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Jitteriness and tremors in the newborn period typically precipitate an extensive, invasive, and expensive search for the etiology. Vitamin D deficiency has not been historically included in the differential of tremors. We report a shivering, jittery newborn who was subjected to a battery of testing, with the only biochemical abnormality being vitamin D deficiency. A second case had chin tremors and vitamin D deficiency. Review of our patients suggests that shudders, shivers, jitteriness, or tremors may be the earliest sign of vitamin D deficiency in the newborn. Neonates who present with these signs should be investigated for vitamin D deficiency., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2017 by the American Academy of Pediatrics.)

Neonatal severe primary hyperparathyroidism presents in the first days of life with severe life-threatening hypercalcemia. It is associated with an inactivating homozygous mutation of the calcium sensing receptor gene. Total parathyroidectomy is the treatment of choice, so the surgeon must identify all the parathyroid tissue, including supernumerary and ectopic glands. We present the case of an infant who underwent total parathyroidectomy at age 4 months in which intraoperative parathyroid hormone monitoring provided immediate confirmation of surgical cure., (Copyright © 2014 by the American Academy of Pediatrics.)

Objective: The goal was to describe the temporal pattern of neonatal plasma glucose levels and associations with maternal glucose levels, cord serum C-peptide levels, and neonatal size and adiposity., Methods: A total of 17,094 mothers and infants were included in the Hyperglycemia and Adverse Pregnancy Outcome Study (15 centers in 9 countries). Mothers underwent a 75-g, 2-hour, oral glucose tolerance test (OGTT) at 24 to 32 weeks of gestation. Cord blood and neonatal blood samples were collected. Biochemical neonatal hypoglycemia was defined as glucose levels of <10th percentile (2.2 mmol/L). Clinically identified hypoglycemia was ascertained through medical record review and associations were assessed., Results: Plasma glucose concentrations were stable during the first 5 hours after birth. Maternal glucose levels were weakly positively associated with biochemical neonatal hypoglycemia (odds ratios: 1.07-1.14 for 1-SD higher OGTT glucose levels). Frequency of neonatal hypoglycemia was higher with higher cord C-peptide levels (odds ratio: 11.6 for highest versus lowest C-peptide category). Larger and/or fatter infants were more likely to have hypoglycemia (P < .001), and infants with hypoglycemia tended to have a higher frequency of cord C-peptide levels of >90th percentile., Conclusions: Mean neonatal plasma glucose concentrations varied little in the first 5 hours after birth, which suggests normal postnatal adjustment. Biochemical and clinical hypoglycemia were weakly related to maternal OGTT glucose measurements but were strongly associated with elevated cord serum C-peptide levels. Larger and/or fatter infants were more likely to develop hypoglycemia and hyperinsulinemia. These relationships suggest physiologic relationships between maternal glycemia and fetal insulin production.

Background: A complete blood count (CBC) with white blood cell differential is commonly ordered to evaluate newborns at risk for sepsis., Objectives: To quantify how well components of the CBC predict sepsis in the first 72 hours after birth., Methods: For this retrospective cross-sectional study we identified 67 623 term and late-preterm (≥ 34 weeks gestation) newborns from 12 northern California Kaiser hospitals and 1 Boston, Massachusetts hospital who had a CBC and blood culture within 1 hour of each other at <72 hours of age. We compared CBC results among newborns whose blood cultures were and were not positive and quantified discrimination by using receiver operating characteristic curves and likelihood ratios., Results: Blood cultures of 245 infants (3.6 of 1000 tested newborns) were positive. Mean white blood cell (WBC) counts and mean absolute neutrophil counts (ANCs) were lower, and mean proportions of immature neutrophils were higher in newborns with infection; platelet counts did not differ. Discrimination improved with age in the first few hours, especially for WBC counts and ANCs (eg, the area under the receiver operating characteristic curve for WBC counts was 0.52 at <1 hour and 0.87 at ≥ 4 hours). Both WBC counts and ANCs were most informative when very low (eg, the likelihood ratio for ANC < 1000 was 115 at ≥ 4 hours). No test was very sensitive; the lowest likelihood ratio (for WBC count ≥ 20 000 at ≥ 4 hours) was 0.16., Conclusion: Optimal interpretation of the CBC requires using interval likelihood ratios for the newborn's age in hours.

Background: The advent of tandem mass spectrometry has made it possible to test newborns for multiple conditions efficiently. It is not known how state newborn screening programs have changed screening practices in response to this technology and how it affects the number of false-positive test results., Methods: We obtained data from the National Newborn Screening and Genetics Resource Center regarding the screening practices for each of the 50 states, to determine the number of mandated disorders added to state newborn screening panels between 1995 and 2005. Combining these data with reported specificities from the literature and the number of births in each state, we estimated the number of infants who would have received false-positive results through screening with tandem mass spectrometry in 2005., Results: The average state mandated screening for 5 disorders in 1995 (range: 0-8 disorders). Wyoming was the only state that decreased its panel size over the next decade. Kansas and Texas were the only states that did not add disorders to their panels between 1995 and 2005; the average state added 19. Iowa, Minnesota, Mississippi, South Dakota, and Tennessee each added > or = 40 disorders. Assuming that an individual test for a disorder had a specificity of 99.995%, we estimated that approximately 2575 infants would have received false-positive results through screening with tandem mass spectrometry in 2005. If specificity was assumed to be 99.9%, then the number increased to > 51000., Conclusions: State newborn screening programs have expanded dramatically in the past decade. Because the benefit of such testing may be unclear in some cases and because the number of infants who may receive false-positive results and may be labeled falsely as having disease is potentially sizeable, a more cautious approach is needed.

Objectives: We sought to determine the long-term clinical and biochemical outcome of newborns with mitochondrial cytopathies (MCs) and to identify possible prognostic factors that may modify the course of these diseases., Material and Methods: Fifty-seven newborns with MCs were identified in a retrospective review (1983-2002). We defined 2 different outcome categories: clinical (neurologic, hepatic, myopathic, and multiorganic) and biochemical (lactate level normalization or initially normal remaining unchanged, decreased but not normalized, and persistently high). We used 2 different statistical approaches: (1) survival studies depending on the initial symptoms and lactate and enzymatic deficiencies using the Kaplan-Meier method; and (2) the same variables compared with different survival age groups and clinical and biochemical outcome categories using the chi2 test., Results: Thirty-three patients died (57.8%), 12 remain alive (21%), and 12 were lost in the follow-up; 6 of them are currently older than 4 years. Most of the patients manifested multiorganic disease (64.8%) and high lactate level (77.1%) over time. Children surviving to 2.5 to 3 years of age were more likely to survive for a long period of time. Initial neurologic and hepatic presentation increased the risk to develop neurologic disease and severe persistent hyperlactacidemia, respectively. Initial severe hyperlactacidemia and combined enzyme deficiencies were significant risk factors for higher mortality and multiorganic disorders. Two patients with exclusively myopathic outcome are alive and cognitively normal at 12 years of life., Conclusions: Children with neonatal-onset MCs have very high mortality and poor prospects. However, some with life-threatening presentations may gradually improve, giving rise to less severe diseases. Those with exclusively myopathic symptoms have a better prognosis.

Objective: Although common in preterm infants, transient hypothyroxinemia (TH) has not been investigated extensively in ill term infants. The objectives of this study were to investigate serum thyroxine (T4) and thyroid-stimulating hormone (TSH) in sick term infants and to determine whether there is any association between measures of thyroid function and short-term outcome in term infants who receive mechanical ventilation., Methods: The investigation consisted of both a prospective observational study and a retrospective cohort study. In the prospective study, T4 and TSH were measured after birth in a group of sick term infants (n = 38) and compared with a group of well term infants (n = 18). Infants in the sick group received mechanical ventilation or continuous positive airway pressure and/or had neonatal seizures. Illness severity was quantified using the Score for Neonatal Acute Physiology. The retrospective cohort study included term infants who required mechanical ventilation and were born over a 5-year period (n = 347). Routine T4 screening was collected on the fifth day of life. TH was diagnosed in infants with a T4 <10%, with a TSH <25 microIU/mL. Clinical outcomes in infants with TH were compared with infants without TH., Results: In the prospective study, infants in the sick group had lower T4 on the fifth day of life as compared with infants in the well group (11.7 +/- 4.9 vs 18.9 +/- 5.4 microg/dL), and 34% of infants in the sick group had a T4 <10th percentile compared with 6% of infants in the well group. T4 on day of life 5 was inversely correlated with Score for Neonatal Acute Physiology (R = -0.52). In the retrospective study, 21% of mechanically ventilated infants developed TH and were given statistically more inhaled nitric oxide, high-frequency ventilation, vasopressors, and pharmacologic paralysis when compared with infants without TH. Moreover, infants with TH were statistically more likely to die or require transfer to an extracorporeal membrane oxygenation center compared with infants without TH., Conclusion: Our data show that, similar to preterm infants, ill term infants develop TH. Term infants with TH required more intensive rescue interventions, including inhaled nitric oxide and transfer to an extracorporeal membrane oxygenation center. However, whether T4 levels are a marker or a mediator of clinical outcome remains to be determined.

Objective: Preterm infants are at greater risk of symptomatic cytomegalovirus (CMV) infection than term infants. Breast milk is the main source of perinatal CMV infections. This study evaluated the kinetics of CMV load in breast milk and the rate of postnatal CMV transmission via breast milk from mothers to their preterm infants., Methods: This was a prospective study of 30 mothers and their 43 preterm infants. The infants either had a gestational age of <34 weeks or weighed <2000 g at birth. Breast milk, serum, and urine samples were collected every 2 weeks until discharge, and screened for CMV infection using a real-time PCR assay. Most of the breast milk had been preserved at -20 degrees C before feeding to the preterm infants., Results: Twenty-four mothers (24 of 30, 80%), who had 34 preterm infants, were CMV immunoglobulin G positive. Twenty-one (87.5%) of the 24 seropositive mothers, who had 30 preterm infants, had detectable CMV deoxyribonucleic acid (DNA) in breast milk during the study period. Most breast milk became positive for CMV DNA 2 weeks after delivery. Viral DNA copy numbers increased until they peaked at 4 to 6 weeks. Afterward, the CMV DNA copy numbers decreased. Of the 30 infants who were fed CMV DNA-positive breast milk, CMV infection was confirmed in 3 infants. However, they had no clinical symptoms of CMV infection., Conclusions: Despite the high rate of CMV DNA in breast milk, symptomatic infections in the preterm infants did not occur. These results might be associated with the method of breast milk preservation and the population we studied. CMV infections transmitted via breast milk feeding did not have much impact on preterm infants in our institutes.

Objective: Multiple platelet transfusions are invariably given to neonates on extracorporeal membrane oxygenation (ECMO), and no alternative to repeated transfusions exists. Before any alternatives, such as administration of thrombopoietic stimulators, could be contemplated, data regarding the number of platelet transfusions received by neonatal ECMO patients is needed, and the mechanisms that cause the thrombocytopenia of these patients must be better defined. As a step toward determining this, we analyzed the use of platelet transfusions in this group of neonates. We conducted a historic cohort study of neonates who were treated with ECMO to determine the number of platelet units received as a function of 1) days on ECMO, 2) medical diagnosis for which ECMO was instituted, and 3) type of ECMO used (venovenous [VV] vs venoarterial [VA])., Methods: We reviewed the hospital records of all neonates who were admitted to the neonatal intensive care units at Shands Children's Hospital, Arnold Palmer Hospital for Children and Women, and Tampa General Hospital and treated with ECMO between January 1, 1995, and June 30, 2000. Data were expressed as the number of platelet transfusions versus number of days on ECMO, diagnosis for which ECMO was instituted, and type of ECMO used., Results: Of the 234 ECMO patients, 81 were placed on VV, 138 were placed on VA, and 15 were converted from VV to VA. The average number of platelet transfusions received per day was 1.3 and varied by diagnosis and by type of ECMO. Neonates with meconium aspiration and sepsis required more platelet transfusions per day than neonates with other conditions. Infants who were converted from VV to VA required more transfusions per day (mean: 1.57) than did patients on VA (1.47) or VV (1.06)., Conclusions: Platelet transfusions among neonates on ECMO are dependent of their medical diagnosis; they average 1.3 transfusions per day and are higher on VA than VV ECMO.

The definition of clinically significant hypoglycemia remains one of the most confused and contentious issues in contemporary neonatology. In this article, some of the reasons for these contentions are discussed. Pragmatic recommendations for operational thresholds, ie, blood glucose levels at which clinical interventions should be considered, are offered in light of current knowledge to aid health care providers in neonatal medicine. Future areas of research to resolve some of these issues are also presented.

Objective: Healthy very-low-birth-weight neonates (VLBW, < or = 1500 g) exhibit a high incidence of neutropenia according to Manroe's reference ranges for neutrophil indices. Since these reference ranges may be inappropriate for VLBW neonates, we determined the reference ranges for circulating peripheral neutrophils in VLBW neonates between birth and 28 days of age., Methods: Serial, timed peripheral white blood cell counts (n = 1788) were prospectively obtained between birth and 28 days from 193 inborn, VLBW neonates delivered between January 1 and December 31, 1990. Data were divided into neutrophil counts obtained prior to (n = 630) and after (n = 1158) 60 hours of age. After excluding counts from neonates with perinatal and/or neonatal complications, values from "normal" neonates were compared to Manroe's reference ranges. Where indicated new ranges were developed., Results: Although immature neutrophil (ATI) and immature:total neutrophil (I:T) values were within Manroe's reference ranges (P > .1) throughout the neonatal period, 67% of total neutrophil values (ATN) obtained prior to 60 hours of age were outside (P < .001) and 95% were considered neutropenic. Newly developed ATN reference ranges for VLBW neonates have a wider range of distribution compared to Manroe's results, primarily reflecting a decrease in the lower boundary. ATN values between 61 hours and 28 days also differed (P < .001), and new ranges had upper and lower boundaries of 6000 and 1100/mm3, respectively. Maternal hypertension was associated with neonatal neutropenia (P < .001) without abnormalities of ATI or I:T prior to day 3 of life; however, neutrophilia predominated after day 7. Between birth and 28 days > 70% of ATN values were abnormal in neonates with apnea, neutrophilia occurring in > 90% of counts; I:T values, however, were normal between 61 hours and 28 days., Conclusions: Normal preterm VLBW neonates have ATN reference ranges that differ significantly from that for larger, older neonates, demonstrating the effects of development on neutrophil dynamics. The predictability of neonatal infection using these new reference ranges requires additional study.

The pharmacokinetics and pharmacodynamics of dobutamine were studied in 13 critically ill neonates requiring inotropic support. Dobutamine was administered as a constant infusion in increasing doses of 2.5, 5, and 7.5 micrograms/kg per minute. During dobutamine infusions, there were significant increases in cardiac output measurements above perinfusion values. There were no statistically significant changes in systolic or diastolic blood pressure or heart rate during the infusions. The mean calculated threshold value, or the minimum plasma concentration necessary for a change in cardiac output, was 39 +/- 8 ng/mL. The mean plasma clearance rate was 90 +/- 38 mL/min per kilogram and was most consistent with first-order kinetics over the range of dosages studied. Plasma catecholamine levels were unchanged during the dobutamine infusions. These data suggest that dobutamine is an effective but limited inotropic agent in the neonate. Dobutamine may be most beneficial when cardiogenic failure is presented.

Volumes of plasma (PV), blood (BV), and red cells (RCV) were estimated within 32 hours of birth in 39 neonates with normal growth, 14 neonates with intrauterine growth retardation, and 20 neonates with macrosomia. Total PV, BV, and RCV increased linearly with birth weight and were unaffected by deviation in the quality of fetal growth. In proportion to body weight, PV/kg, BV/kg, and RCV/kg correlated neither with birth weight nor with the quality of intrauterine growth. Neonates with umbilical vein hematocrit (UV Hct) levels 51% to 60%, 61% to 65%, and 66% to 77% had progressively lower, but not statistically different, mean PV/kg (38.1 +/- 4.49, 37.6 +/- 5.41, and 34.8 +/- 5.16 ml/kg, respectively). On the other hand, they had progressively higher mean BV/kg (90 +/- 10.1 vs 101 +/- 13.7 ml/kg, P less than .002, and vs 110 +/- 19.0 ml/kg, P less than .001). They also had progressively higher mean RCV/kg (52 +/- 7.4, 64 +/- 8.7, and 75 +/- 16.4 ml/kg, P less than .001). Although PV/kg did not correlate with UV Hct, both BV/kg and RCV/kg increased linearly with increasing UV Hct (r = .58 and r = .79, respectively). Volume estimates were repeated after partial exchange transfusion in 29 neonates. Mean UV Hct decreased from 63 +/- 5.9% preexchange to 51 +/- 5.2% postexchange (P less than .001), mean PV increased from 37.7 +/- 5.56 to 47.6 +/- 7.99 ml/kg (P less than .001) and mean RCV decreased from 67 +/- 16.5 to 51 +/- 12.3 ml/kg (P less than .001). Despite precautions to keep the partial exchange isovolemic, mean BV decreased from 105 +/- 18.7 to 98 +/- 18.0 ml/kg (P = .001) and the mean PV increase (10 ml/kg) was less than the mean RCV decrease (16 ml/kg). These data suggest that neonates with polycythemic have normal PV but their RCV and BV are elevated in direct proportion to UV Hct. "Isovolemic" partial exchange transfusion decreases UV Hct, RCV, and BV and increases PV.

In order to determine if prolonged, significant transient neonatal tyrosinemia (TNT) is injurious to the developing central nervous system, 15 term infants who had suffered from this disorder for a mean duration of 50 days underwent comprehensive psychometric evaluations at a mean (+/- 1 SD) age of 56.5 +/- 7.8 months. Their mean maximum detected tyrosine level had been 25.8 mg/dl (range, 13.6 to 42.0) and their defect was considered secondary to a combination of a high protein formula intake and a lack of supplemental vitamin C. Compared to a control group, significantly lower mean scores were obtained by the TNT group on the McCarthy Scale of Children's Abilities (77.1 vs. 92, P = .008) and the Illinois Test of Psycholinguistic Ability (92.3 vs. 109.9, P = .002). Performance scores varied inversely with the duration of TNT. Although these children are not classifiable as "mentally retarded," TNT may cause specific learning disabilities. There is, therefore, a need to determine the frequency of TNT in infants fed evaporated milk and other high-protein milk formulas and to develop ways to prevent its occurrence.

To study the effect of fat-free alimentation on essential fatty acids (EFA), their levels in plasma phospholipids, cholesterol esters, triglycerides, and free fatty acids were measured in five sick newborns. Four patients were under 32 weeks of gestation; three were small for gestational age and one was an infant of a diabetic mother. All developed biochemical evidence of EFA deficiency during the first week of life--the smallest infant did so by the second day. Biochemical evidence of EFA deficiency included a decrease in plasma lipid arachidonic and linoleic acids, an increase in 5,8,11-eicosatrienoic acid, palmitoleic, and oleic acids and a trienoic/tetraenoic ratio of more than 0.4. Oral feeding with EFA reversed these changes. The two infants showing the most severe biochemical evidence of EFA deficiency died. Neither exchange transfusion nor multiple blood transfusions prevented or corrected the development of EFA deficiency. An alternative method for efficient and safe delivery of EFA to such infants is required.

Arterial oxygen tension measurements were performed simultaneously using two different techniques: (1) the conventional method of analyzing a blood sample obtained from the radial artery by means of a Clark electrode and (2) a new method of transcutaneous oxygen tension recording using a newly developed surface electrode containing a built-in heating device to ensure optimal cutaneous perfusion at the site of measurement. Two groups of newborn infants were used as subjects: (1) 70 clinically healthy babies who were tested during normoxia and hyperoxia (breathing 80% to 100% oxygen) and (2) 20 sick preterm and term infants receiving inspired oxygen concentrations of between 21% and 100% during the measurement. Our results indicate a satisfactory accuracy for the transcutaneous oxygen tension measurements in normoxia and hyperoxia (percentage coefficient of variation, 15.9% and 24.1%, respectively). In hypoxia agreement between the two methods varies depending on the degree of circulatory derangement. Overall correlation coefficients were greater than 0.85 in each group.

Serum concentrations and half-life times of digoxin were determined in ten mature and nine premature newborns. Median serum digoxin concentration was 2.3 ng/ml (1.2 to 3.5 ng/ml) in mature newborns and 2.4 ng/ml (1.5 to 4.5 ng/ml) in premature newborns. Median serum digoxin half-life was 35 hours (17 to 52 hours) in mature newborns and 57 hours (38 to 88 hours) in premature newborns. The difference in serum digoxin half-life between the two groups is statistically significant. The relatively long serum digoxin half-life in premature newborns is probably due to immature renal function in this group. The data emphasize the need for cautious digoxin administration, especially in premature infants.

During a three-year period, 26 neonates with bacterial infection and neutropenia were studied. In order to assess the marrow neutrophil reserves, bone marrow aspirates were obtained from each of these patients. The neutrophil storage pool (percent polymorphonuclear + band neutrophils + metamyelocytes in 1,000 nucleated marrow cells) was significantly greater in those who survived their infection (mean = 20.1%, range 3.2% to 60.8%) than in those who died (mean = 1.9%, range 0.4% to 5.2%, P less than .002). In an attempt to improve survival in this group, seven neutrophil-depleted patients with sepsis were given granulocyte transfusions and all survived. In contrast only one of nine nontransfused and all survived. In contrast only one of nine nontransfused, neutrophil-depleted infants with sepsis survived (P less than .01). The seven granulocyte recipients were examined for possible adverse effects of the transfusions and none were detected. It is suggested that infected, neutropenic neonates with depletion of mature marrow neutrophils are at high risk for death from sepsis, and that these infants may benefit from granulocyte transfusion therapy.

Two hundred eighty-two umbilical artery catheters with oxygen electrodes on their tips were passed into the aortas of 268 newborn infants with severe respiratory illnesses between 1974-1977; 254 (90%) of the electrodes recorded PaO2 satisfactorily for a mean of 66 hours; 212 (75%) electrodes were still functioning well when removed, because they were no longer clinically needed, after a mean of 87 hours. The 27 electrodes that failed to record PaO2 on insertion, 42 that failed later, and 25 that temporarily malfunctioned were examined after removal from the infants. A structural cause was found which accounted for the failure or malfunction of 43 electrodes. Problems with the remaining 51 electrodes were thought often to have been due to clotting over the tip of the electrode. The main complication of catheterization was temporary impairment of the circulation to the legs in 69 (26%) infants. Autopsies were done on 69 (85%) of the infants who died; 22 (32%) infants were found to have thrombi in an iliac artery, which spread in ten (15%) of the aorta. It was concluded that the intravascular electrode usually functioned satisfactorily and that the incidence of complications was no higher than that reported with ordinary umbilical artery catheters. Improvements in the performance of the catheter-tip electrode would be expected if structural causes for failure were eliminated and if means to reduce the incidence of clot formation around the catheter and electrode could be found. It is believed that intravascular electrodes cannot be replaced by skin electrodes for the initial management of severe respiratory illnesses.

Colloid osmotic pressure of umbilical cord plasma was measured in 242 healthy infants, in 34 infants with respiratory distress syndrome (RDS), in 18 infants with asphyxia, in 13 infants who were small for gestational age, in 15 infants born to mothers with diabetes mellitus, and in 18 infants born to mothers with pregnancy-induced hypertension. In healthy infants, colloid osmotic pressure correlated highly significantly with umbilical cord blood total protein level, gestational age, and birth weight. In infants with RDS, no correlation between colloid osmotic pressure and gestational age or birth weight was found. Infants with RDS and gestational age between 36 and 38 weeks had significantly lower colloid osmotic pressure than healthy infants, whereas colloid osmotic pressure of infants with RDS and gestational age between 32 and 35 weeks did not differ from that of healthy infants of corresponding gestational age. Healthy term infants delivered by cesarean section had significantly lower colloid osmotic pressure than infants delivered vaginally. Infants with asphyxia had significantly higher colloid osmotic pressure than healthy infants. Colloid osmotic pressure is related to the lung maturity of the near-term and term neonate. Infants with a colloid osmotic pressure greater than 16 mm Hg are unlikely to develop RDS.

Previous studies have established that leukocyte phagocytosis and intracellular killing are normal in term and low-birthweight newborns who are well. To determine the effect of stress or illness on newborn leukocyte function, the phagocytic and bactericidal activity of leukocytes from 40 sick newborns was compared with that of leukocytes from 12 newborns and 23 normal adults. To eliminate abnormal phagocytosis resulting from serum opsonic defects in newborn sera, pooled adult sera were used in all assays. Twenty-five of the 40 stressed newborns (63%) had decreased in vitro activity against either Staphylococcus aureus 502A or Escherichia coli, or both, compared with decreased activity in two of 12 well infants (17%) and in four of 23 adult controls (17%). The mean bactericidal activity (percentage of organisms killed after two hours) of leukocytes from stressed newborns against S. aureus (83% +/- 2 [SEM]) and E. coli. (87% +/- 4 [SEM]) was significantly less than in the combined well infant and adult control group (94% +/- 1 for S. aureus and 97% +/- .5 for E. coli). Although the more severely ill infants had an increased incidence of impaired antibacterial activity, the degree of impairment was not related to the severity of illness. No consistent relationship of decreased activity to birthweight, gestational age, age when studied, or specific diagnosis was seen. The leukocyte abnormality in stressed infants against S. aureus was principally a killing defect, while against E. coli both phagocytosis and killing were abnormal. This study indicates that a wide variety of neonatal disorders may affect one or more of the steps required for normal bacterial killing. The lability of leukocytic antibacterial function under stress is an additional mechanism for the newborn's increased susceptibility to infection.

The interval from the beginning of the Q wave to the origin of the T wave (Q-oTc interval) and total and ionized serum calcium levels were measured in 27 full-term and 77 premature infants. The correlation between Q-oTc and total and ionized calcium levels was significant in both full-term and normal premature infants. No correlation was found in a group of critically ill premature infants, most of whom had evidence of CNS involvement. Constant infusion of calcium gluconate in a number of infants belonging to the latter group produced a significant shortening of the Q-oTc interval. It is speculated that the lack of correlation of Q-oTc interval and total or ionized calcium levels in sick premature infants could be explained on the basis of a dysfunction in cardiac sympathetics or alternatively by marked variations in serum catecholamines.

Eighteen neonates in heart failure were investigated to assess whether high or low serum digoxin levels had differing effects on left ventricular function as determined by systolic time intervals obtained by echocardiography. Nine patients had digoxin levels of 1.99 +/- 0.35 ng/ml (group 1). Nine others had levels of 3.62 +/- 0.95 ng/ml (group 2). Systolic time intervals were obtained by echocardiography before and at 5 days after digoxin and correlated with serum levels. The heart rate, preejection period (PEP), left ventricular ejection time (LVET), electromechanical systole (QS2) and the PEP/LVET ratio were measured. LVET and electromechanical systole were indexed. These measurements were analyzed and the two groups were compared using Student's t test. The clinical improvement in both groups was similar and no difference in ECG changes were noted. Therapy with digoxin produced changes in heart rate and systolic time intervals in both groups. Both showed significant shortening of electromechanical systole index; group 1 significantly shortened the LVET index and PEP/LVET ratio, whereas group 2 significantly shortened the PEP. Statistical analysis comparing the two groups showed no difference between them. Digoxin produces measurable changes in the indices of left ventricular function. The magnitude of these changes suggests no therapeutic advantage to the higher levels.

Capillary hematocrits were performed on 790 infants during the first four hours after birth. These infants were delivered between August 8 and December 7, 1974, at the University of Colorado Medical Center, which is at an altitude of 1,061 m above sea level. When the capillary hematocrit was 7% or greater, venous hematocrit and blood viscosity were determined. Capillary hematocrits obtained from warmed heels in the first hour after birth were spuriously high and not consistently related to venous hematocrit. Venous polycythemia, defined as a hematocrit of 65% or greater, occurred in 4% of the newborn population. Hyperviscosity (greater than 2 SD above the mean for newborns) occurred in 5% of the newborn infants. At a venous hematocrit of 65% or greater, hyperviscosity was predictable, but some infants with venous hematocrits between 60% and 64% also had hyperviscosity of the blood. The incidence of polycythemia and hyperviscosity was further related to birth weight and gestational age. The infants who were small for gestational age were at highest risk of polycythemia and hyperviscosity, followed by infants who were large for gestational age. However, the greatest number of infants with hyperviscosity were term appropriate for gestational age. Preterm infants with gestational ages of less than 34 weeks were not affected.

Consecutive newborn autopsy cases were divided into infected and noninfected groups on the basis of pathologic findings and cultures, and were compared to a concomitant consecutive group of neonatal survivors with proven bacterial sepsis. Newborns dying with bacterial infection often demonstrated leukopenia, neutropenia, and thrombocytopenia, usually associated with normal bone marrow cell production. Those with nonfatal sepsis frequently had neutrophilia with an increase in absolute band counts. Of infected newborns 80% showed one or more hematologic abnormalities as did 43% of newborns dying without bacterial infection. Of newborns dying with bacterial infection 13% had no hematologic abnormality. Blood cultures were negative in 18% (seven) of the infants dying with bacterial infection. Abnormalities of the white blood cell, differential and platelet counts are not invariably specific for bacterial infection nor do normal values adequately exclude it. Blood cultures may be negative in newborns dying with significant foci of bacterial infection.

Transcutaneous oxygen tension (tcPO2), measured by two skin electrodes of different design, and arterial oxygen tension (PaO2), measured by an intravascular oxygen electrode, were continuously recorded for periods of six hours in 15 newborn infants with serious respiratory illnesses. Ten of the infants needed mechanical ventilation and three needed continuous positive airway pressure. One skin electrode had three microcathodes surrounded by a heated ring-shaped anode, and the other had a large heated cathode. The temperature of both electrodes was set at 44 degrees C and they were calibrated in vitro. The tcPO2 recorded by the electrode with the microcathodes was found to estimate PaO2 reasonably accurately for the whole six-hour duration of the study. The tcPO2 recorded by the electrode with the large cathode gave a similar estimate of PaO2 for three hours, but then tcPO2 often fell relative to PaO2. This fall was probably caused by skin changes at the electrode site. For a variety of reasons, our results suggest that measurement of tcPO2 is unlikely to replace continuous intravascular measurement of PaO2 in infants with severe respiratory illnesses.

The case of an infant who developed refractory watery diarrhea at the age of 2 weeks is described. Diarrhea was secretory in type, stool weight on no oral intake was 400 to 600 gm daily. A vasoactive intestinal peptide (VIP)-producing tumor was suspected. At the age of 7 1/2 months an exploratory laparotomy revealed nonbeta islet cell hyperplasia of the pancreas. VIP levels were elevated in plasma and pancreatic tissue. After 95% pancreatectomy, plasma VIP level dropped to normal. Hypokalemia, described in adult patients with VIP-producing pancreatic tumors and refractory watery diarrhea, was not a significant problem in this infant. This is the first report on the association of refractory watery diarrhea with elevated levels of plasma VIP and pancreatic islet nonbeta cell hyperplasia in the pediatric age group.