Effects of blood transfusion on regional tissue oxygenation in preterm newborns are dependent on the degree of anaemia.

AIM: Most of the preterm infants are transfused at least once during their stay in the neonatal intensive care unit (NICU). The aims of this study were to demonstrate if packed red blood cell (pRBC) transfusion modulates regional (cerebral, abdominal, renal) tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) and to demonstrate if we can use NIRS to guide transfusion decisions in neonates. METHODS: A multi-probe NIRS device was applied to anaemic preterm infants of gestational age <33 weeks for 30-60 min before and 24 h after pRBC transfusion. We evaluated the results separately in the subgroup with a pre-transfusion haemoglobin (Hb) < 8 g/dL. Cerebral, abdominal and renal tissue oxygen saturation (rSO2 ) and abdominal/cerebral, abdominal/renal and renal/cerebral rSO2 ratios before and 24 h after transfusion were compared. RESULTS: There was no significant difference in cerebral rSO2 and abdominal/renal rSO2 ratios before and 24 h after transfusion, but abdominal and renal rSO2 and abdominal/cerebral and renal/cerebral rSO2 ratios at the 24th h following transfusion increased significantly. This increase was observed in the subgroup with pre-transfusion Hb < 8 g/dL. Although statistically significant, the increase in renal oxygenation was within the limits of variability. CONCLUSIONS: The increase in tissue oxygenation in abdominal region after pRBC transfusion suggests decreased tissue oxygenation of intestines during severe anaemia despite cerebral oxygenation being maintained at that particular Hb level. The impact of the increase on renal oxygenation with pRBC transfusion is unclear and might need further investigation. Increase in abdominal rSO2 may cause reperfusion injury, oxidative damage and trigger necrotising enterocolitis.

Ventricular Diastolic Function in Normal Fetuses and Fetuses with Hb Bart's Disease Assessed by Color M-Mode Propagation Velocity using Cardio-STIC-M (Spatio-Temporal Image Correlation M-Mode).

Purpose: To determine whether ventricular diastolic dysfunction contributes to the pathogenesis of fetal cardiac failure due to fetal anemia using fetal Hb Bart's disease as a live model and cardio-STIC-M as a diagnostic tool. Materials and Methods: Color cardio-STIC volume datasets were acquired from fetuses at risk for Hb Bart's disease during 18 - 22 weeks of gestation and normal pregnancies and pregnancies with hydrops fetalis caused by Hb Bart's disease at 28 - 32 weeks. The volumes were analyzed off-line for velocity propagation (Vp) of the right and left ventricles to assess ventricular diastolic function using color cardio-STIC-M. Results: The Vp for the right and left ventricles was studied in fetuses at 18 - 22 weeks, including 64 normal fetuses (group 1) and 22 fetuses with Hb Bart's disease (group 2), and in fetuses at 28 - 32 weeks, including 22 normal fetuses (group 3) and 16 fetuses with Hb Bart's hydrops fetalis (group 4). The Vp of the fetuses in group 1 and group 2 was not significantly different. However, the Vp for the right and left ventricles in group 4 was significantly lower than in group 3 (19.02 vs. 9.78, p < 0.001; and 20.24 vs. 13.40, p < 0.001, respectively). The inter-observer variability had fair agreement with the intra-class correlation coefficient of 0.531 (95 % CI 0.393 - 0.646, p < 0.001). Conclusion: Hydrops fetalis secondary to fetal anemia is initially caused by hypervolemia rather than ventricular diastolic dysfunction while ventricular diastolic compromise is a late occurring consequence of persistent hypervolemia, different from the mechanism of hydropic changes caused by cardiac causes.

Twin anemia-polycythemia sequence in monochorionic twins: implications for diagnosis and treatment.

Twin anemia-polycythemia sequence (TAPS) is a recently described complication of monochorionic placentation characterized by discordance in hemoglobin (Hgb) levels in the absence of amniotic fluid abnormality characteristic of classical twin-twin transfusion syndrome (TTTS). The placental angioarchitecture that predisposes to TAPS consists of small diameter arteriovenous anastomoses and the absence of balancing arterioarterial anastomoses. This vascular pattern occurs sporadically in 3 to 5% of monochorionic twins or iatrogenically following 2 to 13% of selective fetoscopic laser surgeries for TTTS. The diagnosis is based on measurement of the middle cerebral artery peak systolic velocity (MCA-PSV) which is not part of the Quintero staging for TTTS. With mild disease increased MCA-PSV in the anemic donor twin and a decreased MCA-PSV in the recipient twin are characteristic while severe disease is associated with critical Doppler findings, hydrops or single twin demise as in TTTS. Treatment options include fetoscopic laser, fetal blood transfusion, conservative management, and often preterm delivery. The most promising approach to TAPS is its prevention since the iatrogenic form comprises the majority of cases. When the fetoscopic laser technique is modified by coagulating the chorionic plate along the vascular equator (equatorial dichorionization or "Solomon" technique) the incidence of postlaser TAPS and recurrent TTTS is significantly reduced, survival is improved, and there is no increase in complications.

A mathematical modeling approach to quantify the role of phlebotomy losses and need for transfusions in neonatal anemia.

BACKGROUND: Very preterm infants commonly develop anemia requiring multiple red blood cell transfusions (RBCTx). This is in part attributable to heavy laboratory phlebotomy loss. Quantification of the extent to which laboratory blood loss contributes to anemia sufficient to prompt RBCTx has not been examined. STUDY DESIGN AND METHODS: Twenty-six preterm infants weighing less than 1500 g at birth requiring ventilator support who received one or more RBCTx were intensively studied during the first month of life. Hemoglobin (Hb) loss via laboratory blood loss and RBC senescence and Hb gain from RBCTx were precisely accounted for in a Hb mass balance mathematical model developed to assess the impact of phlebotomy on RBCTx when restrictive RBCTx criteria were applied. RESULTS: Study subjects had a birth weight of 880 ± 240 g (mean ± SD) and a Hb level of 14.4 ± 2.4 g/dL at birth and received 3.81 ± 2.15 RBCTx during the study period. Modeling indicated that even with the total elimination of laboratory phlebotomy loss, a reduction of 41% to 48% in RBCTx was achievable. CONCLUSION: The present modeling results indicate that while phlebotomy reduction can significantly decrease the number of RBCTx administered to preterm infants, total elimination of all RBCTx will likely require other approaches, for example, stimulation of erythropoiesis with erythropoiesis-stimulating agents.

A novel epsilon gamma delta beta thalassemia presenting with pregnancy complications and severe neonatal anemia.

OBJECTIVE: The epsilon gamma delta beta (εγδß)-thalassemias are rare sporadic disorders caused by deletion of the ß-globin gene cluster. The main clinical feature is marked prenatal and neonatal anemia that resolves spontaneously within a few months. Reports originating mainly from Europe have so far identified 30 such deletions The aim of the present work was to describe a novel 1.78-Mb deletion, the longest ever reported, and to detail the clinical features in 12 members of an extended Bedouin family. METHODS: The deletion was identified by globin gene multiplex ligation-dependent probe amplification (MLPA) of the ß-globin cluster and further characterized by comparative genomic hybridization. Past and present clinical and laboratory data of ten symptomatic and two asymptomatic patients were collected. RESULTS: A 1.78-Mb εγδß-deletion, the largest ever described, was identified in all patients. Although other genes were included in the deletion, no other symptoms were observed. Of the ten symptomatic fetuses and neonates, three died of the disease. The remainder required packed cell transfusions during the first months of life. Pregnancy complications included intrauterine growth restriction and oligohydramnios, as well as additional neonatal complications including prematurity and persistent pulmonary hypertension of the neonate. CONCLUSIONS: We suggest that εγδß-thalassemia be added to the list of hemoglobinopathies that can cause neonatal anemia and that MLPA of the ß-globin cluster be used to confirm its diagnosis. Careful surveillance during pregnancy is important to reduce neonatal mortality and morbidity, especially given the dramatic improvement that occurs later.

Fetal and neonatal anemia associated with anti-Jr(a) : a case report showing a poorly hemolytic mechanism.

Although recently published case reports suggest the significance of Jr(a) alloimmunization in the obstetric setting, the involved mechanism still remains unclear. Here we report a case of severe fetal and neonatal anemia associated with anti-Jr(a) alloimmunization, which was successfully managed using Doppler assessment of peak systolic velocity of the fetal middle cerebral artery (MCA-PSV). A Japanese woman with anti-Jr(a) (titer 1024) was referred to our department at 20 weeks' gestation. As fetal MCA-PSV exceeded 1.5 multiple of median, labor was induced and a female neonate of 1998 g was delivered vaginally at 33 weeks and 5 days of gestation. The infant's hematocrit and hemoglobin levels were 25.4% and 82 g/L, respectively, but her total bilirubin level (15 µmol/L; 0.9 mg/dL) and reticulocyte counts (4.5%) were low. During the course, the infant showed no apparent signs of hemolysis. Jr(a) alloimmunization should be recognized as a possible cause of fetal anemia with no direct hemolytic process.

Isolated early onset anemia after rh isoimmunization: a unique presentation in 3 neonates.

SUMMARY: Rh isoimmunization manifesting as isolated early onset neonatal anemia has not been reported. We describe the presentation of 3 infants who manifested with isolated early severe anemia. All the infants presented early (3 to 7 d of age) with severe pallor. None had clinically significant jaundice. Evidence for hemolysis was present in all and their direct antiglobulin test was positive. To reduce the hemolysis, immunoglobulin was administered after which their hemoglobin improved. This report highlights the possibility of early onset anemia without significant jaundice as the sole manifestation of Rh isoimmunization and the possible beneficial role of immunoglobulin in them.

Middle cerebral artery-peak systolic velocity in dizygotic twins with anti-E alloimmunization.

Middle cerebral artery-peak systolic velocity (MCA-PSV) has been reported to predict fetal anemia with similar accuracy as amniotic ΔOD450 assay. Alloimmunized dizygotic twin pregnancy allows us to compare anemic and non-anemic twins in the same intrauterine environment. We herein present a case of Rh (E)-incompatible dizygotic twin pregnancy, where MCA-PSV could precisely detect the anemia in one of the twins. A 36-year-old woman, whose previous child required exchange transfusion due to hemolytic anemia of newborn (HFDN), conceived twins after in vitro fertilization-embryo transfer. At 24 weeks' gestation, MCA-PSV of twin A and twin B were 23.9 cm/s (0.8 multiples of median; MoM) and 30.7 cm/s (1.0 MoM), respectively. At 31 weeks' gestation, MCA-PSV values of both twins were sharply elevated to nearly 1.4 MoM. Thereafter, MCA-PSV of twin A fell to 1.0 MoM, whereas MCA-PSV of twin B exceeded 1.5 MoM at 34 weeks' gestation. Development of fetal anemia was suspected and emergency cesarean section was performed. Twin B showed moderate anemia with positive direct Coombs' test and was diagnosed as HFDN due to anti-E alloimmunization. Twin B required phototherapy and red cell transfusion, but exchange transfusion was safely obviated.

Perinatal Anemia is Associated with Neonatal and Neurodevelopmental Outcomes in Infants with Moderate to Severe Perinatal Asphyxia.

BACKGROUND: Perinatal anemia may cause perinatal asphyxia. Its pathophysiology and neurodevelopmental effects are theoretically different from other causes of perinatal asphyxia. OBJECTIVE: The study aimed to determine whether perinatal anemia results in different short-term and long-term outcomes than other causes of perinatal asphyxia treated with therapeutic hypothermia. METHODS: We retrospectively included infants with moderate to severe hypoxic-ischemic encephalopathy, born between May 2009 and October 2015. During follow-up, we assessed cognitive and motor development at 2-3 years of age, using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III). Neurodevelopmental outcome (NDO) was classified as abnormal in case of cerebral palsy with Gross Motor Function Classification System ≥III and/or a BSID-III composite score < 85. Outcomes of infants with perinatal anemia (initial hemoglobin < 7 mmol/L) were compared to infants born with perinatal asphyxia due to other causes. RESULTS: In total, 111 infants were included of whom 30 infants (27%) died during the neonatal period. Infants with anemia (n = 23) had a higher mortality risk, OR 3.33, 95% CI 1.27-8.72, p = 0.01. None of the surviving infants with anemia (n = 12) had an abnormal NDO, in contrast to 26/69 (38%) with neurodevelopmental impairments, particularly motor problems, in the non-anemic group, p < 0.01. CONCLUSIONS: Perinatal anemia causing moderate to severe perinatal asphyxia is associated with a higher risk for neonatal mortality. All survivors with perinatal anemia, however, showed a normal NDO in contrast to children who were born asphyxiated due to other causes. The underlying pathophysiological mechanism for the favorable NDO in the perinatal anemia group needs further elucidation.

Do cardiac output and serum lactate levels indicate blood transfusion requirements in anemia of prematurity?

BACKGROUND: Whether and when to transfuse in anemia of prematurity is highly controversial. Some authors suggest transfusions simply if the hemoglobin (Hb) level is below a defined normal range. Others propose the use of clinical or laboratory parameters in anemic patients to decide whether to transfuse or not. HYPOTHESIS: A decreasing amount of circulating Hb should cause a compensatory increase in cardiac output (CO) and an increase in arterial serum lactate. MATERIALS AND METHODS: In 56 anemic preterm infants (not in respiratory or hemodynamic failure) we analyzed CO after the first week of life using a Doppler sonographic method. At the same time serum lactate levels, Hb levels and oxygen saturation were registered. Nineteen of these patients were given transfusion when they demonstrated clinical signs of anemia by tachycardia > 180/min, tachypnea, retractions, apneas and centralization (group 2). The remaining 37 patients were not transfused (group 1). Serum lactate, CO, heart rate (HR), oxygen delivery, respiratory rate, capillary refill and Hb were analyzed in both groups and in group 2 before and 12-24 h after transfusion. Data between groups 1 and 2 and in group 2 before and after transfusion were compared. RESULTS: In the 56 patients studied no linear correlation between Hb and CO or between Hb and serum lactate was found. Nor could any correlation be demonstrated between the other variables studied. Examining the subgroups separately, a negative linear correlation was demonstrated between serum lactate and oxygen delivery in group 2. No other significant correlations were detected. However, when the pre- and post-transfusion data were compared in group 2 (increase of Hb from 9.45 (SD 3.44) to 12.5 (SD 3.8) g/100 ml), the CO decreased from 281.3 (SD 162.6) to 224 (SD 95.7) ml/kg per min (p < 0.01) and serum lactate decreased significantly from 3.23 mmol/l (SD 2.07) before to 1.71 (SD 0.83) after transfusion. Oxygen delivery was 35.8 (+/- 0.19) ml/kg per min group 1, 27.8 (+/- 0.05) pre- and 43.4 (+/- 0.07) post-transfusion in group 2 (p < 0.01). CONCLUSIONS: CO measurements and serum lactate levels add little information to the decision-making process for blood transfusions, as neither CO nor serum lactate levels correlate with HB levels in an otherwise asymptomatic population of preterm infants. In infants where the indication for blood transfusion is made based on traditionally accepted clinical criteria, serum lactate is an additional laboratory indicator of impaired oxygenation, as it correlates significantly with oxygen delivery. A significant lower oxygen delivery in patients in whom blood transfusion is indicated and an increase in oxygen induced by transfusion demonstrate the value of these criteria in identifying preterm infants who benefit from transfusion.

Lessons from the anemia of prematurity.

In our view, three main lessons stem from consideration of the refractory early anemia of prematurity (REAP). These are: (1) Hemoglobin concentration is not enough to describe the anemia. (2) The REAP may be clinically very severe but is often easily missed. It interacts with and worsens other causes of anemia in preterm infants, such as blood losses. Its pathogenesis is multifactorial, but it is generally interrelated with short gestation and its other complications. (3) Prevention, prophylaxis, and if necessary, adequate management are very important.

The role of erythropoietin in the anemia of prematurity.

Neonatal erythropoiesis is limited by a relatively inadequate production of erythropoietin. This is likely the result of dependence on the hepatic production of erythropoietin and an incomplete switchover to renal production. The present model of neonatal erythropoiesis suggests that the use of exogenous erythropoietin should correct the early anemia of prematurity that is observed at 6 weeks of age in premature newborns. Randomized, controlled trials of erythropoietin use in very low birthweight infants are reviewed. The data support the conclusion that erythropoietin at doses of > or = 750 u/kg/wk started at less than 7 days of age results in improved reticulocyte counts and hemoglobin levels, but does not reduce the number of infants who will be exposed to blood products. Erythropoietin at doses of > or = 600 u/kg/wk started at an average of 21 days of life improves reticulocyte counts and hemoglobin levels, and reduces the number of infants will will require late transfusion, but does nothing for the bulk of infants who are transfused before that age.

Anemia of prematurity. Current concepts in the issue of when to transfuse.

At no other time of life is the decision to transfuse potentially as difficult as in the newborn period. Superimposed upon complex "physiologic" changes in the ability to deliver and release oxygen are varying requirements among infants in terms of oxygen need. These are compounded by changes brought about as a direct consequence of frequent phlebotomy in the most ill of preterm infants. Despite the confusion overlying many of the changes occurring at this time of life, certain principles can be applied. Unlike that of the adult, an infant's ability to make oxygen available in response to a specific demand is almost as dependent upon the modifiers of oxygen uptake and release by hemoglobin as upon the hemoglobin concentration itself. These modifiers are constantly changing, sometimes in a predictable fashion, sometimes not. As discussed, some attention to the status of a particular infant's capability in providing oxygen relative to need will assist in the decision when to transfuse. If specific parameters of these assessments can not be determined, it may be necessary to proceed with transfusion based on the clinical presentation of an infant. With regard to the above, any infant sufficiently ill to require frequent blood sampling should have such blood losses replaced, certainly before ten percent of blood volume has been exceeded. This is particularly true in infants who are unable to maintain adequate arterial oxygen tensions with or without the use of supplemental inspired oxygen. At several weeks of age, when the clinical status of a preterm infant may have stabilized, transfusion may or may not be needed during the nadir of the anemia of prematurity. Infants who had been previously transfused or who had earlier received frequent simple transfusions should be able to tolerate lower levels of hemoglobin. Infants without compromised cardiopulmonary function and in whom no unusual metabolic needs exist are unlikely to be aided by transfusions when the hemoglobin concentration is greater than 10 to 11 g/dl. At lower levels of hemoglobin, simple calculations of "available oxygen" may be helpful when it is difficult to determine whether clinical signs and symptoms of anemia exist. Such signs and symptoms may include poor feeding, dyspnea, tachycardia, tachypnea, diminished activity, and pallor. Apnea has not unequivocably been shown to improve following transfusion. Clearly, our current concepts regarding indications for transfusion, even when based upon known principles of physiology, still represent an art form that is less than completely scientific.(ABSTRACT TRUNCATED AT 400 WORDS)

The physiologic impact of anemia in the neonate.

Clinically useful indicators of physiologically significant anemia requiring intervention have yet to be defined in the newborn. Finding a simple noninvasive marker of physiologically significant anemia remains elusive but is a laudable goal considering the risks of transfusion therapy and requirement for repeated parenteral (subcutaneous or IV) administration or r-HuEPO, when chosen as a preventive or therapeutic option. The asymptomatic newborn has shown considerable tolerance to anemia without detrimental effects and need for an iatrogenic increase in RBC mass. Newer guidelines for transfusion are emerging that lower the threshold hematocrit and hemoglobin concentration at which RBC transfusion may be considered. Following those guidelines alone may decrease the need for transfusion and improve our understanding of the physiologic impact of anemia in the neonate. Ongoing investigation in understanding better the physiologic impact and consequences of anemia is critical in that regard.

Hemolytic anemia in the newborn.

Evaluation of hemolytic anemia in the newborn may be complicated owing to the physiologic changes that occur during this time; however, the newborn period is a time when congenital red cell abnormalities may first present and when maternal factors need to be considered. In this article, an approach to the diagnosis of hemolytic disease in the newborn is reviewed. The unique properties of the neonatal red cell, the normal red cell changes present in the neonate, the potential congenital defects and maternal factors that may influence the associated clinical and laboratory findings consistent with the diagnosis of hemolytic anemia, and a brief review of the red cell disorders associated with hemolytic anemia in the newborn are discussed.

Physiologic sequelae of prematurity: the nurse practitioner's role. Part IV. Anemia.

Anemia in the immediate newborn period may be caused by hemolysis, by a failure of red-cell production, or by a combination of both. However, anemia of prematurity often is the result of hemolysis, of a lack of erythropoietin, and/or of nutritional deficits. Transfusion without a search for the cause may obscure the underlying pathology of the anemia. Because severe anemia can be life-threatening, prompt diagnosis and treatment are required. In this article, the fourth of a series of articles on the sequelae of prematurity, a discussion of the pathophysiology, signs and symptoms, data collection, treatment modalities pertinent to the anemia of prematurity, and parental education are discussed.

Blood transfusion in newborn.

Premature infants are among the most frequently transfused groups of patients, usually receiving red cells. The immaturity of the immune system, its lesser ability to cope with a metabolic load and the presence of maternal antibodies, all complicate the picture. Conservation of blood to minimize losses and the need for replacement transfusion is an important strategy that has already been successful in reducing the need for transfusion on neonatal units. The advent of erythropoietin provides another strategy for reducing the need for transfusion. It is unfortunate that the sickest patients who require the most transfusion poorly respond to erythropoietin. Main concern is the long-term consequences of transfusion. Presently the aim is to minimize transfusion risks and give transfusions only when they are indicated.

Effects of anaemia on haemodynamic and clinical parameters in apparently stable preterm infants.

BACKGROUND: The criteria for erythrocyte transfusion in stable premature infants are currently controversial. Haemodynamic measurements are not common in transfusion practice. The purpose of this study was to determine whether haemodynamic measurements could be helpful as objective criterion for transfusion decisions. We, therefore, evaluated clinical and haemodynamic changes in stable, anaemic, premature infants before and after transfusion using our current blood transfusion protocol based on a haematocrit threshold (<24%) and the neonatologist's discretion. MATERIAL AND METHODS: Stable premature infants with a haematocrit level ≤30% were prospectively enrolled into the study. Cerebral, intestinal and renal blood flow velocities, cardiac function parameters and vital signs were measured up to three times following every routine haematocrit analysis. Moreover, transfused infants were evaluated three more times: directly before transfusion, and 24 hours and 72 hours after transfusion. RESULTS: Thirty-six infants were enrolled and 23 of them were transfused. Subgroup analysis of transfused infants showed a significant decrease in cerebral blood flow velocities, cardiac output and heart rate. These changes persisted after transfusion. In the entire cohort, the degree of anaemia correlated with the increase of cerebral blood flow velocities, heart rate and cardiac output. DISCUSSION: Cerebral blood velocities in the anterior cerebral artery might represent an objective Doppler sonographic criterion indicating the need for transfusion. The measurement of these velocities is non-invasive and quick and easy to perform. However, a randomised, controlled trial is necessary before a formal recommendation can be made.