Si Eun Lee

The frequency and significance of intraamniotic inflammation in patients with cervical insufficiency

OBJECTIVE The purpose of this study was to determine the frequency and clinical significance of intraamniotic inflammation in patients with acute cervical insufficiency. STUDY DESIGN Amniocentesis was performed in 52 patients with acute cervical insufficiency (cervical dilation, > or =1.5 cm) and intact membranes and without regular uterine contractions (gestational age, 17-29 weeks). Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and genital mycoplasmas and assayed for matrix metalloproteinase-8. Intraamniotic inflammation was defined as an elevated AF matrix metalloproteinase-8 concentration (>23 ng/mL). Nonparametric statistics and survival techniques were used for analysis. RESULTS The prevalence of intraamniotic inflammation was 81% (42/52); the prevalence of a positive AF culture was 8% (4/52). Intraamniotic inflammation was present in all cases with a positive AF culture. Preterm delivery within 7 days occurred in 50% of cases (19/38), and delivery before 34 weeks of gestation occurred in 84% of cases (32/38) with intraamniotic inflammation but without AF infection. Fifty-five percent of newborn infants (21/38) who were born to mothers with intraamniotic inflammation but without AF infection died immediately after birth (<1 day). The amniocentesis-to-delivery interval was shorter in patients with intraamniotic inflammation than in those without inflammation (P < .05). There were no differences in the interval-to-delivery or the rate of adverse outcome between patients with intraamniotic inflammation and a negative culture and patients with proven AF infection. CONCLUSION Intraamniotic inflammation, regardless of AF culture result, is present in approximately 80% of patients with acute cervical insufficiency and is a risk factor for impending preterm delivery and adverse outcomes.

The frequency of microbial invasion of the amniotic cavity and histologic chorioamnionitis in women at term with intact membranes in the presence or absence of labor

OBJECTIVE The amniotic cavity is normally sterile for bacteria. However, experimental evidence indicates that regular uterine contractions exert a suction-like effect whereby vaginal fluid ascends into the uterine cavity with contractions (demonstrated by sonohysterography contrast media). Consequently, this study was conducted to determine whether the presence and progress of labor are associated with an increased risk of microbial invasion of the amniotic cavity (MIAC), intraamniotic inflammation, and histologic chorioamnionitis in women with term pregnancies with intact membranes. STUDY DESIGN Amniotic fluid (AF) was obtained from term singleton pregnant women with intact membranes at the time of cesarean delivery. AF was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and white blood cell (WBC) count was determined. Patients were divided into 3 groups according to the presence or absence of labor and the progress of labor. Nonparametric statistics were used for analysis. RESULTS Results included: (1) a total of 884 pregnant women were enrolled and divided into 3 groups: group 1, not in labor (n = 775); group 2, in early labor (cervical dilatation less than 4 cm) (n = 86); and group 3, in active labor (cervical dilatation 4 cm or greater) (n = 23); (2) the frequency of MIAC was 1% (6 of 775) in women not in labor, 3.5% (3 of 86) in patients with early labor, and 13% (3 of 23) in patients with active labor; and (3) the median AF WBC count and the frequency of histologic chorioamnionitis were also higher in the presence of labor than in the absence of labor. CONCLUSION We came to the following conclusions: (1) labor is associated with an increased risk of MIAC, a higher median AF WBC count, and histologic chorioamnionitis in term pregnancy with intact membranes; (2) the more advanced the cervical dilatation, the greater the risk of MIAC, a higher median AF WBC count, and histologic chorioamnionitis; and (3) in contrast, fetal inflammation (funisitis) did not increase with the presence of labor or as a function of cervical dilatation. We propose that labor predisposes to MIAC, a higher median AF WBC count, and histologic chorioamnionitis.

Measurement of Placental Alpha- Microglobulin-1 in Cervicovaginal Discharge to Diagnose Rupture of Membranes

OBJECTIVE: To compare the accuracy of an immunoassay to measure levels of placental alpha-microglobulin-1 in cervicovaginal secretions with that of conventional clinical assessment for the diagnosis of rupture of membranes. METHODS: A prospective observational study was performed in consecutive patients with signs or symptoms of rupture of membranes at Seoul National University Hospital from March 2005 to February 2006. Initial evaluation included both the standard clinical evaluation for rupture of membranes and placental alpha-microglobulin-1 immunoassay. Rupture of membranes was diagnosed if fluid was seen leaking from the cervical os or if two of the following three conditions were present: pooling of fluid, positive nitrazine test, or ferning. Rupture of membranes was diagnosed definitively on review of the medical records after delivery. RESULTS: Of 184 patients (11–42 weeks of gestation), rupture of membranes was diagnosed at initial presentation in 76% (139 of 184) using conventional clinical assessment and 88% (161 of 184) using placental alpha-microglobulin-1 immunoassay. Follow-up confirmed that a total of 159 of 183 patients (87%) had rupture of membranes at their initial presentations. Using this longitudinal assessment as the clinical gold standard, placental alpha-microglobulin-1 immunoassay confirmed rupture of membranes at initial presentation with a sensitivity of 98.7% (157 of 159), specificity of 87.5% (21 of 24), positive predictive value of 98.1% (157 of 160), and negative predictive value of 91.3% (21 of 23). Placental alpha-microglobulin-1 immunoassay was better than both the conventional clinical assessment and the nitrazine test alone in confirming the diagnosis of rupture of membranes. CONCLUSION: Measurement of placental alpha-microglobulin-1 in cervicovaginal secretions is superior to conventional clinical assessment in the diagnosis of rupture of membranes. LEVEL OF EVIDENCE: II

Amniotic fluid prostaglandin concentrations increase before the onset of spontaneous labor at term

Objectives. The role of prostaglandins (PGs) in the onset of human parturition has been controversial. Specifically, some investigators have proposed that PGs are the consequence rather than the cause of labor. An important question is whether or not amniotic fluid (AF) PG concentrations increase before the onset of labor in humans. Methods. The concentrations of PGs were determined in AF obtained from 167 singleton pregnant women with intact membranes. Patients were divided into four groups: (1) preterm not in labor (gestational age 15–36 weeks, n = 65); (2) term not in labor (n = 68); (3) spontaneous labor at term with cervical dilatation <4 cm (n = 25); (4) spontaneous labor at term with cervical dilatation ≥4 cm (n = 9). AF was obtained by transabdominal amniocentesis or collected at the time of cesarean delivery. All patients met the following criteria: (1) normal pregnancy outcome; (2) clear AF; (3) no significant medical or obstetric complications such as diabetes mellitus, preeclampsia, preterm birth, fetal growth restriction, or major congenital malformations; and (4) no significant neonatal complications. The concentrations of PGE2 and PGF2a in AF were determined by enzyme-linked immunosorbent assay (ELISA). Non-parametric analysis was performed. Results. (1) AF PG concentrations remained unchanged with advancing gestation until 36 weeks of gestation; (2) however, an abrupt increase in AF PG concentrations was observed before the onset of labor at term; (3) among cases without labor at term, the median AF PGF2a concentration increased with advancing gestation; (4) the presence of labor and the degree of cervical dilatation were significantly associated with a higher concentration of PGF2a. Conclusions. An abrupt increase in AF PG concentrations (25-fold for PGF2a) occurs before the onset of spontaneous labor at term in humans; these observations suggest that PGs increase prior to the onset of labor and contradict the claim that an increase in PG concentrations is the consequence of labor.

Funisitis in term pregnancy is associated with microbial invasion of the amniotic cavity and intra-amniotic inflammation

Objective. Funisitis is the histologic counterpart of the fetal inflammatory response syndrome, which is a multisystemic disorder associated with impending preterm delivery and adverse neonatal outcome. The purpose of this study was to examine the relationship between funisitis and the microbiologic status of amniotic fluid (AF) and AF white blood cell (WBC) count in patients at term. Methods. The relationship between the presence of funisitis, AF culture, and AF WBC count was examined in 832 consecutive patients who delivered a term neonate within 72 hours of amniocentesis. AF was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Whartons jelly. AF WBC count was analyzed in a hemocytometer chamber. Nonparametric statistics were used for data analysis. Results. Funisitis was present in 4% (30/832) of cases. A positive AF culture was more common in cases with funisitis than in those without funisitis (17% vs. 5%; p < 0.05). Patients with funisitis had a significantly higher median AF WBC count than those without funisitis (median >1000 cells/mm3 vs. median 2 cells/mm3; p < 0.001). The frequency of funisitis and of a positive AF culture was 1% in women without labor and with intact membranes and the frequencies and the median AF WBC count increased in the presence of labor or rupture of membranes. Conclusion. Funisitis is present in 4% of women at term and is associated with microbial invasion of the amniotic cavity (MIAC) and inflammation as reflected by increased AF WBC count.

Amniotic fluid prostaglandin F2 increases even in sterile amniotic fluid and is an independent predictor of impending delivery in preterm premature rupture of membranes

Objective. To determine whether amniotic fluid (AF) concentration of prostaglandins (PGs) increases in patients with intra-amniotic inflammation and/or proven AF infection in preterm PROM, and can predict impending delivery. Methods. AF PGF2a concentrations were determined by ELISA in 140 singleton pregnancies with preterm premature rupture of membranes (PROM) (≤35 weeks). AF was cultured for aerobic and anaerobic bacteria, and genital mycoplasmas. Intra-amniotic inflammation was defined as an elevated AF matrix metalloproteinase-8 concentration (>23 ng/ml). Results. (1) Patients with intra-amniotic inflammation and a negative AF culture had a significantly higher median AF PGF2a than those without intra-amniotic inflammation and with a negative culture (p < 0.001); (2) However, there was no difference in the median AF PGF2a between patients with intra-amniotic inflammation with a negative culture and those with culture-proven AF infection (p > 0.1); (3) Patients with an elevated AF PGF2a had a significantly shorter interval-to-delivery than those with a low AF PGF2a (≤170 pg/mL) (p < 0.001); (4) An elevated AF PGF2a (≤170 pg/mL) concentration was a significant predictor of the duration of pregnancy after adjusting for gestational age and AF inflammation/infection (p < 0.005). Conclusions. AF PGF2a (≥170 pg/mL) concentration increased in patients with intra-amniotic inflammation regardless of AF culture results. Moreover, an elevated AF PGF2a concentration was an independent predictor of impending delivery in preterm PROM.

A high Nugent score but not a positive culture for genital mycoplasmas is a risk factor for spontaneous preterm birth.

Objective. This study was performed to evaluate the relationship among the Nugent score for the diagnosis of bacterial vaginosis (BV), the results of vaginal fluid culture for genital mycoplasmas, and the subsequent occurrence of preterm birth. Methods. The Nugent score and culture for genital mycoplasmas were performed in vaginal fluid obtained from 977 pregnant women (gestational age 13–30 weeks). Vaginal samples were obtained with sterile cotton swabs. The relationship among the Nugent score, vaginal fluid culture results and the occurrence of spontaneous preterm birth was examined. Results. (1) Of the 977 women, 14% (137) had a Nugent score of ≥8; (2) The prevalence of a positive vaginal culture for genital mycoplasmas was 30% (288); Ureaplasma urealyticum was isolated in 252 (88%), Mycoplasma hominis in 9 (3%), and both in 27 (9%) women; (3) Cases with a Nugent score of ≥8 had a higher rate of a positive vaginal culture for genital mycoplasmas than those with the lower Nugent score (55%vs. 25%; p < 0.001); (4) Women with a Nugent score of ≥8 had a significantly higher rate of spontaneous preterm birth <37 (10%vs. 4%), <34 (5%vs. 2%), and <32 (4%vs. 1%) weeks of gestation than those with the lower Nugent score (at each gestational age, p < 0.05); (5) In contrast, a positive vaginal culture for genital mycoplasmas was not associated with an increased risk for spontaneous preterm birth; (6) Among patients with a positive culture and a Nugent score of ≥8, the frequency of spontaneous preterm delivery (<37 weeks) was 10% (7/72); (7) There was no difference in the incidence of spontaneous preterm delivery according to the results of vaginal culture in patients with a Nugent score of ≥8, as well as in those with a lower Nugent score. Conclusion. A high Nugent score (≥8) for the detection of BV but not a positive vaginal culture for genital mycoplasmas is a risk factor for spontaneous preterm birth.

Evidence supporting proteolytic cleavage of insulin-like growth factor binding protein-1 (IGFBP-1) protein in amniotic fluid

Abstract Objective: The purpose of this study was to determine if: 1) insulin-like growth factor binding protein-1 (IGFBP-1) in amniotic fluid (AF) exhibited proteolytic cleavage in cases of intra-amniotic inflammation; and 2) if the matrix metalloproteinases (MMP-3, MMP-8, MMP-9) in AF are associated with the degradation of IGFBP-1 in AF. Methods: AF samples (n=20) were obtained from preterm gestations with and without intra-amniotic inflammation. The form of IGFBP-1 in AF was assessed by Western blot analysis and AF MMP-8 concentration was measured by ELISA. Densitometric analysis of Western blot was performed and the fragmented/intact IGFBP-1 ratio was calculated. Proteolysis of AF IGFBP-1 by MMPs was evaluated by incubating AF with exogenous human MMP-3, MMP-8 or MMP-9, and by incubating recombinant human IGFBP-1 in AF with and without inflammation. Results: 1) IGFBP-1 was present in AF without inflammation as an intact form; however, the fragmented form was dominant in AF with inflammation; 2) the ratio of fragmented/intact IGFBP-1 was significantly higher in AF with inflammation than in AF without inflammation; 3) a higher ratio of fragmented/intact IGFBP-1 was associated with a higher concentration of MMP-8; 4) in-vitro proteolysis experiments showed that AF IGFBP-1 was degraded by exogenous human MMP-3, MMP-8 and MMP-9; 5) recombinant human IGFBP-1 was fragmented in AF with inflammation, but not in AF without inflammation. Conclusion: The fragmented form of AF IGFBP-1 was significantly increased in AF with intra-amniotic inflammation, and MMPs produced in AF with intra-amniotic inflammation were associated with the proteolytic change of AF IGFBP-1.

OC18.06: Ultrasonographic, pathologic and clinical prognostic factors in survival of fetuses with antenatally detected sacrococcygeal teratoma

Objective: Sacrococcygeal teratoma (SCT) is the most common congenital tumor. However, if removed successfully and no perinatal accidents occur, long-term prognosis is excellent. We undertook this study to find out prognostic factors that affect the survival by evaluating ultrasonographic, pathologic and clinical characteristics of fetuses and neonates with SCT. Methods: We identified 17 cases with SCT diagnosed antenatally and proved by the pathologic examination (except for one case) after deliveries from 1989 to 2004 at Seoul National University Hospital. The medical records were retrospectively reviewed and the data were analyzed on prenatal ultrasonographic findings, perinatal outcomes and tumor pathologies. Fisher’s exact test and Mann Whitney-U test were used for statistical analyses. Results: Excluding two cases of termination, fifteen cases were evaluated.

OC283: Clinical use of fetal urine production rate for differentiation of the causes of polyhydramnios

included sensitivities, false-positive rates and receiver–operating characteristic (ROC) curves. Results: Of 576 pregnancies studied from 1995 to 2006, 145 (25.2%) were affected. At 12–13 weeks’ gestation, fetal cardiomegaly predicted the affected pregnancies significantly better than placentomegaly (area under ROC curve, 0.949 vs. 0.687, P < 0.05). The sensitivity for prediction of the affected pregnancies was 90.6% for fetal cardiomegaly (CTR ≥ 0.5), 69.8% for placentomegaly (PT > 18 mm) and 65.1% for combined testing. The corresponding false-positive rate was 6.8%, 50.3% and 2.8% respectively. At 14–15 weeks’ gestation, the sensitivity for prediction of affected pregnancies was 93.8% for fetal cardiomegaly, 93.8% for placentomegaly and 87.5% for combined testing. The corresponding false-positive rate was 16.7%, 76.9% and 17.7% respectively. MCAPSV was not predictive in early second trimester. However, at 18–19 weeks’ gestation, MCAPSV (at a cut-off 1.5 multiples of the median) predicted affected pregnancies significantly better than fetal cardiomegaly (area under ROC curve, 0.959 vs. 0.788, P < 0.05). The sensitivity for the prediction of affected pregnancies was 100.0% for fetal cardiomegaly and 57.1% for high MCAPSV while the corresponding false-positive rate was 46.2% and 0% respectively. Conclusions: The best ultrasonographic predictor of affected pregnancies at 12–13 weeks’ and 18–19 weeks’ gestation was fetal CTR and MCAPSV respectively.