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.

Sometimes in the course of care in a neonatal intensive care unit, there may be a rush to intervene in cases where limited intervention is actually the correct course. One such example is that of neonatal adrenal hemorrhage. We present the case of a male term neonate with shock, metabolic acidosis, distended abdomen, and falling hematocrit. His prenatal and delivery histories were uneventful except for a nuchal cord. Apgar scores were 9 and 9. Because of his dramatic presentation, certain members of the medical team suggested immediate surgical intervention. However, a calm and careful evaluation revealed the true diagnosis and course of action. Ultrasound of the abdomen showed a mass between the liver and kidney, but the origin was difficult to identify. A Computed tomography scan supported the diagnosis of right adrenal hemorrhage. His serum cortisol level was normal. The patient was managed conservatively and discharged home after a 1-week stay in the hospital. Subsequent abdominal ultrasound showed resolving adrenal hemorrhage with minimal calcification. A review of the pertinent literature is presented. Physicians should remember adrenal hemorrhage when evaluating a newborn infant with shock, acidosis, abdominal distention, and falling hematocrit and that conservative management is usually indicated.

Objective. The diagnosis of persistent pulmonary hypertension (PPHN) can often be difficult to make, especially in a clinical setting in which pediatric echocardiography is not readily available. A noninvasive test that could differentiate PPHN from other cardiorespiratory disease would be very useful in the early management of the disease, because it would allow rapid identification of those infants at greatest risk of requiring the services of a level 3 nursery. Brain-type natriuretic peptide (BNP) is an endogenous peptide hormone secreted by the cardiac ventricles in response to increased wall stress and related ventricular filling pressures. The purpose of this study was to determine if BNP levels are elevated in newborns with PPHN and therefore may be used as a marker for differentiating PPHN from other forms of respiratory disease during the early newborn period.Method. We used a prospective cohort design with 3 groups. One group was diagnosed with PPHN by clinical and echocardiographic criteria (PPHN group: n = 15). The second group had been diagnosed with respiratory disease; however, PPHN had been ruled out by having no evidence of elevated pulmonary pressure by echocardiography (RD group: n = 17). The third group had no respiratory disease and was breathing room air (RA group: n = 15). BNP levels were measured with a point-of-care fluorescence immunoassay at various time intervals between birth and 150 hours of life.Results. There were no differences between groups for birth weight, gestational age, gender, race, Apgar scores at 1 minute, or age at time of initial blood sampling. Initial BNP levels (pg/mL) were elevated in the PPHN group relative to both the RA and RD groups (median [25%, 75%]: PPHN group = 1610 [1128, 1745]; RD group = 132 [76, 327]; RA group = 248 [127, 395]). There was no difference in the initial BNP level between the RA and RD groups. BNP levels remained elevated in the PPHN group over both groups for the first 4 days of life. BNP levels correlated with the gradient of the tricuspid regurgitation jet and with the ratio of tricuspid regurgitation jet gradient to mean blood pressure. BNP levels were not affected by administration of dopamine or dobutamine. BNP weakly correlated with the oxygenation index but not with the alveolar-arterial oxygenation gradient.Conclusions. Our findings indicate that BNP levels are elevated in infants with PPHN but not in infants with other forms of respiratory distress not associated with PPHN. Elevated BNP levels in term or near-term infants with respiratory distress should increase the suspicion of PPHN. Serial determination may also be helpful in monitoring the clinical course of such infants.

Background: Indomethacin (INDO) is used for of intraventricular hemorrhage prophylaxis and closure of ductus arteriosus in premature infants. Cellular and molecular actions of INDO on brain cells remain unclear. We examined INDO effects on cellular parameters (growth, proliferation, respiratory burst). Methods: Assays for MTT proliferation, proteasome function (chymotrypsin activity), viability testing, and respiratory burst (flow cytometric analysis) were performed on cell lines (N2a neuroblastoma and N9 microglia) and primary neuronal and astrocyte cultures treated with INDO at 0, 100, 250, 500, 750 and 1000uM. Results: Percent viability of N2a cells was significantly higher at 250uM and lowest at 1mM. Percent viability of N9 microglia significantly decreased from baseline (91%) to 71% at 250uM (p<0.0001), precipitously decreasing to 10% at 500uM. Proliferation assays of primary neonatal cells indicate 250–500uM INDO treatment increased astrocyte proliferation while attenuating neuronal proliferation in a dose-dependent manner. Proteasomes play an important role in intracellular degradation of aging and oxidized proteins and in activating signaling proteins like NF-kB. Normal proteasomal function of N2a neuronal cells or N9 microglia was maintained up to 250uM INDO treatment. N9 cells exhibited marked loss of activity at 500uM and 1000uM while N2a maintained activity up to 500uM. Respiratory burst assays on N9 microglial cells showed INDO pretreatment and cotreatment with LPS/IFN-gamma caused a 10% reduction in reactive oxygen species (ROS)-release by N9 cells compared to N9 with LPS/IFN-gamma treatment. Estrogen (1nM)-pretreated N9 cells decreased ROS release by 30%. Conclusion: Cell function and integrity assays indicate a narrow dosage window (250–500uM) where INDO can preserve cellular growth, viability, respiratory burst, and proteasomal function. That estrogen is more efficient than INDO in decreasing ROS production may explain suggested gender differences in efficacy. Results indicate differential susceptibilities of CNS cells, with microglia being most sensitive while neurons and astrocytes tolerate INDO treatment better.

Purpose Cervical auscultation (CA) has been used to describe the stability of swallow-associated sounds of infant feeding. Initial discrete sounds (IDS), signals that predictably occur as the pressure in the pharynx increases with swallow, of low-risk preterm infants became more uniform with increasing postmenstrual age (PMA). This developmental progression is not present in infants with bronchopulmonary dysplasia. The purpose of this study is to identify the IDS signal of adult swallows and compare the stability of IDS signals of infants to that of adults. Additionally, we compared two acoustic detection devices for CA. Methods We performed CA with a microphone and an accelerometer simultaneously fixed to the neck of healthy adults (n = 10). Each participant consumed a liquid, a pureed food (applesauce) and a solid (cookie). The variance index (VI), a measure of the stability of the IDS signal, was used to compare the IDS of adults to that of a group of suckle-feeding low-risk preterm infants (n = 12). Low risk was defined as no ongoing oxygen requirement, no BPD, no IVH ≥ Grade III, and no sepsis. Results The microphone and accelerometer collected signals of similar duration. The signals collected by the microphone were vibratory and artificially amplified/attenuated according to the frequency response curve of the microphone. The signals collected by the accelerometer included additional inaudible signals, such as motion and pressure changes. The mean VI of adults swallowing liquid (29.9 ± 3.1 [SEM]), did not differ from preterm infants > 36 weeks PMA (37.8 ± 2.3) but was lower than the VI of infants < 36 weeks PMA (48.4 ± 1.9; p < .05). Conclusion This is the first real-time comparison of microphones and accelerometers for CA. A microphone may be adequate for simple auditioning of cervical sounds. For more complex applications, an accelerometer should be considered. The stability of IDS signals of low-risk preterm infants approaches that of normal adults as the infants age, suggesting a link between the stability of IDS during early infant feeding and long-term neurologic development.

The pharmacology of most addictive substances is being studied extensively, not just for their acute effects but also the mechanisms that lead to drug seeking and addiction. The understanding of how these drugs alter their effects at the molecular level with continuing use gives promise toward investigation of novel substances that may be used for treatment. Genetic predisposition and gender differences are also some of the areas where more research is needed. Women who are addicted are likely to continue drug use during pregnancy, which can have an impact on the next generation. Prevention measures at the population level are as important. Programs need to address risks, social issues, and environmental factors that promote drug use and addiction.

2002;58;1726 Neurology L. R. Ment, H. S. Bada, P. Barnes, et al. Society Neurology and the Practice Committee of the Child Neurology Quality Standards Subcommittee of the American Academy of Practice parameter: Neuroimaging of the neonate : Report of the April 24, 2013 This information is current as of http://www.neurology.org/content/58/12/1726.full.html on the World Wide Web at: The online version of this article, along with updated information and services, is located

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, Haemophilusb 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 ∼48 hours after routine immunization.

One hundred fifty-five inborn infants with a birth weight <- 1,500 gm were prospectively evaluated for germinal layer/intraventricular hemorrhage. Maternal characteristics, obstetric factors, and neonatal condition in the immediate newborn period were analyzed as possible risk factors for germinal layer/intraventricular hemorrhage. Early germinal layer/intraventricular hemorrhage or hemorrhages identified during the first 24 hours of life were observed in 85 (55%) of these infants. Another 37 (24%) had germinal layer/intraventricular hemorrhage after 24 hours of age (late germinal layer/intraventricular hemorrhage). None of the maternal and obstetric variables, including labor, mode of delivery, and presentation, appeared to increase the risk of germinal layer/intraventricular hemorrhage. The immediate neonatal condition, birth weight, gestational age, and intrauterine growth, all influenced the occurrence of germinal layer/intraventricular hemorrhage, especially early germinal layer/intraventricular hemorrhage. We suggest that future studies to investigate the role of maternal or obstetric factors in the pathogenesis of germinal layer/intraventricular hemorrhage should discriminate early from late germinal layer/intraventricular hemorrhage. Obstetric factors are more likely to influence the early onset of germinal layer/intraventricular hemorrhage; their effect, if any, becomes less discernible later.

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.

We examined the clinical significance of noninvasive intracranial pressure measurements and pulsatility indices in 74 infants with confirmed IC-IVh. The intracranial pressure measurements were obtained using the applanation principle, and the pulsatility indices were calculated from the Doppler flow velocity tracings of the anterior cerebral artery. Fifty-three infants (71.6%) who died had a significantly lower birth weight and gestational age than those who survived. Survival rate decreased significantly with increased intracranial pressure (P less than 0.0002) and increased pulsatility indices (P less than 0.0001). We found no significant relationship between outcome and the size of IC-IVH demonstrated by CT scan. Birth weight, intracranial pressure measurements, and cerebral arterial pulsatile flow changes appear to be major prognostic indicators in neonatal IC-IVH.

Simultaneous blood and saliva samples were drawn for determination of caffeine and theophylline concentrations in 17 infants receiving caffeine or theophylline therapy for apnea of prematurity. The relationship between serum and saliva concentrations in each drug treatment group was explored using (1) regression analysis and (2) serum:saliva ratio. Significant correlations were observed between serum and salivary concentrations. Salivary concentrations approximated 76 to 80% of the serum concentrations based on the derived serum:saliva ratios. When salivary concentrations were less than 8 microgram/ml, the serum concentrations did not exceed therapeutic range and no clinical toxicity was noted. Monitoring of salivary drug concentrations as an alternative to serum drug concentrations may be useful in preterm infants on methylxanthine therapy. When salivary concentrations exceed 8 microgram/ml, serum concentrations should be determined.