Gastroschisis: small hole, big cost.

BACKGROUND/PURPOSE: This study was designed to assess the outcome and financial costs incurred for the treatment of gastroschisis. METHODS: A retrospective analysis was conducted of all patients with gastroschisis at a single institution over the past decade (n = 69). Hospital costs were determined and standardized to December 2001 dollars. RESULTS: Of the 69 patients, average gestational age at delivery was 35.9 weeks. Thirty-six patients had a primary fascial closure; 33 had a silo placed. The mean time to first feeding was 22 days and full feeding, 33 days. Average length of stay was 47 days. There were 3 deaths (2 shortly after birth, and one 131 days later owing to sepsis). The average cost of hospitalization and physician fees for patients with gastroschisis was $123,200. Using multivariate regression analysis, significant variables (P <.05) associated with cost of hospitalization were number of operative procedures, ventilatory days, male gender, and length of stay. Room expenses (43%), physician fees (15%), respiratory and pulmonary care (10%), and supply and devices (10%) made up the majority of costs. CONCLUSIONS: Cost of care associated with treatment for gastroschisis is high. Strategies designed to reduce cost must limit gastrointestinal, respiratory, and operative complications and reduce length of stay.

Thrombopoietin in the thrombocytopenic term and preterm newborn.

OBJECTIVES: Neonatal thrombocytopenia occurs commonly in neonatal intensive care units. The role of the thrombopoietin (Tpo) system in normal neonatal platelet regulation and neonatal thrombocytopenia is not well understood. The purpose of our study was to: 1) determine the normal Tpo level at birth in healthy nonthrombocytopenic term (NTT) and nonthrombocytopenic preterm (NTP) infants and in infants born to women with preeclampsia; and 2) measure Tpo levels in infants during and after the resolution of thrombocytopenia. Characterizing Tpo levels in the healthy and thrombocytopenic newborn is an important step in furthering our understanding of the pathophysiology of neonatal thrombocytopenia. METHODS: This study is comprised of 2 parts. For the first part, cord blood was obtained at birth from both term (gestational age [GA]: 38-42 weeks) and preterm (GA: 25-36 weeks) infants. If birth platelet levels were >/=140 x 10(3)/microL and the infant fit criteria for being normal, or if the infant was born to a women with preeclampsia, Tpo levels were measured. For the second part, serial Tpo levels and concomitant platelet counts (Plts) were measured in both preterm and term infants during a period of marked thromboctyopenia (Plt < 100 x 10(3)/microL) until its resolution (Plt >/= 140 x 10(3)/microL). RESULTS: Median cord blood Tpo levels from NTP infants (n = 35) were higher than those of NTT infants (n = 32; 95 pg/mL vs 48 pg/mL, respectively). In addition, preterm infants born to women with preeclampsia (n = 11) had lower Tpo levels than NTP infants with a similar GA (<41 pg/mL vs 95 pg/mL). For infants with marked thrombocytopenia, median Tpo levels during thrombocytopenia were similar between term (n = 12) and preterm (n = 14) groups (223 pg/mL and 179 pg/mL, respectively), with the majority of individuals showing a decrease in Tpo with resolution of thrombocytopenia. Within each group, there was large variability in the Tpo response to thrombocytopenia. IMPRESSION: These data show that the Tpo system is intact in NTP and NTT neonates. Preeclampsia may be an example of a disorder that perturbs this system. The great variability in Tpo levels seen in infants during thrombocytopenia may be related to the mechanism of thrombocytopenia. The finding that, in general, Tpo levels decreased with resolution of thrombocytopenia is consistent with what has been described in adults and children.

Neurodevelopmental outcome of prematurely born children treated with recombinant human erythropoietin in infancy.

OBJECTIVE: To compare the neurodevelopmental outcome of premature infants treated with recombinant human erythropoietin with that of control infants. STUDY DESIGN: A total of 20 treated infants and 20 control infants who had completed randomized, double-blind, placebo-controlled studies of recombinant human erythropoietin as treatment for anemia of prematurity were followed for growth and developmental outcome in an intensive care nursery follow-up program. Infants were assessed by standard developmental tests. RESULTS: No differences were found between groups for neurologic outcome, cognitive outcome, or growth patterns. All infants treated with recombinant human erythropoietin were neurologically normal. The rate of cognitive deficits was similar in the two groups. CONCLUSION: In this small sample we did not see differences in neurodevelopmental outcome between infants treated with recombinant human erythropoietin and control infants.

Plasma thyroid hormones in premature infants: effect of gestational age and antenatal thyrotropin-releasing hormone treatment. TRH Collaborative Trial Participants.

Thyroid hormones are important for both perinatal adaptation and long-term psychomotor development; however, there is limited information on the effects of extreme prematurity and antenatal TSH-releasing hormone (TRH) treatment on pituitary-thyroid function. In this study we assayed plasma triiodothyronine (T3) and TSH in infants who were part of a collaborative trial of antenatal maternal TRH therapy. Within the control population (n = 166), infants of 24-28-wk and 28-32-wk gestational age had comparable levels of T3 (0.94 and 1.06 nmol/L, respectively) and TSH (5.7 and 7.2 mU/L) at birth, but the increases at 2 h and subsequent T3 levels were less in the 24-28 wk versus 28-32-wk gestation infants. In the TRH-treated group (n = 131), T3 was lower in the first day for infants delivered 7-72 h after antenatal TRH compared with control infants. TSH at birth was approximately 3.5-fold greater for infants delivered at 0-6 h after the last TRH dose compared with the control group and was suppressed in infants delivering at 7-36 h. T3 and TSH levels were not different between control and TRH-treated groups at 3-28 d of age. In TRH stimulation tests on d 28, control and TRH-treated groups had similar peak levels of TSH and incidence of exaggerated response (TSH > or = 35 mU/L). We conclude that extremely premature infants have a reduced postnatal surge in TSH and T3 and maintain lower T3 concentrations, probably reflecting tertiary hypothyroidism. The stimulatory and suppressive effects of antenatal TRH treatment observed at birth are transient and do not affect pituitary-thyroid responsiveness at 28 d of age.

Antenatal thyrotropin-releasing hormone to prevent lung disease in preterm infants. North American Thyrotropin-Releasing Hormone Study Group.

BACKGROUND: Pulmonary disease is common in preterm infants, despite antenatal glucocorticoid therapy. The addition of antenatal thyrotropin-releasing hormone therapy has been reported to decrease pulmonary morbidity in these infants. METHODS: We enrolled 996 women at 13 North American centers who were in preterm labor at <30 weeks' gestation in a double-blind, placebo-controlled, randomized trial of antenatal thyrotropin-releasing hormone, given intravenously in four doses of 400 microg each at eight-hour intervals. The primary outcome was chronic lung disease or death of the infant on or before the 28th day after delivery, and secondary outcomes were respiratory distress syndrome and chronic lung disease or death at 36 weeks' postmenstrual age. Complete data were available for 981 women and their 1134 live-born infants. The 769 infants born at < or = 32 weeks' gestation were defined as the group at risk. RESULTS: There were no significant differences between the at-risk treatment and placebo groups in mean (+/-SD) birth weight (1109+/-354 vs. 1097+/-355 g), gestational age (27.9+/-2.1 vs. 27.9+/-2.1 weeks), sex, or race. The frequencies of respiratory distress syndrome (66 percent vs. 65 percent), death at 28 days (11 percent vs. 11 percent), chronic lung disease or death at 28 days (45 percent vs. 42 percent) and at 36 weeks (32 percent vs. 34 percent), and other neonatal complications as well as the severity of lung disease were not significantly different in the at-risk treatment and placebo groups. Similarly, there were no differences in outcome between the treatment and placebo groups for the infants born at >32 weeks' gestation. CONCLUSIONS: In preterm infants at risk for lung disease, antenatal administration of thyrotropin-releasing hormone and glucocorticoid is no more beneficial than glucocorticoid alone.

The effects of patient volume and level of care at the hospital of birth on neonatal mortality.

OBJECTIVE: To examine the effects of neonatal intensive care unit (NICU) patient volume and the level of NICU care available at the hospital of birth on neonatal mortality. DESIGN: Birth certificate data linked to infant death certificates and to infant discharge abstracts were used in a logistic regression model to control for differences in each patient's clinical and demographic risks. Hospitals were classified by the level of NICU care available (no NICU: level I; intermediate NICU: level II; expanded intermediate NICU: level II+: tertiary NICU: level III) and by the average patient census in the NICU. SETTING: All nonfederal hospitals in California with maternity services. PATIENTS: All births in nonfederal hospitals in California in 1990 (N=594104), 473209 (singletons only) of which were successfully linked with discharge abstracts. Of these infants, 53229 were classified as likely NICU admissions. MAIN OUTCOME MEASURES: Death within the first 28 days of life, or within the first year of life, if continuously hospitalized. RESULTS: Patient volume and level of NICU care at the hospital of birth both had significant effects on mortality. Compared with hospitals without an NICU, infants born in a hospital with a level III NICU with an average NICU census of at least 15 patients per day had significantly lower risk-adjusted neonatal mortality (odds ratio, 0.62; 95% confidence interval, 0.47-0.82; P=.002). Risk-adjusted neonatal mortality for infants born in smaller level III NICUs, and in level II+ and level II NICUs, regardless of size, was not significantly different from hospitals without an NICU, and was significantly higher than hospitals with large level III NICUS. CONCLUSIONS: Risk-adjusted neonatal mortality was significantly lower for births that occurred in hospitals with large (average census, >15 patients per day) level III NICUs. Despite the differences in outcomes, costs for the birth of infants born at hospitals with large level III NICUs were not more than those for infants born at other hospitals with NICUs. Concentration of high-risk deliveries in urban areas in a smaller number of hospitals that could provide level III NICU care has the potential to decrease neonatal mortality without increasing costs.

Potential for treatment of anemia of prematurity with recombinant human erythropoietin.

Anemia of prematurity (AOP) results from several interacting processes, including phlebotomy losses, a temporary failure to release erythropoietin in response to anemia, a short life span of erythrocytes, and rapid growth of body mass and, hence, blood volume after the first few weeks of life. Infants with AOP have erythroid progenitors that respond to erythropoietin in vitro, suggesting that treatment with recombinant erythropoietin might reduce the need for transfusions for AOP. Many pilot studies were needed to define the dose of recombinant erythropoietin (500 to 750 U/kg/wk) that stimulated the early onset of erythropoiesis in infants with AOP. Three large controlled trials have demonstrated that recombinant erythropoietin therapy reduces transfusions in AOP and is apparently safe. Unresolved issues include the ideal dose, the optimal nutrition needed during therapy, the target population, and timing of the start of treatment.

Erythropoietin therapy for extremely premature infants.

It has been well established that erythropoietin (EPO) in the dosage range of 500 units/kilo/week and perhaps slightly lower doses will produce a brisk reticulocyte response in infants with anemia of prematurity. Controlled clinical trials to demonstrate that this therapy can result in significant reductions in transfusion in these babies face several complex issues of experimental design. 1. Should the study population be relatively bigger, healthier babies (< 1500 grams birth weight, not on ventilatory support) who have lower transfusion requirements, or smaller sicker infants (< 1250 grams birth weight and on ventilators) who have higher transfusion requirements? These infants will need adequate nutrition and liberal supplementation with iron if they are to respond adequately, but the sicker smaller infants will take longer to meet these nutritional goals. 2. Timing is important because spontaneous recovery occurs at about 35 to 36 weeks of corrected gestational age, so to be effective, therapy must start before 33 weeks of gestational age and preferably earlier than that. 3. Since the end point is transfusion, the criteria used for transfusions become a critical issue. If liberal transfusion criteria are used, the study will be doubly biased in favor of EPO efficacy. There will be an increased number of transfusion events in the control population and spontaneous recovery from the anemia of prematurity will be overly suppressed in the control population. It's likely that the current transfusion criteria are too liberal thus introducing these biases to experimental design.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost effects of surfactant therapy for neonatal respiratory distress syndrome.

OBJECTIVE: To examine the cost effects of a single dose (5 ml/kg) of a protein-free synthetic surfactant (Exosurf) as therapy for neonatal respiratory distress syndrome, for both rescue and prophylactic therapy. RESEARCH DESIGN: Nonblinded, randomized clinical trials of both rescue and prophylactic therapy. Regression analyses were used to control for the independent effects of sex, multiple birth, delivery method, birth weight, and surfactant therapy. SETTING: The prophylactic trial was conducted at a university medical center only; the rescue trial also included a tertiary community hospital. PATIENTS: Prophylaxis was administered immediately after birth to 36 infants (38 control subjects) with birth weights between 700 and 1350 gm. Rescue therapy was administered at 4 to 24 hours of age to 53 infants (51 control subjects) with established respiratory distress syndrome and birth weights > or = 650 gm (no upper limit). Infants in the prophylactic trial were not eligible for the rescue trial. RESULTS: For the rescue trial, there was a $16,600 reduction in average hospital costs (p = 0.18), which was larger than the cost of the surfactant ($450 to $900), yielding a probable net savings. For the prophylactic trial, hospital costs were larger for treated infants versus control subjects who weighed less than about 1100 gm at birth and lower for treated infants versus control subjects who weighed more than 1100 gm at birth (p < 0.05). For the prophylactic sample, the result was an average cost per life saved of $71,500. CONCLUSIONS: Single-dose rescue surfactant therapy is probably a cost-effective therapy because it produced a lower mortality rate for the same (and probably lower) expenditure. Single-dose prophylactic therapy for smaller infants (< or = 1350 gm) appeared to yield a reduction in mortality rate for a small additional cost. The use of multiple-dose therapy in infants who do not respond to initial therapy may alter the effects described above to either increase or decrease the observed cost-effectiveness of surfactant therapy. Regardless, surfactant therapy will remain a cost-effective method of reducing mortality rates, relative to other commonly used health care interventions.

Enhancement of erythropoiesis by recombinant human erythropoietin in low birth weight infants: a pilot study.

We randomly assigned eight concurrently symptom-free premature infants (birth weight less than or equal to 1250 gm) at high risk of requiring erythrocyte transfusions for anemia of prematurity to 6 weeks of intensive treatment with either subcutaneous recombinant human erythropoietin (r-HuEPO group) or a placebo (control group). Treatment with r-HuEPO was initiated at a dose of 100 units/kg per day 5 days a week, and was increased to 200 units/kg per day after 2 or 3 weeks if target reticulocyte counts were not achieved. All patients were given supplemental oral iron therapy at a dose of 6 mg/kg per day, as tolerated. Mean reticulocyte counts in r-HuEPO-treated and control infants were 64,600 versus 67,500 cells/mm3 at entry; were 245,600 versus 78,000 cells/mm3 after 1 week; and averaged 262,600 versus 136,400 cells/mm3 during the study. Mean reticulocyte counts in r-HuEPO-treated infants were 251,200 cells/mm3 during the week when r-HuEPO, 100 units/kg per day, was given, and were 269,500 cells/mm3 after the dose was increased to 200 units/kg per day. Mean hematocrit values at entry were 33.4% in babies who received r-HuEPO versus 33.6% in the control subjects, and were 31.4% in r-HuEPO-treated and 25.2% in the control subjects at the end of treatment. One r-HuEPO-treated and three control babies received transfusions during the study; the total volume of blood given was 17 ml in the r-HuEPO group and 101 ml in the control subjects. The percentage of hemoglobin F increased in infants not given transfusions. We conclude that r-HuEPO stimulates endogenous erythropoiesis in small premature babies who are receiving supplemental oral iron therapy. A controlled multicenter trial has been undertaken to confirm these promising preliminary observations.

Potential for treatment of anaemia of prematurity with recombinant human erythropoietin: preliminary results.

There is a high level of erythropoiesis in the growing fetus. In utero relative hypoxia results in a relatively high haematocrit and predominant synthesis of haemoglobin F, with erythropoietin (EPO) produced in the liver regulating erythropoiesis. At birth after full-term pregnancy, fetal EPO concentrations are high, but decline progressively thereafter. In pre-term infants the expected postnatal decline in haemoglobin is more prolonged than in full-term infants and the premature infants may become anaemic. It has been shown in a randomized, double-blinded, placebo-controlled trial that recombinant human erythropoietin (r-HuEPO) at a dose of 100 U/kg given intravenously twice weekly for 6 weeks to infants with anaemia of prematurity produced an earlier increase in reticulocyte counts compared with placebo; however, the difference between treatments was not significant. r-HuEPO therapy did not suppress subsequent release of endogenous EPO. It is concluded that a higher dose of r-HuEPO may be required to treat anaemic premature infants.

Initial clinical trial of EXOSURF, a protein-free synthetic surfactant, for the prophylaxis and early treatment of hyaline membrane disease.

EXOSURF is a protein-free surfactant composed of 85% dipalmitoylphosphatidylcholine, 9% hexadecanol, and 6% tyloxapol by weight. A single dose of 5 mL of EXOSURF per kilogram body weight, which gave 67 mg of dipalmitoylphosphatidylcholine per kilogram body weight, or 5 mL/kg air was given intratracheally in each of two controlled trials: at birth to neonates 700 through 1350 g (the prophylactic trial, n = 74) or at 4 to 24 hours after birth to neonates greater than 650 g who had hyaline membrane disease severe enough to require mechanical ventilation (the rescue trial, n = 104). In both studies, time-averaged inspired oxygen concentrations and mean airway pressures during the 72 hours after entry decreased significantly (P less than .05) in the treated neonates when compared with control neonates. Thirty-six percent of the treated neonates in the rescue study had an incomplete response to treatment or relapsed within 24 hours, suggesting the need for retreatment in some neonates. In the rescue trial, risk-adjusted survival increased significantly in the treated group. There were no significant differences in intracranial hemorrhages, chronic lung disease, or symptomatic patent ductus arteriosus between control and treated infants in either trial.

Recombinant human erythropoietin in the anemia of prematurity: results of a placebo-controlled pilot study.

Experimental and clinical data implicate inadequate erythropoietin production as an important reason that infants acquire this anemia and suggest that recombinant human erythropoietin (r-HuEPO) might be used to treat or prevent it. We therefore randomly assigned 20 small premature infants (birth weight less than or equal to 1250 gm) who were highly likely to require erythrocyte transfusions for anemia of prematurity to receive 6 weeks of treatment with either intravenously administered r-HuEPO (at a dose of 100 units/kg twice each week) or a placebo. Hematologic measurements, transfusion requirements, and growth were followed during therapy and for 6 months thereafter. Treated (EPO) and control babies did not differ with respect to weight, hematocrit, overall mean absolute reticulocyte count, calculated erythrocyte mass, or rate of growth. However, reticulocyte counts increased earlier in patients given r-HuEPO. Six of ten babies in the EPO group, and 8 of 10 assigned to the control group, received at least one erythrocyte transfusion during treatment. For all infants the amount of blood sampled for laboratory tests was strongly predictive of the volume of packed erythrocytes transfused (r = 0.890; p = 0.0001). Of nine infants who had less than 20 ml packed erythrocytes removed for laboratory tests, none of four given r-HuEPO received a transfusion, whereas three of five infants assigned to the placebo group received one. No toxic effects were attributable to r-HuEPO, and no significant changes in leukocyte or platelet counts occurred during treatment. Reticulocyte counts were correlated with simultaneous platelet counts and were inversely related to absolute neutrophil counts in both study groups. We conclude that r-HuEPO administration is safe and feasible at the dose studied. Additional controlled trials utilizing higher doses of r-HuEPO and larger numbers of patients are justified.

Age-related differences in erythropoietic response to recombinant human erythropoietin: comparison in adult and infant rhesus monkeys.

Human recombinant erythropoietin (r-HuEPO) was given i.v. to rhesus monkeys to compare its safety, erythropoietic effects, and pharmacokinetics in healthy adult and infant animals. Eighteen adult and 18 infant (9- to 15-d-old) monkeys were divided into three groups each of six animals. One group was given 250 U/kg twice weekly, another was given 100 U/kg twice weekly, and a control group was given the drug vehicle for 6 wk. All animals were healthy throughout this period, and for 10 wk after that. Administration of r-HuEPO at these dosages did not produce any changes in leukocytes, platelets, urea nitrogen, bilirubin, creatinine, alkaline phosphatase, alanine amino transferase, gamma-glutamyl transferase, and blood pressure in either age group. At 6 wk, both adult treatment groups had statistically significant increases in Hb concentration. The same dosages that produced these increases in Hb concentration in adults produced no changes in Hb concentration in infant monkeys. Despite active erythropoiesis, as determined by reticulocytosis and increased total body Hb, Hb concentration decreased similarly in the infant treatment and control groups. Pharmacokinetic profiles were obtained at 5 wk of dosing. One h after administration, both doses of r-HuEPO produced significantly lower serum r-HuEPO concentration in the infant monkeys compared with the adults. These differences appeared to be due to a larger volume of distribution of r-HuEPO in the infant monkeys. The t1/2 of r-HuEPO in circulation was the same in both age groups.

Prevention, recognition, and treatment of perinatal asphyxia.

Management of perinatal asphyxia is one of those rare opportunities in clinical medicine when death or life-long disability can be prevented with several minutes of skillful and judicious action. Fetal and neonatal asphyxia is approached most successfully as a joint obstetric, pediatric, and anesthetic effort. This article reflects the team approach to perinatal asphyxia.

Spinal cord injury in newborns from use of umbilical artery catheters: report of two cases and a review of the literature.

Umbilical artery catheter use in sick newborns has been associated with infarction of major organs such as the intestine and kidneys; spinal cord infarction has also been reported but is rare. We report two cases of spinal cord infarction and review the six others in the literature for preventable or predisposing conditions. Infusion of blood and hypertonic solutions, shock, and high position of the catheter tip were associated with infarction of the anterior spinal cord in these infants.