Urinary NT-proBNP levels and echocardiographic parameters for patent ductus arteriosus.

OBJECTIVE: Patent ductus arteriosus (PDA) is common in preterm infants and is associated with significant morbidities. B type natriuretic peptide (BNP) is synthesized in the ventricles secondary to volume overload and excreted as urinary N-terminal pro-brain natriuretic peptide (NT-proBNP). STUDY DESIGN: We report an observational prospective study of 64 preterm infants with birth weight ⩽1000 g. Echocardiographic parameters were obtained from clinical echocardiograms performed in the first week of life. Urinary NT-proBNP/creatinine ratios (pg mg-1) were measured on the same day of the echocardiograms. RESULTS: Infants with medium to large PDA (n=39) had significantly higher NT-proBNP/creatinine levels compared with infants with small PDA (n=10) (median (IQ range): 2333 (792-6166) vs 714 (271-1632) pg mg-1, P=0.01) and compared with infants with no PDA (n=15) (2333 (792-6166) vs 390 (134-1085) pg mg-1, P=0.0003). Urinary NT-proBNP/creatinine ratios were significantly lower post treatment if PDA closed (n=17), P=0.001 or if PDA became smaller after treatment (n=9), P=0.004. Urinary NT-proBNP/creatinine levels correlated with ductal diameter (P⩽0.0001), but not with LA/Ao ratio (P=0.69) or blood flow velocity through the ductus (P=0.06). CONCLUSION: Our findings indicate that there is a positive correlation between ductal diameter and urinary NT-proBNP in preterm infants.

Practice parameter: neuroimaging of the neonate: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

OBJECTIVE: The authors reviewed available evidence on neonatal neuroimaging strategies for evaluating both very low birth weight preterm infants and encephalopathic term neonates. IMAGING FOR THE PRETERM NEONATE: Routine screening cranial ultrasonography (US) should be performed on all infants of <30 weeks' gestation once between 7 and 14 days of age and should be optimally repeated between 36 and 40 weeks' postmenstrual age. This strategy detects lesions such as intraventricular hemorrhage, which influences clinical care, and those such as periventricular leukomalacia and low-pressure ventriculomegaly, which provide information about long-term neurodevelopmental outcome. There is insufficient evidence for routine MRI of all very low birth weight preterm infants with abnormal results of cranial US. IMAGING FOR THE TERM INFANT: Noncontrast CT should be performed to detect hemorrhagic lesions in the encephalopathic term infant with a history of birth trauma, low hematocrit, or coagulopathy. If CT findings are inconclusive, MRI should be performed between days 2 and 8 to assess the location and extent of injury. The pattern of injury identified with conventional MRI may provide diagnostic and prognostic information for term infants with evidence of encephalopathy. In particular, basal ganglia and thalamic lesions detected by conventional MRI are associated with poor neurodevelopmental outcome. Diffusion-weighted imaging may allow earlier detection of these cerebral injuries. RECOMMENDATIONS: US plays an established role in the management of preterm neonates of <30 weeks' gestation. US also provides valuable prognostic information when the infant reaches 40 weeks' postmenstrual age. For encephalopathic term infants, early CT should be used to exclude hemorrhage; MRI should be performed later in the first postnatal week to establish the pattern of injury and predict neurologic outcome.

The fontogram: a noninvasive intracranial pressure monitor.

The applanation transducer was used to measure intracranial pressure (ICP) through the intact fontanel. The method is painless, rapid, and accurate. The pressures recorded with this fontogram were correlated with direct measurements of ICP. The correlation coefficient of the 21 paired determinations was .98--a very good correlation. Fontanel pressure was determined in 35 normal newborn infants. The mean pressure was 7.37 mm Hg with an SD of +/- 1.45 (range, 3.5 to 9.5 mm Hg). Three clinical cases are presented to illustrate the usefulness of this apparatus in the detection of increased ICP and in monitoring the effectiveness of treatment.

Indwelling umbilical arterial catheter: a preferred sampling site for blood culture.

Indwelling umbilical arterial catheter was evaluated prospectively as an alternative site for blood culture sampling. In 282 infants, 318 paired blood cultures were obtained from the peripheral vein and from the indwelling umbilical arterial line. Duration of umbilical catheter placement ranged from 0.5 to 196 hours; in 17% of the infants, catheters were in place for between 24 and 196 hours. In 13 blood culture pairs the same pathogens were found and had been obtained from the peripheral vein and the umbilical arterial line. Two pairs were positive for discrepant organisms. A total of 11 pairs were positive in one site only, with five positive from peripheral vein only and the other six from the umbilical arterial catheter. However, most of these single-site positive blood cultures were apparently true positives based on supporting laboratory data for infection. Contamination rates were 1.3% and 0.9% for peripheral vein and umbilical arterial catheter blood cultures, respectively. Thus, in sick neonates, the indwelling umbilical arterial line was an alternative and perhaps a preferred site for blood culture sampling.

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.

Blood pressure increases, birth weight-dependent stability boundary, and intraventricular hemorrhage.

The blood pressure (BP) and transcutaneous PO2 (TcPO2) changes associated with intensive care procedures were evaluated to determine whether responses differ between babies with and without periventricular-intraventricular hemorrhage (PV-IVH). Fifty-three inborn babies less than or equal to 1500 g were studied using a microcomputer-based monitoring system. With almost any procedure including a seemingly benign one such as a diaper change, peak systolic BP increased and TcPO2 decreased. However, responses to interventions did not differ between babies with PV-IVH and those without PV-IVH. Neither did these responses differ between those with birth weight less than or equal to 1000 g and greater than 1000 g. When each baby's record was scanned for the highest peak systolic BP before diagnosis of PV-IVH or within 48 hours in those with no PV-IVH and their BP points plotted against birth weight, a stable region was evident wherein PV-IVH occurred at a lower incidence (13%). When peak systolic BP was beyond this stable region, the incidence of PV-IVH was significantly higher, 70% (P less than .0001). The stability boundary for the maximum systolic BP is birth weight-dependent; the limit for the highest tolerable peak systolic BP is lower for the low-birth-weight infant. In over 70% of instances the highest peak systolic BP was associated with motor activities either induced by nursery procedures or spontaneous. We speculate that decreasing the frequency of intensive care interventions may decrease episodic BP increases to levels beyond the birth weight-dependent stability boundary where PV-IVH is likely to occur.

Central and autonomic nervous systems' signs associated with in utero exposure to cocaine/opiates.

In summary, we found that the prevalence of CNS/ANS signs was significantly higher in the infants exposed to cocaine and/or opiates than in nonexposed infants. However, the prevalence of a large number of these signs was less than 5%. The prevalence rates of these signs are lower when exposure involved cocaine only; thus, their assessment has limited clinical utility.

Early and late intraventricular hemorrhage: the role of obstetric factors.

OBJECTIVE: To evaluate the influence of active phase labor and other obstetric factors on the development of periventricular-intraventricular hemorrhage in the neonate. METHODS: A total of 230 infants were studied. Antenatal enrollment was carried out when estimated fetal weight was 1750 g or less. Serial head ultrasound scans were performed to screen for periventricular-intraventricular hemorrhage, with the initial scan performed within minutes of birth. Scan findings and obstetric and neonatal variables collected prospectively at scheduled intervals were analyzed to determine the significant factors that predispose to intraventricular hemorrhage. RESULTS: In 47 infants (20%), intraventricular hemorrhage was detected within 1 hour of birth (early) and in another 49 (21%) at a later age (late). The overall incidence of hemorrhage was similar between vaginal and cesarean deliveries (41 and 44%, respectively). Early hemorrhage was more frequent in vaginal (28%) than cesarean deliveries (11%), whereas late hemorrhage was more frequent in cesarean deliveries. When the role of delivery mode and labor was analyzed by stepwise logistic regression, the odds ratios for development of early intraventricular hemorrhage increased in the following order: cesarean delivery with no labor, cesarean delivery with latent phase labor, vaginal delivery with forceps use, cesarean delivery with active phase labor, and vaginal delivery without forceps use. For late hemorrhage, the odds ratios increased in the following order: vaginal delivery with forceps, vaginal delivery without forceps, cesarean delivery with no labor, cesarean delivery with latent phase labor, and cesarean delivery with active phase labor. CONCLUSIONS: Active phase labor may predispose to early periventricular-intraventricular hemorrhage, but its influence may be attenuated by use of forceps or by abdominal delivery. The protective effect of forceps remains for late periventricular-intraventricular hemorrhage, but abdominal delivery does not seem to protect against late hemorrhage.

Central and autonomic system signs with in utero drug exposure.

AIMS: To determine risk for central nervous system/autonomic nervous system (CNS/ANS) signs following in utero cocaine and opiate exposure. METHODS: A multisite study was designed to determine outcomes of in utero cocaine and opiate exposure. A total of 11 811 maternal/infant dyads were enrolled. Drug exposed (EXP) infants were identified by maternal self report of cocaine or opiate use or by meconium testing. Of 1185 EXP, meconium analysis confirmed exposure in 717 to cocaine (CO) only, 100 to opiates (OP), and 92 to opiates plus cocaine (OP+CO); 276 had insufficient or no meconium to confirm maternal self report. Negative exposure history was confirmed in 7442 by meconium analysis and unconfirmed in 3184. Examiners masked to exposure status, assessed each enrolled infant. Using generalised estimating equations, adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated for manifesting a constellation of CNS/ANS outcomes and for each sign associated with cocaine and opiate exposure. RESULTS: Prevalence of CNS/ANS signs was low in CO, and highest in OP+CO. Signs were significantly related to one another. After controlling for confounders, CO was associated with increased risk of manifesting a constellation of CNS/ANS outcomes, OR (95% CI): 1.7 (1.2 to 2.2), independent of OP effect, OR (95% CI): 2.8 (2.1 to 3.7). OP+CO had additive effects, OR (95% CI): 4.8 (2.9 to 7.9). Smoking also increased the risk for the constellation of CNS/ANS signs, OR (95% CI) of 1.3 (1.04 to 1.55) and 1.4 (1.2 to 1.6), respectively, for use of less than half a pack per day and half a pack per day or more. CONCLUSION: Cocaine or opiate exposure increases the risk for manifesting a constellation of CNS/ANS outcomes.

Prenatal drug exposure and maternal and infant feeding behaviour.

OBJECTIVE: To evaluate feeding difficulties and maternal behaviour during a feeding session with 1 month old infants prenatally exposed to cocaine and/or opiates. METHODS: The study is part of the maternal lifestyle study, which recruited 11 811 subjects at four urban hospitals, then followed 1388 from 1 to 36 months of age. Exposure to cocaine and opiates was determined by maternal interview and meconium assay. At the 1 month clinic visit, biological mothers were videotaped while bottle feeding their infants. This sample included 364 exposed to cocaine, 45 exposed to opiates, 31 exposed to both drugs, and 588 matched comparison infants. Mothers were mostly black, high school educated, and on public assistance. Videotapes were coded without knowledge of exposure status for frequency, duration and quality of infant sucking, arousal, feeding problems, and maternal feeding activity and interaction. RESULTS: No cocaine effects were found on infant feeding measures, but cocaine-using mothers were less flexible (6.29 v 6.50), less engaged (5.77 v 6.22), and had shorter feeding sessions (638 v 683 seconds). Opiate exposed infants showed prolonged sucking bursts (29 v 20 seconds), fewer pauses (1.6 v 2.2 per minute), more feeding problems (0.55 v 0.38), and increased arousal (2.59 v 2.39). Their mothers showed increased activity (30 v 22), independent of their infants' feeding problems. CONCLUSIONS: Previous concerns about feeding behaviour in cocaine exposed infants may reflect the quality of the feeding interaction rather than infant feeding problems related to prenatal exposure. However, opiate exposed infants and their mothers both contributed to increased arousal and heightened feeding behaviour.

Eicosanoid levels in CSF of premature infants with posthemorrhagic hydrocephalus.

The cerebrospinal fluid (CSF) of 11 premature infants suffering from posthemorrhagic hydrocephalus was examined by radioimmunoassay for prostaglandin (PG) E2, PGF2 alpha, PGD2, 6-keto PGF1 alpha, thromboxane B2 (TxB2) and peptidoleukotrienes (LTC4/LTD4). The LTs were detected in the CSF of more of these patients (70%) than any of the other eicosanoids, and usually in the highest concentration. Among the 11 posthemorrhagic patients CSF eicosanoid levels were highest when determined soon after injury. Moreover, the variety of eicosanoids present, as well as concentrations, in these infants decreased with time. The types of eicosanoids most evident in the CSF of patients who required shunting were TxB2 and LTs, being present together in 5 of 6 (83%) of these infants. In contrast, 1 of 5 (20%) of the patients who did not require this neurosurgical intervention contained both TxB2 and LTs, the remaining having only one or neither eicosanoid. The highest average concentration for each eicosanoid studied was (pg/ml): PGE2, 628; PGF2 alpha, 985; PGD2, 1410; 6-keto PGF1 alpha, 544; TxB2, 486 and LTs, 1229. This study is the first to demonstrate that the CSF of preterm infants may contain a wide variety of eicosanoids and indicates that these lipids are a manifestation of neurological assault.

Partial plasma exchange transfusion improves cerebral hemodynamics in symptomatic neonatal polycythemia.

Cerebral arterial pulsatile flow changes and the effect of partial plasma exchange transfusion on these pulsatile flow patterns were studied in neonatal polycythemia/hyperviscosity syndrome by transcutaneous Doppler technique. Twenty-two infants with cord blood hematocrit greater than 58% (greater than 2 SD above the mean) were studied from a total of 2,400 infants who were screened for cord hematocrit over a 6-month period. Each of 22 infants had the following initial studies: radial artery hematocrit, viscosity, intracranial pressure measurement, and anterior cerebral arterial Doppler study to determine pulsatility index, mean systolic, mean end diastolic, and mean flow velocities, and area underneath the curve of the velocity tracings/min. Twelve of 22 infants had radial artery hematocrit less than 63%, were normoviscous (less than 13.5 cps, 11.25 sec-1) and were designated as control infants. Ten (study infants) were polycythemic (hematocrit greater than or equal to 63%) and hyperviscous (greater than or equal to 13.5 cps, 11.25 sec-1). All study patients were treated by partial plasma exchange transfusion. Initial studies were repeated after exchange transfusion. Control infants were not treated. Prior to exchange procedure, the polycythemic hyperviscous infants had significantly higher hematocrit, viscosity, and pulsatility index; the other Doppler measurements and heart rate were lower than those of control babies. The exchange procedure resulted in significantly decreased hematocrit, viscosity, and pulsatility index and increase in the other Doppler measurements, heart rate, and intracranial pressure. All postexchange measurements of study infants were not statistically different from the control infants. These data suggest that neonatal polycythemia/hyperviscosity syndrome may be associated with abnormal cerebral hemodynamics that could improve with partial plasma exchange transfusion.

Cerebral blood flow velocity changes after bovine natural surfactant instillation.

OBJECTIVE: To determine the effects of bovine natural surfactant (beractant) instillation on cerebral hemodynamics in preterm infants with respiratory distress syndrome (RDS). STUDY DESIGN: Preterm infants who required surfactant for RDS were enrolled. Cerebral blood flow velocity (CBFV) waveforms from the pericallosal artery were analyzed by pulsed Doppler ultrasonography with the anterior fontanel serving as an acoustic window. CBFV was measured before and at 5, 10, 20, and 30 minutes after the first dose of a bolus instillation of surfactant in four aliquots. Simultaneously with CBFV measurements, mean blood pressure (MBP), heart rate, and ventilator settings were recorded. pH, PACO2, and PAO2 before and at 30 minutes after surfactant administration were also determined. RESULTS: The 30 enrolled preterm infants had a mean birth weight of 973 gm (513 to 1996 gm) and a mean gestational age of 27 weeks (23 to 33 weeks). Mean postnatal age at surfactant administration was 4.7 +/- 2.7 hours. There were no significant changes in pH and PACO2 before and at 30 minutes after surfactant (before surfactant: mean pH of 7.29 +/- 0.07 and mean PACO2 of 44.4 +/- 7.1 torr; after surfactant: mean pH of 7.31 +/- 0.07 and mean PACO2 of 42.7 +/- 8.3 torr). PAO2 increased significantly from a pre-surfactant mean of 83 torr to 130 torr at 30 minutes after surfactant (p < 0.05), with no significant changes in mean airway pressure. There were no significant changes in MBP, heart rate, mean CBFV, peak systolic flow velocity, and diastolic flow velocity before and after surfactant instillation regardless of gestational age. Individual changes in mean CBFV were related to MBP changes (p < 0.001, linear mixed models with random effects). CONCLUSION: In low birth weight infants with RDS, bovine surfactant instillation is not associated with a significant alteration in cerebral hemodynamics. However, the direct relationship between CBFV and MBP is consistent with the reported pressure-passive cerebral circulation in sick preterm infants.

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.

Pancuronium attenuates associated hemodynamic and transcutaneous oxygen tension changes during nursery procedures.

Intermittent increases in blood pressure (BP) associated with motor activity have been implicated in the pathogenesis of intraventricular hemorrhage in premature infants. Inhibition of motor activity by pancuronium administration has also been shown to stabilize cerebral blood flow velocity (CBFV) and BP patterns. The purpose of this study was to determine whether administration of pancuronium to ill premature infants would attenuate changes in BP and transcutaneous oxygen tension (TcPO2) and the variability of CBFV pattern associated with common nursery procedures. Fourteen premature infants in the study were given a single dose of pancuronium bromide at a dose of 0.1 mg/kg intravenously. BP and TcPO2 changes were monitored during nursery procedures, that is, during radial artery blood gas sampling and a head ultrasonographic/Doppler procedure, before and during pancuronium therapy. During arterial blood gas sampling, mean percent increase in BP was significantly greater (32% +/- 21%) before pancuronium administration compared with 21% +/- 13% during pancuronium use (p < 0.05). Mean percent changes in TcPO2 were -30% +/- 21% and 5.8% +/- 7.2% before and during pancuronium use, respectively (p < 0.05). Similar significant changes in BP and TcPO2 were observed with a head ultrasonographic/Doppler procedure. Coefficients of variation of systolic and mean CBFV also decreased significantly during pancuronium therapy. We observed short-term benefits with pancuronium use on vascular dynamics and oxygenation during nursery procedures. Further studies are needed to evaluate the use of pancuronium in preterm babies supported by mechanical ventilation during the first few days of life for possible prevention of intraventricular hemorrhage, the pathophysiologic mechanism of which may be related to hemodynamic and biochemical derangement.

Immunoassay and GC-MS procedures for the analysis of drugs of abuse in meconium.

The analysis of meconium specimens for metabolites of substances of abuse is a relatively accurate method for the detection of fetal exposure to drugs. Most of the methods reported in the literature before the early 1990s relied on radioimmunoassays. The purpose of this study was to develop and validate methods for meconium sample preparation for the screening and gas chromatography-mass spectrometry (GC-MS) confirmation of meconium extracts for cannabinoids, cocaine, opiates, amphetamines, and phencyclidine. EMIT and TDx immunoassays were evaluated as screening methods. The sample preparation method developed for screening included extraction and purification prior to analysis. Cutoff levels were administratively set at 20 ng/g for 11-nor-delta9-THC-9-COOH (THCCOOH) and phencyclidine and at 200 ng/g for benzoylecgonine, morphine, and amphetamines, although lower levels could be detected in meconium using the EMIT-ETS system. Ninety-five meconium specimens were subjected to the screening procedure with GC-MS confirmation of presumptive positives. In addition, 30 (40 for cocaine) meconium specimens were subjected to GC-MS analysis for all analytes regardless of the screening results to determine the false-negative rate, if any, of the immunoassay. Although there were no false negatives detected, the GC-MS confirmation rate for the immunoassay-positive specimens was generally low, ranging from 0% for amphetamines to 75% for opiates. The lowest rate of confirmed positives was found with the cannabinoids, suggesting that tetrahydrocannabinol (THC) metabolites other than free 11-nor-9-carboxy-delta9-THC may be major contributors to the immunoassay response in meconium.

Microcomputer evaluation of cerebral blood flow velocity studies in the neonate.

A semi-automated system for evaluation of Doppler cerebral blood flow studies obtained from newborn infants is described. A low cost digitizer is used to convert the graphic data from the flow tracing to digital data. A small business computer is used to analyze the data and produce a chartable report. The reliability of the digitizer is also evaluated.