Colloid coload versus crystalloid coload to prevent maternal hypotension in women receiving prophylactic phenylephrine infusion during caesarean delivery: a randomised controlled trial.

BACKGROUND: The optimal fluid strategy to prevent maternal hypotension during caesarean delivery remains unclear. This study aim was to compare the incidence of post-spinal anaesthesia hypotension in women receiving either colloid or crystalloid coload in the setting of prophylactic phenylephrine infusion during caesarean delivery. METHODS: Healthy mothers undergoing elective caesarean delivery under spinal anaesthesia were randomised to receive a rapid intravenous coload with 6% hydroxyethyl starch 130/0.4 10 mL/kg (colloid group) or balanced crystalloid solution (Plasma Solution A) 10 mL/kg (crystalloid group) during spinal anaesthesia. All women had a prophylactic phenylephrine infusion initiated at 25 µg/min immediately after the subarachnoid block and titrated to systolic blood pressure using a standardised protocol. The primary outcome was the incidence of hypotension (systolic blood pressure <80% of baseline) until delivery. RESULTS: The incidence of hypotension was 50% in the colloid group and 62% in the crystalloid group (absolute difference, -12% [95% CI -33% to 9%]; relative risk, 0.8 [95% CI 0.56 to 1.14]; P=0.314). No significant difference between groups was found in the number of hypotensive episodes (median 0.5 [IQR 0 to 1] vs 1 [0 to 2], P=0.132) or phenylephrine dose (675 [IQR 425 to 975] µg vs 750 [625 to 950] µg, P=0.109). The incidence of severe hypotension, symptomatic hypotension, bradycardia, nausea, and the neonatal outcomes were not significantly different. CONCLUSIONS: This study found no benefit of colloid coload compared with crystalloid coload for preventing maternal hypotension in the presence of prophylactic phenylephrine infusion during caesarean delivery.

The concordance rate of non-chromosomal congenital malformations in twins based on zygosity: a retrospective cohort study.

OBJECTIVE: To examine the concordance rate of non-chromosomal congenital malformations in twin pairs based on zygosity. DESIGN: Retrospective cohort study. SETTING: A tertiary hospital in Korea. POPULATION: Twin pairs born at Seoul National University Hospital between 2001 and 2019. METHODS: Congenital malformations were diagnosed by postnatal workups of neonates or autopsy in cases of stillborn infants. Zygosity was confirmed by sex, chorionicity and DNA analysis. MAIN OUTCOME MEASURES: Concordance rate of congenital malformations in twin pairs based on zygosity. RESULTS: In total, 3386 twin pairs were included. The risk of a congenital malformation in the index twin increased significantly if the co-twin had the congenital malformation, and the concordance rate was higher in monozygotic (MZ) than in dizygotic (DZ) twins (37.04 versus 16.77, P < 0.001). An increased risk of a congenital malformation in the presence of the same congenital malformation in the co-twin was observed only for malformations of the nervous system, eye/ear/face/neck, circulatory system, cleft lip/palate, genital organs, urinary system and musculoskeletal system. Significantly higher concordance rates in MZ than in DZ twin pairs were observed only for the nervous system (40.00 versus 0.00, P < 0.001), circulatory system (32.97 versus 19.74, P = 0.021), cleft lip/palate (44.44 versus 0.00, P = 0.017) and urinary system (22.22 versus 0.00, P = 0.004), whereas significant differences were not found for the genital organs or musculoskeletal system. CONCLUSIONS: Monozygotic twins had higher concordance rates than DZ twins only in specific organ systems. It may be speculated that nervous system, circulatory system, cleft lip/palate and urinary system are primarily genetically affected. TWEETABLE ABSTRACT: Monozygotic twins had higher concordance rates than dizygotic twins only in specific organ systems.

Mid-trimester amniotic fluid pro-inflammatory biomarkers predict the risk of spontaneous preterm delivery in twins: a retrospective cohort study.

OBJECTIVE: To evaluate the association between the concentrations of immune-related proteins in mid-trimester amniotic fluid (AF) and the subsequent risk of spontaneous preterm delivery in twins. STUDY DESIGN: The study population consisted of consecutive women with a twin pregnancy who underwent clinically indicated genetic amniocentesis at 15 to 20 weeks, and had a subsequent spontaneous delivery in the early preterm period (<32 weeks (cases)) or at term (37 to 42 weeks (controls)). AF was analyzed for cytokines (interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13 and IL-15, interferon-γ, tumor necrosis factor-α), matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-12), and chemokines (complement factor-D/Adipsin, Serpin E1/PAI-1, Adiponectin/Acrp30, C-Reactive Protein, CCL2/MCP-1, Leptin, Resistin) using multiplex immunoassay kits. The association between AF protein levels and subsequent early preterm birth were examined. RESULT: A total of 96 sets of twins were enrolled, including 17 early preterm birth cases and 79 term controls. AF concentrations of IL-6, IL-8, MMP-3, MMP-8 and MMP-9, and CCL2/MCP-1 were significantly higher in cases than controls. Among these analytes, the combination of AF IL-8 and MMP-9 values had the highest predictive value for early preterm birth. The risk was 8% (10/132) for IL-8<1200 pg ml(-1) and MMP-9<1000 pg ml(-1), 30% (15/50) for IL-8>1200 pg ml(-1) or MMP-9>1000 pg ml(-1), and 90% (9/10) for IL-8>1200 pg ml(-1) and MMP-9>1000 pg ml(-1) (P<0.001). CONCLUSION: High concentrations of IL-8 and MMP-9 in mid-trimester AF in twins predicted well the risk of early preterm birth.

Effect of endoscopy screening on stage at gastric cancer diagnosis: results of the National Cancer Screening Programme in Korea.

BACKGROUND: Although gastric cancer screening is common among countries with a high prevalence of gastric cancer, there is little data to support the effectiveness of this screening. This study was designed to determine the differences in stage at diagnosis of gastric cancer according to the screening history and screening method (upper gastrointestinal series (UGIS) vs endoscopy). METHODS: The study population was derived from the National Cancer Screening Programme (NCSP), a nationwide organised screening programme in Korea. The study cohort consisted of 19 168 gastric cancer patients who had been diagnosed in 2007 and who were invited to undergo gastric cancer screening via the NCSP between 2002 and 2007. RESULTS: Compared with never-screened patients, the odds ratios for being diagnosed with localised gastric cancer in endoscopy-screened patients and UGIS-screened patients were 2.10 (95% CI=1.90-2.33) and 1.24 (95% CI=1.13-1.36), respectively. CONCLUSIONS: Screening by endoscopy was more strongly associated with a diagnosis of localised stage gastric cancer compared with screening by UGIS.

Chronic chorioamnionitis is the most common placental lesion in late preterm birth.

OBJECTIVES: The pathogenesis of late preterm birth remains elusive for the mechanisms of disease responsible. Placental examination can often provide important clues for the pathogenesis of pregnancy complications. This study was conducted to determine placental pathologic findings according to the gestational age and the clinical circumstances of preterm birth. STUDY DESIGN: Placental pathologic findings and obstetrical and neonatal outcomes were reviewed in a consecutive preterm birth cohort from a single tertiary center (N = 1206). Placentas of term births (N = 300) were used as normal controls. RESULTS: Acute chorioamnionitis (22.7% vs. 16.7%), maternal vascular underperfusion (6.4% vs. 0.5%), and chronic chorioamnionitis (20.8% vs. 10.5%) were significantly more frequent in preterm births than in term births (P < 0.05, for each). Among preterm births, chronic chorioamnionitis was the most common pathology of late preterm birth (gestational age <37 and ≥34 weeks), while acute chorioamnionitis was the most common lesion of extremely preterm birth (gestational age <28 weeks). While the frequency of acute chorioamnionitis decreased with advancing gestation, that of chronic chorioamnionitis increased (P < 0.001, for each). The upward trend of the frequency of chronic chorioamnionitis was related to advancing gestation in both spontaneous and indicated preterm births (P < 0.001, for each). CONCLUSIONS: Chronic chorioamnionitis is a common pathology of late preterm birth. It is suggested that chronic chorioamnionitis, a feature of maternal anti-fetal rejection, is an important etiology of preterm birth, especially of late preterm birth.

The presence of funisitis is associated with a decreased risk for the development of neonatal respiratory distress syndrome.

OBJECTIVES: Fetal lung maturation and respiratory outcomes are influenced by the exposure to intrauterine inflammation. Funisitis is considered as the histologic hallmark of fetal inflammatory response. This study was performed to determine if there is a difference in the rate of neonatal respiratory distress syndrome (RDS) according to the presence or absence of funisitis in preterm gestations. STUDY DESIGN: The relationship between the presence of funisitis and the development of neonatal RDS was examined in 301 consecutive singleton preterm births (24-32 weeks' gestation). Cases without placental histological examination and those with major congenital anomalies were excluded. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton's jelly on the placental histological examination. RESULTS: Funisitis was diagnosed in 25% and RDS was diagnosed in 46% of cases. The rate of RDS in babies with funisitis was lower than in those without funisitis (28.4% vs. 51.1%, p = 0.001). Logistic regression analysis demonstrated that the presence of funisitis was associated with a decreased risk for RDS after adjusting for confounding variables (Odds ratio = 0.44, 95% CI 0.22-0.90). The downward trend of the frequency of RDS was related to the presence of histologic chorioamnionitis and funisitis (p < 0.001). CONCLUSIONS: The presence of funisitis is associated with a decreased risk for the development of neonatal RDS in preterm gestations. Furthermore, this observation suggests that the fetal involvement of placental inflammation may be beneficial to the maturation of the fetal lung.

Factors associated with the intention to have colorectal cancer screening in Korean adults.

The purpose of this study was to investigate the factors related to screening intention in a population-based screening programme for colorectal cancer. The data were taken from the 2008 Korean National Cancer Screening Survey. We conducted a nationwide survey with trained interviewers using a questionnaire. A total of 2038 participants agreed to answer the survey. There were 955 study subjects aged ≥ 50 years in the target age group for colorectal cancer screening. Colorectal cancer screening behaviour and demographic characteristics were collected to evaluate intention for colorectal cancer screening and related factors. Descriptive statistics and multiple logistic regression were used in the analysis. The lifetime screening rate was 50.4% (50.9% for men and 49.8% for women). The screening rate with recommendation was 39.7% (39.3% for men and 40.1% of women). The odds ratios of intention to be screened increased significantly in younger subjects and those screened with double-contrast barium enema or colonoscopy. 'Without any symptoms' was reported as the most frequent reason for non-attendance or no intention to be screened. Age and recent screening methods were important factors related to intention to be screened for colorectal cancer. Further research is needed to identify remaining barriers to screening.

Satisfaction with mammography in the National Cancer Screening Programme participants of age 40s in Korea.

The aim of this study was to evaluate satisfaction with the National Cancer Screening Programme of mammography in Korea and to examine the association between subscales of satisfaction and general satisfaction. We conducted a cross-sectional telephone survey for women who had obtained a National Cancer Screening Programme mammographic screening at general hospitals between May and October 2008. The present study included 2005 women in their forties. We performed multivariate linear regression using dependent variable as general satisfaction and independent variables as subscales of satisfaction, such as pre-screening information transfer, staff interpersonal skills, physical surroundings and results reporting. Participants were stratified according to the result of their mammogram as negative or positive. Mean score of satisfaction was above 2.5 of 4 for all subscales. Women who received positive results were less satisfied with all of subscale factors. Staff interpersonal skills were the most important factor that contributed to general satisfaction. Future efforts such as staff training programme of communication/attitude skills, ensuring privacy and explanation of possible discomfort of the screening would be needed.

Histologic chorioamnionitis is more common after spontaneous labor than after induced labor at term.

OBJECTIVE: Inflammation of the chorioamniotic membranes (histologic chorioamnionitis) is a risk factor for adverse neonatal outcome. Labor has many common features with inflammatory processes; therefore, an important question is whether the frequency of histologic chorioamnionitis in spontaneous labor at term is higher than that of women in labor after induction. This study was conducted to address this question. STUDY DESIGN: The frequency of histologic chorioamnionitis was compared between patients who delivered after the spontaneous onset of labor versus those who delivered after induction of labor at term in singleton gestations (> or = 37 weeks). Patients in whom uterotonic agents were used during the latent phase of labor were excluded. RESULTS: (1) The overall frequency of histologic chorioamnionitis was 20.2% (107/531); (2) histologic chorioamnionitis was significantly more frequent in women who delivered after the spontaneous onset of labor than in those who underwent induction of labor (24.3% [81/333] versus 13.1% [26/198], p < 0.005). This difference remained significant after adjusting for parity, gestational age at delivery, total duration of labor, the interval from rupture of membranes to delivery and the mode of delivery. CONCLUSION: Histologic chorioamnionitis is more common in women who delivered after the spontaneous onset of labor than in those who underwent induction of labor at term.

Measurement of fetal urine production to differentiate causes of increased amniotic fluid volume.

OBJECTIVES: In polyhydramnios, amniotic fluid (AF) volume can be increased not only as a result of increased fetal urine production, but also due to several other factors, including impairment of both fetal swallowing and gastrointestinal (GI) absorption of AF. Our aim was to evaluate whether measurement of the fetal urine production rate (UPR) can be used to differentiate the causes of increased AF volume. METHODS: This cross-sectional study included 54 pregnant women with an increased amniotic fluid index (AFI), defined as AFI > or = 18 cm, divided into two groups according to the presence of fetal anomalies that are associated with impairment of fetal swallowing or decreased GI absorption of AF (Group 1, n = 14) or the absence of fetal anomalies (Group 2, n = 40). The control group included 96 normal pregnancies with normal AFI (8 < or = AFI < 18 cm) (Group 3). Fetal UPR was obtained by serial bladder volume measurements (two to four times, with a median interval of 5 min between each) using the rotational method of Virtual Organ Computer-aided AnaLysis (VOCAL()) with three-dimensional ultrasound. To adjust for fetal weight (Wt) and gestational age (GA), UPR_Wt and UPR_SD were calculated using the following formulae: UPR_Wt = measured UPR/estimated fetal weight and UPR_SD = (measured UPR - mean UPR for each GA)/SD of UPR for each GA. RESULTS: The AFI was increased significantly in Groups 1 and 2 compared with Group 3. However, the median fetal UPR in Group 1 did not differ from that of Group 3, in contrast to the higher median fetal UPR in Group 2 compared with Groups 1 and 3; this difference remained significant after adjusting for GA and estimated fetal weight in terms of UPR_SD and UPR_Wt. In Groups 2 and 3, AFI and UPR had a positive correlation in terms of UPR, UPR_SD and UPR_Wt. CONCLUSIONS: Our findings that fetal UPR is significantly increased in cases with increased AFI without fetal anomalies, but not in those with increased AFI and fetal anomalies involving decreased GI absorption of AF, might be used to differentiate causes of increased AF volume. In the absence of fetal anomalies, AFI and fetal UPR correlate positively.

The frequency and clinical significance of intra-uterine infection and inflammation in patients with placenta previa and preterm labor and intact membranes.

OBJECTIVE: Histologic placental and/or intra-amniotic inflammation is frequently documented during ascending intra-uterine infections in patients with preterm labor and intact membranes. Placenta previa can be a clinical situation that shows the successive schema of histologic placental and intra-amniotic inflammation during the process of ascending intra-uterine infections. However, a paucity of information exists about the frequency and clinical significance of intra-uterine infections and inflammation in patients with placenta previa and preterm labor and intact membranes. The purpose of this study was to examine this issue. STUDY DESIGN: Amniocentesis was performed on 42 patients with placenta previa and preterm labor and intact membranes (gestational age <37 weeks). Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and AF white blood cell (WBC) count and matrix metalloproteinase-8 (MMP-8) concentrations were determined. The diagnosis of intra-amniotic inflammation was made in patients with an elevated AF MMP-8 (> or =23 ng/ml). Non-parametric statistics were used for analysis. RESULTS: 1) Intra-amniotic inflammation was present in 16.7% (7/42), proven AF infection in 4.9% (2/41), and histologic chorioamnionitis in 19.0% (8/42) of patients with placenta previa and preterm labor; 2) Patients with intra-amniotic inflammation had significantly higher rates of a positive AF culture, histologic chorioamnionitis, funisitis, and a shorter interval-to-delivery than those without intra-amniotic inflammation (p<0.05 for each); 3) Among patients with histologic chorioamnionitis, inflammation of the choriodecidua, which was exposed to the cervical canal, existed in all cases (8/8), but inflammation of the chorionic plate existed in 63% of patients (5/8); 4) Patients with inflammation of the chorionic plate had significantly higher median AF MMP-8 concentrations and WBC counts, and higher rates of intra-amniotic inflammation than those in whom inflammation was restricted to choriodecidua (p<0.05 for each). CONCLUSIONS: Placental inflammation was present in 19.0% and intra-amniotic inflammation was present in 16.7% of patients with placenta previa and preterm labor and intact membranes. The intra-amniotic inflammatory response was stronger when inflammation was present in the chorionic plate and choriodecidua, than when it was restricted to the choriodecidua only, which was exposed to the cervical canal in placenta previa.

Expression of extracellular signal-regulated kinase1/2 and p38 mitogen-activated protein kinase in the invasive trophoblasts at the human placental bed.

BACKGROUND: Mitogen-activated protein kinases (MAP kinases) participate in signal transduction pathways that control embryogenesis, cell differentiation, cell proliferation and cell death. The roles of extracellular signal-regulated kinase1/2 (ERK1/2) and p38 MAP kinase in the differentiation and invasion of human trophoblasts have been studied. However, the in vivo expression and activation of ERK1/2 and p38 at the placental bed have not been elucidated. METHODS: The study group consisted of placental bed biopsy tissues obtained from the pregnancies without preeclampsia (n=24) and with preeclampsia (n=8) between 31 and 40 weeks of gestation. We evaluated the expressions and phosphorylations of ERK1/2 and p38 MAP kinase in the invasive trophoblasts in the placental bed tissues using immunohistochemistry. RESULTS: p38 and phospho-p38 MAP kinase were not detected in invasive trophoblasts in cases or controls. ERK1/2 and phospho-ERK1/2 were positive in invasive trophoblasts albeit with variable staining. Phosphorylation of ERK1/2 was significantly less frequent in invasive trophoblasts in placental bed biopsies from women with preeclampsia compared with normotensive controls. CONCLUSION: These findings suggest that preeclampsia is associated with decreased activation of ERK1/2 in invasive trophoblasts in vivo.

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

OBJECTIVES: 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). METHODS: One hundred and fifty-four women with a normal singleton pregnancy at 24 to 40 weeks' gestation were enrolled in this cross-sectional study. The women had no medical or obstetric complications affecting amniotic fluid volume. Fetal bladder volume was measured using 3D ultrasound imaging and Virtual Organ Computer-aided AnaLysis (VOCAL) with a rotational angle of 30 degrees and manual surface tracing technique. Bladder volume was measured two or three times within a 5-10-min interval and fetal UPR was calculated from serial measurements. When measurements were performed more than twice, we used the mean rate of calculated UPRs. UPR was then plotted against GA to establish the nomogram. RESULTS: Fetal UPR increased with GA from a median value of 7.3 mL/h at 24 weeks' gestation to 71.4 mL/h at term, and could be calculated from GA using the formula: Ln(UPR) = - 6.29582 + (0.43924 x GA) + (0.000432 x GA2), r2 = 0.63, P = 0.0046. Growth percentiles of UPR according to age are presented. CONCLUSIONS: Fetal UPR can be easily measured by 3D ultrasound assessment of bladder volume. This modality may be a promising alternative to conventional methods of amniotic fluid volume measurement such as amniotic fluid index and single deepest pocket, and might be an alternative option for predicting fetal hypoxia.

CagA-producing Helicobacter pylori and increased risk of gastric cancer: a nested case-control study in Korea.

In a nested-case control study of 100 cases of gastric cancer and 400 matched controls in relation to virulence factors of Helicobacter pylori in a Korean cohort, CagA seropositivity was significantly associated with a higher risk of gastric cancer among H. pylori-infected subjects (OR=3.57, 95% CI 1.05-12.14).

C-reactive protein in umbilical cord blood: a simple and widely available clinical method to assess the risk of amniotic fluid infection and funisitis.

OBJECTIVE: The purpose of this study was to determine whether concentrations of C-reactive protein (CRP) in umbilical cord plasma at birth were elevated in neonates with sepsis, an inflammatory lesion of the umbilical cord (funisitis) or who were born to mothers with microbial invasion of the amniotic cavity. METHODS: Umbilical cord plasma was collected at birth from 313 singleton preterm neonates (20-35 weeks of gestation). The results of amniotic fluid culture performed within 5 days of birth, the occurrence of congenital neonatal sepsis and the presence of funisitis were assessed. Amniocentesis was performed in 152 patients within 5 days of birth. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. The CRP concentration was measured with a highly sensitive immunoassay. RESULTS: The median cord plasma CRP concentration was significantly higher in neonates with a positive amniotic fluid culture than in those with negative culture (median 245.9 (range 11.6-4885.5) ng/ml vs. median 44.3 (range 2.3-7401.8) ng/ml; p < 0.001), in those with congenital proven sepsis than in those without this complication (median 789.5 (range 20.4-2584.3) ng/ml vs. median 41.5 (range 1.3-7401.8) ng/ml; p < 0.005) and in neonates with funisitis than in those without funisitis (median 403.8 (range 4.9-10897.4) ng/ml vs. median 31.0 (range 1.3-7401.8) ng/ml; p < 0.001). The sensitivity of CRP in the identification of amniotic fluid infection, neonatal sepsis and funisitis was similar to that of interleukin-6 (> 17.5 pg/ml). However, the specificity of CRP in the identification of neonatal sepsis and funisitis was significantly higher than that of interleukin-6 (74% vs. 69%, p < 0.05; 83% vs. 76%, p < 0.01). CONCLUSION: Umbilical cord plasma CRP concentrations were elevated in patients with amniotic fluid infection, congenital neonatal sepsis and funisitis.

Clinical significance of intra-amniotic inflammation in patients with preterm labor and intact membranes.

OBJECTIVE: The purpose of this study was to determine the frequency and clinical significance of intraamniotic inflammation in patients with preterm labor and intact membranes. STUDY DESIGN: Amniocentesis was performed in 206 patients with preterm labor and intact membranes. Amniotic fluid was cultured for aerobic and anaerobic bacteria and mycoplasmas. The diagnosis of intraamniotic inflammation was made in patients with a negative amniotic fluid culture on the basis of amniotic fluid concentrations of interleukin-6 (>2.6 ng/mL, derived from receiver operating characteristic curve analysis). Statistical analysis was conducted with contingency tables and survival techniques. RESULTS: Intra-amniotic inflammation (negative amniotic fluid culture but elevated amniotic fluid interleukin-6) was more common than intra-amniotic infection (positive amniotic fluid culture regardless of amniotic fluid interleukin-6 concentration; 21% [44/206 women] vs 10% [21/206 women]; P <.001). The amniocentesisto-delivery interval was significantly shorter in patients with intra-amniotic inflammation than in patients with a negative culture and without an inflammation (median, 20 hours [range, 0.1-2328 hours] vs median, 701 hours [range, 0.1-3252 hours], respectively; P <.0001). Spontaneous preterm delivery of <37 weeks was more frequent in patients with intra-amniotic inflammation than in those with a negative culture and without inflammation (98% vs 35%; P <.001). Patients with intra-amniotic inflammation had a significantly higher rate of adverse outcome than patients with a negative culture and without intra-amniotic inflammation. Adverse outcomes included clinical and histologic chorioamnionitis, funisitis, early preterm birth, and significant neonatal morbidity. There were no significant differences in the rate of adverse outcomes between patients with a negative culture but with intra-amniotic inflammation and patients with intra-amniotic infection (positive culture regardless of amniotic fluid interleukin-6 concentration). CONCLUSION: Intra-amniotic inflammation/infection complicates one third of the patients with preterm labor (32%; 65/206 women), and its presence is a risk factor for adverse outcome. The outcome of patients with microbiologically proven intra-amniotic infection is similar to that of patients with intra-amniotic inflammation and a negative amniotic fluid culture. We propose that the treatment of patients in preterm labor be based on the operational diagnosis of intra-amniotic inflammation rather than the diagnosis of intra-amniotic infection because the latter diagnosis cannot be undertaken rapidly.

An elevated amniotic fluid matrix metalloproteinase-8 level at the time of mid-trimester genetic amniocentesis is a risk factor for spontaneous preterm delivery.

OBJECTIVE: Strong evidence implicates chronic intra-amniotic inflammation in the etiology of mid-trimester abortion and spontaneous preterm delivery. The purpose of this study was to determine if concentrations of amniotic fluid matrix metalloproteinase-8, and cytokines such as interleukin-6 and angiogenin can identify patients at risk for spontaneous preterm delivery in patients undergoing mid-trimester amniocentesis. STUDY DESIGN: A case-control study was conducted to compare mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin in patients who delivered at term and in those who delivered before term. The study included 19 cases with spontaneous preterm delivery and 95 matched controls with normal outcomes. Patients with abnormal fetal karyotypes or major anomalies were excluded. Matrix metalloproteinase-8, interleukin-6, and angiogenin were measured by using specific immunoassays. Mann-Whitney U tests, Fisher exact tests, and receiver-operating characteristic curves were used for statistical analysis. RESULTS: The median amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin concentrations of patients with spontaneous preterm delivery were significantly higher than those of control cases (matrix metalloproteinase-8: median, 3.1 ng/mL [range, 0.3-1954.9 ng/mL] vs median, 1.3 ng/mL [range, <0.3-45.2 ng/mL], P <.01; interleukin-6: median, 0.32 ng/mL [range, 0.04-2.52 ng/mL] vs median, 0.18 ng/mL [range, 0.01-1.81 ng/mL], P <.01; angiogenin: median, 11.1 ng/mL [range, 4.5-30.7 ng/mL] vs median, 6.7 ng/mL [range, 1.3-21.9 ng/mL], P <.001). Amniotic fluid matrix metalloproteinase-8 concentrations higher than 23 ng/mL had the highest specificity and odds ratio (sensitivity, 42% [8/19]; specificity, 99% [94/95]; OR, 68.4 [95% CI, 7.8-599.1]) in the identification of the patients with preterm delivery after genetic amniocentesis. CONCLUSIONS: Elevated mid-trimester concentrations of amniotic fluid matrix metalloproteinase-8, interleukin-6, and angiogenin are a risk factor for early spontaneous preterm delivery (<32 weeks). An elevated matrix metalloproteinase-8 level of >23 ng/mL is a powerful predictor of spontaneous preterm delivery (<32 weeks) with an odds ratio of 68.4. Amniotic fluid studies can be used to improve the risk assessment for preterm delivery in women who undergo mid-trimester amniocentesis for genetic indications.

The relationship between oligohydramnios and the onset of preterm labor in preterm premature rupture of membranes.

OBJECTIVE: The objective of this study was to determine whether a reduced amniotic fluid volume was associated with the onset of preterm parturition in patients with preterm premature rupture of membranes. STUDY DESIGN: An amniotic fluid index was determined before transabdominal amniocentesis in 129 patients with preterm premature rupture of membranes (gestational age < or = 35 weeks). Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. Survival techniques were used for analysis. RESULTS: Amniotic fluid index was < or = 5 cm in 29% of patients (38/129). Patients with an amniotic fluid index of < or = 5 cm had a significantly higher rate of positive amniotic fluid culture than those with an amniotic fluid index of >5 cm (42% [16/38] vs 18% [16/91]; P<.01). Spontaneous preterm delivery within 24 hours and 48 hours was more frequent among patients with an amniotic fluid index of < or = 5 cm than those with an amniotic fluid index of >5 cm (for 24 hours, 29% vs 12%; for 48 hours, 42% vs 21%; P<.05 for each). The amniocentesis-to-delivery interval was significantly shorter in patients with an amniotic fluid index of < or = 5 cm than in patients with an amniotic fluid index of >5 cm (median, 38 hours; range, 0.2-1310 hours; vs median, 100 hours; range 0.1-2917 hours; P<.01). Moreover, Cox proportional hazards model analysis indicated that an amniotic fluid index of < or = 5 cm was a significant predictor of the duration of the pregnancy after adjustment for gestational age and the results of amniotic fluid culture (odds ratio, 2.4; 95% confidence interval, 1.4-3.9; P<.001). CONCLUSION: Patients with preterm premature rupture of membranes and an amniotic fluid index of < or = 5 cm are at increased risk for a shorter interval to delivery.

The relationship among inflammatory lesions of the umbilical cord (funisitis), umbilical cord plasma interleukin 6 concentration, amniotic fluid infection, and neonatal sepsis.

OBJECTIVE: The purpose of this study was to determine whether funisitis (inflammation of the umbilical cord detected by histologic examination of the placenta) is associated with changes in the umbilical cord plasma concentration of interleukin 6, microbial invasion of the amniotic cavity, and neonatal sepsis. STUDY DESIGN: The relationship among the presence of funisitis, interleukin 6 concentrations in umbilical cord plasma at birth, the results of amniotic fluid culture performed within 3 days of birth, and the occurrence of congenital neonatal sepsis was examined in 315 consecutive singleton preterm births (20-35 weeks' gestation). Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton jelly. The interleukin 6 concentration was measured with a specific immunoassay. Amniocentesis was performed in 106 patients within 3 days of birth. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. RESULTS: (1) Funisitis was present in 25% of patients (78/315). (2) Patients with funisitis had a significantly higher median cord plasma interleukin 6 and a lower gestational age at birth than did those without funisitis (cord interleukin 6: median, 52.4 pg/mL; range, 0.9-19,230 pg/mL; vs median, 4.6 pg/mL; range, 0-18,108 pg/mL; gestational age: median, 31.1 weeks' gestation; range, 21.0-35.0 weeks' gestation; vs median, 32.9 weeks' gestation; range, 21.4-35.0 weeks' gestation; P<.001 for each comparison). (3) A cord plasma interleukin 6 of > or =17.5 pg/mL had a sensitivity of 70% and a specificity of 78% in the identification of funisitis. (4) Microbial invasion of the amniotic cavity and clinical chorioamnionitis were more common among patients with funisitis than among those without funisitis (positive amniotic fluid culture: 53% [20/38]; vs. 12% [8/68]; clinical chorioamnionitis: 18% [14/78]; vs. 4% [9/237]; P<.001 for each comparison). (5) Neonates with funisitis had a significantly higher rate of congenital sepsis than did those without this lesion (12% [8/66] vs. 1% [3/216]; P<.001); this difference remained significant after adjustment for gestational age at birth (odds ratio, 7.2; 95% confidence interval, 1.8-29.0). CONCLUSION: (1) Umbilical cord plasma interleukin 6 concentrations were higher in neonates born with funisitis than in those without this lesion. (2) Funisitis is associated with amniotic fluid infection, congenital neonatal sepsis, and the fetal inflammatory response syndrome.