Abnormal fetal heart rate patterns and placental inflammation

Morrow, Ritchie, and Bull

systolic! diastolic ratio, the vascular resistance on the fetal side of the placenta remained unaltered, which suggests it was unaffected by the changes in the maternal circulation. The absence of any sign of fetal distress in response to the maternal changes may indicate that under normal circumstances the fetus has sufficient reserve to compensate for such changes. Further support for this viewpoint is that a similar exercise chal~ lenge caused no change in the mean velocity in the fetal aorta. 6 It may be that changes in the umbilical circulation would occur if the fetus was already compromised or the uterine flow was abnormal before exercise. Bed rest in a hospital is an expensive, largely empirical treatment for intrauterine growth retardation. Our study lends positive support to the value of rest in the improvement of uterine blood flow. We conclude that moderate exercise in the late phase of gestation causes a transient but significant increase in uteroplacental vascular resistance. We have no evidence that this has any harmful effect in the healthy fetus but speculate that it may be harmful when the fetus is already compromised.

January 1989 Am J Obstet Gynecol

REFERENCES 1. Fleischer A, Schulman H, Farmakides G, Bracero L, Blattner P, Randolph G. Umbilical artery velocity waveforms and intrauterine growth retardation. AM] OBSTET GYNECOL 1985;151:502-5. 2. Erskine RLA, Ritchie ]WK. Umbilical artery blood flow in normal and growth-retarded fetuses. Br] Obstet Gynaecol 1985;92:605-10. 3. Trudinger B]. Giles WB, Cook CM. Uteroplacental blood flow velocity-time waveforms in normal and complicated pregnancy. Br] Obstet Gynaecol 1985;92:39-45. 4. Winer B]. Statistical principles in experimental design. 2nd ed. New York: McGraw-Hill 1971. 5. Clapp ]F. Acute exercise stress in the pregnant ewe. AM] OBSTET GYNECOL 1980;136:489-94. 6. Pijpers L, Wladimiroff ]W, McGhie]. Effect of short-term maternal exercise on maternal and fetal cardiovascular dynamics. Br] Obstet GynaecoI1984;91:1081-6. 7. Artal R, Platt LD, Sperling M, Kammula RK, Jilek], Nakamura R. Maternal cardiovascular and metabolic responses in normal pregnancy. AM ] OBSTET GYNECOL 1981; 140:123-7. 8. Artal R, Rutherford S, Romem Y, Kammula RK, Dorey F], Wiswell RA. Fetal heart rate responses to maternal exercise. AM] OBSTET GYNECOL 1986;155:729-33. 9. Clapp ]F. Fetal heart rate response to running in midpregnancy and late pregnancy. AM ] OBSTET GYNECOL 1985;153:251-2.

Abnormal fetal heart rate patterns and placental inflammation Carolyn M. Salafia, MD: Heather E. Mangam: Cristine A. Weigl, BS: Gerald J. Foye, MD,h and Lester Silberman, MDb Danbury, Connecticut Can acute inflammation in the placental membranes, amniotic fluid, or both, predispolle to the development of abnormal fetal heart rate patterns? One hundred cases in which bradycardia was noted were compared with 48 cases in which abnormal fetal heart rate patterns did not occur. Case and control subjects were matched to provide an equivalent risk of developing ascending infection in the two groups. Fetoplacental weight ratio and the presence of other placental diseases were also considered. The presence of acute inflammation in the umbilical cord (p = 0.03), amnion (p = 0.01), and choriodecidua (p = 0.03), and higher grades of inflammation in chorionic plate (p = 0.03) were linked to the presence of abnormal fetal heart rate patterns. No other placental factors were associated with increased risk of fetal bradycardia. The association of abnormal fetal heart rate patterns with acute inflammation suggests that intra-amniotic inflammation is important in the genesis of fetal bradycardias. The inflamed amniotic fluid could alter fetal metabolism via effects on the pulmonary or gastrointestinal systems or effects on umbilical and chorionic vessels. (AM J OBSTET GVNECOL 1989;160:140-7.)

Key words: Chorioamnionitis, fetal heart rate, placenta, intrauterine infection

From the Departments of Laboratory Medicine" and Obstetrics and Gynecology,h Danbury Hospital. Received for publtcatwn December 9, 1987; revised July 20, 1988; accepted July 29, 1988. Reprint requests: Carolyn M. Salafia, MD, Department ofLaboratory Medicine, Danbury Hospital, 24 Hospital Ave., Danbury, CT 06810.

140

Variable and late decelerations and bradycardia are considered indications of fetal hypoxia with present or impending fetal compromise.' They are felt to reflect the effects of umbilical cord compression (variable decelerations), or placental insufficiency (late decelerations and bradycardia). Vintzileos et al. 2 have indicated

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141

Table I. Grading. system for acute intrauterine inflammation Grade 1 Grade 2 Grade 3 Grade 4 Grade Grade Grade Grade

1 2 3 4

Grade Grade Grade Grade

1 2 3 4

Amnion and choridecidua One focus of at least 5 PMNs More than 1 focus of grade 1 inflammation or at least 1 focus of 5-20 PMNs Multiple and/or confluent foci of grade 2 Diffuse and dense acute inflammation Umbilical cord PMNs within the inner one third of the umbilical vein wall PMNs within inner one third of at least 2 umbilical vessel walls PMNs in perivascular Wharton's jelly Panvasculitis and funisitis extending deep into Wharton's jelly Chorionic plate One focus of at least 5 PMNs in subchorionic fibrin Multiple foci of grade 1 in subchorionic fibrin Small number of PMNs in connective tissue of chorionic plate Numerous PMNs in chorionic plate, and chorionic vasculitis

PMNs, Polymorphonuclear leukocytes.

that a low biophysical score is a good predictor of impending fetal infection in patients with premature rupture of membranes. The mechanism of the association is not clear. No sttidies have included placental pathologic processes as factors in the genesis of abnormal fetal heart rate (FHR) patterns. Moberg et al,3 describe an increased prevalence of fetal distress assoCiated with preterm premature rupture of membranes. Specifically, these fetuses demonstrated a predominance of FHR tracings consistent with umbilical cord compression. 3 These authors found no association between the p~esence of fetal distress and clinical evidence of chorioamnionitis. However, clinical diagnosis of chorioamnionitis is an insensitive measure of the presence of acute ascending infection; well over 50% of cases with histologic chorioamnionitis will not be symptomatic and will not have objective signs of infection" Prior work has indicated that when the def'inition of an uncomplicated pregnancy carefully excludes those in which FHR abnormalities are observed, the prevalence of "silent" acute inflammation of the intra-amniotic tissues, the umbilical cord, and chorionic plate is rare, whereas isolated acute deciduitis, an extraamniotic inflammation, is very common. This study was initiated to investigate whether in term deliveries the presence of acute inflammation of the placenta might be linked to an increased prevalence of multiple variable declerations, late decelerations, and bradycardia, FHR patterns not classically considered to reflect acute intrauterine infection.

Material and methods Since 1983 at the Danbury Hospital, placental pathologic study has been a routine part of the evaluation of a complicated pregnancy, delivery, or neonatal course. Clinical data are collected on standard Hollister data forms. Criteria for the selection of pla~entas for pathologic examination include but are not limited to all ma-

Table II. Placental pathology and FHR

I Acute inflammation* Fetoplacental weight ratiot Infarction; Intervillous thrombosis§ Chronic villitisll Hemorrhagic

Abnormal FHR (100)

I

Normal FHR (48)

85

35

6.4 ± 1.36

6.12 ± 1.09

18 26

5 17

21 5

10 2

endovasculitis~

*x' = 3.08, P = 0.07. tt = 1.291, P = 0.196. h 2 = 0.95, P = 0.32. §X2 = 1.395, P = 0.23. IIx2 = 0.001, P = 0.98. ~x' = 0.05, P '" 0.82.

jor maternal medical diseases, past poor pregnancy outcome, all pregnancirelated diseases, abnormal antenatal diagnostic studies, complications of labor and delivery (including all passage of meconium, rupture of membranes greater than 12 hours before delivery, all abnormalities of fetal heart monitoring, and all diagnoses of fetal distress), all neonatal intensive care unit admissions, and all stillbirths. All patients admitted to the labor and delivery suite have fetal heart monitoring performed for 20 minutes. If no FHR abnormalities are observed, continuous monitoring is discontinued. Such patients continue to be monitored while in bed, but are permitted to ambulate. Continuous monitoring is reinstituted at the onset of active labor. Diagnoses of abnormal FHR pattern in this study included: repetitive moderate to severe variable decelerations, late decelerations, and bradycardias. Variable decelerations were graded as moderate if FHR was no less than 70

142 Salafia et al.

January 1989 Am J Obstet Gynecol

Fig. 1. Nonmarginating inflammation within decidua (grade 2). (Hematoxylin-eosin slain; magnification x 4 .)

Fig. 2. Marginating acute inflammation within chorion and decidua (grade 3). (Hematoxylin-eosin stain; magnification x 4.)

beats/min for between 30 to 60 seconds or between 70 and 80 beats/min for greater than 60 seconds and as severe if the fall in FHR was no less than 70 beats/min for longer than 60 seconds. Bradycardia, which was defined as a baseline FHR of 110 beats/ min or less, was classified as severe if the baseline dropped below 100 beats/min. In this study, 100 patients in whom no clinical diagnosis of chorioamnionitis was made were selected, but abnormalities of FHR monitor patterns were observed, and 48 control subjects, in whom chorioamnionitis was not diagnosed clinically, and no FHR abnormality was observed during the standard monitor-

ing period, and no indications to resume monitoring were identified during labor. Selection was confined to deliveries occurring between 37 and 42 weeks' gestation. The first 100 deliveries in which FHR abnormalities were described were considered cases. All available tracings were reviewed by a perinatologist (G . J. F.) and diagnoses confirmed. Twelve subjects were observed to have Apgar scores ~4 at I minute, none of whom had Apgar scores of <7 at 5 minutes. In 24 patients meconium passage was noted before delivery. Control subjects were selected from among all deliveries selected for placental pathologic examination for indications not including abnormal FHR. No instances of meconium

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143

Fig. 3. Polymorphonuclear leukocytes within the chorionic plate and in the ~ubchorionic fibrin (grade 3). (Hematoxylin-eosin stain; magnification x 4.)

Table III. Total of all grades of acute inflammation and the fetoplacental weight ratio among an uncomplicated delivery group compared with the abnormal and normal FHR groups Total Acute inflammation Cord Membranes Plate Fetoplacental ratio

Abnormal FHR

Normal FHR

Uncomplicated

100

48

161

16t 80§ 65~

6.4 (± 1.36)**

I:j: 2511 25# 6.12 (± 1.09)tt

0 88 44 6.92 (± 1.27)

*Alll or t test analyses compare the uncomplicated data set (column 3) to one of the other two data sets. tx2 = 27.4; P < 0.0001. :j:X 2 = 3.37; P = 0.07. §X2 = 17.27; P < 0.0001. IIx' = 0.09; p = 0.75; Fp = 0.44. ~X2 = 35.99; P < 0.0001. #X 2 = 10.25; P = 0.001. **t = 3.12, P = 0.0029. ttl = 3.95, P = 0.0008.

passage were observed, and three of the 48 control infants showed Apgar scores of ~4 at 1 minute, with a fourth infant having a score of ~7 at 5 minutes (cases vs controls, p > 0.1). Case and control su~jects were matched for the following: equivalent durations of rupture of membranes before delivery, 10Gitions of care (clinic vs private), and parity. Clinic patients are generally of lower socioeconomic status than private patients; the increased prevalence of preterm delivery among such a population may reflect an increased risk of ascending intrauterine infection.' Our clinic population demonstrates a threefold greater prevalence of pre term birth and participates in a prematurity prevention program, in which cervical microbiologic specimens are studied during pregnancy

and pertinent pathogens are treated. Thus clinic and private patients may differ in the vaginal microbial flora. Parity was considered since the extent of cervical dilatation in the late third trimester is greater in multiparas than in nulliparas. 6 Differing degrees of cervical dilatation may influence the development of acute ascending infection. The presence of abnormal FHR patterns determined selection as a case; however, the presence of maternal or neonatal disease was not excluded. Thus cases included both pregnancies complicated only by abnormal FHR pattern and those complicated by abnormal FHR pattern and other factors. For these reasons, cases were also compared with a normative data set, which consisted of 161 cases in which no maternal or fetal complications were present. This rep-

144 Salafia at al.

January 1989 Am J Obstet Gynecol

Table IV. Prevalence and distribution of grades of acute inflammation in the umbilical cord, amnion, chorion decidua, and chorionic plate among the normal and abnormal FHR groups Grade 1

Umbilical cord Abnormal FHR Normal FHR Amnion Abnormal FHR Normal FHR Chorion decidua Abnormal FHR Normal FHR Chorionic plate Abnormal FHR Normal FHR

Grade 2

Grade 3

Grade 4

5 0

3 0

5 1

3 0

9 7

5 0

5 0

2 0

32 14

18 6

8 1

2 0

26 9

10 9

12 5

16 2

Cord: (total) abnormal vs normal; X' = 4.25; P = 0.04; Fp = 0.03. Amnion: (total) abnormal vs normal; X' = 16.4; p = 0.01. Chorion: (total) abnormal vs normal; X' = 4.7; P = 0.03; grades'" 2; abnormal vs normal; X' = 3.7; P = 0.05; grades." 3; abnormal vs normal; X' = 3.16; p = 0.07; Fp = 0.06. Plate: (total) abnormal vs normal; X' = 1.63; P = 0.20; grades." 3; abnormal vs normal; X' = 3.23; P = 0.07; Fp = 0.05.

resents a continuous series of patients whose pregnancies excluded standard criteria for selection for placental examination, specifically, and medical or obstetric maternal complications, abnormal antenatal diagnostic testing, or therapeutic intervention during pregnancy, clinically significant intrapartum complications, and any neonatal complications, including admission to special care nursery, congenital anomalies, or stillbirth. Gross and microscopic studies of the placentas were performed according to established pathologic protocols and without knowledge of clinical data. Tissue samples included two sections of umbilical cord, at least one section of chorionic plate taken from an area with minimal subchorionic fibrin, a roll of membranes taken from the area of membrane rupture, and a membrane roll. The prevalence and severity of acute inflammation of the extraplacental membranes, umbilical cord, and chorionic plate were ascertained. The grading system, which specifically includes acute deciduitis and mild degrees of acute inflammation of the chorionic plate, membranes, and umbilical cord, is described in Table I. Examples of grades of acute inflammation in sample tissues are shown in Figs. 1 to 3. Methods of analysis included the X2 test with Fisher's correction for small sample size and the Student t test for unpaired samples.

Results The prevalence of acute inflammation, placental infarction, intervillous thrombosis, chronic villitis, and hemorrhagic endovasculitis in case and control subjects is presented in Table II. The correlation of acute inflammation of the extra placental membranes, chorionic plate, or umbilical cord and abnormal FHR patterns

approached significance. When the specific tissues were examined separately, the presence of acute amnionitis, acute chorionitis, and acute chorionitis with fetal chorionic vasculitis and umbilical vasculitis/funisitis were significantly associated with abnormal FHR patterns (Table III). In 16 of the 17 fetuses whose umbilical cords demonstrated acute inflammation, abnormalities of FHR patterns were observed (p = 0.029). When umbilical vasculitis and chorionitis were excluded from those with acute inflammation, analysis demonstrated no association of acute inflammation of the chorion and decidua only with abnormal FHR (p > 0.20). The presence of acute inflammation in the chorion and decidua was associated with abnormal FHR pattern, but did not show stronger association with increasing grade of inflammation (Table IV). However, the distribution of the inflammation demonstrated an association with abnormal FHR patterns. This study distinguished between "marginating" and "necrotizing" (nonmarginating) choriodeciduitis. The former pattern has been suggested to reflect the effects of an intraamniotic infection. Small numbers of marg-inating- inflammation were observed in this study; howe\'er, those patients with marginating inflammation were most likely those with higher grades of inflammation in the chorion and decidua (X 2 = 17.36; P < 0.0001) and also inflammation in the amnion, chorionic plate and umbilical cord (p < 0.05). Thus marginating choriodeciduitis was indirectly correlated with abnormal FHR patterns by its association with higher grades of inflammation and with other loci of inflammation more directly reflecting intra-amniotic inflammation. The comparison between cases with abnormal FHR patterns and 161 uncomplicated pregnancies demon-

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strated an even stronger association between acute inflammation, and specifically inflammation of the intraamniotic tissues, such as the umbilical cord, with abnormal FHR patterns (Table III). Patients with normal FHR patterns but other pregnancy complications demonstrated a significantly greater prevalence of inflammation of the chorionic plate only. As noted, these grades of inflammation were most frequently mild and may reflect the fact that prolonged asymptomatic rupture of membranes is a risk factor of ascending acute intrauterine infection and a criterion for placental examination. No association between type or severity of abnormal FHR pattern on histopathologic examination was observed. The duration of membrane rupture was examined in association with abnormal FHR and the presence of acute inflammation (Table V). Since rupture of membranes was a condition that was matched between groups, no association between an increased prevalence of abnormal FHR and increased duration of rupture of membranes was detected. More surprisingly, there was no increased prevalence of acute inflammation with prolonged rupture of membranes (p = 0.28). However, the range of durations of rupture of membranes in this study is short: 71 of the 100 with abnormal fetal heart rates had rupture of membranes < 10 hours, and 81 of the 107 cases with acute intrauterine inflammation had rupture of membranes of <10 hours. No significant difference in duration of rupture of membranes was associated with the presence or absence of FHR abnormality or acute intrauterine inflammation. The association between acute inflammation and abnormal FHR pattern was present at both < and> 10 hours (e.g., choriodecidua, < 10 hours of rupture of membranes, abnormal FHR 22/71 vs normal FHR, 4/28, P = 0.09; > 10 hours of rupture of membranes, 11/29 vs 2/20, P = 0.03). No form of placental villous lesion representing vascular disease (infarction, intervillous thrombosis) or infectious/immunologic processes (chronic villitis, hemorrhagic endovasculitis) was associated with an increased prevalence of FHR abnormalities in the overall population (Table II). The fetoplacental weight ratio, a crude reflection of placental insufficiency, indicating the number of grams of placenta available to nutritionally support each gram of fetus, also did not differ significantly in fetuses with and without FHR abnormalities. When only the small number of subjects without any acute inflammation were studied, there was no demonstrable association of any placental factors with the presence of abnormal FHR pattern. Although fetoplacental weight ratio did not differ between case and control subjects, the control group had a significantly lower fetoplacental weight ratio compared with a series

145

Table V. Mean hours of membrane rupture before delivery by FHR pattern and presence of acute inflammation

FHR (abnormal) FHR (normal)

+ Acute inflammation

No acute inflammation

9.69 12.02

8.33 11.07

9.49 11.77

ROM, Rupture of membranes.

of entirely uncomplicated pregnancies (Table III). Again, this may reflect selection of control subjects for the presence of factors such as maternal smoking and neonatal disease.

Comment Our results strongly link the presence of histologic evidence of acute ascending infection of the amniotic fluid space with fetal bradycardia and variable and late decelerations. This study does not include microbial studies of the placentas or amniotic fluid; therefore the question of infection cannot be directly addressed. However, Fox7 has cogently summarized the arguments supporting an infectious cause of acute placental inflammation, including the clear and specific relationship between prolonged membrane rupture and acute intrauterine inflammation, the rarity of acute inflammation in cesarean deliveries, the occurrence of acute inflammation in the twin laying nearer the cevical os, more prominent infection in the area of the cervical os, and the association of acute intrauterine inflammation with maternal pyrexia, postpartum endometritis, and neonatal pneumonia and sepsis. In addition, data indicate that specific patterns and high degrees of severity of acute intrauterine inflammation are tightly correlated with positive cultures of amniotic fluid obtained by amniocentesis (Romero Rj, Salafia eM. Unpublished observations). More sensitive methods have shown that milder degrees of acute ascending infection may be associated with minimal levels of amniotic fluid colonization or contamination of amniotic fluid with nonviable bacterial byproducts. 8 In this study the case and control subjects were matched to provide as equal a risk for the development of acute ascending infection as could be made. Since the duration of rupture of membranes was controlled, the excess of abnormal FHR noted with acute intrauterine inflammation was not simply because of the decrease in amniotic fluid volume after rupture of membranes predisposing to umbilical cord compression. 3 Indirectly, it also speaks against an effect of increased duration of labor. In 1971 Fox and Langley9 noted that "the placentas of hypoxic fetuses show

146 Salafia et al.

leucocytic infiltration more often than do placentas from cases in which the fetus was not hypoxic." However, if both fetal hypoxia and duration of membrane rupture were considered in the analysis, no association between membrane inflammation and fetal hypoxia was observed. Their criteria of what constitutes "fetal hypoxia" are not described. However, we are specific in our criteria. FHR abnormalities were chosen as indexes of fetal distress since they are less subjective than the assessment of meconium, more sensitive indicators than Apgar scores, and more frequently performed in this population than fetal scalp sampling. Maudsley et a\. 10 noted a similar association between histologic indicators of acute intra-amniotic infection and meconium staining of the newborn. The present study specifically excluded preterm, postterm, and by chance, preeclamptic gestations, conditions included in the study of Fox and Langley.9 All three situations were described as those in which prolonged rupture of membranes was frequent; Fox and Langley9concluded that fetal hypoxia is, in fact, related to these pathologic clinical states, and any relationship of fetal hypoxia to chorioamnionitis is spurious. Since 1971, more active obstetric intervention has likely modified the course of prolonged rupture of membranes. Acute inflammation in our population was significantly associated with FHR abnormalities at both < 10 hours and> 10 hours of rupture of membranes. We are able to compare this data with a previously reported data set of uncomplicated term gestations and have found an identical association between histologic indications of subclinical acute amniotic fluid inflammation and fetal distress in a series of pregnancies complicated by gestational diabetes (Salafia CM, Weigl CA, Silberman L. Unpublished observations). Reporting the prevalence of chorioamnionitis in a series of 7505 deliveries, Russell" observed that 82.4% of the cases of "membranitis" had membranes ruptured for <24 hours, and 45.4% for <4 hours. Russell determined that those infants born near term to afebrile mothers and in the absence of prolonged rupture of membranes or cervical ligature showed no infection-related sequelae. In addition, he concluded that "chorioamnionitis occurring under these circumstances is a benign and inconsequential pathological curiosity." The present data indicate that acute intra-amniotic inflammation is the sole significant pathologic correlate of a relatively specific type of fetal distress, namely, FHR patterns of bradycardia and variable and late decelerations in otherwise uncomplicated term deliveries. In growth-retarded term infants, the observation of late FHR decelerations was found to correlate strongly with subsequent poor neonatal neurologic statuS. 12 The view of the "benign" nature of clinically "silent" acute ascending intrauterine

January 1989 Am J Obstet Gynecol

infection must be reevaluated. Alternatively the definition of "silent" must exclude "hypoxic" FHR patterns, as well as more standard infection-related criteria. Vintzileos et a\.2 hypothesized that mild degrees of amniotic fluid infection could predispose to fetal hypoxia by increasing fetal metabolic and oxygen demands. Breathing infected or inflamed amniotic fluid, which contains increased quantities of interleukin 1 and prostaglandins, could alter pulmonary vascular resistance, and affect fetal and fetoplacental hemodynamics. 1s The hypoxia induced by subclinical chorioamnionitis may not be stress sufficient in either duration or severity to alter cord pH, but may cause transient tissue fluctuations in oxygen content and lactic acid concentration. A second mechanism by which acute intrauterine inflammation might lead to fetal hypoxia could involve the known sensitivity of the umbilical and chorionic vessels to the vasoconstrictive effects of thromboxanes and prostaglandins. Such effects have been noted at levels detected in amniotic fluid, which suggests a potential for a physiologic effect of these molecules on the modulation of umbilical and chorionic vascular tone. 14 Increased intra-amniotic levels of prostaglandins and other molecules invoked in the inflammatory response could lead to vasoconstriction and vasospasm of the placental vessels, decreased fetal perfusion, and fetal hypoxia. More specifically, an event of umbilical cord compression could induce a prolonged spasm of such a sensitized vessel and decrease fetal perfusion to a much greater degree for a much longer duration than that that occurs generally observed in noninfected fetuses. That no specific FHR abnormality could be associated with acute umbilical vasculitis and chorionitis may be the result of the small number of such cases in this group, that is, 100. Placental vascular diseases, such as infarction and intervillous thromboses, are associated with conditions in which placental insufficiency is frequently observed. 7 Chronic placental inflammatory diseases, such as chronic villitis and hemorrhagic endovasculitis, are also associated with poor fetal growth. 15 However, neither placental vascular nor infectious/immunologic disease was associated with an increased prevalence of acute development of hypoxic FHR patterns in otherwise healthy fetuses (Table II). Whether these processes may act in synergy with acute peripartum factors, such as acute ascending intrauterine inflammation, deserves further evaluation. Previous investigations indicated that acute intrauterine inflammation is associated with the onset of labor in term deliveries. Acute ascending inflammation and intrauterine inflammation may frequently be present in uncomplicated term pregnancies. This work in-

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dicates that acute intrauterine inflammation may be involved in the genesis of commonly recognized forms of acute hypoxic fetal distress at term. REFERENCES I. Gimovsky ML, Cavitis SN. Diagnosis of hypoxic fetal heart rate patterns. Clin Perinatol 1982;9:313. 2. Vintzileos AM, Campbell WA, Nochimson Cj, Connolly ME, Fuenfer MM, Hoehn GJ. The fetal biophysical profile in patients with premature rupture of the membranesan early predictor of fetal infection. AM J OBSTET GyNECOL 1985;152:510. 3. Moberg LJ, Garite TJ, Freeman RK. Fetal heart rate patterns and fetal distress in patients with preterm premature rupture of membranes. Obstet Gynecol 1984;64:60. 4. HauthJC, Gilstrap LC. Term maternal and neonatal complications of acute chorioamnionitis. Obstet Gynecol 1985;66:59. 5. Guzick DS, Winn K. The association of chorioamnionitis with preterm delivery. Obstet Gynecol 1985;65: II. 6. Hemdricks CH, Brenner WE, Kraus G. Normal cervical dilatation pattern in late pregnancy and labor. AM J OBSTET GYNECOL 1970;106:1065. 7. Fox H. The pathology of the placenta. Vol 7. In: Bennington JL, ed. Major problems in pathology. Philadelphia: WB Saunders, 1978. 8. IamsJD, Clapp DH, Contos DA, Whitehurst R, Ayers LW,

9.

10.

II. 12.

13. 14.

15.

O'Shaughnessy RW. Does extra-amniotic infection cause preterm labor? Gas-liquid chromatography studies of amniotic fluid in amnionitis, preterm labor, and normal controls. Obstet Gynecol 1987;70:365. Fox H, Langley FA. Leukocytic infiltration of the placenta and umbilical cord: a clinico-pathologic study. Obstet GynecoI1971;37:451. Maudsley RF, Brix GA, Hinton NA, Robertson EM, Bryans AM, Haust MD. Placental inflammation and infection-a prospective bacteriologic and histologic study. AM J OBSTET GYNECOL 1966;95:648. Russell P. Inflammatory lesions of the human placenta. l. Clinical significance of acute chorioamnionitis. Ani J Diagn Gynecol Obstet 1979;1:127. Dijxhoorn MJ, Visser GHA, Touwen CL, Huisjes HJ. Apgar score, meconium, and acidaemia at birth in small-for gestational age infants born at term, and their relationship to neonatal neurological morbidity. Br J Obstet Gynaecol 1987;94:873. Cassin S. The role of PG and thromboxanes in the control of the pulmonary circulation in the fetus and newborn. Semin Perinatol 1980;4:101. Howard RB, Hosokawa T, Maquire MH. Pressor and depressor actions of prostanoids in the intact human fetoplacental vascular bed. Prostaglandins Leukotrienes Med 1986;21 :323. Altshuler G. Placentitis. Contrib Gynecol Obstet 1982; 9:113.

Case-fatality rates for tubal sterilization in U. s. hospitals, 1979 to 1980 Luis G. Escobedo, MD, Herbert B. Peterson, MD, Gary S. Grubb, MD, and Adele L. Franks, MD Atlanta, Georgia To update a 1977 to 1978 case-fatality estimate for tubal sterilization in U.S. hospitals, we reviewed the medical records of women reported by the Commission on Professional and Hospital Activities to have died after tubal sterilization procedures in 1979 or 1980. We project that the most reasonable case-fatality rate estimate is slightly >9 per 100,000 sterilizations if all deaths associated with the procedure are considered. Rate estimates that assume minimum and maximum numbers of all associated deaths in our sample are approximately 6 per 100,000 and 10 per 100,000 sterilizations, respectively. However, when only deaths that can be attributed to sterilization per se are considered, the most reasonable case-fatality rate is estimated at between 1 and 2 per 100,000 procedures, a lower rate than previously reported. Rate estimates that assume minimum and maximum numbers of attributable deaths in our sample are approximately 1 per 100,000 and 5 per 100,000 sterilizations, respectively. These results further indicate that death attributable to tubal sterilization is rare. (AM J OBSTET GVNECOL 1989;160:147-50.)

Key words: Tubal sterilization, case-fatality rate, deaths

From the Epldemiologzc Studies Branch, DivisIOn of Reproductive Health, Center for Health Promotion and Education. RecetvedforpublicatlOn November 23,1987; revisedJune 13,1988; accepted July 26, 1988. Repnnt requests: U.S. Department of Health and Human ServIces, Publzc Health Service, Centers for DISease Control, Atlanta, GA

30333.

Tubal sterilization is the most prevalent method of contraception for women in the United States. I Despite frequent use of the procedure, little data exists with regard to the risks of death attributable to it. A previous study reported by the Centers for Disease Control, which used 1977 and 1978 data from the Commission

147