Women In Spontaneous Preterm Labour Research Articles

A Role for the Inflammasome in Spontaneous Preterm Labor With Acute Histologic Chorioamnionitis.

Inflammasomes are cytosolic multiprotein complexes that orchestrate inflammation in response to pathogens and endogenous danger signals. Herein, we determined whether the chorioamniotic membranes from women in spontaneous preterm labor with acute histologic chorioamnionitis (1) express major inflammasome components; (2) express caspase (CASP)-1 and CASP-4 as well as their active forms; (3) exhibit apoptosis-associated speck-like protein containing a CARD (ASC)/CASP-1 complex formation; and (4) release the mature forms of interleukin (IL)-1β and IL-18. We utilized quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, immunoblotting, and immunohistochemistry to determine the messenger RNA (mRNA) and protein expression of major inflammasome components, nucleotide-binding oligomerization domain (NOD) proteins, and the pro- and mature/active forms of CASP-1, CASP-4, IL-1β, and IL-18. The ASC/CASP-1 complex formation was determined using an in situ proximity ligation assay. When comparing the chorioamniotic membranes from women in spontaneous preterm labor with acute histologic chorioamnionitis to those without this placental lesion, we found that (1) the mRNA of NLR family pyrin domain-containing protein ( NLRP) 1, NLRP3, NLR family CARD domain-containing protein 4 ( NLRC4), and NOD2 were higher; (2) the NLRP3 protein was increased; (3) the mRNA and active form (p10) of CASP-1 were greater; (4) the mRNA and active form of CASP-4 were increased; (5) the mRNA and mature form of IL-1β were higher; (6) the mature form of IL-18 was elevated; and (7) ASC/CASP-1 complex formation was increased. In conclusion, spontaneous preterm labor with acute histologic chorioamnionitis is characterized by an upregulation of NLRP3 and the active form of CASP-4, as well as increased ASC/CASP-1 complex formation, which may participate in the activation of CASP-1 and the maturation of IL-1β and IL-18 in the chorioamniotic membranes. These findings provide the first evidence that supports a role for the inflammasome in the pathological inflammation implicated in spontaneous preterm labor with acute histologic chorioamnionitis.

In women in spontaneous preterm labor, what are the benefits and harms of betamimetics compared with placebo or each other?

In women in spontaneous preterm labor, what are the benefits and harms of betamimetics compared with placebo or each other?

Prevalencia de corioamnionitis histológica en pacientes con trabajo de parto pretérmino espontáneo. Popayán, Colombia, 2014–2016

Objetivo: determinar la prevalencia de la co­rioamnionitis histológica en gestantes con trabajo de parto pretérmino espontáneo, evaluar posibles factores de riesgo y la asociación con signos clínicos y paraclínicos.Materiales y métodos: estudio descriptivo de prevalencia, con análisis secundario exploratorio en gestantes con embarazo menor a 37 semanas de gestación, con parto espontáneo, en quienes se dispuso de sus placentas para estudio histopatoló­gico, durante un periodo de 2 años, en un hospital de alta complejidad en Popayán, Colombia. Se ex­cluyeron partos pretérmino secundarios. Muestreo consecutivo, con tamaño muestral de 166 gestantes; se midieron variables sociodemográficas, clínicas, de laboratorio e imágenes diagnósticas, y resultado histopatológico de la placenta. En el análisis se es­timó la prevalencia de periodo de corioamnionitis histológica. Se obtuvo la razón de prevalencias como medida de asociación y el OR diagnóstico (ORD) con su respectivo intervalo de confianza al 95 %.Resultados: en un periodo de 2 años se analizaron 160 gestantes y sus placentas, 110 placentas fueron reportadas como positivas para corioamnionitis his­tológica con una prevalencia de 68,75 % (IC 95 %: 61,49-76,00), esta fue más prevalente en gestaciones menores de 34 semanas (RP = 1,48; IC 95 %: 1,20-1,83). En cuanto a la asociación de los síntomas y signos se encontró asociación significativa con la fiebre (ORD = 4,7; IC 95 %: 1,05-21,09), la taqui­cardia materna (ORD = 4,22; IC 95 %: 1,81-9,81), la taquicardia fetal (ORD = 3,74; IC 95 %: 1,23-11,35), movimientos respiratorios ausentes (ORD = 5,16; IC 95 %: 1,43-18,60), lago de líquido amniótico menor a 2 cm (ORD = 5,67; IC 95 %: 1,24-25,98), y presencia de neutrofilia (ORD = 2,97; IC 95 %: 1,44-6,12).Conclusiones: la prevalencia de corioamnionitis histológica es del 67% en los partos pretérmino y varió en función de la edad gestacional.

Umbilical cord CD71+ erythroid cells are reduced in neonates born to women in spontaneous preterm labor.

Preterm neonates are highly susceptible to infection. Neonatal host defense against infection seems to be maintained by the temporal presence of immunosuppressive CD71+ erythroid cells. The aim of this study was to investigate whether umbilical cord CD71+ erythroid cells are reduced in neonates born to women who undergo spontaneous preterm labor/birth. Umbilical cord blood samples (n=155) were collected from neonates born to women who delivered preterm with (n=39) and without (n=12) spontaneous labor or at term with (n=82) and without (n=22) spontaneous labor. Time-matched maternal peripheral blood samples were also included (n=111). Mononuclear cells were isolated from these samples, and CD71+ erythroid cells were identified and quantified as CD3-CD235a+CD71+ cells by flow cytometry. (i) The proportion of CD71+ erythroid cells was 50-fold higher in cord blood than in maternal blood; (ii) a reduced number and frequency of umbilical cord CD71+ erythroid cells were found in neonates born to women who underwent spontaneous preterm labor compared to those born to women who delivered preterm without labor; (iii) umbilical cord CD71+ erythroid cells were fewer in neonates born to term pregnancies, regardless of the process of labor, than in those born to women who delivered preterm without labor; and (iv) no differences were seen in umbilical cord CD71+ erythroid cells between neonates born to women who underwent spontaneous preterm labor and those born to women who delivered at term with labor. Umbilical cord CD71+ erythroid cells are reduced in neonates born to women who had undergone spontaneous preterm labor.

The ORACLE Children Study: educational outcomes at 11 years of age following antenatal prescription of erythromycin or co-amoxiclav

BackgroundAntibiotics used for women in spontaneous preterm labour without overt infection, in contrast to those with preterm rupture of membranes, are associated with altered functional outcomes in their children.MethodsFrom the...

Critical appraisal and clinical utility of atosiban in the management of preterm labor.

Preterm birth is the major cause of perinatal morbidity and mortality in the developed world, and spontaneous preterm labor is the commonest cause of preterm birth. Interventions to treat women in spontaneous preterm labor have not reduced the incidence of preterm births but this may be due to increased risk factors, inclusion of births at the limits of viability, and an increase in the use of elective preterm birth. The role of antibiotics remains unproven. In the largest of the randomized controlled trials, evaluating the use of antibiotics for the prevention of preterm births in women in spontaneous preterm labor, antibiotics against anaerobes and bacterial vaginosis-related organisms were not included, and no objective evidence of abnormal genital tract flora was obtained. Atosiban and nifedipine are the main tocolytic agents used to treat women in spontaneous preterm labor, but atosiban is the tocolytic agent with the fewest maternal - fetal side effects. A well conducted randomized controlled trial comparing atosiban with nifedipine for their effectiveness and safety is needed.

Brain Natriuretic Peptide (BNP) Produced by the Human Chorioamnion May Mediate Pregnancy Myometrial Quiescence

We aim to demonstrate that Brain Natriuretic Peptide (BNP) is synthesized and released from the fetal membranes and mediates pregnancy myometrial quiescence. Myometrium and fetal membranes (FM) were obtained from term and preterm pregnancies at the time of cesarean section, either in labor or not in labor. BNP was measured in term and preterm FM, in culture cells, and conditioned media. We found BNP (but not ANP or CNP) inhibited contractions of preterm, but not term, human myometrium. BNP (both protein and mRNA) was detected in all tissues, conditioned media and cultured cells. BNP was higher in samples from preterm women not in labor compared to those at term not in labor. BNP concentrations were significantly reduced in women in spontaneous preterm labor. We conclude that locally produced BNP may be involved in generating myometrial quiescence during pregnancy. Further, a premature decrease of BNP production may cause preterm labor.

Childhood outcomes after prescription of antibiotics to pregnant women with spontaneous preterm labour: 7-year follow-up of the ORACLE II trial

The ORACLE II trial compared the use of erythromycin and/or amoxicillin-clavulanate (co-amoxiclav) with that of placebo for women in spontaneous preterm labour and intact membranes, without overt signs of clinical infection, by use of a factorial randomised design. The aim of the present study--the ORACLE Children Study II--was to determine the long-term effects on children after exposure to antibiotics in this clinical situation. We assessed children at age 7 years born to the 4221 women who had completed the ORACLE II study and who were eligible for follow-up with a structured parental questionnaire to assess the child's health status. Functional impairment was defined as the presence of any level of functional impairment (severe, moderate, or mild) derived from the mark III Multi-Attribute Health Status classification system. Educational outcomes were assessed with national curriculum test results for children resident in England. Outcome was determined for 3196 (71%) eligible children. Overall, a greater proportion of children whose mothers had been prescribed erythromycin, with or without co-amoxiclav, had any functional impairment than did those whose mothers had received no erythromycin (658 [42.3%] of 1554 children vs 574 [38.3%] of 1498; odds ratio 1.18, 95% CI 1.02-1.37). Co-amoxiclav (with or without erythromycin) had no effect on the proportion of children with any functional impairment, compared with receipt of no co-amoxiclav (624 [40.7%] of 1523 vs 608 [40.0%] of 1520; 1.03, 0.89-1.19). No effects were seen with either antibiotic on the number of deaths, other medical conditions, behavioural patterns, or educational attainment. However, more children whose mothers had received erythromycin or co-amoxiclav developed cerebral palsy than did those born to mothers who received no erythromycin or no co-amoxiclav, respectively (erythromycin: 53 [3.3%] of 1611 vs 27 [1.7%] of 1562, 1.93, 1.21-3.09; co-amoxiclav: 50 [3.2%] of 1587 vs 30 [1.9%] of 1586, 1.69, 1.07-2.67). The number needed to harm with erythromycin was 64 (95% CI 37-209) and with co-amoxiclav 79 (42-591). The prescription of erythromycin for women in spontaneous preterm labour with intact membranes was associated with an increase in functional impairment among their children at 7 years of age. The risk of cerebral palsy was increased by either antibiotic, although the overall risk of this condition was low. UK Medical Research Council.

40: Maternal serum biomarkers to detect spontaneous preterm birth among women in preterm labor

AMONG WOMEN IN PRETERM LABOR PETER ROBILIO, JANE HITTI, JODI LAPIDUS, XINFANG LU, LEONARDO PEREIRA, MICHAEL GRAVETT, SRINIVASA NAGALLA, University of Washington, Seattle, Washington, Oregon Health & Science University, Portland, Oregon, ProteoGenix, Inc., Beaverton, Oregon OBJECTIVE: To identify potential serum biomarkers to predict spontaneous preterm birth (SPTB) from women in preterm labor by a systematic analysis of the maternal serum proteome. STUDY DESIGN: This is a secondary analysis of archived serum samples collected prospectively from 138 women in spontaneous preterm labor at 20-34 weeks gestation at the University of Washington. SPTB was defined as spontaneous delivery 34 weeks. Women diagnosed with intra-amniotic infection were excluded. Sera were immunodepleted for high abundance proteins and analyzed using fluorescence 2D gel analysis, multidimensional liquid chromatography tandem mass spectrometry (2D-LC-MS/MS), and label-free quantification (spectral counting). Pair-wise comparison was performed using 2 goodness-of-fit tests. Statistical significance was determined after adjusting for multiple comparisons. Immunodetection was used to confirm potential candidate biomarkers. RESULTS: Of 138 subjects, 59 (43%) delivered at 34 weeks (SPTB), while 79 (57%) subjects delivered at term (PTL, term group). There were no significant differences in demographic or reproductive factors between SPTB and PTL term groups. A total of 369 unique serum proteins were identified for label-free quantification. Twenty six proteins were differentially expressed (p 0.05) between PTL and SPTB samples. The majority of these proteins are produced in the placenta or decidua and included immunoregulatory, transport, and extracellular matrix proteins. CONCLUSION: Proteomic analysis identified multiple maternal serum biomarkers that accurately discriminated SPTB from labor without delivery. This may facilitate diagnosis of women in preterm labor destined for delivery from those in false labor and lead to targeted early therapy.

The effect of prepartum antibiotics on the type of neonatal bacteraemia: insights from the MRC ORACLE trials

We analysed the type of bacteraemia before discharge from Neonatal Intensive Care Units in babies born to women randomised to the MRC ORACLE Trials. There was no evidence for an effect of oral antibiotics given prior to delivery on bacteraemia due to gram negative or enterococci bacteria, but Group B streptococcal (GBS) bacteraemia was significantly reduced in women with preterm prelabour rupture of the membranes (1.58% to 0.55%, relative risk 0.34; 95% CI: 0.17-0.70). There was no detectable effect in women in spontaneous preterm labour with intact membranes as the risk of GBS bacteraemia in their babies was very small regardless of treatment.

Broad-Spectrum Antibiotics for Spontaneous Preterm Labour: The ORACLE II Randomised Trial

Summary Background Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue. Methods 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. Findings None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5·6%], co-amoxiclav 76 [5·0%], both antibiotics 91 [5·9%], vs placebo 78 [5·0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection. Interpretation This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.

Broad-spectrum antibiotics for spontaneous preterm labour: the ORACLE II randomised trial

Preterm birth after spontaneous preterm labour is associated with death, neonatal disease, and long-term disability. Previous small trials of antibiotics for spontaneous preterm labour have reported inconclusive results. We did a randomised multicentre trial to resolve this issue. 6295 women in spontaneous preterm labour with intact membranes and without evidence of clinical infection were randomly assigned 250 mg erythromycin (n=1611), 325 mg co-amoxiclav (250 mg amoxicillin and 125 mg clavulanic acid; n=1550), both (n=1565), or placebo (n=1569) four times daily for 10 days or until delivery, whichever occurred earlier. The primary outcome measure was a composite of neonatal death, chronic lung disease, or major cerebral abnormality on ultrasonography before discharge from hospital. Analysis was by intention to treat. None of the trial antibiotics was associated with a lower rate of the composite primary outcome than placebo (erythromycin 90 [5.6%], co-amoxiclav 76 [5.0%], both antibiotics 91 [5.9%], vs placebo 78 [5.0%]). However, antibiotic prescription was associated with a lower occurrence of maternal infection. This trial provides evidence that antibiotics should not be routinely prescribed for women in spontaneous preterm labour without evidence of clinical infection.

Serum levels of ritodrine used for the management of spontaneous preterm labour.

Ritodrine 0·05 mg/min gave a mean scrum level of 3·6ng/ml and 0·55mg/min gave a mean level of 204 ng/ml, when infused intravenously into women in spontaneous preterm labour. Oral administration of ritodrine, 5 mg 3 hourly, gave a mean serum level of 0·3ng/ml; 10 mg 2 hourly gave 1·3ng/ml. The drug crosses the placenta and umbilical vein cord serum levels were higher than maternal levels when it was continued until delivery. Ritodrine was detected in such a baby 24 hours after birth.