Increased leukocyte distribution in the pre-clinical stage of pre-eclampsia.
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Biomedical subjects
Publications and source records attributed to C R Harman.
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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.
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BACKGROUND: Our aim was to test the hypothesis that qualitative ductus venosus and umbilical venous Doppler analysis improves prediction of critical perinatal outcomes in preterm growth-restricted fetuses with abnormal placental function. METHODS: Patients with suspected intrauterine growth restriction (IUGR) underwent uniform fetal assessment including umbilical artery (UA), ductus venosus (DV) and umbilical vein (UV) Doppler. Absent or reversed UA end-diastolic velocity (UA-AREDV), absence or reversal of atrial systolic blood flow velocity in the DV (DV-RAV) and pulsatile flow in the umbilical vein (P-UV) were examined for their efficacy to predict critical outcomes (stillbirth, neonatal death, perinatal death, acidemia and birth asphyxia) before 37 weeks' gestation. RESULTS: Seventeen (7.6%) stillbirths and 16 (7.1%) neonatal deaths were observed among 224 IUGR fetuses. Forty-one neonates were acidemic (19.8%) and seven (3.1%) had birth asphyxia. Logistic regression showed that UA-AREDV had the strongest association with perinatal mortality (R(2) = 0.49, P < 0.001), stillbirth (R(2) = 0.48, P < 0.001) and acidemia (R(2) = 0.22, P = 0.002) while neonatal death was most strongly related to DV-RAV and P-UV (R(2) = 0.33, P = 0.007). UA waveform analysis offered the highest sensitivity and negative predictive value and DV-RAV and P-UV had the best specificity and positive predictive values for outcome prediction. Overall, DV-RAV or P-UV offered the best prediction of acidemia and neonatal and perinatal death irrespective of the UA waveform. In fetuses with UA-AREDV, prediction of asphyxia and stillbirth was significantly enhanced by venous Doppler. CONCLUSION: Prediction of critical perinatal outcomes is improved when venous and umbilical artery qualitative waveform analysis is combined. The incorporation of venous Doppler into fetal surveillance is therefore strongly suggested for all preterm IUGR fetuses.
OBJECTIVE: To evaluate the utility of middle cerebral artery (MCA) and umbilical artery (UA) Doppler to predict anemia in intrauterine growth restricted (IUGR) fetuses. METHODS: Fetuses with an abdominal circumference < 5th percentile had UA and MCA Doppler prior to delivery. The UA pulsatility index (PI), MCA PI, ratio between the MCA/UA PI (cerebroplacental ratio, CPR) and MCA peak systolic velocity (PSV) were measured. A complete blood count was determined from a peripheral venous sample drawn at delivery. Anemia was defined as a hemoglobin value of < 13 g/dL. MCA PSV Z-scores (standard deviation from gestational age mean using references ranges by Mari et al. and Kurmanavicius et al.) were related to hemoglobin using linear regression analysis. In addition, UA absent end-diastolic velocity (AEDV), brain sparing (MCA PI > 2 SDs below gestational age mean), low CPR (> 2 SDs below gestational age mean) and an elevated MCA PSV (> 2 SDs) were evaluated for their predictive accuracy for anemia. RESULTS: Of 97 IUGR neonates 23 were anemic (23.7%). The MCA PSV was significantly related to hemoglobin using either reference range (Mari et al., F = 22.1577, Kurmanavicius et al., F = 21.8188, P < 0.001, respectively). However, using categorical cut-offs as well as regression analysis none of the Doppler parameters could be identified to provide clinically useful prediction of anemia. CONCLUSION: Parameters of MCA and UA vascular impedance and MCA PSV are significantly related to anemia in IUGR neonates. Despite this relationship the predictive accuracy is unacceptable for the clinical application in the setting of IUGR. Altered cardiovascular dynamics in IUGR fetuses may be responsible for this effect.
AIM: The association between fetal viral infection and adverse pregnancy outcome is well documented. However, the prevalence of common viral pathogens in the amniotic fluid of normal pregnancies is not established. The purpose of this study was to determine this prevalence in asymptomatic patients. METHODS: This was a prospective observational study of patients at low risk for viral infection who were referred for second-trimester genetic amniocentesis. In patients with normal fetal anatomy on ultrasound and a normal fetal karyotype, a 2-ml aliquot of amniotic fluid obtained at amniocentesis was analyzed by multiplex polymerase chain reaction for cytomegalovirus (CMV), parvovirus B19, adenovirus, enterovirus, herpes simplex virus (HSV), respiratory syncytial virus (RSV) and Epstein-Barr virus (EBV). RESULTS: Among 686 patients, advanced maternal age was the most common indication for genetic testing (n = 469, 68.4%), followed by elevated aneuploidy risk on triple screen (n = 164, 23.9%), elevated maternal serum alpha-fetoprotein (n = 20, 2.9%), previous aneuploidy (n = 16, 2.3%) and family history of inheritable disease (n = 14, 2.1%). Forty-four (6.4%) amniotic fluid samples were positive for viral genome. A single genome was amplified in 41 samples (93%). In three samples, two viral genomes were identified. Adenovirus was most frequently identified (37/44), followed by CMV (5/44), EBV (2/44), enterovirus (2/44) and RSV (1/44). Parvovirus and HSV were not identified. There was a bimodal seasonal variation in prevalence, with the highest prevalence during the summer and late winter. CONCLUSION: Viral genome is commonly found in amniotic fluid with a sonographically normal fetus, and the prevalence follows a seasonal pattern. The mechanism, significance and effects of this asymptomatic viral presence require further study.
OBJECTIVE: To evaluate relationships between neonatal intraventricular hemorrhage and altered brain blood flow in preterm growth-restricted fetuses. METHODS: One hundred and thirteen growth-restricted fetuses (birth weight < 10th centile and umbilical artery pulsatility index > two standard deviations above gestational age mean) which delivered prematurely (< 34.0 weeks) were studied. Three expressions of altered brain blood flow were defined: 'brain sparing'= middle cerebral artery pulsatility index > two standard deviations below the gestational age mean, 'centralization' = ratio of middle cerebral artery/umbilical artery pulsatility indices (cerebroplacental ratio) > two standard deviations below the gestational age mean, and 'redistribution' = absent or reversed umbilical artery end-diastolic velocity. Intraventricular hemorrhage was graded after Papile (I-IV) by cranial ultrasound performed within 7 days of delivery. RESULTS: Sixty-seven (59.3%) fetuses had brain sparing, 84 (74.3%) had centralization and 51 (45.1%) had redistribution. Fifteen (13.3%) neonates had intraventricular hemorrhage and were more likely to have a biophysical profile < 6, earlier delivery for fetal indications, lower cord artery pH, HCO3, hemoglobin, and platelets, a 10-min Apgar score < 7 and high perinatal mortality (5/15; 33.3%). No associations between intraventricular hemorrhage and brain sparing or centralization were identified. However, neonates with intraventricular hemorrhage had significantly higher umbilical artery pulsatility index deviations from the gestational age mean and a relative risk of 4.9-fold for intraventricular hemorrhage with redistribution (95% confidence interval, 1.5-16.3; P < 0.005). Multiple logistic regression revealed significant associations between intraventricular hemorrhage and a low 10-min Apgar score (r = 0.30, P < 0.005) and low hemoglobin (r = 0.28), gestational age at delivery (r = 0.25) and birth-weight centiles (r = 0.23) (P < 0.05). No Doppler parameter was identified as an independent contributor to intraventricular hemorrhage. CONCLUSION: While loss of umbilical artery end-diastolic velocity early in gestation significantly increases the risk for neonatal intraventricular hemorrhage, prematurity and difficult transition to extrauterine life remain the most important determinants of intraventricular hemorrhage.
OBJECTIVE: To test the hypothesis that hemodynamic changes depicted by Doppler precede deteriorating biophysical profile score in severe intrauterine growth restriction. METHODS: Intrauterine growth-restricted fetuses with elevated umbilical artery Doppler pulsatility index (PI) > 2 standard deviations above mean for gestational age and birth weight < 10th centile for gestational age were examined longitudinally. Fetal well-being was assessed serially with five-component biophysical profile scoring (tone, movement, breathing, amniotic fluid volume and non-stress test) and concurrent Doppler examination of the umbilical artery, middle cerebral artery and ductus venosus, inferior vena cava and free umbilical vein. For fetuses with a final biophysical profile score < 6/10, progression of biophysical profile scoring, arterial PI and venous peak velocity indices were analyzed longitudinally. Gestational age effect was removed by converting indices to Z-scores (deviation from gestational age mean, in standard deviations). RESULTS: Forty-four of 236 intrauterine growth-restricted fetuses (18.6%) required delivery for abnormal biophysical profile scoring. The median gestational age at entry was 25 weeks and 1 day and at delivery was 29 weeks and 6 days. The median interval between examinations was 1.5 days and the majority had daily testing in the week prior to delivery. Between first examination and delivery, significant deterioration was observed for Doppler criteria (chi-square, P < 0.001) and biophysical parameters (Fisher's exact, P = 0.02) predominantly confined to the week prior to delivery/stillbirth. Doppler variables changed first. In 42 fetuses (95.5%), one or more vascular beds deteriorated, accelerating especially in the umbilical artery and ductus venosus at a median of 4 days before biophysical profile scoring deteriorated. Two to 3 days before delivery, fetal breathing movement began to decline. The next day, amniotic fluid volume began to drop. Composite biophysical profile score dropped abruptly on the day of delivery, with loss of fetal movement and tone. Three principal patterns of Doppler deterioration were observed: (i) worsening umbilical artery PI, advent of brain sparing and venous deterioration (n = 32, 72.7%); (ii) abnormal precordial venous flows, advent of brain sparing (n = 6, 13.6%); and (iii) abnormal ductus venosus only (n = 4, 9.1%). In the majority (31, 70.5%), Doppler deterioration was complete 24 h before biophysical profile score decline. In the remainder (11, 25%), Doppler deterioration and biophysical profile score < 6/10 were simultaneous. CONCLUSION: In the majority of severely intrauterine growth-restricted fetuses, sequential deterioration of arterial and venous flows precedes biophysical profile score deterioration. Adding serial Doppler evaluation of the umbilical artery, middle cerebral artery and ductus venosus to intrauterine growth restriction surveillance will enhance the performance of the biophysical score in the detection of fetal compromise and therefore optimizing the timing of intervention.
BACKGROUND: Cardiac anomalies may be associated with abnormal coronary vascular connections. We report the prenatal diagnosis of ventriculocoronary fistula in three fetuses with associated cardiac anomalies. MATERIALS AND METHODS: Fetal echocardiography was performed in three patients referred for suspected cardiac anomaly. Two-dimensional fetal echocardiography was complemented by color Doppler flow imaging and spectral Doppler in all cases. RESULTS: A ventriculocoronary fistula was diagnosed in three patients referred at 22, 23 and 32 weeks. The first patient had hypoplastic left heart associated with transposition of the great arteries and pulmonary atresia with an intact interventricular septum. The coronary fistula arose from the transposed aorta to the left ventricle. In two patients ventriculocoronary fistula was found in association with pulmonary atresia and an intact interventricular septum. In all cases there was bidirectional flow within the fistula (diastolic blood flow towards the ventricle with reversal during ventricular systole). The pregnancy with hypoplastic left heart with transposition, and one of those with pulmonary atresia resulted in neonatal death and stillbirth, respectively. In the third instance the ventriculocoronary fistula was verified by postpartum cardiac angiography. The infant initially received a Blalock-Taussig shunt, subsequently replaced by a bidirectional Glenn shunt, and was doing well at the time of writing. CONCLUSION: A ventriculocoronary fistula can be identified prenatally by color and spectral Doppler. This anomaly should be sought in fetuses with outflow tract obstructive cardiac lesions and an intact interventricular septum. Prenatal diagnosis allows early angiography postnatally. Delineation of coronary vascular regions may therefore facilitate preoperative planning.
Babies who are small due to intrauterine growth restriction are at higher risk for poor perinatal and long-term outcome than those who are appropriately grown. Through multiple antenatal testing modalities a sequence of deteriorating fetal status can be documented in such cases. The nature of this compromise is best reflected by the combination of fetal biometry, biophysical profile scoring and arterial and venous Doppler. This combination accurately defines fetal states and therefore risk of stillbirth or poor transition to extrauterine life. In the preterm neonate, fetal factors, gestational age and neonatal course interact significantly to impact on short- and long-term outcomes. The potential for iatrogenic prematurity is great and ongoing appraisal of peripartum management is critical. An integrated management protocol accounting for these factors is examined in this review.
OBJECTIVE: To examine the relationship between umbilical artery (UA) end-diastolic flow and neonatal thrombocytopenia. METHODS: We prospectively examined 115 anatomically normal single fetuses with UA pulsatility indices more than two standard deviations above the gestational age mean and subsequent birth weights below the tenth percentile. Peripheral neonatal platelet counts in fetuses with positive UA end-diastolic velocity were compared with those of fetuses with absent or reversed UA end-diastolic velocity. RESULTS: Sixty-seven fetuses (58.3%) had positive UA end-diastolic velocity and 48 (41.7%) had absent or reversed UA end-diastolic velocity. Three neonates in the positive-flow group and 22 neonates in the absent- or reversed-flow group had platelet counts of less than 100, 000/mm(3) (relative risk 10.2; 95% confidence interval; 3.2, 32.3; P <.001). Absent or reversed end-diastolic velocity had a sensitivity of 88%, specificity of 71%, positive predictive value of 46%, and negative predictive value of 96% for predicting neonatal thrombocytopenia. Neonates with absent or reversed flow also had lower median platelet counts (101,500/mm(3) versus 208,000/mm(3), P <.001), hemoglobin levels (15.1 versus 16.4 g/dL, P <.01), and hematocrits (47.6 versus 51.1%, P <.05), as well as higher nucleated red blood cell counts (191 versus 15 per 100 white blood cells, P <. 001). CONCLUSION: Absent or reversed UA end-diastolic velocity in growth-restricted fetuses is associated with a statistically significant increase in risk of neonatal thrombocytopenia.
OBJECTIVE: To determine the relationship between fetal coronary blood flow (CBF) visualization in intrauterine growth restriction (IUGR), longitudinal changes in arterial and venous flow velocity waveforms and perinatal outcome. METHODS: A total of 48 IUGR fetuses (abdominal circumference below the 5th percentile for gestational age) with absent or reversed umbilical artery (UA) end-diastolic velocity (AREDV) were examined longitudinally by echocardiography attempting CBF visualization at each examination. Doppler evaluation of the middle cerebral artery, inferior vena cava (IVC), ductus venosus (DV) and umbilical vein (UV) was performed at each examination. Doppler measurements were correct for gestational age by conversion into Z-scores (delta-indices). Doppler results and outcome from fetuses in which CBF was visualized (group 1, n = 20) and those in which CBF was never visualized (group 2, n = 28) were compared. Outcome parameters analyzed included Apgar scores, cord arterial blood gases, perinatal mortality, respiratory distress, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis and postpartum circulatory failure requiring pressor support. RESULTS: There was no difference in Doppler indices between groups at study entry. CBF visualization coincides with a significant increase of UA-, IVC- and DV delta-indices. The greatest rate of change was observed for indices in the ductus venosus which occurred in the 24 h preceding CBF visualization. Group 1 fetuses required earlier delivery (median 27 + 4, vs. median 30 + 0), had lower birthweight (682 +/- 305 g vs. 936 +/- 416 g), lower cord pH (7.21 +/- 0.1 vs. 7.27 +/- 0.06) and cord pO2 (13 +/- 4.5 vs. 24.1 +/- 13.5 mmHg) compared to group 2 (all values P < 0.05). Mortality was similar (group 1 = 6/20, 30%; group 2 = 6/28, 21.4%). CONCLUSIONS: In IUGR, fetuses with AREDV and centralization are at high risk for hypoxemia, acidemia and adverse outcome. CBF visualization coincides with deteriorating venous flows. Operator dependence of CBF visualization and the strong association with abnormal venous flow stresses the importance of venous Doppler surveillance in these fetuses.
OBJECTIVE: The aim of this investigation was to assess the relationship between abnormal arterial and venous Doppler findings and perinatal outcome in fetuses with intrauterine growth restriction (IUGR). METHODS: Doppler velocimetry of the umbilical artery (UA), middle cerebral artery (MCA), inferior vena cava (IVC), ductus venosus (DV) and free umbilical vein was performed in 121 IUGR fetuses with a UA pulsatility index (PI) > 2 SD above the gestational age mean and subsequent birth weight < 10th centile for gestational age. Groups based on the last Doppler exam were: 1 = abnormal UA-PI only (n = 42, 34.7%), 2 = MCA-PI > 2 SD below the gestational age mean (= 'brain sparing') in addition to abnormal UA-PI (n = 29, 24.0%), 3 = DV or IVC peak velocity index (PVIV) > 2 SD above the gestational age mean and/or pulsatile UV flow (n = 50, 41.3%). Z-scores (delta indices) were calculated for Doppler indices. Perinatal mortality, respiratory distress (RDS), bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), circulatory failure and umbilical artery blood gases were recorded. RESULTS: Absence or reversal of umbilical artery end-diastolic flow was observed in 4 (9.5%) of fetuses in group 1, 10 (34.5%) fetuses in group 2 and 41 (82%) fetuses in group 3. A low middle cerebral artery pulsatility index was found in 39 (78%) fetuses in group 3. Multiple regression analysis with gestational age at delivery, delta indices and cord artery blood gas as independent parameters and individual perinatal outcomes as dependent variables was performed. In this analysis the association was strongest with gestational age for each complication. There were no significant differences in Apgar scores between groups. At delivery, 'brain sparing' was associated with hypoxemia and abnormal venous flows with acidemia. Perinatal mortality was highest in group 3 and stillbirth was only observed when venous flow was abnormal. All postpartum complications were more frequent in fetuses with abnormal venous flows. The only statistically significant relation between Doppler indices and outcome was the association between abnormal ductus venosus flow and fetal death (r2 = 0.24, P < 0.05). CONCLUSION: Growth restricted fetuses with abnormal venous flow have worse perinatal outcome compared to those where flow abnormality is confined to the umbilical or middle cerebral artery. In fetuses with low middle cerebral artery pulsatility, venous Doppler allows detection of further deterioration. While abnormal venous flows can be significantly associated with fetal demise, gestational age at delivery significantly impacts on all short-term outcomes.
AIMS: To document the incidence of popliteal lymph node involvement by metastatic melanoma and to consider the implications of this information for clinical management. METHODS: From the computerized database of the Sydney Melanoma Unit, all patients with primary melanomas located at or distal to the knee were identified and their records were examined. Experience with those patients who developed popliteal node metastases was then reviewed. RESULTS: Thirteen of 4262 patients (0.31%) with primary melanomas of the distal lower limb developed popliteal node metastases. Six of the 13 patients had previous, synchronous or subsequent groin node metastases. CONCLUSIONS: Popliteal lymph node involvement by metastatic melanoma is a rare event. The study results suggest only two indications for full popliteal node clearance-either a histologically positive sentinel node in the popliteal fossa or clinical evidence of metastatic disease in a popliteal node.
HYPOTHESIS: Sporadic primary hyperparathyroidism (1 HPT) in young persons is thought to be extremely rare. The exact incidence is unknown and little is known of the characteristics of the disease. METHODS: From 1976 to 1998, 33 patients aged 19 years or younger underwent operation for sporadic 1 HPT at a single institution. Data were recorded regarding the clinical, surgical, pathologic, and biochemical aspects, as well as long-term patient follow-up. RESULTS: There were 17 male subjects and 16 female subjects ranging in age from 9 to 19 years (median age, 17 years). Thirty-one (94%) were symptomatic: 14 (42%) had renal stones, 9 (27%) had bone disease, 1 (3%) had pancreatitis, and 7 (21%) had vague nonspecific symptoms alone. The high incidence of symptoms was matched by correspondingly high biochemical values (mean serum calcium level, 3.02 mmol/L [12.1 mg/dL]) and large adenomas (mean weight, 967 mg). Five patients (15%) underwent exploration for persistent/recurrent 1 HPT. Thirty-one patients (94%) were normocalcemic postoperatively. One patient was temporarily hypocalcemic. No patient had vocal cord paralysis or paresis. Two patients developed recurrent disease in the mean follow-up period of 10.3 years. None have shown evidence of an inherited disorder. CONCLUSIONS: It appears that 1 HPT in young patients presents as a more severe disease, in terms of symptoms, biochemistry, and extent of pathologic findings. Physicians should be aware that 1 HPT does occur in young persons in a nonfamilial setting and that it may be responsible for a wide spectrum of symptoms. As in the adult population, 1 HPT is safely and effectively treated with surgical intervention.
The calculation of incidence rates of melanoma in New Zealand has been hampered in the past by incomplete registration of cases. The aim of this study was to document the incidence of melanoma in the Auckland Caucasian population and to define the pathologic characteristics of these lesions. Data were collected for the Auckland region from the New Zealand Cancer Registry and the Auckland Melanoma Unit database for 1995 and combined with census statistics to give the crude and age-standardized rates for invasive melanoma. The results were analyzed by gender, morphology, body site, and thickness. The crude annual incidence for invasive cutaneous malignant melanoma was 77.7/100,000. The age-standardized annual rate was 56.2/100,000 with no statistically significant differences in the rates for males and females. The cumulative risk of developing melanoma over a lifetime, from age 0 to 74, was 5.7% overall. The age-specific rates steadily increase with advancing age. The lesions were generally thin; 64% were less than 0.76 mm, and only 7% were thicker than 3.00 mm. In conclusion, the Caucasian population in the Auckland region has the highest incidence of melanoma in the world.
OBJECTIVE: It was our goal to determine the false-negative rate of the biophysical profile, characterize an 18-year variation in the false-negative rate, examine the relationship between the last normal biophysical profile score and death, and compare the false-negative rate of 2 disparate populations. STUDY DESIGN: Biophysical profile scores of 86,955 patients at 2 medical centers were collected and recorded prospectively. All perinatal deaths occurring within 1 week of a normal score were similarly recorded. The annual false-negative rate, the cumulative false-negative rate, and the ratio of false-negative results in cases of subsequent fetal death to the perinatal mortality rate were calculated. RESULTS: There were 65 fetal deaths among 86,955 fetuses. Over an 18-year study period at one institution, the false-negative rate varied but not significantly. The cumulative false-negative rate was 0.708 per 1000 at one medical center studied and 2.289 per 1000 at the other center. The average interval between last normal score and fetal death was 3.62 days and did not vary significantly between the medical centers. CONCLUSIONS: False-negative results in cases of subsequent fetal death reflect events that are subsequent to the last normal test result. Fetomaternal hemorrhage was the single most identifiable fetal cause of false-negative results in cases of subsequent fetal death. The ratio of the false-negative rate in cases of subsequent fetal death to the perinatal mortality rate should be used as a more objective approach to reporting this value, because the false-negative rate likely reflects the underlying perinatal mortality.
OBJECTIVE: Elevated nucleated red blood cell count in neonatal blood and Doppler-detected circulatory decompensation in fetuses with intrauterine growth restriction are associated with hypoxemia. We sought to determine the relationship between the nucleated red blood cell count at birth and the circulatory status of fetuses with intrauterine growth restriction. STUDY DESIGN: Eighty-four fetuses with elevated umbilical artery pulsatility index values >2 SD above the gestational age mean and a subsequent birth weight <10th percentile were examined serially. Umbilical and middle cerebral artery pulsatility index, inferior vena cava and ductus venosus peak velocity index, and flow pattern in the umbilical vein (umbilical vein constant vs pulsatile) were recorded. Fetuses were grouped as follows, on the basis of the last examination before delivery: 1, elevated umbilical artery pulsatility index only; 2, middle cerebral artery pulsatility index >2 SD below the gestational age mean in addition to abnormal umbilical artery pulsatility index; 3, either peak velocity index >2 SD above the gestational age mean in the inferior vena cava and ductus venosus or pulsatile flow in the umbilical vein, or both. Nucleated red blood cells per 100 white blood cells were ascertained in a peripheral blood sample obtained within 1 hour of delivery with daily follow-up samples until the nucleated red blood cell count was <5/100 white blood cells. RESULTS: Groups 2 (median 38.5, range 1-273) and 3 (median 145, range 2-3180) had higher nucleated red blood cell counts than group 1 (median 8.5, range 1-270) (P <.05 and P <.005, respectively). The persistence of the nucleated red blood cell count elevation was also longer in groups 3 (median 4 days, range 1-19 days) and 2 (median 2. 5 days, range 1-7 days) than in group 1 (median 1 day, range 1-8 days). Neonates in group 3 also had lower platelet count, hemoglobin value, hematocrit value, and white blood cell count. The umbilical cord artery bicarbonate level was the strongest independent determinant of the peak nucleated red blood cell count and persistence of nucleated red blood cell elevation (r (2) = 0.27, P <. 001 and r (2) = 0.47, P <.0001). CONCLUSION: Increasing abnormality of arterial and venous flows in fetuses with intrauterine growth restriction is associated with increasing nucleated red blood cell count at birth. Metabolic acidemia rather than altered PO (2 ) associated with this circulatory state appears to be the main determinant of the rise in nucleated red blood cells.