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PubMed1998

Changes in polymorphonuclear leukocytes in the vagina of patients with preterm labor.

To evaluate changes in vaginal polymorphonuclear leukocytes (vPMNL) in patients with preterm labor, we obtained vPMNL-rich suspensions from vaginal fluids of 77 women (21 with preterm labor and 56 control women with uncomplicated pregnancy). Total counts of vPMNL and % viability of vPMNL (viable vPMNL:total vPMNL) were significantly higher in patients with preterm labor (37 +/- 92 x 10(5), 23 +/- 29%) vs. controls (11 +/- 15 x 10(5), 6.9 +/- 8.3%). The concentration of granulocyte elastase in vaginal fluid diluted to 20 ml was also higher in patients with preterm labor than in controls (4,806 +/- 3,818 vs. 2,739 +/- 2,556 ng/ml). We conclude that PMNL and granulocyte elastase are abundant in the vagina in patients with preterm labor, which suggests that the PMNL may be involved in the pathogenesis of preterm labor.

Adult↗

PubMed2000

Alterations in the immune system of patients with imminent preterm labour.

Premature labour is the major cause of perinatal morbidity and mortality. The aetiology of most cases of preterm labour remains unknown. We tried to estimate whether immunological changes are present in patients with preterm labour. Fourteen patients with imminent preterm labour and 12 healthy women with uncomplicated pregnancies were included in the study. The specific lymphocyte antigens were determined using direct staining with monoclonal antibodies and analysed by flow cytometry. We observed that CD8+ lymphocyte percentage was significantly lower in the group of patients with preterm labour when compared to controls (p < 0.001). This deficit was related to T CD8+11b+ suppressor lymphocytes, while the percentage of T CD8+11b- cytotoxic lymphocytes did not differ in both studied groups. Furthermore, the percentage of T CD3+ lymphocytes was significantly lower and that of B CD19+ cells higher in the study group when compared to controls. Similarly, the percentage of CD4+45RA naive cells was higher in the group of patients with imminent preterm labour, while the percentage of memory CD4+45RO+ cells was lower in the study group in comparison with the control group. These observations suggest that alterations in maternal immunological parameters can be associated with the mechanisms mediating preterm labour.

Adult↗

PubMed2000

Vascular reactivity to angiotensin II and eicosanoid production in the human placenta from term and preterm pregnancy.

Isolated human placental cotyledons from normal term (37-40 weeks of gestation) and preterm (26-36 weeks of gestation) labor were perfused in vitro, and the effect of angiotensin II (ANG II) and its interaction with prostanoids was measured. In the preterm group, ANG II caused greater maximal increases in perfusion pressure than in normal term pregnancies without affecting sensitivity. Also, preparations from normal term pregnancies showed a marked development of tachyphylaxis compared to placentae from preterm pregnancies. Indomethacin (10(-6) M) increased the maximum pressor response to ANG II by 33.6% in normal term, however, in preterm placentas a 39.2% reduction was observed. Infused ANG II 10(-6) M) decreased the concentrations of thromboxane B(2) and 6-keto-PGF(1alpha) in both pregnancy groups, but this effect was not statistically different from the baseline values. In the current study, we show that the placenta of preterm pregnancies in basal conditions produce 7.6 times as much thromboxane as the normal term placenta (2,800+/-470 vs. 366.5+/-62 pg/min, respectively), without significant change in prostacyclin levels (preterm 88.6+/-11.0 vs. Term 100.6+/-30.7 pg/min). These observations provide evidence that the contribution of basally released thromboxane from placental tissue appears to contribute to abnormalities in the regulation of fetoplacental hemodynamics in premature pregnancies.

6-Ketoprostaglandin F1 alpha↗

PubMed2001

Fetal bile acid metabolism: analysis of urinary 3beta-monohydroxy-delta(5) bile acid in preterm infants.

To elucidate the urinary concentration of total bile acids after birth and the profile of the usual and unusual urinary bile acids, especially 3beta-hydroxy-5-cholen-24-oic acid (Delta(5)-3beta-ol), we measured the concentrations of 13 bile acids in the urine from preterm infants vs. full-term controls by gas chromatography-mass spectrometry. The urinary concentration of total bile acids in early preterm infants below 32 weeks of gestational age significantly exceeded that of the late preterm and full-term infants (p < 0.0005). The major urinary bile acids in early preterm infants were cholic acid, 1beta,3alpha,7alpha,12alpha-tetrahydroxy-5beta-cholan-24-oic acid and Delta(5)-3beta-ol. In conclusion, the high urinary concentrations of total bile acids in preterm infants may be due to an overproduction, or more likely to a low hepatic bile acid clearance. An alternative fetal pathway, the acidic pathway, may be a major route of bile acid biosynthesis in preterm infants.

Bile Acids and Salts↗

PubMedDate not supplied

Persistent detection of alfa-fetoprotein in the vagina without overt preterm premature rupture of the membranes. Clinical and chemical characterizations.

OBJECTIVES: The objectives of this study were to clinically characterize and seek risk factors for the patients with persistently detected alfa-fetoprotein (AFP) in the vagina without showing overt preterm premature rupture of the membranes (PROM). STUDY DESIGN: The cohort study was undertaken using vaginal-cervical specimens collected consecutively between 21 and 40 weeks of gestation from 25 consenting women. Demographic, obstetric, neonatal, and laboratory data from patients with persistent positive results of AFP kit tests without showing overt leakage of amniotic fluid were compared to those from controls. Cervical levels of interleukin-1 alpha, interleukin-1 beta, interleukin-6, interleukin-8, and granulocyte elastase were measured by immunoassay, and the uterine cervix was assessed by transvaginal ultrasonography. Statistical analysis involved Fisher's exact test and Mann-Whitney U test. RESULTS: The incidence of overt preterm PROM was significantly higher in the patients with persistently detected AFP in preterm (3 in 4 cases) than in controls (3 in 21 controls). At sampling before determination of persistently detected AFP, patients with persistently detected AFP had significantly higher cervical levels of interleukin-6 and significantly shorter cervical length than controls. CONCLUSIONS: Patients with persistently detected AFP in the vagina without showing overt preterm PROM have the risk of overt preterm PROM. Increased levels of interleukin-6 in cervical specimens and short cervical length may be risk factors for the occurrence of persistent detection of AFP in the preterm.

Cervix Uteri↗

PubMed2003

Dose-dependent and preterm- accentuated diaplacental transport of nutritive allergens in vitro.

OBJECTIVE: The mechanisms by which nutritive allergens are transported from mother to fetus and the ensuing immunological response are incompletely understood. We investigated the role of different allergen concentrations in influencing the diaplacental allergen transport in preterm and term placentas. METHOD: Twenty-seven human term placentas and 12 preterm placentas were dually perfused in vitro for up to 4 h by adding alternately two different nutritive allergens, beta-lactoglobulin (BLG) or ovalbumin (OVA), at four different allergen concentrations (0.02, 0.2, 2 and 20 mg/ml) to the maternal perfusate medium. Allergen concentrations in fetal venous outflow samples collected during perfusion were measured by using specific ELISAs. RESULTS: Perfusion of increasing allergen concentrations via the maternal circulation resulted in a concentration-dependent increase of fetal allergen uptake in all term and preterm placentas. A mean maternal-to-fetal ratio of 20,000/1 and 3,000/1 for BLG, and 40,000/1 and 5,000/1 for OVA was found in term and preterm placentas, respectively. Preterm placentas (27-36 weeks of gestation) were found to favor the diaplacental passage of nutritive allergens compared with placentas at term (>36 weeks of gestation). CONCLUSION: Maternal-to-fetal allergen transport occurs in a dose-dependent and molecular weight-dependent manner with clear accentuation in preterm placentas.

Allergens↗

PubMed2004

[Gentle obstetrical management for very early preterm deliveries].

OBJECTIVE: In view of the general improvement in survival of very early preterm newborns the contribution of the obstetrical management to this development has been studied. METHODS: A comprehensive literature search was performed concentrating on prospective randomised clinical trials, meta-analyses and review articles dealing with different aspects of the obstetrical management of very early preterm deliveries which were published during the last 10 years. RESULTS: The benefit of antepartal administration of glucocorticoids to the mother for stimulation of pulmonary maturity of the fetus and the overall clinical condition of the preterm newborn at birth has been proven by several prospective randomised studies. In contrast, there is only indirect evidence for the benefit of an early transfer of these pregnancies to a perinatal centre. The benefit of a short-term prolongation of pregnancy by the administration of tocolytics is evident in the context of glucocorticoid administration for pulmonary maturity. There is no clear evidence for the benefit of long-term tocolytic treatment of preterm labour. Various prospective randomised trials comparing delivery by primary or elective caesarean section with vaginal birth combined with selective section as indicated by a deterioration of the condition of the fetus or the mother during the first or second stage of labour have clearly shown increased maternal morbidity in the elective caesarean section group. The expected advantage for the condition of the newborn could not be shown. In a meta-analysis of 6 such trials, the problem of recruiting participants was stressed. All 6 trials had to be terminated before the calculated number of study participants had been recruited. CONCLUSION: For planned early preterm delivery a transfer of the mother into perinatal centre is recommended for pregnancies beyond 22 0/7 weeks. Starting at 24 0/7 weeks, glucocorticoids should be administered. Between 24 0/7 and 24 6/7 weeks, survival chances remain clearly at less than 50%, and up to 50% of those surviving develop moderate to severe handicaps. Obstetrical management, in particular a decision for caesarean section due to fetal indication, must be individualised taking into account the wishes of the parents. Beyond 25 0/7 weeks, newborn survival should be given priority, and although clear evidence for the optimal mode of delivery is missing in cases of spontaneous labour leading to rapid dilatation of the cervix, with a normal singleton cephalic fetus, a vaginal delivery may be attempted. If under close supervision of labour there are signs of fetal or maternal deterioration, a caesarean section should be performed without delay. With breech presentation as well as twins or multiple fetuses there is a general trend towards primary caesarean section. In the absence of spontaneous labour and with an unripe cervix, elective caesarean section is considered as the method of choice for the delivery of the early preterm fetus.

Cesarean Section↗

PubMed2004

Nonassociation of interleukin 4 intron 3 and 590 promoter polymorphisms with bronchopulmonary dysplasia for ventilated preterm infants.

Interleukin 4 (IL-4) stimulates and amplifies the inflammatory response, stimulates collagen synthesis in fibroblasts, promotes the progression to fibrosis and has been shown to inhibit the production of several inflammatory cytokines in the development of bronchopulmonary dysplasia (BPD) and airway hyperreactivity. We aimed to investigate whether IL-4 polymorphisms in ventilated preterm infants were associated with BPD. BPD was defined as infants who remained dependent on active respiratory support or oxygen supplementation at 36 weeks postconceptional age. A case-control study of 224 preterm infants (<30 weeks) who had respiratory distress syndrome and needed intermittent mandatory ventilation (IMV) were undertaken between January 1999 and December 2003. The typing of each genetic polymorphism was performed by polymerase-chain-reaction-based restriction analysis. Genotype distribution and allelic frequencies were compared between ventilated preterm infants who developed BPD and those who did not and the duration of IMV. The demography of these ventilated BPD and non-BPD preterm infants was not different. We observed no significant differences in genotype distribution or allelic frequency of the IL-4 intron 3 or IL-4 promoter polymorphisms between ventilated preterm infants who developed BPD and who did not. There was no significant association of the genotype or allelic frequency of IL-4 polymorphism with duration of IMV. We conclude that neither IL-4 intron 3 nor the 590 promoter polymorphism is a useful marker for predicting the susceptibility to BPD in ventilated Taiwanese preterm infants.

Bronchopulmonary Dysplasia↗

PubMed2005

Accumulation of transforming growth factor-beta2 and nitrated chondroitin sulfate proteoglycans in cerebrospinal fluid correlates with poor neurologic outcome in preterm hydrocephalus.

BACKGROUND: Progressive post-hemorrhagic hydrocephalus in preterm infants strongly predicts abnormal neurologic development, and often accompanies cystic periventricular leukomalacia (cPVL). Transforming growth factor-beta1 (TGF-beta1), associated with hydrocephalus, can upregulate the chondroitin sulfate proteoglycan (CSPG) synthesis. To date, CSPG and their nitrated metabolites (NT-CSPG) have not been evaluated in hydrocephalus. OBJECTIVES: We hypothesized that TGF-beta1, TGF-beta2, CSPG, and NT-CSPG would accumulate in cerebrospinal fluid (CSF) in preterm hydrocephalus, and their concentrations would correlate with poor long-term outcomes. METHODS: TGF-beta1, TGF-beta2, CSPG, and NT-CSPG concentrations in CSF were measured prospectively by ELISA in 29 preterm newborns with (n=22) or without (n=34) progressive post-hemorrhagic hydrocephalus, and correlated with progressive neonatal hydrocephalus and neurologic outcome. Only concentrations from each patient's initial CSF sample were used for statistical analysis. RESULTS: Compared to neonates without hydrocephalus, CSF [TGF-beta1], [TGF-beta2], [CSPG] and [NT-CSPG] were significantly greater by >3-, >35-, >8-, and >3-fold, respectively. Unlike CSF [TGF-beta2] and [CSPG], [TGF-beta1] correlated with CSF [total protein]. Only CSF [NT-CSPG] correlated with cPVL. Unlike [TGF-beta2] or [CSPG], [NT-CSPG] correlation with preterm progressive post-hemorrhagic hydrocephalus (PPHH) was explained entirely by the presence of cPVL among these patients. [TGF-beta2] was >20-fold greater in preterm survivors who required a ventriculoperitoneal shunt for PPHH (n=9), as compared to survivors who did not require a shunt (n=2), or those without hydrocephalus (n=12). [TGF-beta2] and [NT-CSPG] correlated inversely with Bayley Index Scores (15.0 months median adjusted age). CONCLUSIONS: This is the first report that [TGF-beta2], [CSPG], and [NT-CSPG], measured well before term, accumulate abnormally in preterm progressive post-hemorrhagic hydrocephalus CSF, and correlate with adverse neurologic outcome.

Blotting, Western↗

PubMed2005

Effects of hypoxia on megakaryocyte progenitors obtained from the umbilical cord blood of term and preterm neonates.

BACKGROUND: Placental insufficiency is associated with early-onset thrombocytopenia in preterm neonates. Prior studies demonstrated a reduction in circulating megakaryocyte (Mk) progenitors, suggesting decreased platelet production. We hypothesized that decreased Mk production is the result of a direct inhibitory effect of hypoxia on the proliferation of Mk progenitors, or a hypoxia-induced change in the fetal hematopoietic environment. OBJECTIVE: To test the effects of hypoxia on the clonogenic maturation of Mk progenitors obtained from term and preterm cord blood CD34(pos) cells, either cultured alone or in conjunction with CD34(neg) light density mononuclear cells (LDMCs). METHODS: CD34(pos) cells and CD34(neg) LDMCs were isolated from the cord blood of term and preterm deliveries, and mobilized peripheral blood CD34(pos) cells were obtained from healthy adults. CD34(pos) cells were then cultured alone or co-cultured with CD34(neg) LDMCs in a semisolid, serum-free media containing rTpo, IL-3, and IL-6. Cultures were exposed to 20%, 5%, or 1% oxygen for 10-12 days. Mk colonies were then quantified following immunohistochemical staining. RESULTS: Pure CD34(pos) cells from preterm (n = 5) and term (n = 5) neonates and from adults (n = 4) generated similar numbers of Mk colonies in all three oxygen concentrations. However, the number of Mk colonies in preterm co-cultures was progressively lower with decreasing O(2) concentrations. CONCLUSIONS: Hypoxia did not appear to directly inhibit colony formation of Mk progenitors from preterm and term cord blood CD34(pos) cells. However, co-culture studies showed a decrease in Mk colony formation with hypoxia, suggesting an indirect inhibitory effect of hypoxia on Mk clonogenic maturation mediated by non-progenitor cells in the hematopoietic microenvironment.

Antigens, CD34↗

PubMed1994

Sequential changes in pulmonary epithelial permeability after birth in term and preterm rabbits.

We assessed sequential changes in the permeability properties of the pulmonary epithelium in spontaneously breathing, newborn term (30 days of gestation) and preterm (28 days) rabbit pups, using the rate of pulmonary clearance of 99mTc-DTPA (MW = 492) as an index of permeability. In term rabbits, clearance was faster at 1 h of age than at hourly timepoints thereafter (p < 0.05). In preterm rabbits, clearance rates measured from 1 to 5 h after birth were not quite significantly different (p = 0.0519) although the trend to slower clearance with increasing time after birth was significant. When term and preterm rabbits were compared, clearance was similar at 1 h after birth but was faster at both 2 and 3 h in the preterm rabbits (p < 0.05). Pulmonary epithelial permeability appears to be increased in the immediate postnatal period and the duration of increased permeability is longer in preterm rabbits. Because lung water content at birth is greater in the preterm rabbits, we speculate that the permeability changes may be associated with clearance of fetal lung liquid.

Animals↗

PubMed1988

Catecholamine and endorphin responses to delivery in term and preterm lambs.

A marked increase in catecholamines and endorphins at birth has been described in animals and man. Because the factors which regulate catecholamine secretion are incompletely understood and because it has been suggested that endogenous opiates are important in the regulation of catecholamine secretion, we designed studies to compare changes in plasma catecholamines at birth with simultaneously measured endorphins. Catecholamines and beta-endorphin-like immunoreactivity (beta-ELI) were measured at birth in term (145 days) and preterm (130 days) lambs. Preterm lambs were given natural sheep surfactant intratracheally to prevent respiration failure. Following umbilical cord cutting, there was a marked increase in circulating norepinephrine (NE) and epinephrine (E) levels. The peak preterm NE (2.2 +/- 0.3 ng/ml at 1 h) was greater than the peak term NE (1.0 +/- 0.2 ng/ml at 5 min). The peak preterm E occurred later and also was greater than the peak term E (4.0 +/- 0.5 ng/ml at 1 h vs. 1.3 +/- 0.4 ng/ml at 15 min, respectively, p less than 0.01). Baseline beta-ELI in term animals (767 +/- 15 pg/ml) was greater than preterm (456 +/- 12 pg/ml). Following cord cutting peak beta-ELI in term animals rose to 867 +/- 201 pg/ml compared to a peak beta-ELI in preterm animals of 1,866 +/- 450 pg/ml. These results and their significance for neonatal adaptation to extrauterine life are discussed.

Animals↗

PubMed1996

Delayed maturation of Hering-Breuer inflation reflex activity in preterm infants.

We have previously shown that the strength of the Hering-Breuer inflation reflex (HBIR) diminishes between 2 and 12 mo of age in full-term babies. The purpose of this study was to determine whether the onset of this decline had commenced by 3 to 4 mo of age in healthy full-term infants and whether preterm delivery influences the pattern of maturation. Serial measurements of HBIR activity using the end-inspiratory occlusion technique were made in 25 preterm and 27 full-term infants at matched postnatal and postconceptional ages during the first 6 mo of life. Although similar levels of reflex activity were observed at birth (mean +/- SD of 101.2% +/- 42.4% in preterm, and 101.0% +/- 33.9% in full-term infants), by 40 wk postconceptional age (PCA) (i.e., term equivalent) HBIR activity (mean +/- SD) had increased to 121.7% +/- 51.2% in preterm infants, which was significantly greater than that in full-term infants of similar PCA (95% CI of difference: 0.2; 41.2%). By 15 wk postnatal age (PNA), HBIR activity had decreased to 68.8% +/- 26.6% in full-term infants, but remained significantly higher in those delivered prematurely (87.8% +/- 32.7%). However, when measurements were repeated at approximately 4 mo after the expected rather than actual date of delivery, these differences were no longer evident (95% CI difference preterm-full-term: -21.2; 3.8%). This study suggests that important transitions in respiratory control mechanisms occur between 8 and 15 wk PNA in full-term infants and that these changes are delayed in preterm infants.

Aging↗

PubMed1998

Abnormal surfactant metabolism and function in preterm ventilated baboons.

We evaluated surfactant metabolism and function and the effects of antenatal glucocorticoids in very preterm baboons. Pregnant baboons were randomized to receive saline (controls) or 6 mg betamethasone (beta) 48 and 24 h before delivery at 125 +/- 2 d gestation (term is 184 d). The newborn baboons were treated with [14C]dipalmitoylphosphatidylcholine-labeled surfactant and ventilated for 6 d. Lung function for six control and six betamethasone-treated animals was similar. Recoveries of 14C-saturated phosphatidylcholine (Sat PC) were similar: 4.8% (control) and 3.6% (beta) in alveolar wash and 15.4% (control) and 17.7% (beta) in total lungs. Alveolar and total lung pool sizes of Sat PC were about 23 and 190 micromol/kg, respectively. The preterm baboons secreted 8.7% (control) and 6.5% (beta) of de novo synthesized Sat PC labeled with 3H-palmitate from Day 5 to Day 6. These preterm baboons had high estimated Sat PC synthetic and net tissue accumulation rates but low secretion of Sat PC. The large aggregate surfactant fractions from the preterm baboons had high minimal surface tensions and were less effective when used to treat surfactant-deficient preterm rabbits than surfactant from newborn or adult baboons. Ventilation of the preterm baboon was associated with surfactant functional and metabolic abnormalities that were not altered by antenatal glucocorticoids.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2002

Abnormal lung function in healthy preterm infants.

The aim of this study was to assess the consequences of preterm birth for the functional development of the lungs. We studied 32 healthy preterm infants (gestational age 25 to 33 wk at birth) and 53 healthy full-term infants (37 to 42 wk) at the same mean postmenstrual age of 40 wk with a multibreath nitrogen washout technique to assess functional residual capacity (FRC), gas mixing efficiency, and dead space and with the single-breath occlusion technique to calculate compliance and resistance of the respiratory system. Twenty of the preterm infants were also assessed with the same methods at 34.2 (32 to 37) wk. At the same postmenstrual age the preterm infants had lower FRC/kg body weight, lower specific compliance, impaired gas mixing efficiency, and higher total and dead space ventilation/kg than the full-term infants. Specific compliance and specific conductance decreased but gas mixing efficiency increased from 34 to 40 wk. We conclude that premature exposure to extrauterine conditions changes lung function. Preterm infants showed signs of dysfunction of the terminal respiratory units and higher elastic recoil than infants who spent the corresponding time for development in utero. It is suggested that preterm birth per se affects alveolarization and formation of elastic tissue in the lungs.

Airway Resistance↗

PubMed2005

Reduced lung function in healthy preterm infants in the first months of life.

RATIONALE: Preterm delivery has been associated with a higher incidence of respiratory morbidity even in infants that do not have significant respiratory disease during the neonatal period. Reduced flows have been reported in children and adolescents born prematurely. OBJECTIVE: The aim of this study was to assess lung function in healthy preterm infants in the first months of life. METHODS: Preterm infants with less than 48 h of supplemental oxygen were recruited. Lung function was assessed by the raised-volume rapid thoracic compression in the first months of life. The control group consisted of full-term infants without a history of respiratory diseases. MEASUREMENTS AND MAIN RESULTS: Sixty-two preterm (29 male) and 27 full-term (10 male) infants were tested. Adjusting for length, age, and sex, we found a mean significant reduction of 92 ml/s (22%) in FEF(50), 73 ml/s (21%) in FEF(25-75), and 19 ml (28%) in FEV(0.5) in the preterm group. These differences in expiratory flows remained significant using another model that adjusts for lung volume (p < 0.01 for FEF(50), FEF(25-75), and FEV(0.5), and p < 0.05 for FEF(75)). In the preterm group, after adjusting for length, male sex, lower gestational age, and increased weight were significantly and independently associated with reduced flows. CONCLUSIONS: Our findings confirm that prematurity is independently associated with reduced lung function and that this is detectable in the first months of life. Male sex, lower gestational age, and weight are important predictors for reduced expiratory flows in this group.

Child, Preschool↗

PubMed1990

Amniotic fluid interleukin 6 in preterm labor. Association with infection.

To evaluate whether IL-6 participates in the host response to intrauterine infection, we studied IL-6 bioactivity and isoforms in amniotic fluid (AF). Two different assays for IL-6 were used: the hepatocyte stimulating factor assay (in Hep3B2 cells) and the SDS-PAGE/immunoblot assay. IL-6 determinations were performed in 205 AF samples. Samples were obtained from patients in the midtrimester of pregnancy (n = 25), at term with no labor (n = 31), at term in active labor (n = 40), and from patients in preterm labor (n = 109). Higher AF IL-6 levels were observed in women in preterm labor with intraamniotic infection than in women in preterm labor without intraamniotic infection (median = 375 ng/ml, range = 30-5000 ng/ml vs. median = 1.5 ng/ml, range = 0-500, respectively, P less than 0.0001). The 23-25- and 28-30-kD IL-6 species could be readily detected in SDS-PAGE immunoblots performed directly on 10-microliters aliquots of AF from patients with intraamniotic infection. Among women in preterm labor with culture-negative AF, those who failed to respond to subsequent tocolytic treatment had higher AF IL-6 concentrations than those who responded to therapy (median = 50 ng/ml vs. median = 1.2 ng/ml, respectively, P less than 0.05). Only low levels of IL-6 were detected in AF obtained from normal women in the midtrimester and third trimester of pregnancy. Decidual tissue explants obtained from the placentas of women undergoing elective cesarean section at term without labor (n = 11) produced IL-6 in response to bacterial endotoxin. In a pilot study, AF IL-6 was determined in 56 consecutive women admitted with preterm labor. All patients (n = 10) with elevated AF IL-6 (cutoff = 46 ng/ml) delivered a premature neonate. 4 of these 10 patients had positive AF cultures for microorganisms. These studies implicate IL-6 in the host response to intrauterine infection and suggest that evaluation of AF IL-6 levels may have diagnostic and prognostic value in the management of women in preterm labor.

Adult↗

PubMed2005

Patterns of cerebral injury in a primate model of preterm birth and neonatal intensive care.

Very preterm birth is associated with significant neurodevelopmental morbidity, with 10% to 15% of these infants later developing cerebral palsy and up to 50% experiencing learning disabilities. The nature of the cerebral lesion predisposing these infants to such impairments is not fully understood but is likely related to both cerebral injury and alterations in cerebral development associated with neonatal intensive care. To study the impact of both preterm birth and neonatal intensive care on the immature brain, we are studying a preterm primate model delivered at 125 days of a 184-day gestational period and cared for in a neonatal intensive care unit for 2 to 4 weeks in a fashion highly similar to that for human preterm infants. The most common neuropathology in this model is white-matter damage manifested by reactive astrogliosis or activated microglia and enlarged ventricular size. Subarachnoid, germinal matrix, and intraventricular hemorrhages are also common. These preliminary results support the similarity of this model to both the alterations in cerebral developmental and the pattern of cerebral injury found in human preterm infants. We are now investigating the impact of randomized respiratory therapies on the pattern of cerebral injury. The prematurely born baboon appears to be an accurate and relevant model for the study of preterm human birth.

Animals↗