Pregnancy and neonatal outcomes of COVID-19: coreporting of common outcomes from PAN-COVID and AAP-SONPM registries.

OBJECTIVE: Few large cohort studies have reported data on maternal, fetal, perinatal and neonatal outcomes associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy. We report the outcome of infected pregnancies from a collaboration formed early during the pandemic between the investigators of two registries, the UK and Global Pregnancy and Neonatal outcomes in COVID-19 (PAN-COVID) study and the American Academy of Pediatrics (AAP) Section on Neonatal-Perinatal Medicine (SONPM) National Perinatal COVID-19 Registry. METHODS: This was an analysis of data from the PAN-COVID registry (1 January to 25 July 2020), which includes pregnancies with suspected or confirmed maternal SARS-CoV-2 infection at any stage in pregnancy, and the AAP-SONPM National Perinatal COVID-19 registry (4 April to 8 August 2020), which includes pregnancies with positive maternal testing for SARS-CoV-2 from 14 days before delivery to 3 days after delivery. The registries collected data on maternal, fetal, perinatal and neonatal outcomes. The PAN-COVID results are presented overall for pregnancies with suspected or confirmed SARS-CoV-2 infection and separately in those with confirmed infection. RESULTS: We report on 4005 pregnant women with suspected or confirmed SARS-CoV-2 infection (1606 from PAN-COVID and 2399 from AAP-SONPM). For obstetric outcomes, in PAN-COVID overall and in those with confirmed infection in PAN-COVID and AAP-SONPM, respectively, maternal death occurred in 0.5%, 0.5% and 0.2% of cases, early neonatal death in 0.2%, 0.3% and 0.3% of cases and stillbirth in 0.5%, 0.6% and 0.4% of cases. Delivery was preterm (< 37 weeks' gestation) in 12.0% of all women in PAN-COVID, in 16.1% of those women with confirmed infection in PAN-COVID and in 15.7% of women in AAP-SONPM. Extreme preterm delivery (< 27 weeks' gestation) occurred in 0.5% of cases in PAN-COVID and 0.3% in AAP-SONPM. Neonatal SARS-CoV-2 infection was reported in 0.9% of all deliveries in PAN-COVID overall, in 2.0% in those with confirmed infection in PAN-COVID and in 1.8% in AAP-SONPM; the proportions of neonates tested were 9.5%, 20.7% and 87.2%, respectively. The rates of a small-for-gestational-age (SGA) neonate were 8.2% in PAN-COVID overall, 9.7% in those with confirmed infection and 9.6% in AAP-SONPM. Mean gestational-age-adjusted birth-weight Z-scores were -0.03 in PAN-COVID and -0.18 in AAP-SONPM. CONCLUSIONS: The findings from the UK and USA registries of pregnancies with SARS-CoV-2 infection were remarkably concordant. Preterm delivery affected a higher proportion of women than expected based on historical and contemporaneous national data. The proportions of pregnancies affected by stillbirth, a SGA infant or early neonatal death were comparable to those in historical and contemporaneous UK and USA data. Although maternal death was uncommon, the rate was higher than expected based on UK and USA population data, which is likely explained by underascertainment of women affected by milder or asymptomatic infection in pregnancy in the PAN-COVID study, although not in the AAP-SONPM study. The data presented support strong guidance for enhanced precautions to prevent SARS-CoV-2 infection in pregnancy, particularly in the context of increased risks of preterm delivery and maternal mortality, and for priority vaccination of pregnant women and women planning pregnancy. Copyright © 2021 ISUOG. Published by John Wiley & Sons Ltd.

Maternal milk feedings reduce sepsis, necrotizing enterocolitis and improve outcomes of premature infants.

OBJECTIVE: Human milk (donor milk (DM) and/or maternal milk (MM)) feedings protect against late onset sepsis (LOS), necrotizing enterocolitis (NEC) and death. However, DM lacks many anti-infective components of MM. Therefore, we studied exclusive MM feedings to evaluate the full effect of human milk on infectious and other outcomes in premature infants. STUDY DESIGN: All infants born before 33 weeks postmenstrual age (PMA) who received exclusive (>95%) MM or exclusive preterm formula (PF) were included in this prospective investigation. RESULTS: Sixty-three infants (53%) received MM and 55 infants (47%) received PF. Both groups had similar baseline characteristics. Infants in the MM group achieved full enteral nutrition sooner (14±8 vs 19±15 days, P<0.03) and required a shorter duration of central venous lines (14±10 vs 22±21, P<0.005). Fewer infants in the MM group developed LOS (9 vs 19, P<0.05) and pneumonia (8 vs 16, P<0.05) than PF infants. Only one MM and five PF infants developed NEC (Bell stage ⩾II). Logistic regression analysis using PMA and prolonged rupture of membranes as covariates demonstrated an increased rate of NEC (odds ratio=8.85, CI=1.01 to 25.17, P=0.048) in PF infants. Periventricular leukomalacia (PVL) was more common in PF (4 vs 0, P=0.04) than in MM infants. CONCLUSION: Feedings of MM advanced more rapidly and were associated with fewer infections than PF. A possible protective effect of MM against PVL, not previously described, may be related to its immune and anti-inflammatory components.

Early neonatal hypotension in premature infants born to preeclamptic mothers.

BACKGROUND: Early neonatal hypotension (ENH) is common in premature infants and has been claimed to occur more frequently in infants born to mothers with severe preeclampsia. Previous studies that showed a relationship between maternal preeclampsia and neonatal hypotension did not control for potential confounding factors such as birth weight and maternal treatment with magnesium sulfate (MgSO4). OBJECTIVE: To determine whether maternal preeclampsia is an independent risk factor for ENH. STUDY DESIGN: We conducted a retrospective review of all viable singleton infants with gestational age of 23 to 30 weeks who were admitted to the neonatal intensive care unit over a 2-year period. ENH was defined as the persistence of the mean arterial pressure lower than the gestational age in weeks requiring volume expansion and inotropic support in the first 24 h of life. RESULTS: One hundred and eighty four infants were enrolled. Seventy-five (41%) infants met the diagnostic criteria for ENH. Maternal preeclampsia, the presence of labor, maternal treatment with MgSO4, Apgar scores, birth weight, gestational age and respiratory distress syndrome were significantly associated with ENH by univariate analysis. Only gestational age and maternal preeclampsia were significantly associated with ENH by multiple logistic regression. CONCLUSION: Gestational age and maternal preeclampsia were independent risk factors for ENH in our population of premature infants.

Impact of gestational age on the clinical presentation and surgical outcome of necrotizing enterocolitis.

OBJECTIVE: This investigation tests the hypothesis that the clinical presentation and the outcome of necrotizing enterocolitis (NEC) vary with gestational age (GA). METHODS: All infants admitted to our center between October 1991 and September 2003 were evaluated weekly to identify confirmed cases of NEC. Based upon GA, these infants were divided into five groups: Extremely premature (EP, 23 to 26 weeks), very premature (VP, 27 to 29 weeks), moderately premature (MP, 30 to 34 weeks), near-term (NT, 35 to 36 weeks), and term (T, 37 to 42 weeks). RESULTS: A total of 202 infants developed NEC. The most common sign of NEC among EP infants was ileus (77%), followed by abdominal distention (71%), emesis (58%), pneumoperitoneum (54%), fixed intestinal loop (52%), gasless abdomen (42%) and bloody stools (17%). Intramural gas was detected in 100% of T but was present in only 29% of EP infants (P < 0.0001). Similarly, portal venous gas was common in T but infrequent in the EP infants (47 vs 10%, P < 0.0001). Despite a higher peritoneal drain insertion rate (31 vs 5%, P < 0.001) and a higher mortality rate (33 vs 10%, P = 0.05) in EP compared to T infants, other clinical outcomes were not different. CONCLUSIONS: The clinical presentation of NEC is different in EP compared to more mature infants; however, outcome among NEC survivors is similar across all GA. Reliance solely on observation of intramural or on portal venous gas in EP infants may lead to a delay or failure in the diagnosis.

Color Doppler ultrasound of changes in small vessel diameter and cerebral blood flow during acute anemia in the newborn lamb.

RATIONALE AND BACKGROUND: The relationship between changes in small vessel diameter as determined by arteriography and those estimated by color Doppler ultrasound were tested. These techniques were used to examine the effects of acute isovolemic anemia on cerebral blood flow and small vessel diameter in the newborn lamb. MATERIALS AND METHODS: Validation of Doppler measurements was obtained in two lambs. Color Doppler diameter estimates of the anterior tibial artery (1-2 mm) were compared with simultaneous arteriographic measurements during vasodilatation and vasoconstriction effected by intra-arterial infusions of papaverine and norepinephrine, respectively. Acute anemia was produced in five newborn lambs by serial isovolemic exchange transfusions with adult sheep plasma. Doppler estimates of intracranial vessel diameter and mean blood flow velocity were correlated with simultaneous cerebral blood flow (CBF) determinations corrected for cerebral oxygen consumption (CBF/CMRO2). RESULTS: In the anterior tibial artery, color Doppler measurements of vessel diameter correlated well with arteriographic measurements (r2 = .77, P = .001), but overestimated the absolute vessel diameter by 10% to 27%. Hemodilution resulted in significant increases in CBF/CMRO2 (r2 = .61, P = .001), and estimated diameter of small cerebral arteries (r2 = .93, P = .001). Percent change in mean blood flow velocity correlated well with changes in CBF/CMRO2, but underestimated true changes in blood flow by approximately 40% (r2 = .93, P = .0001). Conversely, changes in Doppler volume flow overestimated true change in flow by approximately 50% (r2 = .84, P = .0001). CONCLUSIONS: Under certain physiological conditions, small cerebral arteries may make an important contribution to the overall regulation of CBF. Doppler estimates of relative flow and vessel diameter correlate well with true changes in CBF and small vessel diameter.

Revascularization for bilateral renal artery occlusion after umbilical artery catheterization.

The case of a newborn infant who became hypertensive and oliguric because of bilateral renal artery occlusion following umbilical artery catheterization is presented. Eventual treatment was by microsurgical placement of an aortorenal graft, with subsequent marked improvement in the patient's course. A scan and arteriogram at 1 year showed that the revascularized kidney was responsible for the patient's normal blood urea nitrogen and creatinine concentrations, but the renal artery had recanalized and the graft occluded. The role of umbilical artery catheterization in such catastrophes and the possible future role such microsurgical reconstruction could play in neonatal hypertension are discussed.

Effect of hematocrit on cerebral blood flow with induced polycythemia.

Cerebral blood flow (CBF) is lowered during polycythemia. Whether this fall is due to an increase in red blood cell concentration (Hct) or to an increase in arterial O2 content (Cao2) is controversial. We examined the independent effects of Hct and Cao2 on CBF as Hct was raised from 30 to 55% in anesthetized 1- to 7-day-old sheep. CBF was measured by the radiolabeled microsphere technique before and after isovolemic exchange transfusion with either oxyhemoglobin-containing erythrocytes (in 5 control animals) or with methemoglobin-containing erythrocytes (in 9 experimental animals). Following exchange transfusion in the control animals, Hct rose (30 +/- 1 vs. 55 +/- 1%, mean +/- SE), Cao2 increased (15.1 +/- 0.8 vs. 26.7 +/- 0.9 vol%), and CBF fell (66 +/- 9 vs. 35 +/- 5 ml X min-1 X 100 g-1). Because the fall in CBF was proportionate to the rise in Cao2, cerebral O2 transport (CBF X Cao2) was unchanged. Following exchange transfusion in the experimental animals, Hct rose (32 +/- 1 vs. 55 +/- 1%) but Cao2 did not change. Nevertheless, CBF still fell (73 +/- 4 vs. 48 +/- 2 ml X min-1 X 100 g-1) and, as a result, cerebral O2 transport also fell. The latter cannot be attributed to a fall in cerebral O2 uptake, as cerebral O2 uptake was unaffected during each of these conditions. Comparison of the two groups of animals showed that approximately 60% of the fall in CBF may be attributed to the increase in red cell concentration alone. It is probable that this effect is due largely to changes in blood viscosity.

Hypercapnia and response of cerebral blood flow to hypoxia in newborn lambs.

Individual effects of hypoxic hypoxia and hypercapnia on the cerebral circulation are well described, but data on their combined effects are conflicting. We measured the effect of hypoxic hypoxia on cerebral blood flow (CBF) and cerebral O2 consumption during normocapnia (arterial PCO2 = 33 +/- 2 Torr) and during hypercapnia (60 +/- 2 Torr) in seven pentobarbital-anesthetized lambs. Analysis of variance showed that neither the magnitude of the hypoxic CBF response nor cerebral O2 consumption was significantly related to the level of arterial PCO2. To determine whether hypoxic cerebral vasodilation during hypercapnia was restricted by reflex sympathetic stimulation we studied an additional six hypercapnic anesthetized lambs before and after bilateral removal of the superior cervical ganglion. Sympathectomy had no effect on base-line CBF during hypercapnia or on the CBF response to hypoxic hypoxia. We conclude that the effects of hypoxic hypoxia on CBF and cerebral O2 consumption are not significantly altered by moderate hypercapnia in the anesthetized lamb. Furthermore, we found no evidence that hypercapnia results in a reflex increase in sympathetic tone that interferes with the ability of cerebral vessels to dilate during hypoxic hypoxia.

Early high-frequency oscillatory ventilation versus synchronized intermittent mandatory ventilation in very low birth weight infants: a pilot study of two ventilation protocols.

OBJECTIVE: To evaluate the feasibility of conducting a prospective, randomized trial comparing early high-frequency oscillatory ventilation (HFOV) to synchronized intermittent mandatory ventilation (SIMV) in very low birth weight (VLBW) premature infants. This pilot study evaluated two ventilator management protocols to determine how well they could be implemented in a multicenter clinical trial. Although this pilot study was not powered to detect differences in outcome, we also collected outcome data. DESIGN: Prospective, multicenter, randomized pilot study. SETTING: Seven tertiary-level intensive care nurseries with previous experience with both HFOV and flow-triggered SIMV. PATIENTS: Fifty infants weighing 501 to 1200 g, less than 4 hours of age, who had received one dose of surfactant and required ventilation with mean airway pressure > or =6 cm H2O and F(I)O2 > or =0.25, and had an anticipated duration of ventilation greater than 24 hours. INTERVENTIONS: Patients were stratified by birth weight and prenatal steroid status, then randomized to either HFOV or SIMV with tidal volume monitoring. Ventilator management for patients in both study arms was strictly governed by protocols that included optimizing lung inflation and blood gases, weaning strategies, and extubation criteria. MEASUREMENTS: Data were collected using the tools planned for the larger collaborative study. Protocol compliance was closely monitored, with successive changes in the protocol made as necessary to improve clarity and increase compliance. The incidence of major neonatal adverse outcomes was recorded. MAIN RESULTS: Data are presented for 24 HFOV and 24 SIMV infants (two infants, twins, were withdrawn from the study at parent's request). Nineteen of the 24 HFOV infants and 20 of the 24 SIMV infants survived to 36 weeks corrected age. Age at final extubation for survivors was 16+/-16 (mean+/-SD) days for HFOV infants and 24+/-24 days for SIMV infants. At 36 weeks corrected age, 14 of the 19 HFOV survivors were extubated and in room air, whereas 5 required supplemental oxygen. In comparison, 6 of the 20 SIMV survivors were extubated and in room air, whereas 14 required supplemental oxygen. Grade III/IV IVH and/or periventricular leukomalacia occurred in 2 HFOV and 2 SIMV patients. Overall compliance with the ventilator protocols was 82% for the SIMV protocol, and 88% for the HFOV protocol. CONCLUSIONS: The preliminary outcome data supports conducting the large randomized trial, which began in July of 1998. The protocols for the ventilator management of VLBW infants, both with HFOV and with SIMV were easily implemented and consistently followed, and are presented here.

Packed red blood cell transfusion is not associated with increased risk of necrotizing enterocolitis in premature infants.

OBJECTIVE: Recent reports have posited a temporal association between blood transfusion with packed red blood cells (BT) and necrotizing enterocolitis (NEC). We evaluated the relationship between BT and NEC among infants at three hospitals who were consented at birth into a prospective observational study of NEC. STUDY DESIGN: We used a case-control design to match each case of NEC in our study population of infants born at<33 weeks postmenstrual age (PMA) to one control infant using hospital of birth, PMA, birth weight and date of birth. RESULT: The number of transfusions per infant did not differ between 42 NEC cases and their controls (4.0 ± 4.6 vs 5.4 ± 4.1, mean ± s.d., P = 0.063). A matched-pair analysis did not identify an association of transfusion with NEC in either the 48-h or 7-day time periods before the onset of NEC. Stratifying on matched-sets, the Cox proportional hazard model did not identify any difference in the total number of BTs between the two groups (hazard ratio 0.78, 95% confidence interval 0.57 to 1.07, P = 0.11). CONCLUSION: In contrast to previous studies, our case-control study did not identify a significant temporal association between BT and NEC. Additional large prospective randomized studies are needed to clarify the relationship between BT and NEC.

Prenatal or postnatal indomethacin exposure and neonatal gut injury associated with isolated intestinal perforation and necrotizing enterocolitis.

OBJECTIVE: To examine the role of indomethacin in neonatal gut injury. STUDY DESIGN: Infants born at gestational age 23 weeks and with birth weights 400-1200 g were included in this prospective prevalence study of neonatal gut injury. Infants with isolated intestinal perforation (IIP) confirmed at laparotomy or at autopsy or with necrotizing enterocolitis (NEC) were identified. Data were abstracted bi-weekly. RESULT: Among 992 study infants, 58 infants exposed solely to prenatal indomethacin did not show an increased rate of neonatal gut injury. Any postnatal indomethacin exposure (n=611) increased the odds of IIP (OR 4.17, CI, 1.24-14.08, P=0.02) but decreased the odds of NEC (OR 0.65, CI 0.43-0.97, P=0.04). There was a negative association between the timing of indomethacin-exposure and the odds of developing IIP (OR 0.30, CI 0.11-0.83, P=0.02). Compared with NEC, IIP occurred at an earlier age (P<0.05) and was more common (P<0.05) among infants who received early indomethacin (first dose at <12 h of age) to prevent intraventricular hemorrhage than among infants who were treated with late indomethacin for closure of a patent ductus arteriosus (PDA). Unlike the classic hemorrhagic ischemic lesions of NEC in which large areas of tissue were inflamed or necrotic, the IIP lesions were small and discrete. CONCLUSION: Early (<12 h) postnatal indomethacin exposure was associated with an increased odds of IIP in very low birth weight infants whereas its later use for closure of a PDA appeared to provide protection against NEC. The paradoxical effect of the timing of indomethacin on IIP versus on NEC may be related to the different pathogeneses of the two diseases. Our findings also suggest that PDA may contribute to NEC.

Early neutropenia is not associated with an increased rate of nosocomial infection in very low-birth-weight infants.

BACKGROUND: Evidence is contradictory whether very low-birth-weight (VLBW, birth weight <1500 g) infants with early neutropenia (NP), especially those born to mothers with preeclampsia experience a greater incidence of nosocomial infection (NI). OBJECTIVE: To investigate whether NP within the first 7 days of life is a risk factor for NI in VLBW infants. METHODS: Over a 42-month period, we identified all VLBW infants born at

Differentiation of transient hyperammonemia of the newborn and urea cycle enzyme defects by clinical presentation.

We reviewed clinical data in 33 patients with transient hyperammonemia of the newborn (THAN): six previously unreported cases and 27 from the literature. Thirteen neonates with urea cycle enzyme deficiencies (UCED) served for comparison. No differences were found in the incidence of perinatal complications, route of delivery, Apgar scores, sex, or incidence or time of onset of seizures. On the other hand, neonates with THAN had significantly lower birth weights (mean +/- SEM 2282 +/- 78 gm vs 3336 +/- 222 gm, P less than 0.001) and gestational ages (35.1 +/- 0.5 weeks vs 39.6 +/- 0.5 weeks, P less than 0.001). Mean time of onset of respiratory distress (3.9 +/- 1.4 hours vs 71.5 +/- 26.1 hours, P less than 0.001), ventilatory support (P less than 0.001), lethargy (P less than 0.005), and coma (P less than 0.005) occurred earlier in THAN. Distinctive laboratory findings in patients with THAN included abnormal chest radiographic findings and plasma ammonium concentrations that were higher (1871 +/- 209 microM vs 973 +/- 169 microM, P less than 0.02) at an earlier age. Respiratory distress occurred in all but one patient with THAN before 24 hours; in contrast, only 62% of infants with UCED had respiratory symptoms, and none before 30 hours. In this retrospective study, the clinical presentation alone differentiated THAN from UCED.

Cerebral blood flow response to hypercapnia in immature fetal sheep.

We have reported recently that the cerebral blood flow (CBF) response to isocapnic hypoxic hypoxia is blunted in fetal sheep in utero at 93 days of gestation (term = 145-150 days), a time of rapid brain differentiation in this species. Cerebral O2 transport fell rather than being maintained, as it is in more mature fetuses. The reason for the blunted response was not clear. We hypothesized that the CBF response to hypercapnia also might be blunted. We studied 10 immature fetal sheep in utero at a mean gestational age of 92 days 24 h after catheters were placed into the superior sagittal sinus, axillary artery, and inferior vena cava. We raised the fetal arterial carbon dioxide tension (PaCO2) by changing the mother's inspired PCO2. CBF was measured before and during hypercapnia by the microsphere method. The overall increase in CBF in response to hypercapnia in immature fetuses was lower than in near-term fetuses. However, the difference was eliminated after correcting for differences in cerebral O2 consumption. This study failed to show any defect in the ability of cerebral vessels in immature fetal sheep to respond to carbon dioxide.

Home oxygen therapy for chronic lung disease in extremely low-birth-weight infants.

Chronic lung disease that requires prolonged oxygen therapy commonly complicates the recovery of extremely low-birth-weight infants (less than 1000 g). We report follow-up data through 18.5 +/- 0.9 (mean +/- SEM) months of age in 30 extremely low-birth-weight infants (birth weight, 783 +/- 24 g; gestational age, 26.0 +/- 0.3 weeks) who were discharged home receiving supplemental oxygen. Oxygen was prescribed to maintain arterial oxygen saturation at 95% or greater. At discharge, postconceptional age was 40.5 +/- 0.6 weeks, and weight was 2220 +/- 50 g. Duration of home oxygen therapy was 4.5 +/- 0.5 months. The mean weight percentile increased from less than 5 to 23 between discharge and the last follow-up. All infants survived; only 6 required hospitalization for acute medical illnesses. We conclude that carefully supervised home oxygen therapy permits the safe early discharge of selected extremely low-birth-weight infants with chronic lung disease.

Effects of cocaine on pial arterioles in cats.

We used the closed cranial window technique to observe the responses of pial arterioles to topical application of cocaine in 29 anesthetized cats. Alterations in arteriolar diameter were dependent on the concentration of cocaine applied. Cocaine dissolved in artificial cerebrospinal fluid at concentrations of 10(-8) or 10(-7) M was without effect. Concentrations of 10(-6) and 10(-5) M produced dilation (4.9 +/- 1.5% [mean +/- SEM] and 5.9 +/- 2.0%, respectively) in large arterioles (greater than 100 microns) but no significant change in the diameter of small arterioles (less than 100 microns). A concentration of 10(-4) M dilated both large and small arterioles (20.3 +/- 3.1% and 12.0 +/- 7.1%, respectively). Pretreatment with 1 mg/kg i.v. propranolol blocked the increase in pial arteriolar diameter after application of 10(-4) M cocaine and produced significant vasoconstriction in small arterioles (-8.3 +/- 3.1%). Cocaine produces vasodilation of cat cerebral arterioles. This effect appears to be mediated, at least in part, by mechanisms that depend on stimulation of beta-adrenergic receptors.

Calf lung surfactant extract prophylaxis and retinopathy of prematurity.

Retinopathy of prematurity (ROP) is an important cause of blindness among extremely low birth weight infants (birth weight less than or equal to 1000 g). In the 1990s, greater numbers of extremely low birth weight infants will survive, in part due to routine surfactant replacement therapy for neonatal respiratory distress syndrome. Few studies have evaluated the effect of surfactant therapy on the incidence and severity of ROP. The authors performed a review of the records of extremely low birth weight infants born in two 2-year intervals before and after initiation of a clinical protocol in which all extremely low birth weight infants received prophylactic treatment with calf lung surfactant extract (Infasurf). Surfactant therapy was associated with a significant improvement in survival to discharge (79% [88 of 112] versus 63% [82 of 131]; P = 0.01). Compared with control infants, surfactant-treated infants had a significantly lower incidence of any stage of ROP (64% [56 of 87] versus 85% [68 of 80]; P less than 0.004). The incidence of threshold (Stage 3 plus or greater) ROP was substantially reduced (3.4% [3 of 87] versus 10% [8 of 80]; P = 0.16)). The surfactant-associated reduction in ROP was independent of birth weight, gestational age, race, or sex. These data suggest that Infasurf may substantially reduce the incidence and severity of ROP in the extremely low birth weight population.

Oxygen free radicals and the cerebral arteriolar response to group B streptococci.

We used a cranial window preparation to observe the effects of direct application of group B streptococci to the surface of the brain in the adult rat. Continuous exposure to group B streptococci at concentrations of 10(3) and 10(5) organisms/mL caused progressive dilation of surface (pial) cerebral arterioles that became statistically significant (p less than 0.05) after 2.5 h. These results were reproduced with heat-killed organisms at the same concentration, but not with a bacteria-free filtrate of the growth medium. In separate studies, we found that infusion of alkaline cerebrospinal fluid (pH = 7.8) into the window did not reverse vasodilation, suggesting that it was not due to progressive cerebrospinal fluid acidosis. A solution of nitroblue tetrazolium infused into the window at the end of a 3-h exposure to the organism was promptly reduced, suggesting the presence of oxygen free radicals. Treatment with i.v. polyethylene glycol-superoxide dismutase and polyethylene glycol-catalase in doses of 10,000 and 20,000 U/kg, respectively, was itself without effect on pial arterioles, but treatment with these compounds before exposure to group B streptococci eliminated the vasodilation. These data support a role for oxygen free radicals in the pathogenesis of pial arteriolar dysfunction induced by exposure to group B streptococci.

Role of O2-hemoglobin affinity on cerebrovascular response to carbon monoxide hypoxia.

Our previous studies showed that, in contrast to hypoxic and anemic hypoxia, CO hypoxia increased cerebral O2 delivery and decreased cerebral fractional O2 extraction. These changes were correlated with the accompanying decrease in P50 (PO2 at 50% saturation of non-CO bound sites on hemoglobin). To assess directly the role of P50 in the cerebrovascular response to CO, we first performed isovolemic exchange transfusions on unanesthetized newborn lambs, replacing their high-O2-affinity hemoglobin with low-affinity adult sheep donor blood. Exchange transfusion resulted in an average increase in P50 of 10 Torr and in a uniform decrease of regional cerebral blood flow and cerebral O2 delivery of 14%. Thus shifts in P50 can produce cerebrovascular changes during normoxia, implying that the mechanism regulating cerebral blood flow does not have a discrete threshold to an hypoxic stimulus. Induction of CO hypoxia (20-40% carboxyhemoglobin) after the exchange transfusion returned P50 to the control level, and with it restored both cerebral O2 delivery and fractional O2 extraction to the pretransfusion values. We conclude that the fall in P50, rather than a direct tissue effect of CO, is responsible for the relative cerebral overperfusion during CO hypoxia. The importance of the position of oxyhemoglobin dissociation curve as a determinant of cerebral blood flow supports the presence of a highly sensitive, tissue O2-dependent mechanism regulating the cerebral circulation.

Base-line O2 extraction influences cerebral blood flow response to hematocrit.

We have shown that the fall in cerebral blood flow (CBF) as hematocrit (Hct) rises is due to the independent effects of increasing red blood cell (RBC) concentration and arterial O2 content (CaO2). In the present study, we tested the hypothesis that the magnitude of the effect of RBC concentration depends on the base-line cerebral fractional oxygen extraction (E). E is the ratio of O2 demand (cerebral O2 consumption, CMRO2) to supply (cerebral O2 transport: OT = CBF x CaO2) and is assumed to be inversely related to tissue O2 availability. Pentobarbital-anesthetized 1- to 7-day-old sheep were first exchange transfused with plasma to lower Hct to 20%. Base-line E was set to either high or low levels by induction of hypocarbia [arterial CO2 partial pressure (PaCO2) = 15.3 +/- 0.7 mmHg, means +/- SE; n = 7] or hypercarbia (PaCO2 = 62.7 +/- 1.1 mmHg; n = 5), respectively. A second isovolemic exchange transfusion with pure methemoglobin-containing adult sheep red cells then raised Hct (to 38.5 +/- 0.5%) with no significant increase in CaO2. PaCO2 was maintained and other variables (oxyhemoglobin affinity, pH, mean arterial blood pressure) with potential effect on CBF did not change.(ABSTRACT TRUNCATED AT 250 WORDS)