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T Chaiworapongsa

Publications and source records attributed to T Chaiworapongsa.

At least 19 recordsLinked to original sources
PubMed2006

Dermatitis as a component of the fetal inflammatory response syndrome is associated with activation of Toll-like receptors in epidermal keratinocytes.

AIMS: Microbial invasion of the amniotic cavity (MIAC) elicits a fetal inflammatory response such as funisitis and chorionic vasculitis. However, little is known about the changes of fetal skin during MIAC. Toll-like receptors recognize microbial products and initiate an immune response. The aims of this study were to examine histopathological features of fetal skin exposed to MIAC and to assess the changes in Toll-like receptor (TLR)-2 and TLR-4 expression. METHODS AND RESULTS: Skin samples were obtained from fetal autopsies (n = 12). The cases were classified according to the presence (n = 8) or absence (n = 4) of acute chorioamnionitis and analysed by immunohistochemistry using a panel of antibodies. Leucocytic infiltrates into the superficial dermis were observed in cases with chorioamnionitis; the majority of inflammatory cells were neutrophils, lymphocytes and histiocytes. TLR-2 immunoreactivity in the skin was stronger in fetuses with chorioamnionitis than in those without this condition. However, immunoreactivity of TLR-4 in the fetal skin was constitutively expressed, regardless of the presence or absence of chorioamnionitis. CONCLUSIONS: This study demonstrates for the first time that fetal dermatitis can be detected and is part of the fetal inflammatory response syndrome (FIRS). We propose that this 'FIRS-associated fetal dermatitis' is a fetal counterpart of chorioamnionitis.

Abnormalities, Multiple↗
PubMed2006

The preterm parturition syndrome.

The implicit paradigm that has governed the study and clinical management of preterm labour is that term and preterm parturition are the same processes, except for the gestational age at which they occur. Indeed, both share a common pathway composed of uterine contractility, cervical dilatation and activation of the membranes/decidua. This review explores the concept that while term labour results from physiological activation of the components of the common pathway, preterm labour arises from pathological signalling and activation of one or more components of the common pathway of parturition. The term "great obstetrical syndromes" has been coined to reframe the concept of obstetrical disease. Such syndromes are characterised by: (1) multiple aetiology; (2) long preclinical stage; (3) frequent fetal involvement; (4) clinical manifestations that are often adaptive in nature; and (5) gene-environment interactions that may predispose to the syndromes. This article reviews the evidence indicating that the pathological processes implicated in the preterm parturition syndrome include: (1) intrauterine infection/inflammation; (2) uterine ischaemia; (3) uterine overdistension; (4) abnormal allograft reaction; (5) allergy; (6) cervical insufficiency; and (7) hormonal disorders (progesterone related and corticotrophin-releasing factor related). The implications of this conceptual framework for the prevention, diagnosis, and treatment of preterm labour are discussed.

Cytokines↗
PubMed2005

The prevalence and clinical significance of amniotic fluid 'sludge' in patients with preterm labor and intact membranes.

OBJECTIVE: To determine the prevalence and clinical significance of amniotic fluid (AF) 'sludge' observed during transvaginal ultrasound examination of the cervix in patients with preterm labor and intact membranes, and in those with uncomplicated pregnancies. METHODS: This retrospective study included patients with preterm labor and intact membranes (n = 84) and those with uncomplicated term pregnancies (n = 298). The outcome variables included the occurrence of documented microbial invasion of the amniotic cavity (MIAC), histological chorioamnionitis, examination-to-delivery interval, admission to the neonatal intensive care unit (NICU), a composite neonatal morbidity, perinatal death, and delivery within 48 h, 7 days, and < 35 weeks and < 32 weeks. Statistical analysis included Chi-square test, stepwise logistic regression analysis and survival analysis. RESULTS: The prevalence of AF 'sludge' was 1% (3/298) in patients with uncomplicated term pregnancies and 22.6% (19/84) in those with preterm labor and intact membranes. Among patients with preterm labor and intact membranes: (1) cervical length < or = 15 mm was present in 58.3% (49/84) of the patients; (2) the prevalence of MIAC and histological chorioamnionitis was 12.1% (7/58) and 32.9% (25/76), respectively; (3) the rate of spontaneous preterm delivery within 48 h, 7 days, and < 32 weeks and < 35 weeks of gestation was 13.6% (8/59), 28.8% (17/59), 39.5% (17/43) and 50.8% (30/59), respectively; (4) patients with AF 'sludge' had a higher frequency of positive AF cultures [33.3% (6/18) vs. 2.5% (1/40), P = 0.003] and histological chorioamnionitis [77.8% (14/18) vs. 19% (11/58), P < 0.001] than those without AF 'sludge'; (5) a higher proportion of neonates born to patients with AF 'sludge' was admitted to the NICU [64.3% (9/14) vs. 12.9% (8/62), P < 0.01], had a composite neonatal morbidity [36.8% (7/19) vs. 13.8% (9/65), P = 0.04] and died in the perinatal period [36.8% (7/19) vs. 4.6% (3/65), P = 0.001] than those born to women without 'sludge'; (6) a higher proportion of patients with AF 'sludge' had spontaneous delivery within 48 h [42.9% (6/14) vs. 4.4% (2/45), P = 0.001], within 7 days [71.4% (10/14) vs. 15.6% (7/45), P < 0.001], < 32 weeks [75% (9/12) vs. 25.8% (8/31), P = 0.005] and < 35 weeks [92.9% (13/14) vs. 37.8% (17/45), P < 0.001] than those without AF 'sludge'; and (7) patients with AF 'sludge' had a shorter examination-to-delivery interval than those without AF 'sludge' [AF 'sludge' median, 1 (IQR, 1-5) days vs. no AF 'sludge' median, 33 (IQR, 18-58) days; P < 0.001]. CONCLUSION: The presence of AF 'sludge' in patients with preterm labor and intact membranes is a risk factor for MIAC, histological chorioamnionitis and impending preterm delivery.

Adult↗
PubMed2004

Prenatal diagnosis of membranous ventricular septal aneurysms and their association with absence of atrioventricular valve 'offsetting'.

Congenital aneurysm of the membranous portion of the ventricular septum in association with absence of atrioventricular valve 'offsetting' was diagnosed in two fetuses at 29 and 34 weeks. In the first case the fetus had a normal karyotype and no other structural heart defects, whereas in the second case there was a partial deletion of the long arm of chromosome 5 and an absent pulmonary valve syndrome. The association of absence of 'offsetting' with aneurysms of the membranous ventricular septum may represent spontaneous closure of ventricular septal defects initially extended to the inlet.

Adolescent↗
PubMed2004

Individualized growth assessment of fetal soft tissue using fractional thigh volume.

OBJECTIVES: The main goals of this study were to introduce fractional thigh volume (TVol) as a new soft tissue parameter for fetal growth evaluation, define its relationship to menstrual age, and develop individualized fetal growth standards based on Rossavik growth models. METHODS: A prospective, longitudinal study of 22 fetuses was conducted with conventional biometry and TVol measurements by three-dimensional ultrasonography. Infant growth outcomes were determined from modified neonatal growth assessment scores. Rossavik functions (P = c(t)k+s(t)) were used to fit complete datasets to examine relationships between TVol and model coefficients. Second-trimester models were subsequently specified from the linear slopes of growth curves before 28.0 menstrual weeks with each fetus acting as its own control. Third-trimester trajectories and birth measurements were predicted for standard growth parameters and TVol. Observed and predicted measurements were compared using percent deviations and growth potential realization index values. Four additional infants, with serial prenatal scans and postnatal evidence of intrauterine growth restriction (IUGR), were also evaluated. RESULTS: All 22 fetuses had no evidence of growth abnormalities after delivery. Accelerated soft tissue deposition occurred in the fetal thigh by 28 menstrual weeks. A mean TVol start point of 9.0 +/- 1.4 menstrual weeks was consistent with embryological studies of thigh development. Rossavik functions fitted all TVol trajectories well (mean R2 = 0.998 +/- 0.002). By fixing the coefficient k at its mean value (2.976), the fit did not change and the variabilities of coefficients c and s were reduced. The mean percent deviation between observed and predicted third-trimester TVol measurements was -0.048 +/- 7.5%. Relatively early pathological deviations were observed for TVol in all four fetuses with IUGR; in these cases the abdominal circumference was abnormal in only one fetus and thigh circumference in none. CONCLUSIONS: Individualized growth assessment can be used to accurately predict TVol during the third trimester of pregnancy and at birth. Expected growth trajectories, from second-trimester data, do not rely on population-based standards because each fetus serves as its own control. This new parameter may allow earlier detection and improved monitoring of fetal soft tissue abnormalities such as IUGR.

Female↗
PubMed2004

First-trimester three-dimensional ultrasonographic findings in a fetus with frontonasal malformation.

A case of a frontonasal malformation observed during the first trimester with three-dimensional ultrasonography and fetoscopy is reported. Absence of the nasal bone and a poorly characterized nose were visualized at 11 5/7 weeks by two-dimensional ultrasonography. Rendered three-dimensional ultrasound images revealed absence of the nasal bridge, widely spaced frontal bones and hypertelorism. Fetoscopy, performed at 12 3/7 weeks, confirmed the hypertelorism and showed a broad translucent nose with a flat nasal bridge. The final diagnosis of frontonasal malformation was made at autopsy after pregnancy termination. A review of prenatally diagnosed cases as well as the various syndromes having frontonasal malformation as a common denominator is presented.

Abnormalities, Multiple↗
PubMed2004

Fetal cardiac dysfunction in preterm premature rupture of membranes.

BACKGROUND: Preterm premature rupture of membranes (PROM) is associated with one-third of preterm births. In about 50% of preterm PROM cases, the fetuses will elicit a fetal inflammatory response syndrome (FIRS). FIRS is associated with the impending onset of preterm labor, periventricular leukomalacia, neonatal sepsis, and long-term handicap, including the development of bronchopulmonary dysplasia and cerebral palsy. The fetal myocardium is a potential target organ of proinflammatory cytokines released during FIRS. The objective of this study was to determine whether preterm PROM is associated with functional changes in the fetal heart, as determined by fetal echocardiography. METHODS: A retrospective study was conducted to assess the diastolic function of fetuses with preterm PROM with documented microbial invasion of the amniotic cavity (n = 25), preterm PROM without microbial invasion of the amniotic cavity (n = 42), and fetuses from normal pregnancies (control group = 150). Pregnancies with multiple gestation, fetal distress, fetuses that were small for gestational age, and major congenital anomalies were excluded. Fetal echocardiography studies were performed with two-dimensional ultrasound, color Doppler imaging and pulsed Doppler ultrasound. Non-parametric statistics were used for comparisons. A p value of < 0.05 was considered significant. RESULTS: The prevalence of positive amniotic fluid cultures for micro-organisms in patients with preterm PROM was 35.8% (24/67). Ureaplasma urealyticum was the most frequent isolate, either alone (41.7%; 10/24) or with other micro-organisms (29.2%; 7/24). Fetuses with preterm PROM had a higher delta early diastolic filling/atrial contraction (E/A) peak velocity ratio, a higher delta E/A velocity-time integral (VTI) ratio, a lower delta A peak velocity, a lower delta A VTI, and a lower A VTI/total VTI ratio in the mitral valve compared to those with uncomplicated pregnancies. The delta E/A peak velocity ratio was significantly higher and the delta A VTI significantly lower in fetuses with preterm PROM and microbial invasion of the amniotic cavity than in those with preterm PROM without microbial invasion of the amniotic cavity. CONCLUSIONS: Preterm PROM is associated with changes in fetal cardiac function consistent with increased left ventricular compliance. These observations were also noted in fetuses with microbial invasion of the amniotic cavity. Our findings suggest that fetal cardiac function is altered in preterm PROM and, in particular, in cases with intra-amniotic infection.

Echocardiography↗
PubMed2003

Epithelial cell-derived neutrophil-activating peptide-78 is present in fetal membranes and amniotic fluid at increased concentrations with intra-amniotic infection and preterm delivery.

Intra-amniotic secretion and abundance of epithelial cell-derived neutrophil-activating peptide (ENA)-78, a potent chemoattractant and activator of neutrophils, was studied in the context of term and preterm parturition. Staining of ENA-78 immunoperoxidase was localized predominantly to chorionic trophoblasts and amniotic epithelium in term and preterm gestational membranes, with weaker and less consistent staining in decidual cells. The abundance of ENA-78 in membrane tissue homogenates was significantly increased ( approximately 4-fold) with term labor in amnion (n = 15), and with preterm labor ( approximately 30-fold) in amnion and choriodecidua (n = 31). In amnion tissue homogenate extracts, ENA-78 levels were positively correlated with the degree of leukocyte infiltration (r2 = 0.481). In amniotic fluids, median ENA-78 levels from pregnancies with preterm labor without intra-amniotic infection were significantly lower (P < 0.01 by ANOVA) than those from pregnancies with preterm deliveries with infection; levels in samples derived from term pregnancies were similar before and after labor. Production of ENA-78 by amnion monolayers was stimulated in a concentration-dependent fashion by both interleukin-1beta and tumor necrosis factor alpha. Production of ENA-78 by choriodecidual explants was increased modestly after 2-4 h of exposure to lipopolysaccharide (5 microg/ml). An immunoreactive doublet ( approximately 8 kDa) was detected in choriodecidual explant-conditioned media by immunoblotting. We conclude that ENA-78, derived from the gestational membranes, is present in increased abundance in the amniotic cavity in response to intrauterine infection and, hence, may play a role in the mechanism of infection-driven preterm birth and rupture of membranes secondary to leukocyte recruitment and activation.

Amniotic Fluid↗
PubMed2003

Three-dimensional ultrasound fetal lung volume measurement: a systematic study comparing the multiplanar method with the rotational (VOCAL) technique.

OBJECTIVES: This study was designed to compare a conventional multiplanar technique for three-dimensional (3D) ultrasound measurement of fetal lung volume with a rotational method using VOCAL trade mark (Virtual Organ Computer-aided AnaLysis). METHODS: Thirty-two fetuses with a variety of conditions at risk for pulmonary hypoplasia were studied. 3D volume data sets of the fetal lungs were acquired using a commercially available ultrasound system. The right and left lung volumes were calculated separately using VOCAL and the multiplanar technique. The level of agreement between two independent observers in categorizing the 3D volume data set as measurable or non-measurable was determined. The interobserver and intermethod variabilities were also evaluated for both methods. RESULTS: The intermethod variability was excellent (correlation r = 0.93 and r = 0.96 for the left and right lung, respectively), and there was substantial agreement between the results of both approaches (limits of agreement - 4.4 to 8.9 and - 3.4 to 4.8 mL for the right and left lung, respectively). Fetal lung estimation with VOCAL had a significantly higher interobserver variability than the multiplanar technique. Interobserver agreement in categorizing lung volume data sets as measurable or non-measurable was lower when VOCAL was used. CONCLUSION: Fetal lung volume measurements can be undertaken interchangeably using the multiplanar technique or the rotational method with VOCAL. However, the latter was less reproducible (lower degree of agreement and significantly higher interobserver variability) than the former.

Female↗
PubMed2003

Antimicrobial peptides in amniotic fluid: defensins, calprotectin and bacterial/permeability-increasing protein in patients with microbial invasion of the amniotic cavity, intra-amniotic inflammation, preterm labor and premature rupture of membranes.

OBJECTIVE: Neutrophil defensins (HNP 1-3), bactericidal/permeability-increasing protein (BPI) and calprotectin (MRP8/14) are antimicrobial peptides stored in leukocytes that act as effector molecules of the innate immune response. The purpose of this study was to determine whether parturition, premature rupture of the membranes (PROM) and microbial invasion of the amniotic cavity (MIAC) are associated with changes in amniotic fluid concentrations of these antimicrobial peptides. STUDY DESIGN: Amniotic fluid was retrieved by amniocentesis from 333 patients in the following groups: group 1, mid-trimester with a subsequent normal pregnancy outcome (n = 84); group 2, preterm labor and intact membranes without MIAC who delivered at term (n = 36), or prematurely (n = 52) and preterm labor with MIAC (n = 26); group 3, preterm PROM with (n = 26) and without (n = 26) MIAC; and group 4, term with intact membranes in the absence of MIAC, in labor (n = 52) and not in labor (n = 31). The concentrations of HNP 1-3, BPI and calprotectin in amniotic fluid were determined by specific and sensitive immunoassays. Placentae of patients in both preterm labor with intact membranes and preterm PROM groups who delivered within 72 h of amniocentesis were examined. Non-parametric statistics, receiver-operating characteristic (ROC) curves and Cox regression models were used for analysis. A p value of < 0.05 was considered statistically significant. RESULTS: Intra-amniotic infection was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin in both women with preterm labor and intact membranes, and women with preterm PROM. Preterm PROM was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin. Preterm parturition was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin, while parturition at term was associated with a significant increase in amniotic fluid concentrations of immunoreactive HNP 1-3. Among patients with preterm labor and intact membranes, elevation of amniotic fluid HNP 1-3, BPI and calprotectin concentrations was associated with intra-amniotic inflammation, histological chorioamnionitis and a shorter interval to delivery. CONCLUSION: MIAC, preterm parturition and preterm PROM are associated with increased amniotic fluid concentrations of immunoreactive HNP 1-3, BPI and calprotectin. Moreover, elevated amniotic fluid concentrations of BPI, immunoreactive HNP 1-3 and calprotectin are associated with intra-amniotic inflammation, histological chorioamnionitis and shorter amniocentesis-to-delivery interval in patients presenting with preterm labor with intact membranes.

Amnion↗
PubMed2003

Differences in the fetal interleukin-6 response to microbial invasion of the amniotic cavity between term and preterm gestation.

BACKGROUND/OBJECTIVE: Fetal inflammatory response has been implicated as a mechanism of multi-system organ injury in preterm and term neonates. Microbial invasion of the amniotic cavity (MIAC) is frequently associated with a fetal inflammatory response. However, there are no studies comparing the fetal response to MIAC in term and preterm gestations. The purpose of this study was to compare the umbilical cord plasma interleukin-6 (IL-6) concentrations in term and preterm neonates in the presence or absence of MIAC. STUDY DESIGN: Umbilical cord blood was obtained at birth from 252 neonates whose mothers had an amniocentesis within 48 h of delivery (preterm delivery, n = 62; term delivery, n = 190). MIAC was defined as a positive amniotic fluid culture for bacteria or genital mycoplasmas. IL-6 was measured by a sensitive and specific immunoassay. RESULTS: The median IL-6 concentration in umbilical cord plasma was significantly higher in preterm neonates than in term neonates (median 13.4 pg/ml, range 0.1-676 pg/ml vs. median 3.2 pg/ml, range 0.1-408 pg/ml; p < 0.0001). In the context of MIAC, the median umbilical cord plasma IL-6 concentration was significantly higher in preterm than in term neonates (median 31.6 pg/ml, range 1.4-676 pg/ml vs. median 11.7 pg/ml, range 1.3-82 pg/ml, respectively; p < 0.05). Neonates born to mothers with a positive amniotic fluid culture had a significantly higher median IL-6 concentration than neonates born to mothers with a negative amniotic fluid culture (preterm: median 31.6, range 1.4-676 pg/ml vs. median 8.0, range 0.1-656 pg/ml; p < 0.05 and term: median 11.7, range 1.3-82 pg/ml vs. median 3.1, range 0.1-408 pg/ml; p < 0.01, respectively). CONCLUSIONS: The preterm fetus is capable of mounting a systemic cytokine response as measured by IL-6 in its peripheral blood. In the setting of MIAC, a fetal IL-6 response is higher in preterm than in term gestation.

Amnion↗
PubMed2003

Maternal serum of women with pre-eclampsia reduces trophoblast cell viability: evidence for an increased sensitivity to Fas-mediated apoptosis.

OBJECTIVE: Pre-eclampsia or 'toxemia of pregnancy' has been attributed to the presence of a circulating 'toxin' which disappears from peripheral blood after delivery of the placenta. However, the presence, nature and effects of this toxin have eluded characterization. Increased trophoblast apoptosis has been observed in the placenta of women with pre-eclampsia, and it is possible that this biological phenomenon is important for the genesis of the disease and mediated through a soluble factor(s) present in maternal blood. This study was designed to test the hypothesis that serum from women with pre-eclampsia changes trophoblast viability. Moreover, we sought to examine whether this effect could be mediated through changes in sensitivity to Fas/Fas ligand-mediated apoptosis. STUDY DESIGN: H8 trophoblast cells were cultured with serum obtained from normal pregnant women (n = 48) and patients with pre-eclampsia (n = 12). Cell viability was determined by the Cell Titer 96 assay. Fas sensitivity was determined by treating the cells with an agonist anti-Fas antibody or a blocking anti-Fas ligand antibody. RESULTS: Serum from normal pregnant women did not affect trophoblast cell viability. In contrast, serum from pre-eclamptic women reduced trophoblast viability, and this was enhanced by treatment with an anti-Fas antibody. This effect was reversed by the treatment with a blocking anti-Fas ligand antibody. CONCLUSION: Serum from women with pre-eclampsia induces the cytotoxicity of a first-trimester trophoblast cell line (H8). This effect appears to be related to changes in trophoblast sensitivity to Fas-mediated apoptosis. These findings suggest that a factor present in the maternal blood of patients with pre-eclampsia may have a role in the genesis of the syndrome.

Apoptosis↗
PubMed2003

Amniotic fluid levels of immunoreactive monocyte chemotactic protein-1 increase during term parturition.

OBJECTIVE: Parturition is characterized by an influx of inflammatory cells into gestational tissues, a phenomenon conducive to increased myometrial contractility, cervical ripening and decidual/membrane activation. Monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant and activator of monocytes/macrophages, is expressed in gestational tissues and, thus, may participate in the final common pathway of labor. This study was undertaken to determine whether the amniotic fluid concentrations of immunoreactive MCP-1 are altered with gestational age or spontaneous labor at term with and without prelabor rupture of the gestational membranes. We also sought to identify intrapartum differences in the concentrations of immunoreactive MCP-1 between the upper and lower amniotic fluid compartments. METHODS: A cross-sectional study was conducted to assess the concentrations of immunoreactive MCP-1 in amniotic fluid. Amniotic fluid samples were obtained from 225 women as follows: (1) women undergoing mid-trimester (14-18 weeks of gestation) amniocentesis for genetic indications, whose pregnancy outcome was normal (n = 84); (2) women in labor (n = 52) and not in labor (n = 31) at term, with intact gestational membranes; (3) women with rupture of the gestational membranes in labor (n = 18) and not in labor (n = 26), at term; and (4) women in labor at term for whom paired amniotic fluid samples were obtained through transvaginal and transabdominal amniocenteses (n = 14). Immunoreactive MCP-1 was assessed with a specific and sensitive immunoassay that had been validated for amniotic fluid. Non-parametric statistics were used for analysis. RESULTS: Immunoreactive MCP-1 was detected in all amniotic fluid samples. Spontaneous human parturition was associated with a significant increase in the amniotic fluid concentrations of immunoreactive MCP-1 (not in labor: median 595 pg/ml, range 183-3579 pg/ml vs. in labor: median 862 pg/ml, range 183-9609 pg/ml; p = 0.01). The median amniotic fluid concentrations of immunoreactive MCP-1 were significantly higher in the lower amniotic fluid compartment than in the upper amniotic fluid compartment (lower compartment: median 2913 pg/ml, range 1360-17080 pg/ml vs. upper compartment: median 1603 pg/ml, range 1070-8062 pg/ml; p = 0.004.). Spontaneous rupture of the gestational membranes at term was not associated with a significant change in the amniotic fluid concentrations of immunoreactive MCP-1. CONCLUSIONS: Immunoreactive MCP-1 is a physiological constituent of the amniotic fluid. The amniotic fluid levels of immunoreactive MCP-1 increase during spontaneous labor at term. A topographic difference in the concentration of immunoreactive MCP-1 was observed in the amniotic cavity, with higher concentrations being noted in the lower amniotic fluid compartment, as compared with the upper amniotic fluid compartment. These findings support the hypothesis that MCP-1 may play a role in the final common pathway of spontaneous labor.

Adolescent↗
PubMed2003

The effect of antibiotic therapy on intrauterine infection-induced preterm parturition in rabbits.

OBJECTIVE: The purpose of this study was to determine whether early antibiotic administration to pregnant rabbits with intrauterine infection could prevent preterm delivery and perinatal mortality. STUDY DESIGN: Under hysteroscopic guidance, pregnant rabbits at 70% gestation (21 days) were allocated to three groups: (1) control group, transcervical inoculation of 0.2 ml phosphate-buffered saline (n = 16); (2) infection group, transcervical inoculation of 0.2 ml of 10(5) colony-forming units (CFU) of Escherichia coli (n = 21); (3) infection and antibiotics group, transcervical inoculations of 0.2 ml of 10(5) CFU of E. coli and ampicillin-sulbactam 150 mg/kg every 8 h intramuscularly (n = 32). To examine the consequences of treatment delay, animals in the latter group were subdivided to receive antibiotics at different time intervals of 0, 6, 11 and 18 h after bacterial inoculation. The intervals from bacterial inoculation to delivery and litter survival were documented. Systemic (rectal) temperatures were recorded at 4 h intervals through the first 36 h and every 12 h until delivery. A p value of < 0.05 was considered significant. RESULTS: All rabbits inoculated with E. coli without antibiotic treatment delivered prematurely. The median inoculation-to-delivery interval was significantly shorter in the infected group than in the control group (median 32 h, range 14.9-76.5 h vs. median 219 h, range 173-246 h, respectively; p < 0.0001). Antibiotic administration within 12 h of inoculation, but not after 18 h, increased duration of pregnancy (by reducing the rate of preterm delivery) and neonatal survival (0% vs. 71%; p < 0.0001). The mean temperatures at delivery of animals whose treatments began at 6 and 11 h post-inoculation were significantly lower than those untreated with antibiotics or those treated at 18 h post-inoculation (p < 0.0001 for each comparison). CONCLUSIONS: Antibiotic administration can prolong pregnancy and reduce perinatal mortality if administered early (within 12 h of microbial inoculation) in a rabbit model of ascending intrauterine infection.

Ampicillin↗
PubMed2003

Maternal and fetal inflammatory responses in unexplained fetal death.

OBJECTIVE: The role of intra-amniotic infection in the etiology of fetal death has been proposed. This study was conducted to determine the prevalence of microbial invasion of the amniotic cavity (MIAC) and the frequency of maternal and/or fetal inflammation in patients presenting with a fetal death. METHODS: A prospective study was conducted in patients with a fetal death. Amniocenteses were performed for clinical indications (karyotype), as well as to assess the microbiological and cytological state of the amniotic cavity. Fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. An amniotic fluid white blood cell count and glucose determinations were also performed. Histological examination of the placenta was conducted to identify a maternal inflammatory response (acute chorioamnionitis) or a fetal inflammatory response (funisitis). RESULTS: This study included 44 patients with intrauterine fetal death. The median gestational age at diagnosis was 30.1 weeks (range 16.3-40.4 weeks). One patient had documented MIAC (1/44). Acute histological chorioamnionitis was found in 20.9% (9/43), but a fetal inflammatory response was observed in only 2.3% (1/43) of cases. One patient had a positive amniotic fluid culture for Streptococcus agalactiae (group B streptococcus). CONCLUSION: Histological chorioamnionitis was present in 20.9% of cases, but MIAC could be demonstrated with conventional microbiological techniques in only one case. A fetal inflammatory response was nine times less frequent than a maternal inflammatory response (maternal 20.9% vs. fetal 2.3%, p = 0.008) in cases of fetal death.

Adult↗
PubMed2003

Unexplained fetal death is associated with changes in the adaptive limb of the maternal immune response consistent with prior antigenic exposure.

OBJECTIVE: The causes of fetal death are largely unknown. CD4 T cells have been classified according to the expression of the CD45 isoforms into 'naive-like' T cells (CD45RA) and 'memory-like' T cells (CD45RO). An increase in the percentage of the CD45RO has been interpreted as indicating prior antigenic exposure of the host and, in newborns, evidence of infection. The purpose of this study was to determine whether unexplained fetal death was associated with a change in the proportion of 'naive-like' and 'memory-like T cells' in the maternal blood, as determined by the CD45 isoforms on the surface of CD4+ lymphocytes. STUDY DESIGN: A prospective study was conducted to compare the CD45 sub-population of lymphocytes in patients with intrauterine fetal death (n = 26) and normal pregnancy (n = 89). The percentages of CD45RA+, CD45RO+ and CD45RA+/CD45RO+ on CD4+ T lymphocytes were determined in maternal blood using flow cytometry and monoclonal antibodies. Results were reported as a percentage of CD4+ lymphocytes. Non-parametric statistics were used for analysis. A p value of < 0.05 was considered significant. RESULTS: Patients with intrauterine fetal death had a higher percentage of CD45RO+ CD4+ T lymphocytes than normal pregnant women (fetal death: median 57.7%, range 35.4-78.6 vs. normal pregnancy: median 49.9%, range 19.1-86.8; p = 0.004). Fetal death was associated with a lower median percentage of CD45RA+ CD4+ lymphocytes than in normal pregnant women (fetal death: median 32.3%, range 15.3-58.0 vs. normal pregnancy: median 40.2%, range 11.2-67.3; p = 0.01). There was no significant difference in the percentage of cells with dual expression (CD45RA+/CD45RO+) between the study groups. CONCLUSION: Prior exposure to microbial products (bacterial or viral) or other unidentified antigens may result in a shift of the sub-population of 'naive-like' T cells to 'memory-like' T cells in mothers with unexplained fetal death.

Adolescent↗
PubMed2003

Neonates born to pre-eclamptic mothers have a higher percentage of natural killer cells (CD3-/CD56+16+) in umbilical cord blood than those without pre-eclampsia.

OBJECTIVE: Maternal endothelial dysfunction and intravascular inflammation have been implicated in the mechanisms of disease responsible for the clinical syndrome of pre-eclampsia. Recently, the activation of the innate limb of the immune response (neutrophils and monocytes) in the fetal circulation has been reported in neonates born to mothers with pre-eclampsia. Natural killer (NK) cells are identified morphologically as a subpopulation of lymphocytes, but functionally as one component of the innate immune system. NK cells participate in the control of viral or bacterial infection, regulation of hematopoiesis, production of cytokines and cytotoxicity of neoplastic cells. Accumulating evidence suggests that the innate system is required for mounting an adequate adaptive response. NK cells, originally defined as effector cells of the innate immune system, may also play a role as regulatory cells for the adaptive immune system. This study was designed to determine the proportion of the NK cell subset of lymphocytes in umbilical cord blood of neonates born to mothers with and without pre-eclampsia. METHODS: A cross-sectional study including neonates of mothers with (n = 48) and those without pre-eclampsia (control group) (n = 72) was conducted. Pre-eclampsia was diagnosed in the presence of hypertension and proteinuria. The control group consisted of neonates (premature and term) with no evidence of acute inflammation within the extraplacental membranes (chorioamnionitis). Umbilical cord blood was collected at the time of delivery, and assayed using monoclonal antibodies for selective cluster differentiation (CD) antigens in order to determine the proportion of NK cells as a percentage of total lymphocytes. The immunophenotypic characteristic was determined using flow cytometry, and NK cells were identified by positivity of CD16 and CD56 without CD3 (CD3-/CD56+16+). Log transformation of the percentage of NK cells was performed. Parametric statistics were used for analysis. Multiple regression analysis was utilized to examine the contribution of potentially confounding factors on the proportion of NK cells. A p value of < 0.05 was considered statistically significant. RESULTS: Neonates born to mothers with pre-eclampsia had a significantly higher percentage of NK cells (CD3-/CD56+16+) than those in the control group (pre-eclampsia, mean +/- SD 17 +/- 9% vs. control, mean +/- SD 12 +/- 7.5%; p = 0.001). Multiple regression analysis suggested that umbilical cord blood pH of < 7.2, labor with vaginal delivery and maternal pre-eclampsia were associated with an increased percentage of NK cells in umbilical cord blood. CONCLUSIONS: Pre-eclampsia is associated with a higher NK cell (CD3-/CD56+16+) subset of lymphocytes in umbilical cord blood than in the control group. This difference cannot be explained by fetal acidosis or the presence of labor.

CD3 Complex↗