Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Masked, Placebo Controlled Study to Assess the Safety and Efficacy of Darbepoetin Alfa Administered to Preterm Infants
Brief Summary: Infants born prematurely do not increase production of the primary red cell growth factor, erythropoietin (Epo), and often develop an anemia called the "anemia of prematurity." The anemia of prematurity is the most common anemia seen in neonates, and is due to a failure of Epo production. Human recombinant Epo (rHuEpo), given three to five times a week, is successful in treating the anemia of prematurity. A slightly modified, long-acting version of rHuEpo, called darbepoetin alfa (darbepoetin), is now available and has proven effective in increasing hematocrit (red blood cell levels) in adults. In addition to its red cell stimulating properties, recent evidence has shown that rHuEpo is protective in the developing or injured brain. We have designed a randomized, masked, placebo-controlled study to determine the safety and short and long term efficacy of darbepoetin. At this time, darbepoetin has been studied primarily in adults and pediatric patients, but there is evidence from pilot studies that darbepoetin would be useful in the neonatal setting as well. It also may well improve neurodevelopmental outcomes in preterm neonates. We hypothesize that: 1. The administration of darbepoetin to preterm infants 500 to 1,250 grams birth weight will result in increased reticulocyte counts and decreased transfusions compared to placebo; and 2. The administration of darbepoetin will be associated with an increased mental developmental index at 18-22 months compared to placebo.


Options:
A: Inclusion Criteria (preterm):

* birth weight 500-1,250 grams, gestational age ≤32 weeks
* hematocrit ≤55%
* ≤48 hours of age
* expected to survive greater than 72 hours
* consent signed by parent or guardian

Inclusion Criteria (term):

Former term born infants will be eligible if they have not experienced any episodes of hypoxia, hypoglycemia, hyperbilirubinemia, prenatal drug exposure, or sepsis.

Exclusion Criteria (former preterms):

* hemorrhagic or hemolytic disease
* major congenital anomalies (such as trisomy 13, 18 or 21)
* major neurologic abnormality such as hydrocephalus or meningomyelocele
* complex congenital heart disease
* receiving Epo or are enrolled in an Epo study
* evidence of disseminated intravascular coagulation
* clinical seizures are present
* congenital thrombotic disease is suspected
* systolic blood pressures \>100 mm Hg (while not on pressor support) Infants with minor anomalies such as clinodactyly, single umbilical vessel or patent ductus are not excluded

Exclusion criteria (term):

hypoxia, hypoglycemia, hyperbilirubinemia, prenatal drug exposure, or sepsis
B: Inclusion Criteria:

* Birth weight 500 to 999 grams;
* Postnatal age greater than 2 hours;

Exclusion Criteria:

* Unable to administer study drug within 6 hours of birth;
* Structural heart disease and/or renal disease;
* Dysmorphic features or congenital abnormalities;
* Tocolytic therapy with indomethacin or other prostaglandin inhibitor within 72 hours prior to delivery;
* Overt clinical bleeding from more than one site;
* Platelet count less than 50 x 109/L;
* Hydrops;
* Not considered viable
C: Inclusion Criteria:

* Infants born between 26 0/7 and 31 6/7 gestational weeks
* Postnatal age less than 3 hours
* Informed parental consent (preferably obtained before birth)

Exclusion Criteria:

* Genetically defined syndrome
* Severe congenital malformation adversely affecting life expectancy
* Severe congenital malformation adversely affecting neurodevelopment
* A priory palliative care
* Intracranial haemorrhage grade 3 or more detected before dose 3 of Erythropoietin
D: Inclusion Criteria:

* 500-1250 grams birth weight
* less than or equal to 32 weeks gestation
* less than 2 days of age

Exclusion Criteria:

* severe hemorrhagic disease
* severe hemolytic disease
* DIC
* seizures
* hypertension
* thromboses
* receiving erythropoietin

Answer: D