Preterm labor is a distinct process from term labor following computational analysis of human myometrium.

BACKGROUND: The onset of the term human parturition involves myometrial gene expression changes to transform the uterus from a quiescent to a contractile phenotype. It is uncertain whether the same changes occur in the uterus during preterm labor. OBJECTIVE: This study aimed to compare the myometrial gene expression between term and preterm labor and to determine whether the presence of acute clinical chorioamnionitis or twin gestation affects these signatures. STUDY DESIGN: Myometrial specimens were collected during cesarean delivery from the following 7 different groups of patients: term not in labor (n=31), term labor (n=13), preterm not in labor (n=21), preterm labor with acute clinical chorioamnionitis (n=6), preterm labor with no acute clinical chorioamnionitis (n=9), twin preterm not in labor (n=8), and twin preterm labor with no acute clinical chorioamnionitis (n=5). RNA was extracted, reverse transcribed and quantitative polymerase chain reactions were performed on 44 candidate genes (with evidence for differential expression in human term labor) using the Fluidigm platform. Computational analysis was performed using 2-class unpaired Wilcoxon tests and principal component analysis. RESULTS: Computational analysis revealed that gene expression in the preterm myometrium, irrespective of whether in labor or not in labor, clustered tightly and is clearly different from the term labor and term not-in-labor groups. This was true for both singleton and twin pregnancies. Principal component analysis showed that 57% of the variation was explained by 3 principal components. These 44 genes interact in themes of prostaglandin activity and inflammatory signaling known to be important during term labor, but are not a full representation of the myometrium transcriptional activity. CONCLUSION: The myometrial contractions associated with preterm labor are associated with a pattern of gene expression that is distinct from term labor. Therefore, preterm labor may be initiated by a different myometrial process or processes outside the myometrium.

RNA Sequencing Reveals Distinct Immune Responses in the Chorioamniotic Membranes of Women with Preterm Labor and Microbial or Sterile Intra-amniotic Inflammation.

Preterm labor precedes premature birth, the leading cause of neonatal morbidity and mortality worldwide. Preterm labor can occur in the context of either microbe-associated intra-amniotic inflammation (i.e., intra-amniotic infection) or intra-amniotic inflammation in the absence of detectable microorganisms (i.e., sterile intra-amniotic inflammation). Both intra-amniotic infection and sterile intra-amniotic inflammation trigger local immune responses that have deleterious effects on fetal life. Yet, the extent of such immune responses in the fetal tissues surrounding the amniotic cavity (i.e., the chorioamniotic membranes) is poorly understood. By using RNA sequencing (RNA seq) as a discovery approach, we found that there were significant transcriptomic differences involving host response to pathogens in the chorioamniotic membranes of women with intra-amniotic infection compared to those from women without inflammation. In addition, the sterile or microbial nature of intra-amniotic inflammation was associated with distinct transcriptomic profiles in the chorioamniotic membranes. Moreover, the immune response in the chorioamniotic membranes of women with sterile intra-amniotic inflammation was milder in nature than that induced by microbes and involved the upregulation of alarmins and inflammasome-related molecules. Lastly, the presence of maternal and fetal inflammatory responses in the placenta was associated with the upregulation of immune processes in the chorioamniotic membranes. Collectively, these findings provide insight into the immune responses against microbes or alarmins that take place in the fetal tissues surrounding the amniotic cavity, shedding light on the immunobiology of preterm labor and birth.

Bacteria in the amniotic fluid without inflammation: early colonization vs. contamination.

OBJECTIVES: Intra-amniotic infection, defined by the presence of microorganisms in the amniotic cavity, is often accompanied by intra-amniotic inflammation. Occasionally, laboratories report the growth of bacteria or the presence of microbial nucleic acids in amniotic fluid in the absence of intra-amniotic inflammation. This study was conducted to determine the clinical significance of the presence of bacteria in amniotic fluid samples in the absence of intra-amniotic inflammation. METHODS: A retrospective cross-sectional study included 360 patients with preterm labor and intact membranes who underwent transabdominal amniocentesis for evaluation of the microbial state of the amniotic cavity as well as intra-amniotic inflammation. Cultivation techniques were used to isolate microorganisms, and broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) was utilized to detect the nucleic acids of bacteria, viruses, and fungi. RESULTS: Patients whose amniotic fluid samples evinced microorganisms but did not indicate inflammation had a similar perinatal outcome to those without microorganisms or inflammation [amniocentesis-to-delivery interval (p=0.31), spontaneous preterm birth before 34 weeks (p=0.83), acute placental inflammatory lesions (p=1), and composite neonatal morbidity (p=0.8)]. CONCLUSIONS: The isolation of microorganisms from a sample of amniotic fluid in the absence of intra-amniotic inflammation is indicative of a benign condition, which most likely represents contamination of the specimen during the collection procedure or laboratory processing rather than early colonization or infection.

A high concentration of fetal fibronectin in cervical secretions increases the risk of intra-amniotic infection and inflammation in patients with preterm labor and intact membranes.

Objective To determine whether the risk of intra-amniotic infection/inflammation and spontaneous preterm delivery (SPTD) varies as a function of the concentration of cervical fetal fibronectin (fFN) in patients with preterm labor and intact membranes. Methods This prospective study included 180 patients with preterm labor and intact membranes who had a sample collected for quantitative fFN measurement and underwent amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Results (1) The prevalence of intra-amniotic infection/inflammation and SPTD within 7 days was 32.2% (58/180) and 33.9% (61/178), respectively; (2) The higher the fFN concentration, the greater the risk of intra-amniotic infection/inflammation and SPTD within 7 days (P<0.001, respectively); (3) An fFN concentration 150 ng/mL had a better diagnostic performance than an fFN 50 ng/mL in the identification of intra-amniotic infection/inflammation and SPTD within 7 days; (4) Among the patients with an fFN <50 ng/mL, intra-amniotic infection/inflammation was identified in 7.6% (6/79) of patients and 66.7% (4/6) delivered within 7 days. Conclusion The higher the concentration of fFN, the greater the risk of intra-amniotic infection/inflammation and SPTD in patients with preterm labor and intact membranes.

The frequency and type of placental histologic lesions in term pregnancies with normal outcome.

Objective To determine the frequency and type of histopathologic lesions in placentas delivered by women with a normal pregnancy outcome. Methods This retrospective cohort study included placental samples from 944 women with a singleton gestation who delivered at term without obstetrical complications. Placental lesions were classified into the following four categories as defined by the Society for Pediatric Pathology and by our unit: (1) acute placental inflammation, (2) chronic placental inflammation, (3) maternal vascular malperfusion and (4) fetal vascular malperfusion. Results (1) Seventy-eight percent of the placentas had lesions consistent with inflammatory or vascular lesions; (2) acute inflammatory lesions were the most prevalent, observed in 42.3% of the placentas, but only 1.0% of the lesions were severe; (3) acute inflammatory lesions were more common in the placentas of women with labor than in those without labor; (4) chronic inflammatory lesions of the placenta were present in 29.9%; and (5) maternal and fetal vascular lesions of malperfusion were detected in 35.7% and 19.7%, respectively. Two or more lesions with maternal or fetal vascular features consistent with malperfusion (high-burden lesions) were present in 7.4% and 0.7%, respectively. Conclusion Most placentas had lesions consistent with inflammatory or vascular lesions, but severe and/or high-burden lesions were infrequent. Mild placental lesions may be interpreted either as acute changes associated with parturition or as representative of a subclinical pathological process (intra-amniotic infection or sterile intra-amniotic inflammation) that did not affect the clinical course of pregnancy.

Preterm labor in the absence of acute histologic chorioamnionitis is characterized by cellular senescence of the chorioamniotic membranes.

BACKGROUND: Decidual senescence has been considered a mechanism of disease for spontaneous preterm labor in the absence of severe acute inflammation. Yet, signs of cellular senescence have also been observed in the chorioamniotic membranes from women who underwent the physiological process of labor at term. OBJECTIVE: We aimed to investigate whether, in the absence of acute histologic chorioamnionitis, the chorioamniotic membranes from women who underwent spontaneous preterm labor or labor at term exhibit signs of cellular senescence. STUDY DESIGN: Chorioamniotic membrane samples were collected from women who underwent spontaneous preterm labor or labor at term. Gestational age-matched nonlabor controls were also included. Senescence-associated genes/proteins were determined using reverse transcription quantitative polymerase chain reaction analysis (n = 7-9 each for array; n = 26-28 each for validation), enzyme-linked immunosorbent assays (n = 7-9 each), immunoblotting (n = 6-7 each), and immunohistochemistry (n = 7-8 each). Senescence-associated ß-galactosidase activity (n = 7-11 each) and telomere length (n = 15-22 each) were also evaluated. RESULTS: In the chorioamniotic membranes without acute histologic chorioamnionitis: (1) the expression profile of senescence-associated genes was different between the labor groups (term in labor and preterm in labor) and the nonlabor groups (term no labor and preterm no labor), yet there were differences between the term in labor and preterm in labor groups; (2) most of the differentially expressed genes among the groups were closely related to the tumor suppressor protein (TP53) pathway; (3) the expression of TP53 was down-regulated in the term in labor and preterm in labor groups compared to their nonlabor counterparts; (4) the expression of CDKN1A (gene coding for p21) was up-regulated in the term in labor and preterm in labor groups compared to their nonlabor counterparts; (5) the expression of the cyclin kinase CDK2 and cyclins CCNA2, CCNB1, and CCNE1 was down-regulated in the preterm in labor group compared to the preterm no labor group; (6) the concentration of TP53 was lower in the preterm in labor group than in the preterm no labor and term in labor groups; (7) the senescence-associated ß-galactosidase activity was greater in the preterm in labor group than in the preterm no labor and term in labor groups; (8) the concentration of phospho-S6 ribosomal protein was reduced in the term in labor group compared to its nonlabor counterpart, but no differences were observed between the preterm in labor and preterm no labor groups; and (9) no significant differences were observed in relative telomere length among the study groups (term no labor, term in labor, preterm no labor, and preterm in labor). CONCLUSION: In the absence of acute histologic chorioamnionitis, signs of cellular senescence are present in the chorioamniotic membranes from women who underwent spontaneous preterm labor compared to those who delivered preterm in the absence of labor. However, the chorioamniotic membranes from women who underwent spontaneous labor at term did not show consistent signs of cellular senescence in the absence of histologic chorioamnionitis. These results suggest that different pathways are implicated in the pathological and physiological processes of labor.

Afterbirth oral fluid secretory leukocyte protease inhibitor decreased in acute histologic chorioamnionitis in preterm birth.

BACKGROUND: Secretory leukocyte protease inhibitor (SLPI) is an innate anti-inflammatory and anti-microbial peptide and produced in amnion of fetal membranes during pregnancy. However, studies on the association between SLPI levels in amniotic fluid and acute chorioamnionitis are limited. Afterbirth oral fluid (AOF) of the baby could be useful for representing the intra-amniotic environment precisely just before delivery. This study aimed to determine the relationship between SLPI levels in AOF and acute histologic chorioamnionitis (HC). METHODS: AOF of the baby was obtained during delivery from 24(0/7) to 36(6/7) weeks of gestational age (preterm group, n = 94) and from 37(0/7) to 41(6/7) weeks of gestational age (term group, n = 27) just after birth. SLPI expression levels among five classifications were compared to the intensity of acute HC as follows: no inflammation, acute subchorionitis, acute chorionitis, acute chorioamnionitis, and funisits. The SLPI and matrix metalloproteinase-8 (MMP-8) concentrations of AOF were determined using Enzyme Linked Immunosorbent Assay. Histologic examination of the placenta and membranes was performed after delivery. RESULTS: SLPI concentrations in AOF inversely decreased according to the intensity of acute HC (161.62 ng/mL in funisitis, 134.83 ng/mL in acute chorioamnionitis, 749.35 ng/mL in acute chorionitis, 953.05 ng/mL in acute subchorionitis, and 1126.77 ng/mL in no inflammation [p = .021]). The MMP-8 concentrations in AOF and maternal serum C-reactive protein were the highest in funisitis. The SLPI/ MMP-8 ratio was low in subgroup with acute chorioamnionitis and funisitis. CONCLUSION: Along with increased MMP-8 levels, decreased SLPI levels in AOF of the baby could be an additional factor in predicting acute HC immediately after birth.

Preterm labor with intact membranes: a simple noninvasive method to identify patients at risk for intra-amniotic infection and/or inflammation.

OBJECTIVE: To develop a noninvasive scoring system to identify patients at high risk for intra-amniotic infection and/or inflammation, which would reduce the need for amniocentesis. METHODS: This prospective cohort study comprised patients admitted with preterm labor and intact membranes (20-34 weeks of gestation) who underwent a transabdominal amniocentesis and for whom concentrations of quantitative cervical fetal fibronectin and of maternal serum C-reactive protein (CRP) were determined. Intra-amniotic infection was defined as a positive amniotic fluid culture for microorganisms. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Multivariate logistic regression analysis was performed to identify intra-amniotic infection/inflammtion with noninvasive parameters that had a significant relationship with univariate analysis. With four parameters identified by multivariate analysis, we generated a noninvasive risk scoring system. RESULTS: Of the study population consisting of 138 singleton pregnant women, (1) the overall rate of intra-amniotic infection/inflammation was 28.3% (39/138); (2) four parameters were used to develop a noninvasive risk scoring system [i.e. cervical fetal fibronectin concentration (score 0-2), maternal serum CRP concentration (score 0-2), cervical dilatation (score 0-2), and gestational age at presentation (score 0-1)]; the total score ranges from 0 to 7; 3) the area under the curve of the risk score was 0.96 (95% confidence interval (CI), 0.92-0.99), significantly higher than that of each predictor in the identification of intra-amniotic infection/inflammation (p < .001, for all); 4) the risk score with a cutoff of 4 had a sensitivity of 94.9% (37/39), a specificity of 90.9% (90/99), a positive predictive value of 80.4% (37/46), a negative predictive value of 97.8% (90/92), a positive likelihood ratio of 10.4 (95% CI, 5.6-19.5), and a negative likelihood ratio of 0.06 (95% CI, 0.15-0.22) in the identification of intra-amniotic infection/inflammation. CONCLUSIONS: (1) The combination of four parameters (concentrations of cervical fetal fibronectin and maternal serum CRP, cervical dilatation, and gestational age) was independently associated with intra-amniotic infection and/or inflammation; and (2) the risk scoring system comprised of the combination of 4 noninvasive parameters was sensitive and specific to identify the patients at risk for intra-amniotic infection and/or inflammation.

Retinopathy of prematurity in infants without fetal growth restriction is decreased with the progression of acute histologic chorioamnionitis: New observation as a protective factor against retinopathy of prematurity.

INTRODUCTION: IGF-1 deficiency in prenatal period is known to be a definite pathophysiology of retinopathy of prematurity(ROP), which is more frequent in infants with fetal growth restriction(FGR). Of note, recent reports demonstrated intra-amniotic inflammation(IAI) closely linked to acute histologic chorioamnionitis(acute-HCA) is associated with a decrease in intact-form of IGFBP-1, ultimately rising the probability of an increase in IGF-1. Therefore, we hypothesized ROP in preterm-infants without FGR would be decreased with the progression of acute-HCA. METHODS: The frequency of ROP was examined in 85 singleton preterm-infants(24.5weeks ≤ gestational-age[GA] at delivery<30weeks) due to either preterm-labor and intact-membranes(PTL) or preterm premature rupture of membranes(preterm-PROM) without FGR(birth-weight<5th percentile for GA). Patients were divided according to the progression of inflammation in extra-placental membranes(EPM) and the progression of inflammation in chorionic-vessel(CV) and umbilical-cord(UC). RESULTS: 1) ROP was present in 40%(34/85) of study-population; 2) Of note, there was a significant stepwise-decrease in ROP with the progression of inflammation in EPM(inflammation-free EPM vs. inflammation restricted to CD vs. amnionitis; 55.6%[15/27]vs.39.5%[17/43]vs.13.3%[2/15]) and the progression of inflammation in CV and UC(inflammation-free CV and UC vs. inflammation restricted to CV and umbilical vessels vs. inflammation in Wharton's jelly[WJ]; 49.2%[29/59]vs.25.0%[3/12]vs.14.3%[2/14])(each-for P < 0.05, Chi-square test and each-for P < 0.01, linear-by-linear association); 3) Multiple logistic-regression analysis demonstrated amnionitis(Odds-Ratio 0.120, 95%Confidence-Interval 0.022-0.654, P = 0.014) and inflammation in WJ(Odds-Ratio 0.124, 95%Confidence-Interval 0.022-0.694, P = 0.018) were independent protective-factors against ROP. DISCUSSION: ROP in preterm-infants due to PTL or preterm-PROM without FGR is decreased with the progression of acute-HCA. This finding may be an evidence to suggest the progression of acute-HCA is closely associated with reducing the pathophysiology of ROP.

The Inflammatory Milieu of Amniotic Fluid Increases with Chorio-Deciduitis Grade in Inflammation-Restricted to Choriodecidua, but Not Amnionitis, of Extra-Placental Membranes.

No information exists about whether intra-amniotic inflammatory response increases with a chorio-deciduitis grade in the context of both inflammation-restricted to chorio-decidua and amnionitis of extra-placental membranes among spontaneous preterm births. The objective of current study is to examine this issue. A study population included 195 singleton pregnant women with chorio-deciduitis, and who spontaneously delivered at preterm (21.6~35.7 weeks) within 7 days of amniocentesis. We examined intra-amniotic inflammatory response according to the chorio-deciduitis grade in the context of inflammation restricted to chorio-decidua and amnionitis of extra-placental membranes. Intra-amniotic inflammatory response was measured by MMP-8 concentration (ng/mL) and WBC-count (cells/mm3) in amniotic-fluid (AF). Inflammation restricted to chorio-decidua and amnionitis were present in 47.7% (93/195) and 52.3% (102/195) of cases, respectively. Median AF MMP-8 concentration and WBC-count significantly increased with chorio-deciduitis grade in the context of inflammation restricted to chorio-decidua. However, there was no significant difference in median AF MMP-8 concentration and WBC-count between chorio-deciduitis grade-1 and grade-2 in the context of amnionitis. The inflammatory milieu of AF increases with chorio-deciduitis grade in inflammation-restricted to chorio-decidua, but not amnionitis, of extra-placental membranes. This finding suggests that a chorio-deciduitis grade may have little effect on the intensification of intra-amniotic inflammatory response in the context of amnionitis of extra-placental membranes.

HSP70: an alarmin that does not induce high rates of preterm birth but does cause adverse neonatal outcomes.

OBJECTIVE: Preterm labor and birth are strongly associated with sterile intra-amniotic inflammation, a clinical condition that is proposed to be initiated by danger signals, or alarmins. The aim of this study was to investigate whether the intra-amniotic administration of the alarmin heat shock protein 70 (HSP70) induces preterm labor/birth and adverse neonatal outcomes. METHODS: Pregnant mice received an intra-amniotic injection of 200 ng (n = 8), 400 ng (n = 6), 500 ng (n = 10), or 1 µg of HSP70 (n = 6). Control mice were injected with saline (n = 10). Following injection, the rates of preterm labor/birth and neonatal mortality were recorded. Neonatal weights at weeks 1, 2, and 3 were also recorded. RESULTS: The intra-amniotic injection of 400 ng [late preterm birth 16.7 ± 16.7% (1/6)], 500 ng [early and late preterm birth 10 ± 10% (1/10) each], or 1 µg [early preterm birth 16.7 ± 16.7% (1/6)] of HSP70 induced low rates of preterm/birth. However, the intra-amniotic injection of 500 ng or 1 µg of HSP70 induced significantly higher rates of neonatal mortality compared to controls [saline 14.2% (10/74), 200 ng 9.8% (6/61), 400 ng 17.9% (9/45), 500 ng 28.8% (23/78), and 1 µg 21.4% (13/49)]. Neonates born to dams injected with 200, 500 ng, or 1 µg HSP70 were leaner than controls (p ≤ .05). CONCLUSION: Intra-amniotic administration of the alarmin HSP70 did not induce high rates of preterm labor/birth; yet, it did indeed result in adverse neonatal outcomes.

Subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis in women with spontaneous preterm delivery.

OBJECTIVE: To compare subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis (HCA) in women with spontaneous preterm delivery (SPTD). METHODS: Among 1,706 women who gave birth twice or more at our institution, 138 women delivered spontaneously at preterm (<37.0 weeks). Subsequent deliveries occurred at our institution and placental biopsy results were available. The study population was categorized into 2 groups based on the presence of acute HCA at the time of SPTD: HCA group (n=52) and non-HCA group (n=86). The primary outcome measures were gestational age at delivery, birthweight, and frequency of preterm delivery in subsequent pregnancies. RESULTS: The median gestational age at the time of SPTD was 34.0 weeks (interquartile range [IQR], 28.9-35.3 weeks), and the frequency of acute HCA was 52/138 (38%). There were no differences in gestational age at delivery, birthweight, and frequency of preterm delivery between the HCA group and non-HCA group (median gestational age at delivery, 38.0 weeks (IQR, 36.7-38.8 weeks) in the HCA group vs. 37.9 weeks (IQR, 35.7-39.0 weeks) in the non-HCA group; frequency of preterm delivery, 14/52 (27%) in the HCA group vs. 33/86 (38%) in the non-HCA group; and median birthweight, 3.14 kg (IQR, 2.64-3.45 kg) in the HCA group vs. 2.95 kg (IQR, 2.44-3.36 kg) in the non-HCA group; P>0.1 for all. CONCLUSION: The presence of acute HCA in women at prior SPTD did not significantly affect their subsequent pregnancy outcomes.

Intra-amniotic administration of lipopolysaccharide induces spontaneous preterm labor and birth in the absence of a body temperature change.

OBJECTIVE: Intra-amniotic infection is associated with spontaneous preterm labor. In most cases, the infection is subclinical and bacteria are detected in the amniotic cavity rather than in the chorioamniotic membranes. The aims of this study were to establish a model of intra-amniotic lipopolysaccharide (LPS)-induced preterm labor/birth that resembles the subclinical syndrome and to compare this model to two established models of LPS-induced preterm labor/birth. METHODS: Pregnant B6 mice received an intra-amniotic, intra-uterine, or intra-peritoneal injection of LPS (100 ng/amniotic sac, 15 µg/25 µL, and 15 µg/200 µL respectively) or PBS (control). Following injection, body temperature (every two hours for a 12-h period), gestational age, and the rate of preterm labor/birth were recorded. RESULTS: An intra-amniotic injection of LPS resulted in preterm labor/birth [LPS 80 ± 24.79% (8/10) versus PBS 0% (0/8); p = 0.001] without causing maternal hypothermia. Intra-peritoneal [LPS 100% (8/8) versus PBS 0% (0/8); p < 0.001)] and intra-uterine [LPS 100% (8/8) versus PBS 28.57 ± 33.47% (2/7); p =0 .007] injections of LPS induced preterm labor/birth; yet, maternal hypothermia was observed. CONCLUSION: Intra-amniotic injection of LPS induces preterm labor/birth in the absence of a body temperature change, which resembles the subclinical syndrome.

Gastric fluid versus amniotic fluid analysis for the identification of intra-amniotic infection due to Ureaplasma species.

OBJECTIVE: Early neonatal sepsis is often due to intra-amniotic infection. The stomach of the neonate contains fluid swallowed before and during delivery. The presence of bacteria as well as neutrophils detected by culture or Gram stain of the gastric fluid during the first day of life is suggestive of exposure to bacteria or inflammation. We undertook this study to determine the relationship between gastric fluid analysis and amniotic fluid obtained by transabdominal amniocentesis in the detection of Ureaplasma species, the most frequent microorganisms responsible for intra-amniotic infection. MATERIALS AND METHODS: The study population consisted of 100 singleton pregnant women who delivered preterm neonates (<35 weeks) within 7 days of amniocentesis. Gastric fluid of newborns was obtained by nasogastric intubation on the day of birth. Amniotic fluid and gastric fluid were cultured for genital Mycoplasmas, and polymerase chain reaction (PCR) for Ureaplasma species was performed. Intra-amniotic inflammation was defined as an elevated amniotic fluid matrix metalloproteinase-8 concentration (>23 ng/mL). RESULTS: (1) Ureaplasma species were detected by culture or PCR in 18% (18/100) of amniotic fluid samples and in 5% (5/100) of gastric fluid samples; (2) among the amniotic fluid cases positive for Ureaplasma species, these microorganisms were identified in 27.8% (5/18) of gastric fluid samples; (3) none of the cases negative for Ureaplasma species in the amniotic fluid were found to be positive for these microorganisms in the gastric fluid; (4) patients with amniotic fluid positive for Ureaplasma species but with gastric fluid negative for these microorganisms had a significantly higher rate of intra-amniotic inflammation, acute histologic chorioamnionitis, and neonatal death than those with both amniotic fluid and gastric fluid negative for Ureaplasma species; and (5) no significant differences were observed in the rate of intra-amniotic inflammation, acute histologic chorioamnionitis, and neonatal death between patients with amniotic fluid positive for Ureaplasma species but with gastric fluid negative for these microorganisms and those with both amniotic fluid and gastric fluid positive for Ureaplasma species. CONCLUSIONS: Gastric fluid analysis has 100% specificity in the identification of intra-amniotic infection with Ureaplasma species. However, the detection of Ureaplasma species by culture or PCR in the gastric fluid of neonates at birth did not identify these microorganisms in two-thirds of cases with microbial invasion of the amniotic cavity. Thus, amniotic fluid analysis is superior to that of gastric fluid in the identification of intra-amniotic infection.

Subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis in women with spontaneous preterm delivery

OBJECTIVE: To compare subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis (HCA) in women with spontaneous preterm delivery (SPTD).METHODS: Among 1,706 women who gave birth twice or more at our institution, 138 women delivered spontaneously at preterm (<37.0 weeks). Subsequent deliveries occurred at our institution and placental biopsy results were available. The study population was categorized into 2 groups based on the presence of acute HCA at the time of SPTD: HCA group (n=52) and non-HCA group (n=86). The primary outcome measures were gestational age at delivery, birthweight, and frequency of preterm delivery in subsequent pregnancies.RESULTS: The median gestational age at the time of SPTD was 34.0 weeks (interquartile range [IQR], 28.9–35.3 weeks), and the frequency of acute HCA was 52/138 (38%). There were no differences in gestational age at delivery, birthweight, and frequency of preterm delivery between the HCA group and non-HCA group (median gestational age at delivery, 38.0 weeks (IQR, 36.7–38.8 weeks) in the HCA group vs. 37.9 weeks (IQR, 35.7–39.0 weeks) in the non-HCA group; frequency of preterm delivery, 14/52 (27%) in the HCA group vs. 33/86 (38%) in the non-HCA group; and median birthweight, 3.14 kg (IQR, 2.64–3.45 kg) in the HCA group vs. 2.95 kg (IQR, 2.44–3.36 kg) in the non-HCA group; P>0.1 for all.CONCLUSION: The presence of acute HCA in women at prior SPTD did not significantly affect their subsequent pregnancy outcomes.

The Diagnostic and Prognostic Value of Maternal Blood C-reactive Protein in Patients with Preterm Labor and Intact Membranes / 대한산부인과학회잡지

BACKGROUND: Intrauterine infection has been recognized as a major etiologic factor for preterm labor and delivery. Moreover, an accumulating body of evidence suggests that intrauterine infection is associated with poor perinatal outcome. Several antenatal tests, including amniotic fluid tests, have been proposed to be useful in the identification of intrauterine infection and prediction of adverse perinatal outcome in patients with preterm labor and intact membranes. However, those tests require the performance of an invasive procedure, amniocentesis. Maternal blood C-reactive protein(CRP) has been studied extensively as a noninvasive test in the diagnosis of intrauterine infection. OBJECTIVE: 1) to determine the diagnostic performance of maternal bood CRP in identification of intrauterine infection and 2) to establish the prognostic value of maternal blood CRP as an antepartum test for neonatal morbidity, especially sepsis, in neonates born to mothers with preterm labor and intact membrances. STUDY DESIGN: Maternal blood samples for CRP tests were obtained at the time of admission in 91 patients with preterm labor and intact membranes. Serum CRP concentrations were measured by antibody adsorption-particle agglutination assay technique. Histologic examination of delivered placenta and follow-up for maternal and neonatal outcome were performed. Receiver-operator characteristic(ROC) curve, logistic regression, and survival analysis techniques were used for statistical analysis. RESULTS: Patients with acute histologic chorioamnionitis had significantly higher median maternal blood CRP concentration than did patients without this lesion. ROC curve and survival analysis demonstrated that an elevated CRP concentration was strongly associated with the likelihood of acute histologic chorioamnionitis, shorter admission-to-delivery interval, significant neonatal morbidity, and neonatal sepsis. Multiple logistic regression analysis indicated that maternal blood CRP was a significant independent predictor for the occurrence of neonatal morbidity and neonatal sepsis even after adjustment of other independent variables. CONCLUSION: The results of this study suggest that maternal blood CRP has a diagnostic and prognostic value in patients with preterm labor and intact membranes.

The diagnostic and prognostic value of amniotic fluid white blood cell count in patients with preterm premature rupture of the membranes / 대한산부인과학회잡지

OBJECTIVE: The aim of this study was 1) to determine the diagnostic performance of amniotic fluid white blood cell (WBC) count for the antenatal detection of intrauterine infection and 2) to identify the value in prediction of preterm birth and significant neonatal morbidity in patients with preterm premature rupture of membranes. METHODS: Transabdominal amniocentesis was done in 255 singleton pregnancies with preterm premature rupture of membranes before 36 weeks of gestational age. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. Receiver-operator characteristic curve, survival analysis and logistic regression were used for statistical analysis. RESULTS: 1) Prevalence of positive amniotic fluid culture was 19.6% (50/255). Amniotic fluid WBC count was higher in the patients with positive amniotic fluid culture than those with negative amniotic fluid culture (median 269 [0-19764] cells/mm3 vs median 2 [0-7956] cells/mm3, p or = 20 cells/mm3) had sensitivity of 74%, specificity of 74%, positive predictive value of 41% and negative predictive value of 92% for the positive result of amniotic fluid culture. 3) An increased amiotic fluid WBC was strongly associated with shorter amniocentesis-to-delivery interval even after adjustment of gestational age at amniocentesis(hazard ratio 3.2736, p<0.0001). 4) Amniotic fluid WBC count was higher in patients with significant neonatal morbidity or congenital neonatal infectious morbidity than those without these (p<0.001 and p<0.005 respectively). 5) Patients with increased amniotic fluid WBC count had higher incidence of significant neonatal morbidity and congenital neonatal infectious morbidity than those with low amniotic fluid WBC count and the association between amniotic fluid WBC and significant neonatal morbidity was statistically significant after adjustment of gestational age at amniocentesis (OR 3.3649, p<0.0001). CONCLUSION: Amniotic fluid WBC count is of value in antenatal diagnosis of intrauterine infection and prediction of maternal and neonatal outcomes in patients with preterm premature rupture of membranes.