Amniotic fluid erythropoietin and neonatal outcome in pregnancies complicated by intrauterine growth restriction before 34 gestational weeks

Seikku, Laura; Rahkonen, Leena; Tikkanen, Minna; Hämäläinen, Esa; Rahkonen, Petri; Andersson, Sture; Teramo, Kari; Paavonen, Jorma; Stefanović, Vedran

doi:10.1111/aogs.12553

Cited by 12 publications

(9 citation statements)

References 31 publications

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“…In addition, EPO decreases both autophagy and apoptosis via the Akt/mTOR signaling pathway and the MAPK/ ERK pathway, and thus it reduces intestinal mucosa injury from inflammation [11]. Studies also indicate that EPO reduces the occurrence of NEC in mice and rats by inhibiting the lipid peroxidation mediated by oxygen-free radicals [29] and the excessive production of nitric oxide [9,30,31], both of which are associated with the pathogenesis of NEC. In infants, rhEPO (200 IU/kg twice a week for a total of 1 week) reduced neonatal NEC injury by reducing inflammation [13].…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial

et al. 2020

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Background: Necrotizing enterocolitis (NEC) is one of the most severe complications in very preterm infants, but there are currently no accepted methods to prevent NEC. Studies have shown that erythropoietin (EPO) has the potential to prevent NEC or improve outcomes of preterm NEC. This study aimed to determine whether recombinant human EPO (rhEPO) could protect against NEC in very preterm infants. Methods: The study was a prospective randomized clinical trial performed among four NICU centers. A total of 1327 preterm infants with gestational age ≤ 32 weeks were admitted to the centers, and 42 infants were excluded leaving 1285 eligible infants to be randomized to the rhEPO or control group. Infants in the rhEPO group were given 500 IU/ kg rhEPO intravenously every other day for 2 weeks, while the control group was given the same volume of saline. The primary outcome was the incidence of NEC in very preterm infants at 36 weeks of corrected gestational age. Results: A total of 1285 infants were analyzed at 36 weeks of corrected age for the incidence of NEC. rhEPO treatment significantly decreased the incidence of NEC (stage I, II and III) (12.0% vs. 17.1%, p = 0.010), especially confirmed NEC (stage II and III) (3.0% vs. 5.4%, p = 0.027). Meanwhile, rhEPO treatment significantly reduced the number of red blood cells transfusion in the confirmed NEC cases (1.2 ± 0.4 vs. 2.7 ± 1.0, p = 0.004). Subgroup analyses showed that rhEPO treatment significantly decreased the incidence of confirmed NEC at gestational age < 28 weeks (p = 0.019), and the incidence of all stages NEC in preterm infants with hemoglobin < 90 g/l (p = 0.000) and 5 min Apgar score > 5 (p = 0.028). Conclusion: Repeated low-dose rhEPO treatment is beneficial against NEC in very preterm infants. Trial registration The protocol was registered retrospectively at ClinicalTrials.gov (NCT03919500) on April 18, 2019. https ://clini caltr ials.gov/ct2/show/NCT03 91950 0

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Section: Discussionmentioning

confidence: 99%

Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial

et al. 2020

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“…Erythropoietinis an erythropoietic hormone that increases Fe use in support of RBC production under conditions of hypoxia. Studies assessing cord blood EPO concentrations in neonates under hypoxic in utero conditions (including pre-eclampsia, placental dysfunction, maternal smokers, or intrauterine growth restriction) found that cord EPO concentrations were elevated compared to neonates under non-hypoxic conditions (64)(65)(66)(67). Only 1 of these studies concurrently measured Hb concentrations and found that neonates born to mothers who smoked during pregnancy had higher EPO and Hb concentrations compared to non-smokers (67).…”

Section: Discussionmentioning

confidence: 99%

Umbilical Cord Serum Ferritin Concentration is Inversely Associated with Umbilical Cord Hemoglobin in Neonates Born to Adolescents Carrying Singletons and Women Carrying Multiples

Delaney

Guillet

Fleming³

et al. 2019

The Journal of Nutrition

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Background It has been proposed that the fetus prioritizes iron for hemoglobin production over delivery to tissues. However, few studies have evaluated the interrelations between hemoglobin and multiple iron status biomarkers in umbilical cord blood. A full understanding is needed of how these parameters influence each other within cord blood to fully interpret iron and hematologic status at birth. Objectives We evaluated the determinants of neonatal hemoglobin and assessed the interrelations between hemoglobin, serum iron status indicators, and serum iron regulatory hormones in healthy neonates. Methods This was an observational study that assessed umbilical cord hemoglobin (Hb), serum ferritin (SF), erythropoietin (EPO), soluble transferrin receptor (sTfR), serum iron, hepcidin, vitamin B-12, folate, IL-6, and CRP measured in 234 neonates born to adolescents or to women carrying multiples. Correlations between these indicators were evaluated and mediation models consistent with the observed significant determinants of cord Hb concentrations were developed. Results A highly significant inverse association was found between cord SF and Hb concentrations that was not attributable to neonatal or maternal inflammation (as measured by IL-6 and CRP). The inverse association was present in the combined cohort, as well as in the adolescent and multiples cohorts independently. Mediation analyses found that EPO and hepcidin had significant indirect effects on cord Hb, associations that are explicable by mediation through SF and sTfR. Conclusion In contrast to observations made in older infants, a highly significant inverse association between Hb and SF, as well positive associations between Hb and both sTfR and EPO, were observed in umbilical cord blood from neonates born to adolescents or women carrying multiples. These findings, combined with review of the published literature, indicate a need for analysis of the relations between multiple parameters to assess iron and hematologic status at birth. These clinical trials were registered at clinicaltrials.gov as NCT01582802 (https://clinicaltrials.gov/ct2/show/NCT01582802) and NCT01019902 (https://clinicaltrials.gov/ct2/show/NCT01019902)

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“…EPO is a biomarker of chronic hypoxia, and increased levels can be detected in fetal plasma and amniotic fluid in various pathological pregnancies [7]. An association of high EPO levels during pregnancy and adverse acute neonatal outcome - such as decreased umbilical cord pH, pO 2 , and BE, and increased intensive care unit admission - has also been reported [7,20]. Furthermore, high levels of umbilical plasma EPO at birth are associated with an increased risk for death or abnormal neurological outcome at 2 years of age [8].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Umbilical Serum Copeptin Relative to Erythropoietin and S100B as Asphyxia Biomarkers at Birth

Summanen¹,

Seikku²,

Rahkonen³

et al. 2017

Neonatology

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Background: Birth asphyxia, estimated to account for a million neonatal deaths annually, can cause a wide variety of neurodevelopmental impairments. There is a need to develop new, swift methods to identify those neonates who would benefit from neuroprotective treatments such as hypothermia. Objectives: To examine the utility of cord serum copeptin, a stable byproduct of arginine vasopressin release, as a biomarker of birth asphyxia based on a comparison with 2 biomarkers of hypoxia and brain trauma: erythropoietin and S100B. Methods: The study population consisted of 140 singleton, term neonates: 113 controls and 27 with birth asphyxia (2/3 criteria met: umbilical artery pH <7.10, base excess ≤12 mmol/L, and 5-min Apgar score <7). All deliveries were planned vaginal, but 51 neonates were born by emergency cesarean section. Copeptin, S100B, and erythropoietin levels in umbilical artery samples were measured by immunoassays. Results: Copeptin correlated in the entire study population more strongly with umbilical artery base excess than S100B and erythropoietin, and only copeptin correlated with arterial pH. Furthermore, only copeptin levels were significantly higher in cases of birth asphyxia, and in vaginally born neonates they were found to increase as a function of labor duration. Copeptin was elevated in neonates born via vacuum extraction, whereas erythropoietin levels showed a slight increase after emergency cesarean section. Conclusions: In this study population, S100B and erythropoietin were not valid biomarkers of birth asphyxia. In contrast, our work suggests that copeptin has high potential to become a routinely used biomarker for acute birth asphyxia and neonatal distress.

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Amniotic fluid erythropoietin and neonatal outcome in pregnancies complicated by intrauterine growth restriction before 34 gestational weeks

Cited by 12 publications

References 31 publications

Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial

Erythropoietin prevents necrotizing enterocolitis in very preterm infants: a randomized controlled trial

Umbilical Cord Serum Ferritin Concentration is Inversely Associated with Umbilical Cord Hemoglobin in Neonates Born to Adolescents Carrying Singletons and Women Carrying Multiples

Comparison of Umbilical Serum Copeptin Relative to Erythropoietin and S100B as Asphyxia Biomarkers at Birth

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