Screening umbilical cord blood for congenital Iron deficiency.

OBJECTIVES: Small for gestational age infants (SGA), infants of diabetic mothers (IDM), and very low birth weight infants (VLBW) are at risk for congenital iron deficiency. We evaluated the iron status of SGA, IDM, and VLBW neonates at birth and sought mechanistic explanations in those with iron deficiency. METHODS: This was a prospective study. If congenital iron deficiency was present, maternal iron studies were obtained. When neonates were two weeks old, their iron status was reevaluated. RESULTS: Sixteen of 180 neonates screened were iron deficient at birth. The Body Mass Index of the 16 mothers was high. These mothers often had mild iron deficiency and measurable hepcidin levels. Two weeks after birth, neonates had improved iron measurements. CONCLUSIONS: Among SGA, IDM, and VLBW neonates, maternal obesity is a risk factor for congenital iron deficiency. We speculate that elevated hepcidin levels in obese pregnant women impede iron absorption and interfere with transplacental iron transfer.

Two novel mutations in TMPRSS6 associated with iron-refractory iron deficiency anemia in a mother and child.

In an iron deficient child, oral iron repeatedly failed to improve the condition. Whole exome sequencing identified one previously reported plus two novel mutation in the TMPRSS6 gene, with no mutations in other iron-associated genes. We propose that these mutations result in a novel variety of iron-refractory iron deficiency anemia.

Heart-rate-corrected QT interval evolution in premature infants during the first week of life.

Automated monitoring of the QT interval is increasingly common in a variety of clinical settings. A better understanding of how the heart-rate-corrected QT interval (QTc) evolves in early postnatal life is needed before its clinical utility in neonates can be determined. This study aimed to use real-time bedside monitoring as a tool to describe the QTc evolution of premature neonates during the first week of life. All neonates born at a gestation age (GA) of 31 weeks or later and admitted to the level 2 intensive care nursery of the authors' institution between December 2012 and March 2013 were included in this study. The authors prospectively collected QTc values at 15-min intervals during the first week of life, then used two-way analysis of variance (ANOVA) to compare these data among three GA cohorts: 31 to <34 weeks (cohort A), 34 to <37 weeks (cohort B), and ≥37 weeks (cohort C). All the cohorts demonstrated a statistically significant decline in the 24-h average QTc during the first 3-4 days of life before reaching a stable baseline. No diurnal variation in the QTc was identified in any of the study patients. Marked variability and a progressive decline in the QTc of premature neonates occur during the first 3-4 days of life. Understanding this phenomenon is imperative when screening programs for the early detection of QT prolongation are considered.

Intermolecular C-F...H-C contacts in the molecular packing of three isostructural N-(fluorophenyl)mannopyranosylamines.

Among the three compounds reported here, namely N-(4-fluorophenyl)-ß-D-mannopyranosylamine, (I), N-(3-fluorophenyl)-ß-D-mannopyranosylamine, (II), and N-(2-fluorophenyl)-ß-D-mannopyranosylamine, (III), all with chemical formula C(12)H(16)FNO(5), (I) and (II) are isostructural, whereas (III) assumes the same packing arrangement as the unfluorinated analogue N-phenyl-ß-D-mannopyranosylamine, (IV), which has been reported previously. Similarities with respect to the intermolecular hydrogen-bonding patterns exist across the series (I)-(III). A packing motif that distinguishes the shared packing arrangement of (I) and (II) from that of (III) is a C-F...H-C chain of graph set C(4) that is preserved in the formal exchange of F and H atoms at the 4- and 3-positions on the aromatic ring of (I) and (II), but is replaced by a different chain of graph set C(5) when the F atom is located at the 2-position of the aromatic ring in (III). The steric role of the F atom in (I)-(III) is ambiguous but is examined here in detail.

Automated Quantification of Fragmented Red Blood Cells: Neonatal Reference Intervals and Clinical Disorders of Neonatal Intensive Care Unit Patients with High Values.

BACKGROUND: Schistocytes are circulating erythrocyte fragments. They can be identified microscopically from a blood smear; but automated systems evaluate more cells and avoid inconsistencies in microscopy. Studies using adult subjects indicate that automated quantification of schistocytes can be clinically useful. However, reference intervals for automated schistocyte counts of neonates have not been published, and the relevance of a high automated schistocyte count from neonates has not been reported. OBJECTIVES: Using retrospective automated neonatal complete blood count (CBC) data, we created reference intervals for fragmented red cells (FRCs) and sought to discover the clinical conditions of neonates with high FRCs (above the upper reference interval). RESULTS: We created reference intervals based on 39,949 CBCs from 15,655 neonates 0-90 days old. The lower reference interval was 0 FRC/µL and the upper interval was 100,000/µL. The highest FRCs (96 CBCs from 44 neonates) were > 250,000/µL. These neonates clustered into the following groups: 37% had sepsis, 29% had disseminated intravascular coagulation (DIC), 17% had a genetic syndrome, 14% necrotizing enterocolitis (NEC), and 7% had iron deficiency (some had more than one diagnosis). Based on the reference intervals, we divided the 39,949 FRC values into 3 groups: (1) < 100,000/µL ("normal"), (2) 100,000-200,000/µL ("moderately elevated"), and (3) > 200,000/µL ("extremely elevated"). The odds that a microangiopathic condition (DIC, sepsis, NEC) or a microcytic disorder (iron deficiency) were present were significantly higher in the moderately elevated, and more so in the extremely elevated group. CONCLUSIONS: Our study suggests that a high FRC could prompt investigation into, or inform follow-up of, a neonatal microangiopathic or extremely microcytic disorder.

Non-Immune Hydrops, Hypotonia, Encephalopathy, and Liver Failure with Novel Compound Heterozygous AHCY Mutations.

A late-preterm infant with a prenatal diagnosis of non-immune hydrops was born with hypotonia, poor respiratory effort, chylothorax, encephalopathy, coagulopathy, progressive hepatic failure, and refractory pulmonary hypertension. Life support was withdrawn at 7 days of life due to multisystem organ failure. Rapid whole exome sequencing revealed novel compound heterozygous mutations in the gene encoding S-adenosylhomocysteine hydrolase (AHCY); each novel variant was carried by an asymptomatic parent. Reports of neonates with other AHCY mutations describe a pathology of varying severity. AHCY mutations should be considered when seeking an etiology for neonates with the combination of non-immune hydrops, hypotonia, encephalopathy, and liver failure.

A critical question for NEC researchers: Can we create a consensus definition of NEC that facilitates research progress?

In the last decades the reported incidence of preterm necrotizing enterocolitis (NEC) has been declining in large part due to implementing comprehensive NEC prevention initiatives, including breast milk feeding, standardized feeding protocols, transfusion guidelines, and antibiotic stewardship and improving the rigor with which non-NEC cases are excluded from NEC data. However, after more than 60 years of NEC research in animal models, the promise of a "magic bullet" to prevent NEC has yet to materialize. There are also serious issues involving clinical NEC research. There is a lack of a common, comprehensive definition of NEC. National datasets have their own unique definition and staging definitions. Even within academia, randomized trials and single center studies have widely disparate definitions. This makes NEC metadata of very limited value. The world of neonatology needs a comprehensive, universal, consensus definition of NEC. It also needs a de-identified, international data warehouse.

Iron Supplements for Infants at Risk for Iron Deficiency.

Professional societies have published recommendations for iron dosing of preterm neonates, but differences exist between guidelines. To help develop standardized guidelines, we performed a 10-year analysis of iron dosing in groups at risk for iron deficiency: IDM (infants of diabetic mothers), SGA (small for gestational age), and VLBW premature neonates (very low birth weight, <1500 g). We analyzed iron dosing after red cell transfusions and erythropoiesis-stimulating agents (ESA). Of IDM, 11.8% received iron in the hospital; 9.8% of SGA and 27.1% of VLBW neonates received iron. Twenty percent of those who received iron had it started by day 14; 63% by 1 month. Supplemental iron was stopped after red cell transfusions in 73% of neonates receiving iron. An ESA was administered to 1677, of which 33% received iron within 3 days. This marked variation indicates that a consistent approach is needed, and using this report and a literature review, we standardized our iron-dosing guidelines.