Fetal size monitoring and birth-weight prediction: a new population-based approach.

OBJECTIVE: To develop a complete, population-based system for ultrasound-based fetal size monitoring and birth-weight prediction for use in the second and third trimesters of pregnancy. METHODS: Using 31 516 ultrasound examinations from a population-based Norwegian clinical database, we constructed fetal size charts for biparietal diameter, femur length and abdominal circumference from 24 to 42 weeks' gestation. A reference curve of median birth weight for gestational age was estimated using 45 037 birth weights. We determined how individual deviations from the expected ultrasound measures predicted individual percentage deviations from expected birth weight. The predictive quality was assessed by explained variance of birth weight and receiver-operating characteristics curves for prediction of small-for-gestational age. A curve for intrauterine estimated fetal weight was constructed. Charts were smoothed using the gamlss non-linear regression method. RESULTS: The population-based approach, using bias-free ultrasound gestational age, produces stable estimates of size-for-age and weight-for-age curves in the range 24-42 weeks' gestation. There is a close correspondence between percentage deviations and percentiles of birth weight by gestational age, making it easy to convert between the two. The variance of birth weight that can be 'explained' by ultrasound increases from 8% at 20 weeks up to 67% around term. Intrauterine estimated fetal weight is 0-106 g higher than median birth weight in the preterm period. CONCLUSIONS: The new population-based birth-weight prediction model provides a simple summary measure, the 'percentage birth-weight deviation', to be used for fetal size monitoring throughout the third trimester. Predictive quality of the model can be measured directly from the population data. The model computes both median observed birth weight and intrauterine estimated fetal weight. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Advantages of the population-based approach to pregnancy dating: results from 23,020 ultrasound examinations.

OBJECTIVE: To confirm the results from two previous evaluations of term prediction models, including two sample-based models and one population-based model, in a third population. METHODS: In a study population of 23,020 second-trimester ultrasound examinations, data were prospectively collected and registered over the period 1988-2009. Three different models for ultrasonically estimated date of delivery were applied to the measurements of fetal biparietal diameter (BPD) and two models were applied to the femur length (FL) measurements; the resulting term estimations were compared with the actual time of delivery. The difference between the actual and the predicted dates of delivery (the median bias) was calculated for each of the models, for three BPD/FL-measurement subgroups and for the study population as a whole. RESULTS: For the population-based model, the median bias was + 0.4 days for the BPD-based predictions and - 0.4 days for the FL-based predictions, and the biases were stable over the inclusion ranges. The biases of the two traditional models varied with the size of the fetus at examination; median biases were - 0.87 and + 2.2 days, respectively, with extremes - 4.2 and + 4.8 days for the BPD-based predictions, and the median bias was + 1.72 days with range - 0.8 to + 4.5 days for FL-based predictions. The disagreement between the two sample-based models was never less than 2 days for the BPD-based predictions. CONCLUSION: This study confirms the results from previous studies; median biases were negligible with term predictions from the population-based model, while those from the traditional models varied substantially. The biases, which have clinical implications, seem inevitable with the sample-based models, which, even if overall biases were removed, will perform unsatisfactorily.

A new population-based term prediction model vs. two traditional sample-based models: validation on 9046 ultrasound examinations.

OBJECTIVES: To compare results of predictions of date of delivery from a new population-based model with those from two traditional regression models. METHODS: We included 9046 fetal biparietal diameter (BPD) measurements and 8776 femur length (FL) measurements from the routine ultrasound examinations at Stavanger University Hospital between 2001 and 2007. The prediction models to be validated were applied to the data, and the resulting predictions were compared with the actual time of the subsequent deliveries. The primary measure was the median bias (the difference between the true and the predicted date of delivery), calculated for each method, for the study population as a whole and for three subgroups of BPD/FL measurements. We also assessed the proportion of births within ± 14 days of the predicted day, and rates of preterm and post-term deliveries, which were regarded as secondary measures. RESULTS: For the population-based model, the median bias was -0.15 days (95% confidence interval (CI), -0.43 to 0.12) for the BPD-based, and -0.48 days (95% CI, -0.86 to -0.46) for the FL-based predictions, and both biases were stable over the inclusion ranges. The biases of the traditional regression models varied, depending on the fetal size at the time of the examination; the extremes were -3.2 and + 4.5 days for the BPD-based, and -1.0 and + 5.0 days for the FL-based predictions. CONCLUSIONS: The overall biases, as well as the biases for the subgroups, were all smaller with the population-based model than with the traditional regression models, which exhibited substantial biases in some BPD and FL subcategories. For the population-based model, the FL-based predictions were in accordance with the BPD-based predictions.

Narrowed beam width in newer ultrasound machines shortens measurements in the lateral direction: fetal measurement charts may be obsolete.

OBJECTIVES: Fetal ultrasound measurements are made in axial, lateral and oblique directions. Lateral resolution is influenced by the beam width of the ultrasound system. To improve lateral resolution and image quality, the beam width has been made narrower; consequently, measurements in the lateral direction are affected and apparently made shorter, approaching the true length. The aims of this study were to explore our database to reveal time-dependent shortening of ultrasound measurements made in the lateral direction, and to assess the extent of beam-width changes by comparing beam-width measurements made on old and new ultrasound machines. METHODS: A total of 41,941 femur length measurements, collected during the time-period 1987-2005, were analyzed, with time as a covariate. Using three ultrasound machines from the 1990s and three newer machines from 2007, we performed 25 series of blinded beam-width measurements on a tissue-mimicking phantom, measuring at depths of 3-8 cm with a 5-MHz transducer. RESULTS: Regression analysis showed time to be a significant covariate. At the same gestational age, femur length measurement was 1.15 (95% CI, 1.08-1.23) mm shorter in the time-period 1999-2005 than in the time-period 1987-1992. Overall, the beam width was 1.08 (95% CI, 0.50-1.65) mm narrower with the new machines than with the old machines. CONCLUSIONS: Technical improvements in modern ultrasound machines that have reduced the beam width affect fetal measurements in the lateral direction. This has clinical implications and new measurement charts are needed.

Biases of traditional term prediction models: results from different sample-based models evaluated on 41 343 ultrasound examinations.

OBJECTIVE: To evaluate two Norwegian traditional, sample-based term prediction models as applied to the data from a large population-based registry. The two models were also compared with an established German model. METHODS: Our database included information from 41 343 non-selected ultrasound scans registered over the years 1987-2005. The prediction models were applied to measurements from the ultrasound examinations, and the resulting term predictions were compared with the actual times of the deliveries. The median bias (the difference between the true and the predicted date of delivery) was calculated for each model, both for the study population as a whole and for subgroups of measurements of biparietal diameter (BPD) and femur length (FL). Secondary measures, i.e. proportion of births within ± 14 days and the rates of preterm and post-term deliveries, were also assessed. RESULTS: The analyses showed that the models had significant biases, predicting delivery date either too late or too early. For each model the size of the bias varied, depending on the fetal size at the time of the examination; the extremes were minus 4 and plus 4 days for the BPD-based predictions. There were similar results with the FL-based predictions. CONCLUSION: Term predictions made with traditional sample-based models had significant biases that varied over each method's measurement range. These models have important shortcomings, probably because of strict selection criteria in the process of constructing the models, and because the methods primarily aim at estimating the last menstrual period-based day of conception, not the day of birth.

Evolution of vectorcardiographic QRS changes during myocardial infarction in dogs and their relation to infarct size.

The ability of vectorcardiographic QRS changes to quantify myocardial ischaemia and necrosis in dogs was studied. Myocardial infarction was produced in 21 anaesthetised dogs by inflating a balloon inserted into the right, left anterior descending, or left circumflex coronary artery. A Frank vectorcardiogram was recorded before and every 15-30 minutes for 10 hours after the occlusion. ST vector magnitude (ST-VM), QRS summation vectors, and QRS integral differences (QRS-VD) between the preocclusion recording and subsequent recordings were computed. Twenty four hours after occlusion two vectorcardiograms were obtained, the hearts removed, and the infarcts cut out and weighed. Four dogs were excluded from the study because of persistent arrhythmias, major conduction defects, or sudden death. In the remaining 17 dogs the QRS summation vectors rotated maximally towards the site of infarction 7 minutes after occlusion corresponding to a median minimum QRS-VD of -19 (range -2 to -29) microVs. This coincided with the maximum ST-VM, median 0.43 (range 0.12-0.68) mV. The QRS summation vectors subsequently rotated away from the infarct producing a median maximum QRS-VD of 20 (range 6-28) microVs. The maximum QRS-VD correlated significantly with the percentage of infarcted myocardium (r = 0.82). The correlation between the early minimum QRS-VD and the maximum ST-VM was r = 0.83. The QRS-VD was recomputed with a reference taken 2 or 4 hours after occlusion. The relation between maximum QRS-VD and infarct percentage was not significantly changed with the reference at 2 hours, but with the reference at 4 hours the ability to predict infarct size was lost.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative and temporal relation between the release of myoglobin and creatine kinase and the evolution of vectorcardiographic changes during acute myocardial infarction in man.

The relation in time and magnitude between QRS vector changes (QRS-VD), ST vectors (ST-VM), and the cumulated release of myoglobin, total creatine kinase, and creatine kinase isoenzyme MB was studied. Seventy four patients with a first myocardial infarction and a history of symptoms of up to 5 h were included. Blood samples for enzyme analysis were taken every 4-6 h for 72 h and cumulated enzyme release was calculated from a monocompartmental first order model. QRS-VD and ST-VM were determined every 10 min for 24 h by computer analysis of Frank lead vectorcardiograms. Infarct sizes were visually determined from the different enzymatic and vectorcardiographic evolution curves. Eight patients were excluded from the analysis because they had a QRS width greater than or equal to 120 ms or ill defined plateaus of the release curves. The relation between infarct sizes estimated from QRS-VD and total creatine kinase was r = 0.62; QRS-VD and myoglobin release r = 0.57; total creatine kinase and myoglobin release r = 0.72, showing that these variables are good and complementary indices for estimating myocardial infarct size. Median infarct evolution curves were computed after the individual curves were normalised to 100%. ST-VM fell rapidly during the first 7 h to 40% of the initial values. QRS-VD and myoglobin release were closely associated and completed their development on average 15 h after the onset of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of atherosclerotic lesions in the bifurcation of the main left coronary artery.

The detailed distribution of atherosclerotic lesions in the branching region of the left main coronary artery in man was studied. Tissue cubes of the hearts, containing the left coronary arteries, were removed, and 1.5-mm-thick parallel and consecutive slices were cut perpendicular to the main coronary artery. Histological sections of the slices were stained and photographed. Drawings of the cross-sections of the arteries, including information about thickness of the intima and borders of the atherosclerotic lesions, were fed into a computer, scaled and analyzed. Casts were made of the left main coronary bifurcation from additional hearts. The curvature of the arteries and the angles of the bifurcation were measured. Atherosclerotic lesions have a distinct pattern with a high frequency on the outer walls of the bifurcation and at the inner curvature downstream from the bifurcation. The extent of intimal thickening and the occurrence of atherosclerotic lesions were mostly in agreement.

Effect of timolol on mortality and reinfarction after acute myocardial infarction: prognostic importance of heart rate at rest.

Long-term timolol treatment after acute myocardial infarction is associated with a significant reduction in mortality and nonfatal reinfarction. To evaluate whether the reduction in mortality and morbidity is exclusively or partly dependent on a reduction in heart rate (HR), cardiac events in the Norwegian Timolol Multicenter Study were analyzed according to resting HR at baseline and at 1 month of follow-up Resting HR at baseline was a significant predictor of total death and all events (total death plus nonfatal reinfarction) both in placebo- and in timolol-treated patients. In the placebo group the median resting HR was unchanged from baseline to 1 month control (72 beats/min), but was reduced from 72 beats/min to 56 beats/min in the timolol group. Resting HR during follow-up remained a significant predictor of total death. Further, mortality at a given HR during treatment was not markedly different whether the HR was spontaneous or caused by timolol. Timolol treatment was related to a significant reduction in mortality, and this study suggests that the major effect of timolol treatment on mortality after acute myocardial infarction may be attributed to the reduction in HR. Timolol treatment was also associated with an overall reduction in nonfatal reinfarction. However, nonfatal reinfarction was inversely related to resting HR during follow-up, indicating that although coronary artery occlusion in low-risk patients may cause nonfatal reinfarction, the outcome in high-risk patients is more likely to be death. When analyzing mortality and nonfatal reinfarction combined, timolol treatment was related to a reduction in cardiac events at any given HR, suggesting that factors in addition to HR reduction are important in the protective effects of timolol.

A direct method for ultrasound prediction of day of delivery: a new, population-based approach.

OBJECTIVES: To introduce a direct population-based method for prediction of term based on ultrasound measurements of the biparietal diameter and femur length in the second trimester of pregnancy. METHODS: Our data consisted of 41 343 ultrasound scans from a non-selected population, prospectively collected during the years 1987-2004. Using measurements of biparietal diameter and femur length, we constructed prediction curves for term by computing median remaining time of pregnancy from the ultrasound measurement to birth. A local linear quantile regression method was used to smooth the median and quantile curves. RESULTS: The quality of term prediction was stable over the prediction range for both biparietal diameter (25-60 mm) and femur length (11-42 mm). The femur-based predictions were nearly as good as those of the biparietal diameter. For the biparietal diameter, the median of the prediction residual was -0.09 days; 87.2% of the births fell within +/- 14 days of the predicted day of delivery, 3.5% births were classified as preterm and 4.3% as post-term. The corresponding figures for femur length were - 0.04 days, 86.7%, 3.6% and 4.5%. The covariates maternal age, parity, mother's smoking habits, sex of the fetus and examination year generally affected the predicted term by less than 1 day. CONCLUSIONS: This direct ultrasound-based prediction of term using population-based data avoids selection biases possibly present in smaller prospective samples. The model obviates the dependence on last menstrual period found in standard methods for term prediction, and allows an immediate assessment of prediction quality in a population setting. The femur-based predictions had a quality similar to those based on the biparietal diameter. The model can be updated continuously as new data are collected.

Real-time serial analysis of infarctional changes in the vectorcardiogram.

Infarct size evolution can be readily assessed from spatial QRS and ST segment changes. A computer system for real-time serial analysis of QRS and ST segment changes in the vectorcardiogram has been developed. QRS detection is done by multichannel template matching, the template being the running average complex. Detection of QRS onset and end is done by a two-dimensional pattern recognition technique on the spatial velocity function using fixed templates. Tested on 216 recordings from 11 patients undergoing myocardial infarction 92.9% of 6050 beats were correctly detected with 0 false detections. The differences between program and referee estimates of QRS onset and of QRS end were computed in 1015 average complexes from the same group of patients. The median (0.05 and 0.95 fractiles) differences were 0.6 msec (-1.9 and 3.9 msec) for QRS onset and -2.0 msec (-16.7 and 3.7 msec) for QRS end. A similar test was made on the annotated CSE database. The results were -2.2 msec (-6.9 and 10.6 msec) for QRS onset and -1.6 msec (-14.6 and 5.2 msec) for QRS end. Systematic errors in QRS onset or QRS end of +/- 8 msec will produce 3-4% error of the average infarct size estimated by QRS vector changes. In conclusion, the present system can provide instantaneous information about the development of myocardial infarction which may be of importance in the management of infarct-limiting treatment.

Body hair growth in women: normal or hirsute.

The distribution and density of terminal hair growth in 19 different body regions in 113 women of fertile age complaining of embarrassing hair growth (group A) are compared with the findings in 100 normal women of comparable age (group B). Apart from three regions the former group demonstrated significantly more frequent and heavier hair growth than the latter. A stepwise discriminant analysis showed that the best separation between the two groups could be obtained by assessing the hair growth in the lip, chin, and public region. With this set of variables, four women from group A were incorrectly classified as belonging to group B and one woman from group B was classified as belonging to group A. The serum concentration of testosterone was significantly higher and the serum concentration of TeBG significantly lower in group A than in group B (P less than 0.001). Menstrual pattern, body weight, and hereditary factors in group A vs. group B support the impression that the increased terminal hair growth found in group A is due to physiological factors. From the present data it can be concluded that appraisal of the facial and public terminal hair growth should in most cases be sufficient for separating possible hirsutism from normal hair growth in women.

A comparison of cumulated CK release with three vectorcardiographic methods of estimating myocardial infarct size.

Infarct size estimated by three vectoracardiographic methods was compared with cumulated CK release in 66 patients admitted to hospital within five hours after onset of myocardial infarction. Infarctional changes in the QRS complex were sequentially computed from a continuous 24-hour recording of Frank lead VCG by: (I)-the integrals of QRS vector differences (QRS-VD) relative to the first recording obtained after hospitalization, (II)-the integral of spatial magnitude during the period of initial abnormal depolarization (IAD), (III)-The sum of R-wave amplitude in leads X and Y and Q-wave amplitude in lead Z (sigma R). From the time-trend curves of cumulated CK release, QRS-VD, IAD and sigma R terminal plateau levels were visually determined representing estimated infarct size (ISCK, ISQRS-VD, ISIAD and IS sigma R). The correlation coefficients were: between ISCK and ISQRS-VD r = 0.62, p less than 0.001, ISCK and ISIAD r = 0.22, p = NS, ISCK and IS sigma R r = -0.22, p = NS. The correlation for ISQRS-VD was significantly better than for ISIAD (p = 0.011) and IS sigma R (p = 0.005). The IAD time-trend curves were inconsistent, falling in 24 and rising in 24 patients. For sigma R the corresponding figures were 56 and 10 patients. Thus, neither IAD nor sigma R have been shown to predict infarct size correctly at an early stage or to describe infarct evolution adequately.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of early atherosclerotic lesions in the right carotid bifurcation in humans.

The detailed localization of early atherosclerotic lesions in the right carotid bifurcation was studied in 37 carotid arteries obtained from autopsies of young persons who had suffered a violent and sudden death. Drawings of the sudanophilic lesions in the vessel wall were fed to a computer, scaled to a standardized size and shape, and added together. The results are presented as contour lines connecting points with equal frequency of early lesions. The distribution of early lesions reveals a distinct pattern: The early lesions start to develop on the outer walls of the bifurcation, while the inner walls downstream from the flow divider are left free, as are also the lateral walls. In the carotid sinus the distribution of the lesions has a U-formed pattern.

Estimation of fetal weight by ultrasound measurement. I. Development of a new formula.

A formula for the estimation of fetal weight combining real-time ultrasonic measurement of the fetal biparietal diameter (BPD) and the abdominal transverse diameter (ATD) has been developed. The computer-aided regression analysis was based on measurements of 396 unselected fetuses with birth weight range 680-5080 g. The measurements were made within 4 days of delivery. A main purpose was to construct a formula which could be used for prediction of fetal weight within the range 1000-5000 g and where special emphasis was placed on accuracy in the low and high weight groups. A stratified sample of 150 fetuses was therefore selected at random from the whole group. To obtain an optimum curve fitting between the explanatory variables and birth weight, various regressions of quadratic and cubic degree, regressions of exponential functions and power functions were made. The best fit was provided by a power function of the variables. In the second part of this study, this formula will be tested on a clinical material.

Polycystic ovarian syndrome: a follow-up study on fertility and menstrual pattern in 149 patients 15-25 years after ovarian wedge resection.

BACKGROUND: The aim of this study was to evaluate fertility and menstrual pattern in women with polycystic ovarian syndrome (PCOS) 15-25 years after ovarian wedge resection (OWR). METHODS AND RESULTS: The diagnosis was based on the combination of ovarian pathology and symptoms. The 149 patients, all primarily treated at a university teaching hospital, were studied three times by means of a questionnaire up to 25 years after surgery. Kaplan-Meier analysis showed a cumulative rate of spontaneous pregnancies of 76%, increasing to 88% when induced pregnancies were included. The cumulated live birth rate was 78%. A bootstrap simulation indicated that 69.5% would develop post-operative adhesions, which could impede pregnancy in 13.4%. In the majority of the patients a regular menstrual pattern was restored up to 25 years after OWR. CONCLUSION: The results of OWR in PCOS are favourable to most modern treatments. Laparoscopic electrocautery of the ovaries is the only method equally successful, and, by being less invasive, it has made OWR history in the treatment of PCOS.

Ultrasonic assessment of abdominal venous return. II. Volume blood flow in the inferior vena cava and portal vein.

Eighty-five patients subjected to routine heart catheterization, were examined with duplex scanning of the inferior vena cava and portal vein. Volume blood flow in the two veins was estimated and compared with Fick measured cardiac output and duplex measured flow in the lower thoracic aorta. Inferior vena caval and portal vein flow were found to comprise approximately 30 to 40 per cent and 20 per cent, respectively, of cardiac output, but with a large dispersion of individual percentages. A high correlation (r = 0.88) was found between the sum of inferior vena caval and portal vein flow and duplex measured flow in the lower thoracic aorta, the sum of flow in the two veins comprising approximately 90 per cent of lower thoracic aortic flow. It is concluded that duplex scanning seems to be a useful method in estimating volume blood flow in both the inferior vena cava and portal vein.

A comparison between ultrasound and a reliable last menstrual period as predictors of the day of delivery in 15,000 examinations.

In a non-selected population comprising 15,241 women, an evaluation was performed of the ultrasonic measurement of the biparietal diameter compared with a reliable last menstrual period as the basis for estimation of the day of delivery. In women with a reliable menstrual history and spontaneous onset of labor, the ultrasound estimate was the significantly better predictor of the day of delivery in 52% of cases, and the last menstrual period estimate was the better predictor in 46% of cases. The percentages of women who delivered within 7 days of the predicted day were 61 and 56% for the ultrasound and the last menstrual period estimations, respectively. There was a significantly narrower distribution of births according to the ultrasound estimate (p < 0.001). The proportion of estimated postterm births was 4% using the ultrasound method and 10% using the last menstrual period method (p < 0.001). Even when the difference between the methods in predicting the day of delivery was less than 7 days, the ultrasound method was better than the last menstrual period method. It is concluded that ultrasonic measurement of the biparietal diameter between 15 and 22 weeks of pregnancy is the best method for the estimation of the day of delivery and should be used as a routine procedure.

Quantitative assessment of myocardial ischemia and necrosis by continuous vectorcardiography and measurement of creatine kinase release in patients.

The accuracy of the use of the maximal QRS vector difference to estimate myocardial infarct size irrespective of infarct location was compared with that of measurement of cumulative creatine kinase (CK) release. Sixty patients with acute myocardial infarction and a history of symptoms of less than 4 hr duration were followed for 24 to 72 hr with orthogonal vectorcardiography and CK release analysis. Spatial QRS vector differences were calculated between the first QRS complex recorded and subsequent QRS complexes at timed intervals. The QRS vector difference increased rapidly and reached a plateau at an average 12.1 hr after onset of symptoms, as compared with 34.0 hr for the cumulated CK release. In 42% of the patients a stepwise progression of infarct evolution was observed. Irrespective of infarct location the maximal spatial ST vector magnitude was related to the ultimate QRS vector difference (r = .80) and to the cumulative amount of CK released (r = .64). Furthermore, maximal QRS vector difference correlated well with the maximal cumulative CK release (r = .64) Ten patients had possible infarct expansion, as indicated by recurrent QRS changes without concomitant CK release. Fifteen patients had infarct extension that was indicated by secondary CK release and that in seven patients was associated with further QRS changes. Infarct extension caused an approximate 25% increase in infarct size. Spatial ST vector magnitude, QRS vector difference, and cumulative CK release are complementary measures in the quantification of evolving myocardial injury after acute coronary occlusion and in the determination of sequels to therapeutic interventions.

Pharmacokinetics and protein binding of prednisolone after oral and intravenous administration.

The pharmacokinetics of prednisolone after oral and intravenous administration of 10 and 20 mg have been studied. Serum protein binding of prednisolone was also measured after the i.v. injections. The bioavailability after oral administration was 84.5% after 10 mg and 77.6% after 20 mg (p greater than 0.05). Dose dependent pharmacokinetics were found, the VDss and Clt being significantly larger (p less than 0.01) after 20 mg i.v. than after 10 mg i.v. The protein binding of prednisolone in all subjects was non-linear, and is the most likely cause of the dose dependent pharmacokinetics, as there was no dose dependent variation in elimination half-time.