Whole body massage for newborns: A report on non-invasive methodology for neonatal opioid withdrawal syndrome.

BACKGROUND: Infants with in-utero exposure to opioids are at risk Neonatal Opioid Withdrawal Syndrome (NOWS) and non-pharmacological methods of care, like swaddling, quiet ambient environment are routinely recommended but are not systematically studied. We hypothesized that opioid exposed infants can tolerate whole body massage while hospitalized. METHODS: This is a prospective observational study (August 2017 to January 2019) and infants of mothers having a history of opioids use (OUD) were included. Infants received whole body massage for 30 minutes from birth till discharge home. Infants heart rate (HR), respiratory rate (RR), systolic (sBP) and diastolic blood pressure (dBP) were recorded prior to and at the end of massage session. RESULTS: The pilot study enrolled 30 infants. The mean birth weight and gestational age were 38±1 weeks and 2868±523 grams, respectively. All massage sessions were well tolerated. There was marked decrease in HR, systolic and diastolic BP and RR, (p < 0.01) in all study infants post massage, more profound among infants with NOWS (p < 0.01) than without NOWS. CONCLUSIONS: Whole body massage is very well tolerated by infants with in-utero opioid exposure. Infants with NOWS had marked decrease in their HR and BP from their baseline after massage.

Outcomes of neonates with birth weight⩽500 g: a 20-year experience.

OBJECTIVE: Ethical dilemmas continue regarding resuscitation versus comfort care in extremely preterm infants. Counseling parents and making decisions regarding the care of these neonates should be based on reliable, unbiased and representative data drawn from geographically defined populations. We reviewed survival and morbidity data for our population at the edge of viability. STUDY DESIGN: A retrospective review of our perinatal database was carried out to identify all infants born alive and admitted to the neonatal intensive care unit (NICU) with BW⩽500 g between 1989 and 2009. Data from the initial hospital stay and follow-up at 24 months were collected. RESULT: Out of 22 672 NICU admissions, 273 were eligible: 212 neonates were reviewed after excluding infants with comfort care. BW ranged from 285 to 500 g (mean 448 g) and gestational age range 22 to 28 weeks (median 24 week). Sixty-one (28.8%) survived until discharge. Only 13.8% males survived compared with 39.2% females (P<0.05). Half (49%) were discharged with home oxygen/monitor. Fifty (82%) patients' charts were available to review at the 24-month follow-up. Thirty-three percent of surviving infants had a normal neurodevelopmental assessment at 24 months. Forty-three percent had weight/head circumference<5th percentile at 24 months. CONCLUSION: About a third of neonates admitted to NICU with ⩽500 g BW survived, with 33% of those surviving, demonstrating age-appropriate development at a 24-month follow-up visit.

Fecal short-chain fatty acids of very-low-birth-weight preterm infants fed expressed breast milk or formula.

OBJECTIVES: In preterm infants, the metabolic responses of gastrointestinal (GI) bacteria to different diets are poorly understood despite the possible effects on GI health. Therefore, we tested the hypothesis that diet influences bacterial metabolism by measuring short-chain fatty acids (SCFAs) in stool samples from very-low-birth-weight (VLBW) preterm infants without GI disorder as surrogate biomarkers of bacterial metabolism. METHODS: Ion chromatography was used to measure fecal SCFAs (acetate, formate, propionate, butyrate, and isobutyrate), lactate, and chloride in fresh stool samples collected from 32 preterm infants (without major congenital anomalies, GI disorders, or a recent history of antibiotic administration and on full feed of either expressed maternal breast milk [EBM; n = 13] or a formula for preterm infants [Similac Special Care Formula; preterm formula, PTF; n = 19]). RESULTS: The mean birth weight was 972 g, the mean gestational age was 27 weeks, and the mean postnatal age at first stool sample was 36 days. When adjusted for gestational age, the stools of EBM infants had higher concentrations (micromoles per gram of stool) of total SCFA (128 vs 68; P = 0.002), acetate (41 vs 13; P = 0.005), propionate (15.1 vs 4.4; P = 0.003), and chloride (21,814 vs 10,652; P = 0.02). Interactions between postnatal age and diet were detected for lactate (P = 0.05), propionate (P = 0.03), and butyrate (P = 0.03). CONCLUSIONS: Diets fed to VLBW preterm infants influence fecal SCFA profiles, and hence the metabolism of the GI bacteria, and potentially the health of preterm infants. The responses of bacterial metabolism to diet are influenced with postnatal age and gestational age at birth.

Ruptured remnant of urachal diverticulum: an unusual cause of congenital urinary ascites.

Urachal diverticulum is an infrequent finding and its perforation as a cause of fetal urinary ascites has not been reported before. This is a case report on an infant with antenatal diagnosis of fetal ascites. This infant was delivered via cesarean section and needed mechanical ventilation owing to a massive ascites that required paracentesis. She did not void for 20 h until a urethral catheter was placed. The biochemical analysis of the ascitic fluid compared with the serum and urine was suggestive of urine ascites. The voiding cystourethrogram (VCUG) showed a leakage at the remnant of urachal diverticulum. The urethral catheter was maintained for 3 weeks until the repeated VCUG confirmed a sealed-off urachal diverticulum. With removal of the catheter, the infant was able to void spontaneously and was discharged home on continued prophylactic antibiotics. As symptomatic urachal remnants have an increased potential for malignant transformation, a close follow-up by a urologist was recommended.

Dynamics of nuclear localization sites for COX-2 in vascular endothelial cells.

We investigated the relationships among expression, activity, and spatial organization of cyclooxygenase (COX-1 and COX-2) in endothelial cells from porcine and human cerebral microvessels and from human umbilical vein. In quiescent cells, COX-1 was detected in the perinuclear zone and the cytoplasm, while COX-2 was mainly a nuclear resident possibly connected with the nuclear matrix. COX-2 immunogold labeling was situated in the nuclear envelope, at the nuclear pores, and in connection with the perichromatin regions of the nucleus, considered to be the sites of active transcription. In human endothelial cells transcriptionally activated by interleukin (IL)-1beta, the nucleus remained a major COX-2 localization site during the first 12 h of stimulation, when COX-2 expression was maximally induced. The continuous rise in prostanoid synthesis at 17-23 h of stimulation was associated with COX-2 relocation from the nucleus to the nuclear envelope and the cytoplasm. IL-1beta did not affect COX-1 expression, activity, and localization. COX-2 nuclear localization sites and trafficking between the nucleus and the cytoplasm in endothelial cells may indicate a novel function of COX-2 in regulating gene expression.

Preservation of cerebrovascular tone and reactivity by sodium channel inhibition in experimental prolonged asphyxia in piglets.

Sodium channels using cAMP as a second messenger play a role in the regulation of cerebral circulation and metabolism. Cerebrospinal fluid (CSF) cAMP levels have been shown to correlate with the degree and duration of hypoxic injury and outcome and to be an indicator of cerebral vascular reactivity. We hypothesize that sodium channel inhibition either before or at termination of experimental asphyxia will attenuate cerebrovascular alterations and maintain CSF cAMP levels. Three groups of piglets with closed cranial windows were studied: asphyxia or group 1 (n = 5) and two treatment groups. Pigs were treated with 50 mg/kg of sodium channel blocker before asphyxia (group 2, n = 6) and after the termination of asphyxia and start of reventilation (group 3, n = 6). Asphyxia was sustained over 60 min by ventilating piglets with 10% O2 gas mixture and decreasing minute ventilation followed by 60 min of reventilation with room air. Every 10 min, pial arterial diameters were measured, and CSF samples were collected for cAMP determination. Vascular reactivity to topically applied isoproterenol (10(-4) M) was evaluated 60 min after recovery. During asphyxia, cAMP levels in group 2 peaked and declined at a later time with mean values remaining significantly higher than those of groups 1 and 3. During reventilation, CSF cAMP concentrations were highest in group 3 and lowest in group 1. Pial arteriolar dilation occurred during asphyxia in all three groups but to a lesser degree in the pretreated group compared with groups 1 and 3. Pial arteriolar reactivity to isoproterenol postasphyxia was preserved in both groups 2 and 3. In summary, in newborn pigs, pretreatment with sodium channel blocker resulted in higher CSF cAMP levels and a lesser degree of pial arteriolar dilation during prolonged asphyxia. Pretreatment or treatment at reventilation restored vascular tone and reactivity.

Cerebral hemodynamic measurements in acute versus chronic asphyxia.

In most reports of asphyxia in newborn infants, the occurrence, duration, frequency of episodes, or severity of the asphyxic insult is usually not known, and yet abnormal neurologic outcomes have been observed. The fetus has several innate characteristics that allow compensatory response to lack of oxygen over a reasonable duration of time; however, these inherent capabilities differ among individuals. Therefore, for a given asphyxic insult, the aftermath may be intact survival, some neurologic sequelae, or death. In an asphyxiated infant, an abnormal cerebral blood velocity flow pattern, especially if consistent with vasoparalysis, probably signals that an asphyxic or ischemic neuronal insult has occurred; the integrity of the neurons and their function are dependent on an appropriate uptake of oxygen and nutrients in the presence of adequate perfusion. Hemodynamic changes associated with acute asphyxia are different from those observed in chronic asphyxia. Based on information from experimental studies, less severe but prolonged asphyxia is associated with severer brain injury than when an insult is brief but severe. Thus, when asphyxia or ischemia is suspected based on obstetric monitoring, the fetus should be delivered under appropriate optimal conditions and resuscitative measures initiated if indicated. If all of ACOG's criteria for defining asphyxia are met, it could be assumed that a severe acute asphyxic insult or a repetitive insult has occurred. In cases where the only findings are abnormally low Apgar score and pH, the insult is most probably acute and brief. Thus, survival is likely not associated with any neurologic abnormality. With a likelihood that asphyxia has occurred, available therapeutic intervention should be initiated early, in the first 48 to 72 hours of life, without waiting for neurologic complications or multiorgan system failure to develop.

Cerebrovascular responses to therapeutic dose of indomethacin in newborn pigs.

The aims of this study were 1) to compare the effects of low versus high doses of indomethacin on cerebral blood flow (CBF) responses to hypercapnia and 2) to investigate the effects of low-dose indomethacin on the cerebral vasculature during resting conditions and during vasodilator stimuli. In the first experiment, 27 piglets were randomized into three groups to receive 5 mg/kg indomethacin, 0.2 mg/kg indomethacin, or normal saline. Ninety minutes later, CBF was measured by radioactive microspheres at baseline, during hypercapnia [PaCO2 > or = 70 mm Hg (> or =9.3 kPa)] and normocapnia. Total CBF was comparable among the three groups at baseline. CBF increased during hypercapnia in all groups, but the hyperemic response was significantly attenuated in the high-dose indomethacin group compared with the saline group but not in the group treated with 0.2 mg/kg. CBF returned toward baseline during normocapnia in all piglets. In the second experiment, a closed cranial window was implanted over the parietal cortex of nine piglets. Cerebrovascular responses to hypercapnia and topical application of isoproterenol (10(-7) and 10(-6) M) and histamine (10(-6) and 10(-5) M) were investigated before and after administration of 0.2 mg/kg indomethacin. Within 10 min of indomethacin administration, pial arteriolar diameters decreased from 72 +/- 8 to 58 +/- 6 microm (p < 0.05), and 6-keto-PGF1alpha concentration decreased from 1440 +/- 250 to 570 +/- 30 pg/mL (p < 0.05). Two hours (138 +/- 21 min) later, pial arteriolar diameters had returned toward baseline values (65 +/- 5 microm), whereas 6-keto-PGF1alpha values remained considerably lower than preindomethacin values (530 +/- 30 pg/mL). Cerebrovascular responses to dilator stimuli were preserved after 0.2 mg/kg indomethacin. We conclude that 0.2 mg/kg indomethacin does not markedly affect the cerebral hyperemic responses to hypercapnia in contrast with a very prominent inhibition by 5 mg/kg indomethacin. Also, although indomethacin at a low dose constricts pial arterioles transiently and attenuates cerebral prostanoid production, it does not inhibit the pial arteriolar responsiveness to prostanoid-associated dilator stimuli. This observation may be due to the permissive role that prostacyclin plays in cerebral vasodilatory responses to some vasogenic stimuli such as hypercapnia and histamine.

Prognostic significance of cerebrospinal fluid cyclic adenosine monophosphate in neonatal asphyxia.

OBJECTIVE: In piglets prolonged asphyxia resulted in decreased cerebrospinal fluid (CSF) 3;,5;-cyclic adenosine monophosphate (cAMP) during recovery; this was associated with reduced pial arteriolar responses to stimuli that use cAMP as a second messenger. We hypothesized that asphyxia in human neonates results in decreased CSF cAMP and that low CSF cAMP is associated with abnormal outcome. DESIGN: We studied 27 infants with evidence of hypoxic-ischemic insult; 19 were term (group 1) and 8 were preterm (group 2). The normal values of CSF cAMP were determined from 75 infants with no asphyxia; 44 were term (group 3) and 31 were preterm (group 4). CSF cAMP was measured by using radioimmunoassay procedures. RESULTS: CSF cAMP levels in infants with asphyxia (groups 1 and 2) were 12 +/- 9. 5 and 7.9 +/- 7.1 pmol/mL, respectively, significantly lower than those of groups 3 and 4 (control infants), that is, 21.1 +/- 8.7 and 27.1 +/- 9.2 pmol/mL, respectively (P <.0001). Among infants with asphyxia, 3 died and 10 had abnormal neurologic outcome. Univariate analysis showed that abnormal outcomes were significantly related to CSF cAMP levels, phenobarbital use, and multi-organ failure. However, only CSF cAMP was retained in the model by stepwise logistic regression. CSF cAMP of 10.0 pmol/mL discriminated between those with normal and those with abnormal neurologic outcome. Low CSF cAMP concentration was associated with abnormal long-term outcome, estimated odds ratio of 12.4 (95% CI, 2.1-109.3; P <.006), and sensitivity, specificity, and positive and negative predictive values of 85%, 69%, 73%, and 80%, respectively. CONCLUSION: CSF cAMP concentrations were decreased in infants with asphyxia. Low CSF cAMP levels were associated with poor neurologic outcome.

Interleukin-6, C-reactive protein, and abnormal cardiorespiratory responses to immunization in premature infants.

OBJECTIVE: We report our experience with routine immunization of 89 premature infants in the neonatal intensive care unit because 1) a substantial number of them developed abnormal clinical signs, and 2) all but one of those who received diphtheria, tetanus, and whole-cell pertussis (DTwP) vaccine responded with elevations of interleukin-6 (IL-6) and C-reactive protein (CRP) concentrations that are otherwise characteristic of bacterial disease. METHODOLOGY: We hypothesized that the elevated IL-6 and CRP levels were solely a response to immunization and that treatment with antibiotics was not necessary. We performed this study in two consecutive parts. In part 1, we prospectively evaluated 79 consecutive premature infants who were immunized with DTwP, Haemophilus b conjugate vaccine, hepatitis B vaccine, and inactivated polio vaccine, (Hib, HBV, and IPV). IL-6 and CRP were determined before immunization and every 12 hours on three occasions after immunization. In part 2, we studied an additional 10 infants who received acellular pertussis vaccine (DTaP) and who, 2 days later, received Hib, HBV, and IPV immunization simultaneously. We followed the same schedule of IL-6 and CRP determinations as in part 1. RESULTS: In part 1, 24 infants (30%) developed abnormal cardiorespiratory signs within 24 hours after immunization. CRP and IL-6 values rose to abnormal levels after immunization in all but one infant; that infant was later shown to have a T-cell abnormality. In part 2, 3 infants had abnormal cardiorespiratory signs after simultaneous immunization with Hib, HBV, and IPV, but not after DTaP. IL-6 and CRP levels remained normal in all 10 infants. CONCLUSIONS: Part 1 demonstrates clearly the temporal relationship between IL-6 and CRP increments after DTwP, Hib, HBV, and IPV vaccines. In part 2 (DTaP was substituted for DTwP), there were no elevations of IL-6 or CRP, thus indicating that whole-cell pertussis component of DTwP was responsible for IL-6 and CRP elevations. Abnormal cardiorespiratory signs occurred frequently after immunizations in part 1, but they were unrelated to the magnitude of IL-6 and CRP elevations. The frequency of cardiorespiratory difficulty and its occasional severity suggest a need to monitor premature infants for approximately 48 hours after routine immunization.

The effects of intraventricular/periventricular blood on cerebral 3',5'-cyclic adenosine monophosphate concentration and cerebrovascular reactivity in newborn pigs.

This study investigated the effects of intraventricular/periventricular blood on cerebral cAMP production and cortical cerebrovascular reactivity. Under halothane and N2O anesthesia, 3 mL of either autologous blood or artificial cerebrospinal fluid (CSF) were injected into the left caudate nucleus; volume was adequate to result in extrusion of fluid or blood into the lateral ventricles of 1-2-d-old piglets. Twenty-four hours later, a closed cranial window was implanted over the left parietal cortex. Pial arteriolar responses to vasodilator and vasoconstrictor stimuli were monitored. Before the application of vasoactive agents, cortical periarachioid CSF was collected for cAMP measurement. Pial arteriolar responses to topical application of endothelin-1 (10(-9) and 10(-8) M) and to leukotriene C4 (10(-10) and 10(-9) M) were similar between the two groups. However, pial arteriolar responses to topical application of cAMP-mediated vasodilators, prostaglandin E2 (10(-6) and 10(-5) M), and histamine (10(-6) and 10(-5) M), respectively, were markedly reduced in the blood group when compared with the artificial CSF (control) group. Mean CSF cAMP level in the blood group was significantly lower than the control group (199 +/- 31 versus 1092 +/- 238 fmol/mL, p = 0.0006). We conclude that in newborn pigs intraventricular/periventricular blood results in a marked reduction of CSF cAMP concentration and attenuation of the cerebrovascular responses to cAMP-mediated vasodilators on the cortical surface remote from the site of blood or hematoma.

Changes in cerebral cyclic nucleotides and cerebral blood flow during prolonged asphyxia and recovery in newborn pigs.

Cerebrovascular reactivity is preserved after acute severe asphyxia/reventilation in piglets. We hypothesize that prolonged, partial asphyxia with hypotension causes loss of cerebrovascular reactivity and altered cerebral hemodynamics during recovery. We investigated the changes in cerebrospinal fluid cAMP and cGMP, pial arteriolar diameters and flow, and cerebral blood flow during 1 h of asphyxia and 1 h of recovery. During asphyxia, blood pressure decreased from 10 +/- 0.7 to 4.7 +/- 0.3 kPa and increased during recovery to 6 +/- 0.7 kPa. cAMP increased 3-fold by 20 min of asphyxia, returning to baseline at 40 min of asphyxia. During recovery, cAMP increased 2-fold initially, followed by a decrease to 50% below baseline. cGMP increased after 20 min of asphyxia, with maximum levels observed at 40 min; reventilation resulted in a transient increase in cGMP. Pial arteriolar diameters increased at the onset of asphyxia, then decreased toward baseline; during recovery, a similar pattern occurred. Blood flow to the cerebrum (microspheres) decreased during asphyxia and remained very low during recovery. Pial arteriolar flow but not pial arteriolar diameters followed the changes in cortical cerebral blood flow (i.e. virtually no flow during recovery). During recovery, pial arteriolar reactivity to isoproterenol and histamine decreased significantly. We conclude that 60 min of asphyxic-hypotensive insult results in alterations of cerebral cAMP metabolism which may compromise cellular communications during recovery. Prolonged asphyxia induces "no-reflow" during recovery, even when partial pressures of arterial CO2 and O2 have returned to baseline values, and blood pressure is within the autoregulatory range.

Cerebral blood flow responses to indomethacin in awake newborn pigs.

The prostaglandin H-synthase inhibitor indomethacin decreases cerebral blood flow (CBF) in newborn pigs. The duration of this effect on CBF has not been established in piglets in the awake state. The purpose of the study was to determine in awake piglets the duration of cerebral vascular responses to a single dose of indomethacin and the CBF responses to a second dose of indomethacin. Two groups of animals were studied. Newborn pigs 3-5 d old were instrumented the day before experiments. On the next day, sagittal sinus catheters were placed after the piglets were given local anesthesia. The experiments were performed on unanesthetized piglets that were put in a cloth sling and fed via an orogastric tube. In the first group of piglets (n = 8), the baseline CBF (microspheres) and cerebral metabolic rate for oxygen (CMRO2) measurements were made 30 min after sagittal sinus catheter placement. Indomethacin (5 mg/kg i.v.) was then given slowly over a 5-min period, and CBF and CMRO2 measurements were made at 10, 60, 120, and 240 min. Total CBF (mean +/- SEM) decreased significantly after indomethacin administration from 98 +/- 12 mL.min-1.100 g-1 to 50 +/- 3, 56 +/- 7, and 70 +/- 11 mL.min-1.100 g-1 at 10, 60, and 120 min, respectively. The total CBF returned to baseline levels at 240 min (101 +/- 16 mL-1.min-1.100 g-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Brain superoxide anion generation in asphyxiated piglets and the effect of indomethacin at therapeutic dose.

We have previously shown that generation of superoxide anion occurs in cerebral cortex during asphyxia/reventilation in newborn pigs and that a high dose of indomethacin (5 mg/kg i.v.) abolishes superoxide anion production. The purposes of this study were 1) to determine whether the generation of superoxide anion occurs primarily during asphyxia or whether reventilation must take place, 2) to investigate the effects of indomethacin pretreatment at a therapeutic dose of 0.2 mg/kg i.v. on superoxide anion generation, and 3) to investigate the effects of oxypurinol, an oxygen free radical scavenger, on superoxide anion production during asphyxia/reventilation. Superoxide anion production on cerebral cortex was determined by superoxide dismutase-inhibitable nitroblue tetrazolium (NBT) reduction using closed cranial windows. Superoxide anion generation during asphyxia without reventilation was 4 +/- 2 pmol NBT/mm2 per 20 min, which was significantly lower than during asphyxia/reventilation (16 +/- 4 pmol NBT/mm2 per 20 min) but comparable to the control group (3 +/- 1 pmol NBT/mm2 per 20 min). Indomethacin given at therapeutic dosage before asphyxia/reventilation decreased superoxide anion production to 3 +/- 1 pmol NBT/mm2 per 20 min, values not significantly different from the control group and from piglets pretreated with oxypurinol at a dose of 50 mg/kg i.v. (4 +/- 2 pmol NBT/mm2 per 20 min). We conclude that in newborn pigs 1) superoxide anions are generated largely during reventilation rather than during asphyxia; 2) the therapeutic dose of indomethacin (0.2 mg/kg) is effective in inhibiting the superoxide anion generation during asphyxia/reventilation; and 3) oxypurinol reduces the superoxide anion accumulation on cerebral cortex during asphyxia/reventilation.

Significance of serial C-reactive protein responses in neonatal infection and other disorders.

OBJECTIVE: This study was performed to determine prospectively whether, in the presence of proved or presumed bacterial infection, the sensitivity of serum C-reactive protein (CRP) response could be enhanced by serial rather than single determinations. We also sought to assess CRP responses to clinically identified noninfectious disorders. DESIGN: The CRP responses of 491 infants on 691 occasions of suspected infection were assessed. CRP levels were measured initially and twice again at 12-hour intervals (rate immunonephelometry). Assessments also included a blood culture, complete blood cell count, and chest radiograph and culture of spinal fluid when appropriate. CRP responses were correlated with four designated clinical groups: (1) positive blood or cerebrospinal fluid cultures (n = 190); (2) negative blood culture-definite infection (necrotizing enterocolitis stages 2 and 3, pneumonia, subcutaneous abscess) (n = 52); (3) negative blood culture-possible infection (antenatal risk factors, meconium aspiration, positive urine group B streptococcus antigen, necrotizing enterocolitis stage 1, febrile infants) (n = 287); and (4) negative blood culture-no infection (respiratory distress syndrome, transient tachypnea of the newborn, patent ductus arteriosus, tissue trauma) (n = 160). Diagnoses were made before CRP results were known. RESULTS: In all, 187 (27%) of the blood cultures were positive. A single organism was recovered from 174 of these; two organisms from 13. Among the single-organism cultures, 50 (29%) were Gram-negative, 120 (69%) were Gram-positive, and 4 (2%) were budding yeasts. CRP levels were elevated in various groups as follows: in the positive blood culture group (by organism), Gram-negative rods, 92% (46/50); group B streptococcus, 92% (12/13); Staphylococcus aureus, 89% (8/9); group D streptococcus, 71% (10/14); Streptococcus viridans, 60% (6/10); Staphylococcus epidermidis, 55% (40/73). In the negative blood culture-definite infection group, CRP levels were abnormal in 88%; in the negative culture-possible infection group, CRP was elevated in 33%; and in the negative blood culture-no infection group, CRP was elevated in 9%. Serial determinations of CRP resulted in enhanced sensitivity in the positive blood culture group, the negative blood culture-definite infection group, and the negative blood culture-possible infection group. Initial determinations by themselves were inadequately sensitive. Serial determinations did not enhance sensitivity of the negative blood culture-no infection group. High specificity (91%) is suggested by the low incidence of abnormal CRP levels among infants who were not infected. CONCLUSIONS: These data suggest that it would be appropriate to conduct a cautious, controlled trial to assess the safety of discontinuing antibiotic therapy if three serial CRP measurements are normal and if there are no other clinical factors suggestive of infection. The data also indicate the necessity for serial determinations of CRP for optimal sensitivity.

Overestimation of neonatal PO2 by collection of arterial blood gas values with the butterfly infusion set.

The butterfly, or scalp vein infusion set, is a widely used and convenient way to collect arterial blood gas samples in neonates. Analyzing arterial blood gas values by using this technique in a clinical situation, we obtained elevated values of PO2 in blood samples collected and measured from butterfly tubing in comparison with tuberculin syringe controls. Diffusion of gas through the polyvinylchloride tubing was suggested and proved by a study of pairs of butterfly and tuberculin syringes filled with venous blood from the blood bank. In conclusion, the butterfly gives falsely elevated PO2 values as a result of gas diffusion and is not a reliable technique for arterial blood gas sampling in neonates.

Effects of pancuronium bromide on cerebral blood flow changes during seizures in newborn pigs.

We investigated the effects of pancuronium bromide pretreatment on cerebral blood flow (CBF) during bicuculline-induced seizures in anesthetized piglets. Arterial blood pressure, gases, pH, cerebral electrocortical activity, and CBF (radioactive microsphere) were monitored at baseline, 10 min after administration of pancuronium (0.3 mg/kg i.v.; n = 9) or vehicle (normal saline; n = 8), and again at 5, 15, and 60 min after bicuculline (3 mg/kg i.v.). No change in CBF from baseline was observed at 10 min after either saline or pancuronium treatment, before induction of seizures. In the saline group, CBF was 36 +/- 3 mL.min-1.100 g-1 before bicuculline and increased to 166 +/- 24 and 205 +/- 35 mL.min-1.100 g-1 at 5 and 15 min, respectively, after bicuculline, returning toward baseline by 60 min. In the pancuronium group at 5 min after bicuculline, CBF increased from 45 +/- 7 to 169 +/- 26 mL.min-1.100 g-1, but fell to 88 +/- 17 mL.min-1.100 g-1 at 15 min in contrast to saline-treated piglets. Also, at 15 min of seizures, differences between groups were observed in arterial blood pressure, gases, and pH. Although these variables were in the normal range with pancuronium treatment, the saline-treated animals had increased arterial blood pressure (81 +/- 6 mm Hg) and PCO2 (6 +/- 0.4 kPa) and decreased PO2 (7 +/- 0.5 kPa) and pH (6.91 +/- 0.06). Electrocortical activity was abnormal during seizures in both groups. At 60 min, reversal to normal activity was observed in six of nine pancuronium-treated animals versus two of eight saline-treated animals. These data suggest that pancuronium limits cerebral hyperemia during prolonged seizures by attenuating increases in blood pressure as a result of elimination of skeletal muscle activity. This leads to minimal alteration of arterial PCO2, PO2, and pH during seizures.

Asymptomatic syndrome of polycythemic hyperviscosity: effect of partial plasma exchange transfusion.

We determined the cerebral hemodynamic changes in infants with asymptomatic polycythemic hyperviscosity syndrome and whether treatment with partial plasma exchange transfusion (PPET) would affect hemodynamics as well as outcome. From a routine cord blood hematocrit screening, 71 babies were identified as needing to be tested for polycythemic hyperviscosity. In addition to clinical evaluation, each infant had radial artery hematocrit and viscosity determinations, blood gas determinations, cerebral blood flow velocity studies, cranial ultrasonography, and noninvasive intracranial pressure determination. Babies with symptomatic hyperviscosity (n = 17) were treated by PPET, whereas those with asymptomatic hyperviscosity (n = 28) were randomly selected to have PPET (n = 14) or to be observed (n = 14). The remaining babies (n = 26) with normal viscosity served as control subjects. Both hematocrit and viscosity decreased after PPET but remained unchanged in babies with hyperviscosity who were merely observed. Reversal of cerebral blood flow velocity abnormalities was observed after PPET in the infants with symptomatic hyperviscosity, whereas those who had no symptoms had normal results on Doppler studies at the outset, and no significant changes occurred with either PPET or observation. There were two deaths in the group with symptoms. A total of 46 babies returned for follow-up evaluation at a mean age of 30 +/- 7.7 months. Outcome of the control group was no better than that of those who had hyperviscosity, and outcomes did not differ between the babies with symptomatic and those with asymptomatic hyperviscosity, nor between those treated with PPET and those who were only observed. Multivariate analysis revealed that other perinatal risk factors and race rather than polycythemia or PPET, significantly influenced long-term outcome.

Acute phase reactants in neonatal bacterial infection.

The C-reactive protein (CRP) level was evaluated in 142 infants requiring investigation for suspected infection. After excluding two neonates because of incomplete data, there remained 140 neonates, of whom 16 had septicemia. Fifteen of 16 had increased CRP levels. The CRP value was not elevated in any baby (n = 5) who had positive blood cultures for Staphylococcus epidermidis, all of whom had an uneventful clinical course. The CRP level was elevated in all six babies with meconium-aspiration syndrome, but was normal in five infants whose viral cultures were positive. Ninety-nine percent of uninfected babies had normal CRP values. Overall, CRP was a valuable test for diagnostic confirmation of bacterial infection. Elevated CRP level was always accompanied by at least one abnormality in the other tests performed. Although the study was not intended to predict clinical onset of bacterial disease, our results suggest that the CRP level, because of a high negative predictive value, may be useful in ruling out bacterial infection.

Activated oxygen species do not mediate hypercapnia-induced cerebral vasodilation in newborn pigs.

In newborn pigs, vasodilation in response to hypercapnia is dependent on prostaglandin (PG) H synthase. We investigated the contribution of activated oxygen by-products to hypercapnia-induced PGH synthase-dependent dilation of pial arteries and arterioles in anesthetized newborn pigs. Activated oxygen species were generated on the cerebral surface using xanthine oxidase and hypoxanthine. Catalase, H2O2, and iron or N-(2-mercaptopropionyl)-glycine (MPG) were used to separate effects of superoxide anion and hydroxyl radical. All the activated oxygen species tested caused vasodilation of both arteries and arterioles. Vasodilation to all activated oxygen species was largely reversible with only the hydroxyl radical encouraging combination of xanthine oxidase, hypoxanthine, H2O2, and FeCl3, causing significant dilation 20 min after removal of treatment. Cotreatment with MPG blocked this residual dilation. Neither pretreatment with the extracellular superoxide anion radical scavenger, superoxide dismutase (SOD), the intracellular superoxide anion radical scavenger, Tiron, the H2O2 scavenger, catalase, nor hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and MPG, altered vasodilation of pial arteries or arterioles in response to hypercapnia. Furthermore, the increase in cerebral prostanoid synthesis in response to hypercapnia was not affected by pretreatment with SOD, Tiron, catalase, DMSO, or MPG. We conclude that the progressively reduced forms of oxygen that would be produced during PGH synthase metabolism of arachidonic acid can dilate pial arteries and arterioles of newborn pigs. However, these activated oxygen species are not responsible for the vasodilation to hypercapnia in the newborn pig, suggesting that eicosanoids cause the dilation.