J. K. Jun

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.

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.

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).

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.

Oral health behaviors, periodontal disease, and pathogens in preeclampsia: a case-control study in Korea.

BACKGROUND The aim of this study is to confirm the association among oral health behaviors, periodontitis, and preeclampsia in Korean women. METHODS This study is designed as a case-control study. Sixteen women with preeclampsia and 48 without preeclampsia post-delivery were included in this study from November 2007 to January 2010. Information was collected on demographics, health behaviors, and obstetric and systemic diseases that may influence the periodontal condition and preeclampsia. Full-mouth periodontal probing was conducted by one trained examiner (KHB). Localized periodontitis was defined as periodontal clinical attachment loss (AL) ≥ 3.5 mm on two or three sites not on the same tooth. In addition, generalized periodontitis was defined as clinical AL ≥ 3.5 mm on ≥ 4 sites not on the same tooth. Gingival crevicular fluid was collected using a sterilized paper point for quantitative analysis of Treponema denticola, Porphyromonas gingivalis, Prevotella intermedia (Pi), and Tannerella forsythia (previously T. forsythensis). RESULTS After adjusting for confounders, the adjusted odds ratio (OR) was 4.79 (95% confidence interval [CI]: 1.02 to 29.72) for localized periodontitis and 6.60 (95% CI: 1.25 to 41.61) for generalized periodontitis. In addition, the proportion of floss or interdental brush users in women with preeclampsia was lower than that in women without (adjusted OR: 0.21; 95% CI: 0.02 to 0.93). Pi was significantly more prevalent in women with preeclampsia (P = 0.028). CONCLUSION These results indicate that preeclampsia could be associated with the maternal periodontal condition and interdental cleaning.

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 to differentiate causes of increased amniotic fluid volume

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.

Association Between Obesity and Periodontitis in Pregnant Females

BACKGROUND The purpose of this study is to investigate whether overweight and obesity before pregnancy are associated with periodontitis during pregnancy. METHODS This study examined a total of 315 pregnant females at 21 to 24 weeks of gestation. Overweight and obesity were defined based on criteria proposed by the World Health Organization Expert Consultation. Periodontal conditions were assessed by measuring clinical periodontal attachment loss (AL). To investigate whether obese pregnant females have increased risk according to the extent of periodontitis, the data were divided into two groups: 1) generalized periodontitis and 2) localized periodontitis. A comparison among underweight, normal-weight, and overweight/obese groups for explanatory variables was analyzed using the χ(2) test for categorical variables and an analysis of variance for continuous variables. Multivariate logistic regression analysis was performed with adjustments for age, health and oral health behaviors, and obstetric information. RESULTS Age, age at first delivery, periodontitis, and periodontal conditions (two or more interproximal sites with AL ≥4 mm not on the same tooth) were significantly associated with body mass index (BMI) (P <0.05). The adjusted odds ratio of periodontitis was 4.57 (95% confidence interval = 2.30 to 9.07) for overweight and obese females (BMI ≥23 kg/m(2)), after adjusting for all of the covariates. CONCLUSION There is a strong association between prepregnancy overweight/obesity and periodontitis in pregnant females.

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.

Prenatal ultrasound findings of fetal urethral duplication

Urethral duplication is a rare congenital anomaly with approximately 300 cases described in the literature1–13. Most of the reported cases are of incomplete duplications. The anomaly is more common in males2, with few cases reported in females6, and the embryology of the condition is unclear. Most patients are asymptomatic, except for a double stream on micturition. Some patients present with urinary tract infections, incontinence or bladder outflow tract obstruction. Associated genitourinary anomalies and lumbar spine anomalies have been reported3,11,14,15. We could find no cases of prenatally diagnosed urethral duplication described in the literature. We report the prenatal ultrasound and postnatal imaging findings of a case of fetal urethral duplication. A 36-year-old woman underwent a targeted ultrasound examination at 31 weeks’ gestation because of fetal dilatation of the renal pelves and ureters. This revealed bilateral dilatation of the renal pelves and ureters of a male fetus. Periodic changes of the renal pelvic and ureteral diameters suggested vesicoureteral reflux (VUR). The urinary bladder was dilated for > 2 h, suggesting bladder outlet obstruction, but posterior urethral dilatation was not detected. During fetal urination, the urine flow through the urethra was divided into upper and lower flows on color Doppler ultrasound imaging, suggesting urethral duplication (Figure 1). Postnatal examination revealed two urethral orifices and a duplicated urethra. On voiding cystourethrography, the upper urethral opening was normally located but the lower opening was on the ventral surface. Despite its abnormal location, the ventral urethral opening was almost normal in shape. There was a web-like structure on the proximal portion of the ventral urethra, and the lumen to the bladder was not visualized (Figure 2). The patient frequently voided and had a weak double stream. On follow-up ultrasound examination of the kidney 2 months later, hydroureteronephrosis had progressed and a Tc-99m DTPA renal scan revealed delayed excretion in the left kidney. The patient underwent a vesicostomy, Deflux injection (Oceana Therapeutics Ltd., Dublin, Republic of Ireland) and incision to broaden the meatus at the distal end of the ventral surface. Followup voiding cystourethrography 1 year after the operation showed persistent Grade V right VUR and urethral duplication. The left VUR had resolved. The most widely accepted classification system of urethral duplication is that proposed by Effmann et al.1. According to Effmann’s classification, our case was Type IIA2, in which the second channel arises from the first independently and courses into a second meatus. The urethral duplication was initially detected on prenatal ultrasound examination in association with dilatation of the renal pelves and ureters. The hydroureteronephrosis progressed after birth and the patient underwent a vesicostomy. It is not clear whether or not the hydroureteronephrosis resulted from the urethral duplication. The duplication was first identified on color Doppler imaging of fetal voiding. Fetal voiding is usually visible on color Doppler imaging, and our case illustrates the utility of this imaging modality in providing helpful information in cases with anomalies of the lower urinary tract and external genitalia. Patients with urethral duplication are usually asymptomatic, except for a urinary double stream and cosmetic problems. However, depending on the urethral anatomy, the clinical presentation can vary from no symptoms to VUR or renal dysfunction. In our case VUR developed and the excretory function of the left kidney was decreased. Both cosmetic problems and accompanying VUR can be an indication for surgical treatment. Therefore, in the surgical management of urethral duplication, a thorough work-up is needed to detect associated anomalies and to identify the type of duplication. Our case highlights the need to investigate accompanying co-existing conditions, such as VUR, which can result in kidney dysfunction. Radiological evaluation, including voiding cystourethrography, retrograde urethrogram and renal ultrasound, are important to delineate the physiology of the genitourinary system and the anatomy of the urethral duplication and for comprehensive follow-up.