Interaction of chorioamnionitis at term with maternal, fetal and obstetrical factors as predictors of neonatal mortality: a population-based cohort study.

BACKGROUND: Chorioamnionitis is a frequent complication of pregnancy and is known to be associated with serious adverse post-natal outcomes including death. However, the assessment of fetal well-being in labor in the context of chorioamnionitis is often challenging because of fetal tachycardia. Identifying specific risk factors for adverse neonatal outcomes in the context of chorioamnionitis could therefore be of paramount importance. This study aimed to determine if maternal and fetal risk factors for increased neonatal mortality and early neonatal mortality are modified in the context of chorioamnionitis in term pregnancies. METHODS: A retrospective population-based cohort study using the United States birth/infant death public file from 2011 to 2013 was performed, including all live births at 37 weeks gestation and beyond. Interaction between chorioamnionitis and maternal demographic variables as well as labor and delivery potential risk factors were analyzed for association with neonatal death (< 28 days) and early neonatal death (< 7 days) using multivariate logistic regressions. RESULTS: Among 9,034,428 live births, the prevalence of chorioamionitis was 1.29% (95% CI 1.28-1.30%). The incidence of neonatal death and early neonatal death were 0.09 and 0.06% in the chorioamnionitis group versus 0.06 and 0.04% in the no chorioamnionitis group (p = 0.0003 and < 0.0001), respectively. Smoking was significantly associated with neonatal death and early neonatal death in the context of chorioamnionitis (OR 2.44, CI:1.34-4.43/ 2.36 CI:1.11-5.01) but was either less strongly or not associated in the absence of chorioamnionitis (OR 1.24, CI:1.14-1.35/0.93, CI:0.82-1.05). The association between gestational age (37 weeks compared to 39 weeks) and neonatal death was more important in the context of chorioamnionitis (OR = 3.19, CI: 1.75-5.82 versus 1.63, CI: 1.49-1.79). Multivariate analysis identified the following risk factors for neonatal death and/or early neonatal death: low maternal education, extreme maternal age, obesity (BMI > 35 kg/m2), late or no prenatal care, diabetes, meconium-stained amniotic fluid, gestational ages other than 39 weeks, neonatal weight < 2500 g and delivery by vacuum or caesarian. CONCLUSIONS: Smoking as well as early term have a positive interaction with chorioamnionitis for the risk of neonatal mortality. This should be taken into account when counseling pregnant women and managing laboring pregnant women with suspected chorioamnionitis.

Placenta, Secret Witness of Infant Morbidities: The Relationship Between Placental Histology and Outcome of the Premature Infant.

OBJECTIVE: The microscopic and macroscopic features of the placenta can contribute to the clinical understanding of premature delivery. The aim of our study was to figure out the relationship between the histopathological findings of the placentas of premature deliveries and its effects on neonatal morbidity and mortality. MATERIAL AND METHOD: The placentas of 284 singleton preterm infants with < 35 weeks of gestation were examined. Three groups were created as the normal, chorioamnionitis and vasculopathy groups according to the histopathological findings in the placentas of the subjects. RESULTS: The mean gestational age of the infants in the study group was 30.5 ± 3.2 weeks, and the mean birth weight was 1588 ± 581 g. The pathology was normal in ninety-six (33.8%), vasculopathy in 153 (53.9%) and chorioamnionitis in 35 (12.3%). The gestation age of the infants was lower in the chorioamnionitis group. Moreover, retinopathy of prematurity, early onset neonatal sepsis, and duration of respiratory support were found to be higher in the chorioamnionitis group. In the vasculopathy group, preeclampsia and small for gestational age were found to be significantly higher. CONCLUSION: Histopathological findings of the placentas from preterm deliveries provided important data in determining the etiology of preterm delivery and outcomes of infants. Infants delivered by mothers with chorioamnionitis were particularly found to be more preterm, and these preterm infants would have a longer hospital stay, higher respiratory support requirement, and more serious morbidities.

Effect of chorioamnionitis on mortality, early onset neonatal sepsis and bronchopulmonary dysplasia in preterm neonates with birth weight of < 1,500 grams.

The aim of the study was to investigate the effects of chorioamnionitis on mortality and early onset neonatal sepsis (EONS) and bronchopulmonary dysplasia (BPD) in preterm neonates with birth weight < or = 1,500 g. The study included 395 preterm infants born at the Zagreb Clinical Hospital Center, from January 2001 to December 2005. All the placentas from preterm deliveries were sent for pathological examination. The patients were categorized into two groups: one including patients with chorioamnionitis at placental histology (47%) and the other control group without chorioamnionitis (53%). Neonates were distributed into 3 groups according to gestational age: the first group with 132 (33%) infants born at < or = 28 weeks of gestation, the second with 202 (52%) infant born from 29 to 32 weeks of gestation and the third with 61 (15%) infants born at > or = 33 weeks gestation. Chorioamnionitis was diagnosed significantly more often in the first gestational age group (91/132-69% of infants, chi2 = 51.307, p < 0.05). The outcome was lethal in 67/395 (17%) patients; 55% of them had chorioamnionitis (chi2 = 2.421, p > 0.05). Lethal outcome ensued in 54/132 (41%) infants from the first gestational age group; 30/54 (55%) were born from pregnancies complicated by chorioamnionitis. In comparison with the control group, mortality was significantly higher in the group of premature infants with gestation < or = 28 weeks whose placentas showed chorioamnionitis (chi2 = 7.645, p < 0.01). EONS was probable or confirmed in 100/395 (25%) infants; in 66/100 (66%) infants pregnancy was complicated by chorioamnionitis (chi2 = 22.396, p < 0.01). BPD developed in 25/395 (6%) infants; in 12/25 (48%) infants placentas showed chorioamnionitis (chi2 = 0.022, p > 0.05). In conclusion, premature neonates from pregnancies complicated by chorioamnionitis are more often born at < or = 28 weeks of gestation. Chorioamnionitis in neonates whose gestation is < or = 28 weeks leads to a significantly higher rate of mortality than in neonates with a longer gestation period. A greater incidence of EONS was proven in the group of infants with chorioamnionitis. The difference between the incidence of BPD in preterm infants born from pregnancies complicated by chorioamnionitis and the control group was not significant.

Histological chorioamnionitis: effects on premature delivery and neonatal prognosis.

BACKGROUND: Chorioamnionitis is closely related to premature birth and has negative effects on neonatal morbidity and mortality. METHODS: In this prospective study, 43 mothers who delivered earlier than 35 gestational weeks and their 57 infants were evaluated clinically and with laboratory findings. Placentas and umbilical cords were investigated histopathologically for chorioamnionitis and funisitis. RESULTS: The overall frequency of clinical and histological chorioamnionitis (HCA) was 8.3% and 23.2%, respectively. The frequency of HCA was 47.3% and 83.3% in mothers delivered <32 weeks and <30 weeks, respectively. Maternal demographic and clinical findings and also leukocyte and C-reactive protein values were not indicative of HCA. Infants of mothers with HCA had significantly lower Apgar scores together with higher SNAP-PE-II and CRIB scores. These infants had increased mechanical ventilator and surfactant requirements, higher incidences of patent ductus arteriosus, early sepsis, and bronchopulmonary dysplasia, and higher mortality rates. The effect of HCA on neonatal morbidity and mortality was more prominent than the effect of low birthweight and lower gestational age. CONCLUSION: Chorioamnionitis not only causes premature deliveries, but is also associated with neonatal complications and increased mortality. Clinical findings and infectious markers in mother or infant do not predict the diagnosis of histological chorioamnionitis. Therefore, placental histopathology may have a role in predicting neonatal outcome in premature deliveries, especially those below 30 weeks.

Upregulated amniotic fluid cytokines and chemokines in emergency cerclage with protruding membranes.

PROBLEM To identify the prognostic factors for pregnancy outcome in women who received emergency cerclage for dilated cervix with protruding membranes. METHOD OF STUDY A prospective cohort study was performed, and a total of 14 women who received emergency cerclage were included. Clinical features and laboratory findings including amniotic fluid cytokines and chemokines were compared between women who had successful pregnancy (survival group, n = 6) and those who had perinatal death (non-survival group, n = 8). Five healthy pregnant women served for normal controls for amniotic fluid study. RESULTS The overall neonatal survival was 42.9% in women with emergency cerclage. Serum C-reactive protein levels on postoperative day 3 and 7 were significantly higher in non-survival group when compared with those in survival group (P = 0.002, P = 0.01). Amniotic fluid levels of interleukin (IL)-1α, IL-1ß, IL-6, IL-8, IL-10, tumor necrosis factor-α, and monocyte chemoattractant protein-1 levels of the patients were significantly higher than those of normal controls. Amniotic fluid levels of IL-1α, IL-1ß, and IL-8 were significantly increased in the non-survival group when compared with those of the survival group. CONCLUSION Systemic and local inflammatory markers including proinflammatory cytokines and chemokines may predict pregnancy outcome in women with emergency cerclage for dilated cervix with protruding membranes.

Neonatal and neurodevelopmental outcomes of very low birth weight infants with histologic chorioamnionitis.

OBJECTIVE: To determine survival and neurodevelopmental outcomes at 18 months corrected age among very low birth weight infants ≤ 32 weeks gestation with histologic chorioamnionitis. STUDY DESIGN: Observational, regionalized, single-center cohort study with prospective follow-up. RESULTS: Of the 628 infants meeting the selection criteria, 303 (48%) were born to mothers with evidence of histologic chorioamnonitis. Neonates with histologic chorioamnonitis were of lower gestational age and birth weight. On univariate analysis, they were more likely to have hypotension, bronchopulmonary dysplasia, severe intraventricular hemorrhage, severe retinopathy of prematurity, early-onset sepsis, and death. Infants with histologic chorioamnonitis were more likely to have any neurodevelopmental impairment, specifically, mental delay with a lower mental developmental index. When adjusting for perinatal variables, histologic chorioamnonitis had a protective effect on mortality rates (adjusted OR = 0.44, 95% CI: 0.24-0.8; P = .01; n = 619), had a nonsignificant effect on neurodevelopmental impairment (adjusted odds ratio = 1.33, 95% CI: 0.82-2.17; P = .25; n = 496), and was associated with a 4-point lower mental developmental index at 18-months follow-up (adjusted difference -3.93, 95% CI: -7.52 to -0.33; P = .03; n = 496). CONCLUSIONS: Although infants with histologic chorioamnonitis were at an increased risk for death and neurodevelopmental impairment, after multivariate analyses, histologic chorioamnonitis was not associated with adverse long-term outcomes. Results suggest fetal protection from treatment-responsive maternal infection and inflammation.

Corioamnionitis: repercusión perinatal / Chorioamnionitis: perinatal impact

Determinar en las gestantes complicadas con corioamnionitis las características, factores maternos y las repercusiones maternas y perinatales. Estudio descriptivo, retrospectivo, epidemiológico y analítico. Departamento de Obstetricia y Ginecología, Hospital "Dr. Adolfo Prince Lara", Universidad de Carabobo, Puerto Cabello, Estado Carabobo. En las 44 pacientes las características maternas que predominaron fueron: residentes en barrios (45,45 por ciento), solteras y concubinas (77,27 por ciento), edad materna 20-24 años (40,91 por ciento) y antecedente personal hipertensión (20,45 por ciento). El diagnóstico de ingreso destacó la rotura prematura de membranas 50 por ciento e infección uro-vaginal 13,6 por ciento; eran multigestas 50,0 por ciento, y en 52,28 por ciento la edad del embarazo fue de 36 semanas y menos, en 84,08 por ciento hubo conducción-inducción del trabajo de parto, terminaron en cesárea 45,45 por ciento. Factores de riesgo: múltiples tactos (4 y más) 40,9 por ciento y tiempo entre rotura de membranas e inicio de trabajo de parto mayor de 12 horas 18,44 por ciento. El diagnóstico se hizo por la clínica y laboratorio; tratadas con antibióticos en su totalidad, acompañadas por oxitócicos 68,18 por ciento. Recién nacidos de sexo femeninos 48,84 por ciento, peso entre 3 000- 3 499 g 31,31 por ciento y tallas 45-49 cm 28,89 por ciento; índice Apgar 6 o menos 28,94 por ciento. La morbilidad perinatal neonatal fue 39,47 por ciento, especialmente por sepsis y patología respiratoria; la morbilidad materna 56,81 por ciento, por sepsis y anemia; la perinatal global 28,88 por ciento, la fetal 15,55 por ciento y la neonatal 13,13 por ciento. La corioamninitis se relacionó con múltiples tactos intraparto, el tiempo de rotura prematura de membranas al inicio del parto y las infecciones uro-vaginales; sus repercusiones revelaron elevadas cifras de morbimortalidad materna. Toda señala a implemantar programas preventivos y mejorar la atención materno-neonatal

To study the pregnant women complicated with chorioamnionitis, knowing its impact, identify characteristics and factors related maternal and establish maternal and perinatal impact. Observational, descriptive, retrospective, epidemiological and analytical study of 44 pregnant women complicated with chorioamnionitis, which occurred during the period 2005-2009. Department of Obstetrics and Gynecology, Hospital "Dr. Adolfo Prince Lara ", Universidad de Carabobo, Puerto Cabello, Estado Carabobo. Maternal characteristics were predominant in patients living in urban region (45.45 percent), single and concubines (77.27 percent), maternal age between 20-24 years (40.91 percent) and personal history hypertension (20.45 percent). In obstetrical situation, first admission diagnosis of premature rupture of membranes 50 percent and infection urology and vaginal 13.6 percent, were multiparous 50 percent, with 52.28 percent of gestational age 36 weeks and less, in 84.08 percent were induction-conduction of labor, ending 45.45 percent cesarean. Outstanding risk factors, vaginal digital exam (4 and more) 40.9 percent, exam gynecology and time between rupture of membranes at the onset of labor more than 12 hours 18.44 percent, diagnosis was mainly clinical and laboratory, were treated with antibiotics in its entirety accompanied by oxytocic 68.18 percent. The neonates were 48.84 percent female, weighing between 3 000 and 3 499 g, 31.31 percent and 28.89 percent height 45-49 cm, Apgar Index 6 or less 28.94 percent. Neonatal perinatal morbidity was 39.47 percent, represented especially by sepsis and respiratory disease, maternal morbidity 56.81 percent, given by sepsis and anemia in various forms, the overall perinatal mortality 28.88 percent, fetal mortality 15.55 percent, neonatal mortality 13.13 percent, was decisive sepsis and prematurity in all these deaths. The chorioamnionitis related to exam gynecology, premature rupture of membranes at the start time delivery..

The relationship between leukemoid reaction and perinatal morbidity, mortality, and chorioamnionitis in low birth weight infants.

OBJECTIVES: Neonatal leukemoid reaction (NLR) is relatively rare and considered as a white blood cell (WBC) count ≥50×10(9)/l . The aim of this study was to investigate the association of NLR with neonatal morbidity and mortality and maternal chorioamnionitis in low birth weight infants. METHODS: In this case-controlled retrospective study, the medical records of 1200 newborn infants with a birth weight <2500g admitted to the neonatal unit over a period of 5 years were reviewed. The infants who developed features of NLR (n=17, 1.4%) formed the study group, while the remainder without NLR, matched for gestational age and birth weight (n=123), formed the control group. A chart review was performed and salient demographic, clinical, and laboratory data abstracted. A statistical analysis was subsequently performed on this data. RESULTS: The mean WBC and absolute neutrophil counts of infants with NLR were significantly higher than those in the control group. The peak time of NLR was at 7.9±3.6 (interquartile range (IQR) 1-30) days and on average it improved within 4.1±1.95 (IQR 2-9) days. It was noted that those infants with NLR were mostly born by vaginal delivery and their mothers had a higher rate of early rupture of the membranes and chorioamnionitis. NLR was associated with a 4-fold increase in sepsis, 20-fold increase in intraventricular hemorrhage, 54-fold increase in bronchopulmonary dysplasia, and 6-fold increase in mortality. In the study group, those infants whose mothers had chorioamnionitis had a higher rate of early rupture of the membranes and they developed sepsis and intraventricular hemorrhage more often than those whose mothers did not have clinical chorioamnionitis. CONCLUSIONS: In low birth weight newborn infants, NLR is significantly associated with sepsis, intraventricular hemorrhage, bronchopulmonary dysplasia, and a high mortality rate. Also, those infants with NLR are more likely to be born to mothers with chorioamnionitis and they face sepsis and intraventricular hemorrhage more often.

[Role of chorioamnionitis in the development of sepsis during labor].

The authors emphasize the importance of pyoseptic diseases of the reproductive system, which are a major cause of maternal mortality. Clinical and morphological criteria have been elaborated to diagnose a special form of obstetric sepsis during labor. The inflammatory infiltrate was investigated by immunohistochemical studies using monoclonal antibodies and tumor necrosis factor. Lesions of the fetal integument and placenta have been found to be an initiating factor. The fetal integuments with signs of chorioamnionitis serve as the entry of pathogens during the septic process, promoted the development and course of septicemia during labor and complications, such as disseminated intravascular coagulation and infectious-toxic shock.

Reduced mortality and increased BPD with histological chorioamnionitis and leukocytosis in very-low-birth-weight infants.

OBJECTIVE: To investigate the association between leukocytosis, mortality and bronchopulmonary dysplasia (BPD) in very-low-birth-weight infants (VLBW) born to mothers with histological chorioamnionitis. STUDY DESIGN: A retrospective cohort study from a single level 3 neonatal intensive care unit. The study sample included infants born to mothers with histological chorioamnionitis (n=252). Total white blood cells (WBCs) after birth were measured. Leukocytosis was defined as a total WBC count >30 000 per mm(3) in the first 2 days of life. Outcomes investigated included BPD and death. Both unadjusted and multivariable analyses were carried out. RESULT: After controlling for potential confounding variables, infants who developed a leukocytosis after birth had increased odds of BPD (4.6, 95% confidence interval (95% CI): 2.0 to 10.3), but decreased odds of death (0.3, 95% CI: 0.1 to 0.90). CONCLUSION: In our population of VLBW infants born to mothers with histological chorioamnionitis, leukocytosis after birth is associated with a decrease in mortality but an increase in BPD.

Airway concentrations of angiopoietin-1 and endostatin in ventilated extremely premature infants are decreased after funisitis and unbalanced with bronchopulmonary dysplasia/death.

A systemic inflammatory response of the fetus, reflected by histologic funisitis, is a risk factor for bronchopulmonary dysplasia (BPD). Impaired pulmonary angiogenesis accompanied by simplification and rarification of alveoli is a histologic hallmark of BPD. Angiopoietin-1 mediates vascular development, maturation, and stabilization. Endostatin mainly acts as an angiostatic factor. We hypothesized that funisitis was associated with changes of endostatin and angiopoietin-1 concentrations in the airways and that an imbalance between the factors might be associated with BPD or death. We measured concentrations of angiopoietin-1 and endostatin by enzyme-linked immunosorbent assay in tracheobronchial aspirate fluid samples of 42 ventilated preterm infants during postnatal days 1 through 15. The secretory component for IgA served as reference protein. A standardized histologic examination was used to distinguish three groups: chorioamnionitis, funisitis, and controls without inflammation. Concentrations of the mediators steadily decreased. Funisitis was associated with lower concentrations of both proteins, which might impair their physiologic activities in pulmonary angiogenesis. An increase of the ratio angiopoietin-1/endostatin until day 7 of life indicated a shift of the mediators potentially favoring angiogenesis. However, infants, who developed BPD or died, had a decreased ratio on days 1, 3, and 15, suggesting an imbalance toward inhibition of pulmonary angiogenesis.

Chorioamnionitis and ontogeny of circulating prostaglandin and thromboxane in preterm infants.

Our objective was to determine the effect of chorioamnionitis on plasma prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) during the first week in preterm infants. Plasma PGE2 and TxB2 were measured at 1, 3, and 7 days of age in preterm infants (birth weights 501 to 1500 g), with ( N = 26) and without ( N = 22) chorioamnionitis. Infants with maternal chorioamnionitis had significantly lower mean gestational age ( P = 0.0001) and birth weight ( P = 0.03) and a marginally higher rate of bronchopulmonary dysplasia (37% versus 12.5, P = 0.05), a result that may be related to the lower mean gestational age. Plasma PGE2 and TxB2 varied widely, more so on the first day but did not significantly differ between the two groups. TxB2 was lower among infants who died or developed morbidities. Circulating PGE2 and TxB2 concentrations in preterm infants in the first week vary considerably, are relatively unaltered by chorioamnionitis, and are lower in association with mortality and clinical morbidities. Further research on their role in the causation of adverse neonatal outcomes is necessary.

Cord blood cytokine levels in neonates born to mothers with prolonged premature rupture of membranes and its relationship with morbidity and mortality.

The purpose of this study was to determine cord blood cytokine levels and their relationship with morbidity and mortality in neonates with prolonged, premature rupture of membranes (PPROM). Forty two premature neonates of 29-35 weeks gestational age with PPROM exceeding 24 hours were considered as the PPROM group and simultaneously, 41 premature neonates without PPROM were considered as the control group. All the neonates were admitted to the Neonatology Unit for further evaluation of subsequent complications such as early neonatal sepsis, pneumonia, intraventicular haemorrhage (IVH), respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC) and chronic lung disease (CLD). Cord blood and mothers' blood samples were obtained during delivery in both groups and tested for IL-6, IL-8 and TNF-alpha levels. Twenty one percent of patients with PPROM had histological chorioamnionitis. The risk for developing early neonatal sepsis increased significantly in neonates whose mothers had histological chorioamnionitis (p < 0.05). There was a statistically significant relationship between PPROM and risk of developing NEC (p < 0.05); no significant increase was seen as regards early neonatal sepsis, IVH, RDS, pneumonia, or BPD. The mean IL-8 levels in cord blood and mothers' serum were significantly higher in the PPROM group (p < 0.001, p< 0.005). In addition, IL-6 levels found in mothers' serum were significantly higher than those found in the control group (p < 0.01). However, levels in cord blood were similar (p > 0.05). TNF-alpha levels were similar in both groups (p > 0.05). Neonates who developed NEC had higher IL-8 levels in their cord blood when compared to those without NEC (p < 0.05). In conclusion, the presence of PPROM increases the risk of chorioamnionitis. In addition, PPROM increases the risk of NEC, and patients who developed NEC had significantly higher cord blood IL-8 values. We may conclude that patients with PPROM and higher IL-8 levels in cord blood might be considered as at possible risk of NEC.

Systemic fetal inflammation and reduced concentrations of macrophage migration inhibitory factor in tracheobronchial aspirate fluid of extremely premature infants.

OBJECTIVE: Macrophage migration inhibitory factor is a proinflammatory mediator of innate immunity, enhances cell growth, and plays a role in preterm delivery. We speculated that funisitis, reflecting fetal systemic inflammation, would be associated with higher concentrations of macrophage migration inhibitory factor in airways of extremely premature infants. STUDY DESIGN: We measured macrophage migration inhibitory factor by enzyme linked immunosorbent assay in tracheobronchial aspirate fluid of 35 ventilated infants less than 30 weeks' gestational age, throughout the first week of life. Three groups were distinguished histologically: chorioamnionitis, funisitis, and control. RESULTS: Unexpectedly, funisitis was associated with significantly decreased macrophage migration inhibitory factor in tracheobronchial aspirate fluid on day 1 (P < .01) and levels remained lower than in the chorioamnionitis group thereafter. For the 35 patients in total, macrophage migration inhibitory factor steadily declined. CONCLUSION: Decreased macrophage migration inhibitory factor concentrations in airways of extremely premature infants with systemic fetal inflammation early in life might predispose them to pulmonary infection and interfere with maturation of the lung, contributing to adverse pulmonary outcome.

Impact of subclinical chorioamnionitis on maternal and neonatal outcomes.

BACKGROUND: Chorioamnionitis is considered to be one of the main causes of preterm labor and has been associated with an adverse perinatal outcome in preterm infants. The controversy about the benefits/risks of delaying labor is a critical issue concerning the management of chorioamnionitis. METHODS: The database between July 2001 and March 2006 was reviewed for women with singleton pregnancies between 22 and 28 weeks of gestation and with chorioamnionitis diagnosed on admission by amniotic fluid neutrophil elastase level. Women were classified according to the severity of chorioamnionitis (group A, amniotic fluid neutrophil elastase level of 0.15-1 microg/ml; B, 1-10 microg/ml; and C, > or = 10 microg/ml). During expectant management, serum C-reactive protein levels monitored the remission and aggravation of chorioamnionitis. Following deliveries, placentas were examined for histologic chorioamnionitis. RESULTS: One hundred women were enrolled (group A, 38; B, 34; C, 28). The latency period until delivery was significantly longer in group A than in groups B and C. C-reactive protein levels just before delivery were higher than those on admission in 61% of the overall cases. Histologic chorioamnionitis and funisitis were manifested in 90.4% and 65.5%, respectively. Intrauterine fetal demise (4 cases) and neonatal and postneonatal deaths during admission (10 cases) were observed. Bronchopulmonary dysplasia was the most common major morbidity noted in groups B and C. CONCLUSION: Chorioamnionitis could be controlled but is hard to cure. Higher levels of amniotic fluid neutrophil elastase are associated with a shorter interval from admission to delivery in women with subclinical chorioamnionitis.

Cytokine production and visualized effects in the feto-maternal unit. Quantitative and topographic data on cytokines during intrauterine disease.

BACKGROUND: A large array of cytokines show high activity in amniotic fluid. Attempts have been made to quantify the concentrations or to track rising levels for diagnostic purposes when examining disturbances of the feto-maternal unit. However, the kinetics of cytokine production in the amniotic fluid are not well understood, and there is lack of knowledge about concomitant levels in fetal and maternal blood. EXPERIMENTAL DESIGN: The presence of cytokines in fetal and placental cells was demonstrated by immunohistochemistry using mAb. Cytokines were quantified by enzymimmunoassay in amniotic fluid and fetal and maternal blood. This was done with regard to two disease states that quite frequently complicate the course of pregnancy, namely chorioamnionitis and intrauterine growth retardation. The cytokines examined were G-CSF, GM-CSF, TNF-alpha, IL-1, IL-6, and IL-8. RESULTS: In chorioamnionitis, all cytokines, except GM-CSF, were elevated about 100 times in the amniotic fluid. An accompanying increase in maternal and fetal blood was only found for IL-6 and G-CSF; IL-8 was elevated in fetal blood only. Intrauterine growth retardation was characterized by elevated levels of TNF-alpha in the amniotic fluid, whereas G-CSF, GM-CSF, and IL-1 beta were significantly reduced. Immunohistochemistry showed that under normal conditions the cytokines are to be found in a characteristic distribution in certain cell types in the fetus, the placenta, and the placental bed. With rising concentrations, more cells seemed to be recruited for cytokine production, especially macrophages and decidual cells. In chorioamnionitis, fetal extramedullary granulopoiesis was augmented, and in intrauterine growth retardation, erythropoiesis as well as granulopoiesis were depressed. CONCLUSIONS: Not only inflammatory disease but also intrauterine growth retardation is characterized by a changing cytokine pattern. Alterations in fetal hematopoiesis observed at postmortem examination of perinatal deaths can be correlated to changes in cytokine production within the feto-maternal unit.