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.

Are chorioamnionitis and funisitis associated with lung injury or pulmonary function of premature infants? / 中国新生儿科杂志

Objective To investigate the relationship between histological chorioamnionitis (HCA),funisitis (FV) and lung injury in preterm infants.Method Data of preterm infants with gestational age of less than 34 weeks,who were born in our Hospital and admitted to the neonatal ward during the period of October 2015 to August 2016 were retrospectively collected.According to reports of placenta pathologies,participants were assigned into three groups,non-infection group,HCA group and HCA + FV group.Demographic and infectious characteristics,duration of respiratory support,partial pressure of oxygen (PaO2) and pulmonary function testing results at corrected gestational age 40 weeks were compared among groups.Result A total of 151 preterm infants were included,with 33 cases in noninfection group,61 cases in HCA group and 57 cases in HCA + FV group.Non-invasive ventilation duration and number of days in room air in HCA + FV groups were both longer than those in the non-infection group [0 (0,66) h vs.0 (0,0) h,65 (0,176) h vs.0 (0,8) h].The duration of invasive ventilation and total ventilation days in HCA + FV group were longer than those of the other two groups [0 (0,4) h vs.0 (0,0) and 0 (0,0) h,0 (0,99) h vs.0 (0,0) and 0 (0,52) h],the differences were statistically significant (P ＜ 0.05).However,there was no significant difference of PaO2 after 0.5 hour respiratory support among the three groups (P ＞ 0.05).Pulmonary functional parameters,such as respiratory frequency,VPEF/TE,VPEF/VE,VPEF and TPEF,gradually decreased with the degree of inflammatory progress,but there was no statistically significant difference (P ＞ 0.05).Conclusion HCA and FV are highly associated with premature lung injury.The worse the placental inflammation is,the longer respiratory support duration will be needed or required.However,HCA and FV may have no significant effect on lung function.

Umbilical Cord Blood Matrix Metalloproteinase-9 Levels are associated with Funisitis / 대한주산의학회잡지

PURPOSE: Intrauterine inflammation (IUI) is a leading cause of preterm delivery. Although matrix metalloproteinase-8 (MMP-8) and intercellular adhesion molecule-1 (ICAM-1) are known to be related with IUI, it has not been fully elucidated whether MMP-9 or ICAM-3 is associated with IUI. We performed this study to determine whether the levels of tumor necrosis factor-alpha (TNF-alpha), MMP-9 and ICAM-3 in umbilical cord blood of preterm infants are associated with chorioamnionitis, funisitis or bronchopulmonary dysplasia. METHODS: Eighty-two pairs of pregnant women and their preterm newborns <35 weeks gestation were enrolled. Levels of TNF-alpha, MMP-9 and ICAM-3 in umbilical cord blood were measured using immunoassays and compared with results of histological examination of placenta and clinical data of the study participants. RESULTS: The level of MMP-9 in umbilical cord blood was significantly associated with the presence of funisitis (P =0.007). The level of TNF-alpha in umbilical cord blood was significantly associated with the development of bronchopulmonary dysplasia (P =0.030). However, presence of chorioamnionitis or funisitis was not associated with development of bronchopulmonary dysplasia. With the establishment of receiver operating characteristic (ROC) curve, the best cut-off value for umbilical blood MMP-9 was 99.42 pg/mL in identification of funisitis. The area under a constructed ROC curve for prediction of funisitis was 0.847 (standard error, 0.112; 95% confidence interval, 0.750-0.917). CONCLUSION: Measurement of MMP-9 concentration in umbilical cord blood may be an alternative way to predict whether a preterm infant has been exposed to IUI. Further study with larger numbers of subjects will be necessary to elucidate the association between the presence of IUI and neonatal adverse outcome.

Comparison of the Incidences of Neonatal Morbidities by Different Criteria of Histologic Chorioamnionitis in Extremely Low Gestational Age Newborns

PURPOSE: The objective of the study was to compare the incidences of the neonatal morbidity, using the various criteria of histologic chorioamnionitis (HC) in the extremely low gestational age newborns (ELGANs), who were born before the 28 weeks of gestational age. METHODS: Sixty two ELGANs who were born and admitted to the Seoul National University Bundang Hospital from 2007 to 2011 were included. A total of seven criteria of HC were made according to the site within the placenta and the extent of the neutrophil infiltration. The incidence of the major neonatal morbiditiy was compared between the HC-exposed and the HC-unexposed ELGANs according to each criterion of HC. RESULTS: There were no significant differences in the birth weight, gestational age, and sex between the HC-exposed and the HC-unexposed ELGANs by any criteria. The incidence of respiratory distress syndrome (RDS) was significantly lower in the HC-exposed ELGANs only in the criterion of any extent of the umbilical cord inflammation (funisitis). The incidence of retinopathy of prematurity (ROP) was significantly higher in the HC-exposed ELGANs in the criterion of any extent of amnionitis or funisitis. The incidences of other major morbidities did not differ between the HC-exposed and the HC-unexposed ELGANs by any criteria. CONCLUSION: The presence of funisitis reflected the lung maturation effect of chorioamnionitis, as indicated by the decreased incidence of RDS. Among other major neonatal morbidities, only ROP was significantly associated with HC. The ROP occurred more frequently in the funisitis or amnionitis-exposed ELGANs.

Relationship between Maternal Serum C-Reactive Protein, Funisitis and Early-Onset Neonatal Sepsis

The aim of this study was to determine whether maternal serum C-reactive protein (CRP) is of value in predicting funisitis and early-onset neonatal sepsis (EONS) in women with preterm labor or preterm premature rupture of membranes (PROM). This retrospective cohort study included 306 consecutive women with preterm labor or preterm PROM who delivered preterm singleton neonates (23-35 weeks gestation) within 72 hr of CRP measurement. The CRP level was measured with a highly sensitive immunoassay. The sensitivity, specificity, positive predictive value, and negative predictive value of an elevated serum CRP level (> or = 8 mg/L) were 74.1%, 67.5%, 32.8%, and 92.4% for funisitis, and 67.7%, 63.3%, 17.2%, and 94.6% for EONS, respectively. Logistic regression analysis demonstrated that elevated levels of serum CRP were significantly associated with funisitis and EONS, even after adjusting gestational age. The maternal serum CRP level obtained up to 72 hr before delivery is an independent predictor of funisitis and EONS in women with preterm labor or preterm PROM. A low serum CRP level (< 8 mg/L) has good negative predictive value in excluding funisitis and EONS, and may therefore be used as a non-invasive adjunct to clinical judgment to identify low-risk patients.

The Effects of Histologic Chorioamnionitis and Funisitis on Outcome of Very Low Birth Weight Infants / 대한주산의학회잡지

PURPOSE: The association of chorioamnionitis and preterm birth, chronic lung disease (CLD) and periventricular leukomalacia (PVL) has been reported, however, controversy is still present. The aim of this study was to investigate how the histologic chorioamnionitis (HC) and/or funisitis (F) affected the clinical outcomes of very low birth weight infants (VLBWI, <1,500 g). METHODS: The medical records of VLBWI who were admitted at NICU, Chonnam University Hospital from 2004 to 2008 with placental biopsy results were reviewed retrospectively. Maternal (n=324) and neonatal (n=363) characteristics and their clinical outcomes were investigated according to placental pathology. RESULTS: HC (+) mothers (n=88) had higher premature rupture of membranes and preterm labor, and lower rates of preeclampsia/eclampsia (p<0.05 at each) than HC (-) mothers (n=236). HC (+) infants (n=103) had lower birth weight and Apgar score, higher rate of Cesarean section and lower intrauterine growth restriction (p<0.05 at each) rates than HC (-) infants (n=260). HC (+) infants had higher rates of respiratory distress syndrome and mortality, and lower rate of necrotizing enterocolitis (p<0.05 at each), however, when adjusted for verified multivariables in the multiple regression analysis, HC didn't affect the clinical outcomes. CONCLUSION: It was known that intrauterine infection or fetal inflammatory response syndrome (FIRS) was associated with neonatal outcomes. However, our results suggest that HC with or without funisitis is not an isolated risk factor to affect the clinical outcomes in VLBWI.

Influence of histologic chorioamnionitis and funisitis on the level of peripheral blood C-reactive protein at birth in preterm infants / 소아과

PURPOSE: The objective of this study is to determine the change of C-reactive protein (CRP) levels in the peripheral blood of preterm infants at birth according to the stage of intrauterine inflammation. METHODS: A total of 187 infants (<32 weeks of gestation) were divided into a "no histologic chorioamnionitis" [HCAM (-), n=85] group and a "histologic chorioamnionitis" [HCAM (+), n=102] group according to placental pathologic findings. Furthermore, the HCAM (+) group was subdivided into a "funisitis" [F (+), n=49] group and a "no funisitis" [F (-), n=53] group and also into a "funisitis/amnionitis" [FA (+), n=58] group and an "isolated chorio-deciduitis" [FA (-), n=44] group. High-sensitivity CRP levels in the peripheral blood at birth were measured. RESULTS: Peripheral blood CRP levels were significantly higher in the HCAM (+), F (+), F (-), and FA (+) groups than in the HCAM (-) group, but were not significantly different between the FA (-) and HCAM (-) groups. In addition, peripheral blood CRP levels were significantly higher in the F (+) and FA (+) groups than in the F (-) and FA (-) groups, respectively. For identification of amnionitis or funisitis, a cut-off value of 0.02 mg/dL was chosen. Clinical chorioamnionitis, proven early onset sepsis, histologic chorioamnionitis, and funisitis had higher incidences in infants with peripheral blood CRP levels higher than 0.02 mg/dL. CONCLUSION: The present study shows that peripheral blood CRP levels at birth in preterm infants born before 32 weeks' gestation is significantly increased in amnionitis or funisitis and might reflect the progress of histologic chorioamnionitis.

Falsely diagnosed umbilical edema due to necrotizing funisitis during prenatal ultrasound examination as an umbilical cord cyst corrected by postpartum histological test / 대한산부인과학회지

Umbilical cord cyst is correlated with the fetal chromosomal defects or its structural abnormality; therefore, the follow-up evaluations on fetal growth, lesion size, and concomitant congenital malformation are essential. Thus, when a prenatal ultrasonogram suspects an umbilical cord cyst, karyotyping is strongly recommended to rule out any chromosomal abnormality. The pathologic findings of necrotizing funisitis are paraumbilical exudates due to inflammatory changes, the secondary calcification change of the exudates, thrombosis, and sometimes edema of the umbilical cord. Even though incidence of umbilical cord cyst is rare, it must be differentiated from a cord edema caused by necrotizing funisitis. We have encountered a patient with a suspicious umbilical cord cyst in the third trimester of her pregnancy but the postpartum diagnosis turned out to be an umbilical cord edema by necrotizing funisitis, so we investigated the case with brief comparison to other literature.

Falsely diagnosed umbilical edema due to necrotizing funisitis during prenatal ultrasound examination as an umbilical cord cyst corrected by postpartum histological test / 대한산부인과학회지

Umbilical cord cyst is correlated with the fetal chromosomal defects or its structural abnormality; therefore, the follow-up evaluations on fetal growth, lesion size, and concomitant congenital malformation are essential. Thus, when a prenatal ultrasonogram suspects an umbilical cord cyst, karyotyping is strongly recommended to rule out any chromosomal abnormality. The pathologic findings of necrotizing funisitis are paraumbilical exudates due to inflammatory changes, the secondary calcification change of the exudates, thrombosis, and sometimes edema of the umbilical cord. Even though incidence of umbilical cord cyst is rare, it must be differentiated from a cord edema caused by necrotizing funisitis. We have encountered a patient with a suspicious umbilical cord cyst in the third trimester of her pregnancy but the postpartum diagnosis turned out to be an umbilical cord edema by necrotizing funisitis, so we investigated the case with brief comparison to other literature.

The Relationship Among Umbilical Cord Plasma Matrix Metalloproteinase-8 and Interleukin-6 Concentration, Funisitis, Amniotic Fluid Infection and Neonatal Outcome / 대한산부인과학회잡지

OBJECTIVE: The purpose of this study was to determine whether funisitis is associated with changes in the umbilical cord plasma concentration of interleukin-6 (IL-6) and matrix metalloproteinase-8 (MMP-8), microbial invasion of the amniotic cavity and neonatal outcome. METHODS: The relationship among the presence of funisitis, IL-6 and MMP-8 concentrations in umbilical cord plasma at birth, the results of amniotic fluid culture performed within 5 days of birth was examined in 83 consecutive singleton births (20-35 weeks' gestation). Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel wall or Wharton's jelly. The IL-6 and MMP-8 concentration was measured with a specific immunoassay. Amniocentesis was performed in 47 patients within 5 days of birth. RESULTS: (1) Funisitis was present in 21.7% of patients. (2) Patients with funisitis had a significant higher cord plasma IL-6 concentration, but had no significant difference in cord plasma MMP-8 concentration. (3) Clinical chorioamnionitis was more common in patients with funisitis than those without funisitis. (4) A cord plasma IL-6 > 6.34 pg/ml had a sensitivity of 77.8% and a specificity of 75.4% in the identification of funisitis. (5) No correlation between cord blood plasma IL-6 concentration and MMP-8 concentration was found. (6) There was no significant correlation between gestational age at birth and cord blood plasma MMP-8 concentrations, but there appeared to be a trend to increase of cord plasma MMP-8 concentrations as gestational ages at birth were increased. (7) Neonates with congenital sepsis had a significantly higher cord plasma IL-6 and MMP-8 concentration than those without congenital sepsis. CONCLUSION: In patient with funisitis, umbilical cord plasma IL-6 concentrations were higher than those without funisitis, but umbilical cord plasma MMP-8 concentrations had no significant difference in each group. The umbilical cord plasma IL-6 and MMP-8 can be useful as a predictor of the occurrence of congenital sepsis in preterm infant.