Racial differences in prenatal care of mothers delivering very low birth weight infants.

OBJECTIVES: To determine whether there are any racial differences in the prenatal care of mothers delivering very low birth weight infants (VLBW). STUDY DESIGN: Retrospective cohort study of infants cared for at a single regional level III neonatal intensive care unit over a 9-year period, July 1993-June 2002, N = 1234. The main outcome variables investigated included antenatal administration of steroids, delivery by cesarean section, and use of tocolytic medications. Both univariate and multivariate analyses were performed. RESULTS: After controlling for potential confounding variables, white mothers delivering VLBWs had an increased odds of cesarean delivery (odds ratio 1.5, 95% confidence intervals (CI) 1.1-2.0), receiving antenatal steroids (1.3, CI 1.01-1.8), and tocolysis (1.4, CI 1.1-2.0) compared to black mothers. The models controlled for gestational age, multiple gestation, premature labor, clinical chorioamnionitis, maternal age, income, year of birth, and presentation. CONCLUSIONS: In our population of VLBWs, white mothers are more likely to receive antenatal steroids, tocolytic medications, and deliver by cesarean section when compared to black mothers. From our data we cannot determine the reasons behind these racial differences in care of mothers delivering VLBWs.

Thyroxine and illness severity in very low-birth-weight infants.

The objective of this study was to determine the relationship between thyroxine (T4) and illness severity in a population of preterm infants. We investigated a cohort of infants with birth weights 1,500 g or less from a single level III neonatal intensive care unit who received a minimum of one cranial sonogram to screen for intraventricular hemorrhage (IVH) and one newborn screen for T4 during a 2-year period, (n = 284). The Score for Neonatal Acute Physiology (SNAP) was used to measure illness severity. T4 and SNAP were investigated in relationship to mortality, IVH, and severe IVH. T4 correlated inversely with SNAP (R = -0.46, p < 0.01). Infants with severe IVH and mortality had lower T4 and higher SNAP scores when compared to infants without these conditions. These differences persisted after controlling for the confounding effect of gestational age. Analysis of receiver operator curves indicated that high SNAP and low T4 were equivalently associated with IVH, severe IVH, and mortality. Our data indicate that T4 is associated with illness severity in very low-birth-weight infants. Low T4 levels and high SNAP scores are both associated with the outcomes of IVH and mortality in very low-birth-weight infants.

Prenatal consultation with a neonatologist prior to preterm delivery.

OBJECTIVE: Evaluate the usefulness of prenatal consultation with a neonatologist before preterm birth. STUDY DESIGN: A questionnaire was administered to mothers 1 week before home discharge of their preterm infant in a single regional level III neonatal intensive care unit. RESULTS: Sixty-seven mothers completed the questionnaire; 84% indicated the consult was useful and 71% were comforted by the consult. However, mothers < 30 weeks' gestation were less likely to be comforted after the consult compared to those > or = 30 weeks. Most frequently, mothers indicated that they were provided with too little detail about retinopathy of prematurity and intraventricular hemorrhage. CONCLUSIONS: Most mothers delivering a preterm infant describe the prenatal consultation with a neonatologist as useful. The majority of mothers are comforted by the information presented.

Thyroid function in very-low-birth-weight infants with intraventricular hemorrhage.

The objective of this investigation was to study the natural course of thyroid function in infants with intraventricular hemorrhage (IVH). A cohort of infants < 1,500 grams birth weight, n=247, were included in the analysis. Total T4 and thyrotropin from newborn screening during the 1st week of life (Test 1) and from repeat screening at 2-4 weeks postnatal age (Test 2) were compared in infants with IVH (n=43) and a group of infants without IVH. Fifty-nine percent of infants still had transient hypothyroxinemia at the time of Test 2. After multivariate analysis, infants with IVH had an increased odds of having a T4 < or = 6 microg/dL on Test 1 (OR 2.8, 95% CI 1.2-6.5), but at the time of Test 2 IVH was not associated with an increased odds of having a low T4. Only gestational age (OR 1.6, 95% CI 1.1-2.5) remained associated with an increased odds of having an extremely low T4 (< or = 4 microg/dL) at this time. Transient hypothyroxinemia remains common at 2-4 weeks of age in preterm infants. IVH is not independently associated with having a low T4 at this time.

Increased leukocytes in infants with intraventricular hemorrhage.

The objective of this study was to investigate the relationship between intraventricular hemorrhage (IVH) and cystic periventricular leukomalacia (PVL) with changes in the peripheral blood count. Total peripheral leukocytes, absolute neutrophils, platelets, and nucleated erythrocytes from the first 3 days after birth were compared in very-low-birth-weight infants with (n = 100) and without (n = 388) IVH and cystic PVL (n = 16). After controlling for potential confounding variables, infants with IVH had an increase in total leukocytes and absolute neutrophils and a reduction in nucleated erythrocytes compared with infants without IVH. No difference in any parameters studied was evident with regard to cystic PVL. After controlling for potential confounding variables by logistic regression, infants with a peripheral leukocyte count greater than 25,000/mm(3) beyond 24 hours of age had an odds ratio of 2.1 (95% confidence interval = 1.1-4.3) for developing IVH. We conclude that IVH is associated with an increase in total leukocytes and absolute neutrophils for 72 hours after birth in very-low-birth-weight infants. Further investigation is required to determine whether this leukocytosis is important in the pathophysiology of brain injury or is an associated factor.

Preeclampsia does not increase the risk for culture proven sepsis in very low birth weight infants.

The risk of sepsis associated with neutropenia in infants born to mothers with preeclampsia remains controversial. The objective of this study is to investigate the incidence of culture-proven sepsis along with changes in the complete blood count in very-low-birth-weight infants born to mothers with preeclampsia. We conducted a retrospective cohort study of infants cared for at a single tertiary care neonatal intensive care unit during a 4-year period. Infants born to mothers with preeclampsia (n = 88) were compared to infants born to mothers without preeclampsia (n = 416) by univariate and multivariate analysis. Although infants born to mothers with preeclampsia had lower absolute neutrophil and platelet counts throughout the first week of life, they were no more likely to have a platelet count <100,000 /mm3, and only more likely to be neutropenic at 24 and 72 hr of life compared to infants born to mothers without preeclampsia. After controlling for potential confounding variables, there was no increase in the odds of culture proven sepsis in infants born to mothers with preeclampsia (odds ratio 1.6, 95% confidence intervals 0.7-3.6, p = 0.3) compared to those infants born to mothers without preeclampsia. We conclude that very-low-birth-weight infants born to mothers with preeclampsia are not at increased risk of culture proven sepsis despite a reduction in absolute neutrophils.

Cranial sonography in very-low-birth-weight infants: do all infants need to be screened?

The objective of the study was to develop clinical screening criteria to diagnose infants with intraventricular hemorrhage (IVH) and cystic periventricular leukomalacia (PVL). We performed a case-control investigation of two cohorts of very-low-birth-weight infants (n = 505, combined cohorts). Univariate and multivariate analyses were performed from data obtained in cohort 1 to develop screening criteria for IVH and cystic PVL. The screening criteria were then applied to cohort 2. The screening criteria for IVH had a sensitivity of only 51%, a specificity of 62%, a positive predictive value of 31%, and a negative predictive value of 79%. Screening criteria for cystic PVL had a sensitivity of only 22%, a specificity of 58% a positive predictive value of 2%, and a negative predictive value of 95%. These data suggest that using clinical criteria to determine which infants should receive screening cranial sonography for IVH and cystic PVL would miss a substantial number of infants with these conditions.

Effect of preeclampsia on mortality, intraventricular hemorrhage, and need for mechanical ventilation in very low-birth-weight infants.

Infants born to mothers with preeclampsia have been shown to have a reduction in intraventricular hemorrhage (IVH). The objective of this article is to investigate the relationship between preeclampsia, IVH, neonatal mortality, mechanical ventilation, and other potential confounding variables such as neutropenia and magnesium sulfate. Methods of research include review of infants <1500 g admitted to a single level III neonatal intensive care unit (NICU), n=356. Infants born to mothers with preeclampsia were compared to those without maternal preeclampsia by univariate and multivariate analysis. Overall, 52 mothers were diagnosed with preeclampsia. After multivariate modeling, preeclampsia was not associated with a decrease in mechanical ventilation (odds ratio 0.5, 95% CI 0.2-1.3), IVH (odds ratio 0.5, 0.1-1.9) or mortality (odds ratio 0.6, 0.2-1.9). In our population, after controlling for multiple confounding variables, including MgSO4, neutropenia and thrombocytopenia, there was no difference in the odds of mortality, IVH, or requirement for mechanical ventilation in infants born to mothers with preeclampsia as compared to infants born to mothers without preeclampsia.

Low serum thyroxine on initial newborn screening is associated with intraventricular hemorrhage and death in very low birth weight infants.

UNLABELLED: Transient hypothyroxinemia (TH) of prematurity has been correlated with poor neurodevelopmental outcome. However, the relationship between thyroid function and neonatal mortality and brain injury has not been described. OBJECTIVE: To investigate the relationship between thyroid function and neonatal outcome. METHODS: Review of infants weighing <1500 grams admitted to a single level III newborn intensive care unit (n = 342). Serum total T4 values of initial newborn screening of infants dying before hospital discharge were compared with those of surviving infants. Total T4 values from infants with and without intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) also were compared. RESULTS: T4 values strongly correlated with gestational age (r = .56). Overall, 289 (85%) of 342 infants had TH. None of the infants had true congenital hypothyroidism. T4 values of infants with cystic PVL (n = 15) were not statistically different from those for infants who did not develop cystic PVL. Infants with IVH (n = 58) had a lower T4 value than did infants who did not develop IVH (5.4 +/- 3.4 microg/dL vs 7.8 +/- 3.6 microg/dL). Infants who died before hospital discharge (n = 24) had a lower T4 value than did infants discharged to home (3.4 +/- 2.2 vs 7.9 +/- 3.7 microg/dL). After controlling for potential confounding variables, T4 value remained associated with an increased odds of IVH (odds ratio: 1.2; 95% confidence interval: 1.05 to 1.4) and mortality (odds ratio: 2.3; 95% confidence interval 1.6 to 3.4). CONCLUSIONS: In our population of very low birth weight infants, TH has an incidence of 85%. Very low T4 values on initial newborn screening are associated with increased odds of death and IVH. Additional investigation is needed to determine whether low serum thyroxine level contributes to IVH and neonatal death or whether it is simply an associated factor.

Predicting red blood cell transfusions in very low birth weight infants based on clinical risk factors.

OBJECTIVE: To describe the clinical factors most predictive of red blood cell transfusion in very low birth weight (VLBW) infants. STUDY DESIGN: Retrospective review of VLBW infants cared for at a single level III NICU during a two year period, n = 199. RESULTS: Overall transfusion requirement was 4.6 +/- 6.2 transfusions/infant/hospital course. Length of hospital stay, days of mechanical ventilation, requirement for dopamine support, birth weight, initial hematocrit, periventricular leukomalacia and necrotizing enterocolitis all independently correlated with number of transfusions and donors. Bronchopulmonary dysplasia and patent ductus arteriosus were associated with donor but not transfusion number. CONCLUSIONS: Our data characterize the population of VLBW infants with the greatest blood transfusion and donor requirement. Further investigation is needed to target this population for interventions to reduce blood exposure.

Routine use of fentanyl infusions for pain and stress reduction in infants with respiratory distress syndrome.

OBJECTIVE: To determine whether fentanyl infusions given to premature infants with respiratory distress syndrome reduce stress and improve long- and short-term outcome. METHODS: Twenty premature infants undergoing mechanical ventilation for respiratory distress syndrome were randomly assigned, in a double-blind fashion, to receive fentanyl by continuous infusion or a volume-matched placebo infusion. A behavioral state score was used to assess the infants' behavior. Cortisol and 11-deoxycortisol levels were measured as physiologic markers of stress. Urinary 3-methyl histidine/creatinine molar ratio was determined and the fractional excretion of urea was measured to assess catabolic state. Ventilatory indexes were recorded for each infant. RESULTS: Infants receiving fentanyl showed significantly lower behavioral state scores (p < 0.04) and lower heart rates (p < 0.001) than those receiving placebo. 11-Deoxycortisol levels were lower in the fentanyl group on days 3, 4, and 5 of the study (p < 0.003). 3-Methyl histidine/creatinine ratios and fractional excretion of urea were not significantly different between the two groups. On the third day of the study, infants receiving fentanyl required a higher ventilator rate (p < 0.01), higher peak inspiratory pressures (p < 0.001), and higher positive end-expiratory pressure (p < 0.0001) than those receiving placebo. There was no difference in long-term outcome with respect to the incidence of bronchopulmonary dysplasia, intraventricular hemorrhage, or sepsis or with respect to the duration of ventilator use. CONCLUSIONS: Although there was a reduction in stress markers in the infants receiving fentanyl, we were unable to demonstrate an improvement in catabolic state or long-term outcome. In addition, the infants receiving fentanyl required higher ventilatory support in the early phase of respiratory distress syndrome than did those receiving placebo.

Soluble interleukin-2 receptor as a predictor of neonatal sepsis.

We prospectively measured soluble interleukin-2 receptor levels in 56 premature infants with suspected sepsis and demonstrated significant differences between those with positive results on blood, urine, or cerebrospinal fluid cultures, and those with negative results. Soluble interleukin-2 receptor levels can be used to facilitate the diagnosis of sepsis in premature infants with negative blood culture results.

Umbilical venous catheters: evaluation of radiographs to determine position and associated complications of malpositioned umbilical venous catheters.

To evaluate the ability of radiography to detect malpositioned umbilical venous catheters in the left atrium and to determine the frequency of associated complications, we retrospectively compared radiographs and echocardiograms of 31 infants who had malpositioned catheters in the left atrium by echocardiography (cases) and 31 infants who had properly positioned catheters (controls). The case and control infants were of similar gestational age and birthweight (gestational age, 32 +/- 5 weeks; birthweight, 1672 +/- 899 g for cases; gestational age, 31 +/- 5 weeks; birthweight, 1666 +/- 958 g for controls). Malposition was defined as the catheter tip above the seventh thoracic vertebra by radiography. Radiography had sensitivity of 45%, specificity of 87%, positive predictive value of 77%, negative predictive value of 61%, accuracy of 66%, and prevalence of 50%. Thrombus formation in the heart was detected in 8 of 31 (26%) of cases and in 1 of 31 (3%) of controls (p = 0.03). The incidence of complications, such as necrotizing enterocolitis, culture-positive sepsis, total number of sepsis cases, thrombocytopenia, embolism to extremities, and hematuria were similar in both groups (difference not significant). These results suggest that radiography is unreliable in determining incorrect catheter placement. Catheters malpositioned in the left atrium were associated with thrombus formation. There was no significant increase in systemic complications in the infants with a malpositioned catheter.

Nitrogen balance in extremely low birth weight infants with nonoliguric hyperkalemia.

We measured nitrogen balance and urinary 3-methylhistidine molar ratios in 33 extremely low birth weight infants (12 with hyperkalemia and 21 without) for the first 3 days of life. Although all infants were in negative nitrogen balance during the study, there was no difference in the degree of negative nitrogen balance between the two groups. There was also no difference in the 3-methylhistidine/creatinine molar ratios, indicating that muscle protein catabolism did not differ. We conclude that it is unlikely that catabolism contributes to the development of nonoliguric hyperkalemia in extremely low birth weight infants.

Decreased erythrocyte Na+,K(+)-ATPase activity associated with cellular potassium loss in extremely low birth weight infants with nonoliguric hyperkalemia.

To determine whether a shift of potassium ions from the intracellular space to the extracellular space accounts, in part, for the hyperkalemia seen in extremely low birth weight infants, we examined potassium concentration in serum and erythrocytes from extremely low birth weight infants with hyperkalemia (n = 12) or with normokalemia (n = 27). In addition, to determine whether the shift of potassium was associated with low sodium-potassium-adenosinetriphosphatase (Na+,K(+)-ATPase) activity, we studied the activity of ATPase in the last 16 infants enrolled in the study. Fluid intake and output were measured during the first 3 days of life. Infants were considered to have hyperkalemia if the serum potassium concentration was 6.8 mmol/L or greater. Blood was obtained daily for intracellular sodium and potassium levels by means of lysis of erythrocytes. The remaining erythrocyte membranes were frozen and analyzed for Na+,K(+)-ATPase activity. There were significantly lower intracellular potassium/serum potassium ratios in the infants with hyperkalemia for each day of the 3-day study (p < 0.001). In the hyperkalemic group, there was lower Na+,K(+)-ATPase activity than in the infants with normokalemia (p = 0.006). Low Na+,K(+)-ATPase activity was associated with lower intracellular potassium/serum potassium ratios (p = 0.006), higher serum potassium values (p = 0.02), and lower intracellular potassium concentration (p = 0.009). The urinary data demonstrated that there was no difference in glomerulotubular balance between the two groups. We conclude that nonoliguric hyperkalemia in extremely low birth weight infants may be due, in part, to a shift of potassium from the intracellular space to the extracellular space associated with a decrease in Na+,K(+)-ATPase activity.

Soluble interleukin-2 receptor levels in infants with bronchopulmonary dysplasia.

Soluble interleukin-2 receptors (sIL2R) in plasma have been identified as a marker of lymphocyte activation. Lymphocyte activation as a manifestation of inflammation may be important in the pathogenesis of bronchopulmonary dysplasia (BPD). To test the hypothesis that infants with BPD have higher sIL2R levels, 12 infants with or at risk of developing BPD (GA +/- SD, 27 +/- 5 weeks; BW +/- SD 1,053 +/- 733 g) had plasma sIL2R levels determined and were compared to 20 infants being ventilated for respiratory distress syndrome (RDS) (GA +/- SD, 28 +/- 3.5 weeks; BW +/- SD, 1,133 +/- 390 g: P = NS for both GA and BW, t test). Tracheal aspirates in both groups were also analyzed for sIL2R levels. To control for the effects of postnatal age (PNA) and study weight (SW) on the sIL2R levels, another group of 16 nonventilated babies (NVB) had plasma analyzed for sIL2R (PNA +/- SD: 39 +/- 40 days NVB vs. 48 +/- 36 days BPD; P = NS); (SW +/- SD: 1391 +/- 250 g NVB vs. 1212 +/- 700 g BPD; P = NS). The following data were obtained for the plasma sIL2R levels (mean +/- SEM U/mL): RDS controls, 1,231 +/- 80; BPD infants, 1,790 +/- 120; NVB controls, 1,319 +/- 76; P = 0.0005 RDS vs. BPD and P = 0.002 BPD vs. NVB. There was no significant difference in the sIL2R levels for the infants at risk of developing BPD vs. the infants with established BPD. Also, when analyzed separately, infants at risk of BPD and the infants with established BPD had higher sIL2R levels than the RDS and NVB controls. No differences were noted in the tracheal sIL2R levels in the BPD vs. RDS groups. These data indicate that infants with BPD had significantly higher sIL2R levels in plasma than either RDS or NVB controls. Therefore, lymphocyte activation may play a role in the pathogenesis of BPD.

Prolonged apnea and oxyhemoglobin desaturation in asymptomatic premature infants.

Seventy-eight longitudinal four-channel recordings of heart rate, thoracic impedance, nasal thermistry, and pulse oximetry were performed on 26 asymptomatic premature infants (gestational age, 29.9 +/- 1.58 weeks; birth weight, 1,753 +/- 226 grams; postconceptional age, 34.3 +/- 2.0 weeks; postnatal age, 4.41 +/- 2.40 weeks; all values mean +/- SD). Tracings were scored for central and obstructive apnea, bradycardia, periodic breathing, apnea density, and prolonged apnea. The studies demonstrated 585 episodes (7.41/recording) of oxyhemoglobin desaturation with less than 90%. Recordings had a mean of 16.1 episodes of central apnea, 3.04 episodes of obstructive apnea, and 2.34 episodes of bradycardia. Periodic breathing and short obstructive apneas correlated significantly with the total number of oxyhemoglobin desaturations of less than 80% and 90%. Episodes of prolonged apnea were seen in 20 of 78 recordings. In the latter a significantly higher number of total desaturations (less than 90%), desaturations less than 80% and 90% in association with apnea and with bradycardia, longer desaturations, desaturations during sleep, and isolated bradycardia were observed. Variations in heart rate, thoracic impedance, nasal air flow, and pulse oximetry are associated with episodes of oxyhemoglobin desaturation in asymptomatic premature infants. These infants, although asymptomatic, may be at risk for impaired tissue oxygenation.

Fused eyelids in the extremely premature infant: multivariate analysis of survival and outcome.

The presence of fused eyelids at birth in the extremely low birthweight infant (less than 1000 gm) is often regarded by physicians as an indication of nonviability. This is especially true for the pediatrician who does not have routine exposure to extremely premature infants and may use the presence of fused eyelids to influence the level of resuscitation afforded the infant in the first crucial minutes following birth. Unfortunately, there are scant data in the literature to guide general pediatricians with regard to this issue. The purpose of this study was to examine, with the aid of multivariate statistical analysis, the survival and combined outcome score in extremely premature infants with and without fused eyelids. The combined outcome was a composite of several outcome variables (intraventricular hemorrhage, bronchopulmonary dysplesia, and retinopathy of prematurity); survival was defined employing the standard definition of neonatal survival, that is, alive at 28 days post natal age. Combined outcome and survival were analyzed with regard to several independent variables (birthweight, gestational age, and 5-minute Apgar scores, mode of delivery, race, sex, and maternal age). A regression analysis was performed to determine the effect of the independent variables on the combined outcome. A separate multivariate logistic regression analysis was employed to determine the effect of the same independent variables on neonatal survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Pneumograms in premature infants: a study of longitudinal data.

In order to define longitudinal data in premature infants, impedance pneumograms were performed weekly on 23 healthy premature infants. Studies were performed while infants remained hospitalized and at the discretion of the attending physician following discharge. A total of 97 studies were obtained on the study group. The recordings were analyzed for percentage of sleep time spent in periodic breathing, apnea density, and duration of longest apneic pause. Infants in this study demonstrated decreased percent of periodic breathing and decreased apnea density with increased maturation; longest pause per recording was independent of postconceptional age. Results from this study provide data to assist in the evaluation of pneumograms in the premature infant.

Case report: congenital syphilis associated with persistent pulmonary hypertension of the newborn.

A Newborn infant with prenatally acquired syphilis and persistent pulmonary hypertension is described. The patient had clinical, serologic, and radiologic evidence of syphilis at birth. He demonstrated right to left shunting of blood at the level of the foramen ovale, and responded to hyperventilation. Despite adequate oxygenation with hyperventilation, the patient expired after five days of therapy due to a progressive pneumonia and hypotension. The clinician should be aware of this unusual mode of presentation and anticipate the potential need for early aggressive intervention.