Severe intraventricular hemorrhage and withdrawal of support in preterm infants.

OBJECTIVE: The objective of the study was to determine whether withdrawal of support in severe 'intraventricular hemorrhage' (IVH), that is, IVH grade 3 and periventricular hemorrhagic infarction (PVHI), has decreased after publication of studies that show improved prognosis and to examine cranial ultrasonograms, including PVHI territories defined by Bassan. STUDY DESIGN: Retrospective cohort of preterm infants from 23 0/7 to 28 6/7 weeks' gestation in 1993 to 2013. RESULTS: Among the 1755 infants, 1494 had no bleed, germinal matrix hemorrhage (GMH) or IVH grade 2, 137 had grade 3 IVH and 124 had PVHI. The odds of withdrawal of support, adjusted for severity of GMH-IVH and baseline variables, did not decrease after publications showing better prognosis. Among 82 patients who died with PVHI, 76 had life support withdrawn, including 34 without another contributing cause of death. The median number of PVHI territories involved was three. CONCLUSION: Withdrawal of support adjusted for severity of GMH-IVH did not significantly change after publications showing better prognosis.

Transcutaneous bilirubin levels in an outpatient and office population.

OBJECTIVE: The use of transcutaneous bilirubin (TcB) measurements has been studied extensively in the newborn population, but there have been few studies in outpatient populations and none from the offices of practicing pediatricians. STUDY DESIGN: We performed TcB measurements on a mixed-race population of 120 jaundiced infants, ≥ 35 weeks of gestation, in two hospital-based outpatient clinics, a regional public health nurse follow-up program and two pediatric office practices. Three individual TcB readings were obtained from the mid-sternum, and the average and maximum values were recorded. RESULT: There was good correlation between the TcB and total serum bilirubin (TSB) measurements (r=0.78, P=0.0). 59% of TSB's were ≥15 mg dl(-1) and, although the number of false-negative readings increased when the TSB values exceeded 15 mg dl(-1), it was nevertheless possible to use TcB measurements to accurately predict the risk of TSB levels ≥ 15 mg dl(-1). CONCLUSION: In outpatient settings, a TcB measurement with the JM-103 provides a reliable screening method for the identification of hyperbilirubinemia even when the TSB level exceeds 15 mg dl(-1). Using the maximum of three independent measurements reduces the number of false negatives, but increases the number of false positives. The use of TcB measurements in an outpatient practice should be a valuable tool for the practitioner.

Evaluation of transcutaneous bilirubinometry in preterm neonates.

OBJECTIVE: To determine the accuracy and precision of transcutaneous bilirubin (TcB) measurements in preterm neonates. STUDY DESIGN: Neonates were stratified into three groups on the basis of gestational age: 24 to 28 weeks (Group 1, n=30), 29 to 31 weeks (Group 2, n=29) and 32 to 34 weeks (Group 3, n=31). TcB was measured using the Draeger Air Shields JM-103, and when possible, measurements were made by two observers. TcB and total serum bilirubin (TSB) measurements were compared, and interobserver precision for TcB measurements was assessed. RESULT: Correlations between TcB and TSB ranged from 0.79 to 0.92. Most of the differences between TcB and TSB were +/-2 mg per 100 ml, and there was no trend for the difference to increase with increasing bilirubin values. Sensitivity, specificity and negative predictive values ranged from 0.67 to 1.0, 0.29 to 0.81 and 0.60 to 1.0, respectively. Intraclass correlations were 0.87 to 0.92. CONCLUSION: TcB correlates significantly with TSB in preterm neonates, and interobserver precision is significant. Routine measurement of TcB in preterm neonates may provide enhanced clinical monitoring for hyperbilirubinemia.

Evaluation of a point-of-care direct spectrophotometric method for measurement of total serum bilirubin in term and near-term neonates.

OBJECTIVE: To evaluate point-of-care (POC) measurement of total serum bilirubin (TSB) in the management of neonatal jaundice. STUDY DESIGN: TSB was measured by a POC direct spectrophotometric bilirubin method (Unistat (U/TSB)) and a standard diazo clinical laboratory method (Olympus AU640E analyzer (diazo/TSB)). Agreement between U/TSB and diazo/TSB was assessed by correlation coefficient and Bland-Altman analysis. Transcutaneous bilirubin (TcB) was measured using JM-103 (JM). RESULTS: Correlation between U/TSB and diazo/TSB was 0.99 (n = 120). Maximum difference (U/TSB minus diazo/TSB) was -2.9 mg/dl, and 79% were +/-1 mg/dl; the average difference was -0.37+/-0.70 mg/dl and the average absolute difference was 0.60+/-0.52 mg/dl. Median time to determine U/TSB was 5 min. Correlation between U/TSB and JM was 0.92 (n = 113). Maximum difference (U/TSB minus JM) was 6.3 mg/dl, and 45% were +/-1 mg/dl; the average difference was 0.7+/-1.8 mg/dl and the average absolute difference was 1.4+/-1.2 mg/dl. CONCLUSION: Measurement of TSB using Unistat provides excellent agreement with diazo/TSB and rapid turnaround time. This technique may provide reliable POC confirmation of TcB results that are above a screening cutoff value.

Blood pressure in the very low birth weight neonate.

Few aspects of management of very low birth weight (VLBW; <1500 g) neonates have generated as much controversy as the assessment of blood pressure (BP) and need for treatment of perceived abnormalities of this physiologic variable. The approach to this problem may differ greatly among various institutions and even among clinicians within a given center. The purpose of this manuscript is to review available information regarding physiologic determinants and measurement of BP in VLBW neonates, normative data for BP, clinical factors that may affect BP in these at-risk neonates and studies in which presumed abnormalities of BP resulted in adverse clinical outcomes. Options for treatment of low BP in VLBW neonates also will be discussed.

Neonatal pneumonia: comparison of 4 vs 7 days of antibiotic therapy in term and near-term infants.

OBJECTIVE: To compare a 4-day course of antibiotic therapy to a 7-day course in selected term and near-term neonates with pneumonia. METHODS: The diagnosis of pneumonia was made in neonates admitted to the normal Newborn Nursery (NBN) who later had signs of respiratory distress and whose chest radiographs were consistent with pneumonia. Infants were excluded if any of the following was present: moderate or thick meconium-stained amniotic fluid, prior antibiotic therapy > 24 hours, or need for supplemental oxygen > 8 hours. Infants who were asymptomatic after 48 hours of antibiotic therapy were prospectively randomized to a 4-day group (n = 35) or a 7-day group (n = 38). Infants in the 4-day group were observed in the hospital for 24 hours following cessation of antibiotics and were seen in follow up within several days of discharge. RESULTS: The groups were comparable with regard to demographic factors, duration of rupture of membranes, and incidence of maternal chorioamnionitis. Median postnatal age at the time of identification of respiratory distress symptomatology was 19 hours (range 0.5 to 55 hours) in the 4-day group and 12 hours (range 1 to 72 hours) in the 7-day group. No study infants had a positive blood culture. Mean reduction in length of hospitalization was 2.1 days, with estimated savings of greater than US$700 per shortened hospitalization. Two infants in the 4-day group developed tachypnea during the 24-hour observation period. However, no infants were rehospitalized for sepsis or pneumonia following discharge. With 95% confidence, the true rate of success for the 4-day group was at least 92%. CONCLUSION: Four days of antibiotic therapy plus a 24-hour period of observation for selected cases of neonatal pneumonia appears to be comparable to 7 days of therapy. It is important to note that newborns in our institution receive a single dose of penicillin soon after birth as part of our group B streptococcal sepsis prophylaxis program, and all infants in this study received prophylaxis prior to the onset of respiratory symptoms. Furthermore, only infants who were asymptomatic after 48 hours of antibiotic therapy were included in this study, and a 24-hour observation period at the end of the 4-day course was required. These qualifications should be taken into account before use of this approach is considered, and additional studies are necessary to further establish its safety and benefits.

Determinants of blood pressure in very low birth weight neonates: lack of effect of antenatal steroids.

OBJECTIVES: To define the range of normal blood pressures (BP) for very low birth weight (VLBW;

Acute changes in arterial carbon dioxide tension and acid-base status and early neurologic characteristics in term infants following perinatal asphyxia.

BACKGROUND: Marked acute changes in arterial carbon dioxide tension (PaCO2) and acid-base status occur in the immediate postnatal period in infants delivered in the presence,of pathologic fetal acidemia (FA) in whom the risk for hypoxic-ischemic cerebral injury is high. The cerebral vasculature is extremely sensitive to changes in PaCO2. However, the relationship between the acute changes in PaCO2 and subsequent neonatal neurologic characteristics remains unclear. OBJECTIVES: (1) To determine the extent of the acute changes in PaCO2 and acid-base status following birth in infants delivered in the presence of pathologic FA and (2) to determine the potential relationship of the initial changes in PaCO2 and neonatal neurologic characteristics. METHODS: PaCO2 and acid base status of cord umbilical arterial blood and initial postnatal arterial blood were studied in 73 term infants admitted to the Neonatal Intensive Care Unit. Infants were categorized in three groups: I, no FA, no respiratory support and normal neonatal neurologic examination (n = 49); II, pathologic FA (umbilical artery pH < or = 7.00, base deficit > or = 12 mEq/l), no respiratory support and normal neonatal neurologic examination (n = 17); III, FA, intubated and with evidence of hypoxic ischemic encephalopathy (HIE) including seizures (n = 7). RESULTS: Demographic characteristics were similar among the three groups, although 5-min Apgar score < or = 5 was more common in group II (47%) and group III (100%) than in group I (4%). Umbilical arterial pH was lower in group III (6.75 +/- 0.18) vs. group II (6.90 +/- 0.09) and in group II vs. group I (6.90 +/- 0.09 vs. 7.19 +/- 0.09) (P < 0.005) and the PaCO2 was higher in group III (141 +/- 37 mmHg) vs. group II (94 +/- 22 mmHg) and in group II vs. group I (94 +/- 22 vs. 60 +/- 13 mmHg) (P < 0.05). The mean base deficit was large but comparable between groups III and II, i.e. 18 +/- 6 vs. 18 +/- 5 mEq/l, respectively, and higher than in group I infants (6 +/- 4 mEq/l) (P < 0.00). At 1 h postnatal age, the mean arterial pH had increased in all groups, i.e. 7.06 +/- 0.15 (group III), 7.25 +/- 0.09 (group II), and 7.31 +/- 0.06 (group I); however, the differences amongst the groups remained significant (P < 0.005). The mean PaCO2 decreased from 94 +/- 22 mmHg (12.5 +/- 2.9 kPa) to 30 +/- 6 mmHg (4.0 +/- 0.8 kPa) for the spontaneously ventilating group II infants and from 141 +/- 37 mmHg (18.8 +/- 4.9 kPa) to 45 +/- 14 mmHg (6.0 +/- 1.9 kPa) in the intubated group III infants (P < 0.005). A repeat PaCO2 at 2 h of age in group III infants had decreased to 29 + 2 mmHg (3.9 +/- 0.3 kPa),which was not different from the PaCO2 at 2 h in group II infants (30 +/- 8 mmHg; 4.0 +/- 1.1 kPa). No significant differences were observed for pH or base deficit at this time. CONCLUSIONS: Marked and rapid changes in PaCO2 and pH were observed in term infants delivered in the presence of pathologic FA. Initial postnatal PaCO2 values varied significantly with the lowest values noted in those infants breathing spontaneously and who exhibited an uneventful neonatal course; higher initial postnatal values, despite mechanical ventilation, were noted in infants with HIE including seizures. Further investigation in this area is imperative in order to better define the optimal respiratory management of the neurologically at-risk infant.

Circulating neutrophils in septic preterm neonates: comparison of two reference ranges.

OBJECTIVE: To study the effect of sepsis on circulating neutrophils in very low birth weight neonates and to assess the usefulness of recently revised reference ranges for circulating neutrophils in the diagnosis of sepsis in this population by comparison with previously reported reference ranges. METHODS: Neutrophil parameters (absolute total neutrophils, absolute total immature neutrophils, and the immature:total neutrophil proportion) were analyzed retrospectively in 202 sepsis episodes in 192 neonates (birth weight = 1055 +/- 246 g, X +/- SD; estimated gestational age = 29 +/- 2 weeks) between birth and 30 days of age. The percentage of values lying outside the reference ranges reported recently by Mouzinho et al and previously by Manroe et al were compared. To more accurately assess possible differences in specificity between the two reference ranges, neonates with early-onset group B streptococcal infection (n = 19) were compared with a matched control group (n = 51) using conditional logistic regression. RESULTS: Greater sensitivity was observed using the previous reference ranges of Manroe et al over the entire study period (0 to 720 hours) both for the initial and the second complete blood count (CBC). The previous reference ranges also were more sensitive than the revised ranges for the initial CBC at 0 to 72 and at 73 to 720 hours and for infections attributable to coagulase-negative staphylococci. However, specificity in neonates without group B streptococcal infection was significantly greater with the revised reference ranges compared with those of Manroe et al (initial CBC, 73% vs 45%; serial CBCs, 59% vs 10%). CONCLUSION: The observed differences in sensitivities may be of limited clinical significance because very low birth weight infants often are begun on antibiotic therapy regardless of laboratory values. However, the striking differences in specificity using the revised reference ranges suggest that these ranges may be clinically useful in determining length of antimicrobial therapy in infants in whom cultures remain sterile.

Early minimal feedings promote growth in critically ill premature infants.

Critically ill premature infants requiring mechanical ventilation and an umbilical artery catheter usually do not receive enteral feedings during the acute phase of their illness. We studied the safety and benefit of early minimal enteral feedings during this time in a prospective, controlled, and randomized study. Twenty-nine infants were randomly assigned to receive only standard intravenous fluid and nutrition (nothing per OS, NPO group; n = 13), or in addition to receive small-volume hypocaloric continuous feedings (1 ml/kg/h), beginning at 24 h of age (early-feeding group; n = 16). Standard enteral feedings were begun in both groups at the resolution of the acute phase of the illness and advanced by protocol. The two groups were of comparable birth weight, gestational age, and Apgar scores. There were no significant differences in the episodes of feeding intolerance. Two infants in the NPO group developed clinical signs of necrotizing enterocolitis. Serum diamine oxidase and somatomedin C were measured weekly until 30-60 days of age and were not different between the two groups. The early-feeding group required fewer days to reach 120 ml/kg/day enteral intake (early-feeding group 10 +/- 3 days, NPO group 13 +/- 4 days; p < 0.05). On day 30 of life the early-feeding group was 223 +/- 125 g above birth weight, while the NPO group was 95 +/- 161 g above birth weight (p < 0.05). The average intake (kcal/kg/day) from day 6 to day 30 was not different between the two groups. We conclude that early minimal feedings in critically ill very-low-birth-weight infants requiring mechanical ventilation are well tolerated and result in reduced time to reach 120 ml/kg/day of enteral feeding and in a greater weight gain by day 30 of life.

Development of fetal and neonatal renal function.

The development of renal function in the human is an amazingly intricate and complex process. In the vast majority of preterm and term babies, renal development and function are adequate to meet the homeostatic needs of the rapidly growing infant. However, when normal renal development does not occur the effects can be devastating. Pioneering work in the assessment and treatment of fetal renal anomalies has been carried out, but it appears that further studies will be necessary to demonstrate whether widespread applicability of this technology is indicated.

Evaluation of renal function and acute renal failure in the neonate.

The diagnosis of renal dysfunction in the neonate can be a challenging problem for the practicing pediatrician. Although there are real differences in renal function between term and preterm infants, overall function is quite adequate in both groups when fluid intake and environmental conditions are carefully controlled. When confronted with an infant with a pathologic decrease in urine output, the clinician must provide adequate fluid resuscitation for the infant with prerenal oliguria without inducing fluid overload in the infant with established, intrinsic renal failure. In addition, the infant with obstruction to urine flow must be distinguished. This requires careful assessment of physical findings and a few key laboratory determinations. Once the diagnosis of renal failure is made, frequent clinical monitoring with anticipation of potential complications is critical. Long-term management of renal failure in infancy and intervention for suspected urinary tract malformation in the fetus have emerged as difficult medical and ethical problems as our technology has advanced.

Urinary arginine vasopressin: pattern of excretion in the neonatal period.

The pattern of arginine vasopressin (AVP) secretion in the immediate neonatal period is unclear. Plasma concentrations of AVP are reflected by its urinary excretion, thus providing a noninvasive method for studying the pattern of AVP release in the neonate. In these studies, we determined the pattern of urinary AVP excretion (microU/mg creatinine) during the first 2-4 days after birth in 78 neonates, 53 of whom had various prenatal and/or neonatal complications. In well term (n = 12) and preterm (n = 13) infants mean urinary AVP excretion decreased gradually during the first 24-36 h after birth. Although term and preterm infants with perinatal asphyxia had highest initial levels of urinary AVP (greater than 200 microU/mg creatinine) and a significant negative correlation with the 1-min Apgar score was obtained, their pattern of excretion was similar to respective controls. After delivery, elevated values for urinary AVP excretion were found among infants with neonatal courses complicated by intracranial hemorrhage, hypoxic encephalopathy, and pneumothorax. Urine osmolality did not correlate linearly with urinary AVP levels, but rather attained a maximum value of approximately 400 mosmol/kg at urinary AVP levels less than 200 microU/mg creatinine and then plateaued. It is concluded that the decrease in urinary AVP excretion observed soon after birth generally reflects diminution of the hypersecretion of AVP during parturition; neonates with evidence of intrapartum asphyxia initially have increased urinary AVP excretion; however, the pattern of excretion is similar to normal infants. During the neonatal period insults such as pneumothorax and intracranial hemorrhage may cause hypersecretion of this hormone.

Neutropenia in high-risk neonates.

To determine the usefulness of neutrophil values in diagnosing neonatal sepsis among infants at risk of neutropenia, we evaluated the pattern of sequential absolute total and immature neutrophil counts and the immature to total neutrophil (I:T) proportion over the first 5 days of life in infants with sepsis (n = 13), asphyxia neonatorum (n = 12), or delivered of mothers with pregnancy-induced hypertension (PIH) (n = 20), comparing values to references ranges previously reported by us. Neutropenia was initially present in 67% and 50% of infants with asphyxia and those whose mothers had PIH, respectively, and persisted through the first 3 postnatal days. In contrast, infants with sepsis were less likely to be neutropenic initially (38%), and neutropenia did not persist after 36 hours of age. Elevated values for the total immature neutrophil count and I:T proportion were much more likely to occur in infants with sepsis (46% and 61%, respectively) than in infants of mothers with PIH (4% and 12%) or those with asphyxia (13% and 22%). The importance of considering the perinatal history as well as the differential neutrophil count in the evaluation of neonatal neutropenia is demonstrated.

Urinary potassium excretion in the critically ill neonate.

The possibility that negative potassium balance may occur in critically ill preterm neonates is suggested by factors such as the usual provision of minimal potassium intake, increased plasma aldosterone concentrations, increased prostaglandin synthesis, and the frequent use of diuretic agents. In order to assess the relationship between potassium balance and renal prostaglandins, nine infants with respiratory distress syndrome (mean birth weight 1,264 g, mean gestational age 30.6 weeks) were studied sequentially with timed-urine collections during the first four postnatal days and values were compared with those of 18 preterm infants without respiratory distress syndrome. Mean plasma potassium concentrations decreased significantly from 4.87 +/- 0.19 mEq/L (mean +/- SEM) on day 1 to 3.83 +/- 0.18 mEq/L on day 4, (P less than 0.05), and cumulative potassium balance was -4.07 +/- 0.95 mEq/kg or 10% of estimated total body potassium. Urinary excretion of prostaglandin E2 on day 1 in infants with respiratory distress syndrome was significantly greater than in those without respiratory distress syndrome (22.0 +/- 4.9 v 8.3 +/- 1.6 ng/mg of creatinine) (r = .66, P less than .001). These studies suggest that consideration be given to the importance of providing sufficient potassium to prevent hypokalemia in the stressed preterm infant and that pharmacologic agents that alter prostaglandins or potassium excretion should be used with caution.

Renal handling of beta-2-microglobulin in the human neonate.

Glomerulotubular balance for beta-2-microglobulin (beta 2M) in the human kidney has been reported to occur after 34 weeks conceptional age (CA), and fractional tubular reabsorption of beta 2M (T beta 2M) has been suggested as a useful index of renal tubular maturation. To confirm and extend these observations to include still less mature infants, renal handling of beta 2M was investigated during timed-urine collections with corresponding blood samples obtained from 57 infants with CA of 26 to 43 weeks and postnatal ages (PNA) 0.2 to 12 days (study 1); 18 infants were studied a second time 5 to 17 days later (study 2). GFR was measured by endogenous creatinine clearance (CCr). T beta 2M and fractional reabsorption of sodium (TNa) were calculated. Results indicated that while both increased with CA, T beta 2M (r = -0.69, P less than 0.0001) and TNa (r = -0.79, P less than 0.0001) varied inversely with fractional urine flow rate (V/CCr). Moreover, an inverse relationship between changes in T beta 2M and V/CCr was observed in the same infant between study 1 and study 2 (r = -0.47, P less than 0.05). These data suggest that the renal handling of beta 2M in the human neonate is influenced by physiologic variables that are independent of CA, and thus T beta 2M may not be a reliable predictor of renal tubular maturation in the human neonate.

Diuresis and respiratory distress syndrome: physiologic mechanisms and therapeutic implications.

Previous studies have suggested that spontaneous diuresis may be important to the recovery from respiratory distress syndrome in preterm infants. Daily quantification of fluid intake (1) and urine output (O) were recorded, and O/I and alveolar-arterial oxygen gradients (AaDO2) were determined for sequential eight-hour periods in 10 inborn premature infants with RDS. Sequential timed-urine-plasma collections were obtained during the first four days of life to evaluate the role of hormonal and vasoactive factors in the acute phase of RDS. Diuresis (O/I greater than 0.80) occurred at 25 to 32 hours, preceded any significant improvement in AaDO2 (which occurred at 57 to 64 hours), and was associated with a 6.2 +/- 1.4% decrease in body weight. Although there was no significant change in glomerular filtration rate, plasma AVP concentrations, or urinary excretion of AVP in the infants, there were significant decreases in both plasma concentrations and urinary excretion of 6-keto-PGF1 alpha (stable metabolite of prostacyclin) in sequential studies. These results suggest that changes in renal function or AVP may not be of primary importance in the diuresis associated with RDS, and that decreasing levels of prostacyclin, a prostaglandin that increases vascular permeability and lowers blood pressure, may have an important physiologic role.

Effect of increased radiant warmer power output on state of hydration in the critically ill neonate.

To correlate radiant warmer bed power output with state of hydration in the critically ill infant, warmer power input was measured by a wattmeter and recorded by an on-line computer every 5 sec for 2 periods of 8-24 h each in 11 newborns with respiratory distress syndrome (mean birth weight 1.42 kg, mean gestational age 31.4 weeks). The 2 periods were compared to define a high and a low radiant power period. Fluid intake and urine output, urine and serum osmolalities, serum electrolytes, and free water clearance during each study period (high vs low radiant power) were also compared. Mean radiant power density received during periods of high radiant power output (8.93 mw/cm2) was significantly greater than during periods of low radiant power output (7.85 mw/cm2, p less than 0.001). Mean urine osmolality and fluid intake to output ratio were also significantly increased during periods of high radiant power density. There was a trend toward increased serum osmolality and decreased free water clearance during periods of high radiant power; however, these differences were not significant. This study suggests that prospective measurement of radiant power density delivered to critically ill newborns may be clinically significant in predicting an infant's state of hydration.

Neonatal hyperbilirubinemia and renal function.

It has been suggested that neonates with hyperbilirubinemia may have impaired renal function. In order to study this problem, creatinine clearance, and fractional tubular reabsorption of sodium and beta-2-microglobulin were measured in 22 jaundiced neonates with gestational ages ranging from 33 to 42 weeks and mean postnatal age of 3.9 days. These data were compared with those obtained from 23 nonjaundiced control infants matched for gestational and postnatal ages. In addition, follow-up studies of renal function were conducted in 18 of 22 study infants when serum bilirubin concentration was less than 11 mg/dl at a mean postnatal age of 7.6 days. No significant differences in CCr, T Na, or T beta 2M were observed. We conclude that when gestational age is greater than or equal to 33 weeks, modification of current management of infants with moderate hyperbilirubinemia is unnecessary to prevent nephrotoxicity.