); for cases not classified as sudden unexpected death in infancy (SUDI), the improvement was from 62% in 1993 (40/65) to 97% in 1996 (73/75) (p < 0.0001); and for SUDI cases, the improvement was from 32% in 1993 (10/31) to 91% in 1996 (21/23) (p < 0.0001). The quality of both non-regional and regional necropsies improved. For non-regional cases, the score was above the minimum standard in 28% (51/183) in 1993 compared with 69% (52/75) in 1996 (p < 0.0001); for regional cases it improved from 92% (120/131) in 1993 to 100% (237/237) in 1996 (p < 0.0001). CONCLUSIONS: The quality of perinatal and infant necropsies improved considerably between 1993 and 1996, reflecting better awareness of the importance of good quality examination and an increase in referrals to paediatric centres.

Perinatal and infant postmortem examinations: how well are we doing?

AIM: To investigate the quality of perinatal and infant necropsies and assess the relation between the quality and value of this investigation in different outcome groups. METHODS: Cohort analysis of 540 deaths during 1993 of babies between 20 weeks' gestation and one year of age born to women usually resident in Wales. Cases were identified from the All Wales Perinatal Survey. Each case was assessed to establish whether the necropsy yielded clinically relevant information. The quality of necropsy was assessed by scoring aspects identified as being part of the necropsy. RESULTS: Necropsy was performed in 335 (62%) cases, and the report was available for assessment in 314 cases. The quality of necropsy was below the minimum standard in 46% (143/314) of cases. The highest quality necropsies were carried out on fetal deaths at 20 to 23 weeks' gestation (12% (10/85) below standard), compared with 65% (87/133) below standard on stillbirths and 68% (21/31) on sudden unexpected infant death. Overall, 42% (131/314) of necropsies were performed in a regional paediatric pathology centre including 88% (76/88) of fetal deaths, 23% (31/133) of stillbirths and 30% (29/96) of infant deaths. The quality score for the necropsy performed in a regional centre failed to achieve the minimum acceptable score in 8% (11/131) of cases compared with 72% (132/182) for those done elsewhere. The cause of death was detected by necropsy in 17% (52/314) of cases. The quality of necropsy was significantly higher when the cause of death was revealed than when nothing new was found. CONCLUSIONS: The overall quality of the perinatal and infant necropsy is poor. This is regrettable as valuable information can be revealed frequently by a good quality necropsy. Adherence to Guidelines for Postmortem Reports recently published by the Royal College of Pathologists should improve the situation.

Maternal listeriosis in pregnancy without fetal or neonatal infection.

Maternal infection with Listeria monocytogenes without fetal or neonatal involvement is relatively rare. Eleven cases arising in England and Wales between 1967 and 1988 are presented.

Influence of antenatal steroids and sex on maturation of the epidermal barrier in the preterm infant.

BACKGROUND: The epidermal barrier is well developed in term infants but defective in the immature infant with important clinical consequences. The development of the barrier shares similarities with production of pulmonary surfactant. Studies in the rat have shown that barrier maturation is accelerated by antenatal steroids, both structurally and functionally. Females have a more mature barrier than males at the same gestational age. These factors have not been studied in the human. AIM: To examine the influence of antenatal steroids and sex on maturation of the epidermal barrier in the preterm infant. SUBJECTS: A total of 137 infants born before 34 weeks gestation, 80 boys and 57 girls, were studied: 87 had been exposed to antenatal steroids, and 50 had not; 99 were studied prospectively, and 38 had been studied previously. METHOD: Barrier function was measured as transepidermal water loss from abdominal skin by evaporimetry. Measurements were made within the first 48 hours and corrected to a standard relative humidity of 50% (TEWL(50)). RESULTS: The relation between TEWL(50) and gestation was exponential with very high levels in the most immature infants. No influence of antenatal steroids or sex could be shown. When infants who were optimally exposed to antenatal steroids were considered alone, no effect could be shown. CONCLUSION: Epidermal maturation in the preterm infant does not appear to be influenced by antenatal steroids or sex, suggesting that the mechanism of maturation differs from that of the rat.

Deformation of the palate in preterm infants.

AIM: To investigate the effect of gestation, postmenstrual age, and orotracheal intubation on palate morphology. METHODS: A prospective study was made of 76 newborn infants of 25 to 41 weeks' gestation. Palate dimensions were measured on plaster models produced from serial palatal impressions. Palate size relative to that of the mouth was assessed using a ratio of palate depth to palate width (Palatal Index). RESULTS: Palate depth and width were related to postmenstrual age and gestation. Palatal Index ranged from 0.15 to 0.57, indicating a wide variation in palate shape, but gestation and postmenstrual age had no effect. Prolonged intubation had a small effect, equivalent to an increase in palatal depth of less than 2 mm at 32 weeks' postmenstrual age. The effect was transient. CONCLUSION: Prolonged orotracheal intubation (> 10 days) leads to a small and temporary increase in palatal depth. However, this is unlikely to account for palatal grooving, which is probably caused by an overgrowth of the lateral palatine ridges.

gamma-Glutamyltransferase in the newborn.

gamma-Glutamyltransferase activity was measured serially in newborn infants. Median activity was 94 units/l, with the 95th centile at 243 units/l. It was unrelated to gestation. Significant increases occurred after treatment with phenobarbitone and with the introduction of oral feeding after parenteral nutrition. It was a poor indicator of total parenteral nutrition (TPN) liver damage.

Percutaneous carbon dioxide excretion in the newborn infant.

Percutaneous carbon dioxide excretion was studied in 42 newborn infants between 25 and 39 weeks gestation, using a closed skin cell attached to the abdomen. The rate of excretion during the first few days of life was inversely related to gestation, increasing from a mean of 31 ml/m2/h at term to 198 ml/m2/h below 30 weeks gestation. Postnatally there was a rapid fall in the rate of excretion in very preterm infants to values about twice those found at term. The rate of excretion was linearly related to the CO2 diffusion gradient, and zero diffusion would be expected when there was no diffusion gradient. It is estimated that up to 15% of resting CO2 excretion occurs through the skin of very preterm infants, and more if the tissue PCO2 is elevated.

The scars of newborn intensive care.

Many techniques used in neonatal intensive care are invasive and the risk of producing skin damage is high. To investigate this, 100 consecutive survivors of neonatal intensive care (gestation 26-42 weeks, median 32) were examined in detail by a single observer at 16-29 months of age, and the scar severity, site and likely cause noted. Scarring was present in all infants although it was usually trivial. The total number of scars was inversely related to gestational age and directly related to the duration of intensive care. Eleven children had cosmetically or functionally significant lesions caused by chest drain insertion, extravasation of intravenous fluid or skin stripping by adhesive tape. To reduce the frequency and severity of skin damage, neonatal staff need to be aware that many routine procedures may lead to long term scarring. In particular, more careful wound closure after chest drain removal is needed.

Numbers of deaths related to intrapartum asphyxia and timing of birth in all Wales perinatal survey, 1993-5.

OBJECTIVES: To investigate the relation between the timing of birth and the occurrence of death related to an intrapartum event. DESIGN: Analysis of 107,206 births to Welsh residents in 1993-5, including 608 cases of stillbirth and 407 of neonatal death identified in the all Wales perinatal survey, the cause of death classified with the clinicopathological system. SUBJECTS: 79 normally formed babies stillborn or who died in the neonatal period, birth weight > 1499 g, for whom cause of death was related to an intrapartum event. MAIN OUTCOME MEASURES: Relative risk of death due to an intrapartum event according to the hour, day, and month of birth. RESULTS: Mortality was higher in babies born between 9.00 pm and 8.59 am than in those born between 9.00 am and 8.59 pm; relative risk (95% confidence interval) 2.18 (1.37 to 3.47). July and August births also had a higher death rate than births in other months; relative risk 1.99 (1.23 to 3.23). Weekened births had a higher death rate but it was not significant. CONCLUSIONS: The excess of deaths at night and during months when annual leave is popular may indicate an overreliance on inexperienced staff at these times. Errors of judgement may also be related to physical and mental fatigue, demanding a more disciplined systematic approach at night. Mistakes may be ameliorated by increasing shiftwork, but shifts should be carefully designed to avoid undue disruption of circardian rhythms. In addition, greater supervision by senior staff may be required at night and during summer months.

Routine examination in the neonatal period.

OBJECTIVE: To assess the value of the second neonatal examination as a medical surveillance procedure. DESIGN: Prospective survey of routine neonatal examinations and the abnormalities identified during 8 March-30 June 1988. SETTING: Maternity unit with an annual birth rate of 5700. SUBJECTS: For first neonatal examination: 1795 babies born in the unit during the 115 day observation period. For second routine examination: 1747 babies (97.3%) discharged from postnatal ward. MAIN OUTCOME MEASURES: Missed abnormalities (present but not previously noted); minor abnormalities (superficial infection or trivial or transient abnormalities not requiring intervention); and important abnormalities (unlikely to have been present at first examination but requiring intervention). RESULTS: An abnormality was detected in 158 (8.8%) infants on first neonatal examination. 1428 (79.6%) babies had a routine second examination, which disclosed 63 previously undetected abnormalities. Of these, seven (11%) would have been present on first examination, 49 (78%) were considered minor, and seven (11%) important--the most consequential being dislocatable hips (four infants). Thus an important finding was detected by only 0.5% of second examinations. CONCLUSIONS: A second thorough examination in the early neonatal period cannot be justified as a screening procedure. A repeat examination of the hips alone in the first week of life is necessary.

Value and quality of perinatal and infant postmortem examinations: cohort analysis of 400 consecutive deaths.

OBJECTIVES: To evaluate the contribution that perinatal and infant necropsy makes to clinical practice and to see how this might be influenced by the quality of the investigation. DESIGN: Cohort analysis, with data from the all Wales perinatal survey, of perinatal and infant deaths during 1993 of babies born to mothers usually resident in Wales. The clinicopathological classification of death based on clinical details was compared with the classification after necropsy. Similarly, cases in which necropsy yielded new information were identified. The quality of the necropsy was assessed by scoring six aspects of the examination. SUBJECTS: 400 consecutive deaths at 20 weeks of gestation to 1 year of age. MAIN OUTCOME MEASURES: Necropsy rate, effect of necropsy on clinicopathological classification, new information disclosed by necropsy, quality of necropsies, and the link between new information and quality of the necropsy. RESULTS: Necropsy was performed in 232 cases (58%). The clinicopathological classification was altered by necropsy in 29 cases (13%). New information was obtained in 60 cases (26%), and in 42 (18%) it disclosed the cause of death. The quality of necropsy was substantially higher when the main cause of death was detected than when nothing new was found. CONCLUSION: Necropsy is underused. Clinicians should be more positive about necropsies and realise how much clinically relevant information can be obtained from a good quality examination.

Differences in risk of mortality under 1 year of age between rural and urban areas: an ecological study.

OBJECTIVE: To investigate differences in risk of categories and causes of death before 1 year of age between rural and urban areas. METHODS: Population-based ecological study using Poisson regression analysis of data from all enumeration districts in Wales. Data included all 243,223 registrable births to women resident in Wales, 809 therapeutic and spontaneous abortions, 1302 stillbirths and 1418 infant deaths occurring between 1993 and 1999. MAIN RESULTS: The relative risk of mortality in rural areas compared with urban areas for all deaths before 1 year of age was 0.89 (95% confidence interval 0.82, 0.98, P=0.02). The risk of mortality in rural areas was significantly lower than in urban areas for all categories of deaths occurring after 7 days of life. The relative risk of death due to infection was significantly lower in rural areas compared with urban areas (P=0.04), with similar results for deaths due to sudden infant death syndrome (P=0.03). After adjusting for social deprivation, there were no significant differences in the risk of death between rural and urban areas. CONCLUSIONS: While there were significant differences in crude risk between rural and urban enumeration districts for some causes and age groups before 1 year, after adjusting for social deprivation, these differences were not significant. The lack of significant interaction between rurality and deprivation indicated that the relationship between social deprivation and death before 1 year of age was not significantly different in rural areas compared with urban areas. Collaborative public health programmes to tackle deprivation are necessary in both rural and urban areas.

Effect of changing the stillbirth definition on evaluation of perinatal mortality rates.

The perinatal mortality rate is widely used as a summary statistic for evaluating the effectiveness of perinatal care. Since October, 1992, it has been a legal requirement in England and Wales to register fetal deaths at 24-27 completed weeks of gestation as stillbirths (in addition to those after 28 weeks), thereby altering the definition of perinatal death. In a cohort analysis of all babies born to women resident in Wales during 1993, we assessed whether the revised definition of perinatal mortality rate more appropriately measures effectiveness of care. There were 36,793 births and 313 perinatal deaths (221 stillbirths, 92 early neonatal deaths). At 24-27 weeks' gestation there were 59 (39%) survivors and 93 deaths (52 stillbirths, 36 neonatal deaths [28 early, eight late], and 5 postneonatal deaths). 119 babies had a birthweight below 500 g; one survived and 24 were perinatal deaths. Of the 36 late neonatal deaths all were attributed to perinatally related events. Increased survival of infants at 24-27 weeks' gestation emphasises the importance of including all these infants in the perinatal mortality rate, but it would be a more useful measure of the effectiveness of perinatal care if it excluded babies below 500 g, and included late neonatal deaths.

PIP: The perinatal mortality rate is widely used as a summary statistic for evaluating the effectiveness of perinatal care. A major drawback with using the perinatal mortality rate in such fashion, however, has been the inclusion of all registered live births, irrespective of gestational age, while stillbirths were registered only after 28 completed weeks; fetal deaths before that gestational age were not registered and thus not included in the perinatal mortality rate. Moreover, at very low gestational ages, the expectation of viability may influence the judgement of whether a fetus is stillborn or is born alive but dies shortly after birth. The World Health Organization has recommended that national perinatal statistics include only fetuses and infants of at least 500g at birth, alive or dead. It has been law in England and Wales since October 1992 to register fetal deaths at 24-27 completed weeks of gestation as stillbirths. This legislation has therefore changed the definition of perinatal death in the UK. In a cohort analysis of all babies born to women resident in Wales during 1993, the authors assessed whether the revised definition of perinatal mortality rate more appropriately measures the effectiveness of care. There were 36,793 births, 221 stillbirths, and 92 early neonatal deaths. At 24-27 weeks' gestation there were 59 survivors, 52 stillbirths, 36 neonatal deaths, and 5 postneonatal deaths. 119 babies had a birthweight below 500g, one who survived and 24 who died perinatally. All 36 late neonatal deaths were attributed to perinatally related events. The increased survival of infants at 24-27 weeks' gestation emphasizes the importance of including all these infants in the perinatal mortality rate, but it would be a more useful measure of the effectiveness of perinatal care if the definition excluded babies below 500g and included late neonatal deaths.

Specific malabsorption of vitamin B12 in Down's syndrome.

A 3 year old girl with Down's syndrome became lethargic and withdrawn, and investigations showed a specific malabsorption of vitamin B12 without proteinuria.

Serum albumin concentrations and oedema in the newborn.

Serum albumin concentration was measured in 195 infants of 25 to 42 weeks' gestation during the neonatal period. Concentrations were significantly lower in preterm infants, rising from a mean of 19 g/l at 26 weeks to 31 g/l at term. There was a 15% increase in albumin concentrations in the first three weeks of life. Oedema in the early and late neonatal period was common in preterm infants but correlated poorly with hypoalbuminaemia. Measurement of serum albumin concentrations in preterm infants either routinely or because of oedema is not clinically useful.

Survival of very low birthweight and very preterm infants in a geographically defined population.

OBJECTIVE: To determine in a geographically defined population 1 year survival of infants with a birthweight of less than 1500 g or gestational age less than 32 weeks, and to establish the effect of postnatal age on predicted survival. DESIGN: Cohort analysis of 72,427 births to Welsh residents in 1993-94. Deaths were identified using the All Wales Perinatal Survey, a population-based surveillance of mortality between 20 weeks of gestation and 1 year of age. MAIN OUTCOME MEASURES: Birthweight- and gestation-specific infant mortality, and the effect of postnatal age, gender, and multiple pregnancy on predicted survival. RESULTS: In normally formed infants 1 year survival at 24-25 weeks gestation was 35%, compared to 75% at 27-28 weeks, and 95% at 30-31 weeks. In infants with a birthweight of 500-699 g 1 year survival was 18% compared to 70% at 800-999 g, and 97% at 1300-1499 g. The chances of survival improved markedly with increasing postanatal age; at 24-25 weeks gestation it was 35% at birth, 50% at 12 h. 66% at 7 days and 78% at 4 weeks. Infant mortality was higher in males, but multiple pregnancy had no effect. CONCLUSIONS: Up-to-date birthweight- and gestation-specific survival rates are essential for predicting the outcome of a newborn infant. The rapid change in the chances of survival with increasing postnatal age emphasises especially the importance of revising the prediction as the infant gets older, particularly during the first few days of life.

Percutaneous respiration in the newborn infant. Effect of gestation and altered ambient oxygen concentration.

Percutaneous respiration was studied in 32 newborn infants between 25 and 41 weeks gestation, using a closed skin cell attached to the abdomen. Gas exchange rates in the first few days of life were 6-11 times faster in infants below 30 weeks gestation than in term infants (mean O2 absorption 25.0 vs. 206.5 ml/m2/h, and CO2 excretion 26.0 vs. 294.6 ml/m2/h), but rates were similar by 3 weeks of age. Increasing the ambient oxygen concentration resulted in a non-linear increase in oxygen absorption, particularly in the most immature infants. Below 30 weeks gestation, O2 absorption increased from a mean of 206.5 ml/m2/h in air, to 357.2 ml/m2/h in 40% oxygen and 573.5 ml/m2/h in 90% oxygen. We estimate that an infant below 30 weeks gestation, nursed naked in 90% oxygen, would obtain up to 20% of resting oxygen requirements percutaneously.

Percutaneous oxygen delivery to the preterm infant.

The feasibility of delivering therapeutically useful amounts of oxygen percutaneously was investigated in 13 preterm infants. Their gestation ranged from 25 to 31 weeks and all were being ventilated for severe respiratory distress. Raising the ambient oxygen concentration resulted in an increase in arterial oxygen tension of 4.5 to 13.8 mm Hg (mean 8.9 mm Hg) as a result of percutaneous oxygen absorption. The change was greatest in the least mature infants and in those with the weakest epidermal barrier. Transdermal oxygen therapy can usefully supplement oxygen delivery to very premature infants with poor pulmonary gas exchange.

Percutaneous respiration in the new-born infant. Effect of ambient oxygen concentration on pulmonary oxygen uptake.

The effect of increasing ambient oxygen concentration on percutaneous oxygen absorption was studied by measuring pulmonary oxygen uptake before and after exposure of the skin to 90% oxygen; assuming the metabolic demands of the infant remain unchanged, the pulmonary oxygen uptake should fall as percutaneous absorption increases. During the first few days of life, in infants between 28 and 30 weeks gestation, there was a significant reduction in the mean pulmonary oxygen uptake of 0.27 ml/kg/min (6.2%) when the trunk and limbs were surrounded by 90% oxygen. The calculated fall in pulmonary uptake if the whole body was surrounded by 90% oxygen would be 8-10%. In contrast, the changes seen in more mature infants (32-39 weeks gestation) and older infants (28-29 weeks gestation and 7-17 days old) were small and not significant. Percutaneous oxygen delivery may usefully contribute to the total oxygen requirements of very preterm infants during the early neonatal period.