Doppler and biophysical assessment in growth restricted fetuses: distribution of test results.

OBJECTIVE: Multi-vessel Doppler ultrasonography and biophysical profile scoring (BPS) are used in the surveillance of growth restricted fetuses (IUGR). The interpretation of both tests performed concurrently may be complex. This study examines the relationship between Doppler ultrasonography and biophysical test results in IUGR fetuses. METHODS: Three hundred and twenty-eight IUGR fetuses (abdominal circumference < 5th percentile, elevated umbilical artery (UA) pulsatility index (PI)) had concurrent surveillance with UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler ultrasonography and BPS (fetal tone, movement, breathing, maximal amniotic fluid pocket and fetal heart rate). Patients were stratified into three groups according to their Doppler examination: (1) abnormal UA alone; (2) brain sparing (MCA-PI > 2 SD below mean for gestational age); and (3) abnormal DV (PI > 2 SD above the mean for gestational age) and BPS groups: (1) normal (> 6/10); (2) equivocal (6/10); and (3) abnormal (< 6/10). Predictions of short-term perinatal outcomes by both modalities were compared for stratification. The distribution and concordance of Doppler and BPS test results were examined for the whole patient group and based on delivery prior to 32 weeks' gestation. RESULTS: Abnormal UA Doppler results alone were observed in 109 fetuses (33.2%), brain sparing in 87 (26.5%) and an abnormal DV in 132 (40.2%). The BPS was normal in 158 (48.2%), equivocal in 68 (20.7%) and abnormal in 102 (31.1%). Both testing modalities stratified patients into groups with comparable acid-base disturbance and perinatal outcome. Of the nine possible test combinations the largest subgroups were: abnormal UA alone/normal BPS (n = 69; 21%) and abnormal DV Doppler/abnormal BPS (n = 62; 18.9%). Assessment of compromise by both testing modalities was concordant in 146 (44.5%) cases. In 182 fetuses with discordant results the BPS grade was better in 115 (63.2%, P < 0.0001). Marked disagreement of test abnormality was present in 57 (17.4%) fetuses. Of these, abnormal venous Doppler in the presence of a normal BPS constituted the largest group (Chi-square P < 0.002). Stratification was not significantly different in patients delivered prior to 32 weeks' gestation. CONCLUSION: Doppler ultrasonography and BPS effectively stratify IUGR fetuses into risk categories, but Doppler and BPS results do not show a consistent relationship with each other. Since fetal deterioration appears to be independently reflected in these two testing modalities further research is warranted to investigate how they are best combined.     

Falloposcopy in conjunction with laparoscopy: possibilities and limitations

Falloposcopy is a transvaginal microendoscopic technique to explore the human Fallopian tube from the uterotubal ostium to the fimbrial end. Falloposcopy provides a unique possibility to visualize endotubal disease and may be used therapeutically for removal of debris and for cutting down filmy intraluminal adhesions. To assess the clinical performance of falloposcopy as part of an infertility investigation, a total of 43 women scheduled for laparoscopy as part of an investigation of infertility had a falloposcopy performed in conjunction with the laparoscopy. All women were investigated at Danderyd Hospital, Stockholm and Akademiska Hospital, Uppsala, during 1995 and 1996. Images from the endosalpinx were obtained in 26 of 43 women (60.5%). In 10 women (23.3%), it was possible to obtain images from both tubes. No images were of sufficient quality to describe the entire tubal mucosa in detail. Falloposcopy represents a unique tool for visualization of endotubal disease and may provide a valuable instrument for in-vivo exploration of tubal physiology. However, certain technical problems limit the usefulness of this method in routine clinical practice. These technical problems have to be solved before falloposcopy can achieve a central position in investigation and treatment of tubal disease.      

High level of unequal meiotic crossovers at the origin of the 22q11. 2 and 7q11.23 deletions

Interstitial chromosomal deletions at 22q11.2 and 7q11.23 are detected in the vast majority of patients affected by CATCH 22 syndromes and the Williams-Beuren syndrome, respectively. In a group of 15 Williams- Beuren patients, we have shown previously that a large number of 7q11.23 deletions occur in association with an interchromosomal rearrangement, indicative of an unequal crossing-over event between the two homologous chromosomes 7. In this study, we show that a similar mechanism also underlies the formation of the 22q11.2 deletions associated with CATCH 22. In eight out of 10 families with a proband affected by CATCH 22, we were able to show that a meiotic recombination had occurred at the critical deleted region based on segregation analysis of grandparental haplotypes. The incidences of crossovers observed between the closest informative markers, proximal and distal to the deletion, were compared with the expected recombination frequencies between the markers. A significant number of recombination events occur at the breakpoint of deletions in CATCH 22 patients (P = 2.99x10(-7)). The segregation analysis of haplotypes in three- generation families was also performed on an extended number of Williams-Beuren cases (22 cases in all). The statistically significant occurrence of meiotic crossovers (P = 4.45x10(-9)) further supports the previous findings. Thus, unequal meiotic crossover events appear to play a relevant role in the formation of the two interstitial deletions. The recurrence risk for healthy parents in cases where such meiotic recombinations can be demonstrated is probably negligible. Such a finding is in agreement with the predominantly sporadic occurrence of the 22q11.2 and 7q11. 23 deletions. No parent-of-origin bias was observed in the two groups of patients with regard to the origin of the deletion and to the occurrence of inter- versus intrachromosomal rearrangements.      

Diagnosis of pulmonary embolism: Ventilation perfusion scintigraphy versus helical computed tomography pulmonary angiography

The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses.     

Integrated testing and management in fetal growth restriction

Growth-restricted fetuses are at higher risk for poor perinatal and long-term outcome than those who are appropriately grown. Multiple antenatal testing modalities can help document the sequence of fetal deterioration. The full extent of this compromise is best identified by a combination of fetal biometry, biophysical profile scoring, and arterial and venous Doppler. In the preterm growth-restricted fetus, timing of delivery is critically determined by the balance of fetal versus neonatal risks. In the near-term fetus, accurate diagnosis continues to be a challenge as unrecognized growth restriction contributes to a significant proportion of unexplained stillbirths. In this review, we present an integrated diagnostic and surveillance approach that accounts for these factors.     

Fetal growth restriction

Normal fetal growth is determined by the genetically predetermined growth potential and further modulated by maternal, fetal, placental, and external factors. Fetal growth restriction (FGR) is a failure to reach this potential and is clinically suspected if sonographic estimates of fetal weight, size, or symmetry are abnormal. Integration of fetal anatomy assessment, amniotic fluid dynamics, uterine, umbilical, and fetal middle cerebral artery Doppler is the most effective approach to differentiate potentially manageable placenta-based FGR from aneuploidy, nonaneuploid syndromes, and viral infection. Although placental dysfunction results in a multisystem fetal syndrome with impacts on short- and long-term outcome, only cardiovascular and behavioral responses are helpful to guide surveillance and intervention. Early-onset FGR before 34 weeks gestation is readily recognized but challenging to manage as questions about optimal delivery timing remain unanswered. In contrast, near-term FGR provides less of a management challenge but is often missed as clinical findings are more subtle. Once placenta-based FGR is diagnosed, integrating multivessel Doppler and biophysical profile score provides information on longitudinal progression of placental dysfunction and degree of fetal acidemia, respectively. Choosing appropriate monitoring intervals based on anticipated disease acceleration and intervention when fetal risks exceed neonatal risks are the prevailing current management approaches.     

Protease inhibitor therapy and fetal growth potential in HIV-positive women

Our objective was to test if protease inhibitors (PIs) increase the incidence of fetal growth restriction (FGR). Human immunodeficiency (HIV)-seropositive women were studied. At birth the neonatal weight percentile was assigned by predicted growth potential (GP), accounting for race, parity, weight, height, gestational age, birthweight, and gender (Gardosi, 1992). FGR was defined as GP < 10% percentile. Maternal age, CD4 count, viral load, weight gain, prenatal care, tobacco, alcohol, substance abuse, and PI use were related to FGR using chi-square and multiple regression analysis. Ninety-three of 191 women received PI. In these, FGR occurred in 27 (29%) compared with 15 (15.3%) in the non-PI group ( P = 0.02). Maternal CD4 count ( P < 0.0001) was the primary determinant, and smoking ( P = 0.037) was an independent cofactor for FGR (Nagelkerke r2 = 0.24). Twenty-six of 82 (31.7%) smokers had FGR, versus 16 of 109 (14.7%) of nonsmokers (odds ratio, 2.69; 95% confidence interval, 1.33 to 5.46; P = 0.005). After exclusion of the CD4 count, PI became a cofactor for FGR ( P = 0.021 and Nagelkerke r2 = 0.104). We concluded that maternal HIV status and smoking determine the risk for FGR. Although PIs increase the risk for FGR, this effect appears to depend on maternal disease severity.