First trimester fasting glucose and glycated haemoglobin cut-offs associated with abnormal glucose homeostasis in the post-partum reclassification in women with hyperglycaemia in pregnancy.

Hyperglycaemia first detected during pregnancy is either gestational diabetes mellitus (GDM) or previous undiagnosed diabetes. We aimed to study if there were a first trimester fasting glycaemia (FTG) and a glycated haemoglobin (HbA1c) cut-off values associated with type 2 diabetes mellitus (T2DM) or abnormal glucose homeostasis (AGH) at the post-partum oral glucose tolerance test (OGTT) reclassification. We retrospectively studied a group of pregnant women from the Portuguese National Registry of GDM. Receiver-operating characteristic (ROC) curves were used to determine the best FTG and HbA1c cut-offs to predict T2DM and AGH. We studied 4068 women. The area under the ROC curves (AUC) for the association with T2DM was 0.85 (0.80-0.90) for FTG and 0.85 (0.80-0.91) for HbA1c. The best FTG cut-off for association with T2DM was 99 mg/dL: sensitivity 77.4%, specificity 74.3%, positive predictive value (PPV) 4.8%, and negative predictive value (NPV) 99.5%. The best HbA1c cut-off for association with T2DM was 5.4%: sensitivity 79.0%, specificity 80.1%, PPV 5.7%, and NPV 99.6%. The AUC for the association of FTG and HbA1c with AGH were 0.73 (0.70-0.76) and 0.71 (0.67-0.74), respectively. The best FTG cut-off for predicting AGH was 99 mg/dL: sensitivity 59.4%, specificity 76.2%, PPV 17.0%, and NPV 95.8%. The best HbA1c cut-off was 5.4%: sensitivity 48.7%, specificity 81.5%, PPV 17.8%, and NPV 95.1%. We suggest an FTG of 99 mg/dL and an HbA1c of 5.4% as the best cut-offs below which T2DM is unlikely to be present. Almost all patients with FTG < 99 mg/dL and HbA1c < 5.4% did not reclassify as T2DM. These early pregnancy cut-offs might alert the physician for the possibility of a previous undiagnosed diabetes and alert them to the importance of testing for it after delivery.

Metformin combined with insulin in women with gestational diabetes mellitus: a propensity score-matched study.

AIM: Metformin use in gestational diabetes (GDM) is a common practice. Although its use in combination with insulin might be advantageous, it was never formally tested. We studied whether combined treatment was associated with better obstetric or neonatal outcomes compared to insulin alone. METHODS: This is a retrospective study, using the Portuguese National Registry of GDM (2012-2017), of women treated with insulin ± metformin. Primary endpoints were obstetric and neonatal complications. Secondary endpoints were gestational weight gain (GWG) and insulin dose. A propensity score-matched analysis was performed to balance the distribution of age, BMI, insulin treatment duration, HbA1c, first trimester diagnosis of GDM and previous GDM or macrosomia. Women treated with metformin plus insulin and insulin only were then compared. RESULTS: A total of 4034 women were treated with insulin or insulin plus metformin (10.2%). After propensity score matching, we studied two groups of 386 patients. Obstetric and neonatal complications were similar. Women treated with metformin plus insulin had 201 (52.1%) obstetric complications versus 184 (47.7%) in insulin-only group, p = 0.22; and 112 (29.0%) neonatal complications versus 96 (24.9%), p = 0.19. Patients treated with metformin plus insulin had similar GWG, excessive weight gain and insulin dose compared to the insulin-only group. CONCLUSIONS: Women with GDM treated with insulin plus metformin had similar obstetric and neonatal complications, weight gained and insulin dose compared to those only treated with insulin.

Febrile Neutropenia following Parvovirus B19 Infection and Cross Anti-Kell Reaction to E. Coli in Pregnancy.

Parvovirus B19 has tropism for red line blood cells, causing immune hydrops during pregnancy. A positive anti-Kell Coombs reaction usually happens during pregnancy when there is production of antibodies that target Kell antigens, but cross reactions to other antigens may occur. A 24-year-old Gypsy primigravida, 0 Rhesus positive, presented with persistent isolated hyperthermia for 2 weeks and a positive indirect Coombs test result with anti-Kell antibodies at routine tests. She had a 19-week live fetus. The blood tests revealed bicytopenia with iron deficiency anemia, leucopoenia with neutropenia, and elevated C-reactive protein. She was medicated with imipenem, and had a slow clinical recovery. Blood, urine and sputum samples were taken to perform cultures and to exclude other systemic infections. Escherichia coli was isolated in the urine, which most probably caused a transient cross anti-Kell reaction. Haemophilus influenza in the sputum and seroconversion to parvovirus B19 was confirmed, causing unusual deficits in the white cells, culminating in febrile neutropenia. Despite the patient's lack of compliance to the medical care, both maternal and fetal/neonatal outcomes were good. This a rare case report of 2 rare phenomena, a cross anti-Kell reaction to E. coli and parvovirus B19 infection with tropism for white cells causing febrile neutropenia, both events occurring simultaneously during pregnancy.

O parvovírus B19 tem tropismo para as células sanguíneas da linha vermelha, causando hidropsia imune durante a gravidez. O teste Coombs anti-Kell positivo ocorre durante a gravidez quando há produção de anticorpos contra os antígenos de Kell, mas pode haver reações cruzadas para outros antígenos. Uma grávida primigesta de etnia cigana, de 24 anos, 0 Rhesus positivo, recorreu ao hospital às 19 semanas de gestação por hipertermia isolada persistente por 2 semanas e um teste Coombs indireto positivo por anticorpos anti-Kell em testes de rotina da gravidez. O estudo analítico revelou bicitopenia com anemia ferropênica, leucopenia com neutropenia, e elevação da proteína C-reativa. A paciente foi medicada com imipenem, e teve uma recuperação clínica lenta. Foram colhidas amostras de sangue, urina e expectoração para culturas bacterianas. Na urina, foi isolada Escherichia coli, o que provavelmente causou a reação anti-Kell cruzada transitória. Na expectoração, foi isolada Haemophilus influenza, e foi confirmada seroconversão para o parvovírus B19, que causou um déficit incomum na linhagem sanguínea branca, culminando com neutropenia febril. Apesar da má adesão aos cuidados médicos, os desfechos materno e fetal/neonatal foram bons. Este é um caso de 2 fenômenos raros, uma reação cruzada anti-Kell à infecção por E. coli, e parvovírus B19 com tropismo para células brancas causando neutropenia febril, ambos ocorrendo simultaneamente durante a gravidez.

Febrile neutropenia following parvovirus B19 infection and cross anti-kell reaction to E. coli in pregnancy / Infeção por parvovírus B19 causando neutropenia febril e reação cruzada anti-Kell com E. coli na gravidez

Abstract Parvovirus B19 has tropism for red line blood cells, causing immune hydrops during pregnancy. A positive anti-Kell Coombs reaction usually happens during pregnancy when there is production of antibodies that target Kell antigens, but cross reactions to other antigens may occur. A 24-year-old Gypsy primigravida, 0 Rhesus positive, presented with persistent isolated hyperthermia for 2 weeks and a positive indirect Coombs test result with anti-Kell antibodies at routine tests. She had a 19-week live fetus. The blood tests revealed bicytopenia with iron deficiency anemia, leucopoenia with neutropenia, and elevated C-reactive protein. She was medicated with imipenem, and had a slow clinical recovery. Blood, urine and sputum samples were taken to perform cultures and to exclude other systemic infections. Escherichia coli was isolated in the urine, which most probably caused a transient cross anti-Kell reaction. Haemophilus influenza in the sputum and seroconversion to parvovirus B19 was confirmed, causing unusual deficits in the white cells, culminating in febrile neutropenia. Despite the patient's lack of compliance to the medical care, both maternal and fetal/neonatal outcomes were good. This a rare case report of 2 rare phenomena, a cross anti-Kell reaction to E. coli and parvovirus B19 infection with tropism for white cells causing febrile neutropenia, both events occurring simultaneously during pregnancy.

Resumo O parvovírus B19 tem tropismo para as células sanguíneas da linha vermelha, causando hidropsia imune durante a gravidez. O teste Coombs anti-Kell positivo ocorre durante a gravidez quando há produção de anticorpos contra os antígenos de Kell, mas pode haver reações cruzadas para outros antígenos. Uma grávida primigesta de etnia cigana, de 24 anos, 0 Rhesus positivo, recorreu ao hospital às 19 semanas de gestação por hipertermia isolada persistente por 2 semanas e umteste Coombs indireto positivo por anticorpos anti-Kell em testes de rotina da gravidez. O estudo analítico revelou bicitopenia com anemia ferropênica, leucopenia com neutropenia, e elevação da proteína C-reativa. A paciente foi medicada com imipenem, e teve uma recuperação clínica lenta. Foram colhidas amostras de sangue, urina e expectoração para culturas bacterianas. Na urina, foi isolada Escherichia coli, o que provavelmente causou a reação anti-Kell cruzada transitória. Na expectoração, foi isolada Haemophilus influenza, e foi confirmada seroconversão para o parvovírus B19, que causou um déficit incomum na linhagem sanguínea branca, culminando com neutropenia febril. Apesar da má adesão aos cuidados médicos, os desfechos materno e fetal/neonatal foram bons. Este é um caso de 2 fenômenos raros, uma reação cruzada anti-Kell à infecção por E. coli, e parvovírus B19 comtropismo para células brancas causando neutropenia febril, ambos ocorrendo simultaneamente durante a gravidez.