Severe Neonatal Anemia Research Articles

Fetomaternal Hemorrhage following Placement of an Intrauterine Pressure Catheter: Report of a New Association.

Fetomaternal hemorrhage (FMH) can be associated with significant perinatal mortality. Our review of the literature did not identify any cases of FMH following placement of an intrauterine pressure catheter (IUPC). In our case, an IUPC was inserted in a patient undergoing induction of labor at term. Fetal bradycardia ensued shortly after placement, warranting an emergent cesarean delivery. Severe neonatal anemia was identified, and evaluation of maternal blood was consistent with massive FMH. This is the first reported association between FMH and IUPC placement. If this relationship is validated in future reports, appropriate changes in clinical practice may be warranted.

KLF1 Null Neonates Display Hydrops Fetalis and a Deranged Erythroid Transcriptome

We describe a case of severe neonatal anemia with kernicterus due to compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1 null human. The phenotype of severe DAT-negative non-spherocytic hemolytic anaemia (NSHA), jaundice, hepato-splenomegaly, and marked erythroblastosis is more severe than that present in CDA type IV due to dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found human KLF1 acts like mouse Klf1 to coordinate expression of >500 genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell cycle regulators, and blood group antigens. We interrogated recently published KLF1 ChIP-seq to determine directly regulated KLF1 genes in man. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. KIF23 mutations result in CDA type III so our finding provides a direct link btween CDA IV adn CDA III. We also identify new roles for KLF1 in autophagy, global transcriptional control and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis. DisclosuresNo relevant conflicts of interest to declare.

PO-0326 Comprehensive Analysis Of Exchange Transfusions Performed Over A 6yr Period In A Tertiary Neonatal Intensive Care Unit: Abstract PO-0326 Table 1

<h3>Introduction</h3> In the 1940’s, exchange transfusion (ExT) was introduced to help decrease the morbidity and mortality associated with haemolytic disease of the newborn (HDN) and prevent kernicterus. ExT was subsequently applied to other causes of neonatal hyperbiliribinaemia, severe neonatal anaemia from a variety of causes, some non-immune hydrops cases, Neonatal metabolic conditions such as hyperammonaemia, severe hyperkalaemia and neonatal haemochromatosis. In the 1970’s when ExT was exclusively used for the management of HDN, Lucey <i><i>et al</i>,</i> predicted a decrease in frequency of this procedure for HDN in future. Complications were estimated to increase due to the lack or decreased frequency of ExT with time. <h3>Objectives</h3> To determine. Number of ET done over a 6 yr period. Patients demographics, time of ExT, Indications. Number of Babies who have had Inutero ExT. Maternal details: Blood group, antibodies. The level of bilirubin at which transfusion took place. Prior treatment pre-ExT: In-utero Tx, Intravenous Immunoglobulin (IVIG) use; use of albumin infusion. The ExT-related complications: Any complication not present prior to the ET which occurred within 48 hrs after the ET: Defined as follows- platelet count &lt;150, hypocalaemia, ionised Calcium &lt;0.8, fits, raised INR. <h3>Methods</h3> Setting: Level 3 NICU. Retrospective notes review of patients who underwent ExT. January 2008–March 2014 (6.25 yrs). Exclusion criteria: Those for which notes were not obtained. <h3>Results</h3> Total admissions to the NICU over the period = 5,000. Number of exchange transfusions done= 15 in 14 patients. 0.3% of admissions over the period. Table of cases. Total number of request made to the Blood transfusion department for blood product for exchange. <h3>Conclusion</h3> Average ExT/yr in a Level 3 NICU = 2.4/yr. ExT is currently being used for a variety of causes. There were no complications related to the procedure itself. Complications post-ExT were all biochemical (hypocalcaemia- in 13 cases) or haematologic (low platelets 13 cases) Use of IVIG: Given pre-Ext to all ABO, Rh cases except 2 and to the Non-immune hydrops secondary to Parvovirus. 1st documented case of ExT use in hyperbilirubinaemia secondary to accidental Hyperlipidaemia from TPN-Lipid infusion and Haemolysis with Anaemia post-Octenisan wash treatment for MRSA-colonisation treatment in a preterm baby.

Quantitation of fetomaternal haemorrhage and F cells in unusual maternal blood samples by flow cytometry using anti‐D and anti‐HbF

Fetomaternal haemorrhage (FMH) assessment by the Kleihauer-Betke test (KBT) is rapid but semi-quantitative and liable to false positive results. To compare FMH estimated by KBT with flow cytometry (FC) quantitation for 37 patients with massive FMH, obstetric risk factors or technical problems. Maternal blood was sent for analysis by FC after KBT. A variety of reagents including anti-haemoglobin F (HbF), anti-D and combined anti-HbF/anti-carbonic anhydrase (CA) were used. Eight cases of massive FMH (>100 mL fetal cells) causing fetal death or severe neonatal anaemia in late gestation were confirmed by FC. Anti-HbF FC identified maternal F cells and fetal cells. In some cases these red cell populations merged but they could be differentiated by anti-CA, labelling F cells only. Using KBT, false positive FMH results were obtained for 12 patients, who had strongly stained cells that were then shown by FC to be maternal F cells. All these patients had increased F cells (>5% of total red cells) whereas only 16% of patients with FMH and 22% of donors had elevated F cells. In contrast, anti-D FC was simple and rapid, quantitating D-positive FMH in all 15 D-negative patients except one with massive FMH of weak D fetal cells. Leucocytes in four samples bound anti-D, variably, giving erroneously high FMH, but they could be eliminated from FC analysis using combined anti-D/anti-CD45. FMH quantitation using anti-D by FC is suitable for the majority of maternal samples and could enable accurate targeted dosing of anti-D prophylaxis.

A novel epsilon gamma delta beta thalassemia presenting with pregnancy complications and severe neonatal anemia

The epsilon gamma delta beta (εγδβ)-thalassemias are rare sporadic disorders caused by deletion of the β-globin gene cluster. The main clinical feature is marked prenatal and neonatal anemia that resolves spontaneously within a few months. Reports originating mainly from Europe have so far identified 30 such deletions The aim of the present work was to describe a novel 1.78-Mb deletion, the longest ever reported, and to detail the clinical features in 12 members of an extended Bedouin family. The deletion was identified by globin gene multiplex ligation-dependent probe amplification (MLPA) of the β-globin cluster and further characterized by comparative genomic hybridization. Past and present clinical and laboratory data of ten symptomatic and two asymptomatic patients were collected. A 1.78-Mb εγδβ-deletion, the largest ever described, was identified in all patients. Although other genes were included in the deletion, no other symptoms were observed. Of the ten symptomatic fetuses and neonates, three died of the disease. The remainder required packed cell transfusions during the first months of life. Pregnancy complications included intrauterine growth restriction and oligohydramnios, as well as additional neonatal complications including prematurity and persistent pulmonary hypertension of the neonate. We suggest that εγδβ-thalassemia be added to the list of hemoglobinopathies that can cause neonatal anemia and that MLPA of the β-globin cluster be used to confirm its diagnosis. Careful surveillance during pregnancy is important to reduce neonatal mortality and morbidity, especially given the dramatic improvement that occurs later.

Infantile Pyknocytosis: An Under-Recognized Form of Neonatal Hemolytic Anemia?

Infantile pyknocytosis (IP) is an under-recognized hematological entity of newborns that can cause a severe neonatal hemolytic anemia. A careful, prompt, and accurate peripheral blood smear examination is essential to establish the diagnosis. Here we describe the clinical features and histological parameters of 1 case of IP. Spontaneous resolution usually occurs by 4 to 6 months, but red blood cell transfusion may be needed if the anemia is severe.

Severe neonatal anemia from fetomaternal hemorrhage: report from a multihospital health-care system

The incidence of fetomaternal hemorrhage that is severe enough to cause neonatal anemia is not known. Owing to its relative rarity, much of the literature describing this condition is in the form of case reports and small case series. We performed a large, muiticentered, sequential, case series to determine the incidence, antecedents and outcomes. From the multicentered databases of Intermountain Healthcare, we obtained records of all neonates with hematocrit (Hct) <30% or hemoglobin (Hgb) <10 g dl(-1) on the day of birth, who had Kleihauer-Betke staining or flow cytometric evidence of fetomaternal hemorrhage. Among 219,853 live births, 24 had anemia with evidence of fetomaternal hemorrhage (incidence estimate, 1 per 9160 live births). The initial Hgb ranged from 1.4 to 10.2 g dl(-1) (Hct 29.8%). The initial Hgb was <7 g dl(-1) in 18 (67%), <5 g dl(-1) in 12 (50%) and was <3 g dl(-1) in 7 (29%). All 7 mothers in whom neonatal Hgb was <3 g dl(-1) had reported absent fetal movement, as did 13 of 18 mothers when the initial Hgb was <7 g dl(-1). Outcomes were poorer in those with the lowest initial Hgb; in the two lowest, one died on day 1, and the other developed a grade 4 intraventricular hemorrhage (IVH). The adverse outcomes of death, IVH, periventricular leukomalacia, bronchopulmonary dysplasia or hypoxic-ischemic encephalopathy were common; occurring in 71% (17 of the 24), including all with an initial Hgb <5 g dl(-1) and all born at ≤35 weeks of gestation. Fetomaternal hemorrhage is a rare but sometimes devastating condition. Those with fetomaternal hemorrhage and an initial Hgb of <5 g dl(-1) are expected to need resuscitation at birth, to receive emergent transfusion support and to be at risk for death and major morbidities. Antenatal suspicion of this diagnosis should occur when absent fetal movement is reported. Improvements in rapid diagnosis are needed to prepare first responders and transfusion services.

Severe fetal and neonatal hemolytic anemia due to a 198 kb deletion removing the complete β‐globin gene cluster

Fetal and neonatal hemolytic anemia can be caused by (γδβ)(0)-thalassemia deletions of the β-globin gene cluster. Many of these deletions have not been well characterized, and diagnostic tests are not readily available, thus hampering carrier detection, family counseling, and antenatal diagnosis. We report and define a 198 kb deletion removing the entire β-globin gene cluster, which was found in members of a multigeneration family of Irish/Scottish descent. The proband had life-threatening fetal and neonatal hemolytic anemia which subsided by 1 year of age.

The Xla (X-linked anemia) Mouse: A Transient Neonatal Anemia Caused by a Gata1 Splicing Mutation,

Abstract 3162The Xla (X-linked anemia) mutant mouse was generated by N-ethyl-N-nitrosourea (ENU) mutagenesis and results in a severe and transient neonatal anemia. Xla/+ females exhibit severe anemia with 50% the level of red blood cell number, hematocrit and hemoglobin. Male Xla mice die in utero at 10.5 days gestation. The neonatal anemia observed in Xla/+ female pups is resolved by weaning age at 3 weeks by which time the mice present with a normal hematological phenotype. It is unknown how the neonatal anemia in Xla/+ females is alleviated. Previously, we mapped the Xla locus to the proximal end of the X chromosome near candidate gene Gata1 which showed no change in the coding sequence of GATA1 protein. Now we report the identification of a Gata1 mutation in Xla mice that results in an mRNA splicing defect. A nucleotide change (G to A) was identified 5 base pairs downstream of Exon 1E in intron 1 of the Xla Gata1 gene and results in the lack of incorporation of Exon 1E in the Gata1 mRNA expressed from the mutant locus. Therefore, in some erythroid lineage cells in Xla/+ mice, the normal 1E exon of Gata1 mRNA is replaced by Exon 1Eb/c which is known not to impact erythropoeisis since no GATA1 protein is made by this mRNA due to its inability to bind to ribosomes. These data show the Xla mouse results from a single nucleotide change impacting the normal splicing of the Gata1 gene. A second goal of this study was to understand why Xla/+ mice exhibit the neonatal transient anemia. A contributing factor is X chromosome inactivation which occurs in female mice during development. The short-term anemia in Xla mice was thought to be due to clonal selection of erythroid lineage cells characterized by the expression of GATA1 protein from the active X chromosome expressing only from the wild type Gata1 locus. Using an X-linked gene expressed in red blood cells (Pgk1, phosphoglycerate kinase 1) that varies between Xla mice and a wild derived strain, CAST/Ei, we examined the active state of the X chromosomes based on the expression of Pgk1 RNA in reticulocytes from hybrid Xla mice generated by breeding of these different strains. Examining expression of the X-linked Pgk1 SNP variant in the RNA of reticulocytes from hybrid Xla/+ mice reveals red blood cells are generated from two types of erythroid lineage cells. Pgk1 SNP RT-PCR analysis reveals that red blood cells not only derive from erythroid progenitors with the active X chromosome carrying the wild type Gata1 gene but also red blood cells are produced by erythroid lineage cells expressing the Xla mutant Gata1 mRNA on the active X chromosome (which does not make GATA1 protein). Therefore, some Xla erythroid cells derive from progenitors which express Gata1 transcripts using Exon 1Eb/c that does not stimulate erythropoiesis due to lack of GATA1 protein. The question is how these erythroid precursors generate normal red blood cells without the production of GATA1 protein. We hypothesize there is a developmentally expressed compensatory gene or pathway replacing GATA1 expression in GATA1-lacking erythroid precursors and required for the production of red blood cells in Xla mice. Analysis is underway to identify a potential novel gene or pathway impacting erythropoiesis in these mutant mice. Disclosures:No relevant conflicts of interest to declare.

Fetal and neonatal anemia associated with anti‐Jra: A case report showing a poorly hemolytic mechanism

Although recently published case reports suggest the significance of Jr(a) alloimmunization in the obstetric setting, the involved mechanism still remains unclear. Here we report a case of severe fetal and neonatal anemia associated with anti-Jr(a) alloimmunization, which was successfully managed using Doppler assessment of peak systolic velocity of the fetal middle cerebral artery (MCA-PSV). A Japanese woman with anti-Jr(a) (titer 1024) was referred to our department at 20 weeks' gestation. As fetal MCA-PSV exceeded 1.5 multiple of median, labor was induced and a female neonate of 1998 g was delivered vaginally at 33 weeks and 5 days of gestation. The infant's hematocrit and hemoglobin levels were 25.4% and 82 g/L, respectively, but her total bilirubin level (15 µmol/L; 0.9 mg/dL) and reticulocyte counts (4.5%) were low. During the course, the infant showed no apparent signs of hemolysis. Jr(a) alloimmunization should be recognized as a possible cause of fetal anemia with no direct hemolytic process.

Severe Fetal and Neonatal Anemia Due to Heterozygosity for a 198 Kb Deletion Removing the Entire β-Globin Gene Cluster

AbstractAbstract 5171Infants who are heterozygous for a number of (γδβ)0-thalassemia deletions are known to present with neonatal hemolytic anemia (Koenig et al, Am J Hematol 84:603, 2009). The breakpoints for most of these large deletions have not been identified. Molecular diagnoses of these deletions therefore can be challenging. We now report an infant girl of Irish/Scottish descent with self-limited fetal and neonatal hemolytic anemia, in whom we have defined the extent of the large deletion removing the entire β-globin gene cluster. At 32-week of gestation, fetal tachycardia prompted percutaneous umbilical cord blood sampling, which revealed a hematocrit of 14%. Umbilical cord transfusion was undertaken followed by Caesarean section delivery. Brisk hemolysis continued in the first few days of life (reticulocyte count of 22 – 24%), with no other causes of hemolysis identified. In the following weeks, the infant was transfused on three occasions. After 2-month of age, she became transfusion-independent with a stable microcytic anemia. The infant's mother also had a history of hemolytic anemia requiring transfusion in the neonatal period, and subsequently became transfusion independent with a microcytic anemia. The mother and several of her family members were extensively investigated, and shown to have a novel (γδβ)0-thalassemia deletion of over 100 kb (Pirastu et al, J Clin Invest 72:602, 1983). Multiplex ligation-dependent probe amplification (MLPA) was carried out in the genomic DNA from the present neonate. The infant was heterozygous for a large deletion spanning at least from 5′ to the HS 5 of the LCR to 3′ of the β-globin gene. Sequential gap-PCR reactions and nucleotide sequencing were done. The deletion was characterized with its 5‘ breakpoint at nt 5,376,341 and 3‘ breakpoint at nt 5,178,572 (GenBank NT_009237). The deletion measures 197,770 bp, removing the β-globin LCR, all of the β-like globin genes, and several olfactory receptor genes. A diagnostic gap-PCR test was established for detection of this deletion. This case illustrates the syndrome of neonatal hemolytic anemia caused by large deletions removing the entire β-globin gene cluster. MLPA is a useful tool to screen for these deletions. The pathophysiology of these self-limited and sometimes severe fetal and neonatal hemolytic anemias is presently not understood. We speculate that expression of α-hemoglobin stabilizing protein (AHSP) and/or the proteolytic capacity to degrade excess α-globin chains within erythroid cells might be diminished during fetal and neonatal development, accounting for increased red cell membrane damage and hemolysis in affected fetuses and neonates. Disclosures:No relevant conflicts of interest to declare.

Hematologic characterization and chromosomal localization of the novel dominantly inherited mouse hemolytic anemia, neonatal anemia ( Nan)

One of the most commonly inherited anemias in man is Hereditary Spherocytosis (HS) with an incidence of 1 in 2000 for persons of Northern European descent. Mouse models of HS include spontaneous inherited hemolytic anemias and those generated by gene targeting. The Neonatal anemia ( Nan) mouse is a novel model of HS generated by N-ethyl- N-nitrosurea mutagenesis and suffers from a severe neonatal anemia. Adult Nan mice have a lifelong hemolytic anemia with decreased red blood cell numbers, hematocrit, and hemoglobin, but elevated zinc protoporphyrin levels. Blood smears taken from Nan mice show a hypochromic anemia characterized by poikilocytosis, anisocytosis and polychromasia. The Nan phenotype can be transferred by bone marrow transplantation indicating that the defect is intrinsic to bone marrow. The hemolytic anemia in adult Nan mice can be identified by osmotic fragility testing. Examination of the erythrocyte membrane skeleton proteins (EMS) reveals a global deficiency of these proteins with protein 4.1a being completely absent. The Nan locus maps to mouse Chromosome 8 and does not co-localize with any known EMS genes. The identification of the Nan gene will likely uncover a novel protein that contributes to the stability of the EMS and may identify a new mutation for HS.

Reporte de cinco casos de malaria neonatal grave por Plasmodium vivax en Urabá, Colombia

Neonatal malaria is a type of malaria that occurs during the first month of life. In the last half century, the reports of malaria parasites in neonates generally have been associated with congenital transmission. However, in recent years, cases have appeared with increasing frequency, especially in Africa. In Latin America, the incidence of neonatal malaria is unknown, with only isolated cases reported. Cases of neonatal malaria were identified and characterized to better recognize the frequency and symptoms of cases as they occur in Colombia. Between March 2002-March 2004, a search for cases of neonatal malaria was made in the hospitals of the Turbo and Apartadó counties (Urabá, Antioquia Province). The following date were compiled: (1) characteristics of the mother, (2) demographic characteristics of the neonates, (3) clinical characteristics of the disease, and (4) laboratory results. Five cases were discovered of neonatal vivax malaria; however, only one met the criteria for congenital infection. Three patients had institutional delivery and two had a maternal history of gestational malaria, but none underwent a screening test for malaria. One of the four mothers were primaparous and half of them were younger than 20 years. All neonates had fever and presented some sign of severe disease during the first medical examination; each had hemoglobin levels compatible with severe neonatal anemia. No neonate had received the recommended treatment for this type of malaria. Five cases of severe neonatal malaria were reported, caused by infections of P. vivax, which normally does not produce severe disease. Since none of the malaria cases were recognized or treated at the local hospitals, advisories to medical professionals are recommended concerning neonatal malaria, particularly in endemic regions.

Anti-Glycophorin C Induces a Loss of Mitochondrial Membrane Potential but Fails To Activate Apoptotic Caspases.

The human erythrocyte transmembrane sialoglycoprotein, glycophorin C (GYPC), plays a functional role in regulating red cell shape and mechanical stability. Antibodies to GYPC cause hemolytic disease of the fetus and newborn (HDFN) that is associated with classical Fcγ receptor-mediated phagocytosis. However, in vitro clonogenic studies with cord blood progenitor cells suggest that anti-GYPC also suppresses erythropoiesis, which is consistent with the observations of severe and early fetal anemia and late onset neonatal anemia [Transfus Med 2005; 15:125–32]. The mechanism of the suppressive effect on erythropoiesis is unknown. The K562 erythroleukemic cell line treated with anti-GYPC is a potential model system to study the suppressive effect of anti-GYPC. The present in vitro studies were designed to confirm the effect of anti-GYPC on K562 cell growth and viability, and to evaluate changes in mitochondrial membrane potential, phosphatidylserine (PS) expression, propidium iodide (PI) binding, and caspase activation. K562 cells fail to grow in the presence of anti-GYPC confirming earlier CFU-E/BFU-E studies [Brit J Haematol 2006; 133:443–4], and increased the exofacial expression of PS/PI over time. This process was caspase-independent as demonstrated by the failure of Z-VAD, a caspase inhibitor, to reverse growth inhibition and PS/PI expression. A loss of mitochondrial membrane potential was demonstrated using JC-1, a cationic dye that is sensitive to potential-dependent accumulation or loss in mitochondria. There was a 50% increase in K562 cell mitochondrial membrane potential disruption after 2 days of culture with anti-GYPC (see figure). Morphological examination of May Grunwalde Giemsa-stained K562 cells treated with anti-GYPC for 2 days showed a decrease in mitotic activity compared to isotype treated cells. By day 4, the anti-GYPC treated cells were showing evidence of plasma membrane damage and cell death resulting from fragmentation and dissolution of the cytoplasm. The addition of hemin, an oxidative form of iron protoporphyrin IX known to induce erythroid differentiation of K562 cells, to anti-GYPC treated cells reversed growth inhibition by 45% but did not prevent the loss of mitochondrial membrane potential. Overall, although caspases appear to be unimportant in anti-GYPC induced cell death, the mitchondria play an important role as the early events leading to antibody-mediated suppression of erythropoiesis. [Display omitted]

Blood transfusion therapy in neonates admitted into the Special Care Baby Unit (SCBU) of University of Port Harcourt Teaching Hospital, Port Harcourt

Blood transfusion is associated with potential risks and adverse effects; it is therefore pertinent to ensure that it is given only when it is indicated. The objective of this study is to determine the rate and the indications of blood transfusion in neonates admitted into the Special Care Baby Unit (SCBU) of University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt. A prospective study of Neonates admitted into SCBU between January 1st 2003 and December 31st 2004 and who had blood transfusion during their hospitalization was carried out. Preterm babies are more likely to be transfused and are also more likely to receive multiple blood transfusions. Severe neonatal jaundice and severe anaemia are the commonest indication for blood transfusions in the neonates. Exchange blood transfusions (EBTs) were utilized more often than top up transfusions even among preterms. Adverse events were seen more in those that had EBT CONCLUSION: The rate of blood transfusion is still very high among neonates. Concerted efforts should be made to prevent severe neonatal jaundice and severe anaemia and thus reduce the rate of blood transfusion.

Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the αβ spectrin self-association binding site

We studied an infant with severe neonatal hemolytic anemia and hyperbilirubinemia that evolved into a partially compensated ellipto-poikilocytic anemia. His father had typical elliptocytosis. Their erythrocyte membranes demonstrated structural and functional defects in spectrin. Genetic studies revealed that the proband and his father were heterozygous for an α-spectrin mutation, Ile24Thr, in the αβ spectrin self-association binding site. The proband also carried the low expression allele αLELYin trans, influencing the clinical phenotype. The importance of isoleucine in this position of the proposed triple helical model of spectrin repeats is highlighted by its evolutionary conservation in all α spectrins from Drosophila to humans. Molecular modeling demonstrated that replacement of a hydrophobic isoleucine with a hydrophilic threonine disrupts highly conserved hydrophobic interactions in the interior of the spectrin triple helix critical for spectrin function.

Mutation of a highly conserved isoleucine disrupts hydrophobic interactions in the αβ spectrin self-association binding site

We studied an infant with severe neonatal hemolytic anemia and hyperbilirubinemia that evolved into a partially compensated ellipto-poikilocytic anemia. His father had typical elliptocytosis. Their erythrocyte membranes demonstrated structural and functional defects in spectrin. Genetic studies revealed that the proband and his father were heterozygous for an α-spectrin mutation, Ile24Thr, in the αβ spectrin self-association binding site. The proband also carried the low expression allele αLELY in trans, influencing the clinical phenotype. The importance of isoleucine in this position of the proposed triple helical model of spectrin repeats is highlighted by its evolutionary conservation in all α spectrins from Drosophila to humans. Molecular modeling demonstrated that replacement of a hydrophobic isoleucine with a hydrophilic threonine disrupts highly conserved hydrophobic interactions in the interior of the spectrin triple helix critical for spectrin function.

Preterm Admissions in a Special Care Baby Unit: The Nnewi Experience

A review of all preterm admissions into the Special Care Bay Unit of the Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, over a period of 29 months (May 1998 – October 2000) was carried out. Out of a total of 699 neonatal admissions, 133 (19 percent) were preterms with gestational ages ranging from 24 to 36 weeks and birth weights from 600g to 2490g. Male: female ratio was 1:1.5. Seventy-three patients (54.9 percent) were referred from other health establishments, while 60 (45.1 percent) were born in NAUTH. Thirty-three patients were delivered by Caesarean section, out of which one died. Factors contributing to morbidity were sepsis, asphyxia, jaundice, anaemia and haemorrhagic disease of the newborn. Duration of hospital stay ranged from two hours to 54 days with a mean of 16.7 days. Twenty-four (18 percent) of the 133 patients died. Mortality-associated events were respiratory distress syndrome (40.0 percent), severe birth asphyxia (33.4 percent), neonatal sepsis (13.3 percent), severe neonatal jaundice (6.7 percent) and severe anaemia and haemorrhagic disease of the newborn (3.3 percent) each. The referred cases contributed 75 percent of the mortality. During the period between hospital discharge and one year corrected age, 2.8 percent of the babies died, 1.8 percent developed hydrocephalus, 1.8 percent had cerebral palsy, 2.8 percent had recurrent acute respiratory infections requiring hospital admission and 13.8 percent were lost to follow up. This study illustrates the impact of a newborn unit on a programme designed to reduce perinatal mortality.Nigerian Journal of Paediatrics 2002;29:75-79.

Devenir de 249 prématurés de moins de 29 semaines

The aim of this paper was to report the vital and neurological outcome of 249 preterm infants of less than 29 weeks born between 1990 and 1996, and included in a prospective study until two years of age. Results . – The initial mortality rate was 19%. This was related to gestational age and severe transfontanellar ultrasonographically (TFU) detected abnomalities. The rate of follow-up at two years of age was 98%. Neurological sequelae amounted to 12.8%, including four cases of deafness. The possibility of survival without neurological sequelae increased from 52% at 24–25 weeks to 72% at 26–28 weeks of gestational age ( p < 0.005). The presence of sequelae was significantly related to severe cranial ultrasonographically-detected abnormalities, to parental social level, and to early neonatal anemia. Normal TFU and/or isolated periventricular hyperechogenicity could not exclude the presence of neurological sequelae which, however, appeared to be less severe than at the onset. Conclusion. – Gestational age, severe TFU abnormalities and neonatal anemia play a major role in the rate of mortality and in the neurological sequelae in preterm infants, and can influence the decisions concerning the treatment of this pediatric population.

Hb DARTMOUTH [α66(E15)Leu → Pro (α2) (CTG → CCG)]: A NOVEL α2-GLOBIN GENE MUTATION ASSOCIATED WITH SEVERE NEONATAL ANEMIA WHEN INHERITED IN TRANS WITH SOUTHEAST ASIAN α-THALASSEMIA-1

We report a novel mutation at α66(E15)Leu → Pro (α2) (CTG → CCG), that we have named Hb Dartmouth for the medical center at which the patients were cared for, in monozygotic twins who also inherited the Southeast Asian α-thalassemia-1 deletion. The mother, of Khmer ancestry, is heterozygous for α-thalassemia-1. The father, who is of Scottish-Irish ancestry, is a silent carrier of the codon 66 mutation. The twins had severe neonatal anemia requiring transfusion.