Decreased incidence of retinopathy of prematurity, 1995-1997.

PURPOSE: To report a significant decrease in the incidence of retinopathy of prematurity (ROP), both in our neonatal intensive care unit (NICU) and internationally, and review factors in patient care that may be contributory. METHODS: We retrospectively reviewed the records of all neonates weighing less than 1251 g admitted to our NICU from 1995 to 1997 and evaluated the incidence and stage of ROP. These data on 191 neonates were compared with an international NICU database of 9989 similar neonates, which represents all infants who received an ophthalmologic examination in the Vermont-Oxford Network Database (VOND) in 1997, except those from our institute (the University of Kentucky). In addition to investigating the incidence of ROP, we looked at the use of antenatal corticosteroids given 1 to 7 days prepartum, the use of oxygen at 36 weeks' postconceptional age, and the use of oxygen at home upon discharge. RESULTS: In our center, we had a 36.1% incidence of ROP compared with an international incidence of 57.2% for the VOND in 1997 (P <.0001). Antenatal corticosteroids were given to 62.6% of infants in our center compared with 48.6% in the VOND (P <.005). In addition, 48.5% of our infants weighing less than 1500 g received oxygen at 36 weeks' postconceptional age versus 29.5% of the VOND infants (P <.001). Upon discharge to home, 37.5% of our infants were on oxygen compared with 15.6% of infants from all VOND centers, excluding the University of Kentucky (P <.001). CONCLUSION: The incidence of ROP in our center from 1995 to 1997 and in the VOND in 1997 show a significant decrease from the 65.8% incidence from 1986 to 1987 reported by the Multicenter Trial of Cryotherapy for ROP.

A three-day course of dexamethasone therapy to prevent chronic lung disease in ventilated neonates: a randomized trial.

BACKGROUND: Although several trials of early dexamethasone therapy have been completed to determine if such therapy would reduce mortality and chronic lung disease (CLD) in infants with respiratory distress, optimal duration and side effects of such therapy remain unknown. PURPOSE: The purpose of this study was: 1) to determine if a 3-day course of early dexamethasone therapy would reduce CLD and increase survival without CLD in neonates who received surfactant therapy for respiratory distress syndrome and 2) to determine adverse effects associated with such therapy. DESIGN: This was a prospective multicenter randomized trial comparing a 3-day course of dexamethasone therapy beginning at 24 to 48 hours of life to placebo therapy. Two hundred forty-one neonates (dexamethasone n = 118, placebo n = 123), who weighed between 500 g and 1500 g, received surfactant therapy, and were at significant risk for CLD or death using a model to predict CLD or death at 24 hours of life, were enrolled in the trial. Infants randomized to receive early dexamethasone were given 6 doses of dexamethasone at 12-hour intervals beginning at 24 to 48 hours of life. The primary outcomes compared were survival without CLD and CLD. CLD was defined by the need for supplemental oxygen at the gestational age of 36 weeks. Complication rates and adverse effects of study drug therapy were also compared. RESULTS: Neonates randomized to early dexamethasone treatment were more likely to survive without CLD (RR: 1.3; 95% CI: 1.03, 1.7) and were less likely to develop CLD (RR: 0.6; CI: 0.3, 0. 98). Mortality rates were not significantly different. Subsequent dexamethasone therapy use was less in early dexamethasone-treated neonates (RR: 0.8; CI: 0.7, 0.96). Very early (

House staff supervision, workload, and experience in the neonatal intensive care unit: results of a national survey.

One hundred fifty-nine pediatric chief residents were surveyed regarding characteristics of the neonatal intensive care unit rotation for house staff at their institution. We documented substantial interinstitution variability in house staff NICU rotations in terms of number of rotations, and the workload and supervision of house staff.

Elevated circulating calcitonin gene-related peptide in umbilical cord and infant blood associated with maternal and neonatal sepsis and shock.

The role of the sensory neuropeptide calcitonin gene-related peptide (CGRP) was studied in preterm and term neonates with sepsis and shock. CGRP levels in blood were measured by RIA. The identity of immunoreactive CGRP (irCGRP) in adult and infant human blood was confirmed by reverse phase-HPLC. CGRP levels were analyzed in a total of 189 samples (95 from cord blood and 94 from neonates). The gestational ages ranged from 24 to 43 wk, and the birth weights ranged from 520 to 4445 g. Cord samples were collected immediately after delivery and infant blood samples were collected within 12 h of birth. Samples were coded, and the data were assigned to groups after determination of CGRP levels. There was a weight- and gestation-dependent increase in irCGRP in the newborn population. The direct correlation of circulating CGRP with ascending birth weight and gestation may have significance in the development of the fetus. Infants with and without certain complications were grouped in 500-g intervals. CGRP levels in cord blood were significantly elevated when certain stressful situations existed in the mother. These included culture-positive chorioamnionitis, placental abruption, and severe preeclampsia. There was a similar elevation in CGRP in patient blood in infants with culture-positive sepsis and/or shock with blood pressure <2 SD from the mean for corresponding gestation. CGRP levels did not differ between male and female infants and did not appear to be influenced by type of delivery (vaginal versus cesarean section). There was no significant difference in CGRP level between cord and patient blood in preterm neonates, but at term gestation cord blood levels were slightly higher than those in the patient blood. These results suggest that inflammation and hemodynamic imbalance (e.g. shock) are associated with increased in CGRP levels in the circulation in neonates. Future studies will focus on the biologic effects of elevated CGRP during neonatal complications and will examine the utility of CGRP measurement for diagnosis and treatment of disease in preterm infants.

Elevated laminin concentrations in lung secretions of preterm infants supported by mechanical ventilation are correlated with radiographic abnormalities.

OBJECTIVE: The objective of this study was to test the hypothesis that the presence of laminin in neonatal tracheal aspirates would be indicative of damage to the structural integrity of the basal laminae of the lung caused by barotrauma and hyperoxia. We predicted that disruption of the basal laminae would be a critical determinant of lung injury and fibrotic repair in the preterm infant whose lungs were ventilated with supplemental oxygen. STUDY DESIGN: The study group consisted of 23 premature infants in the neonatal intensive care unit whose lungs were ventilated by supplemental oxygen. We quantitated concentrations of laminin and fibronectin from sequential tracheal aspirates by enzyme-linked immunosorbent assays. A two-way analysis of variance was used to compare laminin and fibronectin concentrations in infants with and without radiographic evidence of coarse pulmonary markings indicative of fibrotic repair of lung injury. RESULTS: The concentrations of laminin, but not fibronectin, were significantly higher throughout the first 5 weeks of life in infants with abnormal chest radiographs at 36 weeks after conception. The concentrations of laminin in infant serum were approximately 1/30 that of tracheal aspirate laminin concentrations, suggesting that little if any of the laminin detected in the tracheal aspirates was derived from the serum. CONCLUSIONS: Increased concentrations of laminin in tracheal aspirates may be an indication of lung injury and fibrotic repair in the preterm infant.

Neurosonographic diagnosis of thalamic/basal ganglia vasculopathy in trisomy 13--an important diagnostic aid.

We performed a retrospective review of all the infants diagnosed with trisomy 13 in our institution from 1982 to 1995 and evaluated the neurosonographic findings along with their clinical information and cytogenetic analysis. Nine babies were admitted with trisomy 13. Sonography of the head was performed on 4 patients, and demonstrated in all of them a linear, branching, echogenic pattern in the thalamus/basal ganglia. Doppler evaluation of the thalamus/basal ganglia was performed in 3 of the 4 cases and confirmed these linear echogenicities to be of vascular origin. This is the first study to evaluated the occurrence of this finding in a specific syndrome, namely trisomy 13.

Endotracheal tolazoline administration in neonates with persistent pulmonary hypertension.

OBJECTIVES: Our purpose was to study the effectiveness of endotracheal tolazoline (ET-Tz) in the treatment of neonatal persistent pulmonary hypertension (PPHN). STUDY DESIGN: ET-Tz was administered to 12 neonates with a clinical diagnosis of PPHN. The gestational age ranged from 25 to 42 weeks, and the birth weights from 850 to 3612 gm. The dose of tolazoline ranged from 1 to 2.5 mg/kg. RESULTS: There was a significant increase (p < 0.005) in the mean levels of oxygen saturation and the arterial oxygen tension, and a significant decrease (p < 0.005) in the oxygenation index, between the pretolazoline and the posttolazoline groups, but arterial carbon dioxide tension did not change. After the initial analysis, the groups were subdivided into preterm and term subgroups, because we secondarily observed that the average changes from predose to postdose levels in the above parameters were significantly different (p < 0.001) in the two subgroups by Student's paired t test. CONCLUSIONS: The data indicate that ET-Tz is effective in improving oxygenation in neonates with PPHN, particularly sick preterm infants. The endotracheal route is preferred because it is devoid of significant side effects (e.g., hypotension and flushing). A randomized, controlled, double-blinded, multicenter trial for the use of ET-Tz in PPHN is warranted.

In vitro inactivation of pulmonary surfactant replacement preparations by serum albumin.

Inactivation of the surface activity of pulmonary surfactant by serum proteins is an important part of neonatal respiratory distress syndrome. The ability of serum proteins to diminish the surface activity of surfactant preparations used to treat respiratory distress syndrome has not been fully described. The sensitivity of clinically useful pulmonary replacement preparations beractant (Survanta) and colfosceril palmitate, cetyl alcohol, and tyloxapol (Exosurf) to albumin inactivation was examined in vitro by the Wilhelmy plate technique. At a final lipid concentration of 0.1 mg/mL and in the absence of albumin, both Survanta and Exosurf exhibited equilibrium surface tensions in the range of 35 dynes/cm. In the presence of albumin, range of 35 dynes/cm. In the presence of albumin, the surface tension of Survanta was markedly higher. Maximal response of Survanta to albumin was observed at about 1 mg/mL protein concentration. When the lipid concentration was raised to 0.3 mg/mL, the presence of albumin had little effect. With Exosurf, the presence of albumin resulted in only minor elevations of surface tension, even at an albumin concentration 10-fold greater than that used in the experiments with Survanta. These results indicate that at lipid concentrations of 0.1 mg/mL and less, the surface activity of the bovine purified lung surfactant Survanta is more sensitive to the presence of albumin than is the synthetic preparation Exosurf.

Intrinsic microbicidal activity and pulmonary hypertension in isolated newborn piglet lungs.

The lung appears to be one of the dominant sites of bacterial clearance from the blood of infant piglets. Part of the lung bacterial clearance involves activation of an oxygen radical bactericidal mechanism that may be central to induction of acute pulmonary hypertension. The present study determined whether this bactericidal activity was intrinsic to resident lung cells. Isolated piglet lung preparations perfused with blood-free salt solution were used to delineate the amount of group B streptococci (GBS) extracted and killed upon transit through pulmonary vasculature. Approximately 45% of infused GBS was deposited in the lung during a single pulmonary transit, whereas nearly 40% of the organisms sequestered in the lung were killed within a 30-min period. Pretreatment with dimethylthiourea, a scavenger of hydroxyl radical that inhibits GBS-induced pulmonary hypertension, attenuated both bacterial uptake and killing to similar extents. Along with its deposition in the lung, GBS also induced concentration-dependent increases in total pulmonary resistance, which were related principally to increases in upstream arterial resistance. Lung weight also increased in a concentration-dependent manner. Both the increase in total pulmonary resistance and lung weight were temporally related to elevation in perfusion medium content of the stable thromboxane degradation product, thromboxane B2. Pretreatment with indomethacin, a prostaglandin H synthase inhibitor, or sodium(E)-3[4-(1-imidazolyl-methyl)phenyl]-2-propenoic acid a thromboxane synthase inhibitor, reduced GBS-induced pulmonary hypertension and edema. These results suggest that, in isolated piglet lungs, GBS evokes an intrinsic bactericidal response residing within lung cells, probably pulmonary intravascular macrophages, which may be responsible for the initiation of pulmonary hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative disposition kinetics of 111In-labeled group B streptococcus and neutrophils during onset of sepsis-induced pulmonary hypertension.

Little is known of the time course by which intravascular group B streptococcus (GBS) distributes into the infant lung, though the prompt onset of pulmonary hypertension in GBS-infected animals suggests that bacteria interact initially with a resident lung cell or that they promote rapid pulmonary influx of circulating effector cells. Using external gamma scintigraphy to monitor the organ-specific disposition kinetics of 111In-oxine-labeled GBS in anesthetized piglets, we found that 80% of the infused bacteria rapidly distributed into the lung and that pulmonary bacterial uptake exhibited a close temporal relationship with the onset of pulmonary hypertension. Companion studies demonstrated that the extent of pulmonary 111In-neutrophil sequestration was unaffected by GBS, although a neutrophil secretagogue, phorbol myristate acetate, caused rapid pulmonary neutrophil uptake. These observations support the hypothesis that the onset of pulmonary hypertension in GBS sepsis can be attributed to interactions between the bacteria and resident lung cells.

Impact of prostaglandin and thromboxane synthesis blockade on disposition of group B streptococcus in lung and liver of intact piglet.

Group B streptococci (GBS) localizing in the lungs of infant piglets is killed in part by an oxygen radical-dependent mechanism (Bowdy BD, Marple SL, Pauly TH, Coonrod JD, Gillespie MN: Am Rev Respir Dis 141:648-653, 1990). The source of bactericidal oxygen radicals is unknown, but cyclooxygenation of arachidonic acid, an initial event in prostanoid synthesis, is accompanied by substantial oxygen radical generation. Because blockade of prostaglandin H synthase (cyclooxygenase) with indomethacin prevents GBS-induced pulmonary hypertension, we reasoned that the salutary effect of indomethacin might be associated with a reduction in the efficacy of bactericidal activity directed against GBS. To address this possibility, the distribution and viability of 111In-labeled GBS (10(8) colony forming units/kg/min i.v. for 15 min) were assessed in lungs and livers of control piglets, piglets treated with indomethacin (1 mg/kg), and piglets treated with OKY-046 (10 mg/kg), an inhibitor of thromboxane synthase that also forestalls GBS-induced pulmonary hypertension. Relative to control animals, indomethacin treatment increased pulmonary GBS uptake with no change in bacterial distribution into the liver. OKY-046 failed to influence pulmonary bacterial uptake but promoted a substantial increase in GBS depositing in the liver. In contrast to its effects on pulmonary bacterial deposition, indomethacin failed to increase lung bacterial viability relative to control animals. Indomethacin also was without effect on hepatic bacterial viability. OKY-046 failed to influence pulmonary bacterial viability but markedly augmented hepatic GBS viability to the extent that significant bacterial proliferation occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Purpura fulminans in three cases of early-onset neonatal group B streptococcal meningitis.

The diagnosis of purpura fulminans was associated with three cases of early-onset group B beta-hemolytic streptococcal (GBS) disease. All three infants had confirmed bacterial disease, extensive purpuric lesions involving the extremities, and laboratory evidence of a consumptive coagulopathy. All three children survived but had markedly compromised neurologic outcomes. Purpura fulminans has not been previously reported with early-onset GBS disease.

Bilirubin as an antioxidant: effect on group B streptococci-induced pulmonary hypertension in infant piglets.

Bilirubin scavenges toxic oxygen radicals in vitro, but it is not known whether this potential salutary effect can be extended to the intact animal. Accordingly, the present experiments tested the hypothesis that bilirubin protects against oxygen radical-dependent pulmonary hypertension and arterial hypoxemia in piglets infected with group B streptococci (GBS). Piglets ranging in age and weight from 7 to 14 days and 1.5 to 2.0 kg, respectively, were infused for 60 min with 108 cfu GBS/kg/min. One group of 7 animals was pretreated with a bolus infusion of 15 mg/kg of bilirubin followed by a continuous bilirubin infusion. A second group of 7 animals was given the vehicle. While plasma bilirubin levels in control animals were negligible, administration of exogenous bilirubin was associated with plasma levels of 13.0 +/- 0.74 mg%. Piglets treated with exogenous bilirubin exhibited GBS-induced increases in pulmonary arterial pressure and decreases in PaO2 of 16.1 +/- 2.0 and 46.5 +/- 4.3 torr, respectively. In control animals, GBS increased pulmonary arterial pressure and decreased PaO2 by 17.5 +/- 1.6 and 47.9 +/- 3.2 torr, respectively. Neither the peak changes in pulmonary arterial pressure or PaO2 nor the time courses of these alterations differed between treatment groups. These observations indicate that bilirubin fails to prevent GBS-induced pulmonary hypertension and arterial hypoxemia in infant piglets and suggests that in this particular model bilirubin does not exhibit appreciable oxygen radical scavenging activity.

Dimethylthiourea reverses sepsis-induced pulmonary hypertension in piglets.

Dimethylthiourea (DMTU), a putative hydroxyl radical scavenger, attenuates thromboxane generation and pulmonary hypertension in the piglet model of group B streptococcal (GBS) sepsis. This study tested the hypothesis that DMTU reverses ongoing GBS-induced pulmonary hypertension coincident with decreased thromboxane production. Piglets (n = 15) received a 60 min infusion of GBS (10(-8) cfu/kg/min). Mean pulmonary artery pressure (Ppa), arterial blood gases (ABGs), and thromboxane B2 (TXB) levels were measured at 10 min intervals throughout the study. GBS infusion resulted in a marked increase in pulmonary artery pressure (mean delta Ppa = 31 mm Hg) and a significant decline in PaO2 (mean = -80 torr) within 10 min of beginning the infusion. pH decreased from a mean of 7.47 to 7.37. DMTU, 750 mg/kg, or normal saline vehicle was infused over 10-15 min beginning 10 min after initiating GBS. Ppa decreased significantly within 10 min of DMTU infusion. Piglets receiving vehicle had a slow decline in Ppa. Piglets receiving DMTU also had an improvement in PaO2 and showed no further drop in pH. Piglets receiving vehicle had no improvement in PaO2 and demonstrated a continued decline in pH. TXB levels did not differ between the groups at any time interval. We conclude that DMTU can partially reverse GBS-induced pulmonary hypertension, but may function through mechanisms independent of thromboxane generation.

Organ-specific disposition of group B streptococci in piglets: evidence for a direct interaction with target cells in the pulmonary circulation.

Despite the serious pulmonary manifestations of early onset group B streptococcal (GBS) sepsis, it is not known whether the organism distributes into lung tissue and whether adverse pulmonary hemodynamic abnormalities relate to an interaction between the organism and target cells in the pulmonary vascular bed. Accordingly, this study evaluated the distribution and fate of GBS in the lung, liver, and spleen of anesthetized infant piglets and in isolated, salt solution-perfused piglet lung preparations. GBS were radiolabeled with 111Indium-oxine and infused at a dose of 10(8) organisms/kg/min for 15 min into anesthetized piglets ranging in age from 5-10 d. Forty-five min after termination of the infusion, animals were killed and specimens of lung, liver, spleen, and blood were excised and the relative deposition and viability of GBS were determined. Most of the recovered bacteria were detected in the lung (53.2 +/- 3.9%) followed by the liver (41.4 +/- 2.0%) and spleen (2.2 +/- 0.38%). GBS detected in the blood was estimated to be only 3.2 +/- 1.0% of the infused dose. Viability of GBS was least in the lung (21.4 +/- 2.6%) relative to the liver (45.7 +/- 11.2%) and spleen (83.4 +/- 19.5%). After a 60-min GBS infusion, transmission electron microscopy localized the organism within pulmonary intravascular macrophages in the lung; there was no evidence for bacterial interaction with either neutrophils or endothelial cells. In the liver, GBS was found exclusively in Kupffer cells. In isolated piglet lungs perfused at a constant flow rate with blood-free physiologic salt solution, GBS (10(6) to 10(8) organisms/mL) provoked concentration-dependent increases in pulmonary vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Group B streptococcus promotes oxygen radical-dependent thromboxane accumulation in young piglets.

Both thromboxane A2 and oxygen-derived free radicals appear to play central roles in group B streptococcus (GBS)-induced pulmonary hypertension in piglets. This study tested the hypothesis that GBS promotes oxygen radical-dependent thromboxane accumulation and pulmonary hypertension in infant piglets. Piglets 4-12 d old were anesthetized and prepared for assessment of pulmonary arterial pressure and arterial blood gases. In control animals, GBS (10(8) organisms/kg/min for 15 min) increased mean pulmonary artery pressure by 30 +/- 1.5 torr and reduced arterial PO2 by 100 +/- 20 torr. Thromboxane A2, radioimmunoassayed in venous blood as thromboxane B2, increased by 2452 +/- 800 pg/mL. A second group of piglets was treated with dimethylthiourea (DMTU: 750 mg/kg), a putative oxygen radical scavenger. In these animals, GBS increased pulmonary arterial pressure by only 7 +/- 1 torr and reduced arterial PO2 by a modest 10 +/- 8 torr. Importantly, thromboxane B2 content in venous blood failed to increase above control levels in DMTU-treated animals. The protective effects of DMTU in GBS-treated piglets could not be ascribed to inhibition of cyclooxygenase or thromboxane synthase because the oxygen radical scavenger failed to attenuate increases in pulmonary arterial pressure and venous thromboxane B2 content or reductions in arterial PO2 caused by i.v. infusions of arachidonic acid. DMTU also did not ameliorate pulmonary hypertension evoked by the thromboxane mimetic U44069, thereby suggesting that the scavenger did not act as an end-organ antagonist of thromboxane receptors. These observations suggest that GBS promotes accumulation of thromboxane A2 and attendant pulmonary hypertension through an oxygen radical-dependent mechanism.

Oxygen radical-dependent bacterial killing and pulmonary hypertension in piglets infected with group B streptococci.

The mechanism by which bacteria are cleared by the pulmonary circulation and the relation of this process to development of hemodynamic abnormalities are not understood. This study tested the hypotheses that clearance of Group B Streptococcus (GBS) during transit through the pulmonary circulation of infant piglets is related to oxygen radical-dependent bacterial killing and that killing of the organism is linked to development of pulmonary hypertension. GBS were radiolabeled with 111In and infused intravenously for 15 min (10(8) organisms/kg/min) into infant piglets ranging in age from 5 to 14 days. Lung specimens were excised at termination of the GBS infusion or 45 min thereafter, and both the relative deposition and viability of the bacteria were determined. The percentage of infused GBS recovered in lung tissue did not differ between the two time points (26 +/- 7% versus 29 +/- 8%), but the relative viability at termination of the infusion, 50 +/- 11%, was reduced to 19 +/- 4% within 45 min. Treatment with an oxygen radical scavenger, dimethylthiourea (DMTU), failed to influence the pulmonary deposition of GBS but significantly increased viability of the organism from 21.4 +/- 2.6 to 33.3 +/- 5.3%. As expected, GBS infusion was accompanied by pulmonary hypertension and arterial hypoxemia; DMTU attenuated these responses by 52 and 78%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidermal growth factor augments reactivity to angiotensin II in the rat pulmonary circulation.

To determine if epidermal growth factor (EGF), a vascular smooth muscle mitogen exhibiting systemic vasoactivity, causes constriction or dilation of the pulmonary vascular bed, this study evaluated the actions of EGF in isolated, buffer-perfused rat lungs and in isolated rat pulmonary arteries. In perfused rat lungs with baseline vasomotor tone, EGF administered at bolus doses of 10(-9) to 3 x 10(-7) M failed to exert either constrictor or dilator actions or to promote edema formation as evidenced by a constant lung wet-to-dry-weight ratio. Elevation of baseline tone with either prostaglandin (PG)F2 alpha or angiotensin II also failed to unmask an effect of EGF on pulmonary vascular resistance. In contrast to these negative observations, pretreatment with 5 x 10(-8) M EGF consistently augmented pressor responses evoked by angiotensin II. Constrictor responses to potassium chloride and to PGF2 alpha were unaffected by EGF pretreatment. In isolated rat extrapulmonary arteries, EGF provoked contraction in 40% of the preparations studied. Responsive vessels exhibited maximal EGF-induced contractions that were approximately 25% of that associated with angiotensin II and were characterized by an ED50 of 7 x 10(-8) M. Relaxant activity of EGF could not be demonstrated in isolated arterial preparations with normal resting tone or with tone elevated by addition of norepinephrine to the tissue bath. Endothelial denudation also failed to unmask contractile or relaxant effects of EGF. Similar to its actions in isolated, perfused rat lungs, EGF potentiated contractions of isolated pulmonary arteries induced by angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for hydroxyl radical involvement in group B streptococcus-induced pulmonary hypertension and arterial hypoxemia in young piglets.

Early onset neonatal GBS infection is associated with pulmonary hypertension, pulmonary edema, and arterial hypoxemia. Although the mechanisms underlying these cardiopulmonary disturbances are not completely understood, multiple lines of evidence suggest that inflammatory mediators may be involved. This study examined the actions of dimethylthiourea (DMTU), a relatively selective scavenger of hydroxyl radical, on GBS-induced pulmonary hypertension, arterial hypoxemia, and pulmonary edema formation in young piglets. Relative to control animals, intravenous infusion of GBS (10(8) organisms/kg/min for 60 min) provoked sustained increases in pulmonary arterial pressure (Ppa: +88%) and total pulmonary resistance (TPR: 128%). GBS infusion also was associated with profound decreases in arterial PO2 (-58%). Pulmonary edema was present in GBS-treated animals as evidenced by an 8.4% increase in the lung wet-to-dry weight ratio. After pretreatment with DMTU (0.75 g/kg administered intravenously over 30 min), GBS increased Ppa by 33% and TPR by only 16%. Similarly, after DMTU pretreatment GBS decreased arterial oxygen tension by only 12%. DMTU also limited the GBS-induced increase in lung wet-to-dry weight ratio to 2.6%. These findings demonstrate that DMTU attenuates GBS-induced pulmonary hypertension, pulmonary edema, and arterial hypoxemia and suggest that hydroxyl radicals play an important role in these cardiopulmonary disturbances.

Fetal tachycardia as an indicator of maternal and neonatal morbidity.

Presented is a prospective, controlled study to determine if intrapartum fetal tachycardia is reliable as an indicator of maternal and fetal infectious morbidity. Thirty neonates with defined intrapartum tachycardia were matched by gestational age and weight with 30 control subjects without defined tachycardia. There was a significant difference in maternal febrile morbidity and a trend toward a difference in maternal infectious morbidity between the two groups. There was no significant difference in maternal complications at delivery or administration of antibiotics to the mother. Among the neonates, there was a significant difference in administration of antibiotics and the incidence of respiratory distress syndrome (RDS) between the two groups; however, both of these were significantly related to birth weight. There was no significant difference between the two groups in duration of ruptured membranes, duration of labor, number of vaginal examinations, or antepartum anemia. Only one study infant had a bacteremia. The data confirm an increased risk of neonatal complications, such as RDS, asphyxia, and meconium aspiration, in association with intrapartum fetal tachycardia.