Chorioamnionitis associated with Crohn's disease and azathioprine treatment: a case report.

This paper reports a case of S. constellatus chorioamnionitis in a pregnant Crohn's disease patient who was taking azathioprine. Chorioamnionitis is a major cause of perinatal morbidity. Azathioprine, an immunosuppressive antimetabolite, is widely used to treat inflammatory bowel disease. Streptococcus constellatus is a Gram-positive bacterium that has not previously been associated with chorioamnionitis. A high index of suspicion for chorioamnionitis and unusual pathogens should be maintained in the management of obstetric patients on immunosuppressive agents.

Benefit of antenatal glucocorticoids according to the cause of very premature birth.

In this observational study performed in a large cohort of very preterm singletons, respiratory outcome was found to be strongly dependent on the cause of premature delivery. Although less apparent in infants born to mothers with chorioamnionitis, exposure to antenatal glucocorticoids remained significantly associated with a decrease in the incidence of respiratory distress syndrome after adjustment for the main cause of premature birth.

Antenatal associations with lung maturation and infection.

Chronic clinically unapparent chorioamnionitis is a common antenatal exposure for very preterm infants, and these infants have variable degrees of lung maturation and a high risk of developing bronchopulmonary dysplasia. Exposure of fetal sheep to intra-amniotic endotoxin or IL-1alpha induces chorioamnionitis and lung injury (decreased alveolarization and microvascular injury), which resolves to a phenotype of striking lung maturation (increased surfactant, improved gas exchange and lung mechanics). The immune responses of the fetus also are suppressed or induced (matured) in time and dose-dependent ways by either chorioamnionitis or antenatal corticosteroids. These experimental observations contribute to explanations of why preterm infants have variable degrees of lung maturation at birth and unpredictably develop bronchopulmonary dysplasia BPD.

The association between early tracheal colonization and bronchopulmonary dysplasia.

OBJECTIVE: To evaluate the relationship between early tracheal colonization and bronchopulmonary dysplasia (BPD). STUDY DESIGN: This is a retrospective cohort study which included 308 inborn neonates admitted to the newborn intensive care unit at the University of Miami Jackson Memorial Medical Center between January 1997 and December 2000 with birthweight 500 to 1000 g, who required mechanical ventilation on the first day of life. Chorioamnionitis was diagnosed by maternal symptoms and histopathopathology. Tracheal cultures were obtained immediately after tracheal intubation. BPD was diagnosed in neonates who had supplemental oxygen requirement for more than 28 days. Pearson's chi(2) and Logistic Regression Analysis were used to evaluate the relationship between chorioamnionitis, positive initial tracheal cultures and BPD, after adjusting for confounding variables. RESULTS: In patients with chorioamnionitis, the incidence of early positive tracheal cultures was 41% compared to 16% in those without chorioamnionitis, (p < 0.00001). In patients with birthweight 700 to 1000 g, a positive early tracheal culture increased the risk of BPD (OR = 2.42, CI 1.05 to 5.62, p < 0.05). CONCLUSION: Preterm infants exposed to chorioamnionitis have an increased incidence of early tracheal colonization. This early tracheal colonization may predispose them to develop BPD.

Histologic chorioamnionitis: an occult marker of severe pulmonary hypertension in the term newborn.

OBJECTIVE: To determine whether the presence of histologic chorioamnionitis is associated with the severity of Persistent Pulmonary Hypertension of the Newborn (PPHN) as evidenced by the use of exogenous nitric oxide (iNO), high-frequency oscillatory ventilation (HFOV), extra-corporeal membrane oxygenation (ECMO) and/or death. METHODS: Retrospective chart review of term neonates > or =37 weeks gestation with PPHN. Placental pathology was reviewed. Primary outcome is the use of iNO. Secondary outcomes include the use of HFOV, ECMO and death. RESULTS: Over 2 years, 29 neonates fulfilled the entry criteria for the study. Interventions included iNO use n=14 (48%), HFOV n=7 (24%) and ECMO n=3 (10%); two neonates died. Histologic chorioamnionitis and/or funisitis was noted in 16 (55%) neonates. The presence of chorioamnionitis and/or funisitis (n=16) versus neither (n=13) was significantly associated with iNO use 11/16 (78%) versus 3/13 (22%) (p=0.02) and HFOV 7/16 (43%) versus 0/13 (0%) (p=0.008) but not to ECMO or death. CONCLUSION: The presence of histologic chorioamnionitis and/or funisitis is associated with more severe PPHN as indicated by the use of iNO as well as an increased requirement for more advanced respiratory support, that is, HFOV. The mechanism/s contributing to these findings are unclear.

Maternal infection and risk of cerebral palsy in term and preterm infants.

OBJECTIVE: We tested the hypothesis that term and preterm infants exposed to maternal infection at the time of delivery are at increased risk of developing cerebral palsy (CP). STUDY DESIGN: A population-based case-control study was conducted using Washington State birth certificate data linked to hospital discharge data. Cases (688) were children

Cervical incompetence and the role of emergency cerclage.

OBJECTIVE: To evaluate the role of emergency cerclage for women who present with a dilated external cervical os and bulging or "hour-glassing" membranes. We examined overall experiences at Kingston General Hospital (KGH) from 2000 to 2004 and conducted a literature review for the period January 1, 1995, to December 31, 2004. METHODS: A search for cerclages placed by operators in Kingston revealed 12 pregnancies in the period between 2000 and 2004. We reviewed the charts for these women and for their infants. We conducted a literature review, using the terms "cerclage," "cervical," "emergent or emergency cerclage," "rescue cerclage," and "incompetent cervix," using an OVID interface to access MEDLINE records. We excluded articles in which the diagnosis of cervical incompetence was made using ultrasound, because its predictive value has not been shown in randomized trials. The most recent review of this type was carried out in 1995; since then, an additional 24 articles have been published that met our inclusion and exclusion criteria. RESULTS: The average time between cerclage placement and delivery at KGH was 7 weeks, which allowed for 10 of 13 infants (one twin pregnancy) to be born at 28 weeks or later. Three infants were born weighing under 1 kg; the 10 remaining infants weighed over 1 kg. Histological data are available for 12 placentas of the 13 infants delivered; 7 infants had a histological diagnosis of chorioamnionitis; none of the blood cultures from any of the infants post-delivery revealed septicemia. The literature review identified 638 women. Where reported, the average prolongation of the pregnancy was 7 weeks plus 1 day. This allowed for 60% of infants (range 26% to 80%) to be born after 28 weeks, with an average neonatal survival of over 70% (range 47.2% to 96%). Preterm premature rupture of membranes complicated an average of 29% of pregnancies (range 1% to 58%), and chorioamnionitis was reported in 5% to 80% of pregnancies. CONCLUSIONS: The KGH data collected and the data available in the literature suggest that emergency cerclage, under ideal circumstances, can significantly prolong pregnancy and increase the chance of viable pregnancy outcome. However, in counselling women about the potential therapeutic benefit of emergency cerclage, the increased risk of chorioamnionitis and its associated risk of fetal inflammatory brain injury, as well as the risk of extending a pregnancy from pre-viability to severe prematurity, should be discussed. A longer-term follow-up than has been carried out here is required for better elucidation of the effect of chorioamnionitis on those infants in childhood and beyond.

Prevalence, management, and outcomes of preterm prelabour rupture of the membranes of women in Canada.

OBJECTIVES: To determine the prevalence of preterm prelabour rupture of the membranes (PPROM) at Canadian university-affiliated perinatal referral centres, to assess the different management strategies, and to review neonatal outcomes. METHODS: Twelve Canadian university-affiliated perinatal referral centres provided information on their management of PPROM, and 9 participated in data collection to determine prevalence. All women presenting with PPROM during a 2-week period were observed until delivery, and obstetric and neonatal outcome data were subsequently obtained. The total number of deliveries in each centre was recorded for the same time period. We also determined the incidence of PPROM and the neonatal outcome for all women presenting with PPROM at the Kingston General Hospital from January 1999 to December 2001 by retrospective chart review. RESULTS: In the 9 academic centres, 27 women (1 with a twin pregnancy) presented with PPROM during the 2-week period. There were 1168 deliveries during the same time period, giving a prevalence of PPROM of 2.3%. Overall, 53% of placentas submitted for histopathology after PPROM demonstrated evidence of chorioamnionitis. In the retrospective chart review, we found 153 cases of confirmed PPROM from January 1999 to December 2001,an incidence of 2.8%. Clinical management in all centres was similar for most women who presented with PPROM prior to 34 weeks' gestation. Management after 34 weeks' gestation varied among the 12 centres, ranging from immediate induction of labour to expectant management and induction at a greater gestational age (GA). CONCLUSIONS: The increased neonatal morbidity associated with PPROM appears to be inversely related to GA. Increased risk of chorioamnionitis is related to increased time from PPROM to delivery.

Maternal corticotropin-releasing hormone is increased with impending preterm birth.

The objective of this study was to test the hypothesis that maternal CRH concentrations are elevated in women experiencing threatened preterm labor who subsequently give birth within 24 h compared to those in women who do not. We also characterized the changes in maternal plasma cortisol, ACTH, corticosteroid binding capacity (CBC), and CRH concentrations in 28 healthy pregnant women between 20-38 weeks gestation. Overall, maternal plasma CRH concentrations were significantly greater (P < 0.05) in those women giving birth within 24 h (1343.3 +/- 143.9 pg/mL; n = 81) compared to those in women who did not (714.5 +/- 64.8 pg/mL; n = 144) or those in normal subjects. This difference was present between 28-36 weeks, but not 24-28 weeks gestation. The ratio of maternal cortisol to CBC was also significantly greater (P < 0.05; 0.65 +/- 0.04; n = 82) in women giving birth within 24 h than in those who did not (0.55 +/- 0.02; n = 136). This difference was significant at all gestational ages studied. Elevated CRH concentrations and bioavailability of free cortisol may both be implicated in the pathogenesis of preterm labor in some women. Further prospective clinical trials are warranted to determine the positive and negative predictive values of maternal CRH concentrations and/or the ratio of cortisol/CBC for identifying women with threatened preterm labor destined to give birth within 24 h.

Maternal body weight and pregnancy outcome.

Pregnancies that produced 56,857 children were analyzed to evaluate the relationship of the mothers' relative pregravid body weight to pregnancy outcome. Perinatal mortality rates progressively increased from 37 of 1000 in offspring of thin subjects to 121 of 1000 in the offspring of obese subjects (p less than 0.001). Nearly half of this mortality increase was due to preterm deliveries, particularly before 31 wk of gestation. More than half of the increase in preterm births was caused by acute chorioamnionitis. Other factors that made major contributions to the overall mortality increase were rises in the frequencies of older gravidas (ages 35-50 y), gravidas who had diabetes mellitus, children who had major congenital malformations, and dizygous twins.

Maternal and neonatal characteristics associated with HIV infection in infants of seropositive women.

In this prospective study of infants born to human immunodeficiency virus (HIV) seropositive mothers, neonatal and maternal characteristics of infected and noninfected infants were compared to determine the factors that may be associated with or contribute to vertical transmission of HIV. Of 134 infants entered as newborns in the study, 31 have definite serological and/or clinical evidence of infection and 103 are considered noninfected (transmission rate, 23.1%). Significantly more of the infected infants had birth weights below 2,500 g (48.4% versus 22.3%), and more infected infants were found to be small for gestational age (16.2% versus 5.8%). A greater number of infected infants experienced two or more problems in the neonatal period than noninfected infants (51.6% versus 24.2%). The incidence of confirmed and suspected bacterial infections was also significantly increased in the infected group. Multiple logistic regression analysis indicated low birth weight had the strongest association with vertical transmission of HIV. There was no significant difference between the two groups in mean maternal age at first pregnancy, mother's marital status, education, type of family, or past history of type of substances abused. Mothers who transmitted HIV to their infants had a trend towards a higher frequency of clinical chorioamnionitis (16.1% versus 5.8%), reported sexually transmitted diseases during pregnancy (45.2% versus 22.3%), and continued illicit drug use (67.7% versus 49.0%). In this group of infants, low birth weight, poor intrauterine growth, neonatal infections and possibly maternal chorioamnionitis, STDs during pregnancy, and continued drug use are associated with vertical transmission of HIV.

Multiple risk factors in neonatal sinovenous thrombosis.

The etiology of neonatal sinovenous thrombosis is poorly understood. The authors report the risk factors and radiologic features of neonatal sinovenous thrombosis seen over an 11-year period. Of 30 patients, 29% received extracorporeal membrane oxygenation treatment, and 23% had congenital heart disease. Genetic thrombophilias were present in four of the seven infants tested. Eighteen neonates had multiple maternal, neonatal, perinatal, or prothrombotic complications. Sinovenous thrombosis was often accompanied by infarction (50%) or intraventricular hemorrhage (33%).

Chorioamnionitis and early lung inflammation in infants in whom bronchopulmonary dysplasia develops.

OBJECTIVE: The development of bronchopulmonary dysplasia (BPD) often has been attributed to injury from mechanical ventilation and supplemental oxygen. Early lung inflammation in infants with BPD has been thought to be secondary to these factors. The purpose of this study was to evaluate whether preexisting (prenatal) inflammation may be a primary causative factor in the development of BPD. METHODS: Intubated newborns of less than 2,000 g birth weight were prospectively enrolled. The presence or absence of chorioamnionitis was documented. Lung inflammation was evaluated on days 1, 2, and 4 of intubation by assaying concentrations of interleukin 1 beta (IL-1 beta), thromboxane B2, leukotriene B4, and prostaglandin E2 in tracheal lavages. Infants in whom BPD developed were compared with those in whom it did not using these measures. RESULTS: Fifty-three infants were enrolled; 41 survived. Thirty-eight had respiratory distress syndrome; 15 were intubated for other diagnoses. Infants prenatally exposed to chorioamnionitis were less likely to present with respiratory distress syndrome; however, chorioamnionitis was significantly associated with both the presence of IL-1 beta from the first day of intubation and the development of BPD. Tracheal lavage concentrations of IL-1 beta were higher in infants in whom BPD developed. Thromboxane B2 concentrations were similar on day 1 but were higher on days 2 and 4 in infants in whom BPD developed. CONCLUSIONS: In this study, intubated infants weighing less than 2,000 g at birth in whom BPD developed had increased exposure to inflammation prenatally (chorioamnionitis) and evidence of increased lung inflammation from the first postnatal day. We speculate that chorioamnionitis may accelerate lung maturation but that it also causes lung inflammation and subsequent lung injury in intubated infants, fostering the development of BPD.

Bilateral cystic periventricular leukomalacia in the premature infant: associated risk factors.

BACKGROUND: Bilateral cystic periventricular leukomalacia (PVL) is a major cause of neurodevelopmental delay in the premature infant. Thus, early identification of the preterm infant at highest risk for the subsequent development of this lesion is critical. OBJECTIVES: The three objectives of this case-control study were: (1) to determine the basic characteristics of cystic PVL, (2) to assess the relationship of perinatal clinical events and PVL, and (3) to ascertain the feasibility of identifying early those preterm infants at highest risk for the development of PVL. METHODS: The medical records and cranial ultrasound scans (HUSs) were reviewed for 632 infants weighing less than 1750 g who were admitted to the neonatal intensive care unit between January 1992 and December 1993. PVL developed in 14 infants of 1285 +/- 301 g birth weight (BW) and 29.4 +/- 1.5 weeks' gestational age (GA); severe intraventricular hemorrhage (n = 21) and intraparenchymal echodensity (n = 12) developed in 33 infants of 904 +/- 248 g BW and 26.6 +/- 1.8 weeks' GA; and 585 infants of 1315 +/- 324 g BW and 29.7 +/- 2.4 weeks' GA with normal HUS findings (n = 473) or grade I or II intraventricular hemorrhage (n = 112) served as a comparison group. RESULTS: Cystic PVL was observed in 14 (2.3%) of 632 infants weighing less than 1750 g, more specifically, in 3.2% of infants weighing less than 1500 g. Cysts were noted from the 7th to 14th days of life in 10 infants and from the 20th to 46th days of life in 4 infants. Ten (70%) of the infants had relatively benign clinical courses, and most cases were detected by routine HUS surveillance. Over hypotension in the immediate perinatal period was noted in 3 (21%) infants; late hypotension developed in 1 additional infant. Univariate analysis indicate that two clinical indicators, prolonged rupture of membranes (PROM) and chorioamnionitis, were significant predictors of PVL. For PROM, the odds ratio estimate and the 95% confidence limit are 6.59 and 1.96 to 22.10, with a sensitivity of 28.6% and positive predictive value of 11.5%. Similar values for chorioamnionitis are 6.77 (1.77 to 25.93), with a sensitivity of 21.4% and positive predictive value of 11.5%. CONCLUSIONS: (1) Most cases of symmetric cystic PVL occurred in infants with relatively benign clinical courses and were only detected by routine ultrasound screening. (2) Postnatal systemic hypotension seems to be an uncommon associated event. (3) Preterm infants born to mothers with PROM and/or chorioamnionitis seem to be at an increased risk for the development of PVL and should be carefully evaluated.

Increased leukocyte elastase of the tracheal aspirate at birth and neonatal pulmonary emphysema.

OBJECTIVE: The authors have previously shown the association of elevated neonatal serum IgM and chorioamnionitis in infants in whom pulmonary emphysema characteristic of Wilson-Mikity syndrome subsequently developed. This paper extends the observation to the measurement of polymorphonuclear leukocyte elastase-alpha 1-proteinase inhibitor complex (PMN elastase-alpha 1-PI) in tracheal aspirates of infants with chronic lung disease. PATIENTS: Tracheal aspirates were obtained from 90 very low birth weight neonates within 24 hours of birth. Serum also was collected within 72 hours of birth, and placentas were examined for signs of inflammation. RESULTS: The mean PMN elastase-alpha 1-PI was significantly elevated (21.8 micrograms/mg albumin) in infants with a pulmonary emphysema syndrome like that designated by Wilson-Mikity compared either with those with bronchopulmonary dysplasia (1.5 micrograms/mg albumin, P < .01) or those with respiratory distress syndrome in whom bronchopulmonary dysplasia did not develop (2.3 micrograms/mg albumin, P < .01). Infants with pulmonary emphysema had a significantly elevated mean serum IgM and a high incidence of chorioamnionitis. CONCLUSIONS: The level of PMN elastase-alpha 1-PI was increased in the tracheal aspirates of newborns in whom pulmonary emphysema developed. Intrauterine inflammation may increase the level of PMN elastase in the fetal respiratory tract. This increase in PMN elastase-alpha 1-PI in fetal lung tissue may cause lung injury in utero, resulting in postnatal pulmonary emphysema consistent with the Wilson-Mikity syndrome following ventilation.

Chronic villitis of unknown aetiology and intrauterine growth-retarded infants of normal and low ponderal index.

Placentae from 211 term pregnancies were studied. The placentae were divided into three groups: group I, 57 placentae from neonates with birthweight over the 25th centile of the normal birthweight curve; group II, 49 placentae from neonates whose birthweight fell between the 10th and 25th centiles of this curve, and group III, 105 placentae from neonates whose birthweights were below the 10th centile of the curve. Each of the studied groups were divided into two subgroups, one comprising those infants with a normal Ponderal Index (PI) and the other comprising those with a low PI. A higher incidence of chronic villitis and of inflamed villi was observed as the average birthweight decreased in cases with normal PI as well as in cases with low PI, the highest incidence being found in placentae from infants with harmonic intrauterine growth retardation (normal PI). The same was observed with respect to the presence of maternal vascular lesions in all groups studied. It is suggested that an infant's birthweight and crown-heel length may be affected as a consequence of the extension and severity of the placental lesions and the timing of their appearance in gestation.

Phagocytosis of chorion laeve trophoblasts in patients with chorioamnionitis-associated preterm delivery: ultrastructural and enzyme-histochemical observations.

The purpose of the present study was to examine morphological evidence for the presence of phagocytosing chorion laeve trophoblasts in fetal membranes from patients who had undergone chorioamnionitis-related preterm delivery. Chorion laeve trophoblasts from six patients, who underwent preterm delivery (28-34 weeks of gestation) complicated with chorioamnionitis, were analysed using transmission electron microscopy and ultrastructural enzyme-histochemistry for acid phosphatase, and compared with those from gestational age-matched chorioamnionitis-negative controls. Cytosomal cell projections, phagosomes, phagocytosis of degenerated cells and cell debris, attachment or fusion of lysosomes to the phagosomal membranes and phagosomal membranes positive for acid phosphatase staining were characteristically observed much more frequently in trophoblasts with chorioamnionitis than those without. The results indicated that chorion laeve trophoblasts in fetal membranes from patients having undergone chorioamnionitis-related preterm delivery underwent phagocytosis. Such phagocytosing trophoblasts may play a role in the pathophysiology or pathogenesis of infection-related preterm delivery.

The severity of fetal membrane infection and pregnancy complications.

The purpose of this report is to examine the association of histologic chorioamnionitis with microorganisms isolated from the fetal membranes and to evaluate whether microorganisms with or without inflammation are associated with labor characteristics and with pregnancy complications. Inflammation was more common among membranes that yielded pathogenic bacteria (47%, P = 0.002) or Urea-plasma urealyticum (34%, P = 0.03) than among membranes that yielded no growth or nonpathogenic bacteria (20%). Prolonged membrane rupture (P = 0.0001), infant birth weight less than 2500 g (P = 0.02), and intraamniotic infection (P = 0.001) occurred more frequently among those women whose membranes yielded pathogenic bacteria than among those whose membranes yielded no growth or nonpathogenic bacteria. Our findings suggest that placental membranes in which pathogenic bacteria are accompanied by inflammation are associated with the highest risk of pregnancy complications.

Effect of interleukin 2 on the production of progesterone and prostaglandin E2 in human fetal membranes and its consequences for preterm uterine contractions.

Our objective was to clarify the mechanism of uterine contraction induced in pregnant women by intrauterine bacterial infection. The concentration of interleukin 2 (IL-2) was measured in amniotic fluids that had been obtained by amniocentesis, transvaginal amniotomy or by transuterine amniocentesis performed at cesarean section in 50 pregnant women. The concentration of IL-2 in those cases with intrauterine infection was significantly higher than that of those without intrauterine infection at preterm. The same tendency was found at term. Scatchard analysis demonstrated the presence of an IL-2 receptor in the fetal membranes. We collected the fetal membranes aseptically for the measurement of progesterone and prostaglandin E2 by radioimmunoassay following incubation with various concentrations of interleukin 1 (IL-1) and IL-2 at 37 degrees C for 16 h. The production of progesterone was inhibited significantly by 10 pmol/l IL-2 but not by 10 pmol/l IL-1. The production of prostaglandin E2 was accelerated significantly by either IL-1 or IL-2 at a dose of 10 pmol/l. The inhibitory effect of IL-2 on the production of progesterone was unaffected by indomethacin, which inhibits the production of arachidonate cycloxygenase metabolites such as prostaglandin E2. Our present data suggest that the presence of intrauterine bacterial infection may stimulate the intrauterine production of IL-2, and that the stimulation of IL-2 and the reduction of progesterone caused by IL-2 may in part explain the mechanism of uterine contraction associated with intrauterine infection during pregnancy.

Acute thymic involution in fetuses and neonates with chorioamnionitis.

Chorioamnionitis represents the leading cause of preterm birth and related pathologic conditions as well as of fetal death and frequently occurs in symptom-free mothers. Recent radiologic findings have indicated that thymus size is significantly reduced in preterm infants born to mothers with subclinical, histologically proven chorioamnionitis. However, an accurate morphologic description of the thymus gland in fetuses and neonates with chorioamnionitis is lacking, although it is known that infection and other stress processes may cause lymphocyte depletion in the thymuses of infants and older babies (acute stress involution). We describe morphologic modifications in the thymus of fetuses with histologically proven chorioamnionitis and newborn infants with chorioamnionitis and proven sepsis. The main findings included (1) decreased organ volume (ANOVA, P < .0024); (2) reduced corticomedullary ratio (P < 10(-6)); (3) significant changes in the relationship between thymic parenchyma and thymic interstitial tissue with resulting increased organ complexity (P = .03); (4) severe reduction of thymocytes; and (5) other degenerative processes such as monocyte/macrophage infiltration of Hassall's bodies. These results indicate that chorioamnionitis, with or without sepsis, is associated with significant morphologic modifications in the thymus. We wish to note that the described thymic pathology is only one aspect of the fetal systemic inflammatory response syndrome with which chorioamnionitis is associated.