Soon-Sup Shim

The clinical significance of detecting Ureaplasma urealyticum by the polymerase chain reaction in the amniotic fluid of patients with preterm labor

OBJECTIVE This study was undertaken to determine the clinical significance of a detection of Ureaplasma urealyticum by using the polymerase chain reaction (PCR) in the amniotic fluid of patients with preterm labor and intact membranes. STUDY DESIGN Amniocentesis was performed in 257 patients with preterm labor and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as genital mycoplasmas. U urealyticum was detected by PCR using specific primers. Patients were divided into 3 groups according to the results of amniotic fluid culture and PCR for U urealyticum: those with a negative culture and negative PCR (n=228), those with a negative culture but positive PCR (n=6), and those with a positive culture regardless of the results of PCR (n=23). RESULTS The prevalence of positive amniotic fluid culture was 9% (23 of 257). U urealyticum was detected by PCR in 6% (15 of 254) of cases. Of the 15 cases with positive PCR for U urealyticum, amniotic fluid culture was negative in 40% (6 of 15). Patients with a negative culture but positive PCR for U urealyticum had significantly shorter median amniocentesis-to-delivery interval and higher amniotic fluid interleukin-6 and white blood cell count than those with a negative amniotic fluid culture and negative PCR (P<.01 for each). Patients with a positive PCR for U urealyticum but a negative amniotic fluid culture had a higher rate of significant neonatal morbidity than those with a negative culture and negative PCR (P<.05). However, no significant differences in perinatal outcome were observed between patients with a negative culture but positive PCR and those with a positive amniotic fluid culture. CONCLUSION Patients with preterm labor and a positive PCR for U urealyticum but negative amniotic fluid culture are at risk for impending preterm delivery and adverse perinatal outcome.

Amniotic fluid matrix metalloproteinase-8 and the development of cerebral palsy.

Abstract Aims: To examine if increased concentrations of matrix metalloproteinase-8 (MMP-8) in amniotic fluid are associated with the development of cerebral palsy at the age of three years. Methods: The relationship between amniotic fluid concentrations of MMP-8 and the development of cerebral palsy was examined in 116 preterm singleton newborns (gestational age at birth < 35 weeks) born to mothers who underwent amniocentesis and were followed for at least 3 years. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. MMP-8 concentrations were measured by specific immunoassays. Cerebral palsy was diagnosed by neuro developmental assessment at the age of three years. Results: Median amniotic fluid concentration of MMP-8 was significantly higher in mothers whose newborns developed cerebral palsy than in mothers whose newborns did not develop cerebral palsy (median 153.9 [range < 0.3–1535.9] ng/ml vs median 6.4 [range < 0.3–3836.8] ng/ml; p < 0.01). Neonates who developed cerebral palsy were delivered at earlier gestational age than those without cerebral palsy. After adjustment for the gestational age at birth and the results of amniotic fluid culture, elevated concentrations of amniotic fluid MMP-8 significantly increased the odds of development of cerebral palsy (odds ratio, 6.0; 95% confidence interval, 1.1–33.0; p < 0.05). Conclusion: Increased concentrations of amniotic fluid MMP-8 are associated with the subsequent development of cerebral palsy at the age of 3 years.

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.

Biovar diversity of Ureaplasma urealyticum in amniotic fluid: distribution, intrauterine inflammatory response and pregnancy outcomes.

Abstract Objective: The objective of this study was to determine the distribution of two biovars of Ureaplasma urealyticum (parvo and T960) in human amniotic fluid and to examine whether the magnitude of the intrauterine inflammatory response and pregnancy outcomes are different between patients with microbial invasion of the amniotic cavity with “parvo biovar” and those with “T960 biovar”. Study design: This cohort included 77 preterm singleton pregnancies (gestational age < 37 weeks) in whom U. urealyticum was detected from amniotic fluid using the polymerase chain reaction (PCR). Amniotic fluid was obtained by transabdominal amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria as well as mycoplasmas. U. urealyticum was biotyped by PCR methods. Amniotic fluid inflammatory response was determined by amniotic fluid white blood cell count and interleukin-6 concentration. Results: 1) The “parvo biovar” was detected in 82% (63/77) and “T960 biovar” was in 18% (14/77) of cases; 2) U. urealyticum was isolated by conventional culture method from amniotic fluid in 56% (35/63) of cases with positive for “parvo biovar” and in 50% (7/14) of cases with positive for “T960 biovar”; 3) There were no significant differences in the median gestational age at amniocentesis, gestational age at delivery, birth weight, amniotic fluid white blood cell count, amniotic fluid interleukin-6 concentration and the rates of clinical chorioamnionitis, histologic chorioamnionitis, funisitis and neonatal morbidity between patients in the two biovar groups. Conclusions: 1) The “parvo biovar” is more frequently isolated from amniotic fluid of preterm gestations than the “T960 biovar”; 2) Biovar diversity of U. urealyticum in amniotic fluid was not associated with different pregnancy outcome and magnitude of the intraamniotic inflammatory response.

Chorionic plate vessels as an origin of amniotic fluid neutrophils

The present study was conducted to investigate the potential anatomical source of amniotic fluid neutrophils. Microdissection of neutrophils from the chorioamnion of the fetal membranes and the amnion of the chorionic plates of 10 preterm placentas with acute chorioamnionitis was performed and the genotypes of the neutrophils were compared with those of the mother and fetus using polymerase chain reaction of nine autosomal STR loci. In separate analyses, we reviewed eight cases of fetal autopsies with increased amniotic fluid neutrophils for the presence of neutrophils in the alveoli, and also analyzed the relationship between the amniotic fluid white blood cell (WBC) count and the histological pattern of placental inflammation. The genotypes of all of the neutrophils found in the chorioamnion of the fetal membrane matched those of the mother (n = 10). The genotypes of neutrophils found in the chorionic plate were of mixed maternal and fetal origin (n = 4). In the autopsy series of the fetuses with amniotic fluid WBC (n = 8), only five cases showed neutrophils in the alveolar space, while all the placentas had chorioamnionitis. There was no significant difference in amniotic fluid WBC count between the cases with or without acute membranitis, while among the cases with placental inflammation, those with inflammation of the chorionic plate had a significantly higher amniotic fluid WBC count than both the membranitis‐only cases (P < 0.001) and the membranitis and funisitis cases (P < 0.05). These results imply that fetal vasculature at the chorionic plate is the main source of amniotic fluid neutrophils, especially in the cases without funisitis.

Measurement of fetal urine production by three‐dimensional ultrasonography in normal pregnancy

Measurement of fetal urine production may provide a means of evaluating amniotic fluid volume, which is difficult to measure directly, and predicting fetal hypoxia. Although there have been some reports on fetal urine production, most of these have used two‐dimensional (2D) ultrasonography to measure bladder volume. Three‐dimensional (3D) ultrasonography is, however, known to be superior to 2D ultrasonography in some organ volume measurements. Thus, we undertook this study to measure bladder volumes using 3D ultrasonography and to establish a nomogram of fetal urine production rate (UPR) according to gestational age (GA).

Amniotic Fluid Tumor Necrosis Factor-Alpha Is a Marker for the Prediction of Early-Onset Neonatal Sepsis in Preterm Labor

Background: Our purpose was to determine whether amniotic fluid concentrations of tumor necrosis factor-α are of value in the prediction of early-onset neonatal sepsis (proven or suspected) in patients with preterm labor and intact membranes. Methods: The relationship between amniotic fluid tumor necrosis factor-α concentrations and early-onset neonatal sepsis was examined in 59 consecutive patients with preterm labor and intact membranes who delivered preterm neonates within 72 h after transabdominal amniocentesis. Early-onset neonatal sepsis was defined either as the presence of a positive blood culture or as suspected sepsis within 72 h of delivery. Tumor necrosis factor-α was determined by enzyme-linked immunosorbent assays. Results: Patients delivering neonates with early-onset neonatal sepsis had significantly higher median amniotic fluid TNF-α concentrations than patients delivering neonates without early-onset neonatal sepsis (p < 0.0005). An amniotic fluid tumor necrosis factor-α concentration ≧41 pg/ml had a sensitivity of 82% (23/29) and specificity of 79% (38/48) in the prediction of early-onset neonatal sepsis. Multiple logistic regression indicated that elevated amniotic fluid tumor necrosis factor-α (≧41 pg/ml) was the only independent predictor of early-onset neonatal sepsis (odds ratio 12.9, 95% confidence interval 1.3–125.3, p = 0.01) after correction for known confounding variables. Conclusions: (1) Amniotic fluid tumor necrosis factor-α is a marker for the prediction of early-onset neonatal sepsis in patients with preterm labor and intact membranes. (2) Amniotic fluid tumor necrosis factor-α is a better independent predictor of early-onset neonatal sepsis than placental histologic finding or amniotic fluid culture.

Fetal plasma cortisol and dehydroepiandrosterone sulfate concentrations in pregnancy and term parturition

Objective. To examine if changes in fetal plasma concentrations of cortisol or dehydroepiandrosterone sulfate (DHEAS) levels are associated with human term parturition. Methods. Umbilical cord plasma cortisol and DHEAS concentrations were measured in 374 singleton pregnancies that delivered at term in the following six groups: group 1, cordocentesis for clinical indications before 36 weeks of gestation (n = 93); group 2, cordocentesis for clinical indications after 36 weeks of gestation (n = 9); group 3, cord blood sampling after elective cesarean section (CS) at term without labor (n = 140); group 4, cord blood sampling after CS at term with early labor (cervical dilatation ≤3 cm, n = 18); group 5, cord blood sampling after CS at term with active labor (cervical dilatation 4 cm or greater, n = 26); group 6, cord blood sampling after vaginal delivery at term (n = 88). Corticosteroids were not administered before blood collection. Results. (1) Fetal plasma cortisol remained unchanged until 36 weeks of gestation and increased thereafter to term; (2) active labor was associated with a significant increase in fetal plasma cortisol; (3) fetal plasma DHEAS increased at term gestation (>36 weeks) but did not increase during active labor; (4) the cortisol/DHEAS ratio (stress index) increased with advancing gestation and with active labor at term. Conclusions. Human parturition at term is associated with an increase in fetal plasma cortisol and in the cortisol/DHEAS ratio, but not in DHEAS.

Angiotensinogen G(–6)A Polymorphism Is Associated With the Elevation of Blood Pressure in the Hypertensive Disorders of Pregnancy

The objective of the present study was to determine whether angiotensinogen G(-6)A polymorphism is associated with the elevation of blood pressure (BP) in the hypertensive disorders of pregnancy in Korean population. The subjects included 201 cases with the hypertensive disorders of pregnancy and 160 healthy controls. The medical records of subjects were reviewed. Cases were classified into the four subtypes (transient hypertension, preeclampsia, chronic hypertension, and preeclampsia superimposed on chronic hypertension) by the diagnostic criteria suggested by the National High Blood Pressure Education Program Working Group. Cases were also divided into the high and low BP group by the elevation of BP (diastolic BP greater than or equal to 110 mmHg). Maternal angiotensinogen G(-6)A polymorphism was determined by restriction fragment length polymorphism. Frequencies of AA genotype were significantly higher in the high than in the low BP group in the preeclampsia, superimposed preeclampsia, and the combined group (N = 201), suggesting that the angiotensinogen G(-6)A allele was significantly associated with the elevation of BP in the hypertensive disorders of pregnancy among South Korean women. The present findings imply that the elevation of BP can serve as an endophenotype for a spectrum of hypertensive conditions in pregnancy.

P11.07: Transvaginal ultrasonographic cervical measurement in predicting failed labor induction and caesarean delivery for failure to progress

Objective: The aim of this study was to find out the relating factors with the actual delivery date in term pregnancy. Methods: Sixty patients with singleton gestation were measured for their lower utrine segment (LUS), cervical length, and cervical gland thickness by transvaginal ultrasonography and for their amnionic fluid index (AFI) by transabdominal ultrasonography from 36 weeks and they were longitudinally followed up until spontaneous vaginal delivery. Regression analysis was used to find out the relevance between these factors and remaining days to delivery date. Results: There was a relationship between cervical length and remaining days to birth in term pregnancy, which could be described as a mathematical equation (remaining days for delivery = 6.12 + 0.24 * cervical length (mm); r = 0.29, p < 0.01). However, no relationship was found between factors such as LUS, AFI, and cervical gland thickness and with remaining days to birth. Conclusions: Remaining days to the actual delivery date in term singletone pregnancy is closely related with cervical length.