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.

Communicating with parents of premature infants: who is the informant?

OBJECTIVES: To determine what sources of information are most helpful for neonatal intensive care unit (NICU) parents, who provides NICU parents with the information, and also what expectations parents have regarding obtaining information. STUDY DESIGN: A 19-item questionnaire was given to the parents of infants 32 weeks or younger prior to discharge from the NICU. RESULTS: Out of the 101 parents who consented, almost all of the parents (96%) felt that 'the medical team gave them the information they needed about their baby' and that the 'neonatologist did a good job of communicating' with them (91%). However, the nurse was chosen as 'the person who spent the most time explaining the baby's condition, 'the best source of information,' and the person who told them 'about important changes in their baby's condition' (P<0.01). CONCLUSION: Although the neonatologist's role in parent education is satisfactory, the parents identified the nurses as the primary source of information.

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.

Immaturity or starvation? Longitudinal study of leptin levels in premature infants.

OBJECTIVE: Leptin, the protein product of the ob gene, is a potential placental growth factor and is integral to the body's system of energy regulation as shown in animal models. Premature infants are especially vulnerable to changes in energy regulation, and several studies have demonstrated a rapid fall in leptin values at birth. The purpose of the present investigation was to measure leptin levels in premature infants throughout hospitalization. METHODS: Eligible infants were less than 32 weeks' gestation, appropriate for gestational age, and hospitalized at Christiana Hospital Special Care Nursery. Serum samples for leptin analysis were drawn within 24 h of birth and twice a week thereafter until discharge. Concurrent growth measurements were obtained with each leptin sample. Body mass index, ponderal index, and midarm circumference/head circumference ratios were calculated to assess growth. RESULTS: Leptin levels were low and remained low for the duration of the premature infants' hospitalization (mean +/- SD = 1.35 +/- 0.63 ng/ml/ml, range 0-3.06). After controlling for weight, there was a small (r(2) = 0.1, p < 0.00001) but significant correlation between leptin and postnatal age after 4 days of age. Despite an increase in caloric intake during the study period, there was no relationship between leptin and caloric intake. There were significant negative correlations between measurements of growth and both leptin and the leptin/weight ratio. Maternal diabetes and the use of steroids had small but significant effects on the leptin/weight ratio. CONCLUSION: In this population of predominantly female premature infants, leptin levels were very low as compared to term infants, children and adults, and did not change appreciably over the study period. The low leptin levels seen in these premature infants are similar to those levels seen in malnourished adults, anorexics, and in animal models of starvation. We speculate that a critical adipose store needs to be reached before increased amounts of leptin can be adequately produced. Persistently low leptin levels may also reflect an immaturity in the hypothalamic-pituitary-adrenal axis.

Leptin levels in preterm human breast milk and infant formula.

OBJECTIVE: Leptin, a hormone present in breast milk, is involved in energy regulation and metabolism. The purpose of this investigation was to determine whether leptin is present in either preterm breast milk (PBM) or preterm formula (PF). The effects of delivery methods and pasteurization on leptin levels also were evaluated. METHODS: PBM samples were obtained from 29 mothers who delivered infants at between 23 and 34 weeks' gestation. Leptin levels were measured in PBM and PF with the use of a radioimmunoassay specific for human and bovine leptin, respectively. Milk samples were pasteurized by fast- and slow-heating methods. PBM and PF spiked with human leptin were delivered through catheters by bolus and continuous administration to determine the effects of delivery method on recoverable leptin levels. RESULTS: Median PBM leptin concentration was 5.28 ng/mL (intraquartile range: 24.79). Birth gestational age, birth weight, and gender of the infant did not significantly influence PBM leptin levels. Neither bolus nor continuous feeding practices affected leptin levels in PBM or spiked PF. However, pasteurization significantly reduced the amount of detectable leptin in PBM. CONCLUSIONS: PBM leptin levels were highly variable and similar to levels reported for term breast milk. There was no effect of postnatal age on PBM leptin concentrations. Sterilization decreased detectable leptin levels, whereas feeding practices had no adverse effect on the quantity of leptin delivered. Although no infant formula contained leptin, leptin could be added to formula and delivered through various feeding methods without loss.

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.

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.

Placental leptin: an important new growth factor in intrauterine and neonatal development?

BACKGROUND: Leptin, the protein product of the ob gene, is produced by the adipocyte and seems to function as a link between adiposity, satiety, and activity. Leptin has also been found to be necessary for pubertal development, conception, and pregnancy in mice, and is increased in prepubertal children, independent of adiposity, suggesting a role in childhood growth and development. This study investigated 100 mother/newborn pairs to determine the role of leptin in neonatal development. Placental tissue was assayed for leptin mRNA to evaluate it as a source of leptin production in utero. METHODS: One hundred mother/newborn pairs were enrolled in this study. Radioimmunoassay was performed for leptin on maternal venous and newborn cord blood. Leptin concentrations were measured in 43 children in Tanner stages 1 and 2 as a control group. Placental tissue was obtained from five mothers and assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR). Human placental cell lines JAR and JEG-3 were also assayed for leptin mRNA expression. RESULTS: Leptin was present in all newborns studied at a mean concentration of 8.8 ng/mL (+/-9.6 standard deviations). Leptin concentrations in cord blood correlated with newborn weight (r = .51), body mass index (BMI) (r = .48), and arm fat (r = .42). There was no correlation between leptin and insulin. When statistically covarying for adiposity for newborns and Tanner stages 1 and 2 children, newborns had greater concentrations of leptin (mean, 10.57 ng/mL) than children (mean, 3.04 ng/mL). Leptin was present in all mothers at a mean value of 28.8 ng/mL (+/-22.2 standard deviations). Leptin concentration correlated with prepregnancy BMI (r = .56), BMI at time of delivery (r = .74), and arm fat (r = .73). Maternal leptin correlated with serum insulin (r = .49). There was no correlation between maternal and newborn leptin concentrations. Thirteen percent of newborns had higher leptin concentrations than their mothers. Placental tissue from five separate placentas expressed leptin mRNA at comparable or greater levels than adipose tissue. Two human trophoblastic placental cell lines, JAR and JEG-3, also expressed leptin mRNA. CONCLUSIONS: The correlation between leptin and adiposity found in children and adults was also found in newborns. Serum leptin concentrations in newborns were increased more than three-fold compared with children in Tanner stages 1 and 2 when controlling for adiposity, suggesting that leptin concentrations in the newborn are not explained by adiposity alone. Maternal leptin concentrations correlated with measures of adiposity at delivery but did not correlate with newborn adiposity or leptin. Leptin mRNA was expressed both in placental tissue and in two human placental cell lines. These data suggest that leptin has a role in intrauterine and neonatal development and that the placenta provides a source of leptin for the growing fetus.

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.