Rania A. El-Farrash

Cord blood iron profile and breast milk micronutrients in maternal iron deficiency anemia

Micronutrient deficiencies among pregnant women are widespread in low‐income countries, including Egypt. Iron deficiency anemia (IDA) is the most frequent nutritional deficiency during pregnancy, with an impact on maternal and fetal morbidity and mortality. We aimed to evaluate the effect of maternal IDA and nutritional status on birth anthropometry, cord blood iron profile and breast milk micronutrients in 50 anemic (hemoglobin <11 g/dl) and 30 healthy pregnant women.

Infants of diabetic mothers: echocardiographic measurements and cord blood IGF-I and IGFBP-1

El‐Ganzoury MM, El‐Masry SA, El‐Farrash RA, Anwar M, Abd Ellatife RZ. Infants of diabetic mothers: echocardiographic measurements and cord blood IGF‐I and IGFBP‐1.

New insights into thrombopoiesis in neonatal sepsis

Thrombocytopenia is one of the most frequent hematologic abnormalities in the neonatal period, affecting about 18–35% of all patients admitted to the Neonatal Intensive Care Unit (NICU), with sepsis being among the most common causes of severe neonatal thrombocytopenia. It is unclear whether decreased platelet production or increased platelet consumption contributes to thrombocytopenia of septic neonates. To answer this question, we evaluated the effects of sepsis on neonatal thrombopoiesis using a panel of tests. This prospective case-control study was conducted on 50 neonates with culture-proven sepsis admitted to NICU at the Pediatrics Department, Ain Shams University Hospitals. Thirty healthy newborns were included as controls. The enrolled neonates were subjected to detailed history taking, thorough clinical examination, and laboratory investigations including complete blood count, C-reactive protein, blood cultures, and tests of thrombopoiesis; namely serum thrombopoietin (TPO) assay, flow cytometric analysis of reticulated platelet percentage (RP%), and calculation of absolute RP counts. Septic neonates comprised 24 males and 26 females with a mean gestational age of 36.0 ± 3.1 weeks. Twenty-eight (56%) of the septic neonates were thrombocytopenic (platelets < 150 000/µl). While platelet and RP counts were decreased, TPO and RP% were increased in septic neonates compared to healthy controls. Neonates with Gram-negative sepsis had the lowest platelet and RP counts and the highest TPO and RP% followed by those with fungal septicemia. Platelet counts showed inverse correlations with TPO and RP% and direct correlation with RP count. Our findings suggest that neonates respond to sepsis by up-regulating thrombopoiesis, where thrombocytopenia ensues when the rate of platelet consumption exceeds the rate of platelet production. Simultaneous measurements of serum TPO levels and RP% are helpful in discriminating hyperdestructive from hypoplastic thrombocytopenia among septic neonates.

Cord blood interleukin-6 and neonatal morbidities among preterm infants with PCR-positive Ureaplasma urealyticum.

Objectives: To evaluate the clinical significance of Ureaplasma urealyticum recovery from umbilical cord blood, using Polymerase Chain Reaction (PCR), and its association with umbilical cord interleukin-6 (IL-6) levels and neonatal morbidity in preterm infants. Methods: Cord blood PCR for Ureaplasma urealyticum, and IL-6 were assessed in relation to neonatal outcomes of 30 preterm deliveries of less than 35 weeks’ gestation. Results: Ureaplasma urealyticum was present in 43.3% of the examined cord blood samples. Positive neonatal Ureaplasma urealyticum was more common in association with premature rupture of membranes, chorioamnionitis, antenatal maternal use of antibiotics, and earlier gestation. Ureaplasma urealyticum was also associated with an early pro-inflammatory immune response (i.e. elevated IL-6 and positive C-reactive protein). Cutoff level of interleukin-6 of 240 pg% predicts the occurrence of respiratory distress syndrome (RDS), in neonates with positive PCR for Ureaplasma urealyticum. Conclusions: Preterm patients with positive cord blood PCR for Ureaplasma urealyticum were more likely to have premature rupture of membrane, antenatal antibiotics, chorioamnionitis, earlier gestation, pro-inflammatory response, and RDS than those with a negative PCR. High IL-6 is more likely associated with RDS in Ureaplasma urealyticum positive neonates.

Size at birth and insulin-like growth factor-I and its binding protein-1 among infants of diabetic mothers

Objective: to estimate the association between intrauterine fetal growth, evaluated by anthropometric measurements, and biochemical growth factors; IGF-I and IGBP-1 among IDMs. Methods: Cross-sectional study carried out on 69 full term IDMs who was admitted to neonatal intensive care units, Ain Shams University Hospitals. Clinical examination including anthropometric measurements; birth weight, length, head circumference, mid-arm circumference, skinfold thickness at triceps and subscapular areas and placental weight. Laboratory investigations included maternal HbA1c and cord blood IGF-I and IGBP-1. They were classified into three groups: 20 small for gestational age (SGA), 25 appropriate for gestational age (AGA) and 24 large for gestational age (LGA). Results: Most of SGA neonates were born to mothers with type I diabetes, while most of AGA and LGA were born to mothers with gestational diabetes. According to maternal HbA1c, SGA and LGA neonates were born to metabolically uncontrolled mothers while AGA neonates were born to well-controlled diabetic mothers. Anthropometric measurements had significant positive correlations with IGF-I and negative correlations with IGFBP-1. Conclusions: Good control of diabetes during pregnancy is essential to improve fetal growth. There is an opposing effect of cord blood IGF-I and IGFBP-1 on anthropometric measurements.

CD144+ endothelial microparticles as a marker of endothelial injury in neonatal ABO blood group incompatibility

BACKGROUND ABO antigens are expressed on the surfaces of red blood cells and the vascular endothelium. We studied circulating endothelial microparticles (EMP) in ABO haemolytic disease of the newborn (ABO HDN) as a marker of endothelial activation to test a hypothesis of possible endothelial injury in neonates with ABO HDN, and its relation with the occurrence and severity of haemolysis. MATERIAL AND METHODS Forty-five neonates with ABO HDN were compared with 20 neonates with Rhesus incompatibility (Rh HDN; haemolytic controls) and 20 healthy neonates with matched mother and infant blood groups (healthy controls). Laboratory investigations were done for markers of haemolysis and von Willebrand factor antigen (vWF Ag). EMP (CD144(+)) levels were measured before and after therapy (exchange transfusion and/or phototherapy). RESULTS vWF Ag and pre-therapy EMP levels were higher in infants with ABO HDN or Rh HDN than in healthy controls, and were significantly higher in babies with ABO HDN than in those with Rh HDN (p<0.05). In ABO HDN, pre-therapy EMP levels were higher in patients with severe hyperbilirubinaemia than in those with mild and moderate disease or those with Rh HDN (p<0.001). Post-therapy EMP levels were lower than pre-therapy levels in both the ABO HDN and Rh HDN groups; however, the decline in EMP levels was particularly evident after exchange transfusion in ABO neonates with severe hyperbilirubinaemia (p<0.001). Multiple regression analysis revealed that the concentrations of haemoglobin, lactate dehydrogenase and indirect bilirubin were independently correlated with pre-therapy EMP levels in ABO HDN. DISCUSSION Elevated EMP levels in ABO HDN may reflect an IgG-mediated endothelial injury parallel to the IgG-mediated erythrocyte destruction and could serve as a surrogate marker of vascular dysfunction and disease severity in neonates with this condition.

Enteral Granulocyte-Colony Stimulating Factor and Erythropoietin Early in Life Improves Feeding Tolerance in Preterm Infants: A Randomized Controlled Trial

OBJECTIVE To evaluate the efficacy and safety of enteral recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human erythropoietin (rhEPO) in preventing feeding intolerance. STUDY DESIGN An interventional randomized control trial was conducted in 90 preterm infants born at ≤33 weeks gestational age. The neonates were assigned to 4 groups; 20 received rhG-CSF, 20 received rhEPO, 20 received both, and 30 received distilled water (placebo control). The test solution was given at the beginning of enteral feeding and was discontinued when enteral intake reached 100 mL/kg/day or after a maximum of 7 days, whichever came first. Feeding tolerance and adverse effects of treatment were assessed. Serum granulocyte colony-stimulating factor and erythropoietin levels were measured on days 0 and 7 of treatment. RESULTS All neonates tolerated the treatment without side effects. Neonates who received rhG-CSF and/or rhEPO had better feeding tolerance, as reflected by earlier achievement of 75 mL/kg/day, 100 mL/kg/day, and full enteral feeding of 150 mL/kg/day with earlier weight gain and a shorter hospital stay (P < .05). The risk of necrotizing enterocolitis was reduced from 10% to 0% in all treatment groups (P < .05). There was a shorter duration of withholding of feeding secondary to feeding intolerance among neonates receiving both rhG-CSF and rhEPO compared with those receiving placebo (P < .05). Serum levels of granulocyte colony-stimulating factor and erythropoietin at 0 and 7 days did not differ across the treatment groups. CONCLUSIONS Enteral administration of rhG-CSF and/or rhEPO improves feeding outcome and decreases the risk of necrotizing enterocolitis in preterm neonates. The mechanism may involve the prevention of villous atrophy.

In vivo effect of recombinant human granulocyte colony-stimulating factor on neutrophilic expression of CD11b in septic neonates: a randomized controlled trial.

Neonates are susceptible to septicemia secondary to quantitative and qualitative neutrophilic defects. Granulocyte colony-stimulating factor (G-CSF) stimulates myeloid progenitor cell proliferation and induces selective neutrophil functions. The authors aimed to evaluate the effect of G-CSF administration in septic neonates on neutrophil production and CD11b expression. Sixty septic neonates were randomized to receive intravenous G-CSF 10 μg/kg/day for 3 days (G-CSF group, n = 30), or not to receive G-CSF (non–G-CSF group, n = 30). Thirty healthy newborns were included as controls. Laboratory investigations included complete blood count, C-reactive protein, blood culture, renal and liver function tests, and assessment of neutrophilic expression of CD11b. Total leukocytes count (TLC), absolute neutrophil count (ANC), and immature myeloid cell count in G-CSF group showed significant difference between post–and pre–G-CSF levels. TLC, ANC, immature myeloid cell count and immature/total myeloid cells ratio were higher in G-CSF group compared to non–G-CSF group on days 1 and 3. Higher neutrophilic expression of CD11b was reported in both septic groups on day 0 compared to control group. On day 5, CD11b was higher in G-CSF group than non–G-CSF group. G-CSF improved CD11b% in neutropenic and non-neutropenic septic neonates. No significant difference was found between pre- and posttreatment renal and liver function tests. Lower duration of antibiotic intake and hospitalization was observed in G-CSF group compared to non–G-CSF group. G-CSF administration as an adjuvant therapy for neonatal septicemia, whether neutropenic or not, improves neutrophilic count and function and contributed to early healing from sepsis.

Methylation pattern of calcitonin (CALCA) gene in pediatric acute leukemia.

Disruption of deoxyribonucleic acid (DNA) methylation patterns has emerged as one of the possible origins of leukemogenesis. Calcitonin (CALCA) gene is a hot-spot for gene hypermethylation in acute leukemias. This study aimed to systematically analyze the methylation status of CALCA gene in pediatric acute leukemia using methylation-specific polymerase chain reaction (MSP) and assess its value as a potential prognostic biomarker. The study population consisted of 70 children divided into; 35 acute myeloblastic leukemia (AML) and 35 acute lymphoblastic leukemia (ALL) patients. CALCA gene was found to be hypermethylated in 54.3% of AML and 65.7% of ALL patients. CALCA hypermethylation was neither correlated to any of the clinicopathologic characteristics of patients, standard prognostic factors nor response to induction therapy (P>0.05). Hypermethylated AML and ALL patients displayed poorer clinical outcome when compared with hypomethylated counterparts as evidenced by high relapse and mortality rates with the occurrence of early relapse (P<0.05). The estimated overall and disease-free survival rates at 2.5-years were significantly shorter for hypermethylated patients in both groups (P<0.01). Our results suggest that CALCA gene methylation pattern is an independent prognostic factor in pediatric acute leukemia that could characterize a group of patients with enhanced risk of relapse and death.

Antenatal administration of vitamin K1: relationship to vitamin K-dependent coagulation factors and incidence rate of periventricular-intraventricular hemorrhage in preterm infants; Egyptian randomized controlled trial.

Abstract Objectives: To determine the effect of maternal antenatal administration of vitamin K1 on activity level of vitamin K-dependent coagulation factors and on the occurrence of periventricular-intraventricular hemorrhage (PIVH). Methods: This study was conducted on 90 infants who were classified into; Group A: 30 preterm whose mothers received antenatal vitamin K1, Group B: 30 preterm whose mothers did not receive antenatal vitamin K1, and Group C: 30 healthy full term newborns as a control group. All newborns were subjected to measurement of the activity level of vitamin K-dependent coagulation factors (FII, FVII, FIX and FX). Cranial ultrasound was done on the 1st, 3rd and 7th days of life. Results: Group B showed significantly lower activity level of FII and FX with higher incidence of PIVH compared with group A. Neonates who developed PIVH by the 7th day in both group A and B had significantly lower activity level of vitamin K-dependent coagulation factors. Conclusion: when antenatal vitamin K1 was given to pregnant women at imminent risk of preterm labor, their preterm neonates were able to achieve a clotting status approaching that of full term neonates and are less liable to develop PIVH.