WiSSP Scientific Publications Abstracts

Noel R. Dasgupta, Richard M. Pauli, V. Kim Horton, and Catherine A. Reiser, Undergraduate Honors Program (NRD) and Departments of Pediatrics (RMP) and Medical Genetics (RMP, VKH, CAR), University of Wisconsin—Madison, Madison, Wisconsin. American Journal of Medical Genetics in press,1997.

We assessed the utility of radiographic features as aids to the diagnosis of Down syndrome (DS) in stillborn infants. The iliac index may help to confirm the diagnosis of DS in stillborn infants in whom it is suspected clinically but in whom it can not be confirmed cytogenetically. It also can serve as a screening procedure to select stillborns in whom fluorescent in situ hybridization of fixed tissues should be completed. An iliac index of 59 differentiates between control and affected stillborns with the highest accuracy, but false positives persist above 55 and false negatives are common below 64 . We recommend that a conservative cutoff value of 55 be used if the radiographic data serve as the principal means of diagnosing DS in stillborn infants. A cutoff value of 64 may be appropriate if the radiographic data are used to screen stillborn infants for fluorescent in situ hybridization studies.

The Wisconsin Stillbirth Service Program: I. Establishment and assessment of a community based program for etiologic investigation of intrauterine deaths.

Richard M. Pauli, Catherine A. Reiser, Ruth M. Lebovitz, and Susan J. Kirkpatrick, Departments of Pediatrics (RMP) and Medical Genetics (RMP, CAR, RML, SJK), University of Wisconsin—Madison, Madison, Wisconsin. American Journal of Medical Genetics 50:116-134 (1994).

Although stillbirth is a common event, few programs have previously been established for the comprehensive etiologic investigation of intrauterine death. Fewer still have been prospective, unbiased in ascertainment, and consistent in protocol utilization. The Wisconsin Stillbirth Service Program was established in 1983 as a unique model for the investigation of the causes of stillbirth. This community-based, University-supported model for health care delivery is here described. Through it more than a thousand infants have been etiologically investigated. We demonstrate that a community-based program of stillbirth assessment can succeed, that compliance with recommended protocols is high and that a specific primary cause of fetal death can be demonstrated in about 40% of referrals. A majority of the established causes of intrauterine death are fetal etiologies. Furthermore, it appears that there are no substantial referral biases. Lack of such biases, together with the prospective, protocol driven nature of the program provides a unique population upon which to base estimates of the frequency of various etiologic diagnoses and classes and categories of cause.

The Wisconsin Stillbirth Service Program: II. Analyses of diagnoses and diagnostic categories in the first 1000 referrals.

Richard M. Pauli and Catherine A. Reiser, Departments of Pediatrics (RMP) and Medical Genetics (RMP, CAR, RML, SJK), University of Wisconsin—Madison, Madison, Wisconsin. American Journal of Medical Genetics 50:135-153 (1994).

The Wisconsin Stillbirth Service Program has provided a mechanism for the collection and analysis of unbiased and representative information concerning stillborn infants. Generated diagnoses and diagnostic categories within the first 1,000 referrals (including 789 stillbirths) are summarized here. Among all referred stillborns, 24.5% were found to have an identifiable intrinsic fetal cause of death. Specific diagnoses were extraordinarily heterogeneous, with about 85 different processes identified with this group. No single diagnosis was found in more than 1¹/₂% of the evaluated stillborns. Distribution by classes of fetal causes (as a percent of all fetal causes in stillborns) included malformation syndromes in 44%, single malformations and defined sequences in 34%, disruptions in 10%, and dysplasias in 3%. The heterogeneity of syndromic causes is illustrated, examples of previously undescribed syndromic processes provided and the problems experienced in generating specific diagnoses discussed. Specific single malformations, sequences, disruptions, and dysplasias are also tabulated and illustrated. Distribution by etiologic categories (as a percent of all fetal causes in stillborns) included defined sporadic conditions in 29%, cytogenetic aberration in 25%, presumed multifactorial processes in 12%, Mendelian disorders in 5%, and environmental events in less than 4%. A fourth of all fetal causes could not be sufficiently defined to allow for certainty in assigning a specific etiologic category. The materials summarized provide reference data regarding the frequency of classes and categories of fetal diagnoses generated from an unbiased and non-selected series of stillborns.

Lower mesodermal defects - a common cause of fetal and early neonatal death.

Richard M. Pauli, Departments of Pediatrics and Medical Genetics, University of Wisconsin—Madison, Madison, Wisconsin. American Journal of Medical Genetics 50:154-172 (1994).

Among the first 1,130 referrals to the Wisconsin Stillbirth Service Program, 17 infants have been recognized to share phenotypic characteristics involving the genital, urinary, lower gastrointestinal, and axial skeletal systems. The pattern of abnormalities identified appears to be limited to structures sharing a common embryologic origin. These features, for the most part, are shown to be non-randomly associated. No clearly definable subgroups within this population are demonstrable. The pattern of abnormalities is defined to include abnormalities of the following structures as pathogenetically primary features: lumbosacral vertebrae, kidneys, ureters, uterus/fallopian tubes, vagina, bladder, urethra, adrenals, gonads, anorectum, external genitalia, and umbilical arteries. An embryologic mechanism is proposed which explains this non-random association as arising secondary to disruption of structures derived from the lower portion of the primitive intraembryonic mesoderm. The Lower Mesodermal Defects Sequence appears to be a rather common (and under-recognized) cause of stillbirth and immediate neonatal death.

Fetal disruptions: Assessment of frequency, heterogeneity and embryologic mechanisms in a population referred to a community-based stillbirth assessment program.

Heidi J. Luebke, Catherine A. Reiser, and Richard M. Pauli, Departments of Pediatrics (RMP) and Medical Genetics (HJL, RMP, CAR), University of Wisconsin—Madison, Madison, Wisconsin. American Journal of Medical Genetics 36:56-72 (1990).

The Wisconsin Stillbirth Service Project (WiSSP) is a community-based program for the investigation of the cause of fetal death. From its inception in 1983 through July 1988, 629 referrals were made to WiSSP. All referrals were assessed for the presence of disruptional characteristics, and 23 were found to have major or primary disruptive effects. Most of these were either early amnion disruption/limb-body wall disruption (treated as a single group, since analysis suggests a continuum of clinical characteristics) and twin-twin disruptions. Therefore, disruptions accounted for 3.6% of all referrals (including liveborn and miscarriage referrals) to WiSSP. When only stillborn fetuses are considered, approximately 2.4% appear to have died because of disruptions. This makes disruptions one of the most frequent, identifiable causes of late intrauterine death. We estimate that 0.6—1.4% of all stillborn fetuses die because of early amnion disruption/limb-body wall disruption which, when taken with previous estimates of the frequency of such problems in early miscarriages and liveborn infants, suggests that these disruptions result in a 95% prenatal mortality rate. We suggest a unified model of likely pathogenetic mechanisms which may help explain the continuum of multisystem involvement seen in those with early amnion disruption/limb-body wall disruption. In addition, 3 patients with atypical disruptions are reviewed who exemplify the difficulty and importance of differentiating disruptional and malformational processes.

Accuracy of fetal death reports: Comparison with data from an independent stillbirth assessment program.

Anne E. Greb, Richard M. Pauli, and Russell S. Kirby, Departments of Pediatrics (RMP) and Medical Genetics (AEG, RMP), University of Wisconsin—Madison, and Wisconsin Center for Health Statistics (RSK) Madison, Wisconsin. American Journal of Public Health 77(9) 1202-1206 (1987).

We evaluated the completeness and accuracy of reporting on Wisconsin fetal death report forms (FDF) through case by case comparison with data from the Wisconsin Stillbirth Service Project (WiSSP), which uses extensive protocols for etiologic investigation of stillborns. Fetal deaths are underreported: no FDF was submitted for 17.8 per cent of fetal deaths evaluated through the WiSSP. For those for whom FDF were submitted, fetal anomalies were often unrecognized or unreported: only 60 per cent of stillborns identified by the WiSSP as having fetal anomalies had any indication of the presence of such anomalies on FDF. When causes of death were classified into fetal, placental/cord, maternal/environmental, and unknown, comparison of reported underlying cause of death revealed marked inaccuracies on FDF. Placental/cord causes reported on FDF often could not be documented subsequently while, in contrast, fetal causes of death were underreported. Few accurate fetal diagnoses were present on FDF. Even among common lethal malformations misdiagnosis occurred frequently.

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