Neonatal Anemia Research Articles

Mutation in Erythroid-Specific Transcription Factor EKLF/KLF1 Elevates Erythroid Metabolism and Induces Inflammation

EKLF/Klf1 a master transcriptional activator that regulates erythroid maturation and fate specification. The C-terminus of EKLF contains three Zn-fingers that bind to DNA. A semi-dominant mutation at a single position (E339D) in one allele of the mouse EKLF Zn-finger causes neonatal anemia (Nan). Interestingly, a mutation at the same position in human EKLF (E325K) causes type IV congenital dyserythropoietic anemia (CDA IV). Bulk RNA-seq analysis of Nan/+ fetal liver (FL) erythroid cells reveals that several enzymes involved in metabolic pathways are altered in their expression compared to wild-type (WT) littermates. Here we address metabolomic consequences in the erythroid cell of the Nan-EKLF genetic mutation to understand better the processes that regulate red cell metabolism. Using liquid chromatography (LC) and gas chromatography (GC) mass spectrometry (MS) platforms, we analyzed the metabolome of erythroid cells isolated from embryonic day (E.13.5) Nan/+ FL compared with their WT littermates. After quality control and identification, PCA and PLS-DA plots of total metabolites demonstrated a clear separation between the 2 groups. We find a significant elevation of the L-carnitine levels that normally decrease during erythroid differentiation besides other intermediate metabolites. L-carnitine is involved in lipid metabolism by transporting fatty acids into mitochondria, which oxidize and convert into energy through the tricarboxylic acid (TCA) cycle. Moreover, pyrimidine and purines, which are the basic components of nucleotides and provide the necessary energy and cofactors for cell survival and proliferation, are significantly reduced in Nan/+. We find that intermediate metabolites related to the TCA cycle and glycolysis are significantly elevated in Nan/+. This, together with the increase of glucose and lactic acid, suggests rapid and high glucose consumption during glycolysis in Nan/+ compared to WT. TCA cycle converts acetyl-CoA from carbohydrates, fats, and amino acids into ATP, thus regulating oxidative metabolism in cells. Glycerolipid metabolism-related metabolites are significantly elevated in Nan/+. Dysregulation of glycerolipid may contribute to high glucose consumption. We also find several essential and non-essential amino acids required for L-carnitine synthesis and in mitochondrial metabolism are elevated significantly in Nan/+. Furthermore, several metabolites essential for the transport of electrons in the mitochondrial respiratory chain are increased in Nan/+ significantly. Fatty acids are metabolites required for structural and functional membrane synthesis, and these are significantly elevated in Nan. Altogether these analyses of Nan/+ FL erythroid cells show that there is a general dysregulation of metabolites in the Nan/+ red cell resulting from the genetic changes that follow Nan-EKLF expression. To complement these latter studies, we measured mitochondrial activities in FL erythroid cells isolated from Nan/+ or WT. We observe increased mitochondrial DNA (mtDNA), membrane potential, and reactive oxygen species in Nan/+ FL erythroid cells as compared to WT. Intracellular ATP levels are enhanced in Nan/+ FL erythroid cells, which also show a higher uptake of glucose and contain more 2NBDG+ cells as compared to WT. Electron and super resolution microscopy analysis of Nan/+ FL erythroid cells show extended, linked mitochondrial networks consistent with a hyperfused phenotype compared to WT. We discovered that cytosolic mtDNA release in Nan/+ FL erythroid cells results in higher expression of interferon-stimulated genes, activation of the cGAS-STING pathway, enhanced phosphorylation and nuclear accumulation of p-IRF-3 and -7, and increased transcription of IFNα, ß, and γ. In sum, Nan-EKLF expression, even in the presence of WT EKLF, exerts dramatic, dominant effects on the metabolic properties of the erythroid cell. A range of amino acids, nucleotides, and intermediary metabolites of all types are altered from their normal levels. As a result: mutant EKLF-expressing cells require more energy for their survival and longevity; the increase in mitochondrial metabolism generates a greater uptake of glucose; mitochondrial morphology is altered; and an inflammatory response is generated. These observations model and are likely directly relevant to the dyserythropoiesis seen in CDA type IV patients.

The inner nuclear membrane protein NEMP1 supports nuclear envelope openings and enucleation of erythroblasts.

Nuclear envelope membrane proteins (NEMPs) are a conserved family of nuclear envelope (NE) proteins that reside within the inner nuclear membrane (INM). Even though Nemp1 knockout (KO) mice are overtly normal, they display a pronounced splenomegaly. This phenotype and recent reports describing a requirement for NE openings during erythroblasts terminal maturation led us to examine a potential role for Nemp1 in erythropoiesis. Here, we report that Nemp1 KO mice show peripheral blood defects, anemia in neonates, ineffective erythropoiesis, splenomegaly, and stress erythropoiesis. The erythroid lineage of Nemp1 KO mice is overrepresented until the pronounced apoptosis of polychromatophilic erythroblasts. We show that NEMP1 localizes to the NE of erythroblasts and their progenitors. Mechanistically, we discovered that NEMP1 accumulates into aggregates that localize near or at the edge of NE openings and Nemp1 deficiency leads to a marked decrease of both NE openings and ensuing enucleation. Together, our results for the first time demonstrate that NEMP1 is essential for NE openings and erythropoietic maturation in vivo and provide the first mouse model of defective erythropoiesis directly linked to the loss of an INM protein.

RHESUS (RH) AND KELL ANTIGEN INCOMPATIBILITY – INDICATIONS FOR PREIMPLANTATION GENETIC TESTING

Rh or Kell incompatibility occurs when an antigen-negative woman is exposed to antigen-positive blood cells during pregnancy or transfusion. After the initial exposure, antibodies persist and cross the placenta into fetal circulation in subsequent pregnancies, causing destruction of antigen-positive fetal red blood cells1, or suppressing the production of fetal red blood cells.2 Complications can include miscarriage, stillbirth, fetal or neonatal anemia, or hyperbilirubinemia.1,2 If the male partner is heterozygous, preimplantation genetic testing (PGT) for monogenic conditions (PGT-M) is an option to identify embryos that are Rh or Kell-negative, preventing incompatibility and associated complications.

Prevalence and Risk Factors of Apnea in Preterm Neonates Admitted to the French Medical Institute for Mothers and Children Hospital in Kabul City: An Analytic Cross-Sectional Study

Introduction: Prematurity is one of the leading causes of neonatal death in Afghanistan and complicates many serious problems including apnea. Although recurrent and prolong apnea of prematurity (AOP) may be directly or indirectly associated with significant adverse outcomes, there isn’t enough scientific information regarding the prevalence and risk factors of this problem in Afghanistan, therefore, this study is performed to obtain such information. Objective: To determine the prevalence rate and risk factors for apnea of prematurity in neonates admitted to the Neonatal Intensive Care Unit of the French Medical Institute for Mothers and Children Hospital, Kabul City. Patients and Methods: This analytic cross-sectional study was conducted at the Neonatal Intensive Care Unit of the French Medical Institute for Mothers and Children Hospital in Kabul City, Afghanistan. The study participants were preterm neonates. Statistical analysis was performed by SPSS 24. Results: 75 preterm newborns were enrolled in this study and the apnea of prematurity were developed in 48% of them. Extremely low birth weight preterm neonates had a 71.4% prevalence rate of such apnea, while in very low birth weight and low birth weight the rates were 47.4% and 36.4% respectively. Based on gestational age, the prevalence rates of apnea in the early and moderate preterm neonates were 55.6% and 52.8% respectively, whilst also in late preterm neonates it was 42.8%. The apnea of prematurity appeared more prevalent in boys (54.3%) than girls (45.7%). The preterm neonates in the apnea group versus the non-apnea group had the mean birth weight of (1233.33 ± 235.25g vs 1333.46 ± 274.44g, 90%CI= -198 _ -1.4), mean maternal age of (24.78 ± 3.68y vs 26.62 ± 4.58y, 90%CI= -3.44_-0.23) and RR of anemia (2.2, P=0.05). Conclusion: The overall prevalence rate of AOP in preterm neonates was 48% and the highest rates were seen within extremely low birth weight and early preterm neonates. The lower neonatal birth weight, neonatal anemia and younger maternal age were found to be the risk factors for apnea of prematurity.

Effect of placenta previa on umbilical cord hematocrit value

Objective Placenta previa is one of the causes of neonatal anemia. This condition is mainly explained by antenatal hemorrhage and incision of the anteriorly located placenta during cesarean section. However, the mechanism of neonatal anemia in placenta previa has not been extensively studied or well elucidated. This study investigates whether placenta previa is associated with lower hematocrit levels in newborns with no antenatal hemorrhage and placental incision. Key findings This prospective study investigated 47 patients with previa and 43 control patients who gave birth with a cesarean section at 34–38 weeks of gestation. Blood samples were obtained from the fetal end of the umbilical vein. The mean umbilical cord hematocrit value was 49.3% in the control patients and 46.7% in the patients with previa, and the difference was statistically significant (p = .029). No significant association was observed between hematocrit value and birth weight, gestational age, newborn gender, placenta position, or preoperative maternal hemoglobin level. Conclusion The study findings reveal that even if not complicated by antepartum or intrapartum hemorrhage, placenta previa may be associated with lower hematocrit values in newborns. Although in none of the cases, the umbilical cord hematocrit value was not as low as to be defined as anemia, this effect of previa on newborns should be considered because of the importance of iron status.

Unrecognized Severe Anemia in Neonates

Unrecognized Severe Anemia in Neonates

Study of correlation of neonatal low birth weight and maternal anemia in first, second and third trimester of pregnancy

In Indian antenatal scenario , anemia in pregnant women is one of the commonest pathology routinely encountered. the most common cause of anemia during pregnancy is Iron deficiency anemia. Objective: To identify and analyze the real impact of Anemia during pregnancy individual all three trimesters of pregnancy in Indian pregnant women and its real effect on fetal weight. Materials and Methods: Retrospective evaluation of about 400 pregnant women who came for delivery during the study period February 2022 to May 2022 in Dhiraj hospital, Pipariya was done. The status and level of hemoglobin of these pregnant women during all three trimesters of pregnancy was done by proper detailed record of laboratory investigations and record of neonatal birth weight was done. Results: Among 400 Pregnant patients who had been delivered at Dheeraj Hospital , more than 72 % mothers were anemic in any of the three trimester of pregnancy. The rate of low birth weight baby was higher in these anemic mother than nonanemic mother in any of the three trimester. Conclusions: Considering the relationship between maternal anemia and LBW in the third trimester of pregnancy, anemia in third trimester can be used as a preventable factor for infant LBW.

Establishment of a nomogram model for predicting necrotizing enterocolitis in very preterm infants

To investigate the risk factors for necrotizing enterocolitis (NEC) in very preterm infants and establish a nomogram model for predicting the risk of NEC. A total of 752 very preterm infants who were hospitalized from January 2015 to December 2021 were enrolled as subjects, among whom 654 were born in 2015-2020 (development set) and 98 were born in 2021 (validation set). According to the presence or absence of NEC, the development set was divided into two groups: NEC (n=77) and non-NEC (n=577). A multivariate logistic regression analysis was used to investigate the independent risk factors for NEC in very preterm infants. R software was used to plot the nomogram model. The nomogram model was then validated by the data of the validation set. The receiver operating characteristic (ROC) curve, the Hosmer-Lemeshow goodness-of-fit test, and the calibration curve were used to evaluate the performance of the nomogram model, and the clinical decision curve was used to assess the clinical practicability of the model. The multivariate logistic regression analysis showed that neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding were independent risk factors for NEC in very preterm infants (P<0.05). The ROC curve of the development set had an area under the curve (AUC) of 0.833 (95%CI: 0.715-0.952), and the ROC curve of the validation set had an AUC of 0.826 (95%CI: 0.797-0.862), suggesting that the nomogram model had a good discriminatory ability. The calibration curve analysis and the Hosmer-Lemeshow goodness-of-fit test showed good accuracy and consistency between the predicted value of the model and the actual value. Neonatal asphyxia, sepsis, shock, hypoalbuminemia, severe anemia, and formula feeding are independent risk factors for NEC in very preterm infant. The nomogram model based on the multivariate logistic regression analysis provides a quantitative, simple, and intuitive tool for early assessment of the development of NEC in very preterm infants in clinical practice.

ASSOCIATION BETWEEN THIRD TRIMESTER MID-UPPER ARM CIRCUMFERENCE (MUAC) AND ANEMIA IN NEONATUS

Introduction: Nutritional problems in pregnant women in Indonesia reach 50%, this is still a concern. Based on Basic Health Research (Riskesdas) 2018, 17.5% CED pregnant women in Central Java. Mid-Upper Arm Circumference (MUAC) is an examination to determine nutritional status of pregnant women. Poor nutritional status can cause anemic neonates. According to research at RSUP Dr. Hasan Sadikin Bandung 2018, prevalence of anemic neonates is 14.5% which is still a problem. Objectives: This study aimed to determine relationship between MUAC in third trimester and incidence of anemic neonates. Methods: This study used a cohort study of pregnant women and neonates at Dr. Oen Solo Baru. The sampling technique was purposive sampling. The samples were 80 respondents with the independent variable being MUAC in third trimester and the dependent variable being anemic neonates. Data were analyzed using Spearman's correlative test. Results: In 40 (50%) respondents with normal MUAC which is 23.5 – 28.5 cm, there were 31 (77.5%) normal haemoglobin (Hb) neonates and 9 (22.5%) anemic neonates. In 40 people (50%) were malnourished which is &lt;23.5 cm, there were 13 (32.5%) normal Hb levels neonates and 27 (67.5%) anemic neonates. Based on statistical tests, there is a relationship between third trimester MUAC and incidence of anemic neonates with p = 0.000 (&lt;0.05) and the correlation coefficient value is 0.452 which indicates a sufficient correlation. Conclusions: The conclusion is there is a relationship between MUAC for pregnant women in third trimester and incidence of anemic neonates.

Hemoglobin concentration in ill neonates in early neonatal period

Background: Abnormal changes in blood hemoglobin (Hb) levels depend on maternal and neonatal factors, and could be an important indicator to evaluate the progression of neonatal diseases. This study aims to describe the hemoglobin concentration in ill neonates and to identify several factors associated with anemia and polycythemia status in newborns in early neonatal period. Methods: A cross-sectional descriptive was conducted. A convenient sample included 169 ill neonates less than 7 day-old at Hue University of Medicine and Pharmacy Hospital from July 2021 to May 2022. Results: Mean gestational age in study group was 38.5 ± 2.2 weeks. The mean Hb concentration of study group was 180 ± 26.4 g/l. Prevalence of anemia and polycythemia were 18.9% and 6.5%, respectively. The mean Hb level in common diseases such as early-onset neonatal sepsis (EOS), meconium aspiration syndrome (MAS), ABO hemolytic disease of newborn (ABO HDN) was 181.7 ± 24.5 g/l, 164.5 ± 20.5g/l and 136.2 ± 18.5g/l, respectively. The incidence of anemia in EOS was 18.8%, in ABO HDN was 80.0%, in MAS was 33.3%. Factors significantly associated with neonatal anemia were ABO HDN (OR = 17.9, p &lt; 0.05), maternal anemia (OR = 3.57, p &lt; 0.05). Low birth weight neonates (&lt; 2500 gram) increased the risk of polycythemia with OR = 3.94 (p &lt; 0.05). Conclusion: The abnormal changes of hemoglobin concentration appears in 25.4% of ill neonates. The hemoglobin level should be screened to evaluate the disease characteristics of neonates. Key words: ill neonates, neonatal anemia, polycythemia.

Differential effects of delayed cord clamping on bilirubin levels in normal and diabetic pregnancies

Delayed cord clamping increased the risk of jaundice in newborns born to diabetic mothers, but had no effect in newborns from mothers with normal pregnancies. DCC may be a risk factor for increased bilirubin in infants of diabetic mothers. ClinicalTrials.gov: NCT04369313; date of registration: April 27, 2020 (retrospectively registered). • Delayed cord clamping had significant benefits for newborns by increasing neonatal hemoglobin levels and reducing the risk of neonatal anemia, etc. • Delayed cord clamping may lead to neonatal hyperemia, erythrocytosis, and hyperbilirubinemia, which increases the risk of neonatal jaundice. • Our trial focused on the differential effects of delayed cord clamping on jaundice in full-term newborns between diabetic pregnancies and normal pregnancies. And newborns of diabetic mothers who received delayed cord clamping had a significantly increased risk of jaundice compared to newborns with normal pregnancy. • Delayed cord clamping may be a risk factor for increased bilirubin levels in neonates of diabetic mothers.

High Magnitude of Neonatal Anemia Among Sick Newborns Admitted to University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.

IntroductionAnemia is a global health problem that affects all ages, particularly children under five years. If not treated early, childhood anemia results in impaired growth, delayed cognitive development, and organ dysfunction. There is a scarcity of studies on the prevalence of anemia among hospitalized sick neonates, especially in developing countries.ObjectiveThis study aimed to determine the magnitude of anemia and associated factors among hospitalized sick newborns at the University of Gondar Comprehensive Specialized Hospital (UOGCSH).MethodsAn institutional-based cross-sectional study was conducted among admitted newborns from June 1 to September 30, 2020. All newborns whose gestational age (GA) ≥28 weeks and postnatal age ≤28 days, admitted to UOGCSH during the study period were included in the study. Data were collected by pediatric residents and a systematic random sampling technique was used to select the study participants. Statistical analysis was performed using SPSS version 20. Binary logistic regression was used to identify associated factors with neonatal anemia. P-value <0.05 was considered statistically significant.ResultsDuring the study period, 272 newborns were enrolled. The mean hemoglobin value was 15.74 ± 4.27 gm/dL. The prevalence of neonatal anemia in the study population was 30.1% (95% CI: 24.6–35.7). Neonatal age >7 days (AOR = 4.41, 95% CI: 1.86–10.5), maternal anemia (AOR = 9.93, 95% CI: 4.36–21.6), antepartum hemorrhage (AOR = 4.05, 95% CI: 1.54–10. 7), being multiple births (AOR = 4.70, 95% CI: 1.73–12.8), subgaleal hemorrhage (AOR = 7.56, 95%: 1.87–30.6), and hyperbilirubinemia (AOR = 3.84, 95% CI: 1.58–9.31) were associated with neonatal anemia.Conclusion and RecommendationThe prevalence of anemia among hospitalized newborns was high. The current study recommends that healthcare providers should screen anemia among sick newborns who had risk factors. Prevention of maternal anemia and early treatment of obstetric complications will reduce the burden of anemia in sick neonates.

Does placental abruption cause neonatal anemia?

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. 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. 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 16.5g/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. 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.

Ablation of Tmcc2 Gene Impairs Erythropoiesis in Mice.

(1) Background: Transcriptomic and proteomic studies provide a wealth of new genes potentially involved in red blood cell (RBC) maturation or implicated in the pathogenesis of anemias, necessitating validation of candidate genes in vivo; (2) Methods: We inactivated one such candidate, transmembrane and coiled-coil domain 2 (Tmcc2) in mice, and analyzed the erythropoietic phenotype by light microscopy, transmission electron microscopy (TEM), and flow cytometry of erythrocytes and erythroid precursors; (3) Results: Tmcc2−/− pups presented pallor and reduced body weight due to the profound neonatal macrocytic anemia with numerous nucleated RBCs (nRBCs) and occasional multinucleated RBCs. Tmcc2−/− nRBCs had cytoplasmic intrusions into the nucleus and double membranes. Significantly fewer erythroid cells were enucleated. Adult knockouts were normocytic, mildly polycythemic, with active extramedullary erythropoiesis in the spleen. Altered relative content of different stage CD71+TER119+ erythroid precursors in the bone marrow indicated a severe defect of erythroid maturation at the polychromatic to orthochromatic transition stage; (4) Conclusions: Tmcc2 is required for normal erythropoiesis in mice. While several phenotypic features resemble congenital dyserythropoietic anemias (CDA) types II, III, and IV, the involvement of TMCC2 in the pathogenesis of CDA in humans remains to be determined.

Two-year neurodevelopmental outcomes of preterm infants who received red blood cell transfusion.

Studies aimed at reducing neonatal anaemia or transfusing higher blood volumes did not find improvement in neurodevelopmental function at two years of age. This study investigated the relationship between the receipt, timing, and number of red blood cell (RBC) transfusions and neurodevelopmental outcomes among preterm infants. This is a retrospective review of preterm infants (gestational age <34 weeks) with a full neurodevelopmental assessment at 18-36 months corrected age from October 2008 to September 2020. Bayley Scales of Infant and Toddler Development, third edition and the Modified Checklist for Autism in Toddlers were collected. Multivariable regressions were used to evaluate neurodevelopmental outcomes. 654 preterm infants were evaluated with a mean follow-up of 25 months. 295 infants (45%) received a total of 1,322 blood transfusions. After adjustment for gestational age, baseline morbidity, and socioeconomic status, receipt of RBC transfusion was associated with decreased two-year cognitive and motor function, but not language (p=0.047, 0.025, and 0.879, respectively). There was no significant difference in outcomes between receipt of transfusion in the first week of life compared to after. Number of transfusions was associated with decreased cognitive, language, and motor function (all p<0.001), and increased likelihood to develop severe neurodevelopmental impairment (adjusted-odds ratio, 1.09; 95% confidence interval, 1.03-1.15; p=0.004). Our study demonstrates an association between RBC transfusion and lower cognitive and motor outcomes at two-years after adjustment for prematurity and illness at birth. Increasing number of transfusions worsened neurodevelopmental outcomes.

Investigating effect of mutation on structure and function of G6PD enzyme: a comparative molecular dynamics simulation study.

Several natural mutants of the human G6PD enzyme exist and have been reported. Because the enzymatic activities of many mutants are different from that of the wildtype, the genetic polymorphism of G6PD plays an important role in the synthesis of nucleic acids via ribulose-5-phosphate and formation of reduced NADP in response to oxidative stress. G6PD mutations leading to its deficiency result in the neonatal jaundice and acute hemolytic anemia in human. Herein, we demonstrate the molecular dynamics simulations of the wildtype G6PD and its three mutants to monitor the effect of mutations on dynamics and stability of the protein. These mutants are Chatham (A335T), Nashville (R393H), Alhambra (V394L), among which R393H and V394L lie closer to binding site of structural NADP+. MD analysis including RMSD, RMSF and protein secondary structure revealed that decrease in the stability of mutants is key factor for loss of their activity. The results demonstrated that mutations in the G6PD sequence resulted in altered structural stability and hence functional changes in enzymes. Also, the binding site, of structural NADP+, which is far away from the catalytic site plays an important role in protein stability and folding. Mutation at this site causes changes in structural stability and hence functional deviations in enzyme structure reflecting the importance of structural NADP+ binding site. The calculation of binding free energy by post processing end state method of Molecular Mechanics Poisson Boltzmann SurfaceArea (MM-PBSA) has inferred that ligand binding in wildtype is favorable as compared to mutants which represent destabilised protein structure due to mutation that in turn may hinder the normal physiological function. Exploring individual components of free energy revealed that the van der Waals energy component representing non-polar/hydrophobic energy contribution act as a dominant factor in case of ligand binding. Our study also provides an insight in identifying the key inhibitory site in G6PD and its mutants which can be exploited to use them as a target for developing new inhibitors in rational drug design.

Additional Adverse Perinatal Outcomes With No Effect on Neonatal Mortality and Birth Defects in Pregnancies Conceived by Assisted Reproductive Technology.

BackgroundPregnancy outcomes and perinatal diseases of children conceived by assisted reproductive technology (ART) and spontaneous conception (SC) are still unclear. We sought to compare the effects of ART and SC on adverse neonatal outcomes.MethodsWe included 5,913 neonates admitted to the neonatal intensive care unit (NICU) of the First Affiliated Hospital of the University of Science and Technology of China between January 2017 and December 2020. There were 1,112 (18.8%) ART pregnancies and 4,801 (81.2%) SC pregnancies. Data on maternal characteristics, comorbidities during pregnancy, and neonatal outcomes were collected and analyzed. Logistic regression models estimated the odds ratios (ORs) and 99% CIs of neonatal outcomes according to ART pregnancy. Neonatal outcomes primarily included neonatal respiratory distress syndrome (NRDS), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), neonatal anemia, birth defects, and mortality.ResultsAmong 5,913 neonates, 485 (8.2%) had NRDS, 165 (2.8%) had BPD, 113 (1.9%) had ROP, 602 (10.2%) had neonatal anemia, and 1,112 (18.8%) were ART infants. The incidence of pregnancy-related complications, such as gestational diabetes mellitus (GDM), gestational hypothyroidism, and rheumatic immune diseases, in mothers receiving ART, was higher than that in the SC group. On multivariate analysis, ART was independently associated with NRDS (OR = 1.46; 95% CI, 1.11–1.93; p = 0.008) and ROP (OR = 1.79; 95% CI, 1.06–3.05; p = 0.031). Moreover, the association persisted after adjustment for maternal age, history of cesarean section, preconception factors, and pregnancy complications. For BPD (OR = 1.44; 95% CI, 0.91–2.27; p = 0.117) and neonatal anemia (OR = 1.12; 95% CI, 0.87–1.45; p = 0.373), the associations were attenuated substantially when adjusting for pregnancy complications. ART was associated with neither birth defects (OR = 0.98; 95% CI, 0.77–1.25; p = 0.889) nor mortality (OR = 0.98; 95% CI, 0.51–1.91; p = 0.961).ConclusionART was independently associated with adverse neonatal outcomes, including NRDS and ROP. Therefore, women who conceive by ART must improve their perinatal health and management of pregnancy-related comorbidities to enhance the quality of life of their offspring.

Hematological changes in neonatal mice with phlebotomy-induced anemia.

Anemia is a nearly universal diagnosis in preterm infants, caused by phlebotomy, and exacerbated by the underlying erythropoietic immaturity. Newborn infants are exposed to the unique stressor of fetal-to-neonatal transition, which requires significant adaptation ex utero. Accordingly, the preterm infant's response to anemia may alter the ability to confront underlying illness. This study utilized our preclinical mouse model of phlebotomy-induced anemia (PIA) to comprehensively investigate associated hematological changes. C57BL/6 mice were subjected to timed phlebotomy between postnatal days 2--10 to induce severe anemia. Complete blood counts were determined by the Sysmex XT-2000iV analyzer. Anemic pups showed a gradual reduction of RBC and hemoglobin (Hb) and increased reticulocyte (RET) counts and red cell distribution width (RDW), however, with reduced RET-Hb from postnatal day (P) of 4 onwards. Elevated levels of high fluorescent RET and immature reticulocyte fraction (IRF) were noted in anemic mouse pups, but low and medium fluorescent RET were reduced. Also, the reduction of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were noted in anemic pups. No changes were seen in lymphocytes, but monocytes and neutrophils were significantly elevated from P4-P6. PIA in mouse pups is associated with hematological changes that may be exacerbating factors in neonatal diseases. Anemia is common and often severe in premature infants. Investigation of hematological parameters in settings of preclinical anemia may be an index of therapeutic strategies. Preclinical model evaluating the effects of neonatal anemia on the remainder of complete blood count. Detailed time kinetic phlebotomy-induced anemic mice enable us to study the impact on developmental delays in erythropoiesis and possible strategic intervention. Hematological effects of severe anemia in mice might provide insight on how best to investigate anemia in preterm infants.

Case Report: Clinical and Hematological Characteristics of εγδβ Thalassemia in an Italian Patient

Introductionεγδβ thalassemia is a rare form of β-thalassemia mostly described in children originating from Northern Europe. Only anecdotic cases from the Mediterranean area are reported. The diagnosis is challenging, considering the rarity of the disease and its heterogeneous clinical presentation. Most patients have neonatal microcytic anemia, sometimes requiring in utero and/or neonatal transfusions, and typically improving with age.Case DescriptionWe report on an Italian newborn presenting with severe neonatal anemia that required red blood cell transfusion. After the first months of life, hemoglobin levels improved with residual very low mean corpuscular volume. β and α thalassemia, IRIDA syndrome, and sideroblastic anemia were excluded. Finally, a diagnosis of εγδβ thalassemia was made after microarray analysis of single nucleotide polymorphisms revealed a 26 kb single copy loss of chromosome 11p15.4, including the HBD, HBBP1, HBG1, and HBB genes.ConclusionsDespite its rarity, the diagnosis of εγδβ thalassemia should be considered in newborns with severe neonatal anemia requiring in utero and/or neonatal transfusions, but also in older infants with microcytic anemia, after excluding more prevalent red blood cell disorders.

570 Severe fetomaternal hemorrhage. a report of eight cases

BackgroundFetomaternal hemorrhage (FMH) is a poorly understood condition in which involves fetal blood loss into the maternal circulation of more than 150ml or more than half fetal blood volume. Massive fetomaternal hemorrhage (>150 ml) occurs in 0.12 to 0.5% of pregnancies. Very small amount of fetal red cells are normally detectable in all pregnancies. Massive fetomaternal bleed is very rare and even rarer is the resultant severe anemia causing early neonatal death, up to 0 0,04% of all births, despite an uneventful normal pregnancy until the end. Some predisposing factors such as abdominal injury, placenta abruption and chorionic villus sampling have been described. The presentation is frequently without an evident precipitating factor. Recognition may become apparent only after injury has occurred, if at all. Case Report: We report 8 cases of severe fetomaternal transfusion in our institute at the time 2011-2021. 3 of them were preterm infants and 5 of them were mature infants. The type of admission at 5 of them was Caesarean section und 3 of them were born normally. The mean Hb concentration was 4,6 g/dl. The reasons for the Caesarean section as a delivery method were placenta abruption in one case, pathological CTG in 2 cases and abnormal position of the fetus during birth in the other 2 cases. Complications and/or diseases reported during pregnancy were gestational diabetes (at 1 pregnant), thyroid dysfunction (2 pregnants) und thalassemia minor (1 pregnant). 7 of the 8 neonates underwent a neonatal resuscitation. Neonatal resuscitation included positive pressure ventilation, oxygen, and intubation. This neonates responded well to blood transfusions, a pressor, and respiratory support. One of them was cardiovasculary and respiratory stable and needed neither a neonatal resuscitation nor a blood transfusion. The accepting neonatology team consulted with the obstetrician and a Kleihauer-Betke test was performed on mother's blood confirming a large fetal-maternal hemorrhage. All of them were discharged home at a good clinical condition. All of them had normal brain sonographic findings at the time of home discharge. Conclusion: FMH may be a significant cause of neonatal anemia. Diagnosis of FMH is highly dependent on physician awareness of the condition.Management remains challenging.Although the occurrence of large antenatal fetomaternal hemorrhage is fortunately rare, this entity likely remains underreported and underrecognized. A long term follow up of these children is necessary.