INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.
Abortion, Spontaneous/epidemiology* ; Adult ; COVID-19/transmission* ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; Cohort Studies ; Disease Transmission, Infectious/statistics & numerical data* ; Female ; Fetal Blood/immunology* ; Humans ; Infectious Disease Transmission, Vertical/statistics & numerical data* ; Live Birth/epidemiology* ; Maternal Age ; Milk, Human/virology* ; Obesity, Maternal/epidemiology* ; Placenta/pathology* ; Pregnancy ; Pregnancy Complications, Infectious/physiopathology* ; Pregnancy Outcome/epidemiology* ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Prospective Studies ; RNA, Viral/analysis* ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Singapore/epidemiology* ; Umbilical Cord/pathology* ; Young Adult

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

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

BackgroundFacing the increasing prevalence of gestational diabetes mellitus (GDM), this study aimed to evaluate the management of GDM and its association with adverse pregnancy outcomes.

MethodsThe data of 996 inpatients with GDM who terminated pregnancies in our hospital from January 2011 to December 2015 were collected. Treatments during pregnancy and the last hospital admission before delivery were analyzed. Pregnancy outcomes of the GDM patients were compared with 996 nondiabetic subjects matched by delivery year and gestational age. The association between fasting plasma glucose (FPG) and adverse pregnancy outcomes was examined by logistic regression analyses.

ResultsThe average prevalence of GDM over the 5 years was 4.4% (1330/30,191). Within the GDM patients, 42.8% (426/996) received dietary intervention, whereas 19.1% (190/996) received insulin treatment. Adverse outcomes were more likely to occur in patients with unsatisfactory control of blood glucose such as respiratory distress syndrome (RDS, χ = 13.373, P < 0.01). Elevated FPG was identified as an independent risk factor for premature birth (odds ratio [OR] = 1.460, P < 0.001), neonatal care unit admission (OR = 1.284, P < 0.001), RDS (OR = 1.322, P = 0.001), and stillbirth (OR = 1.427, P < 0.001).

ConclusionsManagement of GDM in the real world of clinical practice was unsatisfactory, which might have contributed to adverse pregnancy outcomes.

Blood Glucose ; analysis ; Diabetes, Gestational ; blood ; Female ; Humans ; Pregnancy ; Pregnancy Complications ; blood ; Pregnancy Outcome ; Retrospective Studies ; Risk Factors

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

A 33-year-old woman visited the emergency department presenting with fever and dyspnea. She was pregnant with gestational age of 31 weeks and 6 days. She had dysuria for 7 days, and fever and dyspnea for 1 day. The vital signs were as follows: blood pressure 110/70 mmHg, heart rate 118 beats/minute, respiratory rate 28/minute, body temperature 38.7℃, and oxygen saturation by pulse oximetry 84% during inhalation of 5 liters of oxygen by nasal prongs. Crackles were heard over both lung fields. There were no signs of uterine contractions. Chest X-ray and chest computed tomography scan showed multiple consolidations and air bronchograms in both lungs. According to urinalysis, there was pyuria and microscopic hematuria. She was diagnosed with community-acquired pneumonia and urinary tract infection (UTI) that progressed to severe sepsis and acute respiratory failure. We found extended-spectrum beta-lactamase producing Escherichia coli in the blood culture and methicillin-resistant Staphylococcus aureus in the sputum culture. The patient was transferred to the intensive care unit with administration of antibiotics and supplementation of high-flow oxygen. On hospital day 2, hypoxemia was aggravated. She underwent endotracheal intubation and mechanical ventilation. After 3 hours, fetal distress was suspected. Under 100% fraction of inspired oxygen, her oxygen partial pressure was 87 mmHg in the arterial blood. She developed acute kidney injury and thrombocytopenia. We diagnosed her with multi-organ failure due to severe sepsis. After an emergent cesarean section, pneumonia, UTI, and other organ failures gradually recovered. The patient and baby were discharged soon thereafter.
Acute Kidney Injury ; Adult ; Anoxia ; Anti-Bacterial Agents ; beta-Lactamases ; Blood Pressure ; Body Temperature ; Cesarean Section ; Dyspnea ; Dysuria ; Emergency Service, Hospital ; Escherichia coli ; Female ; Fetal Distress ; Fever ; Gestational Age ; Heart Rate ; Hematuria ; Humans ; Inhalation ; Intensive Care Units ; Intubation, Intratracheal ; Lung ; Methicillin-Resistant Staphylococcus aureus ; Oximetry ; Oxygen ; Partial Pressure ; Pneumonia ; Pregnancy Complications, Infectious ; Pregnancy ; Pyuria ; Respiration, Artificial ; Respiratory Insufficiency ; Respiratory Rate ; Respiratory Sounds ; Sepsis ; Sputum ; Thorax ; Thrombocytopenia ; Urinalysis ; Urinary Tract Infections ; Uterine Contraction ; Vital Signs

Congenital fibrinogen deficiency is an autosomal recessive or dominant disorder in which quantitative (afibrinogenaemia or hypofibrinogenaemia) or qualitative (dysfibrinogenaemia) defects in the fibrinogen Aa, Bb or c protein chains that lead to reduced functional fibrinogen. We now report the perioperative management of 4 pregnant women suffering from hypofibrinogenaemia scheduled for elective caesarean section from December 2012 to October 2016 in Peking University First Hospital and review this disease with reference to classification, symptom, replacement therapy, and selection of the modes of pregnancy termination and anesthesia. The four patients were all asymptomatic, whereas there existed recurrent pregnancy loss (case 3), family history (case 2), and offspring heredity (cases 3 and 4). Routine clotting studies revealed low fibrinogen levels and prolonged thrombin time (TT) during pregnancy and on admission. However, the platelet (PLT) count, prothrombin time (PT) and activated partial thromboplastin time (APTT) were normal. All the patients were administered fibrinogen concentrate perioperatively, and underwent uncomplicated combined spinal-epidural anesthesia and uneventful surgical procedure without postpartum hemorrhage. The replacement therapy of fibrinogen or fresh frozen plasma administration was essential to avoid anesthesia and obstetric complications. Regional blockade could safely be offered in the caesarean section, providing that their coagulation defect was corrected by availability of therapeutic products and adequate response to treatment. In addition, the point-of-care rotational thrombelastometry (ROTEM) or thrombelastogram (TEG) could play an important role in an optimal perioperative management for such patients. Management plans must be tailored to each individual, taking into consideration their bleeding risk as well as potential maternal and neonatal complications.
Afibrinogenemia/therapy* ; Blood Coagulation Tests ; Cesarean Section ; Female ; Fibrinogen ; Humans ; Partial Thromboplastin Time ; Pregnancy ; Pregnancy Complications/therapy* ; Thrombelastography

Objective: To explore the relationship between the status of HBsAg-positive infection of mothers and the non/low-response to hepatitis B vaccine of their infants. Methods: A total of 225 pairs of mothers and their infants were recruited in our cohort from June 2011 to July 2013. Infants were given three doses of hepatitis B vaccine at hour 24, first month and month 6(t)h respectively and were followed up for one year after birth. HBV serological markers and HBV DNA in the peripheral blood of both mothers and infants were detected by Electro-chemiluminescence immunoassay and fluorescence quantitative Polymerase Chain Reaction. Results: Six HBV infection models were detected in HBsAg-positive mothers, and "HBsAg (+), HBeAg (+), anti-HBc (+)" (model one) and "HBsAg (+), anti-HBe (+), anti-HBc (+)" (model two) accounted for 92.5%(208/225) of all the models. Rate of non/low-response to hepatitis B vaccine in infants born to mothers in model one was lower than those in model two, the differences are statistically significant (χ(2)=4.80, P=0.029). The rate of non/low-response to hepatitis B vaccine in infants showed a downward trend with the rising of HBeAg level in their mothers (χ(2)=4.86, P=0.028). Results from the unconditional logistic regression analysis showed that the HBeAg of the HBsAg-positive mothers was significantly correlated with the low risk of non/low-response to hepatitis B vaccine in infants (OR=0.598, 95%CI: 0.378-0.947). The positive rate of serum HBV DNA in HBsAg-positive mothers was 54.2%, while the rate of non/low-response to hepatitis B vaccine in infants born to HBV DNA positive mothers was similar to those infants born to HBV DNA negative mothers (χ(2)=0.22, P=0.640). Conclusions: "HBsAg (+), HBeAg (+), anti-HBc (+)" and "HBsAg (+), anti-HBe(+), anti-HBc (+)" were the common models seen in HBsAg-positive mothers, and the rate of non/low-response to hepatitis B vaccine was different between the two models. HBeAg of HBsAg-positive mothers might have positive effects on the immune response to hepatitis B vaccine in infants but the mechanisms remained not clear. HBV DNA of the HBsAg-positive mothers did not seem to be correlated with the immune response to hepatitis B vaccine in infants.
Adult ; Biomarkers/blood* ; DNA, Viral/blood* ; Diagnostic Tests, Routine ; Female ; Hepatitis B/prevention & control* ; Hepatitis B Antibodies/blood* ; Hepatitis B Surface Antigens/blood* ; Hepatitis B Vaccines/pharmacology* ; Hepatitis B e Antigens/blood* ; Hepatitis B virus/isolation & purification* ; Humans ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Mothers ; Pregnancy ; Pregnancy Complications, Infectious/virology*

The Ministry of Health (MOH) has updated the Clinical Practice Guidelines on Lipids to provide doctors and patients in Singapore with evidence-based treatment for lipids. This article reproduces the introduction and executive summary (with recommendations from the guidelines) from the MOH Clinical Practice Guidelines on Lipids, for the information of SMJ readers. Chapters and page numbers mentioned in the reproduced extract refer to the full text of the guidelines, which are available from the Ministry of Health website: http://www.moh.gov.sg/content/moh_web/healthprofessionalsportal/doctors/guidelines/cpg_medical.html.
Adult ; Cardiovascular Diseases ; complications ; therapy ; Child ; Coronary Artery Disease ; complications ; therapy ; Decision Support Systems, Clinical ; Dyslipidemias ; blood ; complications ; therapy ; Evidence-Based Medicine ; Female ; Humans ; Kidney Failure, Chronic ; complications ; therapy ; Life Style ; Lipids ; blood ; Lipoproteins, LDL ; blood ; Male ; Practice Guidelines as Topic ; Pregnancy ; Pregnancy Complications ; Risk Assessment ; Risk Factors ; Singapore

BACKGROUNDHyperglycemia is associated with adverse pregnancy outcomes. However, the relationships between them remain ambiguous. This study aimed to analyze the effect of different oral glucose tolerance test (OGTT) results on adverse perinatal outcomes.

METHODSThis retrospective cohort study included data from 15 hospitals in Beijing from June 20, 2013 to November 30, 2013. Women with gestational diabetes mellitus (GDM) were categorized according to the number and distribution of abnormal OGTT values, and the characteristics of adverse pregnancy outcomes were evaluated. Chi-square test and logistic regression analysis were used to determine the associations.

RESULTSIn total, 14,741 pregnant women were included in the study population, 2927 (19.86%) of whom had GDM. As the number of hyperglycemic values in the OGTT increased, the risk of cesarean delivery, preterm births, large-for-gestational age (LGA), macrosomia, and neonatal complications significantly increased. Fasting hyperglycemia had clear associations with macrosomia (odds ratios [OR s]:1.84, 95% confidence intervals [CI s]: 1.39-2.42,P < 0.001), LGA (OR: 1.70, 95% CI: 1.29-2.25,P < 0.001), and cesarean delivery (OR: 1.33, 95% CI: 1.15-1.55,P < 0.001). The associations were stronger as fasting glucose increased. GDM diagnosed by hyperglycemia at OGTT-2 h was more likely to lead to preterm birth (OR: 1.50, 95% CI: 1.11-2.03,P < 0.01).

CONCLUSIONSVarious characteristics of OGTTs are associated with different adverse outcomes. A careful reconsideration of GDM with hierarchical and individualized management according to OGTT characteristics is needed.

Birth Weight ; physiology ; Blood Glucose ; metabolism ; Body Mass Index ; Cesarean Section ; Chi-Square Distribution ; Diabetes, Gestational ; blood ; physiopathology ; Female ; Fetal Macrosomia ; blood ; physiopathology ; Glucose Tolerance Test ; methods ; Humans ; Pregnancy ; Pregnancy Complications ; Pregnancy Outcome ; Premature Birth ; blood ; physiopathology ; Retrospective Studies