Mediators of fetal inflammation in extremely low gestational age newborns.

To establish levels of mediators of inflammation in cord blood and postnatal serum from extremely low gestational age newborns (ELGANs, < or =28 weeks), we measured sixteen markers of inflammation by recycling immunoaffinity chromatography in 15 ELGANs who had serum sampled at days 2-5. Median levels of IL-1, IL-6, IL-8, IL-11, IL-13, TNF-alpha, G-CSF, M-CSF, GM-CSF, MIP-1alpha, and RANTES were considerably higher than published values of these inflammatory mediators from term newborns. In three of eight ELGANS who had serial measurements taken, levels of IL-1, IL-6, IL-8, IL-11, TNF-alpha, G-CSF, and MIP-1alpha declined from initially very high levels to reach an apparent baseline towards the end of the first postnatal week. In these same three infants, GM-CSF and TGF-beta1 levels increased continuously during the first week. In the other five ELGANs, no consistent changes were observed. We speculate, that in some ELGANs, a fetal systemic inflammatory response is characterized by an antenatal wave of pro-inflammatory cytokines, followed by a second, postnatal wave of anti-inflammatory cytokines. Large epidemiologic studies are needed to clarify relationships among inflammation markers and their expression in the fetal and neonatal circulation over time. Such studies would also add to our understanding of the possible role of inflammatory mediators in the pathophysiology of the major complications of extreme prematurity.

Platelet and platelet-derived microparticle surface factor V/Va binding in whole blood: differences between neonates and adults.

Platelet-derived microparticles (PDMP) appear to play a major role in the generation of procoagulant activity. In this study, we describe a novel flow cytometric method that allows direct evaluation of the procoagulant activity of PDMP and platelets in the physiological milieu of whole blood. The percent PDMP generated in response to calcium ionophore A23187 and calcium was increased in preterm neonates (67.5+/-3.4%, mean +/- S.E.M., n = 8, p <0.05) and term neonates (67.2+/-2.7%, n = 7, p<0.05) compared with adults (49.5+/-3.4%, n = 13). However, in preterm neonates A23187/calcium-induced binding of factor V/Va to PDMP and platelets (22.8+/-5.6 fluorescence units) was markedly reduced (p <0.05) compared to term neonates (58.2+/-7.2) and adults (50.6+/-6.3). In preterm blood, A23187/calcium-induced binding of factor V/Va to PDMP and platelets returned to adult levels when: a) adult plasma, rather than autologous preterm neonatal plasma, was added; or b) factor V, but not factor VIII, was added to autologous preterm neonatal plasma. In summary: 1) We have developed a flow cytometric method for the direct detection of procoagulant PDMP and platelets in whole blood. 2) Compared to adults and term neonates, PDMP and platelets of preterm neonates bound markedly less factor V/Va (reflecting reduced procoagulant activity), because of a relative lack of factor V in preterm neonates. 3) This procoagulant defect in PDMP and platelets may contribute to the propensity of preterm neonates, but not term neonates, to intraventricular hemorrhage. 4) The percent PDMP does not necessarily reflect the degree of procoagulant activity of PDMP or platelets.

Nephrocalcinosis in premature infants: variability in ultrasound detection.

OBJECTIVE: To measure variability among radiologists in the ultrasound diagnosis of nephrocalcinosis in premature infants. METHODOLOGY: In this prospective multicenter study, renal ultrasounds were performed on 54 very low birth weight infants using a 5.0- and 7.5-MHz transducer, and these ultrasounds were read independently by three radiologists. kappa coefficients were calculated to assess variability in identification of nephrocalcinosis among the radiologists. RESULTS: The kappa coefficient (+/- confidence intervals) using a 5.0-MHz transducer was 0.143 (0.108, 0.178); using the 7.5-MHz transducer, the kappa coefficient was 0.268 (0.243, 0.293). All three radiologists agreed in their identification of nephrocalcinosis on 3 of 54 ultrasounds using a 5.0-MHz transducer; a total of 6 of 54 ultrasounds obtained using a 7.5-MHz transducer were read as positive by all three radiologists. CONCLUSION: There is significant variability among radiologists in the ultrasound identification of nephrocalcinosis in premature infants; a 7.5-MHz ultrasound transducer is associated with less variability in recognizing this lesion.

Variations in blood transfusions among newborn intensive care units. SNAP II Study Group.

OBJECTIVES: Very low birth weight (< 1500 g) infants frequently require packed red blood cell transfusions, and transfusion rates vary among neonatal intensive care units (NICUs). We analyzed transfusions and compared outcomes among NICUs. STUDY DESIGN: In a 6-site prospective study, we abstracted all newborns weighing < 1500 g (total = 825) born between October 1994 and September 1995. Transfusion frequency and volume and phlebotomy number were analyzed by site and adjusted for birth weight and illness severity. We compared rates of intraventricular hemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia, growth, and length of stay between the high and low transfuser NICUs. RESULTS: Sites differed significantly in mean birth weight, illness severity, number of transfusions, pretransfusion hematocrit, blood draws, and donor number. Multivariate adjustment for these risks showed that the highest transfusing NICU transfused an additional 24 cc/kg per baby during the first 14 days and 47 cc/kg per baby after 15 days, relative to the lowest transfusing NICU. The presence of arterial catheters increased the frequency of blood transfusions. The rates of intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia were not higher in the 2 lowest transfusing NICUs, nor were there differences in 28-day weight gain or length of stay. CONCLUSIONS: Major differences in transfusion practices for very low birth weight infants exist among NICUs. Because clinical outcomes were no different in lower transfuser NICUs, it is likely that transfusion and phlebotomy guidelines could result in fewer transfusions, fewer complications, and reduced cost.

Routine skin cleansing with povidone-iodine is not a common cause of transient neonatal hypothyroidism in North America: a prospective controlled study.

A high incidence of transient neonatal hypothyroidism has been observed in premature infants after routine skin cleansing with iodine. Because these reports have been predominantly from Europe, a borderline, iodine-deficient area, we wished to determine whether this was also true in North America, an iodine-sufficient area. A prospective, controlled study was performed in premature babies < or = 36 weeks gestation admitted to a neonatal intensive care nursery. Thyroxine (T4) and thyrotropin (TSH) were measured at day 1, days 4 to 6, and 10 to 12 after skin preparation with iodine or with a noniodine-containing antiseptic solution (chlorhexidine) that served as control. If repeat cleansing was required, this sequence was repeated. Urinary iodine was quantitated on days 1 to 3 to estimate iodine exposure. There was no difference in the mean T4 concentration at any of the time points evaluated nor in the incidence of transient hypothyroidism between the iodine-exposed (2/17) and control babies (0/14) despite urinary iodine excretion up to 88 times the control value. Unexpectedly 5 iodine-exposed but 0 control babies developed severe hypothyroxinemia (T4 < 40 nmol/L), compatible with the sick euthyroid syndrome; one of them died. We conclude that, unlike in Europe, transient hypothyroidism is not a common sequela of routine skin cleansing with iodine in premature newborn infants in North America. This difference in incidence may be due to prior iodine status. Whether excessive iodine absorption in premature infants is associated with thyroid-independent toxic effects remains to be clarified.

Platelet hyporeactivity in very low birth weight neonates.

Very few studies have examined platelet function in very low birth weight (VLBW) preterm neonates, because of the relatively large volumes of blood required. In this study, platelet function in clinically stable VLBW neonates was examined by whole blood flow cytometry, which requires only 5 microliters of whole blood per assay. The following monoclonal antibodies were used: S12 (P-selectin-specific, reflecting alpha granule secretion), PAC1 (directed against the fibrinogen binding site exposed on the GPIIb-IIIa complex of activated platelets), F26 (directed against a conformational change in fibrinogen bound to the GPIIb-IIIa complex), and 6D1 (directed against the von Willebrand factor binding site on the GPIb-IX-V complex). VLBW neonates, like normal adults, did not have circulating activated platelets, as determined by the lack of binding of S12, PAC1, and F26 in the absence of an added agonist. VLBW neonatal platelets were markedly less reactive than adult platelets to thrombin, ADP/epinephrine, and U46619 (a stable thromboxane A2 analogue), as determined by the extent of increase in the platelet binding of S12, PAC1, and F26, and the extent of decrease in the platelet binding of 6D1. In summary, compared to adults, the platelets of VLBW neonates are markedly hyporeactive to thrombin, ADP/epinephrine and a thromboxane A2 analogue in the physiologic milieu of whole blood, as determined by: 1) the increase in platelet surface P-selectin; 2) the exposure of the fibrinogen binding site on the GPIIb-IIIa complex; 3) fibrinogen binding; and 4) the decrease in platelet surface GPIb. This platelet hyporeactivity may be a factor in the propensity of VLBW neonates to intraventricular hemorrhage. In addition to its previously defined use as a test of platelet hyperreactivity, the present study suggests that whole blood flow cytometry may be useful in the clinical assessment of platelet hyporeactivity.

Effect of time and temperature on inactivation of aminoglycosides by ampicillin at neonatal dosages.

The administration of gentamicin at least 1 hour before administration of ampicillin in neonates has been advocated because of in vitro inactivation of aminoglycosides by beta-lactam antibiotics. This method would cause a delay in ampicillin dosing in the treatment of serious bacterial infections and unnecessarily complicate nursing procedures. We studied the effect of varying concentrations of ampicillin (50, 100, 200, and 400 micrograms/ml) on aminoglycosidic antibiotics in vitro with the use of stock solutions diluted in pooled sera obtained from cord blood and incubated samples at 25 degrees C, 37 degrees C, and 40 degrees C. We found inactivation of aminoglycosides to be dependent on time, temperature, and ampicillin concentration, but the degree of inactivation was small and does not support temporal separation of parenteral administration of ampicillin and aminoglycosides to neonates.

Aggressive respiratory support and unilateral nephrectomy for infants with severe perinatal autosomal recessive polycystic kidney disease.

Newborn infants with severe autosomal recessive polycystic kidney disease often receive minimal intervention because poor respiratory and renal outcomes are anticipated. We describe two patients whose respiratory failure was successfully treated with aggressive intervention. Massive kidneys restricted gastrointestinal capacity and limited feedings. Uninephrectomy allowed adequate enteral feedings and preserved sufficient renal function for homeostasis and growth.

Neonatal platelets are less reactive than adult platelets to physiological agonists in whole blood.

Previous studies have reported that the platelets of healthy term neonates have either diminished or normal reactivity compared to the platelets of adults. To circumvent the methodologic problems of previous studies, we used a whole blood flow cytometric method to study neonatal platelet reactivity to thrombin, a combination of ADP and epinephrine, and U46619 (a stable thromboxane A2 analogue). Inclusion in the assay of the peptide GPRP (an inhibitor of fibrin polymerization) enabled us to study platelet reactivity to human alpha-thrombin in whole blood. Umbilical cord blood and day 1 peripheral blood were collected from 30 healthy term neonates and compared to peripheral blood from 20 normal adults. In whole blood samples without added agonist, there were no significant differences between neonates and adults in the platelet binding of monoclonal antibodies 6D1 (GPIb-specific) or 7E3 (GPIIb-IIIa complex-specific). As determined by S12 (a P-selectin-specific monoclonal antibody), neither neonates nor adults had circulating degranulated platelets. However, in both cord and peripheral whole blood samples, neonatal platelets were significantly less reactive than adult platelets to thrombin, ADP/epinephrine, and U46619, as determined by the extent of increase in the platelet surface expression of P-selectin and the GPIIb-IIIa complex, and the extent of decrease in the platelet surface expression of the GPIb-IX complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Meningitis, ventriculitis, and hydrocephalus: a complication of fetal monitoring.

A case is presented of meningitis, ventriculitis, and hydrocephalus secondary to the use of fetal scalp monitoring. The most commonly reported fetal complication related to the application of the scalp electrode is the development of a scalp abscess; the incidence varies between 0.45 and 4.5%, but several other complications have also been reported and the overall incidence is not well established. Infants in whom a scalp electrode has been used should be carefully examined to detect potential serious complications.

Treatment of apnea of prematurity with aminophylline.

The effectiveness of aminophylline in the treatment of apnea of prematurity was evaluated in 13 premature infants (mean birthweight, 1.13 kg; mean gestational age, 29 weeks). Apnea was recorded by direct observation in combination with impedance monitoring. Rectal suppositories of aminophylline (5 mg) were given at six-hour intervals. The average dose was 4.1 mg/kg. No toxicity or complications were noted. The parents became free of apneic episodes during therapy. The response for each eight-hour interval of treatment over 72 hours when compared to pretreatment was significant (P less than .01; paired t-test), after the first eight hours. Only one patient required mechanical ventilation for apnea. Treatment was continued for 2 to 14 days (mean, 5 days). A recurrence of apnea was noted in nine patients after discontinuing aminophylline. All patients except one survived. No change in Po2, Pco2, pH, mean heart and respiratory rates, and blood pressure was noted. A direct effect on the respiratory center is postulated.

Diagnosis of pneumothorax or pneumomediastinum in the neonate by transillumination.

Transillumination of the neonatal chest is described as an aid in the diagnosis of pneumothorax or pneumomediastinum. Sudden severe tension pneumothorax or pneumomediastinum can be localized for immediate treatment and the success of therapy can be immediately assessed using transillumination.

Endotracheal tube placement in infants determined by suprasternal palpation: a new technique.

In order to decrease complications of improper endotracheal tube positioning, a method of placing the tube by palpation within the suprasternal notch was devised. The method proved to be simple and effective. The accuracy was verified by fluoroscopy and a clinical study comparing this technique with others is reported. No complications of the technique were noted. Once palpation was reliable, the proper position of the tube tip was defined. From measurements taken from routine inspiratory chest radiographs on 142 infants, it was found that a point midway between the medial ends of the clavicle (IMP) was a good position because it approximates the true tracheal midpoint and, therefore, is a good landmark on a chest radiograph. This point allows for movement of the tube tip with head positioning and of the carina with respiration. The tube tip can be placed near the IMP by the suprasternal palpation technique. This method, therefore, is useful in emergency situations or on initial intubations to avoid improper position of the tube tip prior to radiograph verification.