Transfusiones en el prematuro

Marzo 2009

I.- Anemia in the preterm infant : erythropoietin versus erythrocyte transfusion - it's not that simple.

IsabelleVon Kohorn

Clin Perinatol 36 : 111–123 , March 2009

Since the late 1980s recombinant human erythropoietin (r-EPO) has been studied as an alternative to packed red blood cell (RBC) transfusion in the treatment of anemia of prematurity (AOP). Two decades later hematologists and neonatologists have not reached consensus on when r-EPO should be used in very low birth weight (VLBW, <1500 g) infants. Initial trials and reports focused on the use of r-EPO to prevent or treat AOP with the goal of eliminating RBC transfusion. Later studies found response to r-EPO was influenced by (1) significant volumes of blood loss, especially in the smallest, sickest infants, (2) the physiology of r-EPO, which requires days to weeks to increase hematocrit, and (3) the need for supplementation with protein, iron, folate, and vitamin E. In addition, recent reports have warned of undesirable side effects, including a possible increase in retinopathy of prematurity (ROP) with early administration of r-EPO.

This article reviews the history of AOP treatment, starting with the physiology of AOP and the development of specialized transfusion techniques for the VLBW population. It then describes the initial trials of r-EPO to prevent or treat AOP and the implementation

of restrictive RBC transfusion criteria. Finally, it discusses recent concerns about the side effects of r-EPO administration and outlines therapies that may limit the need for r-EPO administration, shifting the cost–benefit balance away from treatment with r-EPO to prevent or treat AOP.

Current conservative RBC transfusion criteria for VLBW infants

1. For infants requiring moderate or significant ventilation (defined as mean airway pressure > 8 cm H2O and fraction of inspired oxygen [FIO2] > 0.40): transfuse if hematocrit ≤  35% (hemoglobin ≤  11 g/dL).

2. For infants requiring minimal mechanical ventilation, defined as all other infants requiring (a) positive-pressure ventilation or (b) continuous positive airway pressure (endotracheal or nasal continuous positive airway pressure) of 6 cm H2O or higher and FIO2 higher than 0.40: transfuse if hematocrit is 30% or higher (hemoglobin ≤ 10 g/dL).

3. For infants receiving supplemental oxygen who do not require mechanical ventilation: transfuse if hematocrit 25% or higher (hemoglobin ≤ 8 g/dL) and one or more of the following is present :

   • Tachycardia (heart rate > 180 beats/min) or tachypnea (respiratory rate > 80 breaths/min) lasting more than 24 hours

   • An increased oxygen requirement from the previous 48 hours, defined as :

     • A fourfold or greater increase in nasal cannula flow (ie, from 0.25 L/min to 1 L/min) OR

     • An increase in nasal continuous positive airway pressure of 20% or more from previous 48 hours (ie, from 5 to 6 cm H2O) OR

     • An absolute and sustained increase in FIO2 of 0.10 or higher (via oxyhood, nasal continuous positive airway pressure, or cannula).

   • Weight gain of less than 10 g/kg/d over the previous 4 days while receiving 100 or more kcal/kg/d

   • Multiple episodes of apnea and bradycardia (≥ 10 episodes in a 24-hour period or two or more episodes in a 24-hour period requiring bag-mask ventilation) while receiving therapeutic doses of methylxanthines

   • Undergoing surgery

4. For infants without any symptoms: transfuse if hematocrit is 20% or lower (hemoglobin < 7 g/dL) and the absolute reticulocyte count is lower than 100,000 cells/uL (< 2%)

II.- Iron therapy for preterms infants

Raghavendra Rao

Clin Perinatol 36 :  27–42, March 2009

Initiation of Supplementation

The initiation of iron supplementation in preterm infants has been debated since the 1950s and has ranged from 14 days to 10 weeks among the neonatal units. The current recommendation is to begin supplementation between 4 and 8 weeks of age, irrespective of gestational age or birth weight.

Beginning supplementation earlier may be prudent for the more immature preterm infants, many of who may be in negative iron balance by 1 month of age.Compared with unsupplemented infants or those who first received supplementation between 4 and 8 weeks of age, supplementing 2 to 5  mg/kg/d of iron from 2 weeks of age reduces the need for erythrocyte transfusions and the risk of iron deficiency between 2 and 6 months of age. Cumulative iron intake was calculated to be more than three times greater with early supplementation than with late supplementation. 

Hemoglobin, serum iron, and ferritin concentrations were higher, and serum transferrin receptor concentrations were lower at 2 months of age with early iron supplementation,  suggesting better iron stores at discharge. Early iron supplementation was tolerated well and was not associated with morbidities. A follow-up study demonstrated a lower incidence of mild motor signs and a trend toward better cognitive function at 5 years of age in those supplemented from age 2 weeks,  suggesting potential long-term benefits with early supplementation. The lack of long-term neurologic morbidity also supports the safety of early iron supplementation.

On the other hand, the risk of iron-induced hemolysis in preterm infants who have vitamin E deficiency is maximal during the first 6 weeks of life. Serum iron and  ferritin concentrations remain elevated during the first 4 to 6 weeks of life even without supplementation.  There is a potential for iron excess with higher doses of supplementation, because enteral iron absorption seems to be poorly regulated during the first month of life in ELBW infants. Furthermore, supplemental iron is better incorporated into red blood cells when it is administered after the onset of erythropoiesis. These studies support delaying iron supplementation until 4 to 6 weeks.