Genetic hemoglobin disorders are caused by mutations and/or deletions in the α-globin or β-globin genes. Thalassemia is caused by quantitative defects and hemoglobinopathies by structural defect of hemoglobin. The incidence of thalassemia and hemoglobinopathy is increased in Korea with rapid influx of people from endemic areas. Thus, the awareness of the disease is needed. α-thalassemias are caused by deletions in α-globin gene, while β-thalassemias are associated with decreased synthesis of β-globin due to β-globin gene mutations. Hemoglobinopathies involve structural defects in hemoglobin due to altered amino acid sequence in the α- or β-globin chains. When the patient is suspected with thalassemia/hemoglobinopathy from abnormal complete blood count findings and/or family history, the next step is detecting hemoglobin abnormality using electrophoresis methods including high performance liquid chromatography and mass spectrometry. The development of novel molecular genetic technologies, such as massively parallel sequencing, facilitates a more precise molecular diagnosis of thalassemia/hemoglobinopathy. Moreover, prenatal diagnosis using genetic testing enables the prevention of thalassemia birth and pregnancy complications. We aimed to review the spectrum and classification of thalassemia/hemoglobinopathy diseases and the diagnostic strategies including screening tests, molecular genetic tests, and prenatal diagnosis.
Amino Acid Sequence ; Anemia ; Blood Cell Count ; Chromatography, Liquid ; Classification ; Clinical Laboratory Techniques ; Diagnosis ; Electrophoresis ; Erythrocytes ; Genetic Testing ; Hematology ; Hemoglobinopathies ; High-Throughput Nucleotide Sequencing ; Humans ; Incidence ; Korea ; Mass Screening ; Mass Spectrometry ; Molecular Biology ; Parturition ; Pregnancy Complications ; Prenatal Diagnosis ; Thalassemia

INTRODUCTION: Haemoglobinopathy testing is performed for carrier screening and evaluation of microcytic anaemia. We evaluated the effectiveness of thalassaemia screening tests at our institution and suggest ways of improving the testing algorithm. MATERIALS AND METHODS: A total of 10,084 non-antenatal and 11,364 antenatal samples with alkaline gel electrophoresis (AGE), capillary electrophoresis (CE), haemoglobin H (HbH) inclusion test, mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV) were retrospectively reviewed. A subgroup of 187 samples with genetic testing was correlated with HbH inclusions and MCH/ MCV. The effect of iron deficiency on percentage hemoglobin A2 (HbA2) was studied. RESULTS: HbH inclusion test showed low sensitivity of 21.43% for α-thalassaemia mutations but higher sensitivity of 78.95% for deletion. By receiver operating characteristic (ROC) analysis, MCH ≤28 pg or MCV ≤80 fl for non-antenatal samples and MCH ≤27 pg or MCV ≤81 fl for antenatal samples had >98% sensitivity for HbH inclusions. Above these thresholds, the probability that HbH inclusions would be absent was <99% (negative predictive value [NPV] >99%). MCH ≥28 pg had 100% sensitivity (95% CI 95.63%-100%) for α-thalassaemia mutations and 97.68% calculated NPV in the antenatal population. Detection of haemoglobin variants by CE correlated highly with AGE (99.89% sensitivity, 100% specificity). Severe iron deficiency reduced HbA2 in hemoglobin ( <0.001) and α-thalassaemia ( = 0.0035), but not in β-thalassaemia. CONCLUSION MCH/MCV thresholds have adequate sensitivity for α-thalassaemia in the antenatal population, and genotyping plays an important role as HbH inclusion test shows low sensitivity. CE without AGE, may be used as initial screening for haemoglobin variants. Our study provides contemporary data to guide thalassaemia screening algorithms in Singapore.
Blood Protein Electrophoresis ; Electrophoresis, Capillary ; Erythrocyte Inclusions ; pathology ; Erythrocyte Indices ; Female ; Genetic Testing ; Hemoglobin H ; analysis ; Humans ; Male ; Mass Screening ; Pregnancy ; Pregnancy Complications, Hematologic ; blood ; diagnosis ; Retrospective Studies ; Sensitivity and Specificity ; Singapore ; alpha-Thalassemia ; blood ; diagnosis

PURPOSE: Urosepsis in adults comprises approximately 25% of all sepsis cases, and is due to complicated urinary tract infections in most cases. However, its mechanism is not fully clarified. Urosepsis is a very complicated disease with no effective strategy for early diagnosis and treatment. This study aimed to identify possible target-related proteins involved in urosepsis using proteomics and establish possible networks using bioinformatics. METHODS: Fifty patients admitted to the Urology Unit of Lanzhou General PLA (Lanzhou, China), from October 2012 to October 2015, were enrolled in this study. The patients were further divided into shock and matched-pair non-shock groups. 2-DE technique, mass spectrometry and database search were used to detect differentially expressed proteins in serum from the two groups. RESULTS: Six proteins were found at higher levels in the shock group compared with non-shock individuals, including serum amyloid A-1 protein (SAA1), apolipoprotein L1 (APOL1), ceruloplasmin (CP), haptoglobin (HP), antithrombin-III (SERPINC1) and prothrombin (F2), while three proteins showed lower levels, including serotransferrin (TF), transthyretin (TTR) and alpha-2-macroglobulin (A2M). CONCLUSION Nine proteins were differentially expressed between uroseptic patients (non-shock groups) and severe uroseptic patients (shock groups), compared with non-shock groups, serum SAA1, APOL1,CP, HP, SERPINC1and F2 at higher levels, while TF, TTR and A2M at lower levels in shock groups.these proteins were mainly involved in platelet activation, signaling and aggregation, acute phase protein pathway, lipid homeostasis, and iron ion transport, deserve further research as potential candidates for early diagnosis and treatment. (The conclusion seems too simple and vague, please re-write it. You may focus at what proteins have been expressed and introduce more detail about its significance.).
Adult ; Aged ; Antithrombin III ; Apolipoprotein L1 ; blood ; Ceruloplasmin ; Female ; Haptoglobins ; Humans ; Male ; Middle Aged ; Prealbumin ; Pregnancy-Associated alpha 2-Macroglobulins ; Proteomics ; Prothrombin ; Sepsis ; blood ; diagnosis ; etiology ; genetics ; Serum Amyloid A Protein ; Transferrin ; Urinary Tract Infections ; complications

: Fetal hydrops is a serious condition which can be caused by immune and non-immune aetiologies. We aimed to review the management of fetal hydrops at our hospital.: A retrospective review of all cases of fetal hydrops diagnosed in our institution from 2006 to 2013 was carried out.: Out of the 30 cases of fetal hydrops diagnosed antenatally, 17 were cases of Bart's hydrops which were all terminated in-utero. Of the remaining 13 cases, 11 cases consisted of non-immune causes of hydrops. Planned antenatal interventions including in-utero blood transfusions (n = 4) and thoracentesis (n = 5) as well as planned caesarean deliveries (n = 11) were performed in the majority of cases. Postnatal neonatal intensive care with interventions including chest drainage and transfusions were also performed. A majority, 92%, of the cases survived the perinatal period following a variable length of hospital stay ranging from a week to 3 months.: Management of fetal hydrops is complex. Close coordination between the obstetric and neonatal teams was the key to good short-term survival of neonates with antenatally diagnosed hydrops, as it allows timely antenatal intervention and anticipation of potential perinatal complications.
Abortion, Induced ; Blood Transfusion ; Cesarean Section ; Disease Management ; Drainage ; Female ; Fetal Therapies ; Hemoglobins, Abnormal ; Humans ; Hydrops Fetalis ; blood ; etiology ; therapy ; Infant, Newborn ; Intensive Care Units, Neonatal ; Pregnancy ; Prenatal Diagnosis ; Retrospective Studies ; Singapore ; Survival Rate ; Tertiary Care Centers ; Thoracentesis ; alpha-Thalassemia ; blood ; complications

Subclinical hypothyroidism (SCH) represents a mild or compensated form of primary hypothyroidism. The diagnosis of SCH is controversial, as its symptoms are non-specific and its biochemical diagnosis is arbitrary. The treatment of SCH was examined among non-pregnant adults, pregnant adults and children. In non-pregnant adults, treatment of SCH may prevent its progression to overt hypothyroidism, reduce the occurrence of coronary heart disease, and improve neuropsychiatric and musculoskeletal symptoms associated with hypothyroidism. These benefits are counteracted by cardiovascular, neuropsychiatric and musculoskeletal side effects. SCH is associated with adverse maternal and fetal outcomes that may improve with treatment. Treating SCH in children is safe and may improve growth. Importantly, the evidence in this field is largely from retrospective and prospective studies with design limitations, which precludes a conclusive recommendation for the treatment of SCH.
Adolescent ; Biomarkers ; metabolism ; Bone and Bones ; Child ; Coronary Disease ; blood ; Disease Progression ; Female ; Goiter ; complications ; Humans ; Hypothyroidism ; blood ; diagnosis ; therapy ; Male ; Migraine Disorders ; physiopathology ; Pregnancy ; Pregnancy Complications ; Prospective Studies ; Retrospective Studies ; Risk Factors ; Treatment Outcome

PURPOSE: Moyamoya disease (MMD) occurs predominantly in Korean and Japanese women. The aim of this study was to investigate clinical features and pregnancy outcomes in women with MMD. MATERIALS AND METHODS: We conducted a retrospective chart review of women with MMD who visited our Department of Obstetrics and Gynecology between January 2005 and October 2013. For all study subjects, clinical features, demographic characteristics, and perinatal outcomes were recorded. RESULTS: We identified 28 pregnancies in 22 patients who had been diagnosed with MMD. The mean maternal age at delivery was 31.9+/-3.5 years old. The mean gestational age at delivery was 38.0+/-0.9 weeks. Among the 28 pregnancies, 25 (92.5%) underwent cesarean section; 19 (76.0%) of them were performed under regional anesthesia and six (24.0%) under general anesthesia. The mean newborn weight was 3233.7+/-348.2 g. The 5-minute Apgar score in 85% of the newborns was higher than 8, with no other apparent complications. During the puerperal period, transient ischemic attack symptom or seizure occurred in 4 cases, although patients recovered within a few days. CONCLUSION: For pregnant women with MMD, it is important to control blood pressure and prevent hyperventilation during the intrapartum period, and the best methods of delivery and anesthesia should be considered to avoid unfavorable sequelae. Additionally, a multidisciplinary approach (i.e., neurosurgery) is necessary to constantly manage underlying diseases.
Adult ; Blood Pressure/physiology ; Cesarean Section ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Maternal Age ; Moyamoya Disease/*diagnosis/epidemiology ; Pregnancy ; *Pregnancy Complications ; Pregnancy Outcome/*epidemiology ; Republic of Korea/epidemiology ; Retrospective Studies

During the first trimester of pregnancy, thyroid-stimulating hormone (TSH) >2.5 mIU/L has been suggested as the universal criterion for subclinical hypothyroidism. However, TSH levels change continuously during pregnancy, even in the first trimester. Therefore the use of a fixed cut-off value for TSH may result in a different diagnosis rate of subclinical hypothyroidism according to gestational age. The objective of this study was to obtain the normal reference range of TSH during the first trimester in Korean gravida and to determine the diagnosis rate of subclinical hypothyroidism using the fixed cut-off value (TSH >2.5 mIU/L). The study population consisted of pregnant women who were measured for TSH during the first trimester of pregnancy (n=492) and nonpregnant women (n=984). Median concentration of TSH in pregnant women was lower than in non-pregnant women. There was a continuous decrease of median TSH concentration during the first trimester of pregnancy (median TSH concentration: 1.82 mIU/L for 3+0 to 6+6 weeks; 1.53 mIU/L for 7+0 to 7+6 weeks; and 1.05 mIU/L for 8+0 to 13+6 weeks). Using the fixed cut-off value of TSH >2.5 mIU/L, the diagnosis rate of subclinical hypothyroidism decreased significantly according to the gestational age (GA) at TSH (25% in 3+0 to 6+6 weeks, 13% in 7+0 to 7+6 weeks, and 9% for 8+0 to 13+6 weeks, P<0.001), whereas the diagnosis rate was 5% in all GA with the use of a GA-specific cut-off value (P=0.995). Therefore, GA-specific criteria might be more appropriate for the diagnosis of subclinical hypothyroidism.
Adult ; *Algorithms ; Biomarkers/blood ; Diagnosis, Computer-Assisted/*methods ; *Diagnostic Techniques, Obstetrical and Gynecological ; Female ; *Gestational Age ; Humans ; Hypothyroidism/blood/*diagnosis ; Pregnancy ; Pregnancy Complications/blood/*diagnosis ; Reproducibility of Results ; Republic of Korea ; Sensitivity and Specificity ; Thyrotropin/*blood

OBJECTIVETo summarize and review the clinical characteristics including clinical features, prenatal characteristics, diagnosis, treatments and short-term outcomes of the twin anemia-polycythemia sequence (TAPS) to improve the recognition of the disease.

METHODThe clinical data of one case with twin anemia-polycythemia sequence and the reports of 15 cases seen in the past 5 years were reviewed and analyzed.

RESULTThere was an increasing number of reports of cases with TAPS. Prenatal manifestation: among the 16 cases, TAPS occurred in 13 cases naturally and in 3 cases occurred after laser treatment. Amniotic fluid volume showed no significant difference in 16 cases. Middle cerebral artery peak systolic velocity (MCA-PSV) > 1.5 multiples of the median (MoM) in the donor were 11/16 cases and 3/16 cases were not tested. MCA-PSV < 1.0 MoM in the recipient were seen in 10/16 cases and in 3/16 cases MCA-PSV was not tested. Hydrops fetalis was found in 6/16 cases. Intrauterine intervention: intrauterine blood transfusion was performed in 4/16 cases, fetoscopic laser occlusion of chorioangiopagus vessels was performed in 4/16 cases, umbilical cord occlusion selective feticide was done in 2/16 cases and intrauterine hemodilution in the recipient was performed in 1/16 case. Postnatal manifestation: average hemoglobin concentration in the anemic neonate was 95 g/L and in the polycythemic one was 208 g/L, intertwin Hb difference was > 80 g/L in 10/16 cases and < 80 g/L in 2/16 cases (after intrauterine laser treatment). Intertwin reticulocyte count ratio was > 1.7 in 5/16 cases and < 1.7 in 1/16 case (after intrauterine laser treatment). Postnatal treatment: 9/16 cases of donor had anemia, among them, 6/16 cases were given blood transfusions, 6/16 cases of recipient with hyperviscosity underwent partial exchange transfusions. Neurodevelopmental follow-up during neonatal period was normal in 11/16 cases, in our case, neurodevelopmental follow-up at the corrected gestational age 3 months was normal.

CONCLUSIONTAPS is a new atypical form of twin-twin transfusion syndrome (TTTS) that presents as a large intertwin hemoglobin difference with one twin developing anemia and the other developing polycythemia, without oligohydramnios-polyhydramnios sequence that is required for the diagnosis of TTTS. We suggest that routine doppler studies and MCA-PSV measurements should be performed during each follow-up visit in all uncomplicated monochorionic twin pregnancies, in order to find out the cases required intrauterine intervention to decrease neonatal mortality rates and improve the prognosis.

Anemia ; diagnosis ; etiology ; therapy ; Blood Flow Velocity ; Blood Transfusion, Intrauterine ; Female ; Fetofetal Transfusion ; complications ; diagnosis ; Gestational Age ; Hemoglobins ; analysis ; Humans ; Infant, Newborn ; Laser Coagulation ; Male ; Middle Cerebral Artery ; diagnostic imaging ; physiopathology ; Polycythemia ; diagnosis ; etiology ; therapy ; Pregnancy ; Pregnancy Complications, Hematologic ; diagnosis ; therapy ; Prognosis ; Twins, Monozygotic ; Ultrasonography, Prenatal

Our objective was to evaluate the relationship between intrauterine exposure to cadmium and the presence of atopic dermatitis in infants 6 months of age, adjusted for covariates including exposure to other heavy metals. The present research is a component of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project conducted in Korea. Study subjects were restricted to pregnant women in whom cadmium and lead levels were measured at delivery and whose infants were assessed for the presence of atopic disease at 6 months of age. The odds ratio (OR) for the presence of atopic dermatitis in 6-month-old infants whose cord blood had elevated cadmium levels, after adjustment for other covariates, was 2.350 (95% CI, 1.126-4.906). The OR for the presence of atopic dermatitis in infants whose cord blood had elevated lead levels was not significant. In the present study, the cord blood cadmium level was significantly associated with the presence of atopic dermatitis in 6-month-old infants; this was not true of the cord blood lead level. To the best of our knowledge, this is the first prospective study to show a relationship between prenatal exposure to cadmium and atopic dermatitis in infancy.
Adult ; Cadmium/analysis ; Cadmium Poisoning/*complications ; Cohort Studies ; Dermatitis, Atopic/diagnosis/*etiology ; Female ; Fetal Blood/chemistry ; Gestational Age ; Humans ; Infant ; Lead/analysis/toxicity ; Male ; Odds Ratio ; Pregnancy ; Prenatal Exposure Delayed Effects

We report a case of neonatal thyrotoxicosis with concurrent respiratory failure in an infant born to a mother with Graves' disease and review the published literature describing neonatal hyperthyroidism. The male infant who was born by spontaneous delivery at 35 weeks of gestational age presented with fever, tachycardia and tachypnea at rest on day 11 after birth, and developed severe apnea on day 14. Thyroid function studies revealed hyperthyroidism in the infant, and his mother was confirmed to have Grave's disease during pregnancy. Literature review showed that among the 33 infants with similar conditions, tachycardia, tachypnea and poor weight gain were the most distinct clinical features of congenital hyperthyroidism. Accurate diagnosis of Graves' disease in the mother during pregnancy and awareness of the clinical presentations of neonatal hyperthyroidism are key to reducing missed diagnosis or misdiagnosis of neonatal hyperthyroidism.
Antithyroid Agents ; therapeutic use ; Apnea ; etiology ; Female ; Graves Disease ; blood ; Humans ; Hyperthyroidism ; blood ; complications ; diagnosis ; drug therapy ; Infant, Newborn ; Infant, Newborn, Diseases ; blood ; diagnosis ; drug therapy ; Infant, Premature ; Male ; Maternal-Fetal Exchange ; Pregnancy ; Pregnancy Complications ; blood ; Propylthiouracil ; therapeutic use ; Thyrotropin ; blood ; Thyroxine ; blood ; Triiodothyronine ; blood