Stored RBC transfusions leads to the systemic inflammatory response syndrome in anemic murine neonates.

OBJECTIVE: RBC transfusions (RBCT) are life-saving treatment for premature and critically ill infants. However, the procedure has been associated with the development of systemic inflammatory response syndrome (SIRS) and potentially multiple organ dysfunction syndrome (MODS) in neonates. The present study aimed to investigate the mechanisms of RBCT-related SIRS in severely anemic murine neonates. METHODS: C57BL/6 (WT), TLR4-/- and myeloid-specific triggered myeloid receptor-1 (trem1)-/- mouse pups were studied in 4 groups (n = 6 each): (1) naïve controls, (2) transfused control, (3) anemic (hematocrit 20-24%) and (4) anemic with RBC transfused using our established murine model of phlebotomy-induced anemia (PIA) and RBC transfusion. Plasma was measured for quantifying inflammatory cytokines (IFN-γ, IL-1ß, TNF-α, IL-6, MIP-1α, MIP-1ß, MIP2 and LIX) using a Luminex assay. In vitro studies included (i) sensitization by exposing the cells to a low level of lipopolysaccharide (LPS; 500 ng/ml) and (ii) trem1-siRNA transfection with/without plasma supernatant from stored RBC to assess the acute inflammatory response through trem1 by qRT-PCR and immunoblotting. RESULTS: Anemic murine pups developed cytokine storm within 2 h of receiving stored RBCs, which increased until 6 h post-transfusion, as compared to non-anemic mice receiving stored RBCTs ("transfusion controls"), in a TLR4-independent fashion. Nonetheless, severely anemic pups had elevated circulating endotoxin levels, thereby sensitizing circulating monocytes to presynthesize proinflammatory cytokines (IFN-γ, IL-1ß, TNF-α, IL-6, MIP-1α, MIP-1ß, MIP2, LIX) and express trem1. Silencing trem1 expression in Raw264.7 cells mitigated both endotoxin-associated presynthesis of proinflammatory cytokines and the RBCT-induced release of inflammatory cytokines. Indeed, myeloid-specific trem1-/- murine pups had significantly reduced evidence of SIRS following RBCTs. CONCLUSION: Severe anemia-associated low-grade inflammation sensitizes monocytes to enhance the synthesis of proinflammatory cytokines and trem1. In this setting, RBCTs further activate these monocytes, thereby inducing SIRS. Inhibiting trem1 in myeloid cells, including monocytes, alleviates the inflammatory response associated with the combined effects of anemia and RBCTs in murine neonates.

Analysis of risk factors and changes in myocardial biomarker levels in 122 cases of early neonatal anemia.

Background/aim: Anemia in the first week after birth, which could affect growth, development, and organ function, should be an important warning sign to clinicians. The aim of this study was to assess the related risk factors of early neonatal anemia and to analyze the effect of anemia on the expression levels of myocardial markers in newborns. Materials and methods: Clinical data from 122 confirmed cases of anemic newborns and 108 nonanemic newborns were collected to analyze the independent risk factors for early anemia using logistic regression analyses. Blood samples were collected from both groups for the detection of myocardial markers, including the protein marker cardiac troponin T (cTnT), as well as enzyme markers creatine kinase isoenzyme MB (CK-MB) and lactate dehydrogenase (LDH). Results: Multivariate logistic regression analysis revealed that preterm birth (OR: 3.589 [1.119-11.506], p < 0.05), multiple pregnancy (OR: 4.117 [1.021-16.611], p < 0.05), and abnormal placenta (OR: 4.712 [1.077-20.625], p < 0.05) were independent risk factors for early neonatal anemia. The levels of myocardial markers, including cTnT (303.1 ± 244.7 vs. 44.2 ± 55.41 ng/L), CK-MB (6.803 ± 8.971 vs. 2.5326 ± 2.927 µkat/L), and LDH (32.42 ± 35.26 vs. 19.73 ± 17.13 µkat/L), were significantly higher in the anemic group than in the nonanemic group. Conclusion: Multiple pregnancy, preterm birth, and abnormal placenta were identified as risk factors for early neonatal anemia. The occurrence of early neonatal anemia was associated with increased levels of myocardial markers.

Does placental abruption cause neonatal anemia?

INTRODUCTION: Placental abruption can result in serious perinatal morbidity and mortality. However, it is not clear whether placental abruption could lead to neonatal anemia, as a direct relation has not been described yet. The objective of this study is to investigate whether there is a relation between occurrence of placental abruption and neonatal anemia. MATERIAL AND METHODS: All women with a clinical diagnoses of placental abruption between January 2016 and April 2021 in Amsterdam UMC, from both the VU University Medical Center and Amsterdam Medical Center, were included. Demographic data and delivery outcomes were collected retrospectively using the medical files. The primary outcome was neonatal anemia, defined as hemoglobin levels less than the fifth percentile for gestational age. RESULTS: A total of 65 mothers and 65 neonates were included in our study. Average gestational age was 30 + 5 weeks. Mean hemoglobin level of the neonates at birth was 16.5 g/dl (10.2 mmol/L) with hemoglobin levels comparable to the reference curve. Two neonates (3.6%) were diagnosed with anemia based on their hemoglobin level at birth, and six (9.2%) neonates received a blood transfusion within 24 h after birth. CONCLUSIONS: With this study, we found that the hemoglobin levels of the neonates born after placental abruption are comparable to the reference curve and do not show more neonates than expected below the fifth percentile for gestational age. It remains unclear whether there is fetal blood loss during a placental abruption but our results suggest that at least a big amount of fetal blood is not lost, since we did not found a large number of anemic neonates. Severe neonatal anemia in the case of placental abruption does not need to be expected.

Fetomaternal hemorrhage: evaluation of recurrence within a large integrated healthcare system.

BACKGROUND: Fetomaternal hemorrhage is associated with severe fetal morbidity and mortality. The recurrence risk of fetomaternal hemorrhage is unknown. OBJECTIVE: We sought to establish the recurrence rate of fetomaternal hemorrhage in a large integrated healthcare system over a 10-year period. STUDY DESIGN: In this retrospective study within the Kaiser Permanente Northern California medical system, cases of fetomaternal hemorrhage were defined by either an elevated fetal hemoglobin level as determined by flow cytometry for a concerning pregnancy outcome (preterm delivery, perinatal demise, neonatal anemia, or transfusion within the first 2 days of life) or by perinatal demise with autopsy findings suggestive of fetomaternal hemorrhage. The outcomes of subsequent pregnancies were reviewed for features of recurrence. RESULTS: Within the 2008 to 2018 birth cohort of 375,864 pregnancies, flow cytometry testing for fetal hemoglobin levels was performed in 20,582 pregnancies. We identified 340 cases of fetomaternal hemorrhage (approximately 1 in 1100 births). Within the cohort of 340 affected pregnancies, perinatal loss was recorded for 80 (23.5%) pregnancies and 50 (14.7%) pregnancies delivered neonates who required transfusion. The affected patients had 225 subsequent pregnancies of which 210 were included in the analysis. Of these, 174 (82.9%) advanced beyond the threshold of viability and were delivered within our healthcare system. There was 1 case of recurrent fetomaternal hemorrhage identified. The recurrent case involved a spontaneous preterm delivery of an infant who was noted to have an elevated reticulocyte count but was clinically well. CONCLUSION: Within our large integrated healthcare system, approximately 1 in 1100 pregnancies was affected by fetomaternal hemorrhage within a 10-year period, which is comparable with previous studies. We identified 1 case of recurrence, yielding a recurrence rate of 0.5%. This infant did not have features of clinically important fetomaternal hemorrhage. This information can inform counseling of patients with affected pregnancies.

The landscape of pediatric Diamond-Blackfan anemia in Switzerland: genotype and phenotype characteristics.

Diamond-Blackfan anemia (DBA) is caused mainly by genetic mutations in large (RPL) or small ribosomal subunit genes (RPS) and presents with macrocytic anemia and congenital malformations. Clinical differences between genotypes are insufficiently understood. The aim of this study was to assess clinical features, treatment strategies, and genotypes in the Swiss pediatric DBA population. We retrospectively reviewed medical charts of pediatric patients with DBA in Switzerland and stratified patients by RPL versus RPS mutations. We report 17 DBA patients in Switzerland who were all genetically investigated. In our cohort, patients showed a wide spectrum of clinical presentations and treatment needs. We found a high proportion of physical malformations (77%) including lower limb (17%) and anorectal (12%) malformations. The two patients with anorectal malformations presented both with antepositioning of the anus needing surgery within the first 15 months of life. One of these patients had sphincteric dysfunction, the other coccygeal agenesis. We found that included patients with an RPL mutation more frequently tended to have physical malformations and a milder anemia compared to patients with an RPS mutation (median hemoglobin at diagnosis 76 g/l versus 22 g/l).Conclusion: We illustrate the wide clinical and genetic spectrum of DBA in Switzerland. Our findings highlight the need to take this diagnosis into consideration in patients with severe anemia but also in patients with mild anemia where malformations are present. Lower limb and anorectal malformation extend the spectrum of DBA-associated malformations. What is Known? • There is a large variation in the phenotype of Diamond-Blackfan Anemia (DBA) and diversity of genetic mutations. • Malformation of the upper limbs, head and face, heart, and genitourinary system is frequently identified. What is New? • Patients with lower limb and anorectal malformations were repetitively found in our cohort enlarging the clinical spectrum of malformations. • We show two patients of the same family with a DBA-like condition where the same RPL17 variant was identified.

Association of maternal hemoglobin and iron stores with neonatal hemoglobin and iron stores.

BACKGROUND: One of the commonest causes of anemia in pregnancy is iron deficiency. This study aims at understanding and exploring the association between fetal and maternal iron status. Predelivery maternal hemoglobin (Hb) and iron stores, serum iron, ferritin, and soluble transferrin receptor (sTfR), were assessed and compared to the cord blood Hb and iron stores with an attempt to identify the level of maternal Hb and ferritin at which the fetal iron stores reduce, helping to identify the neonates who will require earlier iron supplementation. METHOD: Four hundred eight participants were enrolled, and maternal and cord blood was collected at the time of delivery and tested for Hb and iron parameters. The results were statistically analyzed. RESULTS: Of all mothers, 27.2% mothers were anemic (Hb less than 11 g/dl). Of all newborns, 15.4% newborns had Hb less than 14 g/dl. There was a significant association between the maternal and cord blood iron, ferritin, sTfR and sTfR/log ferritin index. Eighty-five percent of the babies with cord blood Hb <14 g/dl had maternal serum ferritin (SF) <50 µg/L. Maternal SF <10 µg/l was associated with a significant number of babies with cord blood SF <75 µg/l (77.7%). One hundred sixty six neonates had sTfR 2 µg/ml or more. Of these, 80.7% had maternal SF <50 µg/l. Of the 115 newborns with a high sTfR/log ferritin index (>1.5), 56.5% had raised maternal sTfR (>2µg/ml). CONCLUSION: In view of a significant association between maternal and neonatal Hb and iron stores, newborns of mothers with iron deficiency anemia (IDA) during pregnancy should be monitored and followed up after birth for development of IDA and early iron supplementation.

A disadvantage of cesarean section en caul: Umbilical velamentous insertion, a risk factor and proposed mechanism of neonatal anemia.

Cesarean section en caul could cause neonatal anemia, but the mechanism remains unknown. We demonstrate an association between neonatal anemia and velamentous insertion of the umbilical cord in cesarean section en caul, and suggest a way to make this procedure safer. We performed cesarean section en caul, but the placenta and the membrane sac were delivered separately. The neonate was severely anemic. The umbilical cord was attached to the membrane and the blood vessel connecting the umbilical cord and placenta was torn. The amniotic membrane covering the placental surface had peeled away. Velamentous insertion of the umbilical cord could be a cause of neonatal anemia associated with cesarean section en caul.

Delayed clamping vs milking of umbilical cord in preterm infants: a randomized controlled trial.

BACKGROUND: It has been established that delayed umbilical cord clamping in preterm infants results in improvement in neonatal anemia, need for transfusion, incidence of necrotizing enterocolitis, and intraventricular hemorrhage by increasing neonatal circulating blood volume. However, the effects of umbilical cord milking as an alternative to delayed clamping in preterm infants are unclear. OBJECTIVE: The primary objective of this study was to compare the effect of delayed clamping vs milking of the umbilical cord on the initial hematocrit concentration in preterm births (23-34 weeks gestation). In addition, we sought to compare the effects of delayed clamping vs milking on the incidences of intraventricular hemorrhage, necrotizing enterocolitis, and need for transfusion (secondary objectives). STUDY DESIGN: The study was an unblinded randomized controlled trial of singleton preterm infants who were born 23 weeks 0 days to 34 weeks 6 days gestation and were assigned to 1 of 2 controlled study groups: delayed cord clamping for 60 seconds or milking of the cord towards the infant 4 times before clamping. Randomization occurred via block randomization with an allocation ratio of 1 to 1. The patients' third stage of delivery was standardized for route of delivery and randomization arm. All comparisons were preformed with an intent-to-treat analysis approach. The study was powered at 80% with a probability value of .05 for the primary outcome measure of a hematocrit difference of 3% between the 2 groups. RESULTS: Of the 204 randomized patients, 104 were assigned to the delayed subgroup, and 100 were assigned to the milking subgroup. There were no significant differences in baseline maternal characteristics noted between groups. Though there was not any statistically significant difference in neonatal outcomes between the cord clamping and milking groups, the occurrences of transfusion (15.5% vs 9.1%; P=.24), necrotizing enterocolitis (5.8% vs 3.0%; P=.49), and intraventricular hemorrhage (15.5% vs 10.1%; P=.35) were all lower in the milking group. The milking group had higher initial hematocrit concentration compared with the delayed clamping group, although this was not significant (51.8 [6.2%] vs 49.9 [7.7%]; P=.07]. Peak bilirubin levels and need for phototherapy were similar between groups. CONCLUSION: This study demonstrates that milking the umbilical cord may be an acceptable alternative to delayed cord clamping because there were similar effects on neonatal hematocrit concentrations and the need for neonatal transfusions and no increased risk for complications or neonatal morbidity. The present data support the concept that milking of the umbilical cord may offer an efficient and timely method of providing increased blood volume to the infant.

First Report of a Novel Deletion Due to εγδß-Thalassemia in a Chinese Family.

A fetus of Chinese descent presented with ultrasound features of anemia at 20 weeks' gestation. Father had low a mean corpuscular volume (MCV) level. Multiplex gap-polymerase chain reaction (gap-PCR) excluded common α-thalassemia (α-thal) deletions and mutations and PCR sequencing of the α1- and α2-globin genes were negative. The fetus had a normal karyotype. Array comparative genomic hybridization (aCGH) showed a single copy loss of 189.87 kb in chromosome 11p15.4, involving the whole ß-globin gene cluster, inherited from the father. Multiplex ligation-dependent probe amplification (MLPA) confirmed the deletion included the ε-globin gene, confirming the diagnosis of heterozygous (εγδß)0-thalassemia [(εγδß)0-thal], also inherited from the father. The fetus had a worsening anemic condition in utero and required a transfusion at 26 weeks' gestation, raising the hemoglobin (Hb) level from 5.3 to 12.6g/dL. A cesarean-section was subsequently performed at 32 weeks' gestation because of reduced fetal movements, and a 1650g baby girl with good Apgar scores was delivered. Hemoglobin at birth was 12.8g/dL, gradually dropping to 6.8 g/dL, requiring three neonatal transfusions. Her condition gradually stabilized after 2 months with Hb stable at 8.0 g/dL. Family screening by MLPA showed that the paternal grandmother carried the same deletion. The deletion in this case is distinct and is the reported first case. The deletion transmitted across three successive generations with great phenotypic variation. The final adult phenotype of (εγδß)0-thal is usually mild, therefore, with accurate prenatal diagnosis this condition is salvageable by in utero and early neonatal transfusions, preventing adverse pregnancy and neonatal outcomes.

Case Report: Fetomaternal hemorrhage and its association with pronounced neonatal anemia.

Fetomaternal hemorrhage (FMH) is a perplexing obstetric condition that predominantly occurs during the third trimester or at the time of delivery. Its insidious and non-specific onset often leads to diagnostic challenges. The underlying pathophysiology of FMH remains incompletely understood, though it is primarily attributed to compromise of the placental barrier. The severity of the condition is intrinsically associated with the volumn of blood loss, the hemorrhage rate, and the presence of alloimmunity. Upon the occurrence of severe FMH, it can rapidly lead to intrauterine distress, fetal anemia, and the possibility of fetal demise, presenting a considerable threat to both maternal and neonatal well-being. In this article, I present a substantial case of FMH and conduct a systematic review of the current scientific literature regarding the etiology, clinical manifestations, diagnostic approaches, treatment highlights, and prognosis of this condition. The objective of this work is to improve clinicians' comprehension and diagnostic proficiency concerning FMH.

Placental ferroportin protein abundance is associated with neonatal erythropoietic activity and iron status in newborns at high risk for iron deficiency and anemia.

BACKGROUND: Murine data suggest that the placenta downregulates ferroportin (FPN) when iron is limited to prioritize iron for its own needs. Human data on the impact of maternal and neonatal iron status on placental FPN expression are conflicting. OBJECTIVES: This study aimed to identify determinants of placental FPN protein abundance and to assess the utility of the placental iron deficiency index (PIDI) as a measure of maternal/fetal iron status in newborns at high risk for anemia. METHODS: Placental FPN protein abundance was measured by western blots in placentae collected from 133 neonates born to adolescents (17.4 ± 1.1 y) carrying singletons (delivery gestational age [GA]: 39.9 ± 1.3 wk) and from 130 neonates born to 65 females (30.4 ± 5.2 y) carrying multiples (delivery GA: 35.0 ± 2.8 wk). Placental FPN and the PIDI (FPN:transferrin receptor 1) were evaluated in relation to neonatal and maternal iron-related markers (hemoglobin [Hb], serum ferritin [SF], soluble transferrin receptor [sTfR], total body iron [TBI], hepcidin, erythropoietin [EPO], erythroferrone). RESULTS: FPN protein was detected in all placentae delivered between 25 and 42 wk GA. Placental FPN protein abundance was associated with neonatal iron and erythropoietic markers (EPO: ß: 0.10; 95% confidence interval [CI]: 0.06, 0.35; sTfR: ß: 0.20; 95% CI: 0.03, 0.18; hepcidin: ß: -0.06; 95% CI: -0.13, -0.0003; all P < 0.05). Maternal sTfR was only indirectly associated with placental FPN, with neonatal sTfR as the mediator (ß-indirect: 0.06; 95% CI; 0.03, 0.11; P = 0.003). The PIDI was associated with neonatal Hb (ß: -0.02; 95% CI: -0.03, -0.003), EPO (ß: 0.07; 95% CI: 0.01, 0.14), and sTfR (ß: 0.13; 95% CI: 0.004, 0.3) and with maternal SF (ß: 0.08, 95% CI: 0.02, 0.14), TBI (ß: 0.02; 95% CI: 0.009, 0.04), EPO (ß: -0.10; 95% CI: -0.19, -0.01), sTfR (ß: -0.16: 95% CI: -0.27, -0.06), and hepcidin (ß: 0.05; 95% CI: 0.002, 0.11) at delivery (all P < 0.05). CONCLUSIONS: Placental FPN abundance was positively associated with neonatal indicators of increased erythropoietic activity and poor iron status. The PIDI was associated with maternal and neonatal iron-related markers but in opposite directions. More data are needed from a lower-risk normative group of females to assess the generalizability of findings. These trials were registered at clinicaltrials.gov as NCT01019902 and NCT01582802.

40 years neonatology : An academic life.

BACKGROUND: A complete review of the development of neonatology in the last 40 years would probably require a compendium with several volumes, to bring to view the remarkable improvements in survival rates and neurodevelopmental outcomes of ill babies in Austria, most industrial countries and to some extent worldwide. The challenge I had to solve here was to integrate my own contributions to the field of neonatology during this period and particularly the contributions of my team from the Division of Neonatology and Pediatric Intensive Care Medicine, Department of Pediatrics and Adolescence Medicine, Medical University Vienna where I was working first as an intern and resident and later had the privilege to become head of department. AIM: This very personal review was conceived to showcase the milestones of neonatology where, in my opinion, our department made some meaningful contributions in research and clinical practice during the past 40 years. METHODS: A total of 10 areas of interest were selected which most likely influenced survival rates of preterm infants born at increasingly younger gestational ages and ameliorated long-term clinical and neurodevelopmental outcomes, including: 1) Construction and continuous modernization of neonatal intensive care units (NICUs). 2) Installation of the "Regionalization Program for NICUs in Vienna". 3) Treatment of respiratory distress syndrome (RDS) of premature babies. 4) Fine tuning of glucose metabolism for growth and outcome. 5) Neurodevelopmental care. 6) Neonatal hematology. 7) Infection control. 8) The toxoplasma screening program. 9) The newborn screening program. 10) Quality control: the Vermont Oxford Neonatal Network (VONN). RESULTS: Over the past four decades advancements in research and technology have allowed a transformative development of neonatal medicine. Survival rates without increased morbidity for very premature infants with gestational ages reaching to what we consider nowadays the border of viability have constantly increased. In my professional life as a neonatologist in Austria I have had the possibility to support and shape some of these developments together with my team. CONCLUSION: As we look ahead it is imperative to build upon the progress made, harnessing the power of science and technology to further improve the survival and quality of life for preterm infants in Austria and worldwide. At the same time, neonatology must continue to prioritize ethical reflection and education, fostering a culture of integrity, interdisciplinary collaboration, and the development of guidelines and protocols that uphold ethical standards while addressing the evolving needs and complexities of neonatal medicine.

A Study on the Effect of Umbilical Cord Milking Along With Delayed Cord Clamping on Hematological Parameters in Comparison to Delayed Cord Clamping Alone in Moderate-to-Late Preterm Newborns.

Background Anemia, particularly iron deficiency anemia (IDA), is a global public health issue with serious implications for infant cognitive and developmental outcomes. Preterm infants are especially vulnerable to IDA due to reduced placental blood transfer at birth. Delayed cord clamping (DCC) and umbilical cord milking (UCM) are interventions aimed at enhancing this blood transfer, thereby improving neonatal iron status. While DCC allows passive blood transfer by delaying cord clamping, UCM actively expedites the process. However, there remains a lack of consensus on the comparative benefits of these methods, particularly in preterm infants. This study aims to clarify the efficacy of UCM combined with DCC versus DCC alone in improving hematological outcomes in moderate-to-late preterm newborns. Methodology This comparative study was conducted at Maharaja Agrasen Medical College, Agroha, Hisar, Haryana, over a 12-month period. The study included 200 moderate-to-late preterm infants (32-36+6 weeks of gestation), divided into two groups: Group A (DCC alone) and Group B (DCC combined with UCM). The study aimed to compare the effects of these two interventions on hematological outcomes. Data were collected on baseline characteristics, birth weight, hemoglobin (Hb) levels at birth and at six weeks, serum ferritin levels at six weeks, and any complications. Statistical analyses included independent t-tests for continuous variables and chi-squared tests for categorical variables to assess the differences between the two groups. Results There were no significant differences in the baseline characteristics, birth weight, or clamping time between the two groups. Mean Hb levels at birth were 15.46 g/dL in the DCC group and 15.72 g/dL in the DCC+UCM group (p = 0.429). At six weeks, the mean Hb levels were 13.10 g/dL for the DCC and 13.24 g/dL for the DCC+UCM (p = 0.541). Serum ferritin levels at six weeks were 239.26 ng/mL for the DCC and 258.06 ng/mL for DCC+UCM (p = 0.146). Complications were similar between the groups, with no significant differences in the rates of intraventricular hemorrhage (IVH), jaundice, or polycythemia. Conclusion In this study, the combination of UCM with DCC did not show significant differences in hematological outcomes compared to DCC alone in moderate-to-late preterm infants. Both interventions demonstrated similar results for hemoglobin and ferritin levels, and there were no notable differences in adverse outcomes. Further research with larger sample sizes and longer follow-ups is necessary to better understand the potential benefits of UCM in preterm neonates.

Kasabach-Merritt Syndrome, an underdiagnosed swollen leg in newborn with anemia and jaundice.

Key Clinical Message: Kasabach-Merritt syndrome is a rare disease. Early recognition, timely transfer, and proper management are crucial in reducing bleeding complication and mortality. Abstract: The authors report a rare case of Kasabach-Merritt syndrome in a Cambodian neonate presenting with anemia and jaundice at Day 5 of life. Since the mass was not recognized at birth, the diagnosis and treatment were delayed, thus leading to demise.

Thiopurine Exposure During Pregnancy is Not Associated With Anemia in Infants Born to Mothers With IBD.

Background: Thiopurines are commonly used to treat inflammatory bowel disease (IBD). Thiopurines are considered safe throughout pregnancy. However, a published study suggested the risk of neonatal anemia was increased if exposed to thiopurines in utero. This prospective cohort study aimed to determine if there is an increased risk of cytopenia among infants born to pregnant people with IBD, exposed or unexposed to thiopurines, compared to infants born to those without IBD. Methods: Pregnant IBD patients, with and without thiopurine exposure, and one cohort of control individuals were recruited over a 5-year period. Consenting individuals completed a questionnaire and infants had a complete blood cell count at the newborn heel prick. Anemia was defined as hemoglobin (Hb) < 140g/L. Descriptive statistics were used to characterize the study population. Fisher exact tests were used to examine differences in outcomes between groups, a P-value of < 0.05 was deemed significant. Results: Three cohorts were recruited: 19 IBD patients on thiopurines, 50 IBD patients not on thiopurines, and 37 controls (total of 106). Neonatal median Hb was not different with 177g/L (IQR 38g/L) for the IBD thiopurine group, 180.5g/L (IQR 40g/L) for the IBD non-thiopurine group, and 181g/L (IQR 37g/L) for the controls. Nineteen infants (18%) were cytopenic with 12 (11%) anemic, 6 (5.6%) thrombocytopenic, and 1 (0.94%) lymphopenic. Thiopurine exposure was only in one, mildly anemic, infant. Conclusions: These findings further support physicians and IBD patients contemplating pregnancy that current guidelines recommending thiopurine adherence do not lead to increased perinatal risk of anemia or cytopenia.

Effect of delayed cord clamping on red blood cell alloimmunization: a retrospective cohort study.

BACKGROUND: Although delayed cord clamping has well-known benefits for preterm and term neonates, it has been inadequately assessed in alloimmunized neonates. OBJECTIVE: This study aimed to evaluate the benefits and risks of delayed cord clamping in alloimmunized neonates. STUDY DESIGN: This was a retrospective comparative pre-post cohort study conducted from 2003 to 2018 in a tertiary care center in France. All living singleton neonates whose mothers were followed up for red blood cell alloimmunization during gestation and confirmed at birth (N=224) were included. Neonates were either exposed to immediate (n=125) or delayed cord clamping (n=99). Our main outcome was the time from birth to first exchange transfusions and/or transfusions. Secondary outcomes were hemoglobin level at birth, rate of exchange transfusion, number of postnatal transfusions, maximum bilirubin level, and number of phototherapy hours. RESULTS: Hemoglobin at birth was significantly higher in case of delayed cord clamping (mean difference, 1.7 g/dL; 95% confidence interval, 0.7-2.8). Among infants treated with exchange transfusion or transfusion, the time to initial treatment was higher in case of delayed cord clamping (median difference, 8 days; rate ratio, 1.51; 95% confidence interval, 1.09-2.10). There were no significant differences in the need for exchange transfusion, the number of transfusions, the maximum total bilirubin level, nor the number of phototherapy hours. In the subgroup analysis of neonates needing intrauterine transfusion during pregnancy (ie, severe alloimmunization), neonates had a lower rate of exchange transfusion in case of delayed cord clamping (odds ratio, 0.36; 95% confidence interval, 0.15-0.82). CONCLUSION: Our results indicate a benefit of delayed cord clamping in alloimmunization, regardless of pathology severity, without increased risk of jaundice.

Characterization of Neutropenia in Preterm Neonates Following Administration of Darbepoetin Alfa.

OBJECTIVE: This study is to evaluate the effects of darbepoetin alfa (darbe) on neutrophil count in preterm neonates treated for anemia of prematurity. METHODS: This was a retrospective chart review comparing the absolute neutrophil counts (ANCs) of neonates administered 2 doses of subcutaneous darbe 10 mcg/kg to that of a randomly selected comparator group of neonates not administered the drug. Neonates <34 weeks gestational age, gestational age between 23w1d and 33w4d, born between July 2016 and June 2019, were included in the study. RESULTS: The ANCs of 45 darbe-treated neonates compared with those of 45 randomly selected comparator control neonates revealed no difference in the rate of occurrence of neutropenia (ANC ≤1000/µL) between the darbe-treated neonates (26.7%) and comparator neonates (24.4%) (p > 0.99). There was also no difference in the rate of occurrence of severe neutropenia (ANC ≤500/µL) between the darbe-treated neonates (11.1%) and comparator neonates (6.7%) (p = 0.70). Darbepoetin alfa did not lead to differences in rates of resolution of neutropenia or severe neutropenia. CONCLUSIONS: Short-term administration of darbe did not affect the ANCs of preterm neonates treated for anemia of prematurity. There was no difference in the rates of occurrence of neutropenia, severe neutropenia, or resolution of either between the darbe-treated neonates and comparator neonates.