- Email: [email protected]
Biophysical profile in the treatment of intrauterine growth-restricted fetuses who weigh <1000 g
SMFM Papers
www. AJOG.org
Biophysical profile in the treatment of intrauterine growth-restricted fetuses who weigh <1000 g Satinder Kaur, MD; Jason L. Picconi, MD, PhD; Rati Chadha, MD; Michael Kruger, MS; Giancarlo Mari, MD OBJECTIVE: The aim of this study was to determine the biophysical profile (BPP) usefulness in the prediction of cord pH, base excess, and guidance regarding the timing of delivery in preterm intrauterine growth-restricted (IUGR) fetuses. STUDY DESIGN: A BPP was performed daily in 48 IUGR fetuses and was considered abnormal when it was 2/10 on 1 single occasion or 4/10 on 2 consecutive occasions 2 hours apart.
fetuses with a BPP of 8, there were 3 deaths, and 12 fetuses were acidemic. CONCLUSION: BPP alone is not a reliable test in the treatment of preterm IUGR fetuses, because of high false-positive and -negative results. The common notion of a good BPP providing reassurance for at least 24 hours is not applicable in severely preterm IUGR fetuses who weigh ⬍1000 g.
RESULTS: The median gestational age and fetal weight for the total
population was 27.6 weeks and 632 g, respectively. In 13 fetuses with a BPP of 6, there were 3 deaths, and 7 fetuses were acidemic. In 27
Key words: biophysical profile, Doppler study, intrauterine growth restriction (IUGR)
Cite this article as: Kaur S, Picconi JL, Chadha R, Kruger M, Mari G. Biophysical profile in the treatment of intrauterine growth-restricted fetuses who weigh ⬍1000 g. Am J Obstet Gynecol 2008;199:264.e1-264.e4.
T
he biophysical profile (BPP) and fetal heart rate monitoring non-stress test (NST) are the most common tests used in the United States to assess fetal well-being in women with high-risk factors for stillbirth.1 The BPP was developed by Manning et al2 in 1980 and incorporates fetal tone, movements, breathing, amniotic fluid, and a NST. A normal BPP has been associated with decreased fetal death in 1 week.1,2
From the Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI (Drs Kaur, Picconi, and Chadha and Mr Kruger) and the Department of Obstetrics and Gynecology, Tennessee Institute of Feto-Maternal and Infant Health, University of Tennessee Health Science Center, Memphis, TN (Dr Mari). This research was presented at the 28th Annual Meeting of the Society for Maternal–Fetal Medicine, Dallas, TX, Jan. 28-Feb. 2, 2008. Received March 8, 2008; accepted June 24,2008 Reprints not available from the authors. 0002-9378/$34.00 © 2008 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2008.06.074
For Editors’ Commentary, see Table of Contents 264.e1
M ATERIALS AND M ETHODS The addition of Doppler studies for the assessment of intrauterine growthrestricted (IUGR) fetuses are believed to provide a better approach for the treatment of IUGR fetuses, but few studies have indicated a relationship between Doppler changes and the BPP in which Doppler changes are noted before the development of an abnormal biophysical score.3,4 In IUGR fetuses with an abnormal umbilical artery (UA) Doppler result, the BPP is initiated as early as 26-28 weeks of gestation and is performed twice a week.1 Despite these guidelines, most obstetricians perform BPPs every day and repeat the NST between 2 and 3 times per day. There are no data, however, that have evaluated the accuracy of the BPP to predict the perinatal outcome in severely growth-restricted fetuses who weigh ⬍1000 g at an early gestational age. The aim of this study was to assess whether a daily BPP is reassuring for the next 24 hours in IUGR fetuses with an abnormal UA Doppler result that is diagnosed at ⬍32 weeks of gestation and who weigh ⬍1000 g.
American Journal of Obstetrics & Gynecology SEPTEMBER 2008
The patients who were included in this study delivered between 1998 and 2006 and were selected retrospectively from an IUGR fetus database; their inclusion for this study was approved by the Human Investigation Committee at Wayne State University. The statistics for the patients of the database have been used for other studies. However, the BPP data have not been reported previously. We selected singletons who were diagnosed with IUGR who were delivered at ⬍32 weeks of gestation. Inclusion criteria for the IUGR fetuses were (a) an estimated weight of ⬍10th percentile (weight confirmed at birth), (b) UA pulsatility index ⬍95th CI of our reference range, (c) a normal anatomy, and (d) a BPP performed ⬍24 hours before delivery. Fetuses with an abnormal karyotype were not included in the study. Gestational age was based on certain last menstrual period or second trimester ultrasound dating. Before delivery, fetal weights were calculated and evaluated with the reference range established by Hadlock et al.5 All patients were admitted to the hospital and monitored with the BPP once daily and with a NST every 8 hours until delivery, when the BPP was normal and
SMFM Papers
www.AJOG.org
TABLE 1
TABLE 2
Variable
Indications for delivery of the study population (n ⴝ 48)
Characteristics of the study population (n ⴝ 48) Median (range)
Indication
Gestational age at delivery (wk)
.....................................................................................................................................................................................................................................
N
Total population
27.6 (23.1-31.5)
IUFD
Fetal death (n ⫽ 7)
26.3 (23.1-28.2)
Nonreassuring fetal testing
Neonatal death (n ⫽ 12)
26.4 (24.6-30.3)
Preeclampsia
7
Neonatal survival (n ⫽ 29)
28.4 (25.6-31.5)
Hemolysis, elevated liver enzymes, and low platelets
4
Poor growth
5
Abruption
2
Chorioamnionitis
1
..................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................... ..............................................................................................................................................................................................................................................
24
........................................................................................................... ...........................................................................................................
...........................................................................................................
Birthweight (g)
.....................................................................................................................................................................................................................................
Total population
632 (282-1000)
Fetal death (n ⫽ 7)
439 (282-680)
Neonatal death (n ⫽ 12)
540 (400-693)
Neonatal survival (n ⫽ 29)
697 (365-1000)
..................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................... .....................................................................................................................................................................................................................................
Kaur. Biophysical profile. Am J Obstet Gynecol 2008.
the fetal heart rate was reassuring. When the NST was nonreassuring, as determined by the treating physician, the BPP was repeated. In the presence of a BPP of 4, the BPP was repeated 2 hours later. When the maternal condition deteriorated, the patient was maintained on continuous fetal monitoring. Fortythree fetuses received 1 course of steroids. Delivery was indicated in the presence of (a) a BPP of 4 on 2 repeated occasions or a BPP score of 2, (b) continuous variable/late decelerations, (c) fetal death, or (c) worsening maternal conditions, as determined by the treating physician. Doppler ultrasound was not an indication for delivery. The BPP was performed in accordance with the procedure reported by Manning et al.6 For each parameter, we assigned a score of 2 or 0. Fetal breathing movements received a score of 2 in the presence of ⱖ1 episodes of rhythmic fetal breathing movements of ⱖ30 seconds within 30 minutes. Fetal movements received a score of 2 in the presence of ⱖ3 body or limb movements within 30 minutes. A score of 2 was given in the presence of ⱖ2 episodes of lower extremities extension with return to flexion or opening or closing of a hand (fetal tone). A score of 2 was also given when a single vertical pocket of amniotic fluid exceeded 2 cm. For the NST, we assigned a score of 2, when ⱖ2 episodes of acceleration of ⱖ15 beats/min and ⬎15 seconds
7
...........................................................................................................
........................................................................................................... ...........................................................................................................
Kaur. Biophysical profile. Am J Obstet Gynecol 2008.
R ESULTS occurred that were associated with fetal movements in 20 minutes. Umbilical cord segments were collected immediately after delivery for arterial cord blood pH and base excess determination. Fetal acidemia was diagnosed by arterial cord blood pH ⱕ7.10 or base excess ⱕ ⫺9.0, as described by Dickinson et al.7 We defined chronic hypertension as a blood pressure value ⬎140/90 mm Hg that was diagnosed before 20 weeks of gestation or before the pregnancy. Preeclampsia was defined by hypertension and proteinuria that occurred after 20 weeks of gestation in a patient with previously normal blood pressure. Hypertension was defined as a blood pressure value ⬎140/90 mm Hg on at least 2 occasions, 6 hours apart. Proteinuria was defined as the presence of ⬎300 mg of protein in a 24-hour urine specimen. Data were analyzed with SPSS statistical software (version 15.0; SPSS Inc, Chicago, IL). The BPP score was compared with arterial cord blood pH and base excess by Spearman’s rank correlation coefficient. Statistical analysis of the BPP score, compared with fetal outcome, was performed with chisquare and Fisher’s exact tests. A chisquare test was also used to compare the UA Doppler results to fetal outcome. A probability value of ⬍.05 was considered statistically significant.
Forty-eight fetuses met the entry criteria. The characteristics of the study population and indications for delivery are reported in Tables 1 and 2. The median gestational age and fetal weight for the total population was 27.6 weeks (range, 23.1-31.5) and 632 g (range, 282-1000), respectively. There were 7 cases that resulted in fetal death, 12 cases that resulted in neonatal death, and 29 cases that resulted in neonatal survival at the time of discharge from the hospital. All fetuses, with the exception of those who died in utero, were delivered by cesarean delivery. When the fetuses were at ⬍24 weeks of gestation, the reason for admission to the hospital was the maternal condition. The most common indicator for delivery was nonreassuring fetal testing (50%). In 3 intrauterine fetal deaths (IUFDs), the parents declined any intervention because the estimated fetal weight was ⬍500 g. In these 3 fetuses, the BPP scores were 4, 6, and 8 at 20, 12, and 12 hours, respectively. The BPP was performed in all fetuses within 24 hours of delivery or fetal death. Arterial cord blood pH and base excess for the study population are given in Table 3. The median arterial cord blood pH and base excess for the total population was 7.20 (range, 6.92-7.35) and ⫺8.9 (range, ⫺1.0 to ⫺18.0), respectively. Stratification of fetal biophysical scores with acid-base status at the time of birth is given in Table 4. In this Table, the data represent the BPP score and outcome in the study population that was performed
SEPTEMBER 2008 American Journal of Obstetrics & Gynecology
264.e2
SMFM Papers TABLE 3
Cord gases of live births (n ⴝ 41) Variable
www.AJOG.org
TABLE 4
BPP score and acid-base status of fetuses (n ⴝ 48)
Median (range)
Cord pH
BPP score
...........................................................................................................
Acid-base status
2
4
Total population
7.20 (6.92-7.35)
IUFD
0 (3)
1
3
3
7
Neonatal death (n ⫽ 12)
7.19 (6.92-7.33)
Acidemic
0 (6)
3
7
12
22
Neonatal survival (n ⫽ 29)
7.21 (6.93-7.35)
Normal
0 (1)
4
3
12
19
Total
0 (10)
8
13
27
48
...........................................................................................................
8
Total
.............................................................................................................................................................................................................................................. ..............................................................................................................................................................................................................................................
...........................................................................................................
...........................................................................................................
Base excess
...........................................................................................................
Total population
⫺8.9 (⫺1.0-⫺18.0)
Neonatal death (n ⫽ 12)
⫺9.9 (⫺1.6-⫺17.0)
Neonatal survival (n ⫽ 29)
⫺8.5 (⫺1.0-⫺18.0)
...........................................................................................................
...........................................................................................................
Kaur. Biophysical profile. Am J Obstet Gynecol 2008.
as scheduled antenatal surveillance. Ten fetuses were noted to have nonreassuring fetal tracings between 3.5 and 24 hours after a BPP of 8 (normal). Repeat BPPs demonstrated scores of 2 in all 10 fetuses, which precipitated immediate delivery. Of these 10 fetuses, 3 fetuses resulted in fetal death; 6 fetuses had acidemic UA blood gases, and 1 fetus had normal UA blood gases. These numbers are reported in Table 4. The BPP score correlated with arterial cord blood pH, with a correlation coefficient of 0.35 (P ⬍ .05), and with arterial cord base excess, with a correlation coefficient of 0.43 (P ⬍ .05). Chi-square analysis of the BPP (2, 4, 6, and 8), compared with fetal acid-base status (IUFD, acidemia, and normal), showed no statistical significance (P ⫽ .24). Even with BPP scores of 6 and 8 combined and with IUFD and acidemic fetuses combined, these variables were not statistically significant (P ⫽ .10). Table 5 shows the UA Doppler results in 3 groups of fetuses: (1) IUFDs, (2) neonatal deaths, and (3) infants who were discharged home. The chi-square analysis did not show any difference between the UA Doppler results of the 3 groups of fetuses. When we analyzed the data of the combined group (IUFD and neonatal death) and the discharged home group, we noticed that 74% of the fetuses in the combined group had UA reversed flow vs 41% in the discharged home group. The proba264.e3
6
.............................................................................................................................................................................................................................................. ..............................................................................................................................................................................................................................................
BPP scores during scheduled daily fetal surveillance within 24 hours of delivery or death. Results in parentheses represent BPP scores that were repeated because of nonreassuring fetal heart rate. Kaur. Biophysical profile. Am J Obstet Gynecol 2008.
bility value was .058, which suggests that, with a larger number of fetuses, the UA Doppler results might be different between those fetuses who die and those who survive. The Fisher’s exact test showed similar results. Nonparametric binomial analysis for combined fetal death and acidemic fetuses, compared with a BPP of 6 and 8 with an expected normal of 0%, showed an actual normal value of 47% (P ⬍ .001), which indicated that a BPP of 6 or 8 predicted fetal normal acid-base status in 53% of the cases. Of the 30 fetuses who were identified to have BPP scores of 8 (normal) or 6 (equivocal) ⬍24 hours before delivery or death, 3 fetuses died, and 13 fetuses had acidemia by arterial cord blood pH or base excess. Eight fetuses were found to have scores of 4 on 2 consecutive BPPs, which precipitated immediate delivery. Of these 8 fetuses, 1 died; 3 were acidemic, and 4 had normal UA pH and base excess.
C OMMENT In this study, we used the BPP in a group of fetuses with severe IUGR that was diagnosed at ⬍32 weeks of gestation. In 13 fetuses with a BPP of 6, 3 fetuses died, and 7 fetuses were acidemic; in 27 fetuses
with a BPP of 8, 3 fetuses died, and 12 fetuses were acidemic. In 10 fetuses with initial BPP score of 8, the BPP was repeated because of nonreassuring fetal heart rate monitoring; in this group, 3 fetuses died, and 6 fetuses were acidemic. Had we relied on a scheduled BPP that was normal as a predictor of fetal wellbeing for the next 24 hours, the 6 other fetuses who were acidemic may have died. On the other hand, an abnormal BPP was not always associated with an abnormal cord arterial pH or base excess: 5 fetuses with a BPP of 2 or 4 demonstrated normal blood gases. Our data suggest that the BPP alone, in this group of early IUGR fetuses, is not a reliable test for the prediction of fetal well-being for the next 24 hours. The BPP has been proposed as the antenatal testing modality of choice in the treatment of IUGR fetuses, even when compared with Doppler results alone or Doppler results in combination with the BPP.8 Our study brings into question how predictable the BPP is in fetuses with severe early diagnosed IUGR and whether there is a safe time duration after a BPP during which we can be reassured of the fetal status. The BPP in severe IUGR fetuses can change rapidly
TABLE 5
UA Doppler results of the study population UA
IUFD (n ⴝ 7)
Neonatal death (n ⴝ 12)
Discharged home (n ⴝ 29)
Abnormal pulsatility index (n)
1
3
9
Absent end-diastolic velocity (n)
0
1
8
Reversed blood flow (n)
6
8
12
.............................................................................................................................................................................................................................................. ..............................................................................................................................................................................................................................................
Kaur. Biophysical profile. Am J Obstet Gynecol 2008.
American Journal of Obstetrics & Gynecology SEPTEMBER 2008
SMFM Papers
www.AJOG.org over a period of a few hours and result in adverse perinatal outcomes. The same concern was raised earlier by Sherer and Kogan, 9 in which a 29-week pregnancy that was complicated by IUGR was delivered finally because of a nonreassurring NST, although the BPP continued to be normal. The fetus was born severely acidemic with a massive antepartum intracranial insult. Hence, the question arises: What is the optimal management of such pregnancies in terms of the antenatal surveillance? The strength of our study is that the false-positive and -negative rates that are reported in this study are higher than those previously reported in the literature because our study concentrated on a particular group of fetuses with severe IUGR.10 Data previously reported in the literature have included fetuses that were studied at gestational ages of ⬎32 weeks. Therefore, our population is different, compared with that previously reported in the literature. Our results also clearly show that the BPP alone in severely premature fetuses is not a good test of fetal well-being. Therefore, other tests should be used to monitor these fetuses. It is important to emphasize, however, that, at the present time, there is no single or optimal test to monitor these IUGR fetuses. Although the NST is part of the BPP, our study has demonstrated that, in these early IUGR fetuses, it is rare to have a reactive NST. Therefore, the subjective interpretation of the fetal heart rate monitoring remains an important tool to treat these fetuses. Further studies are needed to determine whether computerized cardiotocography might become an acceptable diagnostic tool in these fetuses. It would be important to find a test that can predict fetal well-being, especially at a gestational age of ⬍29 weeks. IUGR fetuses between 25 and 29 weeks of gestation represent a group in which optimal treatment can make a difference in terms of survival rate, because for each week the fetus remains in utero the mor-
tality rate decreases by approximately 48%.11 We recently reported that Doppler ultrasound results undergo a series of changes that precede fetal death or nonreassuring fetal testing.12 In that study, we divided IUGR fetuses into subgroups and determined that there is a group of IUGR fetuses in which the cause of placental insufficiency is not known. These fetuses, in which IUGR was diagnosed without any medical complications in pregnancy, undergo a series of changes that are well-defined by Doppler ultrasound until fetal cardiac failure occurs or until the fetus is delivered because of nonreassuring testing. This is a group of fetuses in which Doppler ultrasound may play an important role for timing the delivery of IUGR fetuses because changes can be predicted by Doppler study. On the other hand, in patients with preeclampsia, the sequential changes found by Doppler ultrasound are seen in only a few patients, because most of these fetuses are often delivered for maternal indication before the full range of changes occur on Doppler ultrasound. Therefore, in this group of fetuses, Doppler ultrasound may play a less important role in regard to timing of the delivery. At the current time, we believe that early diagnosed, severe IUGR fetuses should be treated with daily BPPs and with NSTs that are performed at intervals more frequent than 8 hours (ie, every 6 hours); when the physician who is managing the case does not feel comfortable with the fetal status, the fetal heart rate should be monitored continuously. It is not known whether a combined Doppler result and BPP represents a better test than the BPP alone. Doppler ultrasound, however, as reported, may play an important role in timing the delivery of IUGR fetuses in whom no maternal or fetal abnormality is detected. In conclusion, BPP alone is not a reliable test in the treatment of preterm IUGR fetuses, because of high false-positive and -negative results. The common
notion that a good BPP provides reassurance for at least 24 hours is not applicable in severely preterm IUGR fetuses who f weigh ⬍1000 g. REFERENCES 1. American College of Obstetricians and Gynecologists. Antepartum fetal surveillance: Practice Bulletin No. 9. Washington (DC): The College; 1999:592-602. 2. Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation: development of a fetal biophysical profile. Am J Obstet Gynecol 1980; 136:787-95. 3. Baschat AA, Gembruch U, Harman CR. The sequence of changes in Doppler and biophysical parameters as severe fetal growth restriction worsens. Ultrasound Obstet Gynecol 2001; 18:571-7. 4. Cosmi E, Ambrosini G, D’Antona D, Saccardi C, Mari G. Doppler, cardiotocography, and biophysical profile changes in growth-restricted fetuses. Obstet Gynecol 2005;106:1240-5. 5. Hadlock FP, Harrist RB, Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology 1991;181:129-33. 6. Manning, FA, Morrison I, Lange IR, Harman CR, Chamberlain PF. Fetal biophysical profile scoring: selective use of the nonstress test. Am J Obstet Gynecol 1987;156:709-12. 7. Dickinson JE, Eriksen NL, Meyer BA, Parisi VM. The effect of preterm birth on umbilical cord blood gases. Obstet Gynecol 1992;79:575-8. 8. Odibo AO, Quinones JN, Lawrence-Cleary K, Stamilio DM, Macones GA. What antepartum fetal test should guide the timing of delivery of the preterm growth-restricted fetus? A decision analysis. Am J Obstet Gynecol 2004;191: 1477-82. 9. Sherer DM, Kogan MG. Abnormal nonstress test yet otherwise reassuring biophysical profile in a compromised fetus with severe antepartum intracranial hemorrhage. Gynecol Obstet Invest 2001;52:66-70. 10. Dayal AK, Manning FA, Berck DJ, et al. Fetal death after normal biophysical profile score: an eighteen-year experience. Am J Obstet Gynecol 1999;181:1231-6. 11. Mari G, Hanif F, Treadwell MC, Kruger M. Gestational age at delivery and Doppler waveforms in very preterm IUGR fetuses as predictors of perinatal mortality. J Ultrasound Med 2007;26:555-9. 12. Mari G, Hanif F, Kruger M. Cardiovascular changes sequence in IUGR in pregnancies with and without preeclampsia. Prenat Diagn 2008;28:377-83.
SEPTEMBER 2008 American Journal of Obstetrics & Gynecology
264.e4
www. AJOG.org
Biophysical profile in the treatment of intrauterine growth-restricted fetuses who weigh <1000 g Satinder Kaur, MD; Jason L. Picconi, MD, PhD; Rati Chadha, MD; Michael Kruger, MS; Giancarlo Mari, MD OBJECTIVE: The aim of this study was to determine the biophysical profile (BPP) usefulness in the prediction of cord pH, base excess, and guidance regarding the timing of delivery in preterm intrauterine growth-restricted (IUGR) fetuses. STUDY DESIGN: A BPP was performed daily in 48 IUGR fetuses and was considered abnormal when it was 2/10 on 1 single occasion or 4/10 on 2 consecutive occasions 2 hours apart.
fetuses with a BPP of 8, there were 3 deaths, and 12 fetuses were acidemic. CONCLUSION: BPP alone is not a reliable test in the treatment of preterm IUGR fetuses, because of high false-positive and -negative results. The common notion of a good BPP providing reassurance for at least 24 hours is not applicable in severely preterm IUGR fetuses who weigh ⬍1000 g.
RESULTS: The median gestational age and fetal weight for the total
population was 27.6 weeks and 632 g, respectively. In 13 fetuses with a BPP of 6, there were 3 deaths, and 7 fetuses were acidemic. In 27
Key words: biophysical profile, Doppler study, intrauterine growth restriction (IUGR)
Cite this article as: Kaur S, Picconi JL, Chadha R, Kruger M, Mari G. Biophysical profile in the treatment of intrauterine growth-restricted fetuses who weigh ⬍1000 g. Am J Obstet Gynecol 2008;199:264.e1-264.e4.
T
he biophysical profile (BPP) and fetal heart rate monitoring non-stress test (NST) are the most common tests used in the United States to assess fetal well-being in women with high-risk factors for stillbirth.1 The BPP was developed by Manning et al2 in 1980 and incorporates fetal tone, movements, breathing, amniotic fluid, and a NST. A normal BPP has been associated with decreased fetal death in 1 week.1,2
From the Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI (Drs Kaur, Picconi, and Chadha and Mr Kruger) and the Department of Obstetrics and Gynecology, Tennessee Institute of Feto-Maternal and Infant Health, University of Tennessee Health Science Center, Memphis, TN (Dr Mari). This research was presented at the 28th Annual Meeting of the Society for Maternal–Fetal Medicine, Dallas, TX, Jan. 28-Feb. 2, 2008. Received March 8, 2008; accepted June 24,2008 Reprints not available from the authors. 0002-9378/$34.00 © 2008 Mosby, Inc. All rights reserved. doi: 10.1016/j.ajog.2008.06.074
For Editors’ Commentary, see Table of Contents 264.e1
M ATERIALS AND M ETHODS The addition of Doppler studies for the assessment of intrauterine growthrestricted (IUGR) fetuses are believed to provide a better approach for the treatment of IUGR fetuses, but few studies have indicated a relationship between Doppler changes and the BPP in which Doppler changes are noted before the development of an abnormal biophysical score.3,4 In IUGR fetuses with an abnormal umbilical artery (UA) Doppler result, the BPP is initiated as early as 26-28 weeks of gestation and is performed twice a week.1 Despite these guidelines, most obstetricians perform BPPs every day and repeat the NST between 2 and 3 times per day. There are no data, however, that have evaluated the accuracy of the BPP to predict the perinatal outcome in severely growth-restricted fetuses who weigh ⬍1000 g at an early gestational age. The aim of this study was to assess whether a daily BPP is reassuring for the next 24 hours in IUGR fetuses with an abnormal UA Doppler result that is diagnosed at ⬍32 weeks of gestation and who weigh ⬍1000 g.
American Journal of Obstetrics & Gynecology SEPTEMBER 2008
The patients who were included in this study delivered between 1998 and 2006 and were selected retrospectively from an IUGR fetus database; their inclusion for this study was approved by the Human Investigation Committee at Wayne State University. The statistics for the patients of the database have been used for other studies. However, the BPP data have not been reported previously. We selected singletons who were diagnosed with IUGR who were delivered at ⬍32 weeks of gestation. Inclusion criteria for the IUGR fetuses were (a) an estimated weight of ⬍10th percentile (weight confirmed at birth), (b) UA pulsatility index ⬍95th CI of our reference range, (c) a normal anatomy, and (d) a BPP performed ⬍24 hours before delivery. Fetuses with an abnormal karyotype were not included in the study. Gestational age was based on certain last menstrual period or second trimester ultrasound dating. Before delivery, fetal weights were calculated and evaluated with the reference range established by Hadlock et al.5 All patients were admitted to the hospital and monitored with the BPP once daily and with a NST every 8 hours until delivery, when the BPP was normal and
SMFM Papers
www.AJOG.org
TABLE 1
TABLE 2
Variable
Indications for delivery of the study population (n ⴝ 48)
Characteristics of the study population (n ⴝ 48) Median (range)
Indication
Gestational age at delivery (wk)
.....................................................................................................................................................................................................................................
N
Total population
27.6 (23.1-31.5)
IUFD
Fetal death (n ⫽ 7)
26.3 (23.1-28.2)
Nonreassuring fetal testing
Neonatal death (n ⫽ 12)
26.4 (24.6-30.3)
Preeclampsia
7
Neonatal survival (n ⫽ 29)
28.4 (25.6-31.5)
Hemolysis, elevated liver enzymes, and low platelets
4
Poor growth
5
Abruption
2
Chorioamnionitis
1
..................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................... ..............................................................................................................................................................................................................................................
24
........................................................................................................... ...........................................................................................................
...........................................................................................................
Birthweight (g)
.....................................................................................................................................................................................................................................
Total population
632 (282-1000)
Fetal death (n ⫽ 7)
439 (282-680)
Neonatal death (n ⫽ 12)
540 (400-693)
Neonatal survival (n ⫽ 29)
697 (365-1000)
..................................................................................................................................................................................................................................... ..................................................................................................................................................................................................................................... .....................................................................................................................................................................................................................................
Kaur. Biophysical profile. Am J Obstet Gynecol 2008.
the fetal heart rate was reassuring. When the NST was nonreassuring, as determined by the treating physician, the BPP was repeated. In the presence of a BPP of 4, the BPP was repeated 2 hours later. When the maternal condition deteriorated, the patient was maintained on continuous fetal monitoring. Fortythree fetuses received 1 course of steroids. Delivery was indicated in the presence of (a) a BPP of 4 on 2 repeated occasions or a BPP score of 2, (b) continuous variable/late decelerations, (c) fetal death, or (c) worsening maternal conditions, as determined by the treating physician. Doppler ultrasound was not an indication for delivery. The BPP was performed in accordance with the procedure reported by Manning et al.6 For each parameter, we assigned a score of 2 or 0. Fetal breathing movements received a score of 2 in the presence of ⱖ1 episodes of rhythmic fetal breathing movements of ⱖ30 seconds within 30 minutes. Fetal movements received a score of 2 in the presence of ⱖ3 body or limb movements within 30 minutes. A score of 2 was given in the presence of ⱖ2 episodes of lower extremities extension with return to flexion or opening or closing of a hand (fetal tone). A score of 2 was also given when a single vertical pocket of amniotic fluid exceeded 2 cm. For the NST, we assigned a score of 2, when ⱖ2 episodes of acceleration of ⱖ15 beats/min and ⬎15 seconds
7
...........................................................................................................
........................................................................................................... ...........................................................................................................
Kaur. Biophysical profile. Am J Obstet Gynecol 2008.
R ESULTS occurred that were associated with fetal movements in 20 minutes. Umbilical cord segments were collected immediately after delivery for arterial cord blood pH and base excess determination. Fetal acidemia was diagnosed by arterial cord blood pH ⱕ7.10 or base excess ⱕ ⫺9.0, as described by Dickinson et al.7 We defined chronic hypertension as a blood pressure value ⬎140/90 mm Hg that was diagnosed before 20 weeks of gestation or before the pregnancy. Preeclampsia was defined by hypertension and proteinuria that occurred after 20 weeks of gestation in a patient with previously normal blood pressure. Hypertension was defined as a blood pressure value ⬎140/90 mm Hg on at least 2 occasions, 6 hours apart. Proteinuria was defined as the presence of ⬎300 mg of protein in a 24-hour urine specimen. Data were analyzed with SPSS statistical software (version 15.0; SPSS Inc, Chicago, IL). The BPP score was compared with arterial cord blood pH and base excess by Spearman’s rank correlation coefficient. Statistical analysis of the BPP score, compared with fetal outcome, was performed with chisquare and Fisher’s exact tests. A chisquare test was also used to compare the UA Doppler results to fetal outcome. A probability value of ⬍.05 was considered statistically significant.
Forty-eight fetuses met the entry criteria. The characteristics of the study population and indications for delivery are reported in Tables 1 and 2. The median gestational age and fetal weight for the total population was 27.6 weeks (range, 23.1-31.5) and 632 g (range, 282-1000), respectively. There were 7 cases that resulted in fetal death, 12 cases that resulted in neonatal death, and 29 cases that resulted in neonatal survival at the time of discharge from the hospital. All fetuses, with the exception of those who died in utero, were delivered by cesarean delivery. When the fetuses were at ⬍24 weeks of gestation, the reason for admission to the hospital was the maternal condition. The most common indicator for delivery was nonreassuring fetal testing (50%). In 3 intrauterine fetal deaths (IUFDs), the parents declined any intervention because the estimated fetal weight was ⬍500 g. In these 3 fetuses, the BPP scores were 4, 6, and 8 at 20, 12, and 12 hours, respectively. The BPP was performed in all fetuses within 24 hours of delivery or fetal death. Arterial cord blood pH and base excess for the study population are given in Table 3. The median arterial cord blood pH and base excess for the total population was 7.20 (range, 6.92-7.35) and ⫺8.9 (range, ⫺1.0 to ⫺18.0), respectively. Stratification of fetal biophysical scores with acid-base status at the time of birth is given in Table 4. In this Table, the data represent the BPP score and outcome in the study population that was performed
SEPTEMBER 2008 American Journal of Obstetrics & Gynecology
264.e2
SMFM Papers TABLE 3
Cord gases of live births (n ⴝ 41) Variable
www.AJOG.org
TABLE 4
BPP score and acid-base status of fetuses (n ⴝ 48)
Median (range)
Cord pH
BPP score
...........................................................................................................
Acid-base status
2
4
Total population
7.20 (6.92-7.35)
IUFD
0 (3)
1
3
3
7
Neonatal death (n ⫽ 12)
7.19 (6.92-7.33)
Acidemic
0 (6)
3
7
12
22
Neonatal survival (n ⫽ 29)
7.21 (6.93-7.35)
Normal
0 (1)
4
3
12
19
Total
0 (10)
8
13
27
48
...........................................................................................................
8
Total
.............................................................................................................................................................................................................................................. ..............................................................................................................................................................................................................................................
...........................................................................................................
...........................................................................................................
Base excess
...........................................................................................................
Total population
⫺8.9 (⫺1.0-⫺18.0)
Neonatal death (n ⫽ 12)
⫺9.9 (⫺1.6-⫺17.0)
Neonatal survival (n ⫽ 29)
⫺8.5 (⫺1.0-⫺18.0)
...........................................................................................................
...........................................................................................................
Kaur. Biophysical profile. Am J Obstet Gynecol 2008.
as scheduled antenatal surveillance. Ten fetuses were noted to have nonreassuring fetal tracings between 3.5 and 24 hours after a BPP of 8 (normal). Repeat BPPs demonstrated scores of 2 in all 10 fetuses, which precipitated immediate delivery. Of these 10 fetuses, 3 fetuses resulted in fetal death; 6 fetuses had acidemic UA blood gases, and 1 fetus had normal UA blood gases. These numbers are reported in Table 4. The BPP score correlated with arterial cord blood pH, with a correlation coefficient of 0.35 (P ⬍ .05), and with arterial cord base excess, with a correlation coefficient of 0.43 (P ⬍ .05). Chi-square analysis of the BPP (2, 4, 6, and 8), compared with fetal acid-base status (IUFD, acidemia, and normal), showed no statistical significance (P ⫽ .24). Even with BPP scores of 6 and 8 combined and with IUFD and acidemic fetuses combined, these variables were not statistically significant (P ⫽ .10). Table 5 shows the UA Doppler results in 3 groups of fetuses: (1) IUFDs, (2) neonatal deaths, and (3) infants who were discharged home. The chi-square analysis did not show any difference between the UA Doppler results of the 3 groups of fetuses. When we analyzed the data of the combined group (IUFD and neonatal death) and the discharged home group, we noticed that 74% of the fetuses in the combined group had UA reversed flow vs 41% in the discharged home group. The proba264.e3
6
.............................................................................................................................................................................................................................................. ..............................................................................................................................................................................................................................................
BPP scores during scheduled daily fetal surveillance within 24 hours of delivery or death. Results in parentheses represent BPP scores that were repeated because of nonreassuring fetal heart rate. Kaur. Biophysical profile. Am J Obstet Gynecol 2008.
bility value was .058, which suggests that, with a larger number of fetuses, the UA Doppler results might be different between those fetuses who die and those who survive. The Fisher’s exact test showed similar results. Nonparametric binomial analysis for combined fetal death and acidemic fetuses, compared with a BPP of 6 and 8 with an expected normal of 0%, showed an actual normal value of 47% (P ⬍ .001), which indicated that a BPP of 6 or 8 predicted fetal normal acid-base status in 53% of the cases. Of the 30 fetuses who were identified to have BPP scores of 8 (normal) or 6 (equivocal) ⬍24 hours before delivery or death, 3 fetuses died, and 13 fetuses had acidemia by arterial cord blood pH or base excess. Eight fetuses were found to have scores of 4 on 2 consecutive BPPs, which precipitated immediate delivery. Of these 8 fetuses, 1 died; 3 were acidemic, and 4 had normal UA pH and base excess.
C OMMENT In this study, we used the BPP in a group of fetuses with severe IUGR that was diagnosed at ⬍32 weeks of gestation. In 13 fetuses with a BPP of 6, 3 fetuses died, and 7 fetuses were acidemic; in 27 fetuses
with a BPP of 8, 3 fetuses died, and 12 fetuses were acidemic. In 10 fetuses with initial BPP score of 8, the BPP was repeated because of nonreassuring fetal heart rate monitoring; in this group, 3 fetuses died, and 6 fetuses were acidemic. Had we relied on a scheduled BPP that was normal as a predictor of fetal wellbeing for the next 24 hours, the 6 other fetuses who were acidemic may have died. On the other hand, an abnormal BPP was not always associated with an abnormal cord arterial pH or base excess: 5 fetuses with a BPP of 2 or 4 demonstrated normal blood gases. Our data suggest that the BPP alone, in this group of early IUGR fetuses, is not a reliable test for the prediction of fetal well-being for the next 24 hours. The BPP has been proposed as the antenatal testing modality of choice in the treatment of IUGR fetuses, even when compared with Doppler results alone or Doppler results in combination with the BPP.8 Our study brings into question how predictable the BPP is in fetuses with severe early diagnosed IUGR and whether there is a safe time duration after a BPP during which we can be reassured of the fetal status. The BPP in severe IUGR fetuses can change rapidly
TABLE 5
UA Doppler results of the study population UA
IUFD (n ⴝ 7)
Neonatal death (n ⴝ 12)
Discharged home (n ⴝ 29)
Abnormal pulsatility index (n)
1
3
9
Absent end-diastolic velocity (n)
0
1
8
Reversed blood flow (n)
6
8
12
.............................................................................................................................................................................................................................................. ..............................................................................................................................................................................................................................................
Kaur. Biophysical profile. Am J Obstet Gynecol 2008.
American Journal of Obstetrics & Gynecology SEPTEMBER 2008
SMFM Papers
www.AJOG.org over a period of a few hours and result in adverse perinatal outcomes. The same concern was raised earlier by Sherer and Kogan, 9 in which a 29-week pregnancy that was complicated by IUGR was delivered finally because of a nonreassurring NST, although the BPP continued to be normal. The fetus was born severely acidemic with a massive antepartum intracranial insult. Hence, the question arises: What is the optimal management of such pregnancies in terms of the antenatal surveillance? The strength of our study is that the false-positive and -negative rates that are reported in this study are higher than those previously reported in the literature because our study concentrated on a particular group of fetuses with severe IUGR.10 Data previously reported in the literature have included fetuses that were studied at gestational ages of ⬎32 weeks. Therefore, our population is different, compared with that previously reported in the literature. Our results also clearly show that the BPP alone in severely premature fetuses is not a good test of fetal well-being. Therefore, other tests should be used to monitor these fetuses. It is important to emphasize, however, that, at the present time, there is no single or optimal test to monitor these IUGR fetuses. Although the NST is part of the BPP, our study has demonstrated that, in these early IUGR fetuses, it is rare to have a reactive NST. Therefore, the subjective interpretation of the fetal heart rate monitoring remains an important tool to treat these fetuses. Further studies are needed to determine whether computerized cardiotocography might become an acceptable diagnostic tool in these fetuses. It would be important to find a test that can predict fetal well-being, especially at a gestational age of ⬍29 weeks. IUGR fetuses between 25 and 29 weeks of gestation represent a group in which optimal treatment can make a difference in terms of survival rate, because for each week the fetus remains in utero the mor-
tality rate decreases by approximately 48%.11 We recently reported that Doppler ultrasound results undergo a series of changes that precede fetal death or nonreassuring fetal testing.12 In that study, we divided IUGR fetuses into subgroups and determined that there is a group of IUGR fetuses in which the cause of placental insufficiency is not known. These fetuses, in which IUGR was diagnosed without any medical complications in pregnancy, undergo a series of changes that are well-defined by Doppler ultrasound until fetal cardiac failure occurs or until the fetus is delivered because of nonreassuring testing. This is a group of fetuses in which Doppler ultrasound may play an important role for timing the delivery of IUGR fetuses because changes can be predicted by Doppler study. On the other hand, in patients with preeclampsia, the sequential changes found by Doppler ultrasound are seen in only a few patients, because most of these fetuses are often delivered for maternal indication before the full range of changes occur on Doppler ultrasound. Therefore, in this group of fetuses, Doppler ultrasound may play a less important role in regard to timing of the delivery. At the current time, we believe that early diagnosed, severe IUGR fetuses should be treated with daily BPPs and with NSTs that are performed at intervals more frequent than 8 hours (ie, every 6 hours); when the physician who is managing the case does not feel comfortable with the fetal status, the fetal heart rate should be monitored continuously. It is not known whether a combined Doppler result and BPP represents a better test than the BPP alone. Doppler ultrasound, however, as reported, may play an important role in timing the delivery of IUGR fetuses in whom no maternal or fetal abnormality is detected. In conclusion, BPP alone is not a reliable test in the treatment of preterm IUGR fetuses, because of high false-positive and -negative results. The common
notion that a good BPP provides reassurance for at least 24 hours is not applicable in severely preterm IUGR fetuses who f weigh ⬍1000 g. REFERENCES 1. American College of Obstetricians and Gynecologists. Antepartum fetal surveillance: Practice Bulletin No. 9. Washington (DC): The College; 1999:592-602. 2. Manning FA, Platt LD, Sipos L. Antepartum fetal evaluation: development of a fetal biophysical profile. Am J Obstet Gynecol 1980; 136:787-95. 3. Baschat AA, Gembruch U, Harman CR. The sequence of changes in Doppler and biophysical parameters as severe fetal growth restriction worsens. Ultrasound Obstet Gynecol 2001; 18:571-7. 4. Cosmi E, Ambrosini G, D’Antona D, Saccardi C, Mari G. Doppler, cardiotocography, and biophysical profile changes in growth-restricted fetuses. Obstet Gynecol 2005;106:1240-5. 5. Hadlock FP, Harrist RB, Martinez-Poyer J. In utero analysis of fetal growth: a sonographic weight standard. Radiology 1991;181:129-33. 6. Manning, FA, Morrison I, Lange IR, Harman CR, Chamberlain PF. Fetal biophysical profile scoring: selective use of the nonstress test. Am J Obstet Gynecol 1987;156:709-12. 7. Dickinson JE, Eriksen NL, Meyer BA, Parisi VM. The effect of preterm birth on umbilical cord blood gases. Obstet Gynecol 1992;79:575-8. 8. Odibo AO, Quinones JN, Lawrence-Cleary K, Stamilio DM, Macones GA. What antepartum fetal test should guide the timing of delivery of the preterm growth-restricted fetus? A decision analysis. Am J Obstet Gynecol 2004;191: 1477-82. 9. Sherer DM, Kogan MG. Abnormal nonstress test yet otherwise reassuring biophysical profile in a compromised fetus with severe antepartum intracranial hemorrhage. Gynecol Obstet Invest 2001;52:66-70. 10. Dayal AK, Manning FA, Berck DJ, et al. Fetal death after normal biophysical profile score: an eighteen-year experience. Am J Obstet Gynecol 1999;181:1231-6. 11. Mari G, Hanif F, Treadwell MC, Kruger M. Gestational age at delivery and Doppler waveforms in very preterm IUGR fetuses as predictors of perinatal mortality. J Ultrasound Med 2007;26:555-9. 12. Mari G, Hanif F, Kruger M. Cardiovascular changes sequence in IUGR in pregnancies with and without preeclampsia. Prenat Diagn 2008;28:377-83.
SEPTEMBER 2008 American Journal of Obstetrics & Gynecology
264.e4