Neonatologists' Perspectives on Exploring Parental Spirituality in Prenatal Consultations.

Background and Objectives: Values of religion, spirituality, and faith (RSF) are central to decision making for many parents facing extremely preterm labor or prenatal diagnoses of potentially life-limiting congenital anomalies. Neonatologists' opinions and comfort with discussing parental RSF are not well known. We sought to understand neonatologists' current practices and perceptions of exploring parental RSF in prenatal consultations. Methods: A retrospective chart review was performed at a single U.S. academic institution to evaluate the inclusion of spiritual terminology in documentation. All mothers who were admitted with anticipated extremely preterm delivery as well as those with prenatal diagnoses of potentially life-limiting congenital anomalies were included in analysis. After chart review, an anonymous survey was distributed to neonatology attendings and fellows to examine perspectives on exploring parental RSF. Results: The chart review indicated that RSF terminology was absent from the documentation of all prenatal consultations performed by neonatology. Sixty-five percent of survey respondents considered RSF important in their personal lives and 47% considered RSF important in clinical practice. The three most significant barriers to exploring RSF were lack of training or education in spiritual care, differences between physicians' and patients' personal beliefs, and insufficient time. Conclusions: Our study highlights a gap between the goal for prenatal counseling in cases of extreme prematurity and potentially life-limiting congenital anomalies and current practices that frequently exclude the values most important to many parents. Lack of training in spiritual care is a significant barrier to neonatologists exploring parental RSF.

Intrauterine growth restriction increases TNF α and activates the unfolded protein response in male rat pups.

Intrauterine growth restriction (IUGR) programs adult disease, including obesity and insulin resistance. Our group previously demonstrated that IUGR dysregulates adipose deposition in male, but not female, weanling rats. Dysregulated adipose deposition is often accompanied by the release of proinflammatory signaling molecules, such as tumor necrosis factor alpha (TNF α ). TNF α contributes to adipocyte inflammation and impaired insulin signaling. TNF α has also been implicated in the activation of the unfolded protein response (UPR), which impairs insulin signaling. We hypothesized that, in male rat pups, IUGR would increase TNF α , TNFR1, and components of the UPR (Hspa5, ATF6, p-eIF2 α , and Ddit3) prior to the onset of obesity. We further hypothesized that impaired glucose tolerance would occur after the onset of adipose dysfunction in male IUGR rats. To test this hypothesis, we used a well-characterized rat model of uteroplacental insufficiency-induced IUGR. Our primary findings are that, in male rats, IUGR (1) increased circulating and adipose TNF α , (2) increased mRNA levels of UPR components as well as p-eIF2a, and (3) impaired glucose tolerance after observed TNF α increased and after UPR activation. We speculate that programmed dysregulation of TNF α and UPR contributed to the development of glucose intolerance in male IUGR rats.

A randomized, masked study of weekly erythropoietin dosing in preterm infants.

OBJECTIVE: To compare reticulocyte responses of once-per-week erythropoietin (EPO) dosing with 3-times-a-week dosing in preterm infants. STUDY DESIGN: Infants weighing ≤ 1500 g and ≥ 7 days of age were randomized to once-per-week EPO, 1200 U/kg/dose, or 3-times-a-week EPO, 400 U/kg/dose, subcutaneously for 4 weeks, along with iron and vitamin supplementation. Complete blood counts, absolute reticulocyte counts (ARCs), transfusions, phlebotomy losses, and adverse events were recorded. RESULTS: Twenty preterm infants (962 ± 55 g, 27.9 ± 0.4 weeks, 17 ± 3 days of age) were enrolled. Groups were similar at baseline. Infants in both groups had increased ARCs, which were similar between treatment groups at the start and end of 4 weeks. Hematocrit remained stable, and similar numbers of transfusions were administered. No adverse effects of either dosing schedule were noted. CONCLUSIONS: Preterm infants respond to weekly EPO by increasing ARCs and maintaining hematocrit. We speculate that once-per-week EPO dosing might be beneficial to preterm infants requiring increased erythropoiesis.

Erythropoietin increases reticulocyte counts and maintains hematocrit in neonates requiring surgery.

BACKGROUND: Limited erythropoietin (Epo) production diminishes neonates' ability to regenerate blood removed by phlebotomy. Neonates requiring surgery are at risk to receive multiple transfusions. We sought to determine if recombinant Epo administration to neonates requiring surgery would stimulate erythropoiesis. METHODS: Infants were randomized in double-masked fashion to receive Epo (200 units kg(-1) d(-1)) or placebo for 14 days. Complete blood count, absolute reticulocyte count (ARC), phlebotomy losses, and transfusions were measured during the study period. Infants were transfused using a strict transfusion protocol. RESULTS: In the Epo group (n = 10, 2034 +/- 308 g, 8 +/- 2 days old; mean +/- SEM), ARC increased significantly, whereas in the placebo group (n = 10, 2400 +/- 184 g, 7 +/- 2 days old), ARC remained low. Hematocrits in the Epo group trended upward from 34.4 1.7% to 37.3 1.9% (although not statistically significant) despite phlebotomy losses of 53 +/- 12 mL/kg. Hematocrits in the placebo group were 35.9 1.8% and 33.2 1.6% on days 1 and 15, respectively, with phlebotomy losses of 27 +/- 5 mL/kg. There were no differences in absolute neutrophil counts or platelet counts between groups at the end of the study. No adverse effects were noted. CONCLUSIONS: Infants randomized to Epo increased reticulocyte counts and hematocrits without adverse effects. Erythropoietin administration may provide an adjunct to present care in decreasing or eliminating erythrocyte transfusions in surgical neonates.

Erythropoietin concentrations and neurodevelopmental outcome in preterm infants.

OBJECTIVE: Erythropoietin therapy is effective in decreasing transfusions to varying degrees in preterm infants. Recent animal studies using erythropoietin doses to achieve serum concentrations > 1000 mU/mL report neuroprotective effects. We evaluated the relationship between erythropoietin concentrations and neurodevelopmental outcome in extremely low birth weight infants. METHODS: Preterm infants who weighed < or = 1000 g at birth were randomly assigned to erythropoietin (400 U/kg 3 times per week) or placebo/control. Therapy was initiated by 4 days after birth and continued through the 35th postmenstrual week. All infants received supplemental parenteral and enteral iron. Peak serum erythropoietin concentrations were obtained every 2 weeks. Follow-up evaluation included anthropometric measurements, Bayley scales of mental and psychomotor development, neurologic examination, and determination of overall neurodevelopmental impairment. Data were collected at 18 to 22 months' corrected age by certified examiners who were masked to the treatment group. Analyses were performed to identify correlations between erythropoietin concentrations and outcomes. RESULTS: Sixteen extremely low birth weight infants were enrolled; 1 infant died at 2 weeks (placebo/control), and 15 had erythropoietin concentrations measured (7 erythropoietin, 8 placebo/control). Peak erythropoietin concentrations were significantly different between groups during the study (erythropoietin: 2027 +/- 1464 mU/mL; placebo/control: 26 +/- 11 mU/mL). Before follow-up, 3 infants died (1 erythropoietin, 2 placebo/control), and 12 were available for follow-up (6 erythropoietin, 6 placebo/control). At 18 to 22 months' follow-up, none of the erythropoietin recipients and 2 of the placebo/control infants had Mental Development Index scores < 70. Erythropoietin recipients had Mental Development Index scores of 96 +/- 11, and placebo/control infants had Mental Development Index scores of 78 +/- 7. Psychomotor Development Index scores were similar between groups (87 +/- 13 vs 80 +/- 7). There were no differences between groups with respect to anthropometric measurements. Two of 6 infants in the erythropoietin group and 4 of 6 infants in the placebo/control group had some form of neurodevelopmental impairment. Posthoc analysis showed that infants with erythropoietin concentrations > or = 500 mU/mL had higher Mental Development Index scores than infants with erythropoietin concentrations < 500 mU/mL. CONCLUSIONS: Erythropoietin concentrations did not correlate with Psychomotor Development Index or overall incidence of neurodevelopmental impairment; however, infants with elevated erythropoietin concentrations had higher Mental Development Index scores than those with lower erythropoietin concentrations. Close follow-up of infants who are enrolled in large, multicenter, high-dose erythropoietin studies is required to determine whether a correlation exists between elevated erythropoietin concentrations and improved neurodevelopmental outcome.