Emedicine - Biophysical Profile, Ultrasound Article by Peter A Gearhart, MD - MHT

eMedicine - Biophysical Profile, Ultrasound : Article by Peter A Gearhart, MD
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Biophysical Profile, Ultrasound

Last Updated: June 10, 2005
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Synonyms and related keywords: antenatal ultrasound fetal surveillance, prenatal ultrasound, BPP, fetal asphyxia, fetal heart rate monitoring, FHR monitoring, FHR, amniotic fluid volume, AFV, antepartum fetal surveillance, biophysical profile score, BPS, nonstress test, antepartum testing, antenatal testing, prenatal testing
AUTHOR INFORMATION
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Author Information Introduction Nonstress Test Pathophysiologic Basis Of The Biophysical Profile Biophysical Profile Procedure Amniotic Fluid Index The Modified Biophysical Profile Application Of The Biophysical Profile Reliability Of The Biophysical Profile Pictures Bibliography
Author: Peter A Gearhart, MD, Staff Physician, Department of Obstetrics and Gynecology, Pennsylvania Hospital Coauthor(s): Harish M Sehdev, MD, Assistant Professor of Clinical Obstetrics and Gynecology, Department of Obstetrics and Gynecology, University of Pennsylvania; Consulting Staff, Pennsylvania Hospital, University of Pennsylvania Health System; William GM Ritchie, MD, Former Clinical Professor of Radiology, University of Pennsylvania School of Medicine; Former Chief, Department of Radiology, Section of Ultrasound, Pennsylvania Hospital Peter A Gearhart, MD, is a member of the following medical societies: American College of Obstetricians and Gynecologists Editor(s): Christopher L Sistrom, MD, Associate Chair for Research, Assistant Professor, Department of Radiology, University of Florida School of Medicine; Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand; Karen L Reuter, MD, FACR, Professor, Department of Radiology, Lahey Clinic Medical Center; Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute; and Eugene C Lin, MD, Consulting Staff, Department of Radiology, Virginia Mason Medical Center Disclosure INTRODUCTION
Section 2 of 11
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The biophysical profile (BPP) is a noninvasive test that predicts the presence or absence of fetal asphyxia and, ultimately, the risk of fetal death in the antenatal period. When the BPP identifies a compromised fetus, measures can be taken to intervene before progressive metabolic acidosis leads to fetal death. The BPP combines data from two sources, ie, ultrasound imaging and fetal heart rate (FHR) monitoring. Dynamic realtime B-mode ultrasound is used to measure the amniotic fluid volume (AFV) and to observe several types of fetal movement. The FHR is obtained using a pulsed Doppler transducer integrated with a high-speed microprocessor, which provides a continuously updated reading. Originally described by Manning and colleagues, the BPP has become a standard tool for providing antepartum fetal surveillance. The BPP integrates 5 parameters to yield a biophysical profile score (BPS) and includes (1) the nonstress test (NST), (2) ultrasound measurement of the AFV, (3) observation of the presence or absence of fetal breathing movements, (4) gross body movements, and (5) tone. Table 1 describes specific criteria for the BPS. The BPP allows 2 points for each parameter that is present, yielding a maximum score of 10; however, if all the ultrasound variable findings are normal, the FHR variable may be excluded because no change is made in the predicative accuracy of the BPP by including the FHR. If one or more ultrasound variable findings are abnormal, the NST should be performed. A basic principle of antepartum testing is that a more accurate prediction of fetal wellness is achieved in direct proportion to the number of variables considered. The BPP is a clinical tool that integrates levels
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of dynamic biophysical activities into a useable standard. The BPP allows 2 points for each parameter that is present, yielding a maximum score of 10; however, if all ultrasound variables are normal, the FHR variable may be excluded because no change is made in the predictive accuracy of the BPP by including the FHR. If one or more ultrasound variable is abnormal, the NST should be performed. Table 1. Criteria for Coding Fetal Biophysical Variables as Normal or Abnormal Biophysical Variable Fetal breathing movements Gross body movements Normal (Score = 2) 1 or more episodes of >20 s within 30 min 2 or more discrete body/ limb movements within 30 min (episodes of active continuous movement considered as a single movement) 1 or more episodes of active extension with return to flexion of fetal limb(s) or trunk (opening and closing of hand considered normal tone) 2 or more episodes of acceleration of >15 bmp* and of >15 s associated with fetal movement within 20 min 1 or more pockets of fluid measuring >2 cm in vertical axis Abnormal (Score = 0) Absent or no episode of >20 s within 30 min <2 episodes of body/limb movements within 30 min
Fetal tone
Slow extension with return to partial flexion, movement of limb in full extension, absent fetal movement, or partially open fetal hand 1 or more episodes of acceleration of fetal heart rate or acceleration of <15 bmp within 20 min Either no pockets or largest pocket <2 cm in vertical axis
Reactive FHR
Qualitative AFV
*Beats per minute Reprinted with permission from Manning, 1999 NONSTRESS TEST
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The NST is a noninvasive method used to evaluate fetal well-being. The NST is derived from observations that a fetus that is not acidotic and has an intact normally functioning autonomic nervous system will have periodic accelerations of the FHR. Acceleration is defined as a rise in the FHRbaseline rate that peaks at least 15 bmp above the baseline and lasts for at least 15 seconds from the beginning of the rise until the return to the FHR baseline. Accelerations almost always occur with fetal movement. Partial umbilical cord compression with transient occlusion of the umbilical vein also can cause accelerations. This occurs with normal autonomic function, which acts to preserve cardiac output by increasing heart rate in response to decreased blood return to the fetal heart. NSTs are described as either reactive or nonreactive. An NST is considered reactive if at least 2 accelerations are present in a 20-minute period. Occasionally, the NST may require 40 minutes or more of FHR recording to account for variations of the fetal sleep-wake cycle. An NST is considered nonreactive if sufficient accelerations are absent within a 40-minute period. Decelerations of the FHR may be seen in as many as 50% of NSTs. If decelerations are nonrepetitive and less than 30 seconds in duration, obstetric intervention is not needed; however, repetitive decelerations or decelerations that last longer than 60 seconds are associated with an increased risk of fetal demise and cesarean delivery for the diagnosis of nonreassuring FHR pattern. Image 1 shows a reactive NST. PATHOPHYSIOLOGIC BASIS OF THE BIOPHYSICAL PROFILE
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Hypoxemia and acidemia have been shown to interfere with measures of central nervous system (CNS) performance, such as FHR patterns, fetal movement, and tone, in both animals and humans. Most likely, oligohydramnios results from decreased fetal urine production, which is seen with fetal hypoxemia as a result of blood flow redistributed away from the fetal kidneys and viscera in favor of the
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brain, heart, and adrenal glands. Each of the movements evaluated in the BPP results from efferent signals originating in different CNS centers, which mature at different gestational ages (see Table 2). When activities known to originate from each of these oxygen-dependent centers are observed, it can be assumed that brain function is normal and systemic hypoxia is not present. Conversely, if one or more of the BPP activities is not observed within the prescribed observation period of 30 minutes, hypoxemia must be assumed to be the cause of the absence of that activity. Table 2. Maturation of Central Nervous System Regulatory Centers Activity Gross body movements Breathing movements FHR accelerations resulting from fetal movement Sleep-wake cycles Integrated behavioral patterns Gestational Age of Maturation (wk) 6 12-14 18-20 18-22 28
However, the clinical reality is that hypoxemia is the least likely reason for the absence of a particular activity. In most fetuses, absence of a particular activity results from normal variations in fetal movements. Usually, this results from fetal sleep-wake cycles, which are approximately 20 minutes in length. The observation period of 30 minutes was chosen arbitrarily to exclude the effects of the fetal sleep-wake cycle on the majority of biophysical activities. Table 3 shows a variety of factors, other than hypoxemia, that have been shown to affect different BPP parameters. Table 3. Factors Affecting the Biophysical Profile Activity Fetal sleep Early gestational age (<33 wk) Late gestational age (>42 wk) Maternal glucose ingestion Maternal alcohol ingestion Maternal magnesium administration Artifical rupture of membranes Premature rupture of membranes Labor FHR Accelerations / / Tone Gross Movement Fetal Breathing AFV
Key: A blank box indicates that no data are available for that parameter. Horizontal lines indicate that the parameter has been studied and that no change is demonstrated. Arrows indicate that the parameter has been studied and that it increases or decreases as shown. BIOPHYSICAL PROFILE PROCEDURE
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The ultrasound portion of the BPP should begin by noting the starting time. The profile may be completed when all of the variables have been observed; however, a full 30 minutes must elapse before the profile is judged to be abnormal. The scan should start with a general survey, noting the position of the fetus and the presence of cardiac activity. Although not part of the BPP, surveying the placental position and grade and the fetal morphology is common practice during observation of fetal activity.
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AFV is assessed as normal if at least one or more pockets of fluid are detected that measure at least 2 cm along the vertical axis. Oligohydramnios is present if the largest pocket measures less than 2 cm. The video in Image 6 shows 4 pockets of fluid being measured. The pressure applied to the transducer by the sonographer is inversely proportional to the depth of the fluid pocket. Careful attention to transducer pressure is required to avoid a false diagnosis of oligohydramnios, which can result from excessive transducer pressure compressing the maternal abdomen. Fetal movements are judged as normal or abnormal according to the criteria established in Table 1. The video in Image 2 shows breathing movements, while the video in Image 3 shows movements that can be mistaken for fetal breathing. The videos in Image 4 and Image 5 demonstrate gross movements and tone. The video in Image 6 demonstrates the amniotic fluid index (AFI). Section 6 of 11 AMNIOTIC FLUID INDEX
The AFI is a semiquantitative method for evaluating the AFV. The AFI is derived by adding the largest vertically measured fluid pocket from each uterine quadrant. This method appears to be at least as accurate as the largestpocket-of-fluid method and can be reasonably substituted as an alternate method for evaluating AFV in the BPP. Using this method, oligohydramnios is defined as an AFI of less than 5. To obtain an AFI, the mother must be in the supine position and the linear ultrasound probe must be parallel to the maternal spine and perpendicular to the floor for all measurements. The abdomen is divided into 4 quadrants, with the umbilicus delineating the upper and lower halves and the linea nigra delineating the left and right halves. The largest pocket of fluid in each quadrant is measured along the vertical dimension, which is the dimension perpendicular to the ultrasound probe. The pockets must be free of umbilical cord or fetal extremities, although brief appearances of these are acceptable. The video in Image 6 demonstrates measurement of the AFI. Section 7 of 11 THE MODIFIED BIOPHYSICAL PROFILE
A modified BPP consisting of an NST and an AFI is used widely. If either the NST or the AFI is abnormal, a complete BPP or a contraction stress test (CST) is performed. The modified BPP, CST, and complete BPP have similarly low false-negative mortality rates, defined as the number of fetal deaths within 1 week of a normal test result. Nevertheless, no clear evidence exists that the 2 variables used in the modified BPP are better predictors than the other variables omitted from the BPP. Furthermore, this method requires 2 modalities for fetal evaluation, while normal ultrasound findings in a BPP eliminate the need for an NST. Section 8 of 11 APPLICATION OF THE BIOPHYSICAL PROFILE
Antepartum testing using the BPP or any other method should not be performed earlier than the gestational age at which extrauterine survival or active intervention for fetal compromise is possible. Furthermore, no indications exist for testing in a fetus at term when likelihood of successful induction is high or when vaginal delivery is contraindicated for obstetric reasons. For patients with a low probability of successful induction, the BPP is a useful tool that can be used while waiting for cervical ripening. In these patients, the purpose of the BPP is to avoid the maternal morbidity resulting from failed induction followed by cesarean delivery. The frequency of testing varies according to the clinical variables in each patient. In most high-risk pregnancies, testing plans start with weekly testing, although twice-weekly testing is the standard for pregnancies beyond 42 weeks and for patients with insulin-dependent diabetes. Frequency of testing increases in direct proportion to the severity of the maternal or fetal condition. In unstable pregnancies with progressive deterioration of the fetal condition, abnormal umbilical cord blood flow patterns occur first. Subsequently, FHR variation is reduced, followed by loss of breathing movements, while general fetal movements and tone are the last parameters to demonstrate abnormal results. Frequent assessment of fetal BPP movements may help prolong the pregnancy in fetuses with a marginally reduced FHR variation. An abnormal BPS should prompt further evaluation or intervention depending on the circumstances. If an abnormal score occurs in a term fetus, preparation should be made for delivery. An abnormal score in a fetus who is remote from term requires conservative management, since the risk of fetal death is similar to the neonatal mortality rate resulting from prematurity. In these patients, daily testing often is performed. Table 4 provides general guidelines for treatment following the BPS. Table 4. Recommended Fetal Treatment According to the Biophysical Profile Score Risk of Asphyxia* (%) 0 0 Risk of Fetal Death (per 1000/wk) 0.565 0.565
Result
Interpretation
Recommended Treatment
10/10 8/10 (normal
Nonasphyxiated Nonasphyxiated
Conservative Conservative
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AFV) 8/8 (NST not performed) 8/10 (decreased AFV) 6/10 (normal AFV) 6/10 (decreased AFV) 4/10 (normal AFV) 4/10 (decreased AFV) 2/10 (normal AFV) 0/10 Nonasphyxiated Chronic compensated asphyxia Acute asphyxia possible Chronic asphyxia with possible acute Acute asphyxia likely Chronic asphyxia with acute asphyxia likely Acute asphyxia almost certain Gross severe asphyxia 0 5-10 (estimate) 0 0.565 20-30 Conservative If mature (>37 wk), deliver If immature, serial testing (twice weekly) If mature (>37 wk), deliver If immature, repeat test in 24 h and if <6/10, deliver Factor in gestational age If >32 wk, deliver If <32 wk, test daily Factor in gestational age If >32 weeks, deliver If <32 wk, test daily If >26 wk, deliver
50
>10
>50
36
115
>36
>115
73
220
If >26 wk, deliver
100
100
If >26 wk, deliver
*Umbilical venous blood pH less than 7.25 Reprinted with permission of Manning, 1999 RELIABILITY OF THE BIOPHYSICAL PROFILE
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The BPP is a reliable method of predicting fetal survival. Data have been collected on this and other antepartum testing procedures for more than 20 years. Testing methods usually are evaluated by comparing the false-negative mortality rate for each method. The false-negative mortality rate is defined as the number of fetal deaths, corrected for lethal congenital anomalies and unpredictable causes of demise, that occur within 1 week of a normal test result. The BPP has a false-negative mortality rate of 0.77 deaths per 1000 tests. Furthermore, the BPS highly correlates with the antepartum fetal umbilical venous cord pH level. Cordocentesis performed immediately following a BPP demonstrated that a poor BPS was always associated with a pH of less than 7.20, while a score of 10 of 10 always yielded a pH of greater than 7.20. The false-negative mortality rate for NST alone is 1.9 per 1000 tests, more than twice that of the BPP. The modified BPP has a mortality rate of 0.8. The low false-negative rates of these testing methods depend on an appropriate response to an abnormal result. Intervention and retesting are the usual responses. Section 10 of 11 PICTURES
Caption: Picture 1. Reactive nonstress test. The top graph plots the fetal heart rate over time. Each small box represents 10 seconds along the horizontal axis and 10 beats per minute along the vertical axis. The baseline fetal heart rate is from 140150 beats per minute. This tracing is reactive, since at least 2 accelerations of the fetal heart rate occur within less than 20 minutes. View Full Size Image eMedicine Zoom View (Interactive!) Picture Type: Graph Caption: Picture 2. Fetal breathing movements. Video shows a rhythmic deflection of the fetal chest wall and diaphragm that is clearly distinct from the rhythmic motion of the fetal heart. Note that the image begins in the transverse view, but the ultrasound transducer is then rotated to show a sagittal view and, finally, an oblique view. The episode of continuous fetal breathing lasts well in excess of the required 20-second period.
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Picture Type: Movie Caption: Picture 3. False fetal breathing movements. Although some transient fetal breathing movements are seen, the video does not include 20 seconds of continuous fetal breathing. Note that the maternal breathing and aortic pulse seen posteriorly and the fetal aortic pulse seen on the sagittal view, along with fetal cardiac activity, can cause deflections of the fetal chest wall, which can be mistaken for fetal breathing movements.
Picture Type: Movie Caption: Picture 4. Gross fetal movements and tone. Video demonstrates generalized movements of the fetal lower extremities, including 1 episode of flexion and extension.
Picture Type: Movie Caption: Picture 5. Gross fetal movements and tone. Video demonstrates generalized movements of the fetal upper extremities. The upper extremity rests in front of the fetal chest and chin. Although the ultrasound transducer is moving laterally across the maternal abdomen, 2 distinct episodes of flexion and extension are seen. Note the many cross-sectional views of the 3-vessel umbilical cord and the floating echogenic particles of vernix in the amniotic fluid.
Picture Type: Movie Caption: Picture 6. Amniotic fluid index. The largest pocket of fluid is measured in each quadrant of the maternal abdomen in the vertical dimension. Then, each value is added to yield the amniotic fluid index.
Picture Type: Movie BIBLIOGRAPHY

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ACOG: Antepartum fetal surveillance. In: Practice Bulletin 9. American College of Obstetrics and Gynecology; Oct 1999. Baskett TF: Gestational age and fetal biophysical assessment. Am J Obstet Gynecol 1988 Feb; 158(2): 332-4[Medline]. Bocking A, Adamson L, Cousin A, et al: Effects of intravenous glucose injections on human fetal breathing movements and gross fetal body movements at 38 to 40 weeks' gestational age. Am J Obstet Gynecol 1982 Mar 15; 142(6 Pt 1): 606-11[Medline]. Bourgeois FJ, Thiagarajah S, Harbert GM Jr: The significance of fetal heart rate decelerations during nonstress testing. Am J Obstet Gynecol 1984 Sep 15; 150(2): 213-6[Medline]. Boylan P, Lewis PJ: Fetal breathing in labor. Obstet Gynecol 1980 Jul; 56(1): 35-8[Medline]. Campbell K: Ultradian rhythms in the human fetus during the last ten weeks of gestation: a review. Semin Perinatol 1980 Oct; 4(4): 301-9[Medline]. Castillo RA, Devoe LD, Ruedrich DA, Gardner P: The effects of acute alcohol intoxication on biophysical activities: a case report. Am J Obstet Gynecol 1989 Mar; 160(3): 692-3[Medline]. de Vries JI, Visser GH, Mulder EJ, Prechtl HF: Diurnal and other variations in fetal movement and heart rate patterns at 20-22 weeks. Early Hum Dev 1987 Nov; 15(6): 333-48[Medline]. Eden RD, Seifert LS, Kodack LD, et al: A modified biophysical profile for antenatal fetal surveillance. Obstet Gynecol 1988 Mar; 71(3 Pt 1): 365-9[Medline]. Eglinton GS, Paul RH, Broussard PM, et al: Antepartum fetal heart rate testing. XI. Stimulation with orange juice. Am J Obstet Gynecol 1984 Sep 1; 150(1): 97-9[Medline]. Flack NJ, Dore C, Southwell D, et al: The influence of operator transducer pressure on ultrasonographic measurements of amniotic fluid volume. Am J Obstet Gynecol 1994 Jul; 171(1): 218-22[Medline]. Freeman RK, Garite TJ, Nageotte MP: Instrumentation and artifact detection. In: Fetal Heart Rate Monitoring. 2nd ed. Baltimore, Md: Williams & Wilkins; 1991: 35-57. Freeman RK, Garite TJ, Nageotte MP: Basic pattern recognition. In: Fetal Heart Rate Monitoring. 2nd ed. Baltimore, Md: Williams & Wilkins; 1991: 69-92. Freeman RK, Anderson G, Dorchester W: A prospective multi-institutional study of antepartum fetal heart rate monitoring. I. Risk of perinatal mortality and morbidity according to antepartum fetal heart rate test results. Am J Obstet Gynecol 1982 Aug 1; 143(7): 771-7[Medline]. Hanley ML, Vintzileos AM: Biophysical testing in premature rupture of the membranes. Semin Perinatol 1996 Oct; 20 (5): 418-25[Medline]. Lin CC, Pielet BW, Poon E, Sun G: Effect of magnesium sulfate on fetal heart rate variability in preeclamptic patients during labor. Am J Perinatol 1988 Jul; 5(3): 208-13[Medline].
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Manning FA, Platt LD, Sipos L: Antepartum fetal evaluation: development of a fetal biophysical profile. Am J Obstet Gynecol 1980 Mar 15; 136(6): 787-95[Medline]. Manning FA: Fetal biophysical profile. Obstet Gynecol Clin North Am 1999 Dec; 26(4): 557-77, v[Medline]. Manning FA, Platt LD: Maternal hypoxemia and fetal breathing movements. Obstet Gynecol 1979 Jun; 53(6): 758-60 [Medline]. Manning FA, Morrison I, Lange IR, et al: Fetal biophysical profile scoring: selective use of the nonstress test. Am J Obstet Gynecol 1987 Mar; 156(3): 709-12[Medline]. Manning FA, Snijders R, Harman CR, et al: Fetal biophysical profile score. VI. Correlation with antepartum umbilical venous fetal pH. Am J Obstet Gynecol 1993 Oct; 169(4): 755-63[Medline]. Meis PJ, Ureda JR, Swain M, et al: Variable decelerations during nonstress tests are not a sign of fetal compromise. Am J Obstet Gynecol 1986 Mar; 154(3): 586-90[Medline]. Miller DA, Rabello YA, Paul RH: The modified biophysical profile: antepartum testing in the 1990s. Am J Obstet Gynecol 1996 Mar; 174(3): 812-7[Medline]. Murata Y, Martin CB Jr, Ikenoue T, et al: Fetal heart rate accelerations and late decelerations during the course of intrauterine death in chronically catheterized rhesus monkeys. Am J Obstet Gynecol 1982 Sep 15; 144(2): 218-23 [Medline]. Nageotte MP, Towers CV, Asrat T, Freeman RK: Perinatal outcome with the modified biophysical profile. Am J Obstet Gynecol 1994 Jun; 170(6): 1672-6[Medline]. Natale R, Clewlow F, Dawes GS: Measurement of fetal forelimb movements in the lamb in utero. Am J Obstet Gynecol 1981 Jul 1; 140(5): 545-51[Medline]. Natale R, Patrick J, Richardson B: Effects of human maternal venous plasma glucose concentrations on fetal breathing movements. Am J Obstet Gynecol 1978 Sep 1; 132(1): 36-41[Medline]. Nicolaides KH, Peters MT, Vyas S, et al: Relation of rate of urine production to oxygen tension in small-for- gestationalage fetuses. Am J Obstet Gynecol 1990 Feb; 162(2): 387-91[Medline]. O'Leary JA, Andrinopoulos GC, Giordano PC: Variable decelerations and the nonstress test: an indication of cord compromise. Am J Obstet Gynecol 1980 Jul 15; 137(6): 704-6[Medline]. Peaceman AM, Meyer BA, Thorp JA, et al: The effect of magnesium sulfate tocolysis on the fetal biophysical profile. Am J Obstet Gynecol 1989 Sep; 161(3): 771-4[Medline]. Peeters LL, Sheldon RE, Jones MD Jr, et al: Blood flow to fetal organs as a function of arterial oxygen content. Am J Obstet Gynecol 1979 Nov 1; 135(5): 637-46[Medline]. Phelan JP, Smith CV, Broussard P, Small M: Amniotic fluid volume assessment with the four-quadrant technique at 3642 weeks' gestation. J Reprod Med 1987 Jul; 32(7): 540-2[Medline]. Rabinowitz R, Persitz E, Sadovsky E: The relation between fetal heart rate accelerations and fetal movements. Obstet Gynecol 1983 Jan; 61(1): 16-8[Medline]. Ribbert LS, Visser GH, Mulder EJ, et al: Changes with time in fetal heart rate variation, movement incidences and haemodynamics in intrauterine growth retarded fetuses: a longitudinal approach to the assessment of fetal well being. Early Hum Dev 1993 Jan; 31(3): 195-208[Medline]. Rutherford SE, Phelan JP, Smith CV, Jacobs N: The four-quadrant assessment of amniotic fluid volume: an adjunct to antepartum fetal heart rate testing. Obstet Gynecol 1987 Sep; 70(3 Pt 1): 353-6[Medline]. Vintzileos AM, Gaffney SE, Salinger LM, et al: The relationships among the fetal biophysical profile, umbilical cord pH, and Apgar scores. Am J Obstet Gynecol 1987 Sep; 157(3): 627-31[Medline].
NOTE:
Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this journal have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER
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