Anemia, Hepcidin, and Vitamin D in Healthy Preterm Infants: A Pilot Study

Objective The etiology of anemia in premature neonates is multifactorial and may involve anemia of inflammation mediated by hepcidin. Hepcidin expression is suppressed by vitamin D. We aimed to investigate the interrelationship between hepcidin, anemia, and vitamin D status in preterm infants. Study Design Preterm infants aged 1 to 5 weeks were prospectively recruited at the neonatal intensive care unit of the Dana Dwek Children Hospital. Blood counts and serum levels of hepcidin, ferritin, iron, 25-hydroxyvitamin D [25(OH)D] and C-reactive protein (CRP) were measured and compared between anemic and nonanemic preterm infants. Results Forty-seven preterm infants (mean ± standard deviation gestational age at birth 32.8 ± 1.1 weeks, 66% males) were recruited. In total, 36% of the preterm infants were vitamin D deficient [25(OH)D < 20 ng/mL] and 15% were anemic. Hepcidin levels were significantly higher in anemic premature infants than in the nonanemic group (55.3 ± 23.9 ng/mL vs. 30.1 ± 16.3 ng/mL, respectively, p < 0.05). No differences were found in iron, ferritin, 25(OH)D, and CRP levels between anemic and nonanemic premature newborn infants. A positive correlation was found between hepcidin and ferritin (R2 = 0.247, p = 0.02) and a negative correlation was found between 25(OH)D and CRP (R2 = 0.1, p = 0.04). No significant correlations were found between 25(OH)D and hepcidin, iron, ferritin, or CRP. Conclusion Anemia of prematurity was associated with high hepcidin serum levels. The exact mechanisms leading to anemia and the role of vitamin D warrant further investigation. Key Points

The Extremely Low Birth Weight Infant

Extremely low birth weight infants (ELBW) are defined by birth weight of less than 1000 g and are frequently born at 27 weeks’ gestation (GW) or younger. The neonatologists’ efforts focused on improvement of intact survival rate, especially for those born at the frontiers of viability at 22/23 GW. Survival rates of >80% for the advanced gestations and > 50% for 23–24 GW have been reported. Higher gestational age and birth weight, female gender, better maternal education, and white race have been recognized as significant predictors of decreased morbidity in ELBW infants. Although the mortality rate has significantly contracted for this group with improved technology and better understanding of pathophysiology, the proportion of surviving infants without sequelae, has not improved as noticeably. We review the short and long-term morbidities in ELBW infants and compare own and literature data. We analyze some of the specific immediate problems for this group such as: respiratory problems, infection, thermoregulation, impaired glucose homeostasis and disturbed cardiovascular and excretory functions as well as late morbidities such as bronchopulmonary dysplasia, late-onset infections, central nervous system occurrences, retinopathy and anemia of prematurity. We also deal with preventive and therapeutic strategies for improved outcome in this sensitive group of patients.

Survey on clinical use and non-use of recombinant human erythropoietin in European neonatal units

ObjectivesRecombinant human erythropoietin (rhEPO) has been shown to effectively and safely prevent the anemia of prematurity and to reduce the transfusion need in very low birth weight (VLBW) infants and has been licensed for this indication in Europe in 1997. The objective of the study was to obtain information on the use or non-use of rhEPO in neonatal units in Germany and other European countries.MethodsAnonymized 14-questions web-based questionnaire.ResultsSeventy-nine questionnaires from Germany and 63 questionnaires from other 15 European countries were completed. Of the responders, 39% indicated to use rhEPO routinely or occasionally in VLBW infants, whereas 61% responded to never use rhEPO in this population. The major reasons given for non-use were lack of recommendation in national guidelines (69%) and/or doubt about efficacy of rhEPO to reduce transfusion need (53%). Twenty-seven percent of the responders indicated to use rhEPO for neonates with birth weights above 1,500 g. Neuroprotection in VLBW infants (26%) and hypoxic ischemic encephalopathy in term neonates (27%) were given as indications for off label use of rhEPO.ConclusionsThis survey indicates that rhEPO is used for the anemia of prematurity as licensed in less than half of neonatal units in Germany and other European countries. On the other hand it seems to be used off label in neonates for neuroprotection in a considerable number of units although there is no final evidence on its neuroprotective effects.

Epidemiology, treatment and outcomes of anemia in premature newborn babies in Centre Hospitalierd’Essos, Yaounde, Cameroon.

IntroductionAt birth, all newborns experience a decrease in hemoglobin levels; this decrease is more emphasized in premature babies. The objective of this work was to study the epidemiological, therapeutic and outcomesof anemia amongst preterm birthsin a reference hospital in Cameroon.MethodologyThis was a two-year retrospective cohort study (January 1, 2016 to December 31, 2017). All premature infants with a hemoglobin level below 14g/dl at a given time of hospitalization were included in the study; these were divided into two groups: group A transfusion recipients and group B non-transfusion recipients. The main measurements were prevalence of premature anemia and incidence of blood transfusion, features of population and outcomes.Results142 cases of anemic premature infants (56.34% female) with a mean gestationalage of 31.58 +/- 2.81 weeks of amenorrhea and a mean birth weight of 1652.78 +/- 514.77g were included in the study. The prevalence of premature anemia was 24.2%. Blood transfusion was the most widely used therapeutic method with an incidence of 57.75%, follow by iron (56.34%) and Erythropoietin (EPO) (4.93%). Out of the 142 cases recruited, 82 were in the transfusion group and 60 in the non-transfusion group. Predictive factors of blood transfusion were gestational age (33 weeks), birth weight (less than 1500g) and non-administration of vitamin K and Uvesterol®. Premature infants transfused compared to those not transfused had a longer duration of hospitalisation (p<0,001) and more complications during hospitalization (p<0,001). The overall mortality rate was 21.13% with a higher rate in the transfused group (12,68% vs. 8, 45%) but no significant (p=0.96).ConclusionAnemia of prematurity isa frequent pathology in this setting, with Blood transfusion as main therapy. Administration of vitamin K and Uvesterol®should be ensured in this population while advocating for the access to EPO.

Anemia of Prematurity and Oral Feeding Milestones in Premature Infants

Objective Anemia of prematurity (AOP) and oral feeding problems are common in premature infants. This study aimed to determine the influence of AOP on aerodigestive outcomes and the duration to full Per Oral (PO). Study Design Prospectively collected data on premature infants who initiated oral feeds at ≤ 34 weeks' postmenstrual age were examined. Infants were categorized into “AOP+” and “AOP−” based on hematocrit at initial PO, that is, < 29 or ≥ 29%. Results Forty-four infants in AOP+ compared with 74 in AOP−. AOP+ infants had lower birth gestation and weight (p < 0.001). The anthropometrics at initial PO were similar. AOP+ had lower mean hematocrit and higher oxygen need at initial PO, and at full PO (p < 0.05). AOP+ reached full PO at a later gestation and took longer days from initial PO to full PO (p < 0.01). BPD, intraventricular hemorrhage (IVH ≤ 2), and hospital stay were greater in the AOP+ (p < 0.05). After adjusting for covariates, initial PO hematocrit was not predictive of time to full PO [hazard ratio 1.3 (CI 0.88–2.0), p = 0.18]. Conclusion AOP is not independently associated with the duration to full PO. Supplemental oxygen for associated comorbidities may have compensated for the underlying anemia.

The recombinant human erythropoietin therapy for extremely and very low birth weight infants

Anemia of prematurity is a common pathology in premature infants. The prevalence of anemia of prematurity is inversely proportional to the gestational age and body weight at birth. The pathogenetic importance of impaired erythropoietin (EPO) production in anemia of prematurity provides the rationale for therapy with erythropoiesis stimulating agents (ESAs) including recombinant EPO. A comparative analysis of the effectiveness of different regimens of recombinant human erythropoietin in extremely and very low birth weight infants (ELBW and VLBW) was studied. Research has been set as a prospective analysis of 133 VLBW and ELBW infants (in the period from December 2017 to February 2019). Gestational age (GA) of the children ranged from 26 to 33 weeks, of these, GA of 75 children (56%) was 30 weeks or less. Depending on the treatment of anemia of prematurity all infants were divided into 5 groups: group 1 (n = 26) – premature babies who were prescribed ESAs since 3 day of life 200 IU/kg 3 times per week subcutaneously; group 2 (n = 21) – premature babies who were prescribed ESAs since 3 day of life 400 IU/kg 3 times per week subcutaneously; group 3 (n = 37) – premature babies who were prescribed ESAs since 8 day of life 200 IU/kg 3 times per week subcutaneously; group 4 (n = 18) – premature babies who were prescribed ESAs since 8 day of life 400 IU/kg 3 times per week subcutaneously; group 5 (n = 31) premature infants who did not receive treatment with recombinant human erythropoietin (control group). Subgroups of children of gestational age ≤ 30 weeks were identified in each group. The groups and subgroups did not differ significantly in gestational age, weight, birth length, and Apgar score at 1 and 5 minutes of life, p > 0.05. Also, there were no statistically significant differences in the age of the 1st transfusion, the frequency and total volume of transfusions, the duration of respiratory therapy, the duration of hospitalization, including treatment in NICU, body weight and age at discharge. The frequency of retinopathy of prematurity stage ≥ 3, periventricular leukomalacia, bronchopulmonary dysplasia of moderate and severe severity, intraventricular hemorrhages of varying severity, necrotizing enterocolitis was not statistically significant in the study groups and subgroups. Statistically significant differences in the concentration of hemoglobin in the peripheral blood of premature infants were revealed at discharge. In the control group, children had a lower level of hemoglobin at discharge (94 g/l) compared with the groups with early appointment of ESAs (109 g/l and 107 g/l in groups 1 and 2, respectively, P0-1 = 0.048 and P0-2 = 0.047) due to newborn GA ≤ 30 weeks. It is preferable to use of the drug ESAs at a dose of 200 IU/kg 3 p/week p/, starting from the 3rd day of life. The effectiveness of erythropoietin therapy, the time of its start and various treatment regimens remain controversial issues that require further study. The study was approved by the Independent Ethics Committee of the National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov.