Perinatal and postneonatal mortality among Indigenous and non-Indigenous infants born in Western Australia, 1980-1998.

OBJECTIVE: To describe cause-specific perinatal and postneonatal mortality for Indigenous and non-Indigenous infants using a new classification system. DESIGN: Total population retrospective cohort study. PARTICIPANTS AND SETTING: All registered births in Western Australia of birthweight greater than 399 g from 1980 to 1998, inclusive. MAIN OUTCOME MEASURES: Rates and time trends for all births 1980-1998, and cause-specific rates for births 1980-1993 of fetal, neonatal and postneonatal mortality among Indigenous and non-indigenous infants, using a classification system designed for use in perinatal, postneonatal and childhood deaths. RESULTS: For Indigenous infants born 1980-1998, the mortality rate before the first birthday was 2.7 times (95% CI, 2.5-2.9 times) that for non-Indigenous infants. Indigenous infants born 1980-1993 had a higher mortality rate in all cause-of-death categories. The highest relative risk was for deaths attributable to infection (8.1; 95% CI, 6.5-10.0) which occurred primarily in the postneonatal period; the source of the infection was less likely to be identified in Indigenous deaths. From 1980-1998, the rate of neonatal deaths decreased at a greater rate for Indigenous than for non-Indigenous infants. However, while stillbirth and sudden infant death syndrome rates for non-Indigenous births fell, they remained static for Indigenous births. CONCLUSIONS: The new classification system, which considers the underlying rather than immediate cause of death, enables investigation of the causes of all deaths, from stillbirths to childhood. This system has highlighted the comparative importance of infection as a cause of death for Indigenous infants, particularly in the postneonatal period.

Why is the placenta being ignored?

The relationship between the frequency of published recommended indications for placental pathological examination and the frequency of requests for such examination in a population-based study of term newborn encephalopathy was examined. Only 11.2% of placentas among 276 case infants and 0.7% of placentas among 564 term control infants were examined. Using the criteria set out in a consensus statement by the American College of Pathologists, all 276 cases fulfilled multiple maternal, fetal and placental indications for placental examination. Furthermore 43.3% of control infants fulfilled at least one criterion. Of the 25 case placentas that underwent pathological review, 16 were reported as having no diagnostic abnormality Six cases (24%) showed clinically important findings: four had evidence of infection, one had multiple chorangiomata and one had thrombosis and rupture of the umbilical vein. Of the three remaining placentas, one showed funisitis, one showed minor lymphohistiocytic villitis and one was from monochorionic twins. To our knowledge there are no agreed Australian guidelines for when a placenta should be submitted for pathological examination. We suggest that until guidelines based on properly designed studies are developed it may be appropriate to store all placentas for at least 72 hours. If the infant develops neurological symptoms or requires unexpected admission to a neonatal intensive care unit then placental examination may reveal important aetiological diagnostic and prognostic information.

Support for women/families after perinatal death.

BACKGROUND: Provision of an empathetic caring environment, and strategies to enable the mother and family to accept the reality of perinatal death, are now part of standard nursing and social support in most of the developed world. OBJECTIVES: The objective of this review was to assess the effects of the provision of any form of medical, nursing, social or psychological support and/or counselling to mothers and families after perinatal death. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register, the Cochrane Controlled Trials Register, Medline (1966 to 1998) and reference lists of articles. SELECTION CRITERIA: Randomised trials of any form of general support aimed at encouraging acceptance of loss, specific bereavement counselling, or specialised psychological support/counselling including psychotherapy for women and families experiencing perinatal death. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed eligibility of trials. MAIN RESULTS: No trials were included. REVIEWER'S CONCLUSIONS: No information is available from randomised trials to indicate whether there is or is not a benefit from providing specific psychological support or counselling after perinatal death.

Intrauterine infection and spontaneous midgestation abortion: is the spectrum of microorganisms similar to that in preterm labor?

OBJECTIVE: To determine whether microorganisms associated with intrauterine infection and preterm labor play a contributing role in midgestation abortion. METHODS: A 4 year retrospective review of spontaneous midgestation abortions for which autopsy and microbiological cultures of placental and fetal tissue were performed was conducted for a tertiary obstetrics hospital, which included a regional referral service for perinatal and fetal pathology. One hundred twenty-nine spontaneously delivered, nonmacerated, midgestation fetuses or stillbirths (of between 16 and 26 weeks' gestation) and placentas were examined and cultured for aerobic and anaerobic bacteria, yeasts, and genital mycoplasmas. RESULTS: Microorganisms were recovered in 85 (66%) cases (57% placentas, 49% fetuses). Among the culture positive cases, 81% had histological chorioamnionitis, 28% fetal pneumonitis, 38% clinical signs of infection, and 62% ruptured membranes at the time of miscarriage. These differed significantly from culture-negative cases (44%, 5%, 13%, and 34%, respectively). Group B streptococcus (GBS) was the most significant pathogen, recovered in 21 cases, 13 as the sole isolate, 94% with chorioamnionitis, and 47% in women with intact membranes. Escherichia coli and Ureaplasma urealyticum (22 and 24 cases, respectively) occurred mostly as mixed infections, with ruptured membranes. GBS, MU urealyticum, and Streptococcus anginosus group were individually associated with chorioamnionitis, Bacteroides/Prevotella and S. anginosus with fetal pneumonitis. The spectrum of microorganisms was similar to that in preterm labor at later gestations; however, GBS appeared to be the most significant pathogen in midgestation miscarriage, especially with intact membranes. CONCLUSIONS: Unsuspected intrauterine infection underlies many spontaneous midgestation abortions. GBS is a key pathogen in this setting.

Cumulative mortality in children aged 1 to 6 years born in Western Australia from 1980-89.

PURPOSE: To investigate cumulative mortality for children aged 1-6 years born in Western Australia from 1980 to 1989. STUDY DESIGN: Births and deaths were ascertained from a linked total population database supplemented by information from postmortem records. Deaths were classified according to the underlying cause, and mortality rates, including factor specific rates, were calculated. Trends were investigated and comparisons were made using relative risks with 95% confidence intervals. RESULTS: Cumulative mortality was 2.2/1000 infant survivors, with a significant decrease during the years studied. Mortality was almost four times higher for Indigenous children, with no decrease. Accidents comprised 45.6% of all deaths, birth defects 17.3%, cancer and leukaemias 12.5%, and infections 11.0%. Low birth weight, preterm birth, and young maternal age significantly increased the risk of death in both Indigenous and non-Indigenous children; single marital status was also a significant risk factor for non-Indigenous children. CONCLUSION: High quality data and appropriate classification systems are essential to enable effective monitoring of childhood deaths and the planning of preventive programmes. Further decreases in mortality rates might be dependent on ensuring that resources are directed towards improving social and economic conditions for Indigenous and other disadvantaged families.

Observer reliability in assessing placental maturity by histology.

AIMS: To evaluate the ability of five experienced perinatal pathologists to assess placental maturity reliably by histology. METHODS: Twenty four haematoxylin and eosin slides, six each from placentas of 27, 31, 35, and 39 weeks' gestation, were circulated to five pathologists on three separate occasions. The slides were labelled with the correct or incorrect gestational ages. RESULTS: The mean absolute error over all 360 readings was 2.72 weeks. Only 54% of the slides were assessed within two weeks of the correct gestation. Pathologist tended to overestimate younger gestations and underestimate older gestations. Two, and possibly three, pathologist were influenced by the gestational age state on the label. One pathologist, who did not appear to be influenced by the label, was more accurate in diagnosing gestation of the placentas than other colleagues. CONCLUSIONS: Experienced pathologists can have difficulty in assessing the villous maturity of placentas by histology. They can also be influenced by clinical information provided, such as gestational age. Other observer reliability studies must address the issue of the influence of labelled information on observer variation. A difference in maturation would have to be of a six week magnitude to have a chance of being detected by current methods. This may limit the value of the histological diagnosis of placental dysmaturity as a surrogate marker for uteroplacental ischaemia.

The usefulness of human placental lactogen and keratin immunohistochemistry in the assessment of tissue from purported intrauterine pregnancies.

This study compared conventional light microscopy with immunohistochemistry in the histopathologic diagnosis of intrauterine pregnancy in curettings in which fetal parts and chorionic villi were absent. Hematoxylin and eosin-stained sections of the curettings, which were from 50 consecutive patients in whom incomplete abortion had been diagnosed clinically, were circulated to four pathologists who graded their diagnoses with a confidence score. Immunohistochemical examination using a standard streptavidin-biotin-peroxidase method with anti-HPL and antikeratin antisera was performed. The pathologists in the maternity hospitals achieved a high level of diagnostic confidence compared with those working in the general hospitals. However, there were erroneous diagnoses by the one pathologist in the former group and none by the latter. Critical path analysis showed that the best performing pathologist could accurately diagnose all but two of the cases that had been diagnosed with a degree of doubt by the other pathologists without recourse to immunohistochemical examination. These results suggest that immunohistochemistry may be used discriminately in uncertain cases or if relatively inexperienced pathologists are reporting.

Acceptance of mementos of fetal and perinatal loss in a south Australian population.

A package of mementos of a fetal or perinatal loss has been shown to help with the grieving process. The level of acceptance and the factors influencing acceptance of these mementos in a South Australian population was examined over a 27-month period. Data were available on 447 women and the acceptance rate was 79.6%. Major influences on the acceptance of mementos were maternal age and gestational age. Mothers in the 20-30 year age group were more likely to accept mementos than younger and older mothers. This age-related effect was more noticeable among genetic terminations and neonatal deaths than among spontaneous abortions or stillbirths. Memento acceptance of miscarriages and stillbirths over 20 weeks' gestation was significantly greater than for younger gestation. These findings may have an impact on the psychosocial management of perinatal loss. The high level of acceptance of these mementos is encouraging and vindicates our current practice which we recommend to others involved in the management of perinatal loss.

A report of human parvovirus B19 infection in hydrops fetalis. First Australian cases confirmed by serology and immunohistology.

OBJECTIVE: To present the first Australian cases of fetal hydrops induced by parvovirus B19. CLINICAL FEATURES: Autopsies on two cases of intrauterine fetal death with hydrops fetalis and pallor revealed evidence of myocarditis and widespread characteristic inclusion-bearing cells, predominantly erythroblasts. The diagnosis of hydrops fetalis induced by parvovirus B19 was confirmed in both cases by immunohistological localisation of the viral inclusions by means of a monoclonal antibody to the VP1 and VP2 proteins of parvovirus B19. A low level of parvovirus B19 IgM antibodies was detected in the second case. CONCLUSIONS: It is possible that our relatively small population and lack of familiarity with the histopathological features may have led to underdiagnosis rather than a true absence of fetal parvovirus B19 infection in Australia. The condition can be diagnosed and treated antenatally and therefore should be included in the differential diagnosis of causes of hydrops fetalis.

Continuous low-dose oestrogen and progestogen hormone replacement therapy: a randomised trial.

OBJECTIVE: To establish the efficacy and acceptability of combined continuous low-dose oestrogen and low-dose progestogen therapy, to determine whether any of three commercially available progestogens had any advantages or disadvantages in these circumstances and whether use of the lowest clinically effective oestrogen dose affected other outcomes being measured. DESIGN: A 12-month, prospective, open label, single centre, randomised trial. PATIENTS AND METHODS: Seventy-five postmenopausal women already receiving hormone replacement therapy in the form of conjugated equine oestrogens (CEE) (0.625 mg daily) and cyclical medroxyprogesterone acetate (10 mg) and experiencing withdrawal bleeding were changed to a continuous daily regimen of 0.3 mg CEE and a random allocation of one of three low-dose progestogens (medroxyprogesterone acetate 2.5 mg, levonorgestrel 30 micrograms or norethisterone 350 micrograms). Return to a dose of 0.625 mg CEE was permitted if required to control menopausal symptoms with separate analysis of this group when appropriate. OUTCOMES MEASURED: Menopausal symptom score, clinical bleeding pattern, endometrial biopsy results, forearm bone density and content, serum lipids and side effects. RESULTS: Fifteen women withdrew from the trial, five because of irregular bleeding. In the remainder, amenorrhoea was achieved in 53% by three months, in 67% by six months and in 93% by 12 months. Endometrial biopsy showed atrophic endometrium by 12 months in all but one patient, in whom minimal proliferative activity was seen. Twenty-seven women chose to return to a dose of 0.625 mg CEE. In all groups, final control of menopausal symptoms improved. All regimens were bone sparing and the lipid profile was unchanged. Minimal side effects were experienced by the patients. There was little difference in outcome between the three progestogens except that norethisterone therapy was associated with a greater prevalence of amenorrhoea at six months than was seen in the levonorgestrel and medroxyprogesterone acetate groups. CONCLUSIONS: These low-dose continuous oestrogen and progestogen regimens appear an appropriate option for the postmenopausal woman wishing to eliminate withdrawal bleeding and reduce both hormonal side effects and menopausal symptoms. The long term benefits of these regimens with regard to the prevention of osteoporotic fractures, cardiovascular disease and endometrial cancer need to be further assessed over time.

Anthropometric measurements in the second trimester fetus.

Normal anthropometric measurements, of accepted value for clinicians and pathologists in the assessment of the dysmorphic neonate, have not in the past been available for the second trimester fetus, in which dysmorphic features are often more subtle and objective measurements most needed. In order to establish these values 19 anthropometric measurements, comparable to those published for the larger fetus and neonate, were recorded at autopsy on each of 260 overtly normal non-macerate singleton fetuses between 13 and 26 weeks gestation. Regression lines for each parameter, and growth ratios of potential value for description and assessment of dysmorphic features, were derived. The sex ratio was 1.27 and as there was no statistically significant sex difference for any of the 19 measurements chosen, the data was subsequently pooled. There were linear correlations between gestational age and each growth parameter, all but three exceeding 0.90. The linear correlations between pairs of growth parameter were higher than the correlations between gestational age and individual growth parameters. This suggests that growth parameter pairs, expressed as a ratio, are less affected by errors in gestational age estimation. Ratios enabling the dysmorphologist to more objectively assess common observations such as abnormalities of head shape, relationship between limb and trunk length and gross proportional relationships between major body segments were derived. Collected measurements were compared with established ultrasound reference ranges. While reference ranges for biparietal diameter and head circumference showed close concordance with those derived from ultrasound measurements, the abdominal circumference was consistently lower than that measured by ultrasound possibly because of differing trunk positions in utero compared with after death. The graphs and ratios derived in this study can be rapidly applied to confirm visual impressions at clinical examination and at autopsy.

Alternative method of sampling placentas for the assessment of uteroplacental vasculature.

A new method for the taking and embedding of placental blocks to obtain maximum information regarding the uteroplacental vasculature was developed. This method involves taking en face blocks of the basal plate of the placenta. Results show that normal and abnormal maternal vessels are clearly delineated. In addition to conventional full thickness blocks, which provide information about the chorionic plate such as inflammation and meconium pigment uptake, and about the parenchyma in the other zones remote from the basal plate of the placenta, it is recommended that en face blocks be taken for histological assessment of the placenta.

The OEIS complex (omphalocele-exstrophy-imperforate anus-spinal defects): recurrence in sibs.

The OEIS complex comprises a combination of defects including omphalocele, exstrophy of the cloaca, imperforate anus, and spinal defects. It may represent the most severe manifestation of a spectrum of birth defects, the exstrophy-epispadias sequence. The OEIS complex affects 1 in 200,000 to 400,000 pregnancies and is of unknown cause. The purpose of the current report is to document the occurrence of OEIS in sibs from separate pregnancies and suggest that some cases may have a genetic basis.

Oestrogen and cyclical progestogen in postmenopausal hormone replacement therapy.

OBJECTIVE: To ascertain the effectiveness, safety and incidence of side effects of a postmenopausal hormone replacement regimen consisting of continuous conjugated equine oestrogens and cyclical medroxyprogesterone acetate given for the first 14 days of each calendar month. DESIGN: A six month, prospective, open label, two centre, outpatient study of continuous Premarin (0.625 mg; Wyeth-Ayerst) and cyclical Provera (10 mg; Upjohn). Dosage adjustment was allowed in one centre. STUDY POPULATION: Seventy-six postmenopausal women in Adelaide and Brisbane. MAIN OUTCOME MEASURES: Menopausal symptom score, serum lipid levels, routine biochemical and haematological indices, endometrial histology and clinical bleeding pattern, blood pressure, weight changes, side effects, withdrawal from the study, compliance and necessary dose adjustment. MAIN RESULTS: Eight women withdrew from the study and nearly 50% experienced some minor side effect. Where dosage adjustment was allowed, almost all side effects were eliminated. Most patients had acceptable regular withdrawal bleeds although some were deemed heavy. There was a statistically highly significant 54% reduction in the menopausal symptoms score at three months and a 62% reduction at six months. Endometrial biopsy at six months showed atrophic or secretory endometrium with no inappropriate proliferation or hyperplasia. Total cholesterol and low density lipoprotein (LDL) cholesterol levels were significantly decreased. The high density lipoprotein (HDL) cholesterol level remained unchanged and triglyceride levels were raised within the normal range. There were no other clinically relevant biochemical, haematological or clinical changes. CONCLUSION: Continuous conjugated equine oestrogens (0.625 mg) and cyclical medroxyprogesterone acetate (10 mg) for the first 14 days of each calendar month proved to be a safe and effective postmenopausal therapy regimen. Initial minor side effects were common but could be readily ameliorated with early follow-up and dose titration.

Necropsy findings in a fetus with a 46,XY,dic t(X;21)(p11.1;p11.1).

We report the findings in a fetus terminated because of multiple abnormalities diagnosed on ultrasound, including asymmetry of the limbs, a hypoplastic diaphragm, unilateral duplex kidney with a double ureter, unilateral cystic kidney, and congenital heart disease including total pulmonary atresia. Cytogenetic studies showed an unbalanced translocation of the long arm of the X chromosome to chromosome 21, resulting in a 46,XY,dic t(X;21)(p11.1;p11.1) karyotype. The cytogenetics were confirmed by non-isotopic in situ hybridisation using probes specific to pericentric alphoid repeats. Parental chromosomes were normal indicating this to be a de novo translocation. It is suggested that the inactivation of the long arm of the X chromosome has resulted in an effective monosomy for chromosome 21.

The perinatal autopsy: a contemporary approach.

As autopsy rates in general hospitals decline, interest in the perinatal autopsy continues to rise, reflecting the emergence of a vigorous specialty growing in parallel with fetal medicine, prenatal diagnosis and clinical genetics. Perinatal autopsies are best carried out in tertiary centres which provide these services. Meticulous documentation, flexibility of technique, intelligent use of laboratory tests and wide systematic histopathologic sampling are emphasized. Microbiologic examination is of particular value when carried out by a laboratory having a special interest in genital tract and perinatal pathogens. Karyotyping must be selective if resources are to be conserved and is most productive when there are multiple malformations. Perinatal autopsy is not complete without examination of the placenta and significant lesions should be clearly distinguished from curiosities and from changes secondary to fetal death. The pathologist's wider contribution to perinatal medicine includes providing high quality data to epidemiology units and auditing committees, contributing to the multidisciplinary management of prenatally diagnosed fetal abnormalities, monitoring iatrogenic disease patterns and supporting the process of perinatal grief management. Special problems and diagnostic challenges are to be found when investigating sudden, unexplained intrauterine fetal death, hydrops, bone dysplasias and complicated multiple pregnancies.

Monocytosis in preterm infants.

In sick preterm neonates receiving intensive care a spectacular rise in monocyte count has frequently been observed in sequential full blood examinations. The etiology of this has not previously been investigated and this study examines clinical factors that may contribute to this finding. Thirty (5.1%) of the 587 neonates who required intensive care during the study period had significant monocytosis (absolute count greater than 1700/mm3). Their mean gestation was 29 weeks (range 26-32 weeks). Monocytic response occurred at an age of 5.5 +/- 3 (mean +/- S.D.) days with 20% occurring at birth, 57% in the first week and 23% in the second week of life and lasted for 19.8 +/- 16 days (mean +/- S.D.). Most reached peak levels within two weeks and these ranged between 2,170 and 7176 per mm3. Analysis of the clinical variables against 37 controls revealed lower mean birth weight and gestational age, and higher incidence of leukocytosis, multiple transfusions, albumin infusions and theophylline therapy in the study group in comparison to the controls (P less than 0.001). No significant difference was found in maternal risk factors (pre-eclampsia, diabetes and amnionitis), birth asphyxia, respiratory disease, parenteral nutrition, proven infection and antibiotic therapy. An unexpected association with maternal steroid therapy was demonstrated. It is speculated that monocytosis represents a physiological though immature response of the marrow of small premature infants to a variety of exogenous stimuli including drugs and foreign protein infusions.

A normal 46,XX infant with a 46,XX/69,XXY placenta: a major contribution to the placenta is from a resorbed twin.

A predominantly triploid 69,XXY placenta was found associated with a normal 46,XX infant. Therefore, a triploid placenta is apparently capable of supporting normal fetal development. The chromosome and pathological results support the conclusion that the triploid placenta originates from a 'vanishing twin' pregnancy. This case is unusual in that persistence of the placenta from the vanished twin has virtually replaced most of the normal placenta.

Congenital acinar aplasia: an extreme form of pulmonary maldevelopment.

A case is reported of an extreme form of intrauterine pulmonary maldevelopment in a term infant characterized by almost total failure of development of terminal respiratory units with arrest of pulmonary growth early in the second trimester. This is believed to be only the second reported case of this condition.