Absence Of Chorioamnionitis Research Articles

Death of children with Down syndrome by gestational age and cause.

We often encounter preterm infants with Down syndrome (DS) who die in the neonatal intensive care unit (NICU). In this study, we examined survival until NICU discharge and assessed the developmental prognosis of preterm infants with DS. We retrospectively reviewed 416 infants with DS hospitalized during the past 27 years at our NICU. Death occurred in 8/20 (40%) infants at <32 weeks' gestation, 11/23 (48%) at 32-33 weeks, 9/99 (9%) at 34-36 weeks, and 9/274 (3%) at >36 weeks. In total, 84% of infants who died and 25% of those who survived had a non-reassuring fetal status (p < 0.001). Sex, small-for-gestational-age status, and postnatal transport were not associated with death. The main causes of death were bronchopulmonary dysplasia in 4/8 (50%) infants at <32 weeks' gestation, transient abnormal myelopoiesis in 11/20 (55%) and lymphatic dysplasia in 6/20 (30%) at 32-36 weeks, and varied causes at >36 weeks. Among survivors born at <34 weeks' gestation, 6/19 (32%) aged >2 years had moderate or severe cerebral palsy. These data on the high mortality and morbidity of preterm infants with DS may be useful for patient treatment and parent counseling in NICUs treating critically ill infants. Most infants with Down syndrome born at <34 weeks' gestation are born by cesarean section because of the non-reassuring fetal status. The mortality rate before discharge for infants with Down syndrome born at <34 weeks' gestation was 40%, and 30% of survivors developed moderate or severe cerebral palsy. The risk of death due to bronchopulmonary dysplasia and pulmonary hypertension was high in very preterm infants with Down syndrome despite the absence of chorioamnionitis. Infants with Down syndrome were born 1-2 weeks earlier than unaffected controls.

Individualized treatment of preterm premature rupture of membranes to prolong the latency period, reduce the rate of preterm birth, and improve neonatal outcomes

Preterm premature rupture of membranes complicates approximately 3% of pregnancies. Currently, in the absence of chorioamnionitis or placental abruption, expectant management, including antenatal steroids for lung maturation and prophylactic antibiotic treatment, is recommended. The benefits of individualized management have not been adequately explored. This study aimed to compare the impact of 2 different management strategies of preterm premature rupture of membranes in 2 tertiary obstetrical centers on latency of >7 days, latency to birth, chorioamnionitis, funisitis, and short-term adverse maternal and neonatal outcomes. This was a multicenter retrospective study of women with singleton pregnancies with preterm premature rupture of membranes from 23 0/7 to 33 6/7 weeks of gestation between 2014 and 2018 and undelivered within 24 hours after hospital admission managed at Sunnybrook Health Sciences Center, Toronto, Canada (standard management group), and BCNatal (Hospital Clínic of Barcelona and Hospital Sant Joan de Déu Barcelona), Barcelona, Spain (individualized management group), following local protocols. The standard management group received similar management for all patients, which included a standard antibiotic regimen and routine maternal and fetal surveillance, whereas the individualized management group received personalized management on the basis of amniocentesis at hospital admission (if possible), to rule out microbial invasion of the amniotic cavity and targeted treatment. The exclusion criteria were cervical dilatation >2 cm, active labor, contraindications to expectant management (acute chorioamnionitis, placental abruption, or abnormal fetal tracing), and major fetal anomalies. The primary outcome was latency of >7 days, and the secondary outcomes included latency to birth, chorioamnionitis, and short-term adverse maternal and neonatal outcomes. Statistical comparisons between groups were conducted with propensity score weighting. A total of 513 pregnancies with preterm premature rupture of membranes were included in this study: 324 patients received standard management, and 189 patients received individualized management, wherein amniocentesis was performed in 112 cases (59.3%). After propensity score weighting, patients receiving individualized management had a higher latency of >7 days (76.0% vs 41.6%; P<.001) and latency to birth (18.1±14.7 vs 9.7±9.7 days; P<.001). Although a higher rate of clinical chorioamnionitis was suspected in the individualized management group than the standard group (34.5% vs 22.0%; P<.01), there was no difference between the groups in terms of histologic chorioamnionitis (67.2% vs 73.4%; P=.16), funisitis (57.6% vs 58.1%; P=.92), or composite infectious maternal outcomes (9.1% vs 7.9%; P=.64). Prolonged latency in the individualized management group was associated with a significant reduction of preterm birth at <32 weeks of gestation (72.1% vs 90.5%; P<.001), neonatal intensive care unit admission (75.6% vs 83.0%; P=.046), and neonatal respiratory support at 28 days of life (16.1% vs 26.1%; P<.01) compared with that in the standard management group. Moreover, prolonged latency was not associated with neonatal severe morbidity at discharge (survival without severe morbidity, 80.4% vs 73.5%; P=.09). Individualized management of preterm premature rupture of membranes may prolong pregnancy and reduce preterm birth at <32 weeks of gestation, the need for neonatal support, and neonatal intensive care unit admissions, without an increase in histologic chorioamnionitis, funisitis, neonatal infection-related morbidity, and short-term adverse maternal and neonatal outcomes.

VP31.08: Placental profiling in women with confirmed COVID‐19 infection

to profile the typical lesion characteristics found in placentas of women with COVID-19. Consecutive placental specimens were acquired from pregnant women with confirmed COVID-19 infection by RT-PCR delivering between May 2019 – June 2021 in a tertiary reference hospital. Histological analysis of the placenta was carried out by the same pathologist in all cases and categorised according to the Amsterdam classification for histopathology analysis of the placenta. A principal component analysis was performed to assess the typical placental profile in women with COVID-19 infection. A total of 351 positive-COVID-19 consecutive placentas were analysed. Three main COVID-19 placental profiles were found after principal component analysis. The first profile comprised maternal venous malperfusion, deciduitis, thrombosis, and atherosis with absence of chorioamnionitis, explaining 16% of all placentas. The second placental profile was made of fetal venous malperfusion, placental chorangiosis, thrombosis with absence of atherosis and fibrinoid necrosis explaining 13% of all observations. The third profile comprised placental villitis, thrombosis, and fibrinoid necrosis with absence of fetal venous malperfusion, and deciduitis, explaining 12% of all observations. The most common COVID-19 placental lesion profile comprises maternal venous malperfusion, deciduitis, thrombosis, and atherosis followed by fetal venous malperfusion, placental chorangiosis, and thrombosis. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

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

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

Nucleic Acid-Based Screening of Maternal Serum to Detect Viruses in Women with Labor or PROM.

The purpose of this study was todetermine whether timing of the initiating event of spontaneous labor (either uterine contractions with intact fetal membranes or rupture of membranes prior to labor (PROM)) is associated with maternal viral infection. It was a prospective case control study of women with either spontaneous labor or PROM occurring < 37weeks' gestation ("cases") or at term ("controls"). An initial unbiased screen for viruses was performed with next-generation sequencing (NGS) in serum pooled from eight cases delivered by C/S and represents a range of gestational ages, membrane rupture status, and presence or absence of chorioamnionitis. Custom PCR was used to query individual patient samples from the original cohort. The NGS screen generated 15 million reads. Seven unique viral sequences were detected in two cases, all identified as torque teno virus (TTV), an ubiquitous DNA anellovirus of no known pathogenicity. Using nested and semi-nested PCR, sera from 72 patients (47 cases and 25 matched controls, stratified by ROM status) were screened for the 3 subtypes of anelloviruses (TTV, TTMDV, or TTMV). These were found in 43/47 cases (91%) and 16/25 controls (64%) (p = 0.012, OR = 5.9 (95% CI = 1.4-29.9)). In logistic regression, pregnant women with at least one type of anellovirus were more likely to experience preterm labor than those with no anellovirus (p = 0.03, aOR = 4.6, CI = 1.2-18.7). Among women experiencing a spontaneous initiating event of labor, TTV virus was more likely to be present in the serum of preterm than term patients. TTV may have a role in determining the timing of parturition.

Preterm birth subtypes, placental pathology findings, and risk of neurodevelopmental disabilities during childhood

IntroductionPreterm birth (PTB) and in-utero inflammation are recognized risk factors of neurodevelopmental disabilities (NDDs); however, their combined role in NDDs is unknown. We examined the independent and joint association of PTB and placental histological findings with the childhood risk of NDDs (overall and by subgroups including autism spectrum disorder (ASD) and ADHD). MethodsWe analyzed data from the Boston Birth Cohort, where mother-infant pairs were enrolled at birth and followed from birth onwards. Birth outcomes, placental pathology and NDDs were obtained from electronic medical records. Placental pathology was categorized using a standardized classification system proposed by the Amsterdam Placental Workshop Group. ResultsPTB (all, including spontaneous, medically indicated) was an independent risk factor for NDDs. Placental histological chorioamnionitis (CA) and PTB additively increased the odds of NDDs (aOR: 2.16, 95% CI: 1.37, 3.39), as well as ADHD (aOR: 2.75, 95% CI: 1.55, 4.90), other developmental disabilities (aOR: 1.96, 95% CI: 1.18, 3.25) and possibly ASD (aOR: 2.31, 95% CI: 0.99, 5.39). The above associations were more pronounced in spontaneous than medically indicated PTB. PTB alone in the absence of CA only had a moderate association with ASD and ADHD. Placental maternal vascular malperfusion alone or in combination with PTB was not associated with the risk of NDDs. DiscussionOur study provided new insights on PTB and NDDs by further considering preterm subtypes and placental histology. We revealed that children of spontaneous PTB along with histological CA were at the highest risk for a spectrum of NDDs.

Histologic chorioamnionitis in preterm infants: correlation with brain magnetic resonance imaging at term equivalent age

BackgroundTo explore the associations between histologic chorioamnionitis with brain injury, maturation and size on magnetic resonance imaging (MRI) of preterm infants at term equivalent age.MethodsPreterm infants (23–36 weeks’ gestational age) were recruited into two longitudinal cohort studies. Presence or absence of chorioamnionitis was obtained from placental histology and clinical data were recorded. MRI at term-equivalent age was assessed for brain injury (intraventricular haemorrhage, cysts, signal abnormalities), maturation (degree of myelination, gyral maturation) and size of cerebral structures (metrics and brain segmentation). Histologic chorioamnionitis was assessed as a predictor of MRI variables using linear and logistic regression, with adjustment for confounding perinatal variables.ResultsTwo hundred and twelve infants were included in this study, 47 (22%) of whom had histologic chorioamnionitis. Histologic chorioamnionitis was associated with higher odds of intraventricular haemorrhage (odds ratio [OR] (95% confidence interval [CI]) = 7.4 (2.4, 23.1)), less mature gyral maturation (OR (95% CI) = 2.0 (1.0, 3.8)) and larger brain volume (mean difference in cubic centimeter (95% CI) of 14.1 (1.9, 26.2)); but all relationships disappeared following adjustment for perinatal variables.ConclusionHistologic chorioamnionitis was not independently associated with IVH, less mature gyral maturation or brain volume at term-equivalent age in preterm infants.

Magnesium sulfate for neuroprotection in the setting of chorioamnionitis

Purpose: We examined the effects of magnesium on premature neonatal outcomes complicated by chorioamnionitis. Materials and methods: We conducted a secondary analysis of data from the BEAM Trial, an RCT to determine if antenatal magnesium decreases the incidence of CP in preterm birth. We compared the effect of magnesium sulfate by the presence or absence of chorioamnionitis. Outcomes examined include CP, IVH, NEC, BPD, and assessments of mental and motor disability. Logistic regression was used to estimate adjusted odds ratios of each outcome. Results: About 1944 women were included in this analysis of which 228 were diagnosed with chorioamnionitis. Demographic characteristics were similar between women randomized to receive magnesium or placebo. Magnesium therapy demonstrated no significant reduction in CP in the presence of chorioamnionitis (OR 0.76, CI: 0.19–2.76) but does demonstrate benefit in the absence of chorioamnionitis (OR 0.52, CI: 0.31–0.86). Conclusions: Antenatal magnesium did not show a clear neuroprotective effect in the setting of chorioamnionitis.

The placental membrane microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnionitis

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality and is not uncommonly associated with chorioamnionitis. We recently have demonstrated that the placenta harbors a unique microbiome with similar flora to the oral community. We also have shown an association of these placental microbiota with PTB, history of antenatal infection, and excess maternal weight gain.On the basis of these previous observations, we hypothesized that the placental membranes would retain a microbiome community that would vary in association with preterm birth and chorioamnionitis. In the current study, we aimed to examine the differences in the placental membrane microbiome in association with PTB in both the presence and absence of chorioamnionitis and/orfunisitis using state-of-the-science whole-genome shotgun metagenomics. This was a cross-sectional analysis with 6 nested spontaneous birth cohorts (n = 9-15 subjects/cohort): Term gestations without chorioamnionitis, term with chorioamnionitis, preterm without chorioamnionitis, preterm with mild chorioamnionitis, preterm with severe chorioamnionitis, and preterm with chorioamnionitis and funisitis. Histologic analysis was performed with Redline's criteria, and inflammatory cytokines were analyzed in the cord blood. DNA from placental membranes was extracted from sterile swabs collected at delivery, and whole-genome shotgun sequencing was performed on the Illumina HiSeq platform. Filtered microbial DNA sequences were annotated and analyzed with MG-RAST (ie, Metagenomic Rapid Annotations using Subsystems Technology) and R. Subjects were assigned to cohorts on the basis of gestational age at delivery and independent scoring of histologic chorioamnionitis. We found that preterm subjects with severe chorioamnionitis and funisitis had increases in cord blood inflammatory cytokines. Of interest, although the placental membrane microbiome was altered in association with severity of histologic chorioamnionitis (permutational multivariate analysis of variance P= .005), there was no observable impact with either betamethasone or antibiotic treatment. In preterm subjects with chorioamnionitis, we found a high abundance of both urogenital and oral commensal bacteria. These alterations in the microbiome were accompanied by significant variation (P < .05) in microbial metabolic pathways important in the glucose-fed pentose phosphate pathway (term subjects), or glycerophopholipid metabolism, and the biosynthesis of the siderophore group nonribosomal peptides (preterm subjects). Consistent with ours and others previous findings, women who experienced spontaneous PTB harbor placental microbiota that further differed by severity of chorioamnionitis. Integrative metagenomic analysis revealed significant variation in distinct bacterial metabolic pathways, which we speculate may contribute to risk of preterm birth with and without severe chorioamnionitis.

Risk of Early-Onset Sepsis following Preterm, Prolonged Rupture of Membranes with or without Chorioamnionitis.

This study aims to determine whether preterm prolonged rupture of membranes (PPROM) increases the risk for early-onset sepsis (EOS) in preterm infants. Retrospective cohort study of infants 30 to 34 weeks' gestation from 2005 to 2014. Exposure to PPROM (rupture of membranes ≥ 18 hours) or chorioamnionitis (maternal temperature ≥ 38°C during delivery plus notation of chorioamnionitis in the medical record) was collected. The primary outcome was proven or suspected EOS. A total of 2,192 infants were included. Overall, 1,750 (80%) were not exposed to PPROM or chorioamnionitis (group 1), 381 (17%) were exposed to PPROM without chorioamnionitis (group 2), and 61 (3%) were exposed to chorioamnionitis ± PPROM (group 3). There was no difference in the incidence of proven or suspected EOS between groups 1 and 2 (5.4 vs. 5.5%, p = 0.86). Group 3 had a higher rate of EOS (24.6%) relative to groups 1 and 2 (p < 0.001). In multivariate analysis, risk of EOS was 4.1 times higher in infants exposed to chorioamnionitis. PPROM did not increase the risk of EOS in bivariate or multivariate analysis. In the absence of chorioamnionitis, PPROM does not increase the risk of proven or clinically suspected EOS in 30 to 34 weeks' gestation infants.

Rupture prématurée des membranes : peut-on proposer une prise en charge à domicile ?

Compare the maternal and neonatal outcomes in pregnancies complicated by preterm prelabour rupture of membranes (PPROM), which were managed either at home (HAD) or hospital (HC). Retrospective study in two level III maternities during 2 years. Inclusion criteria in HAD were: singleton pregnancy, PPROM between 24 and 35 weeks of gestation, absence of chorioamnionitis, clinical stability at D7 of the rupture, cervical dilatation <3 cm, patient residing in the geographic area. Thirty-two patients were included in the HAD group and 24 in the HC group. Our populations were similar in the 2 groups. The duration of latency was longer in the HAD group than in the HC group (27.5 d [20-37] versus 16.5 d [12.5 to 29.5]; P=0.026). Patients in the HAD group received fewer antibiotics with a similar rate of chorioamnionitis. No difference in terms of obstetrical and neonatal outcomes was observed. Number of days in neonatal resuscitation was lower in the HAD group than in the HC group (12.5 d [10-22] versus 43 d [20-52]; P=0.003). HAD seems to be an alternative to continuous hospitalization for patients followed for PPROM between 24 and 35 weeks. A randomized study with a larger number of patients, including other data such as maternal satisfaction and cost analysis, would be interesting to confirm those preliminary results.

Do maternal factors influence neonatal thyroid status in the extreme premature infant?

Background: In early pregnancy, maternal transfer of thyroxine (T4) significantly contributes to the foetal T4 requirements. Interruption of the maternal transfer of T4 may lead to inadequate T4 exposure, potentially leading to neurodevelopmental deficits.Aim: To determine if maternal factors are associated with the thyroid hormone status of extremely premature infants during the first five days of life.Method: This prospective study looked at 117 mothers and their extremely premature babies (born before 28 weeks’ gestation). The relationship between neonatal thyroid hormone status and maternal factors (gestation, route of delivery, exogenous maternal glucocorticoid administration, maternal free T4 (FT4), presence or absence of maternal chorioamnionitis, maternal smoking status, maternal body mass index (BMI) index, maternal thyroid peroxidase antibody status (TPO) and maternal haemoglobin levels) were evaluated. Multiple linear regression was used to study independent factors affecting neonatal thyroid function.Results: Mean gestational age was 25+5 ± 1.3 weeks (range 22+0 to 27+6). Neonatal FT4 strongly correlated with gestation, with a greater severity of hypothyroxinaemia associated with lower gestation (r = 0.6, p < 0.0001). Multiple regression found gestation to be the only independent factors affecting thyroid status (beta coefficient = 0.08, p = 0.01), and no maternal factors were found to be associated with neonatal thyroid status.Conclusion: Neonatal thyroid status in extreme preterm infants is independently affected by gestation and not maternal factors such as route of delivery, exogenous maternal glucocorticoid administration, third trimester maternal FT4, presence or absence of chorioamnionitis, smoking status, BMI, TPO status or haemoglobin levels. The severity of neonatal hypothyroxinaemia increases with lower gestational age.

Robust Early Immune Function in Preterm Infants

Aims: To detail the systemic inflammatory response in the preterm infant by examining functional neutrophil activation over the first week of life. Method: We prospectively collected serial blood samples from premature infants (n=51; < 32 weeks gestation) on day 0, 1, 2 and 7 of life and from adult controls (n=12). Whole blood CD11b and Toll-like Receptor 4 (TLR4) expression as well as reactive oxygen intermediate (ROI) production were evaluated using appropriate antibodies and fluorescent substrates via flow cytometry at baseline. Premature infants were divided into normal and abnormal outcome groups according to Cranial USS findings [Normal (n=41): Grade 0-2 intraventricular haemorrhage (IVH); Abnormal (n=10): Grade 3-4 IVH, Periventricular Leukomalacia or death]. Results: Preterm infants in both outcome groups have elevated baseline CD11b, TLR4 expression, and ROI production compared with adults over the first week of life. These results were not associated with the presence or absence of chorioamnionitis. Figure Conclusions: Preterm infants have robust baseline immune responses irrespective of outcome. These results are comparable to the adult immune response.

Antenatal steroids may reduce adverse neurological outcome following chorioamnionitis: Neurodevelopmental outcome and chorioamnionitis in premature infants

To examine the effect of antenatal steroid exposure and in utero inflammation on the development of severe intraventricular haemorrhage, periventricular leukomalacia and long-term neurological outcome in infants less than 30 completed weeks gestation. Infants less than 30 completed weeks gestation from January 1996 to July 2001 were identified from a prospectively managed database. Placental pathology was reviewed for the presence or absence of chorioamnionitis and funisitis. Infants were divided into three groups depending on the degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, birthweight, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen requirement were collected. Cerebral ultrasound studies were examined for evidence of intraventricular or intraparenchymal echodensity and periventricular leukomalacia. Long-term neurological outcome was assessed by neurological examination for cerebral palsy and by Griffiths Mental Developmental Assessment for general developmental quotient. Two hundred and twenty infants were identified. The mean gestational age was 27.7 weeks and the mean birthweight 1092 g. Seventy-two per cent of mothers had received a complete course of antenatal steroids. The risk of Grade III intraventricular haemorrhage or intraparenchymal echodensity was associated with exposure to in utero inflammation if a complete course of antenatal steroids had not been received (P = 0.002). This association did not exist if a complete course of antenatal steroids was given (P = 0.62). Fourteen infants had cerebral palsy (7%). The presence of cerebral palsy was also associated with in utero inflammation in the absence of complete antenatal steroid cover (P = 0.03) and not in the presence of complete cover (P = 0.59). The mean general developmental quotient on Griffiths Mental Developmental Assessment at 12 months or 3 years was not affected by exposure to in utero inflammation regardless of antenatal steroid exposure. Risk of intraventricular haemorrhage or intraparenchymal echodensity and cerebral palsy was associated with in utero inflammation in the absence of a complete course of antenatal steroids. A complete course of antenatal steroids appeared to extinguish any association between in utero inflammation and adverse neurological outcome.

Interleukin-1 Balance in the Lungs of Preterm Infants Who Develop Bronchopulmonary Dysplasia

Background: The local pulmonary balance between the agonist and antagonist of interleukin-1 (IL-1) may influence the development of inflammatory disease and resultant structural damage in a variety of human diseases including adult respiratory distress syndrome and asthma. Objectives: We tested the hypothesis that IL-1 cytokines are early markers for bronchopulmonary dysplasia (BPD), when measured in tracheal aspirates (TAs) obtained from premature infants being ventilated for respiratory distress syndrome during the first week of life. Methods: Serial TAs were collected on days 1, 3, 5 and 7 from 35 preterm infants (16 BPD, 19 non-BPD) in the absence of chorioamnionitis, and were assayed for IL-1 cytokines and leukocytes. Results: In spite of comparable maternal demographic and clinical characteristics, premature infants who developed BPD had higher levels of IL-1 receptor antagonist (Ra) in their airways on the first day of life. This antagonist IL-1Ra was an early and persistent marker for BPD during the first week of life. The agonist IL-1β also increased significantly for BPD patients early, both compared to non-BPD patients, and also within the BPD group. While the early (day 1) IL-1 antagonist/agonist molar balance offered protection, by days 5 and 7, a threshold for IL-1Ra in the presence of increasing IL-1β expression-favored pro-inflammation in the BPD group. Conclusions: We conclude that a strong and early expression of airway antagonist (IL-1Ra) proves ultimately to be sub-optimal and non-protective due to the robust expression of airway agonist (IL-1β) seen by day 5 in premature infants who develop BPD.

Host defense proteins in vernix caseosa and amniotic fluid

This study was undertaken to define the spectrum, activity, and spatial distribution of antimicrobial peptides in vernix caseosa and amniotic fluid in the absence of clinical chorioamnionitis. Characterization of innate immune proteins in vernix and amniotic fluid obtained from pregnancies with gestational ages greater than 37 weeks by Western analysis, immunohistochemistry, and antimicrobial growth inhibition assay. Lysozyme, lactoferrin, human neutrophil peptides 1-3, and secretory leukocyte protease inhibitor were identified by Western analysis in vernix suspensions (n = 25) and amniotic fluid samples (n = 10). Three other important antimicrobial proteins, human beta defensin-2, lactoperoxidase, and LL-37 were not detected. Amniotic fluid and soluble extracts of vernix exhibited muramidase (lysozyme) activity, and there was selective efficacy in inhibiting growth of common perinatal pathogens. Antimicrobial peptides were concentrated in discrete, organized, acellular "granules" embedded in the vernix lipid matrix. In the absence of chorioamnionitis, vernix and amniotic fluid contain an organized pool of antimicrobial peptides with a defined spectrum of bioactivity against common bacterial and fungal pathogens.

Chorioamnionitis/funisitis and the development of bronchopulmonary dysplasia.

To examine the association between chorioamnionitis with or without funisitis and bronchopulmonary dysplasia in infants less than 30 completed weeks gestation given the current standards of antenatal steroid and surfactant use. Infants included in the study were those delivered at less than 30 completed weeks gestation from January 1996 to July 2001, identified from a prospectively managed database. Placental pathology was reviewed for the presence or absence of chorioamnionitis and funisitis. Infants were divided into three groups depending on degree of exposure to fetal inflammation (no inflammation, chorioamnionitis only and chorioamnionitis and funisitis). Data relating to gestational age, sex, antenatal steroid exposure, surfactant treatment, days of positive pressure ventilation and days of oxygen required were collected. Bronchopulmonary dysplasia was defined as death due to respiratory failure or any oxygen requirement at 36 weeks postmenstrual age. Two hundred and forty-one infants were included in the study. The mean gestational age was 27.7 weeks and mean birthweight 1089 g. One hundred and sixty-one infants were not exposed to any in utero inflammation, 40 showed chorioamnionitis and 40 showed chorioamnionitis and funisitis. There was no significant difference between antenatal steroid and surfactant treatment between the three groups. There was no significant difference between the three groups in the development of bronchopulmonary dysplasia. Low gestational age was the most significant predictor of developing bronchopulmonary dysplasia. The risk of developing bronchopulmonary dysplasia is not increased following exposure to chorioamnionitis or funisitis in the context of current antenatal steroid and surfactant use. The most significant predictor for developing bronchopulmonary dysplasia is gestational age at the time of delivery.

Eosinophilic/T-cell chorionic vasculitis.

Chorionic vasculitis is the hallmark of a fetal response in chorioamnionitis. There are five highly characteristic findings: (1) leukocyte migration is not concentric but rather radiates toward the infected amniotic fluid; (2) the infiltrate is primarily neutrophils; (3) multiple chorionic vessels, first veins and then arteries, are usually involved; (4) the infiltrate never extends into the vasculature of stem villi; and (5) it is rare in the absence of chorioamnionitis (or its precursors). Here we describe a new form of chorionic vasculitis characterized by an infiltrate composed primarily of eosinophils and CD3+ T lymphocytes that very focally involves a single chorionic vessel (artery or vein), that radiates away from the amniotic fluid (i.e., toward the intervillous spaces), and that may extend into the stem villous vasculature; this lesion occurs in the absence of any evidence of chorioamnionitis. During the past 7+ years, using accepted placental review criteria, we have examined 7104 placentas and identified 14 cases of eosinophilic/T-cell chorionic vasculitis (or related lesions). Although the frequency of diagnosis in the placentas examined was 0.197%, its true incidence cannot be estimated because of its very focal nature and the limited nature of placental disk sampling. Its etiology and significance are unknown, but it may represent a focal immune-mediated vasculitis.

Ultrasonographic evaluation of cervical length in pregnancies complicated by preterm premature rupture of membranes.

To evaluate the usefulness of transvaginal ultrasonography in the determination of the risk of preterm delivery and chorioamnionitis in pregnancies affected by preterm premature rupture of membranes preterm premature rupture of membranes. One hundred and one singleton pregnancies with preterm premature rupture of membranes were included in this prospective study over a 3-year period. Patients underwent cervical length measurement by transvaginal ultrasonography at admission and thereafter, in the absence of chorioamnionitis, were managed expectantly. The median time interval between admission and delivery (latency period) was 48 h. A cervical length of less than 20 mm was associated with a significant risk of early delivery (mean latency period was 59.44 +/- 159.93 h vs. 240.94 +/- 364.67; P < 0.05). There was no relation between cervical length and occurrence of chorioamnionitis or neonatal sepsis. These data suggest that the use of transvaginal ultrasonography for cervical length measurement during preterm premature rupture of membranes may predict an early delivery but cannot anticipate the risk of chorioamnionitis or neonatal sepsis.

Chorioamnionitis and inflammation of the fetal lung

Objective: Fetal intrauterine exposure to proinflammatory cytokines present in amniotic fluid has been associated with an increased risk of chronic lung disease. However, the impact of histologically confirmed chorioamnionitis on the fetal lung has not yet been elucidated. We therefore investigated cellular immune response, cell proliferation, and messenger ribonucleic acid cytokine expression in fetal pulmonary tissue in the presence or absence of chorioamnionitis. Study Design: Serial tissue sections were obtained from 27 fetuses at the time of autopsy. Three mothers had received antibiotics for treatment of clinical chorioamnionitis before abortion. Immunohistochemical staining of lung tissue comprised lineage-specific markers (CD68+, CD3+, neutrophil elastase). Positively stained cells were evaluated with a graticule, and cells per 5 mm2 were counted. We undertook in situ hybridization to assess the expression of interleukin 8 messenger ribonucleic acid in the fetal lung. Results: Seven of 27 fetuses had been exposed to chorioamnionitis. Fetal lungs showed a marked increase in the presence of histologically confirmed chorioamnionitis in densities of CD68+ macrophages (68 vs 9.5 cells/5 mm2, median group vs control group; P =.02) and lymphocytes (7 vs 2.5 cells/5 mm2, median chorioamnionitis vs control group; P =.05) and a similar but lesser increase in neutrophil density (16 vs 4 cells/5 mm2; difference not significant). Interleukin 8 messenger ribonucleic acid was expressed in 4 of 6 tissue specimens investigated in the chorioamnionitis group. Exposure to chorioamnionitis resulted in interleukin 8 messenger ribonucleic acid expression 7-fold higher than in the nonchorioamnionitis group; however, this difference did not achieve statistical significance. Conclusion: Chorioamnionitis was associated with an intrauterine inflammatory response of the fetal lung characterized by a severe infiltration of macrophages, neutrophils, and lymphocytes and also by an increased expression of interleukin 8 messenger ribonucleic acid. (Am J Obstet Gynecol 2001;184:173-7.)