Imperforate anus: A relatively common anomaly rarely diagnosed prenatally.

OBJECTIVE: Despite the relatively common occurrence of imperforate anus, prenatal diagnosis is rarely reported. In this study, we investigated the presence and diagnosis of imperforate anus along with strategies for improving prenatal diagnosis of the condition. PATIENTS AND METHODS: Fetuses and infants with imperforate anus who had been examined prenatally by ultrasound at the National Center for Fetal Medicine (NCFM) from 1987 to 2004, were evaluated. RESULTS: Of 69 cases with imperforate anus, only 11 (15.9%) were diagnosed prenatally, at a median gestation of 18 + 4 (range, 15 + 6 to 35 + 6) weeks. In all 11, dilatations of the rectum or lower part of the bowel were seen. Additional anomalies, most of them diagnosed prenatally, were present in 59/69 (85.5%) of the cases. The most frequent additional anomalies were urogenital (53.6%). The karyotype was abnormal in nine cases (13.0%). A retrospective evaluation of available videotapes of 22 cases of imperforate anus that were not diagnosed prenatally revealed that it was possible to suspect the diagnosis in 11/22 (50%) cases. Sixteen infants were born with imperforate anus without prenatal diagnosis of any abnormality. In total, 31/69 (44.9%) cases were terminated, two (2.9%) died in utero and 12 (17.4%) died postnatally. Twenty-four (34.8%) infants survived, including all 10 with isolated imperforate anus and seven of eight cases with only one additional anomaly. CONCLUSIONS: The prenatal detection rate of imperforate anus was only 15.9%. Imperforate anus is often associated with other anomalies; in this study, 85.5% had additional anomalies. Prenatal diagnosis makes prenatal counseling possible and facilitates optimized postnatal care. We believe that the prenatal detection rate of imperforate anus could be improved. Examiners should intensify their search for typical findings of imperforate anus especially when other anomalies that frequently accompany this condition are present.

Brains and faces in holoprosencephaly: pre- and postnatal description of 30 cases.

OBJECTIVE: To investigate the prenatal appearance of the holoprosencephaly spectrum. METHODS: A database of 1750 fetuses with congenital anomalies identified by ultrasound was prospectively collected from 1987 to 2000. Among them, 30 cases (1.7%) with holoprosencephaly were prenatally identified and described. RESULTS: The prevalence of holoprosencephaly in the Health Region of the National Center for Fetal Medicine in Norway was 1.26 : 10 000; the sex distribution (male : female) was 1.4 : 1. Holoprosencephaly was found in one dichorionic twin pregnancy and one pair of conjoined twins. Among the 30 cases of holoprosencephaly, 18 were alobar, five were semilobar, two were lobar, two were lobar variants, and three were anencephalic. The facial features varied considerably. Sixty-seven per cent (20/30) had associated structural anomalies that were not related to the cerebral and facial holoprosencephaly condition. Thirty-seven per cent (11/30) had detectable chromosome aberrations and 23% (7/30) had nonchromosomal syndromal origin. The size or shape of the head was abnormal in 83% (25/30) of holoprosencephaly cases. CONCLUSION: This study indicates that holoprosencephaly represents a heterogeneous entity with different etiologies and clinical appearances. The fact that holoprosencephaly features are found associated with particular conditions such as fronto-nasal dysplasia (2/30; 6.7%), agnathia-otocephaly (3/30; 10%), and anencephaly (3/30; 10%), suggests that these may be underreported conditions in other large holoprosencephaly series.

The detection of spina bifida before 10 gestational weeks using two- and three-dimensional ultrasound.

We present three cases of spina bifida during the embryonic period detected by ultrasound before 10 weeks' gestational age. The last-menstrual-period-based ages ranged from 9 weeks 1 day to 9 weeks 4 days and the crown rump lengths ranged from 22 mm to 28 mm. The cases were identified prospectively in a program of targeted ultrasound examination of high-risk pregnancies, using a 7.5 MHz annular array transvaginal transducer. The use of 3D ultrasound made additional diagnostic ultrasound tomograms possible, but was not necessary for the definite diagnosis. The scalloping of the frontal bones and the Arnold Chiari malformation did not occur before 12 weeks.

A correlative study of prenatal ultrasound and post-mortem findings in fetuses and infants with an abnormal karyotype.

OBJECTIVE: To compare ultrasound and post-mortem findings in 98 fetuses and infants with an abnormal karyotype. DESIGN: Criteria for inclusion were an ultrasound examination at the National Center for Fetal Medicine (NCFM), an abnormal karyotype, and an autopsy performed during the period 1985-94. RESULTS: Trisomy 18 and 21 were the two most common abnormal karyotypes. The highest number of congenital anomalies was observed in cases with trisomy 13 and 18; congenital heart defects (CHD) were most prevalent among fetuses with trisomy 18. In 80% of cases there was full agreement between the ultrasound and autopsy findings; in another 8% of cases there was nearly complete concordance. Thus, in 88% of cases, the main prenatal sonographic diagnosis was correct. In 6% major autopsy findings were not detected by ultrasound examination, in 1% none of the autopsy findings were detected by routine ultrasound and in 5% ultrasound findings were not verified at autopsy. Where the correlation was related to individual autosomal trisomies, structural anomalies were most often correctly diagnosed in fetuses with trisomy 13, with the main diagnosis correct in all cases; second in accuracy were the ultrasound diagnoses in fetuses with trisomy 21 with the main diagnosis correct in 96%; for trisomy 18 the concordance was less good, with the main diagnosis correct in 71%. CONCLUSION: The present comparison of sonographic diagnoses with post-mortem findings demonstrates good accordance between the two methods. It also demonstrates the importance of awareness of the anomalies known to occur with different aneuploidies.

Fetuses and infants with congenital urinary system anomalies: correlation between prenatal ultrasound and postmortem findings.

OBJECTIVE: Detection of congenital urinary system anomalies is an important part of the prenatal ultrasound examination. The present study compares prenatal ultrasonographic findings and postmortem examinations of fetuses and infants with renal and urinary tract anomalies. DESIGN: Criteria for inclusion were an ultrasound examination at the National Center for Fetal Medicine (Trondheim, Norway) and autopsy performed during the period 1985-94. Results from the ultrasound examination and autopsy regarding urinary system anomalies were categorized according to the degree of concordance. RESULTS: Urinary system anomalies were found in 112 (27%) of 408 fetuses with congenital anomalies. The renal and/or urinary tract anomaly was the principal reason for induced abortion or cause of death in 50 cases (45%). In 97 (87%) of the 112 cases there was full agreement between the ultrasound observations and the autopsy findings. In five cases the autopsy revealed minor findings not mentioned in the ultrasound report. The main diagnosis was thus correct in 102 cases (91%). In four cases major autopsy findings had not been found by ultrasound examination; in another four, none of the autopsy findings were suspected by ultrasound, and in two, minor ultrasound findings were not confirmed at autopsy. CONCLUSIONS: The accordance between ultrasound diagnoses and postmortem examinations proved to be satisfactory. The close co-operation between ultrasonographers and perinatal pathologists is mutually beneficial. In addition to complementing prenatal diagnosis, postmortem examination is of vital importance for the quality control of ultrasonography in fetal diagnosis and plays an important role in genetic counseling.

Sibs with anencephaly, anophthalmia, clefts, omphalocele, and polydactyly: hydrolethalus or acrocallosal syndrome?

Major characteristics of the acrocallosal syndrome include severe mental retardation, agenesis or hypoplasia of the corpus callosum, and polydactyly of fingers and toes. In the past few years, anencephaly has also been noted, together with other midline defects. We report on a nonconsanguineous, Norwegian couple with a history of two pregnancies with a male and a female fetus, respectively, with anencephaly, median cleft lip and palate, omphalocele, and preaxial polydactyly, suggesting the diagnosis of the acrocallosal syndrome. Both fetuses also lacked eyes and nose, a finding not previously reported in the acrocallosal syndrome. Microphthalmia has been reported in the hydrolethalus syndrome, which may be caused by mutations in the same gene as the acrocallosal syndrome. The present report adds support to the hypothesis that the acrocallosal and hydrolethalus syndromes may be allelic conditions. The family history is consistent with autosomal recessive inheritance.

Alobar holoprosencephaly at 9 weeks gestational age visualized by two- and three-dimensional ultrasound.

We present the ultrasound detection of alobar holoprosencephaly (HPE) with cyclopia in an embryo of 9 weeks 2 days last menstrual period (LMP)-based gestational age; the crown-rump length (CRL) was 22 mm. The use of three-dimensional (3-D) ultrasound made additional diagnostic ultrasound tomograms possible, and the volume reconstructions improved the imaging and the understanding of the condition.

Detection of trisomy 18 on formalin-fixed and paraffin-embedded material by fluorescence in situ hybridization.

Formalin-fixed and paraffin-embedded autopsy material from 10 fetuses and infants with unknown karyotype and anomalies suggestive of trisomy 18 were subjected to fluorescence in situ hybridization (FISH). Nuclei were extracted from the tissues and hybridized with a chromosome 18-specific centromere probe. The hybridization was successful in 9 of 10 cases. Two cases showed three hybridization signals in most of the nuclei (74% and 85%). These had anomalies frequently occurring with trisomy 18 (congenital heart defect, omphalocele, and horseshoe kidney). Two cases showed a mixture of two and three signals (47%/49% and 59%/36%), suggesting the possibility of mosaicism. One of these cases had anomalies consistent with a trisomy 18 phenotype. In the other case intrauterine growth retardation and syndactylies suggested triploidy. Hybridization with a chromosome 8-specific probe gave a distribution of two and three signals (34% and 62%, respectively). This result strengthened the suspicion of a possible triploid mosaicism. In five of the cases most of the nuclei showed two signals (85% to 88%). However, as only one type of tissue was examined for enumeration of chromosome 18, the possibility of organ mosaicism or other chromosome aberrations cannot be excluded. The FISH technique is applicable on macerated and autolysed formalin-fixed tissue, making it possible to retrospectively analyze autopsy material from aborted and stillborn fetuses and infants. This analysis contributes to a better quality of perinatal autopsies and is helpful in parental counseling.

Human papillomavirus (HPV) in high-grade cervical intraepithelial neoplasia (CIN) detected by morphology and polymerase chain reaction (PCR)-- a cytohistologic correlation of 277 cases treated by laser conization.

The aims of this study were to evaluate the cytohistologic correlation in women treated for high-grade lesions of the cervix uteri (HG CIN), to assess the distribution of HPV features and finally to test the validity of the morphological criteria of HPV infection. The smears and biopsy specimens from 277 women treated for HG CIN by laser conization were re-evaluated blindly. Tissue blocks (n = 188) and 52 archival smears were examined for HPV DNA using PCR. HPV changes were detected with equal frequency in the smears and biopsy specimens by light microscopy; 63% and 65%, respectively. The prevalence of HPV DNA in biopsies was 88% and in archival smears 85%; agreement was found in 89% of the cases. Using PCR as the gold standard, we found a sensitivity of 63% for cytology and 70% for histology; the specificity was 41% and 37%, respectively. The positive predictive value was > 80%, but the negative predictive value was < 20%. Our study confirms that HPV features are frequently associated with HG CIN and that morphology is a non-specific method of identifying HPV infection and should be followed by PCR, also allowing detection of oncogenic HPV types and latent infections.

Comparison of prenatal ultrasound and postmortem findings in fetuses and infants with congenital heart defects.

OBJECTIVE: Detection of congenital heart defects by prenatal ultrasound examination has been one of the great challenges since the investigation for fetal anomalies became part of the routine fetal examination. This prospective study was designed to evaluate the concordance of prenatal ultrasound findings with autopsy examination in a population consisting of both referred women and non-selected pregnant women. DESIGN: Criteria for inclusion were an ultrasound examination at the National Center for Fetal Medicine and an autopsy performed during the years 1985-94. Results from the ultrasound and autopsy examinations were systematized into categories depending on the degree of concordance. RESULTS: Of 408 infants and fetuses with developmental anomalies, 106 (26%) had congenital heart defects. In 63 (59%) of these 106 cases, the heart defect was the principal reason for the termination of pregnancy or the cause of death. Excluding five cases with a secundum atrial septal defect, there was complete agreement between the ultrasound examination and the autopsy findings in 74 (73%) of 101 cases. In 18 cases, there were minor discrepancies between ultrasound and autopsy findings. The main diagnosis was thus correct in 92 cases (91%). From the first time period (1985-89) to the second (1990-94), the detection rate of all heart defects increased from 48% to 82%. CONCLUSION: This study confirms a good correlation between ultrasound and autopsy diagnoses in fetuses and infants with congenital heart defects. A significant improvement in the detection of heart defects occurred from the first time period to the second and was probably due to increased experience and technical advances.

Comparison of prenatal ultrasound and postmortem findings in fetuses and infants with central nervous system anomalies.

Detection of fetal developmental abnormalities by ultrasound examination of pregnant women has become a specialized field of medicine. Quality control of this field requires detailed examination of aborted fetuses. In 408 fetuses and infants with developmental anomalies, the prenatal ultrasound findings were compared with the post-mortem findings. This study focused on 140 central nervous system (CNS) anomalies. Criteria for inclusion were an ultrasound examination at the National Center for Fetal Medicine (NCFM) and an autopsy performed during the period 1985-94. Results of the ultrasound and autopsy examinations were systematized into six different categories. Hydrocephaly and anencephaly were the most frequent abnormalities, together accounting for 50% of the CNS anomalies. In 20 cases (14%), the CNS anomalies were associated with other important anomalies or chromosomal aberrations. In 125 of the cases (89%), there was complete concordance between the ultrasound and autopsy diagnoses. Of the 15 CNS cases with discrepancies, seven had nearly complete concordance; if we include these, the correlation was 94%. In conclusion, this study confirms that developmental anomalies in the central nervous system are frequent and that ultrasound diagnoses are in good concordance with the autopsy diagnoses.

Hypochondroplastic dwarfism in the Irish setter.

Two test matings in the irish setter were performed, and genetic, clinical, morphometric, radiographic, bone histological and plasma and urine biochemical features of dwarfism were studied. All offspring were phenotypically normal at birth and weaning, but at the age of 2.5 to 4 months the longitudinal growth of the spine and leg bones was retarded in the dwarfs compared with the normal littermates. Most dwarfs performed well, even in the field. Radiographic and histological evaluations revealed a hypochondroplasia. A morphometric diagnostic method for Irish setter dwarfism was developed. A single autosomal recessive mode of inheritance was verified.

Pre-pregnancy risk factors of small-for-gestational-age births and perinatal mortality.

The Scandinavian part of the NICHD study of successive small-for-gestational-age (SGA) births included 5722 parous women from Trondheim and Bergen (in Norway) and Uppsala (in Sweden). Study enrollment took place from January 1986 through March 1988. The aim of the main study was to investigate factors associated with inhibited intrauterine growth. This paper reports on the fetal, perinatal, and neonatal deaths among the births in the study in relation to different risk factors. The cause of deaths were analyzed to see if there were any associations with the risk factors. There was a total of 84 deaths, 65 of these were fetal, perinatal or neonatal deaths and included in this analysis. The remaining 19 are for different reasons excluded. Thirty-two (60%) of the autopsies regarded the high risk group who comprised only 42.4% of the total study population. The high risk group was selected using the following risk criteria: a previous low weight birth or perinatal death, maternal low weight (pre-pregnancy weight < 50 kg), the presence of a chronic maternal disease, and smoking at the time of conception. A significant association was found between perinatal mortality and the presence of one or more of the defined risk criteria (relative risk 2.0; 95% CI 1.2, 3.4). Asphyxia and related disorders was the most important single cause of death and was found to be associated with the maternal risk factors (RR 3.9; 95% CI 1.5, 9.8). A significant association was found between maternal risk factors and SGA autopsies (RR 3.9; 95% CI 1.7, 8.9). No association was found between asphyxia and SGA. It is concluded that women with risk factors based on complications in a previous pregnancy are more prone to stillbirths, perinatal, and neonatal deaths, and with asphyxia as the most prominent cause of death.

Malignant fibrous histiocytoma of the uterus. Some immunohistochemical and ultrastructural observations.

Hysterectomy was performed in a 64-year-old woman because of a uterine malignant tumor which extensively involved both the endometrium and the myometrium. Histological examination revealed a malignant fibrous histiocytoma (MFH) of the pleomorphic-storiform type. The presence of epithelial or heterologous mesenchymal tumor components or cells of smooth muscle derivation was ruled out by immunohistochemistry and electron microscopy. The patient developed pulmonary metastases and died six months after surgery. MFH is a rare primary tumor of the uterus, but it should be considered in cases of malignant mesenchymal tumors without heterologous elements or signs of smooth muscle derivation.