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PubMed2005

Effect of dose on response to adrenocorticotropin in extremely low birth weight infants.

CONTEXT: Various cosyntropin doses are used to test adrenal function in premature infants, without consensus on appropriate dose or adequate response. OBJECTIVE: The objective of this study was to test the cortisol response of extremely low birth weight infants to different cosyntropin doses and evaluate whether these doses differentiate between groups of infants with clinical conditions previously associated with differential response to cosyntropin. DESIGN: The design was a prospective, nested study conducted within a randomized clinical trial of low-dose hydrocortisone from November 1, 2001, to April 30, 2003. SETTING: The setting was nine newborn intensive care units. PATIENTS: The patients included infants with 500-999 g birth weight. INTERVENTION: The drug used was cosyntropin, at 1.0 or 0.1 microg/kg, given between 18 and 28 d of birth. MAIN OUTCOME MEASURE: We measured the cortisol response to cosyntropin. RESULTS: Two hundred seventy-six infants were tested. Previous hydrocortisone treatment did not suppress basal or stimulated cortisol values. Cosyntropin, at 1.0 vs. 0.1 microg/kg, yielded higher cortisol values (P < 0.001) and fewer negative responses (2 vs. 21%). The higher dose, but not the lower dose, showed different responses for girls vs. boys (P = 0.02), infants receiving enteral nutrition vs. not (P < 0.001), infants exposed to chorioamnionitis vs. not (P = 0.04), and those receiving mechanical ventilation vs. not (P = 0.02), as well as a positive correlation with fetal growth (P = 0.03). A response curve for the 1.0-microg/kg dose for infants receiving enteral nutrition (proxy for clinically well infants) showed a 10th percentile of 16.96 microg/dl. Infants with responses less than the 10th percentile had more bronchopulmonary dysplasia and longer length of stay. CONCLUSIONS: A cosyntropin dose of 0.1 microg/kg did not differentiate between groups of infants with clinical conditions that affect response. We recommend 1.0 microg/kg cosyntropin to test adrenal function in these infants.

Bronchopulmonary Dysplasia↗
PubMed1999

Mucinase and sialidase activity of the vaginal microflora: implications for the pathogenesis of preterm labour.

Evidence linking bacterial vaginosis (BV) to chorioamnionitis and spontaneous preterm birth is mounting. Successful treatment of BV could reduce the rate of late miscarriage and preterm birth. Mucinase and sialidase activity have been implicated in the pathogenesis of BV. This study extends the work of previous studies to investigate sialidase, other known mucin degrading enzymes and overall mucin degrading activity in samples of vaginal fluid from women with and without BV. Samples from 31 women were diagnosed for BV, and tested for enzyme activity using established assays. Activity was recorded in all samples. Significant increases in activity were detected in BV samples for sialidase using a mucin (BSM P<0.005) and serum type glycoprotein (AGP P<0.005) substrates, beta-galactosidase (P<0.001), and beta-N-acetylhexosaminidase (P<0.01). No significant increases in BV patients were detected in O-glycanase, proteinase, arylesterase, sulphatase or whole mucinase activities. These results support the hypothesis that certain BV-associated enzymes may detrimentally affect the mucosal barrier, permitting bacteria access to the uterus.

Bacterial Proteins↗
PubMed2002

Choriodecidual infection and preterm birth.

Of all U.S. births, 11% occur preterm. These infants are responsible for the majority of perinatal mortality and morbidity. Infants at highest risk are those born weighing < 1000 g and those born at <28 weeks gestation. Recent evidence suggests that the majority of these preterm births are caused by bacterial infections of the chorioamnion, with the organisms originating in the vagina. The mechanisms leading to preterm labor and rupture of membranes involve an inflammatory response involving increased production of cytokines, prostaglandins, and metalloproteases. Results of treatment trials to eradicate the infection and reduce preterm birth have been mixed.

Amniotic Fluid↗
PubMed2003

Myometrial inflammation in human delivery and its association with labor and infection.

The presence of inflammation in decidual and myometrial samples as defined by histopathologic examination and the association between the myometrial inflammation and different maternal infectious morbidity and labor-related clinical variables were evaluated in 648 consecutive women who underwent cesarean section at various gestational periods. Altogether, 1,205 histologic (559 decidual and 646 myometrial) samples were studied. In normal pregnancies, myometrial inflammatory lesions were detected rarely before parturition, indicating their abnormality in these cases. After ruptured fetal membranes with advanced cervical dilatation and in patients with clinical chorioamnionitis, myometrial samples commonly were infiltrated by leukocytes, up to moderate and marked densities. Moderate to marked myometrial inflammation showed no diagnostic value in high-risk term parturients for the prediction of postoperative endometritis. Our study is the first to show the frequency of myometrial inflammation in nonselected consecutive pregnant women and, thus, is important for better understanding the myometrial inflammatory response during human parturition.

Adolescent↗
PubMed2003

Infectious diseases detected at autopsy at an urban public hospital, 1996-2001.

Previous studies have demonstrated significant discrepancy rates between clinical and autopsy diagnoses. However, infectious diseases have not received emphasis in these studies. We conducted a study to determine whether the clinical and autopsy diagnoses of infectious diseases are concordant or discrepant and to determine discrepancy rates. Retrospective reviews of the records of 276 patients (adults, 182; fetuses and neonates, 94) who underwent autopsy during the years 1996 through 2001 were performed. Comparison of clinical and autopsy diagnoses was performed using the Goldman classification scheme. Of 182 adult patients, 137 (75.3%) had an infectious disease at autopsy. In 59 (43.1%) of 137 patients, the infectious disease diagnoses were unknown clinically. Of 94 fetuses and neonates, 45 (48%) had an infectious disease at autopsy. In 26 (58%) of 45 patients, the infectious disease diagnoses were unknown before death. There are substantial discrepancies between clinical and autopsy diagnoses of infectious diseases. In adults, acute bronchopneumonia is the infectious disease most often missed clinically; in fetuses and neonates, it is acute chorioamnionitis.

Adult↗
PubMed2004

Atypical chronic lung disease in preterm infants.

An atypical pattern of chronic lung disease (CLD) has been described in preterm infants and a potential association with intrauterine inflammation has been proposed. We aimed to describe patterns of CLD, to determine the incidence of atypical CLD, and to compare the distribution of various perinatal factors in infants with classic and atypical CLD. Information about demographics, respiratory status and various perinatal variables was collected for all neonatal admissions <1250 g. CLD was defined as oxygen dependency at 28 days of age. Ninety (51%) survivors at 28 days of age developed CLD; of these 37 (41%) were classified as atypical CLD. Factors significantly and independently associated with development of atypical CLD included being inborn, receiving natural surfactant, fewer days of mechanical ventilation within the first 28 days of life and higher birthweight. Chorioamnionitis, postnatal infection and symptomatic PDA were not found to be significantly associated with atypical CLD. Atypical CLD is a common pattern of prolonged oxygen dependency in preterm survivors and is a feature of larger, more mature babies. Our findings do not support the hypothesis that exposure to intrauterine inflammation is an important aetiological factor in the development of atypical CLD.

Bronchopulmonary Dysplasia↗
PubMed2005

Special relationships between fetal inflammatory response syndrome and bronchopulmonary dysplasia in neonates.

OBJECTIVE: To confirm previous known relationships between Fetal Inflammatory Response Syndrome (FIRS) and neonatal bronchopulmonary dysplasia (BPD) and to present information on previously unknown special relationships between inflammatory variables and BPD. STUDY DESIGN: At delivery, we obtained biological specimens including umbilical cord venous blood for plasma interleukin-6 levels, as well as placental histology and bacteriology. Among other neonatal outcomes, we collected prospective information on BPD. RESULTS: Of 141 newborns in the study, 16 had BPD; 79% of these had antecedent FIRS, 27% of those without FIRS had BPD. By multivariable regression, only very low birth weight (adjusted [adj] odds ratio [OR] 32.0, 95% Confidence Interval [CI] 5.0 to positive infinity) and FIRS (adj OR 5.7, 95% CI 1.1 to 42.3) remained significant risk factors. Escherichia coli, perhaps due to its pyogenic nature (strongly elicits inflammatory responses), may have had a special relationship with BPD. CONCLUSIONS: In our data, FIRS and neonatal BPD are highly associated. It is possible that certain pyogenic bacteria in the chorioamnion space may be implicated more often than others. CONDENSATION: Neonates having Fetal Inflammatory Response Syndrome at delivery may later develop BPD. Pyogenic bacteria, such as Escherichia coli, may be implicated more frequently.

Bronchopulmonary Dysplasia↗
PubMed2006

A sonographic short cervix as the only clinical manifestation of intra-amniotic infection.

OBJECTIVE: A sonographically short cervix is a powerful predictor of spontaneous preterm delivery. However, the etiology and optimal management of a patient with a short cervix in the mid-trimester of pregnancy remain uncertain. Microbial invasion of the amniotic cavity (MIAC) and intra-amniotic inflammation are frequently present in patients with spontaneous preterm labor or acute cervical insufficiency. This study was conducted to determine the rate of MIAC and intra-amniotic inflammation in patients with a cervical length < 25 mm in the mid-trimester. STUDY DESIGN: A retrospective cohort study was conducted of patients referred to our high risk clinic because of a sonographic short cervix or a history of a previous preterm birth. Amniocenteses were performed for the evaluation of MIAC and for karyotype analysis in patients with a short cervix. Fluid was cultured for aerobic and anaerobic bacteria, as well as genital mycoplasmas. Patients with MIAC were treated with antibiotics selected by their physician. RESULTS: Of 152 patients with a short cervix at 14-24 weeks, 57 had amniotic fluid analysis. The prevalence of MIAC was 9% (5/57). Among these patients, the rate of preterm delivery (< 32 weeks) was 40% (2/5). Microorganisms isolated from amniotic fluid included Ureaplasma urealyticum (n=4) and Fusobacterium nucleatum (n=1). Patients with a positive culture for Ureaplasma urealyticum received intravenous Azithromycin. Three patients with Ureaplasma urealyticum had a sterile amniotic fluid culture after treatment, and subsequently delivered at term. The patient with Fusobacterium nucleatum developed clinical chorioamnionitis and was induced. CONCLUSION: (1) Sub-clinical MIAC was detected in 9% of patients with a sonographically short cervix (< 25 mm); and (2) maternal parenteral treatment with antibiotics can eradicate MIAC caused by Ureaplasma urealyticum. This was associated with delivery at term in the three patients whose successful treatment was documented by microbiologic studies.

Adult↗
PubMed2006

Maternal venous procalcitonin levels do not correlate with umbilical cord blood and venous blood concentrations in the neonate.

BACKGROUND: To compare procalcitonin (PCT) concentrations between maternal blood and levels in umbilical cord or venous blood of neonates who were born with or without infection. METHODS: Forty-six women with singleton pregnancies, complicated by premature rupture of membranes, preterm delivery and/or chorioamnionitis, were enrolled in this study. The study group comprised 15 patients and their infected newborns. The control group consisted of 31 women and their healthy newborns. We compared PCT concentrations between maternal, umbilical cord and neonatal serum, in both study and control groups. Additionally, PCT levels were compared between the corresponding compartments. RESULTS: PCT concentrations in the umbilical cord and venous blood in infected newborns, but not in non-infected neonates, were significantly higher than maternal serum PCT levels. PCT concentrations of mothers who delivered infected newborns were comparable to those in the controls. However, PCT concentrations in the umbilical cord and in the venous blood of the infected newborns were higher than in healthy newborns. CONCLUSION: Measurement of maternal PCT concentration during labor does not contribute to early prediction of infection in the neonate. However, umbilical cord PCT concentrations, as well as its neonatal venous levels on the second day of life, seem to be related to intrauterine infection, and may be a useful tool in the diagnosis of early neonatal infection.

Bacterial Infections↗
PubMed1998

Risk factors for neonatal sepsis in offspring of women with prelabor rupture of the membranes at 34-42 weeks.

One thousand three hundred eighty-five women with PROM (prelabor rupture of the membranes) participated in a prospective randomized study. Women with PROM were randomized to induction the following morning after PROM (early induction group) or induction two days later (late induction group). If contractions started within 2 hours after admission these women were included in the short latency group. All neonatal infections were classified as verified sepsis (positive culture) or clinical sepsis. The aim of the study was to compare the perinatal infectious outcome between the groups with different expectant managements in women with PROM and to study the association between demographic, intrapartum and postpartum variables and neonatal sepsis. In the short latency group one neonate had a proven sepsis while four neonates with proven sepsis were found in the early induction group. No proven sepsis was detected in the late induction group. Univariate analyses showed a significant association between clinical sepsis and: induction of labor (OR = 2.94, 95% CI 1.30-6.68), established labor 24.1-32 hours after ROM (OR = 5.89, 95% CI 1.68-20.63), established labor > 32 hours after ROM (OR = 4.59, 95% CI 1.52-13.87), time from ROM to delivery > 32 hours (OR = 5.07, 95% CI 1.40-18.39), cesarean section (OR = 11.03, 95% CI 4.10-29.68), chorioamnionitis before or during delivery (OR = 27.14, 95% CI 2.38-309.16), endometritis (OR = 18.08, 95% CI 1.82-179.87), CRP over 20 mg/l in the umbilical cord (OR = 17.12, 95% CI 5.68-52.12) and Apgar score < 7 after 1, 5 or 10 minutes. In a stepwise logistic regression analysis a significant association was found between clinical sepsis and cesarean section (OR = 10.08, 95% CI = 3.26-31.20), time from ROM to delivery > 32 h (OR = 3.74, 95% CI 1.62-8.62), gestational age 34-36 weeks (OR = 3.16, 95% CI 1.11-8.96) and parous women (OR = 2.41, 95% CI 1.04-5.57). In conclusion, this study indicates that that there was no difference in the incidence of neonatal infections between those with early and late induction. Clinical neonatal sepsis was associated with time from PROM to delivery over 32 hours, cesarean section, parous women and gestational age between 34 and 36 weeks.

Apgar Score↗
PubMed2005

Septicemia in the first week of life in a Norwegian national cohort of extremely premature infants.

OBJECTIVES: To investigate the incidence, causes, predictors, and outcomes of septicemia in the first week of life in a national cohort of extremely premature infants. METHODS: A prospective study of survival of all infants with gestational age of <28 weeks or birth weight of <1000 g who were born in Norway in 1999-2000 was performed. Data on the maternal prenatal history, delivery, and neonatal course, including detailed information on episodes of microbiologically verified septicemia, were collected on predefined forms. Septicemia was reported in 2 groups, ie, episodes diagnosed on the day of delivery (ie, very early-onset septicemia [VEOS]) and episodes diagnosed from day 2 to day 7 of life (ie, early-onset septicemia [EOS]). Logistic regression models were used for the selection of variables for predictor analysis in each group. RESULTS: Of 462 included infants, VEOS occurred for 15 (32.5 per 1000 population) and EOS for 15 (35.5 per 1000 population). The most prevalent bacteria were Escherichia coli in VEOS (n = 9) and staphylococci (coagulase-negative staphylococci and Staphylococcus aureus) (n = 15) in EOS. Case fatality rates were 40% and 13%, respectively. Independent predictive factors for VEOS were clinical chorioamnionitis (odds ratio [OR]: 10.5; 95% confidence interval [CI]: 3.3-33.4) and high maternal age (OR: 1.2; 95% CI: 1.0-1.3), whereas not receiving systemic antibiotic therapy within 2 days of age (OR: 13.6; 95% CI: 3.7-50.2) and receiving nasal continuous positive airway pressure (n-CPAP) support at 24 hours of age (OR: 9.8; 95% CI: 2.5-38.4) independently predicted septicemia after the first day of life. CONCLUSIONS: Whereas vertically transmitted septicemia was dominated by Gram-negative bacteria, with predictors being exclusively of maternal origin, EOS was dominated by typically nosocomial flora, with n-CPAP treatment at 24 hours of age being a powerful predictor. Early n-CPAP treatment, as opposed to mechanical ventilation, as a powerful predictor of septicemia in the early neonatal period, even with adjustment for early systemic antibiotic treatment, is a new observation among extremely premature infants that warrants additional study.

Chorioamnionitis↗
PubMed2001

The relationship between infections and adverse pregnancy outcomes: an overview.

Preterm birth with its subsequent morbidity and mortality is the leading perinatal problem in the United States. Infants born before the thirty-seventh week of gestation account for approximately 6% to 9% of all births, but 70% of all perinatal deaths and half of all long-term neurologic morbidity. Current approaches focus on symptomatic treatment. Despite widespread use of drugs to arrest preterm labor (tocolytics), there has been no decrease in low birth weight or preterm infants in the last 20 years. It is likely that therapy directed at preventing or treating underlying causes would be more successful. Evidence from many sources links preterm birth to symptomatic infections, for example, of the urinary or respiratory tracts. In the last decade, great interest has been generated to support the hypothesis that subclinical infection is an important cause of preterm labor. Evidence to support this may be categorized as follows: histological chorioamnionitis is increased in preterm births; clinical infection is increased after preterm birth; there is significant association of some lower genital tract organisms and infections with preterm birth or preterm premature rupture of the membranes; there are positive cultures of amniotic fluid or membranes from some patients with preterm labor and preterm birth; there are markers of infections in preterm birth; bacteria or their products induce preterm birth in animal models; and some antibiotic trials have shown a lower rate of preterm birth or have deferred preterm birth. In the last 5 years, additional exciting information has suggested that not only is subclinical infection responsible for preterm birth but also many serious neonatal sequelae including periventricular leukomalacia, cerebral palsy, respiratory distress, and even bronchopulmonary dysplasia and necrotizing enterocolitis. In sum, a large body of clinical and laboratory information suggests that subclinical infection is a major cause of preterm birth, especially those occurring before 30 weeks. This concept holds promise that new approaches can be developed to prevent prematurity.

Animals↗
PubMed2001

Maternal periodontitis and prematurity. Part I: Obstetric outcome of prematurity and growth restriction.

Oral Conditions and Pregnancy (OCAP) is a 5-year prospective study of pregnant women designed to determine whether maternal periodontal disease contributes to the risk for prematurity and growth restriction in the presence of traditional obstetric risk factors. Full-mouth periodontal examinations were conducted at enrollment (prior to 26 weeks gestational age) and again within 48 hours postpartum to assess changes in periodontal status during pregnancy. Maternal periodontal disease status at antepartum, using a 3-level disease classification (health, mild, moderate-severe) as well as incident periodontal disease progression during pregnancy were used as measures of exposures for examining associations with the pregnancy outcomes of preterm birth by gestational age (GA) and birth weight (BW) adjusting for race, age, food stamp eligibility, marital status, previous preterm births, first birth, chorioamnionitis, bacterial vaginosis, and smoking. Interim data from the first 814 deliveries demonstrate that maternal periodontal disease at antepartum and incidence/progression of periodontal disease are significantly associated with a higher prevalence rate of preterm births, BW < 2,500 g, and smaller birth weight for gestational age. For example, among periodontally healthy mothers the unadjusted prevalence of births of GA < 28 weeks was 1.1%. This was higher among mothers with mild periodontal disease (3.5%) and highest among mothers with moderate-severe periodontal disease (11.1%). The adjusted prevalence rates among GA outcomes were significantly different for mothers with mild periodontal disease (n = 566) and moderate-severe disease (n = 45) by pair-wise comparisons to the periodontally healthy reference group (n = 201) at P = 0.017 and P < 0.0001, respectively. A similar pattern was seen for increased prevalence of low birth weight deliveries among mothers with antepartum periodontal disease. For example, there were no births of BW < 1000 g among periodontally healthy mothers, but the adjusted rate was 6.1% and 11.4% for mild and moderate-severe periodontal disease (P = 0.0006 and P < 0.0001), respectively. Periodontal disease incidence/progression during pregnancy was associated with significantly smaller births for gestational age adjusting for race, parity, and baby gender. In summary, the present study, although preliminary in nature, provides evidence that maternal periodontal disease and incident progression are significant contributors to obstetric risk for preterm delivery, low birth weight and low weight for gestational age. These studies underscore the need for further consideration of periodontal disease as a potentially new and modifiable risk for preterm birth and growth restriction.

Adult↗
PubMed1990

Perinatal and neonatal significance of bacteria-related placental villous edema.

In a study of 82 cases of clinical chorioamnionitis in which no antibiotics were administered antenatally, significant villous edema was observed in 51 placentas (62%). Polymorphonuclear leukocyte invasion of the placental plate was found in 53 placentas (65%). The presence of SVE was significantly associated with placental bacterial recovery, occurrence of prolonged rupture of membranes, lower one minute Apgar score, the need for resuscitation and significant neonatal respiratory problems. Findings suggest that bacteria-related placental villous edema can lead to significant perinatal and neonatal morbidities.

Adult↗
PubMed1985

Fatal adenovirus pneumonia in two newborn infants, one case caused by adenovirus type 30.

Adenovirus rarely causes pneumonia in the newborn infant. We added 2 cases of fatal adenovirus neonatal pneumonia to the 3 cases previously reported. One of our cases was caused by adenovirus type 30, which is not previously known to be a pathogen. While the pneumonia could have been acquired in the nursery, the presence of chorioamnionitis and mixed infection with group B beta-hemolytic streptococcus suggests that an ascending infection from the birth canal might be another mode of transmission for neonatal adenovirus pneumonia.

Adenoviridae Infections↗
PubMedDate not supplied

Streptococcus viridans infections in midgestation.

During a 14-year period Streptococcus viridans was isolated at autopsy from 18 neonates or stillborn fetuses delivered in midgestation (18-28 weeks) at Women & Infants' Hospital in Providence, Rhode Island. Evidence of swallowed and/or aspirated, infected amniotic fluid by the fetus was found in 16 of 18 cases along with chorioamnionitis and funisitis. Of the 18 cases, maternal infection was documented in 6 cases; delivery was preceded by spontaneous rupture of membranes in 9 cases and vaginal bleeding in 7 cases. Poor maternal obstetric history was indicated by only 12 living children from 42 total pregnancies in the 12 multigravidas in the study. It is concluded that S. viridans may have a significant role in the pathogenesis of second trimester amniotic fluid infections with abortions and fetal and neonatal sepsis.

Chorioamnionitis↗
PubMedDate not supplied

Lattice theory analysis of the relationship of hyaline membrane disease and fetal pneumonia in 96 perinatal autopsies.

A previous study of hyaline membrane disease of the newborn demonstrated that the hyaline membrane was derived from necrotic epithelial cells, and it was suggested that a no flow-reflow episode affecting the pulmonary circulation might account for the cell necrosis. An unexpected statistical finding in that study was a highly significant negative correlation between hyaline membrane disease and chorioamnionitis. Because it seemed to us that fetal infection could be expected to produce the circulatory pathophysiology suggested to produce hyaline membrane disease, we reexamined the issue by reviewing a group of autopsied infants. Data were collected on clinicopathologic variables from 42 stillborn and 54 liveborn infants less than or equal to 12 h of age with lung and placenta slides available for review. Correlations and multivariate regression analysis showed that the inflammatory responses in membranes, cord, and lung are interrelated but that hyaline membrane disease develops independently. However, lattice theory analysis, which represents the pathogenesis of a progressive disease process as edges along a mathematical lattice or hyperdimensional cube, showed that this separation was not absolute. Despite the negative correlation of hyaline membrane disease and fetal pneumonia, there were 10 (10%) patients with both conditions and a total of 19 (20%) with hyaline membrane disease and inflammation of membranes, cord, and/or lung. We suggest that the coexistence of hyaline membrane disease and fetal pneumonia in some patients implies a possible pathogenetic relationship between the two entities. Given the nature of the two processes, it seems likely that the direction of causality is that fetal pneumonia would give rise to the hyaline membrane disease of the newborn.

Autopsy↗
PubMedDate not supplied

Necrotizing funisitis associated with Actinomyces meyeri infection: a case report.

Necrotizing funisitis is associated with an increased rate of stillbirth, perinatal infection, and preterm delivery. No one organism has been associated with necrotizing funisitis, although this condition has been linked with congenital syphilis in some studies. We report a case of necrotizing funisitis in a 24-year-old G2P0A2 woman who experienced preterm labor at 31 weeks of gestation. Examination of the placenta revealed severe chorioamnionitis and necrotizing funisitis; large numbers of gram-positive filamentous branching organisms could be seen on the surface of the cord and within Wharton jelly. Initial cultures of the placenta, which had not been maintained under anaerobic conditions after delivery, were negative. A fragment of the cord was then homogenized; anaerobic culture on brain-heart infusion agar yielded Actinomyces meyeri. This organism usually resides in the periodontal sulcus and has not been previously reported in the female genital tract. The mother gave a history of a dental abscess that flared up and drained with each of her three pregnancies; the pain was particularly severe during the last 2 months of this pregnancy, so she had the tooth removed after delivery. The infant was treated for prematurity and presumed sepsis and did well.

Actinomyces↗