Abstract
OBJECTIVE: The objective of this study was to determine the frequency and clinical significance
of a systemic inflammatory response as defined by an elevated plasma interleukin-6
concentration in fetuses with preterm labor or preterm premature rupture of membranes.
STUDY DESIGN: Amniocenteses and cordocenteses were performed in 157 patients with preterm labor
and preterm premature rupture of membranes. Written informed consent and multi-institutional
review board approvals were obtained. Amniotic fluid was cultured for aerobic and
anaerobic bacteria, as well as mycoplasmas. Amniotic fluid and fetal plasma interleukin-6
concentrations were measured with a sensitive and specific immunoassay. Statistical
analyses included contingency tables, receiver operating characteristic curve analysis,
and multiple logistic regression.
RESULTS: One hundred five patients with preterm labor and 52 patients with preterm premature
rupture of membranes were included in this study. The overall prevalence of severe
neonatal morbidity (defined as the presence of respiratory distress syndrome, suspected
or proved neonatal sepsis, pneumonia, bronchopulmonary dysplasia. intraventricular
hemorrhage, periventricular leukomalacia, or necrotizing enterocolitis) among survivors
was 34.8% (54/155). Neonates in whom severe neonatal morbidity developed had higher
concentrations of fetal plasma interleukin-6 than fetuses without development of severe
neonatal morbidity (median 14.0 pg/mL, range 0.5 to 900 vs median 5.2 pg/mL, range
0.3 to 900, respectively; P < .005). Multivariate analysis was performed to explore the relationship between
the presence of a systemic fetal inflammatory response and subsequent neonatal outcome.
To preserve a meaningful temporal relationship between the results of fetal plasma
interleukin-6 concentrations and the occurrence of severe neonatal morbidity, the
analysis was restricted to 73 fetuses delivered within 7 days of cordocentesis who
survived. The prevalence of severe neonatal morbidity in this subset of patients was
53.4% (39/73). A fetal plasma interleukin-6 cutoff value of 11 pg/mL was used to define
the presence of a systemic inflammatory response. The prevalence of a fetal plasma
interleukin-6 level >11 pg/mL was 49.3% (36/73). Fetuses with fetal plasma interleukin-6
concentrations >11 pg/mL had a higher rate of severe neonatal morbidity than did those
with fetal plasma interleukin-6 levels ≤11 pg/mL (77.8% [28/36] vs 29.7% [11/37],
respectively; P < .001). Stepwise logistic regression analysis demonstrated that the fetal plasma
interleukin-6 concentration was an independent predictor of the occurrence of severe
neonatal morbidity (odds ratio 4.3, 95% confidence interval 1 to 18.5) when adjusted
for gestational age at delivery, the cause of preterm delivery (preterm labor or preterm
premature rupture of membranes), clinical chorioamnionitis, the cordocentesis-to-delivery
interval, amniotic fluid culture, and anmiotic fluid interleukin-6 results.
CONCLUSION: A systemic fetal inflammatory response, as determined by an elevated fetal plasma
interleukin-6 value, is an independent risk factor for the occurrence of severe neonatal
morbidity. (Am J Obstet Gynecol 1998;179:194-202.)
Keywords
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References
- Maternal placental vasculopathy and injection: two distinct subgroups among patients with preterm labor and preterm ruptured membranes.Am J Obstet Gynecol. 1993; 168: 585-591
- Subclinical intra-amniotic infection in asymptomatic patients with refractory preterm labor.Obstet Gynecol. 1987; 69: 756-759
- Infection and labor. V. Prevalence, microbiology, and clinical significance of intraamniotic infection in women with preterm labor and intact membranes.Am J Obstet Gynecol. 1989; 161: 817-824
- The diagnostic and prognostic value of amniotic fluid white blood cell count, glucose, interleukin-6, and Gram stain in patients with preterm labor and intact membranes.Am J Obstet Gynecol. 1993; 169: 805-816
- Chorioamnionitis in the preterm gestation.Obstet Gynecol. 1982; 59: 539-545
- lntra-amniotic infection and the onset of labor in preterm premature rupture of membranes.Am J Obstet Gynecol. 1988; 159: 661-666
- Amniocentesis with premature rupture of membranes.Obstet Gynecol. 1986; 68: 147-152
- A comparative study of the diagnostic performance of amniotic fluid glucose, white blood cell count, interleukin-6, and Gram stain in the detection of microbial invasion in patients with preterm premature rupture of membranes.Am J Obstet Gynecol. 1993; 169: 839-851
- The use of polymerase chain reaction to detect bacteria in amniotic fluid in pregnancies complicated by preterm labor [abstract 100].Am J Obstet Gynecol. 1997; 176: S39
- Bacterial 165 rDNA polymerase chain reaction in the detection of intra-amniotic infection.Br J Obstet Gynaecol. 1996; 103: 664-669
- Pathogenesis of preterm labor and preterm premature rupture of membranes associated with intraamniotic infection.Infect Dis Clin North Am. 1997; 11: 135-176
- The natural history of the systemic inflammatory response syndrome (SIRS): A prospective study.JAMA. 1995; 273: 117-123
- Infection and labor. III. Interleukin 1: a signal for the onset of parturition.Am J Obstet Gynecol. 1989; 160: 1117-1123
- The onset of spontaneous preterm parturition is preceded by an intense pro-inflammatory cytokine response in human fetus [abstract 8].Am J Obstet Gynecol. 1997; 176: S3
- A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition.Am J Obstet Gynecol. 1998; 179: 186-193
- Ultrasound guided sampling of umbilical blood and placental blood to assess fetal well being.Lancet. 1986; 1: 1065-1067
- The fetal biophysical profile in patients with premature rupture of membranes—an early predictor of fetal infection.Am J Obstet Gynecol. 1985; 152: 510-516
- Obstetric antecedents of intraventricular hemorrhage and periventricular leukomalacia in the low-birth-weight neonate.Am J Obstet Gynecol. 1997; 176: 275-281
- Changing trends in the epidemiology and pathogenesis of neonatal chronic lung disease.J Pediatr. 1995; 126: 605-610
- Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia.Am J Obstet Gynecol. 1996; 174: 1433-1440
- Interleukin-6: a sensitive parameter for the early diagnosis of neonatal bacterial infection.Pediatrics. 1994; 93: 54-58
- Evidence that the injury responsible for the development of bronchopulmonary dysplasia may begin in utero [abstract 131].Am J Obstet Gynecol. 1997; 176: S47
- High expression of tumor necrosis factor-α and interleukin-6 in periventricular leukomalacia.Am J Obstet Gynecol. 1997; 177: 406-411
- The preterm labor syndrome: biochemical, cytologic, immunologic, pathologic, microbiologic, and clinical evidence that preterm labor is a heterogeneous disease [abstract 9].Am J Obstet Gynecol. 1993; 168: 288
- The preterm labor syndrome.Ann N Y Acad Sci. 1994; 734: 414-429
- Fetal biophysical profile scoring: current status.Clin Perinatol. 1989; 16: 661-689
Article info
Publication history
Accepted:
January 15,
1998
Received in revised form:
January 8,
1998
Received:
June 23,
1997
Footnotes
☆From the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Wayne State University/Hutzel Hospital,a the Perinatology Research Branch, National Institute of Child Health and Human Development,b the Department of Obstetrics and Gynecology, Sotero del Rio Hospital,c the Department of Obstetrics and Gynecology, Seoul National University,d and the Department of Obstetrics and Gynecology, Ben-Gurion University.e
☆☆Reprint requests: Roberto Romero, MD, Department of Obstetrics and Gynecology, Hutzel Hospital, Perinatology Research Branch, NICHD, 4707 St. Antoine Blvd, Detroit, MI 48201.
★6/1/89113
Identification
Copyright
© 1998 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
