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PubMed2003

Complications of second and third trimester pregnancies.

The second and third trimester of pregnancy is a period of extensive physical growth and maturation of the fetus. Unfortunately, it is also a period that is marked by complications that can be life threatening for both the mother and fetus. The top three complications that affect pregnancy are hemorrhage, infection, and the hypertensive diseases of pregnancy. This article focuses on preterm labor, premature rupture of membranes, chorioamnionitis, bleeding in later pregnancy, and the hypertensive diseases of pregnancy.

Anti-Bacterial Agents↗

PubMed1997

Preterm labor and preterm premature rupture of the membranes. Diagnosis and management.

Preterm delivery due to preterm labor and pPROM is responsible for most infant morbidity and mortality in the United States. The patient who presents with suspicious symptoms should undergo a thorough evaluation to confirm the diagnosis of either entity and identify a treatable cause. Determination of gestational age, fetal well-being, and the presence of intrauterine infection is a crucial step in subsequent management. Corticosteroid therapy has been demonstrated to be one of the most effective antenatal interventions to reduce infant morbidity and should be administered to patients with preterm labor, if feasible, when fetal pulmonary maturity is absent or undocumented. We recommend a similar protocol regarding gravidas with pPROM remote from term but recognize the need for further study in this area. Acute tocolytic therapy has been demonstrated to offer short-term benefit to enhance corticosteroid effect. However, all of the available tocolytic agents carry significant risks to the mother and fetus. As such, administration of these agents should be given only when the potential benefits outweigh the risks of administration. Evaluation for fetal pulmonary maturity and intrauterine infection, in concert with evaluation of gestational age-dependent risks of prematurity, may be helpful in determining whether tocolysis should be attempted. Adjunctive antibiotic administration has not been shown to reduce maternal or infant morbidity in the face of preterm labor. However, such treatment offers a reduction of chorioamnionitis, prolongation of latency, and a possible reduction of neonatal infectious and gestational age-dependent morbidity in the setting of pPROM remote from term. Finally, current guidelines recommend the administration of intrapartum GBS prophylaxis when preterm birth or prolonged membrane rupture is anticipated if GBS carrier status is unknown or positive. Intrapartum treatment with intravenous penicillin or ampicillin is appropriate.

Adrenal Cortex Hormones↗

PubMed1996

Fibronectin binding and cell surface hydrophobicity contribute to adherence properties of group B streptococci.

The matrix protein, fibronectin, which is detectable in various tissues, when present in the vaginal fluid of women in labour, indicates the rupture of membranes. It is known that many bacteria adhere to fibronectin, thus establishing a first step of infection. In women in labour, group B streptococci are common agents of chorioamnionitis. For group B streptococci, unspecific adherence mechanisms like negative net charge and hydrophobic interactions have already been discussed in literature. In the present study, group B streptococci isolates from 57 patients with premature rupture of membranes were studied for fibronectin binding activities, using a particle agglutination assay and for cell surface hydrophobicity, by testing adhesion to hydrocarbons. Particle agglutination assays and adhesion assays were done with strains grown on blood-containing media and media without blood. Fibronectin binding was shown to be present in 14 and 11 out of 57 isolates grown on Mueller-Hinton and Tryptic Soy agar, respectively. When the strains were grown on blood-containing media, fibronectin-binding was found to be concomitant with decreased hydrophobicity. According to the results obtained in a total of 57 strains, cell surface hydrophobicity is an unspecific adhesion factor in group B streptococci. Fibronectin binding seems to be an additional adherence factor in some of the strains and may be assumed to play a major role in establishing infectious processes.

Bacterial Adhesion↗

PubMed2003

Soluble L-selectin, a marker of immune activation, in neonatal infection.

L-Selectin is an adhesion molecule shed from the surface of lymphocytes and granulocytes upon activation. Soluble L-selectin in the plasma can thus reflect immune activation and is elevated in several pathological states. Our objective was to evaluate plasma levels of L-selectin as an immune activation marker in neonates and to determine whether it can serve as a marker of infection, either neonatal or congenital, or if it is affected by the mode of delivery and obstetrical or perinatal complications. A solid-phase ELISA was used on 89 sera from neonates less than 2 days of age, according to the manufacturer's instructions. Levels of soluble L-selectin in the neonate were lower than those of older infants and children and comparable to the levels seen in adults. There was no difference between levels of soluble L-selectin of premature (median, 1172 ng/ml) and full-term babies (median, 1151 ng/ml) or between babies born via vaginal (median, 1233 ng/ml) or cesarean delivery (median, 1146 ng/ml). Conditions such as preeclampsia or administration of steroids to the mother did not affect the levels of L-selectin in the neonate. In contrast, the presence of maternal clinical chorioamnionitis resulted in an increase in levels of L-selectin in the neonate (median, 1377 vs 1072 ng/ml, p = 0.02), as did neonatal sepsis (median, 1331 vs 1149 ng/ml, p = 0.026). Soluble L-selectin, and thus immune activation level, is highest in neonates with neonatal infection and needs to be further evaluated as a surrogate marker for diagnosing sepsis in the neonate.

Biomarkers↗

PubMed2004

Pre- and postnatal inflammatory mechanisms in chronic lung disease of preterm infants.

Epidemiological data suggest a strong association between chorioamnionitis and the development of chronic lung disease in preterm infants. Increased concentrations of proinflammatory cytokines present in the amniotic fluid and the systemic fetal circulation seem to be important mediators in the early inflammatory response by recruiting and activating inflammatory cells and by inducing pathways of lung injury. As a consequence vascular cell adhesion molecules are upregulated and a marked infiltration of neutrophils and macrophages as well as an increased expression of interleukin-8 mRNA in the bronchoalveolar epithelium and in the interstitial tissue takes place. These antenatal events may prime the lungs such that various injurious factors in the postnatal period provoke an excessive inflammatory response: oxygen toxicity, mechanical ventilation, inappropriate resuscitation, pulmonary and systemic infections, persistent ductus arteriosus. Besides proinflammatory cytokines, toxic oxygen radicals, lipid mediators and potent proteases may be responsible for acute and chronic lung injury. In general, an imbalance between pro- and anti-inflammatory factors can be considered as a hallmark of lung injury, and may considerably affect normal alveolarisation and pulmonary vascular development by inducing growth arrest of the immature lung.

Cell Adhesion Molecules↗

PubMed2001

Maternal antecedents for cerebral palsy in extremely preterm babies: a case-control study.

The study aimed to identify significant antenatal risk factors for cerebral palsy (CP) among extremely preterm infants with a matched case-control design. Infants born between 1989 and 1996 at 24 to 27 weeks' gestation who survived to hospital discharge were evaluated: 30 with a proven diagnosis of CP at 2 years corrected for prematurity and 120 control children matched for gestational age without CP. Information on maternal obstetric risk factors and medication was obtained. Matched analyses were performed and odds ratios (OR) and 95% confidence intervals (CI) were calculated. An antenatal diagnosis of intrauterine growth restriction was associated with an increased risk of CP (OR 6.6; 95% CI 1.8 to 25.2), while maternal administration of corticosteroids was associated with a reduced risk of CP (OR 0.4; 95% CI 0.1 to 0.98). A high rate of placental histopathology was achieved but no relation between clinical or histological chorioamnionitis or funisitis and CP was demonstrated. Maternal preeclampsia was not associated with a statistically significant reduction in the risk of CP. It is concluded that a reduced risk of CP in extremely preterm infants is associated with the antenatal use of corticosteroids.

Adrenal Cortex Hormones↗

PubMedDate not supplied

The fetus with gastroschisis managed by a trial of labor: antepartum and intrapartum complications.

OBJECTIVE: To assess the rate of antepartum and intrapartum complications of fetuses with antenatally diagnosed gastroschisis managed in a center that advocates a trial of labor. STUDY DESIGN: A retrospective review. The medical records of 49 fetuses (1988 to 1997) who were prenatally diagnosed with gastroschisis by a sonologist in the Ultrasound Genetic Unit, Department of Obstetrics and Gynecology at Washington University, were reviewed. RESULTS: Oligohydramnios and intrauterine growth restriction were diagnosed in 23% and 49% of the pregnancies, respectively. A total of 22 women underwent induction of labor nine for nonreassuring fetal testing, four for premature rupture of membranes, five for marked bowel dilatation, one for preeclampsia, and three for other reasons. Cesarean section (CS) was performed in 16 of 43 (37%) of women. The indications for CS were fetal distress (9 of 16 women), chorioamnionitis (2 of 16 women), breech presentation (3 of 16 women), and physician discretion (2 of 16 women). No significant differences in Apgar scores were observed between the fetuses. Fetuses who were delivered by CS for fetal distress were more likely to have undergone an induction of labor (91% versus 44%), and they were smaller than fetuses with no evidence of fetal distress (2220 +/- 105 gm versus 2613 +/- 80 gm, p < 0.05). CONCLUSION: The incidence of antepartum and intrapartum complications in fetuses with gastroschisis is high. The rate of CS can reach 37%. These data may aid clinicians in counseling patients with gastroschisis.

Adult↗

PubMed2002

Indices of hemodynamic and respiratory functions in premature infants at risk for the development of cerebral white matter injury.

OBJECTIVE: To examine potential differences in clinical risk factors, including indices of hemodynamic and respiratory functions, of premature infants developing periventricular hemorrhagic infarction (PHI) or periventricular leukomalacia (PVL). STUDY DESIGN: Indices of hemodynamic stability and respiratory function were measured prospectively during the first week of life in a cohort of 100 premature infants with respiratory distress. Maternal history was retrospectively reviewed. These data were correlated with cranial ultrasonography using one-way ANOVA, Bonferroni multiple comparisons, and Wilcoxon rank sum tests. Longitudinal analysis was performed using Generalized Estimating Equations. RESULTS: Fifty-two infants with normal cranial ultrasound studies were compared to 12 with PHI and 9 with PVL. Infants developing PHI had significantly lower birth weights, lower Apgar scores, were more often male and multiple gestations, and required more vasopressor support than infants with normal ultrasound studies. Infants with PHI had significantly worse indices of respiratory function than either normal infants or those with PVL. PVL was significantly associated with maternal chorioamnionitis, whereas PHI was not. CONCLUSION: These data suggest that there are important differences in the pathogenesis of PHI and PVL. A clear understanding of these differences is required before future preventive strategies can be formulated.

Brain Damage, Chronic↗

PubMed2004

The histologic fetoplacental inflammatory response in fatal perinatal group B-streptococcus infection.

OBJECTIVE: To determine the rate of histologic fetoplacental inflammation in fetuses and newborns with fatal perinatal Group B-Streptococcus (GBS) infection. STUDY DESIGN: Autopsy files (1990 to 2002) were searched for fetuses and newborns with GBS-positive post-mortem blood and/or lung cultures. The rate of histological fetoplacental inflammation in preterm (< 36 weeks gestational age) and term (> or =36 weeks) fetuses/infants was compared using chi(2) test. RESULTS: GBS infection was diagnosed in 4.9% (61/1236) of perinatal autopsies and was considered the exclusive cause of death in 58 cases (16 to 41 weeks gestation, median: 26 weeks). A total of 43 fetuses/infants (74%) were preterm, 24 (41%) were male and 33 (57%) stillborn. The histologic fetoplacental inflammatory response was age-dependent for the following variables: acute chorioamnionitis (seen in 67% of preterm vs 33% of term fetuses/infants, p < 0.05), multiple-vessel umbilical vasculitis (37 vs 7%, p < 0.05), funisitis (37 vs 13%, p < 0.05), and the presence of neutrophils in the gastrointestinal tract (35% vs none, p < 0.05). Neutrophils in the pulmonary airspaces (47 vs 33%) and pneumonia (16 vs 27%) were found with similar frequency in both groups. CONCLUSION: Histologic fetoplacental inflammation is a poor indicator of perinatal GBS infection; the sensitivity is 67% in preterm and 33% in term fetuses/newborns (overall sensitivity 59%). The higher rate of histologic inflammation in preterm fetuses/newborns suggests age-specific interactions between microorganism, host and placenta.

Chorioamnionitis↗

PubMed2006

Hyperglycemia in extremely low birth weight infants in a predominantly Hispanic population and related morbidities.

OBJECTIVE: This study describes the incidence, correlates and subsequent morbidities of hyperglycemia, a highly prevalent condition in extremely low birth weight (ELBW) infants. STUDY DESIGN: A retrospective chart review of 169 infants with birth weight (BW)<1000 g was conducted. Hyperglycemia was defined as plasma glucose level > or =150 mg/dl during the first 2 weeks of life. Data were analyzed by logistic regression, multivariate analysis and Fisher exact test. RESULTS: Overall, 88% of the study sample developed hyperglycemia in the first 2 weeks of life. Both gestational age (GA) (odds ratio (OR) 0.11, 95% confidence interval (CI)=0.01-0.89) and chorioamnionitis (OR 0.10, 95% CI=0.01-0.64) were inversely associated with hyperglycemia, whereas BW, sepsis and postnatal steroid exposure were not. After adjusting for GA, BW and postnatal steroids, hyperglycemia was associated with a statistically significant increase in retinopathy of prematurity (ROP) (OR 4.6, 95% CI 1.12-18.9). No association was found with bronchopulmonary dysplasia, intraventricular hemorrhage, death or prolonged hospital stay. CONCLUSION: Lower GA was identified as the main factor associated with hyperglycemia in ELBW infants during the first 2 weeks of life. Hyperglycemia was associated with an increased incidence of ROP; further studies need to determine if this association is causal.

Chorioamnionitis↗

PubMed2002

Expression of vascular endothelial growth factor, placental growth factor, and their receptors Flt-1 and KDR in human placenta under pathologic conditions.

The vascular endothelial growth factor (VEGF) family and its receptors have multifunctional activities besides angiogenesis, and some of these molecules are induced by hypoxia/ischemia. They are known to be expressed in human placenta, but little is known about their involvement in pathologic conditions. We have investigated the expression patterns of VEGF, placental growth factor (PlGF), and their receptors fms-like tyrosine kinase (Flt-1) and kinase insert domain-containing region (KDR) in placentas with histopathological changes. Forty-two placentas from normal and complicated pregnancies delivered in the second and third trimesters were fixed with paraformaldehyde and embedded in paraffin. In situ hybridization and immunohistochemistry were performed on serial sections. In the villi with characteristic hypoxic/ischemic changes (HIC), including increased syncytial knots, infarction, or hypercapillarization, intense immunostaining for VEGF was detected in the media of blood vessels, and increased staining for KDR was demonstrated in the endothelial cells. Strong PlGF immunoreactivity was localized to the degenerative trophoblasts around the infarctions. Marked Flt-1 mRNA expression in the syncytiotrophoblast layers of HIC villi was identified, but some samples did not show ligand expression in these regions. Positive immunostaining for VEGF, PlGF, and Flt-1 was observed in infiltrated neutrophils and macrophages in the placentas with chorioamnionitis (CAM). These findings suggested that in the hypoxic/ischemic regions, VEGF and KDR expression is increased within the villous vessels by paracrine regulation, whereas the expression of PlGF and Flt-1 is enhanced in villous trophoblasts by autocrine regulation. The Flt-1 gene may also be up-regulated directly by hypoxia/ischemia independently of ligand mediation. Furthermore, the results indicated that VEGF and PlGF stimulate inflammatory cell migration by autocrine regulation via the Flt-1 receptor in the CAM placenta. Thus, various functions of VEGF family members participate in the development of pathologic changes in the placenta.

Adult↗

PubMedDate not supplied

Amniotic fluid lactoferrin in intrauterine infection.

Lactoferrin (LF) has been found in most biological fluids including amniotic fluid and cervical mucus in pregnant women and is released from neutrophils in response to inflammation. It is an important component of the host defence against microbial infections due to its antimicrobial properties. Premature labour is caused by amniotic infection and high concentrations of inflammatory cytokines in amniotic fluid with infection are well established. In the present study, LF levels of intrauterine infection in amniotic fluid were measured and the biological significance of LF was investigated. The effects of LF on IL-6 production in cultured amnion cells were also investigated. The concentrations of LF and IL-6 in amniotic fluid with chorioamnionitis (CAM) were 8.76+/-0.65 microg/ml and 6.92+/-4.88 ng/ml (n = 28), respectively, and both were significantly higher (P<0.01) than those without CAM (0.86+/-0.81 microg/ml and 0.34+/-0.25 ng/ml; n = 31). LF and IL-6 levels were significantly higher (P<0.01) with CAM. A significant positive correlation between LF and IL-6 levels in amniotic fluid was found (r = 0.91, P<0.01). To our knowledge, this was the first study of its kind, which shows that IL-6 production induced by lipopolysaccharide in cultured cells was significantly inhibited below physiological concentration of LF in the amnion. In addition, the immunohistochemical localization of LF in fetal membranes was investigated. In the fetal membranes with CAM, strong positive staining was observed in amniotic and chorionic membranes, with leucocyte migration, while weak staining was observed in membranes without CAM. These results show conclusively that LF suppresses amniotic IL-6 production under the conditions of intrauterine infection.

Amnion↗

PubMed2000

Risk factors for neonatal intraventricular haemorrhage in spontaneous prematurity at 32 weeks gestation or less.

In this study we aimed to establish which clinical and histopathological factors are associated with early-onset neonatal intraventricular haemorrhage (IVH) in non-iatrogenic preterm delivery before 32 weeks of gestation. We retrospectively reviewed all singleton pregnancies delivered before 32 weeks of gestation after spontaneous onset of preterm labour or preterm membrane rupture during the period January 1993 to June 1997. Clinical and histopathological data in cases with IVH diagnosed at neonatal cranial ultrasound within 72 h of birth (n = 17) were compared with those of neonates not experiencing this complication (non-IVH) (n = 54). Histological lesions analysed were those of acute inflammation and those on a uteroplacental vascular basis. Statistical methods included the Wilcoxon rank sum test, Fisher's exact test, and logistic regression analysis. A P<0.05 was considered significant.IVH and non-IVH groups were not significantly different in birthweight, gestational age at delivery, cord pH at birth, rates of 5-min Apgar score below 7, caesarean delivery, diagnosis of clinical chorioamnionitis or antenatal administration of steroids. Respiratory distress syndrome was more frequently diagnosed in the IVH than non-IVH group (64 per cent versus 33 per cent, P=0.02). Placental acute inflammatory or uteroplacental vascular lesions were present in 100 per cent of IVH neonates versus 22 per cent of non-IVH cases (P<0.001). Logistic regression analysis demonstrated that only respiratory distress syndrome (P = 0.04) and histological evidence of acute placental inflammation (P = 0.02) were significantly and independently associated with IVH. Histopathological evidence of acute inflammatory placental lesions is the best predictor of occurrence of neonatal IVH.

Adult↗

PubMed2001

Antenatal corticosteroids and placental histology in preterm birth.

To assess the effects of antenatal corticosteroid use on placental histopathology, we have reviewed a database of 463 consecutive non-anomalous singleton liveborns delivered at less than 32 weeks between April 1988 and December 1994, of which 280 received one or more doses of corticosteroids for promotion of fetal lung maturation. Patients were grouped by the number of corticosteroid doses received (analyzed as none, 1, 2 and 3 or more doses). Clinical and demographic factors were recorded prospectively. Placental histopathology was reviewed blinded to clinical factors except gestational age, and 42 distinct placental lesions were examined and scored for severity. Data were analyzed by contingency tables, one-way analysis of variance, and linear regression analysis. Among clinical variables, univariate analysis showed that the number of corticosteroid doses was significantly related to presence of labour prior to delivery, pre-eclampsia, premature rupture of membranes and clinical suspicion or diagnosis of chorioamnionitis. Using linear regression analysis with these clinical variables as confounders, increased number of doses of antenatal corticosteroids was related to increased severity of villous fibrosis and stromal mineralization, and fewer villous infarcts.

Adrenal Cortex Hormones↗

PubMed2002

The origins of stillbirth: infectious diseases.

This article reviews the literature on infectious diseases as a cause of stillbirth. Identifying a specific infection as a cause of stillbirth is limited by many obstacles. Nevertheless, "good faith" efforts estimate that approximately 9% to 15% of stillbirths are caused by infections. Infection may be especially important as a cause of stillbirth occurring early in pregnancy. Recognized causes include syphilis, toxoplasmosis, parvovirus B-19, chorioamnionitis, and Listeria monocytogenes. Other organisms that are "purported to cause" stillbirth include the genital mycoplasmas, Chlamydia trachomatis, HIV, group B streptococci, and others. No single strategy has been developed for effective prevention of stillbirth caused by infection. Six potential strategies and their rationale are presented, but the low rate of stillbirth in most situations would require large intervention trials for hypothesis testing. Infection is an important cause of stillbirth. Within the framework if determining epidemiological etiology, research should be initiated in the role of infectious causes.

Chlamydia Infections↗

PubMed2004

Placental findings in low-risk, singleton, term pregnancies after uncomplicated deliveries.

Should all placentas be sent to pathology for examination after delivery room triage? A cohort of 88 placentas was prospectively obtained and examined from low-risk, singleton, term pregnancies after uneventful delivery. All patients had a normal prenatal testing and anatomy ultrasound. Fifty-one placentas (58%) were normal. Thirty-seven of the placental cohort (42%) had abnormal findings. Thirteen of the abnormal placentas (35.1%) showed pathology unassociated with fetal compromise. Twenty-four of the placentas (27.3% of the total cohort and 64.9% of the abnormal placentas) showed findings associated with fetal compromise. The most common pathologies were marginal cord insertion, chorioamnionitis, and abruption. Routine placental examination is not indicated, according to our data, in low-risk, singleton, and term pregnancy unless the placenta is determined to be abnormal at delivery examination.

Adult↗

PubMed2007

The role of inflammation and infection in preterm birth.

Inflammation has been implicated in the mechanisms responsible for preterm and term parturition, as well as fetal injury. Out of all of the suspected causes of preterm labor and delivery, infection and/or inflammation is the only pathological process for which both a firm causal link with preterm birth has been established and a molecular pathophysiology defined. Inflammation has also been implicated in the mechanism of spontaneous parturition at term. Most cases of histopathological inflammation and histological chorioamnionitis, both in preterm and term labor, are sub-clinical in nature. The isolation of bacteria in the amniotic fluid, known as microbial invasion of the amniotic cavity, is a pathological finding; the frequency of which is dependent upon the clinical presentation and gestational age. This article reviews the role of inflammation in preterm and term parturition.

Amnion↗

PubMed1993

[Diagnostic results and their clinical interpretation--or: what you never wanted to know about diagnosis].

Diagnostic test results become only relevant if clinically interpreted. A key issue in clinical interpretation is the predictive value which, however, in daily practice and even in medical literature, is frequently misunderstood, as if the predictive value would be about the same as sensitivity. Sensitivity and specificity of a test only together with the prevalence of the target disease allow estimation of the predictive values. This correlation will be exemplified with the diagnosis of chorioamnionitis measuring C-reactive protein: The predictive value is not constant, but depends on prevalence. Prevalence, however, changes with clinical situation, therefore similar test results must be clinically interpreted very differently. Finally, considering these correlations, decision analysis using the "threshold model" shows how to develop a rational, quantitative approach to the selection and interpretation of diagnostic tests. Although more and more studies on decision analysis in diagnostics are published, up to now, there is little response in day-to-day practice. This situation should be changed for the sake of our patients.

C-Reactive Protein↗