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Causes of stillbirth: an analysis of 77 cases.

OBJECTIVE: To devise preventive measures for stillbirths, which account for more than 70% of perinatal deaths in Japan. METHODS: We retrospectively reviewed the medical records of 77 women with singleton pregnancies who gave birth to stillborn infants at > or = 30 weeks between 1979 and 1996 at our hospital. RESULTS: Major malformations were present in 21 (27%) of 77 infants, including 11 infants with anencephaly. Two infants (2.6%) were severely hydropic. Preeclampsia preceded the stillbirth and might have been an indirect cause of stillbirth in 21 (39%) of 54 women whose infants had normal formations. The cause of stillbirth in 33 non-preeclamptic women was unclear in 15 (28%), abruptio placentae in 9, fetal growth retardation in 3, the HELLP syndrome in 3, chorioamnionitis in 2, and cord accident in 1. Abruptio placentae also occurred in 9 of 21 preeclamptic patients. Thus, abruptio placentae was responsible for 18 (33%) of 54 stillborn infants with a grossly normal appearance. An autopsy was performed on only 13 (24%) of 54 infants with grossly normal appearance and did not provide new information relating to deaths. CONCLUSIONS: The causes of stillbirth were many and varied, with a large proportion having no obvious cause, although autopsies were underused. Increased monitoring for women with preeclampsia and early diagnosis and prompt delivery for women with abruptio placentae might be helpful in reducing the number of stillbirths.

Abruptio Placentae↗

Is C-reactive protein really useful in preterm premature rupture of the membranes?

In a prospective blind study 380 daily serum samples from 55 women with preterm premature rupture of the membranes were analysed for C-reactive protein (CRP). Although the last CRP before delivery was higher in patients with histological chorioamnionitis (P = 0.007), considerable overlap between infected and non-infected pregnancies occurred, precluding the use of CRP as a diagnostic test if published normal levels were used. When upper limits were set at 30, 35, or 40 mg/l, the last CRP before delivery proved 90, 95 and 100% specific and 88, 92 and 100% positively predictive of infection in singleton pregnancies. Such high specificities are needed to prevent inappropriate intervention based on false positive results. We therefore propose upper limits for single estimations of 30, 35, or 40 mg/l depending on the relative risks of preterm delivery versus infection at various gestational ages. In addition, consecutive values greater than 20 mg/l appeared highly predictive of infection.

C-Reactive Protein↗

Partial placenta membranacea.

Seven pregnancies complicated by partial placenta membranacea occurring over a 2-year period are described. The condition is encountered more frequently than the total or near-total form, but is similarly associated with recurrent antepartum haemorrhage, miscarriage or preterm delivery. Diagnosis by ultrasound scan may prove difficult. Five pregnancies had histological evidence of chorioamnionitis, which may have helped to precipitate labour; three fetuses showed pulmonary inflammatory changes of at least 2 days' duration. No maternal predisposing factors could be elicited.

Chorioamnionitis↗

A randomised trial of two expectant managements of prelabour rupture of the membranes at 34 to 42 weeks.

OBJECTIVE: To compare obstetric and perinatal outcome between two different expectant managements in women with prelabour rupture of the membranes (PROM). DESIGN: A randomised study. PARTICIPANTS: One thousand three hundred and eighty-five women with rupture of the membranes at 34 to 42 weeks without contractions. INTERVENTIONS: Women without contractions 2 h after admission were randomised to early induction the following morning after PROM (early induction group) or induction two days later (late induction group). Women with contractions starting within 2 h after admission were included in the calculations as a short latency group. Digital examinations of the cervix were avoided until onset of active labour. Labour was induced with oxytocin in both groups if no spontaneous contractions occurred or if chorioamnionitis or fetal distress was detected. MAIN OUTCOME MEASURES: The frequency of spontaneous deliveries, operative deliveries, maternal and neonatal infections. RESULTS: In nulliparous women, a higher rate of spontaneous deliveries was found in the late induction group (89%) compared with the early induction group (81%) (P < 0.05). The ventouse extraction rate was 7% and 14% respectively (P < 0.05). A low (2-4%) caesarean section rate was recorded and did not differ between the groups. Endometritis was detected in six women after delivery. Sixty-one children were treated with antibiotics, and no difference could be detected between the groups. CONCLUSIONS: A higher rate of spontaneous deliveries was found among nulliparous women with prolonged latency as compared with brief latency prior to induction. A protocol of no digital examination before labour was associated with infrequent maternal and fetal morbidity, regardless of latency.

Adult↗

Possible causes linking asphyxia, thick meconium and respiratory distress.

The cause of fetal distress and neonatal respiratory distress (RD) in association with meconium-stained liquor is not always clear. To clarify this, a prospective study was undertaken in a tertiary referral maternity hospital for 1 year. In all infants born after meconium-stained liquor who developed RD, evidence was sought for 1) fetal distress (from the cardiotocograph (CTG), the cord blood pH, the Apgar score and the asphyxial complications in the neonate) 2) causes of fetal distress (including maternal risk factors, fetal infection and fetal malnutrition) 3) causes of respiratory distress (including meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN) and infection). Of 4,026 livebirths, 717 (17.8%) had meconium-stained liquor and 44 term and 5 preterm infants developed RD. In the 44 term infants, there was frequent evidence of fetal distress possibly caused by previously unrecognized factors such as fetal malnutrition with reduced neonatal skinfold thickness in 35% triceps and 41% subscapular measurements, and histological chorioamnionitis (CA) in 74%. The cause for respiratory distress was identified in only 48% of infants, and included clinical evidence of PPHN (41%), MAS (16%) and infection (2%). However in preterm infants, 80% had definite or suspected infection. The findings indicate that fetal distress is common in infants who develop respiratory distress after meconium-stained liquor. A role for histological CA and reduced nutrition in the fetus, as factors contributing to the vulnerability of the term infant to intrapartum fetal distress, is suggested.

Apgar Score↗

Pregnancy outcome following preterm premature rupture of the membranes at less than 26 weeks' gestation.

The outcome of 71 singleton pregnancies where premature rupture of the membranes (PROM) occurred at gestations of less than 26 weeks was assessed retrospectively. The incidence of chorioamnionitis was 39.4% and the overall maternal morbidity rate was 53% but there were no long-term maternal sequelae. The latent period from PROM until delivery ranged from less than 12 hours to 77 days, with 41% of women delivering within 1 week. There was no increased risk of infection with increasing latent period. The perinatal mortality was 66.2% (26.7% stillbirths and 39.4% neonatal deaths). There was a 65% chance of a live baby if PROM occurred between 24-26 weeks but only 5 of 40 fetuses (12.5%) survived if PROM occurred before 24 weeks. The use of antibiotics, tocolytics and steroids in an uncontrolled manner is reported. Overall there is little serious risk to the mother if a conservative approach is adopted but only about one-third of such women will take home a live baby.

Chorioamnionitis↗

The significance of amniotic fluid interleukin-6 levels in preterm labour.

This study was performed to determine the prevalence of subclinical intraamniotic infection in patients with preterm labour and intact membranes, and to evaluate the significance of interleukin-6 levels for diagnosis and prognosis of tocolysis failure, amniocentesis-delivery interval and neonatal mortality and morbidity. Transabdominal amniocentesis was performed on 74 randomly-selected patients with preterm labour and intact membranes. The prevalence of amniotic fluid infection in this group was found to be 33.7% (25 of 74). The most sensitive test to identify the intraamniotic infection was found to be the measurement of interleukin-6 level. However the most specific test was confirmed to be Gram staining. Interleukin-6 level measurement was the best test to correlate with positive amniotic fluid culture and histological chorioamnionitis. Also, interleukin-6 level measurement had the advantage of predicting preterm delivery risk and neonatal complications compared to the other tests.

Adult↗

Ultrastructural alterations of term human amnionic epithelium following incubation with group B beta-hemolytic streptococci.

The association between the group B beta-hemolytic streptococcus (GBBHS) and premature labor, premature rupture of the membranes, and chorioamnionitis with intact membranes is well known. However, the mechanisms involved in this association remain unclear. In this study we incubated term chorioamniotic membranes from patients undergoing elective repeat cesarean section in double-armed incubation vessels that isolated the maternal from the fetal surfaces. The GBBHS was placed adjacent to the maternal surface and incubated for 2, 4, 8, 12, and 24 hr. Control membrane specimens from the same patient were incubated under identical conditions for identical time periods but without the presence of GBBHS. Examination of the specimens by transmission electron microscopy revealed progressive nuclear and basement membrane alteration in the study group that was maximal at 12 hr. There was also a progressive decrease in desmosome counts in the study membranes. These in vitro changes support the in vivo association of GBBHS with the aforementioned obstetric complications.

Amnion↗

Amniotic fluid interleukin-6 determinations are of diagnostic and prognostic value in preterm labor.

PROBLEM: The purpose of this study was to determine if amniotic fluid concentrations of the interleukin-6 (IL-6) are of value in diagnosis of microbial invasion of the amniotic cavity and in the prediction of failure of tocolysis, preterm delivery and perinatal morbidity and mortality. METHOD: Amniotic fluid was obtained by transabdominal amniocentesis from 146 consecutive patients admitted with the diagnosis of preterm labor and intact membranes. Fluid was cultured for aerobic and anaerobic bacteria as well as for mycoplasmas. Amniotic fluid IL-6 levels were measured using a monoclonal antibody-based enzyme-linked immunosorbent assay with a sensitivity of 0.03 ng/ml. Logistic regression and Cox's proportional hazards model were used to examine the effect of several variables on dichotomous outcomes or interval to delivery. RESULTS: Patients with a positive amniotic fluid culture had a significantly higher amniotic fluid IL-6 concentrations than patients with a negative culture (median 91.2 ng/ml, range 0.9 to 437 ng/ml versus median 0.4 ng/ml, range < 0.3 to 195 ng/ml, respectively; P < .0001). An amniotic fluid IL-6 concentration of greater than or equal to 11.3 ng/ml had a sensitivity of 93.3% (14 of 15) and a specificity of 91.6% (120 of 131). All patients with an amniotic fluid IL-6 concentration above 11.3 ng/ml and a negative amniotic fluid culture (N = 11) delivered preterm and all placenta available for examination (N = 7) had histologic evidence of chorioamnionitis. Amniotic fluid concentrations of IL-6 were an independent predictor of preterm delivery, amniocentesis-to-delivery interval and neonatal morbidity and mortality. Moreover, IL-6 concentrations added significant information to the prediction of these outcomes to that provided only by clinical information such as cervical dilatation, gestational age at admission or at delivery. CONCLUSION: IL-6 is a sensitive and rapid test for the detection of microbial invasion of the amniotic cavity and for identifying women at risk for spontaneous preterm delivery and neonates at risk for morbidity and mortality.

Adult↗

Risk factors and mechanisms of preterm delivery in Malawi.

PROBLEM: We examined risk factors and mechanisms of preterm delivery (PTD) in malaria-exposed pregnant women in Blantyre, Malawi. METHOD OF STUDY: The human immunodeficiency virus (HIV), malaria, syphilis, and anemia were assessed in a cross-sectional study of 572 pregnant women. In a nested case-control study, chorioamnionitis (CAM) was examined; tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, macrophage inflammatory protein (MIP)-1alpha, monocyte chemotactic protein (MCP)-1, transforming growth factor (TGF)-beta, cortisol, and corticotropin-releasing hormone were measured in placental, maternal and/or cord blood. RESULTS: HIV, infrequent antenatal clinic attendance, low-maternal weight, no intermittent preventive malaria therapy (IPT), and CAM were associated with PTD, while malaria was not. Of the 18 compartmental cytokine measurements, elevations in placental and/or cord IL-6 and IL-8 were associated with both CAM and PTD. In contrast, there was no overlap between the cytokines affected by malaria and those associated with PTD. CONCLUSIONS: The HIV and CAM were the major infections associated with PTD in this study. CAM, but not malaria, causes PTD via its effect on proinflammatory cytokines.

Anemia↗

Mycoplasma hominis in maternal and fetal infections.

Although prevalence of M. hominis colonization during pregnancy varies from 12-50%, its role in infections of the mother and newborn infants is unclear. Definite correlations exist with chorioamnionitis and amniotic fluid infections, but as it is rarely isolated alone during these infections, its pathogenic role is uncertain. Its association with septic abortion is similarly questioned. Prevalence and antibody titers to M. hominis increase with increasing parity. Transient bacteremia occurs in approximately 2.5% of normal deliveries. M. hominis does have a significant role in postpartum fever. Women harboring the organism during labor with low predelivery antibody titers are at risk. Approximately 30% of exposed infants are colonized (4% of all infants) but there are only a few reports of neonatal meningitis, pneumonia, or skin abscesses due to M. hominis. Most recover without specific therapy. The role of antimicrobial therapy of M. hominis in pregnancy and the neonatal period is unclear. Further studies of these issues should simultaneously consider all potential genital tract pathogens.

Abortion, Spontaneous↗

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.

Chorioamnionitis↗

Streptococcus milleri and second trimester abortion.

Review of 214 fetal necropsies performed in the department of pathology, University of Aberdeen, showed 40 cases of chorioamnionitis or intrauterine pneumonia, five of which were associated with Streptococcus milleri. In two cases there was good evidence to implicate S milleri as the cause of infected abortion while in the other cases its pathogenic role was less clear.

Abortion, Spontaneous↗

Role of Campylobacter jejuni as a placental pathogen.

Members of the genus Campylobacter are well recognised as enteric pathogens but have rarely been implicated as human placental pathogens. A case of septic abortion due to C jejuni is reported. This occurred in a previously healthy woman with a diarrhoeal illness. The presence of chorioamnionitis raises the possibility of ascending infection rather than septicaemic spread as the pathogenesis. Members of the genus Campylobacter have special culture requirements and their incidence as placental pathogens may therefore be underestimated.

Abortion, Septic↗

Initial responses to ventilation of premature lambs exposed to intra-amniotic endotoxin 4 days before delivery.

Preterm delivery is frequently preceded by chorioamnionitis, resulting in exposure of the fetal lung to inflammation. We hypothesized that ventilation of the antenatally inflamed lung would result in amplification of the lung injury. Therefore, we induced fetal lung inflammation with intra-amniotic endotoxin (10 mg of Escherichia coli 055:B5) 4 days before premature delivery at 130 days of gestation. Lung function and lung inflammation after surfactant treatment and 4 h of mechanical ventilation were evaluated. Inflammatory cell numbers in amniotic fluid were increased >10-fold by antenatal endotoxin exposure. Antenatal endotoxin exposure had minimal effects on blood pressure, heart rate, lung compliance, and blood gas values. The endotoxin-exposed lungs required higher ventilation pressures. Ventilation did not increase the number of inflammatory cells or the protein in bronchoalveolar lavage fluid of the endotoxin-exposed animals above that measured in endotoxin-exposed fetuses that were not ventilated. IL-1beta, IL-6, and IL-8 mRNA in cells from bronchoalveolar lavage fluid were increased by antenatal endotoxin exposure but not changed by ventilation. IL-1beta and IL-8 protein was increased in lung tissue by 4 h of ventilation. Very little inflammation was induced by ventilation in this premature lamb model of surfactant treatment and gentle ventilation. After lung inflammation was induced by intra-amniotic endotoxin injection, ventilation did not increase lung injury.

Animals↗

Chronic endotoxin exposure does not cause sustained structural abnormalities in the fetal sheep lungs.

Chronic early gestational chorioamnionitis is associated with development of bronchopulmonary dysplasia in preterm infants. A single intra-amniotic exposure to endotoxin decreased alveolarization and reduced expression of endothelial proteins in 125-day gestational age preterm lambs. We hypothesized that prolonged exposure to intra-amniotic endotoxin would cause progressive lung inflammation and inhibit alveolar and pulmonary vascular development. Endotoxin (1 mg/day) or saline was administered via an intra-amniotic osmotic pump from 80 to 108 days of gestational age (continuous pump) or by four weekly 10-mg intra-amniotic endotoxin injections starting at 100 days of gestational age (multiple dose). Lung morphometry, lung inflammation, vascular effects, and lung maturation were measured at delivery. The continuous pump lambs delivered at 100 days (approximately 70% of total endotoxin exposure) had lung inflammation, fewer saccules, and decreased endothelial proteins endothelial nitric oxide synthase and VEGF receptor 2 expression compared with controls. The continuous pump (delivered at 138 days) and multiple dose lambs (delivered at 130 and 145 days) had mild persistent lung inflammation and no significant differences in lung morphometry or expression of endothelial proteins compared with controls. Surfactant saturated phosphatidylcholine pool sizes were increased in all endotoxin-exposed groups, but lung function was not changed relative to controls. Contrary to our hypothesis, a prolonged fetal exposure to intra-amniotic endotoxin caused mild persistent inflammation but did not lead to progressive structural abnormalities in lungs of near-term gestation lambs.

Amniotic Fluid↗

Very prolonged membrane rupture and delayed delivery of the second twin.

OBJECTIVES: To present the complications of twin pregnancies with delayed delivery of the second twin, 32 days after expulsion of the first twin. CASE: A 29-year-old woman with a twin pregnancy at gestational age 13 weeks and 5 days presenting with a rupture of the membranes of the first twin. At 21 completed weeks the umbilical cord prolapsed and at 23 weeks the first twin was stillborn with the placenta in the uterus. After maternal septicemia the second twin was delivered by caesarian section, at 28 complete weeks, liveborn. The mother and child were discharged from hospital 10 weeks later, corresponding to 38 completed weeks of pregnancy. CONCLUSIONS: A very early premature rupture of membrane (PROM) occurs more often in twin pregnancies. The delivery of one twin most often results in expulsion of the second twin. With PROM there is a great risk of chorioamnionitis, as in our case, which resulted in an acute cesarean section. In this case, conservative management achieved a viable fetus in spite of very early and serious complications.

Adult↗

Cytokines, pulmonary surfactant and consequences of intrauterine infection.

Excess of inflammatory cytokines is implicated in the sequence of inflammatory diseases during the perinatal period. Specific cytokines induce spontaneous premature labor and accelerate fetal lung maturity in case of chorioamnionitis. In addition, they are involved in the pathogenesis of chronic lung disease, periventricular white matter damage, shock and multiorgan damage. Deficient cytokine response of the immature lung is associated with severe respiratory distress syndrome and persistent fetal circulation syndrome. Surfactant supplementation remains the cornerstone among therapies in the premature infant. Brief courses of glucocorticoids, antioxidants or inhaled nitric oxides remain to be fully evaluated as possible adjunct therapies shortly after birth in small premature infants with severe cardiorespiratory failure.

Animals↗