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The fetal biophysical profile in patients with premature rupture of the membranes—An early predictor of fetal infection
The fetal biophysical profile in patients with premature rupture of the membranes-An early predictor of fetal infection Anthony M. Vintzileos, M.D., Winston A. Campbell, M.D., David J. Nochimson, M.D., Mary E. Connolly, M.D., Michael M. Fuenfer, M.D., and GeorgeJ. Hoehn, M.D. Farmington, Connecticut A modified fetal biophysical profile (nonstress test, fetal movements, f~:~tal breathing movements, fetal tone, amniotic fluid volume, and placental grading) was serially assessed in 73 patients who presented with premature rupture of the membranes and were not in labor. The last study before delivery was compared with the outcome of pregnancy. The relationships between individual variables and combinations of variables (biophysical scoring) and the outcome of pregnancy-as reflected by the development of chorioamnionitis and/or neonatal sepsis-were determined. These data suggest that the fetal biophysical profile is a useful tool for evaluating patients with rupture of the membranes. Rupture of the membranes by itself does not alter the biophysical scoring of the healthy fetus; however, a low biophysical score (,;;7) was a good predictor of impending fetal infection in patients with premature rupture of the membranes. (AM J 0BSTET GYNECOL
1985;152:510-6.)
Key words: Fetal biophysical profile, premature rupture of membranes, fetal infection The fetal biophysical profile (nonstress test, fetal movements, fetal breathing movements, fetal tone, amniotic fluid volume, placental grading) has been shown to be more accurate in the identification of the hypoxic fetus than any other single test during the antepartum period. Its predictive value in antepartum fetal surveillance has been very well documented. 1• 2 However, no data are available to support the use of the fetal biophysical profile in patients with premature rupture of the membranes. The purpose of this prospective study was to determine the value of the fetal biophysical profile in evaluating patients who presented with premature rupture of the membranes and were not in labor. In this study, six fetal biophysical variables (nons tress test, fetal movements, fetal breathing movements, fetal tone, amniotic fluid volume, placental grading) were measured by a method previously described, 1 to determine the relationships between single variables or combinations of variables and the outcome of pregnancy. Measures of pregnancy outcome included the presence of amnionitis and/or neonatal sepsis. Material and methods A total of 73 patients entered the study. The majority of these patients (94.5%) were transferred to the Uni-
From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, and the Division of Neonatology, Department of Pediatrics, University of Connecticut Health Center. Received for publication October 25, 1984; revised January 30, 1985; accepted February 11, 1985. Reprint requests: Anthony M. Vintzileos, M.D., Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT 06032-9984.
510
versity of Connecticut Health Center because of preterm rupture of the membranes. Only singleton pregnancies with gestational ages ;:;.:25 weeks, premature rupture of the membranes, and no labor were included. Patients with signs oflabor, chorioamnionitis, bleeding, or fetal distress were excluded. The prior use of tocolysis and the presence of other complicating factors (for instance, pregnancy-induced hypertension, diabetes, intrauterine growth retardation) were also considered as contraindications for entering the study. In all study patients, rupture of the membranes was documented by sterile speculum examination with pooled fluid, ferning, and alkaline pH determination (Nitrazine paper). Bimanual examination had been performed on several patients prior to transfer, but none was done after admission to our institution. Routine vital signs were obtained on admission. Electronic fetal heart rate monitoring was used to detect signs of fetal distress, as well as to document any uterine activity. If there was no evidence of labor, fetal distress, or infection, the fetal biophysical profile was determined with a technique previously described. 1 The ultrasound evaluation was done by means of a linear array realtime ultrasound method (Picker LS-2000) equipped with a 3.5 MHz transducer. Real-time scanning consisted of a maximum 30-minute observation period during which fetal movements and fetal breathing movements were counted and fetal tone, amniotic fluid volume, and placental grading were estimated. Each biophysical variable (modified from the biophysical scoring of Manning et aJ.2) was scored as 2, 1, or 0 according to the criteria cited in our previous study. 1 The maximal score was 12 and the minimal 0. The patients were advised that the results of the biophysical
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Table I. Predictive value of the biophysical scoring for development of infection in groups 1, 2, and 3 Infection Group
Biophysical score
No. of patients
Group 1 (53 patients)
;;.8
37 16 15 0 3 2
,.;,_7 Group 2 (15 patients)
;;.8
Group 3 (5 patients)
;;.8
,.;,_7 ,.;,_7
scoring would not influence further management, since there are no data to support its usefulness in patients with premature rupture of the membranes. The patients were observed in the hospital and were managed conservatively with bed rest and bathroom privileges. Corticosteroid therapy was administered in the majority of patients (60 of 73). Gestational ages were confirmed by complete ultrasound profiles. Temperature was taken four times a day and white blood cell counts were performed daily. Bimanual pelvic examinations were avoided unless the patient was believed to be in active labor or a decision had been made to induce labor because of amnionitis. The biophysical profile determinations were repeated every 24 to 48 hours if patients remained undelivered. A low biophysical score (,.;,_7) was not an indication for delivery. Indications for delivery included labor, diagnosed amnionitis, persistent spontaneous variable decelerations (moderate to severe) on electronic fetal heart rate monitoring, or gestational age >37 weeks after a 24-hour period of observation if the cervix was favorable. The clinical diagnosis of amnionitis was made in the presence of two or more of the following criteria: Maternal fever >37.8° C, maternal tachycardia (120 bpm or more), leukocytosis (white blood cell count ;;.:20,000/mm3 in the absence of prior corticosteroid administration), fetal tachycardia (> 160 bpm), uterine tenderness, and foul-smelling amniotic fluid. Antibiotics were administered to the mother only after clamping of the cord. One patient who was given antibiotics before cord clamping was excluded from the study. On admission to the neonatal intensive care unit, all infants had cultures performed (blood, urine, cerebrospinal fluid, tracheal, nasogastric, external ear). All neonates at <34 weeks' gestation received prophylactic antibiotics (ampicillin and kanamycin), which were discontinued when cultures demonstrated no growth. Neonatal sepsis was diagnosed only in the presence of positive cultures of blood, urine, or cerebrospinal fluid. Possible neonatal sepsis was diagnosed in the absence of positive cultures when two or more of the following criteria were present: White blood cell count <5000/mm3 , polymorphonuclear leukocyte count <1800/mm 3 , I:T ratio (ratio of bands to total neutrophil count) >0.2, or positive gastric aspirate for poly-
No. 1/37 15/16 2/15 3/3 1/2
I
% 2.7 93.7 13.3
I
p value <0.001 <0.01
100 50
morphonuclear leukocytes showing >5 per high-power field. When neonatal sepsis or possible neonatal sepsis was diagnosed, the antibiotics were continued for approximately 7 to 10 days. Data collected after delivery included Apgar scores, birth weight, cord blood pH (umbilical artery and umbilical vein), route of delivery, placental cultures, and neonatal septic workup. For the purpose of this report, infection outcome was defined as the presence of clinical amnionitis, possible neonatal sepsis, or neonatal sepsis. The last study before delivery was compared with the outcome of pregnancy, as reflected by the development of infection (amnionitis, possible neonatal sepsis, neonatal sepsis). The association of each biophysical variable as well as combinations of variables (biophysical scoring) and the outcome was determined.
Results There were 148 examinations in these 73 patients (2.02 examinations per patient). The earliest gestational age tested was 25 weeks, the latest was 41 weeks, and the mean was 31.9 weeks. Nine examinations were the most done on one patient. The average time of the ultrasound fetal biophysical assessment was 15 minutes. Of the 73 pregnancies, 69 (94.5%) were preterm (<37 completed weeks) and four (5.4%) were term (;;.:37 weeks) at delivery. In only two patients was labor induced for the presence of a favorable cervix after 37 weeks' gestation and failure to go into spontaneous labor after a 24-hour period of observation. The mean prolongation of pregnancy was 6. 7 days and the infection rate (amnionitis, possible neonatal sepsis, neonatal sepsis) was 30.1% (22 of 73 patients). Of the 73 patients, 53 (72.6%) were delivered within 24 hours of the final examination (group 1), 15 (20.5%) between 24 and 48 hours (group 2), and five (6.8%) >48 hours from the last examination (group 3). The predictive value of the biophysical scoring for the development of infection is illustrated in Table I (X2 analysis). As can be seen, group 3 was too small to derive any meaningful statistical conclusions; however, it appears that there was no predictive value of the biophysical score in patients who were delivered >48 hours after the last examination. In group 1, a biophysical score of ;;.:8 was associated with an infection
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Vintzileos et al.
July 1, 1985 Am J Obstet Gynecol
BIOPHYSICAL SCORE 12 11 10
9
8 7 6
5 4 3 2
TOTAL NO. OF PATIENTS= 53
0 0 + 0 0
0 0 0 0 0 X
••"' "' • • • • • "'
0 0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0
"'
X
X
+
0
0
0
0
0
0
0
0
(14) (6) (5) (6) (6) (3) (6) (1) (2) (2) (2)
0 0
Fig. I. Scatter diagram of the distribution of individual scores of both infected and noninfected cases of group 1. Number of patients is shown in parentheses. o = Noninfected. • = Amnionitis and neonatal sepsis. • = Neonatal sepsis . .A. = Amnionitis and possible neonatal sepsis. X = Possible neonatal sepsis. + = Amnionitis.
Table II. Mean ± 2 SD of the biophysical score, Apgar scores <7, umbilical cord pH, and gestational age of the infected versus the noninfected cases of group I Apgar scores <7 1 min No. of patients
Biophysical score
Infected (16) Noninfected (37) p value
5.2 ± 4.0 10.3 ± 3.2 <0.01
No.
I
Umbilical cord pH 5 min
%
10116 62.5 21.6 8/37 <0.01
No.
I
%
8/16 50 1137 2.7 <0.01
Artery
Vein
Gestational age (wk)
7.29 ± 0.14 7.31 ± 0.10 NS
7.34 ± 0.12 7.36 ± 0.10 NS
30.2 ± 6.0 32.7 ± 6.1 <0.01
Total number of patients = 53.
rate of 2.7%, and a low biophysical score (,;;7) was associated with an infection rate of 93.7% (p < 0.001). In group 2, a biophysical score of ;;;.8 was associated with an infection rate of 13.3%. This was significantly lower than the overall infection rate of 30.1% (p < 0.01). Subsequently, groups 2 and 3 were eliminated and further statistical analysis was therefore confined only to group 1. Of the 16 infected cases in group 1, delivery was performed in three because of persistent spontaneous variable decelerations, in five because of diagnosed antepartum amnionitis, in five because of simultaneous onset of labor and amnionitis, and in three because of spontaneous onset of labor alone. Of the 37 noninfected cases of group 1, delivery was performed in 28 patients because they went into labor, in seven because of persistent spontaneous variable deceleratiof1s, and in two for the presence of a favorable cervix at a gestational age of ;;;.37 weeks and no labor after a 24-hour period of observation. The distribution of individual biophysical scores is provided in Fig. 1 (scatter diagram) for both infected and noninfected cases of group 1. Table II illustrates the mean ± 2 SD of the biophysical score, Apgar scores, umbilical cord pHs, and gestational ages of the infected versus the noninfected cases of group 1 (Wilcoxon signed rank test). The infected group had significantly lower mean biophysical scores and Apgar scores (1 and 5 minutes) and earlier ges-
tational ages (<0.01). There was no significant difference in cord pH between the infected and noninfected cases. The final study before delivery was compared with the outcome of pregnancy as reflected by the development of amnionitis, possible neonatal sepsis, or neonatal sepsis (infection). The relationship between each biophysical variable and infection outcome is illustrated in Table III. A stepwise logistic regression analysis was used to determine the value of the biophysical score and the value of each biophysical variable in order of importance in predicting infection versus noninfection outcome. The best predictor of infection was found to be the biophysical score (F statistic 96.22). Of the individual biophysical variables, the nonstress test, fetal breathing movements, fetal movements, and fetal tone were found to be important in the above sequence (F statistic values 20.97, 20.38, 13.57, 12.18). Placental grading was not found to have any significant predictive value. The relationship between the combination of variables (mean biophysical scoring) and the different infection outcomes is shown in Table IV. As can be seen, the lowest biophysical scores were encountered in patients with positive neonatal cultures (neonatal sepsis). The biophysical profile of the infected cases is analyzed in Table V. As can be seen, when fetal movements were compromised (fetal movement score 1 or 0), the recovery of positive neonatal cultures (neonatal sepsis) was 75% (six of eight). There were a total
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Table III. Relationship between each biophysical variable and infection outcome (group 1) Infected Biophysical variable NST2 NST l NSTO FBM 2 FBM l FBM 0 FM 2 FM l FM 0 FT 2 FT l FT 0 AF 2 AF 1 AF 0 PL 2 PL 1 PL 0
No. of patients*
Total last tests(%)
No.t
27 8 18 24 3 26 43 4 6 46 5 2 27 13 13 50 1 2
50.9 15.0 33.9 45.2 5.6 49.0 81.1 7.5 11.3 86.7 9.4 3.7 50.9 24.5 24.5 94.3 1.8 3.7
l/27 2/8 13/18 0/24 0/3 16/26 8/43 2/4 6/6 9/46 5/5 2/2 3/27 4/13 9/13 14/50 111 112
I
Noninfected %:t
No.§
3.7 25.0 72.2 0.0 0.0 61.5 18.6 50.0 100.0 19.5 100.0 100.0 ll.l 30.7 69.2 28.0 100.0 50.0
26/27 6/8 5/18 24/24 3/3 10/26 35/43 2/4 016 37/46 0/5 0/2 24/27 9/13 4/13 36/50 0/1 112
I
%11 96.2 75.0 27.7 100.0 100.0 38.4 81.3 50.0 0.0 80.4 0.0 0.0 88.8 69.2 30.7 72.0 0.0 50.0
NST = Nonstress test; FBM = fetal breathing movements; FM = fetal movements; FT = fetal tone; AF = amniotic fluid; PL = placental grading. *Total number of patients = 53. tTotal number = 16. tPercent of infected cases = 30.1. §Total number = 37. II Percent of noninfected cases = 69.8.
of seven instances of positive neonatal cultures. Of these, four were recovered from the blood (two group B Streptococcus, one Bacillus sp., and one Escherichia coli), two from the urine (one positive for group B Streptococcus and one positive for Peptostreptococcus), and one from cerebrospinal fluid (group B Streptococcus). There were only two neonatal deaths in the population tested. Both infants were delivered at 26 weeks' gestation because of amnionitis and severe variable decelerations. The last biophysical scores before delivery were 2 and 3, respectively (perinatal mortality 27.3/ 1000).
Comment Premature rupture of the membranes constitutes one of the most common complications of pregnancy. In the literature, the reported incidence ranges from 5% to 40%. 3 • 4 Although premature rupture of membranes before 37 weeks' gestation is hazardous to the fetus in terms of perinatal morbidity and mortality, its occurrence at term (after 37 weeks) also subjects the mother and fetus to increased risks. 5 Many investigators recommend prompt delivery of the fetus when premature rupture of the membranes occurs at term, because of the increased incidence of amnionitis with prolonged rupture of the membranes. 6 However, this action will usually result in an increased incidence of primary cesarean sections for failed induction of labor and cephalopelvic disproportion. 5
Table IV. Relationship between mean biophysical score and different infection outcomes (group 1)
Diagnosis Amnionitis Possible neonatal sepsis Amnionitis-possible neonatal sepsis Neonatal sepsis Amnionitis-neonatal sepsis
No. of patients
2 3 4
3 4
Mean biophysical score 8.0 6.3 5.5 4.3 3.5
As the biophysical score decreased, the severity of the infection increased (Spearman rank correlation - 0.75, p,:;; 0.001).
When premature rupture of the membranes occurs in a preterm gestation (<37 weeks), the management is even more controversial. In preterm gestations, immediate delivery of the fetus carries a significant risk of hyaline membrane disease, which still remains a major contributor to neonatal morbidity and mortality; therefore conservative management has been advocated by previous investigators.' However, the conservative approach carries an increased risk of fetal/neonatal infection and cord prolapse. Other management protocols involve the use of amniocentesis 8 • 9 in patients with preterm rupture of the membranes to detect not only the fetus with a mature lung profile but also the fetus most likely to develop sepsis. The problems as-
514 Vintzileos et al.
July I, 1985 Am J Obstet Gynecol
Table V. Analysis of biophysical profile of 16 infected cases (group I) Case Diagnosis
No.
1
2
2
0 0 0 0 0 1 0 0 0 1 0 0 0 0 0
3 4 5 6 7 8 9 10 11 12 13 14 15 16
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
2 2 2 2 2 2 0 2 0 1 2 0 0 1 0 0
2
2
1 2 2 2 2 1 2 1 2 0 0 2 1 2 1
1 1 0 0 1 2 0 0 1 2 0 0 0 0 0
2 2 2 2 2 2 2 2 1 2 0 2 2 2 1 2
10 6 7 6 6 7 6 6 2 6 5 2 4 4 3 3
Amnionitis Amnionitis Possible neonatal sepsis Possible neonatal sepsis Possible neonatal sepsis Amnionitis-possible neonatal Amnionitis-possible neonatal Amnionitis-possible neonatal Amnionitis-possible neonatal Neonatal sepsis Neonatal sepsis Neonatal sepsis Amnionitis-neonatal sepsis Amnionitis-neonatal sepsis Amnionitis-neonatal sepsis Amnionitis-neonatal sepsis
sepsis sepsis sepsis sepsis
NST = Nonstress test; FBM = fetal breathing movements; FM = fetal movements; FT = fetal tone; AF = amniotic fluid; PL = placental grading.
sociated with this approach have been the inability to obtain fluid in almost half of these patients," the invasiveness of the procedure, and the lack of strong correlation between the presence of bacteria in the amniotic fluid and fetal sepsis."· 9 The presence of bacteria in the amniotic fluid (Gram stain and culture) obtained by transabdominal amniocentesis has been strongly correlated with the development of amnionitis and/or postpartum endometritis but not with fetal/neonatal sepsis as determined by the presence of positive neonatal cultures (blood, cerebrospinal fluid, urine). The incidence of fetal/neonatal sepsis with positive amniocentesis was only 14.2% (one of seven) in the study of Cotton eta!." and 22.2% (two of nine) in that of Garite et a!." In summary, a uniform approach to the management of patients with premature rupture of the membranes has not yet been elucidated. Until recently, the antepartum fetal evaluation of patients with premature rupture of the membranes has been solely confined to nonstress testing. The contraction stress test is contraindicated and has no place in the antepartum fetal evaluation of these patients because of the theoretical risk of initiating labor. The value of the fetal biophysical profile has been documented' in high-risk patients with intact membranes; however, its value in the antepartum fetal evaluation of patients with premature rupture of the membranes has not been previously determined. The relatively high neonatal sepsis rate in our study population is probably the result of the expectant management of premature rupture of the membranes in a selected group of high-risk patients referred to a tertiary care center. The inclusion of the possible neonatal sepsis group in the present study is in accordance with the current pediatric and obstetric literature. 10' 12 This
group is usually defined as the group with strong clinical and laboratory evidence of bacterial infection but with negative cultures (blood, cerebrospinal fluid). The negative cultures in this group of infants may be related to inadequate culturing techniques or the inherent difficulty encountered by most laboratories in isolating anaerobic bacteria. Nevertheless, these infants are usually treated after birth with intensive antibiotic therapy as are infants with positive cultures. The inclusion of the "possible neonatal sepsis" group in our study therefore allows comparison with other studies because it was clearly defined according to published data. 10' 12 According to our data, the rupture of membranes by itself does not alter the biophysical activities of the healthy fetus. However, a low biophysical score ('";:7) was a good predictor of impending fetal infection in patients with premature rupture of the membranes. In cases of impending fetal infection, the fetal biophysical activities are altered in a manner very similar to alteration of activities in the hypoxia of uteroplacental insufficiency. The first manifestations of impending fetal infection were nonreactive nonstress testing and absence of fetal breathing. Loss of fetal motion and poor fetal tone were late signs of fetal infection, since the majority of these infants had positive cultures in the immediate neonatal period (Table V). The presence of fetal breathing (Table III) had the highest specificity in predicting absence of fetal infection. There were no cases of fetal infection when breathing was present within 24 hours prior to delivery. It has been reported that the incidence of fetal breathing movements is decreased prior to the onset of labor, but these observations were made in chronic fetal lamb preparations.'' It is not yet clear whether fetal breathing movements are diminished prior to labor in humans. The data of
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PROM* Term (;.37 weeks)
~
~ BS;;,8 7
l
RipetceNix
BS~7
I
Delivery
Delivery
Preterm ( < 37 weeks)
~. l t
BS > 8
BS< 7 (perSIStently)
Expectant management. Repeat BS q 24 hours
Consider delivery. If NST·O and FBM·O.
May wail X 24 hours for SOL
Fig. 2. Proposed protocol for management of premature rupture of the membranes. *Premature rupture of the membranes. BS = Biophysical score. NST-0 = Nonreactive nonstress test. FBM0 = Fetal breathing absent. SOL = Spontaneous onset of labor.
Patrick and Challis, 14 however, which are based on human fetal breathing movements, suggest that, prior to normal spontaneous labor in humans, fetal breathing movements may be decreased but that when labor follows spontaneous rupture of the membranes-as in our study population-fetal breathing movements do not decrease until accelerated labor occurs. In fact, these investigators reported an increase in fetal breathing movements in two fetuses which were observed during early labor. In our study group (group 1) there was a lower incidence of spontaneous onset of labor in the infected group (eight of 16, or 50%) versus the noninfected group (28 of 37, or 75.6%). Therefore the absence of fetal breathing in the infected group cannot be attributed to impending spontaneous onset of labor but rather to fetal infection. The relationship between gestational age and fetal biophysical profile scoring has been investigated in our institution by a recent retrospective study of 1151 biophysical profiles and scores of pregnancies with good outcome. In that study [Vintzileos AM, Feinstein SJ, Lodeiro JG, Campbell WA, Weinbaum PJ, Nochimson DJ. The biophysical profile of the healthy fetus from 25 to 44 weeks of gestation and the effect of premature rupture of the membranes (submitted for publication)] the incidence of fetal biophysical scoring of ~8, as well as mean biophysical scoring, was found to remain unchanged from 25 to 44 weeks' gestation regardless of the status of the membranes. Therefore the low scores of the infected cases in the present study cannot be attributed to lower mean gestational age (Table II) but rather to fetal infection. A tendency for an increased incidence of infection with diminishing amniotic fluid volume was also observed (Table III). It could be speculated that patients with decreased amniotic fluid volume are deprived of the bacteriostatic effect of a normal amniotic fluid volume. The loss of fetal movement (fetal movement score 0) and fetal tone (fetal tone score 0) was the
best predictor of fetal infection, but as it has been already stated, this is a late sign of infection. The decrease in fetal biophysical activities prior to the development of clinical infection makes sense, especially in cases of an ascending infection where the fetus seems to be the first target. Fetal infection that may lead to acidosis and perinatal hypoxic-ischemic encephalopathy has already been described.15 The mechanism by which fetal infection diminishes fetal biophysical activities without acidosis, as determined by cord blood pH measurements, is unknown. Our speculation is that early fetal infection may increase fetal oxygen demands and cause local tissue hypoxia and, thereby, malfunction of the central nervous system centers that control the reflex biophysical activities. 1 Only late stages of fetal infection are manifested by blood acidosis and possible neurological damage due to hypoxic-ischemic encephalopathy. 15 When premature rupture of the membranes occurs at term, the fetal biophysical profile should be used to select those patients who are candidates for fetal infection and therefore in need of prompt delivery. In preterm rupture of the membranes, the use of the fetal biophysical profile could replace amniocentesis in selecting those patients who are less likely to develop fetal infection and may be benefited by expectant management. For the majority of these patients, labor may be arrested for at least 48 hours, the minimum period required to enhance fetal lung maturity with corticosteroids. Fig. 2 illustrates a proposed protocol which we currently use in an ongoing prospective study to test its efficacy in improving pregnancy outcome in patients with premature rupture of the membranes. A persistently low biophysical score (,;:;7) with a nonreactive nons tress test and absence of fetal breathing movements is highly predictive of fetal infection in patients with premature rupture of the membranes and has been used by us as an indication for immediate delivery.
516 Vintzileos et al.
In summary, the fetal biophysical profile is a simple, noninvasive, and reliable tool for evaluating patients with premature rupture of the membranes. REFERENCES I. Vintzileos AM, Campbell WA, Ingardia CJ, et al. The fetal biophysical profile and its predictive value. Obstet Gynecol 1983;62:271. 2. Manning FA, Morrison I, Lange I. Fetal biophysical profile scoring: a prospective study in 1184 high-risk patients. AM j 0BSTET GYNECOL 1981; 140:289. 3. Gunn GC, Mishell DR, Morton DG. Premature rupture of the fetal membranes. AM J 0BSTET GYNECOL 1970; 106:469. 4. Niswander KR, Gordon M. The women and their pregnancies. The Collaborative Perinatal Study of the National Institute of Neurological Diseases and Stroke of the U. S. Department of Health, Education, and Welfare, Public Health Service, and National Institutes of Health. Philadelphia: WB Saunders, 1972:427-34. 5. Lanier LR, Scarbrough RW, Fillingim DW, et al. Incidence of maternal and fetal complications associated with .rupture of membranes before the onset of labor. AM J 0BSTET GYNECOL 1965;93:398. 6. Russel KP, Anderson GV. The aggressive management of ruptured membranes. AM j 0BSTET GYNECOL 1962; 83:930.
July I, 1985 Am J Obstet Gynecol
7. Kappy KA, Cetrulo CL, Knuppel RA, et al. Premature rupture of the membranes: a conservative approach. AM j 0BSTET GYNECOL 1979;134:655. 8. Garite TJ, Freeman RK, Linsey M, et al. The use of amniocentesis in patients with premature rupture of the membranes. Obstet Gynecol 1979;54:226. 9. Cotton DB, Hill LM, Strassner HT, et al. Use of amniocentesis in preterm gestation with ruptured membranes. Obstet Gynecol1984;63:38. 10. Zipursky A, Palko J, Milner R, et al. The hematology of bacterial infections in premature infants. Pediatrics 1976; 57:839. 11. Akenzua Gl, Hui YT, Milner R, et al. Neutrophil and band counts in the diagnosis of neonatal infections. Pediatrics 1974;54:38. 12. Andreyko JL, Chen CP, Shennan AT, et al. Results of conservative management of premature rupture of the membranes. AM j 0BSTET GYNECOL 1984; 148:600. 13. Boddy K, Dawes GS. Fetal breathing. Br Med Bull 1975;31:1. 14. Patrick J, Challis J. Measurement of human fetal breathing movements in healthy pregnancies using a real-time scanner. Semin Perinatol 1980;4:275. 15. Peevy KJ, Chalhub EG. Occult group B streptococcal infection: an important cause of intrauterine asphyxia. AM j 0BSTET GYNECOL 1983;146:989.
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1985;152:510-6.)
Key words: Fetal biophysical profile, premature rupture of membranes, fetal infection The fetal biophysical profile (nonstress test, fetal movements, fetal breathing movements, fetal tone, amniotic fluid volume, placental grading) has been shown to be more accurate in the identification of the hypoxic fetus than any other single test during the antepartum period. Its predictive value in antepartum fetal surveillance has been very well documented. 1• 2 However, no data are available to support the use of the fetal biophysical profile in patients with premature rupture of the membranes. The purpose of this prospective study was to determine the value of the fetal biophysical profile in evaluating patients who presented with premature rupture of the membranes and were not in labor. In this study, six fetal biophysical variables (nons tress test, fetal movements, fetal breathing movements, fetal tone, amniotic fluid volume, placental grading) were measured by a method previously described, 1 to determine the relationships between single variables or combinations of variables and the outcome of pregnancy. Measures of pregnancy outcome included the presence of amnionitis and/or neonatal sepsis. Material and methods A total of 73 patients entered the study. The majority of these patients (94.5%) were transferred to the Uni-
From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, and the Division of Neonatology, Department of Pediatrics, University of Connecticut Health Center. Received for publication October 25, 1984; revised January 30, 1985; accepted February 11, 1985. Reprint requests: Anthony M. Vintzileos, M.D., Department of Obstetrics and Gynecology, University of Connecticut Health Center, Farmington, CT 06032-9984.
510
versity of Connecticut Health Center because of preterm rupture of the membranes. Only singleton pregnancies with gestational ages ;:;.:25 weeks, premature rupture of the membranes, and no labor were included. Patients with signs oflabor, chorioamnionitis, bleeding, or fetal distress were excluded. The prior use of tocolysis and the presence of other complicating factors (for instance, pregnancy-induced hypertension, diabetes, intrauterine growth retardation) were also considered as contraindications for entering the study. In all study patients, rupture of the membranes was documented by sterile speculum examination with pooled fluid, ferning, and alkaline pH determination (Nitrazine paper). Bimanual examination had been performed on several patients prior to transfer, but none was done after admission to our institution. Routine vital signs were obtained on admission. Electronic fetal heart rate monitoring was used to detect signs of fetal distress, as well as to document any uterine activity. If there was no evidence of labor, fetal distress, or infection, the fetal biophysical profile was determined with a technique previously described. 1 The ultrasound evaluation was done by means of a linear array realtime ultrasound method (Picker LS-2000) equipped with a 3.5 MHz transducer. Real-time scanning consisted of a maximum 30-minute observation period during which fetal movements and fetal breathing movements were counted and fetal tone, amniotic fluid volume, and placental grading were estimated. Each biophysical variable (modified from the biophysical scoring of Manning et aJ.2) was scored as 2, 1, or 0 according to the criteria cited in our previous study. 1 The maximal score was 12 and the minimal 0. The patients were advised that the results of the biophysical
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Table I. Predictive value of the biophysical scoring for development of infection in groups 1, 2, and 3 Infection Group
Biophysical score
No. of patients
Group 1 (53 patients)
;;.8
37 16 15 0 3 2
,.;,_7 Group 2 (15 patients)
;;.8
Group 3 (5 patients)
;;.8
,.;,_7 ,.;,_7
scoring would not influence further management, since there are no data to support its usefulness in patients with premature rupture of the membranes. The patients were observed in the hospital and were managed conservatively with bed rest and bathroom privileges. Corticosteroid therapy was administered in the majority of patients (60 of 73). Gestational ages were confirmed by complete ultrasound profiles. Temperature was taken four times a day and white blood cell counts were performed daily. Bimanual pelvic examinations were avoided unless the patient was believed to be in active labor or a decision had been made to induce labor because of amnionitis. The biophysical profile determinations were repeated every 24 to 48 hours if patients remained undelivered. A low biophysical score (,.;,_7) was not an indication for delivery. Indications for delivery included labor, diagnosed amnionitis, persistent spontaneous variable decelerations (moderate to severe) on electronic fetal heart rate monitoring, or gestational age >37 weeks after a 24-hour period of observation if the cervix was favorable. The clinical diagnosis of amnionitis was made in the presence of two or more of the following criteria: Maternal fever >37.8° C, maternal tachycardia (120 bpm or more), leukocytosis (white blood cell count ;;.:20,000/mm3 in the absence of prior corticosteroid administration), fetal tachycardia (> 160 bpm), uterine tenderness, and foul-smelling amniotic fluid. Antibiotics were administered to the mother only after clamping of the cord. One patient who was given antibiotics before cord clamping was excluded from the study. On admission to the neonatal intensive care unit, all infants had cultures performed (blood, urine, cerebrospinal fluid, tracheal, nasogastric, external ear). All neonates at <34 weeks' gestation received prophylactic antibiotics (ampicillin and kanamycin), which were discontinued when cultures demonstrated no growth. Neonatal sepsis was diagnosed only in the presence of positive cultures of blood, urine, or cerebrospinal fluid. Possible neonatal sepsis was diagnosed in the absence of positive cultures when two or more of the following criteria were present: White blood cell count <5000/mm3 , polymorphonuclear leukocyte count <1800/mm 3 , I:T ratio (ratio of bands to total neutrophil count) >0.2, or positive gastric aspirate for poly-
No. 1/37 15/16 2/15 3/3 1/2
I
% 2.7 93.7 13.3
I
p value <0.001 <0.01
100 50
morphonuclear leukocytes showing >5 per high-power field. When neonatal sepsis or possible neonatal sepsis was diagnosed, the antibiotics were continued for approximately 7 to 10 days. Data collected after delivery included Apgar scores, birth weight, cord blood pH (umbilical artery and umbilical vein), route of delivery, placental cultures, and neonatal septic workup. For the purpose of this report, infection outcome was defined as the presence of clinical amnionitis, possible neonatal sepsis, or neonatal sepsis. The last study before delivery was compared with the outcome of pregnancy, as reflected by the development of infection (amnionitis, possible neonatal sepsis, neonatal sepsis). The association of each biophysical variable as well as combinations of variables (biophysical scoring) and the outcome was determined.
Results There were 148 examinations in these 73 patients (2.02 examinations per patient). The earliest gestational age tested was 25 weeks, the latest was 41 weeks, and the mean was 31.9 weeks. Nine examinations were the most done on one patient. The average time of the ultrasound fetal biophysical assessment was 15 minutes. Of the 73 pregnancies, 69 (94.5%) were preterm (<37 completed weeks) and four (5.4%) were term (;;.:37 weeks) at delivery. In only two patients was labor induced for the presence of a favorable cervix after 37 weeks' gestation and failure to go into spontaneous labor after a 24-hour period of observation. The mean prolongation of pregnancy was 6. 7 days and the infection rate (amnionitis, possible neonatal sepsis, neonatal sepsis) was 30.1% (22 of 73 patients). Of the 73 patients, 53 (72.6%) were delivered within 24 hours of the final examination (group 1), 15 (20.5%) between 24 and 48 hours (group 2), and five (6.8%) >48 hours from the last examination (group 3). The predictive value of the biophysical scoring for the development of infection is illustrated in Table I (X2 analysis). As can be seen, group 3 was too small to derive any meaningful statistical conclusions; however, it appears that there was no predictive value of the biophysical score in patients who were delivered >48 hours after the last examination. In group 1, a biophysical score of ;;.:8 was associated with an infection
512
Vintzileos et al.
July 1, 1985 Am J Obstet Gynecol
BIOPHYSICAL SCORE 12 11 10
9
8 7 6
5 4 3 2
TOTAL NO. OF PATIENTS= 53
0 0 + 0 0
0 0 0 0 0 X
••"' "' • • • • • "'
0 0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0
"'
X
X
+
0
0
0
0
0
0
0
0
(14) (6) (5) (6) (6) (3) (6) (1) (2) (2) (2)
0 0
Fig. I. Scatter diagram of the distribution of individual scores of both infected and noninfected cases of group 1. Number of patients is shown in parentheses. o = Noninfected. • = Amnionitis and neonatal sepsis. • = Neonatal sepsis . .A. = Amnionitis and possible neonatal sepsis. X = Possible neonatal sepsis. + = Amnionitis.
Table II. Mean ± 2 SD of the biophysical score, Apgar scores <7, umbilical cord pH, and gestational age of the infected versus the noninfected cases of group I Apgar scores <7 1 min No. of patients
Biophysical score
Infected (16) Noninfected (37) p value
5.2 ± 4.0 10.3 ± 3.2 <0.01
No.
I
Umbilical cord pH 5 min
%
10116 62.5 21.6 8/37 <0.01
No.
I
%
8/16 50 1137 2.7 <0.01
Artery
Vein
Gestational age (wk)
7.29 ± 0.14 7.31 ± 0.10 NS
7.34 ± 0.12 7.36 ± 0.10 NS
30.2 ± 6.0 32.7 ± 6.1 <0.01
Total number of patients = 53.
rate of 2.7%, and a low biophysical score (,;;7) was associated with an infection rate of 93.7% (p < 0.001). In group 2, a biophysical score of ;;;.8 was associated with an infection rate of 13.3%. This was significantly lower than the overall infection rate of 30.1% (p < 0.01). Subsequently, groups 2 and 3 were eliminated and further statistical analysis was therefore confined only to group 1. Of the 16 infected cases in group 1, delivery was performed in three because of persistent spontaneous variable decelerations, in five because of diagnosed antepartum amnionitis, in five because of simultaneous onset of labor and amnionitis, and in three because of spontaneous onset of labor alone. Of the 37 noninfected cases of group 1, delivery was performed in 28 patients because they went into labor, in seven because of persistent spontaneous variable deceleratiof1s, and in two for the presence of a favorable cervix at a gestational age of ;;;.37 weeks and no labor after a 24-hour period of observation. The distribution of individual biophysical scores is provided in Fig. 1 (scatter diagram) for both infected and noninfected cases of group 1. Table II illustrates the mean ± 2 SD of the biophysical score, Apgar scores, umbilical cord pHs, and gestational ages of the infected versus the noninfected cases of group 1 (Wilcoxon signed rank test). The infected group had significantly lower mean biophysical scores and Apgar scores (1 and 5 minutes) and earlier ges-
tational ages (<0.01). There was no significant difference in cord pH between the infected and noninfected cases. The final study before delivery was compared with the outcome of pregnancy as reflected by the development of amnionitis, possible neonatal sepsis, or neonatal sepsis (infection). The relationship between each biophysical variable and infection outcome is illustrated in Table III. A stepwise logistic regression analysis was used to determine the value of the biophysical score and the value of each biophysical variable in order of importance in predicting infection versus noninfection outcome. The best predictor of infection was found to be the biophysical score (F statistic 96.22). Of the individual biophysical variables, the nonstress test, fetal breathing movements, fetal movements, and fetal tone were found to be important in the above sequence (F statistic values 20.97, 20.38, 13.57, 12.18). Placental grading was not found to have any significant predictive value. The relationship between the combination of variables (mean biophysical scoring) and the different infection outcomes is shown in Table IV. As can be seen, the lowest biophysical scores were encountered in patients with positive neonatal cultures (neonatal sepsis). The biophysical profile of the infected cases is analyzed in Table V. As can be seen, when fetal movements were compromised (fetal movement score 1 or 0), the recovery of positive neonatal cultures (neonatal sepsis) was 75% (six of eight). There were a total
Fetal biophysical profile in PROM 513
Volume 152 Number 5
Table III. Relationship between each biophysical variable and infection outcome (group 1) Infected Biophysical variable NST2 NST l NSTO FBM 2 FBM l FBM 0 FM 2 FM l FM 0 FT 2 FT l FT 0 AF 2 AF 1 AF 0 PL 2 PL 1 PL 0
No. of patients*
Total last tests(%)
No.t
27 8 18 24 3 26 43 4 6 46 5 2 27 13 13 50 1 2
50.9 15.0 33.9 45.2 5.6 49.0 81.1 7.5 11.3 86.7 9.4 3.7 50.9 24.5 24.5 94.3 1.8 3.7
l/27 2/8 13/18 0/24 0/3 16/26 8/43 2/4 6/6 9/46 5/5 2/2 3/27 4/13 9/13 14/50 111 112
I
Noninfected %:t
No.§
3.7 25.0 72.2 0.0 0.0 61.5 18.6 50.0 100.0 19.5 100.0 100.0 ll.l 30.7 69.2 28.0 100.0 50.0
26/27 6/8 5/18 24/24 3/3 10/26 35/43 2/4 016 37/46 0/5 0/2 24/27 9/13 4/13 36/50 0/1 112
I
%11 96.2 75.0 27.7 100.0 100.0 38.4 81.3 50.0 0.0 80.4 0.0 0.0 88.8 69.2 30.7 72.0 0.0 50.0
NST = Nonstress test; FBM = fetal breathing movements; FM = fetal movements; FT = fetal tone; AF = amniotic fluid; PL = placental grading. *Total number of patients = 53. tTotal number = 16. tPercent of infected cases = 30.1. §Total number = 37. II Percent of noninfected cases = 69.8.
of seven instances of positive neonatal cultures. Of these, four were recovered from the blood (two group B Streptococcus, one Bacillus sp., and one Escherichia coli), two from the urine (one positive for group B Streptococcus and one positive for Peptostreptococcus), and one from cerebrospinal fluid (group B Streptococcus). There were only two neonatal deaths in the population tested. Both infants were delivered at 26 weeks' gestation because of amnionitis and severe variable decelerations. The last biophysical scores before delivery were 2 and 3, respectively (perinatal mortality 27.3/ 1000).
Comment Premature rupture of the membranes constitutes one of the most common complications of pregnancy. In the literature, the reported incidence ranges from 5% to 40%. 3 • 4 Although premature rupture of membranes before 37 weeks' gestation is hazardous to the fetus in terms of perinatal morbidity and mortality, its occurrence at term (after 37 weeks) also subjects the mother and fetus to increased risks. 5 Many investigators recommend prompt delivery of the fetus when premature rupture of the membranes occurs at term, because of the increased incidence of amnionitis with prolonged rupture of the membranes. 6 However, this action will usually result in an increased incidence of primary cesarean sections for failed induction of labor and cephalopelvic disproportion. 5
Table IV. Relationship between mean biophysical score and different infection outcomes (group 1)
Diagnosis Amnionitis Possible neonatal sepsis Amnionitis-possible neonatal sepsis Neonatal sepsis Amnionitis-neonatal sepsis
No. of patients
2 3 4
3 4
Mean biophysical score 8.0 6.3 5.5 4.3 3.5
As the biophysical score decreased, the severity of the infection increased (Spearman rank correlation - 0.75, p,:;; 0.001).
When premature rupture of the membranes occurs in a preterm gestation (<37 weeks), the management is even more controversial. In preterm gestations, immediate delivery of the fetus carries a significant risk of hyaline membrane disease, which still remains a major contributor to neonatal morbidity and mortality; therefore conservative management has been advocated by previous investigators.' However, the conservative approach carries an increased risk of fetal/neonatal infection and cord prolapse. Other management protocols involve the use of amniocentesis 8 • 9 in patients with preterm rupture of the membranes to detect not only the fetus with a mature lung profile but also the fetus most likely to develop sepsis. The problems as-
514 Vintzileos et al.
July I, 1985 Am J Obstet Gynecol
Table V. Analysis of biophysical profile of 16 infected cases (group I) Case Diagnosis
No.
1
2
2
0 0 0 0 0 1 0 0 0 1 0 0 0 0 0
3 4 5 6 7 8 9 10 11 12 13 14 15 16
0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
2 2 2 2 2 2 0 2 0 1 2 0 0 1 0 0
2
2
1 2 2 2 2 1 2 1 2 0 0 2 1 2 1
1 1 0 0 1 2 0 0 1 2 0 0 0 0 0
2 2 2 2 2 2 2 2 1 2 0 2 2 2 1 2
10 6 7 6 6 7 6 6 2 6 5 2 4 4 3 3
Amnionitis Amnionitis Possible neonatal sepsis Possible neonatal sepsis Possible neonatal sepsis Amnionitis-possible neonatal Amnionitis-possible neonatal Amnionitis-possible neonatal Amnionitis-possible neonatal Neonatal sepsis Neonatal sepsis Neonatal sepsis Amnionitis-neonatal sepsis Amnionitis-neonatal sepsis Amnionitis-neonatal sepsis Amnionitis-neonatal sepsis
sepsis sepsis sepsis sepsis
NST = Nonstress test; FBM = fetal breathing movements; FM = fetal movements; FT = fetal tone; AF = amniotic fluid; PL = placental grading.
sociated with this approach have been the inability to obtain fluid in almost half of these patients," the invasiveness of the procedure, and the lack of strong correlation between the presence of bacteria in the amniotic fluid and fetal sepsis."· 9 The presence of bacteria in the amniotic fluid (Gram stain and culture) obtained by transabdominal amniocentesis has been strongly correlated with the development of amnionitis and/or postpartum endometritis but not with fetal/neonatal sepsis as determined by the presence of positive neonatal cultures (blood, cerebrospinal fluid, urine). The incidence of fetal/neonatal sepsis with positive amniocentesis was only 14.2% (one of seven) in the study of Cotton eta!." and 22.2% (two of nine) in that of Garite et a!." In summary, a uniform approach to the management of patients with premature rupture of the membranes has not yet been elucidated. Until recently, the antepartum fetal evaluation of patients with premature rupture of the membranes has been solely confined to nonstress testing. The contraction stress test is contraindicated and has no place in the antepartum fetal evaluation of these patients because of the theoretical risk of initiating labor. The value of the fetal biophysical profile has been documented' in high-risk patients with intact membranes; however, its value in the antepartum fetal evaluation of patients with premature rupture of the membranes has not been previously determined. The relatively high neonatal sepsis rate in our study population is probably the result of the expectant management of premature rupture of the membranes in a selected group of high-risk patients referred to a tertiary care center. The inclusion of the possible neonatal sepsis group in the present study is in accordance with the current pediatric and obstetric literature. 10' 12 This
group is usually defined as the group with strong clinical and laboratory evidence of bacterial infection but with negative cultures (blood, cerebrospinal fluid). The negative cultures in this group of infants may be related to inadequate culturing techniques or the inherent difficulty encountered by most laboratories in isolating anaerobic bacteria. Nevertheless, these infants are usually treated after birth with intensive antibiotic therapy as are infants with positive cultures. The inclusion of the "possible neonatal sepsis" group in our study therefore allows comparison with other studies because it was clearly defined according to published data. 10' 12 According to our data, the rupture of membranes by itself does not alter the biophysical activities of the healthy fetus. However, a low biophysical score ('";:7) was a good predictor of impending fetal infection in patients with premature rupture of the membranes. In cases of impending fetal infection, the fetal biophysical activities are altered in a manner very similar to alteration of activities in the hypoxia of uteroplacental insufficiency. The first manifestations of impending fetal infection were nonreactive nonstress testing and absence of fetal breathing. Loss of fetal motion and poor fetal tone were late signs of fetal infection, since the majority of these infants had positive cultures in the immediate neonatal period (Table V). The presence of fetal breathing (Table III) had the highest specificity in predicting absence of fetal infection. There were no cases of fetal infection when breathing was present within 24 hours prior to delivery. It has been reported that the incidence of fetal breathing movements is decreased prior to the onset of labor, but these observations were made in chronic fetal lamb preparations.'' It is not yet clear whether fetal breathing movements are diminished prior to labor in humans. The data of
Fetal biophysical profile in PROM
Volume 152 Number 5
515
PROM* Term (;.37 weeks)
~
~ BS;;,8 7
l
RipetceNix
BS~7
I
Delivery
Delivery
Preterm ( < 37 weeks)
~. l t
BS > 8
BS< 7 (perSIStently)
Expectant management. Repeat BS q 24 hours
Consider delivery. If NST·O and FBM·O.
May wail X 24 hours for SOL
Fig. 2. Proposed protocol for management of premature rupture of the membranes. *Premature rupture of the membranes. BS = Biophysical score. NST-0 = Nonreactive nonstress test. FBM0 = Fetal breathing absent. SOL = Spontaneous onset of labor.
Patrick and Challis, 14 however, which are based on human fetal breathing movements, suggest that, prior to normal spontaneous labor in humans, fetal breathing movements may be decreased but that when labor follows spontaneous rupture of the membranes-as in our study population-fetal breathing movements do not decrease until accelerated labor occurs. In fact, these investigators reported an increase in fetal breathing movements in two fetuses which were observed during early labor. In our study group (group 1) there was a lower incidence of spontaneous onset of labor in the infected group (eight of 16, or 50%) versus the noninfected group (28 of 37, or 75.6%). Therefore the absence of fetal breathing in the infected group cannot be attributed to impending spontaneous onset of labor but rather to fetal infection. The relationship between gestational age and fetal biophysical profile scoring has been investigated in our institution by a recent retrospective study of 1151 biophysical profiles and scores of pregnancies with good outcome. In that study [Vintzileos AM, Feinstein SJ, Lodeiro JG, Campbell WA, Weinbaum PJ, Nochimson DJ. The biophysical profile of the healthy fetus from 25 to 44 weeks of gestation and the effect of premature rupture of the membranes (submitted for publication)] the incidence of fetal biophysical scoring of ~8, as well as mean biophysical scoring, was found to remain unchanged from 25 to 44 weeks' gestation regardless of the status of the membranes. Therefore the low scores of the infected cases in the present study cannot be attributed to lower mean gestational age (Table II) but rather to fetal infection. A tendency for an increased incidence of infection with diminishing amniotic fluid volume was also observed (Table III). It could be speculated that patients with decreased amniotic fluid volume are deprived of the bacteriostatic effect of a normal amniotic fluid volume. The loss of fetal movement (fetal movement score 0) and fetal tone (fetal tone score 0) was the
best predictor of fetal infection, but as it has been already stated, this is a late sign of infection. The decrease in fetal biophysical activities prior to the development of clinical infection makes sense, especially in cases of an ascending infection where the fetus seems to be the first target. Fetal infection that may lead to acidosis and perinatal hypoxic-ischemic encephalopathy has already been described.15 The mechanism by which fetal infection diminishes fetal biophysical activities without acidosis, as determined by cord blood pH measurements, is unknown. Our speculation is that early fetal infection may increase fetal oxygen demands and cause local tissue hypoxia and, thereby, malfunction of the central nervous system centers that control the reflex biophysical activities. 1 Only late stages of fetal infection are manifested by blood acidosis and possible neurological damage due to hypoxic-ischemic encephalopathy. 15 When premature rupture of the membranes occurs at term, the fetal biophysical profile should be used to select those patients who are candidates for fetal infection and therefore in need of prompt delivery. In preterm rupture of the membranes, the use of the fetal biophysical profile could replace amniocentesis in selecting those patients who are less likely to develop fetal infection and may be benefited by expectant management. For the majority of these patients, labor may be arrested for at least 48 hours, the minimum period required to enhance fetal lung maturity with corticosteroids. Fig. 2 illustrates a proposed protocol which we currently use in an ongoing prospective study to test its efficacy in improving pregnancy outcome in patients with premature rupture of the membranes. A persistently low biophysical score (,;:;7) with a nonreactive nons tress test and absence of fetal breathing movements is highly predictive of fetal infection in patients with premature rupture of the membranes and has been used by us as an indication for immediate delivery.
516 Vintzileos et al.
In summary, the fetal biophysical profile is a simple, noninvasive, and reliable tool for evaluating patients with premature rupture of the membranes. REFERENCES I. Vintzileos AM, Campbell WA, Ingardia CJ, et al. The fetal biophysical profile and its predictive value. Obstet Gynecol 1983;62:271. 2. Manning FA, Morrison I, Lange I. Fetal biophysical profile scoring: a prospective study in 1184 high-risk patients. AM j 0BSTET GYNECOL 1981; 140:289. 3. Gunn GC, Mishell DR, Morton DG. Premature rupture of the fetal membranes. AM J 0BSTET GYNECOL 1970; 106:469. 4. Niswander KR, Gordon M. The women and their pregnancies. The Collaborative Perinatal Study of the National Institute of Neurological Diseases and Stroke of the U. S. Department of Health, Education, and Welfare, Public Health Service, and National Institutes of Health. Philadelphia: WB Saunders, 1972:427-34. 5. Lanier LR, Scarbrough RW, Fillingim DW, et al. Incidence of maternal and fetal complications associated with .rupture of membranes before the onset of labor. AM J 0BSTET GYNECOL 1965;93:398. 6. Russel KP, Anderson GV. The aggressive management of ruptured membranes. AM j 0BSTET GYNECOL 1962; 83:930.
July I, 1985 Am J Obstet Gynecol
7. Kappy KA, Cetrulo CL, Knuppel RA, et al. Premature rupture of the membranes: a conservative approach. AM j 0BSTET GYNECOL 1979;134:655. 8. Garite TJ, Freeman RK, Linsey M, et al. The use of amniocentesis in patients with premature rupture of the membranes. Obstet Gynecol 1979;54:226. 9. Cotton DB, Hill LM, Strassner HT, et al. Use of amniocentesis in preterm gestation with ruptured membranes. Obstet Gynecol1984;63:38. 10. Zipursky A, Palko J, Milner R, et al. The hematology of bacterial infections in premature infants. Pediatrics 1976; 57:839. 11. Akenzua Gl, Hui YT, Milner R, et al. Neutrophil and band counts in the diagnosis of neonatal infections. Pediatrics 1974;54:38. 12. Andreyko JL, Chen CP, Shennan AT, et al. Results of conservative management of premature rupture of the membranes. AM j 0BSTET GYNECOL 1984; 148:600. 13. Boddy K, Dawes GS. Fetal breathing. Br Med Bull 1975;31:1. 14. Patrick J, Challis J. Measurement of human fetal breathing movements in healthy pregnancies using a real-time scanner. Semin Perinatol 1980;4:275. 15. Peevy KJ, Chalhub EG. Occult group B streptococcal infection: an important cause of intrauterine asphyxia. AM j 0BSTET GYNECOL 1983;146:989.
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