Pregnancy complicated by type I, type II and gestational diabetes: experiences from the diabetic-obstetric center of Białystock

The aim of the study was the analysis of pregnancy outcome, newborn status, metabolic control and obstetric failure in 365 pregnant diabetic patients treated in Bia?ystok Diabetic-Obstetric Center. Abortions occurred in 1.64% of pregnancies, intrauterine deaths--in 1.1%, and newborns deaths--in 2.47% cases. Macrosomia was observed in 14.8% of children (from 12% in type 1--up to 25% in gestational diabetes class G2). Congenital malformations were seen in 16 newborns of type 1 diabetic women (9.6%), 2 newborns of type 2 diabetics (22.2%), 6 children of mothers with gestational diabetes class G1 (4.2%) and 4 (8.3%)--class G2. The discussion underlines the role of a long duration of the disease as a key factor increasing the risk of complications and the importance of a good metabolic control before and shortly after conception.     

妊娠期病毒性肝炎对围产儿的影响

目的 探讨妊娠期病毒性肝炎对围产儿的影响。方法 测定４７名正常孕妇和４９５例病毒性肝炎孕妇所生新生儿Ａｐｇａｒ评分和出生时体重,并检测新生儿血清肝炎病毒标志。结果 肝炎孕妇所生新生儿Ａｐｇａｒ评分和出生时体重均显著低于对照组（均Ｐ〈０．０１）,急性肝炎孕妇所生新生儿１ｍｉｎ Ａｐｇａｒ评分和出生时体重均显著低于乙型肝炎病毒（ＨＢＶ）携带和慢性肝炎组（均Ｐ〈０．０１）,甲型肝炎未见宫内感染。ＨＢＶ,     

Two case studies of chronic idiopathic neutropenia preceding acute myeloid leukaemia

Chronic idiopathic neutropenia is regarded as a benign disorder without risk of malignant transformation. We present two patients with chronic idiopathic neutropenia who showed disease progression to acute myeloid leukaemia. Sequence analysis of the granulocyte-colony stimulating factor receptor (G-CSFR) gene from leukaemic DNA did not reveal any mutations and microsatellite analysis provided no evidence of microsatellite instability or loss of constitutional heterozygosity. These case studies suggest that chronic idiopathic neutropenia may constitute a preleukaemic condition in some patients. Alterations of the G-CSFR or defective DNA mismatch repair do not appear to be involved in malignant transformation.     

Safety and efficacy profile of G-CSF therapy in patients with acute on chronic liver failure

BACKGROUND/AIM: We aimed to evaluate safety and efficacy of granulocyte-colony stimulating factor treatment in patients with acute on chronic liver failure and the effect of granulocyte-colony stimulating factor on the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4. METHODS: Twenty-four patients with acute on chronic liver failure were randomised to receive standard therapy, standard therapy+granulocyte-colony stimulating factor (5 microg/kg/day for 6 days) and standard therapy+granulocyte-colony stimulating factor (15 microg/kg/day s.c. for 6 days). Data on CD34+cell mobilisation were compared to age-matched peripheral blood haematopoietic stem cell donors treated with granulocyte-colony stimulating factor. On day third of treatment, the expression level of CXCR4, vascular endothelial growth factor receptor and very late activation antigen 4 was analysed in mobilised CD34+ cells. RESULTS: CD34 cell count increased after the second day of granulocyte-colony stimulating factor injection in both treatment groups compared to the linear increase observed in control. After the fifth day the increase was significantly higher in healthy donors versus patients with acute on chronic liver failure. A decrease in the expression of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor compared to premobilisation values was observed. No major side effects were observed. CONCLUSIONS: Granulocyte-colony stimulating factor treatment is able to induce CD34 mobilisation in patients with acute on chronic liver failure. The expression pattern of CXCR4, very late activation antigen 4 and vascular endothelial growth factor receptor suggests that these molecules are involved in the granulocyte-colony stimulating factor-induced stem cell mobilisation.     

Incidence of severe congenital neutropenia in Sweden and risk of evolution to myelodysplastic syndrome/leukaemia

Severe congenital neutropenia (SCN) is characterized by low blood neutrophil counts, early bacterial infections, and risk of leukaemia development. As yet, no population-based incidence estimates of SCN have been reported. Children less than 16 years of age with SCN were sought in Sweden during the 20-year period 1987-2006 by a questionnaire to all Swedish Departments of Paediatrics and by reviewing the Swedish Health and Welfare Statistical Databases. Thirty-two patients were diagnosed with congenital neutropenia during this period. All received treatment with recombinant granulocyte-colony stimulating factor (G-CSF). Twenty-one patients were diagnosed as SCN or probable SCN, corresponding to 1·0 per 100,000 live births. Nine (43%) had ELANE mutations, four (19%) HAX1 mutations and eight (38%) were children with disease of unknown genetic aetiology. Four out of 21 patients (19%) developed myelodysplastic syndrome/leukaemia and three (14%) died, all with leukaemia. The cumulative incidence of myelodysplastic syndrome/leukaemia was 31%. The observed incidence of SCN in this population-based study was higher than previously estimated, possibly because genetic testing now can identify SCN cases previously thought to be idiopathic or benign neutropenia. The risk of developing myelodysplastic syndrome/leukaemia is considerable. ELANE mutations are the most commonly identified genetic defects.     

Beclomethasone diproprionate for severe asthma during pregnancy

The safety of using inhaled beclomethasone dipropionate for the treatment of severe asthma during pregnancy was evaluated during 45 pregnancies in 40 women. Despite chronic administration of theophylline and, in some women, ephedrine, the asthma was so severe that corticosteroids were essential to prevent emergency room visits and status asthmaticus. At conception, beclomethasone dipropionate was being used regularly during 38 pregnancies and was initiated during the first trimester in 4 other pregnancies. The range of beclomethasone dipropionate inhalations was 4 to 16/d with a mean of 9.5/d (336 micrograms). Prednisone administration was necessary during 37 pregnancies. Status asthmaticus occurred in five women but no mothers or fetuses died. Cardiac malformations occurred in an infant born to a woman who was diabetic and schizophrenic whose pregnancy was complicated by diabetic ketoacidosis and status asthmaticus. It is not known whether beclomethasone dipropionate was the cause of these malformations. The prevalence of congenital malformations (1 of 43 live births) is within the normal range and shows that treatment with beclomethasone dipropionate is safe during pregnancy when recommended doses are used.     

Prospective study of pregnancy in systemic lupus erythematosus. Results of a multidisciplinary approach

Our prospective study attempted to better define the reciprocal relation between pregnancy and systemic lupus erythematosus (SLE), to reduce maternal morbidity/mortality, and fetal loss. Our protocol included all the pregnancies in our total of patients with SLE between the years 1974-1983. There were 102 pregnancies in 75 patients during this period; SLE was exacerbated in 59.7% that started with inactive disease, most with mild episodes. Hematologic manifestations and renal disease, however, required moderate or high doses of steroids. There were no maternal deaths. There were 49% premature newborns in the entire group and this increased to 59% in mothers with active SLE; 23% of newborns were small for gestational age in the entire group and the rate increased to 65% in mothers with active SLE. There was a 16% spontaneous abortion rate with no difference between mothers with active or inactive disease, 5 stillbirths and one neonatal death, with a total fetal loss of 22% (compared with 6.7% in the control group p less than 0.001). There were 32 cesarean sections with live outcomes and 14 newborn infants with a weight below 1.5 kg survived. Our study shows that in patients with SLE planned rheumatologic care of the mother, with special obstetrical and perinatal attention, may reduce the high maternal and fetal morbidity/mortality.     

Safety of Topical 5-Aminosalicylic Acid in Pregnancy

Objectives: To assess the safety and efficacy of topical 5-aniinosalicylic acid preparations for therapy of distal colitis during pregnancy. Methods : Nineteen pregnancies in sixteen consecutive patients with proven distal colitis were identified prospectively at a tertiary care center. All patients were given trials of weaning off medication and all failed. All subjects were on maintenance topical 5-aminosalicylic acid therapy at the time of conception. They were followed throughout their pregnancy and thereafter. Their children were also closely examined and followed by a pediatrician. Results : The mean age at delivery was 25.8 yr, and the mean duration of illness was 4.6 yr. After taking topical therapy, there were no relapses during the pregnancy. There were 19 successful full-term pregnancies with no fetal abnormalities. The mothers and children were followed for more than 6 months. Conclusion : In this series, topical 5-aniinosali-cylic acid appears safe, effective, and well tolerated in the management of pregnant patients with distal colitis.     

Safety of hydroxychloroquine in pregnant patients with connective tissue diseases: a study of one hundred thirty-three cases compared with a control group

OBJECTIVE: The use of hydroxychloroquine (HCQ) in pregnancy remains controversial. The recent demonstration that HCQ passes across the placenta, with cord blood concentrations nearly identical to those found in maternal blood, emphasizes the need for careful evaluation of pregnancies in women receiving HCQ. However, only small series of HCQ-treated pregnant women have been reported, and most of these studies had no control group. We now report our experience with 133 pregnancies in women being treated with HCQ, resulting in 117 live births. Results in the HCQ group are compared with those in a control group. METHODS: One hundred thirty-three consecutive pregnancies in 90 women treated with 200 mg of HCQ either twice daily (122 pregnancies) or once daily (11 pregnancies) were studied. These pregnancies were compared with 70 consecutive pregnancies in 53 women with similar disorders who did not receive HCQ. Electrocardiography was performed in 47 children of mothers treated with HCQ and in 45 children in the control group. RESULTS: Eighty-eight percent of pregnancies in the HCQ group and 84% of those in the control group ended successfully with a live birth. The outcomes of pregnancy were not statistically different between groups. One child in each group died of causes related to prematurity. Three malformations were observed in the HCQ group (1 hypospadias, 1 craniostenosis, and 1 cardiac malformation) versus 4 in the control group. On the electrocardiograms, the PR interval and the corrected QT interval were not statistically different between groups. No visual, hearing, growth, or developmental abnormalities were reported in any of the children at the last follow-up (ages 12-108 months; mean age 26 months). CONCLUSION: Our findings support preliminary evidence for the safety of HCQ therapy during pregnancy. This treatment probably should be maintained throughout pregnancy in patients with systemic lupus erythematosus.     

Imatinib mesylate plus G-CSF therapy for chronic myelogenous leukemia in the blastic crisis

Imatinib mesylate (imatinib) has shown significant effects in patients with chronic myelogenous leukemia. However, hematological toxicity often occurs and requires dosage reduction or discontinuation of imatinib treatment. A patient with chronic myelogenous leukemia in the blastic crisis received granulocyte-colony stimulating factor (G-CSF) simultaneously with imatinib. The patient was continuously treated with imatinib and G-CSF and achieved remission without any severe infection or neutropenia. There are a few reports on the efficacy of combined therapy with G-CSF and imatinib; however, the results in our case are rare suggesting that the use of G-CSF is effective for preventing severe infection. G-CSF enables continuous treatment with high-dose imatinib.     

Hemophagocytosis exacerbated by G-CSF/GM-CSF treatment in a patient with myelodysplasia

We describe a 75-year-old man with neutropenia in whom bone marrow aspirate and biopsy demonstrated hemophagocytosis associated with myelodysplasia (MDS). Therapy with granulocyte-colony stimulating factor (G-CSF) and granulocyte-monocyte-colony stimulating factor (GM-CSF) caused splenomegaly and severe thrombocytopenia, which recurred upon rechallenge. We propose that myeloid growth factors may be detrimental in patients with MDS-associated hemophagocytosis.     

Safety of azathioprine in pregnancy in inflammatory bowel disease

Although azathioprine has been reported to be safe during pregnancy in renal transplant recipients and patients with systemic lupus erythematosus, opinions vary whether it should be continued in pregnancy in inflammatory bowel disease. A retrospective analysis of the outcome of 16 pregnancies in 14 women receiving azathioprine for inflammatory bowel disease was performed. There was one infective complication of pregnancy (hepatitis B virus infection), but there were no congenital abnormalities or subsequent health problems in the children. This preliminary study suggests that azathioprine is safe in pregnancy in inflammatory bowel disease patients and that termination of pregnancy is not mandatory for those who conceive while taking the drug.     

Outcome of 100 pregnancies initiated under treatment with cabergoline in hyperprolactinaemic women

Context Data concerning the safety for pregnancy of cabergoline treatment in hyperprolactinaemic women are still scarce. Objective To exclude a higher than normal risk for miscarriage and congenital malformation in pregnancies initiated under cabergoline treatment. Design A retrospective study of 100 pregnancies in 72 hyperprolactinaemic women treated with cabergoline at the time of conception and follow‐up of the 88 newborn children. Methods Cabergoline was interrupted in 99 pregnancies and continued in one case. Foetal exposure dose to cabergoline was calculated for each pregnancy. Complications of pregnancy and neonatal status were compared to those observed in an age‐and delivery time‐matched control group of 163 women. Results The mean foetal exposure dose to cabergoline was 3·6 ± 4·7 mg. The rate of spontaneous miscarriages was 10%. Three medical terminations of pregnancy were performed for a foetal malformation (3%). Minor to moderate complications were observed in 31% of the pregnancies, a figure similar to that found in the control group. An increase in tumour size (2–8 mm) was observed in 17/37 evaluated cases, needing reintroduction of cabergoline during pregnancy in five patients. The 84 deliveries resulted in 88 infants, three of them presenting with a malformation (3·4%). Neonatal status was comparable to the control group, where a malformation rate of 6·3% was observed. Postnatal development of the children was normal. Conclusion Cabergoline treatment at the time of conception appears to be safe for both the pregnancy and the neonate, although more data are still needed on a larger number of pregnancies.     

Serum G-CSF levels are not increased in patients with antibody-induced neutropenia unless they are suffering from infectious diseases

By the use of a G-CSF-specific ELISA we determined the serum granulocyte-colony stimulating factor (G-CSF) levels in 63 patients with antibody-induced neutropenia including neonatal immune neutropenia, autoimmune neutropenia, and drug-induced immune neutropenia. In the sera of 20 patients, elevated G-CSF levels of 60-1006 pg/ml (normal <39 pg/ml) were observed. These patients suffered from infectious diseases at the time of blood collection. G-CSF levels normalized after successful antibiotic treatment, indicating that increased G-CSF production in patients with immune neutropenia may be primarily the result of infection and not of neutropenia.     

Perinatal outcomes associated with the use of glargine during pregnancy

Aims Insulin glargine (IG), with its non‐peaking action profile, might be useful in diabetic pregnancy. However, data on its safety are limited and its use during pregnancy is not recommended. This study focused on the effects of IG on perinatal outcome, particularly to estimate the rate of congenital anomalies and birthweight. Methods This retrospective study included women with pre‐gestational diabetes who used IG before (at least 1 month) and during pregnancy. For all women we recorded data regarding maternal glycaemic control and pregnancy outcome. We also compared women treated with IG throughout pregnancy and women who stopped taking IG at an earlier stage. Results From 27 centres, 107 Type 1 diabetic pregnancies were identified. IG was started 10.3 ± 6.9 months before conception and in 57.4% of cases was stopped during the first trimester; 42.6% of women continued using it until the end of pregnancy. There were six abortions (four spontaneous and two induced) and five newborns (4.9%) with congenital anomalies. Glycaemic control, birthweight and the prevalence of macrosomia and neonatal morbidity were similar in women who used IG for the full term compared with those who stopped IG earlier during pregnancy. Conclusions This study, although limited, suggests that IG is safe and effective; the rate of congenital malformations was within the range expected for diabetic pregnancies treated with more traditional forms of insulin. IG used throughout pregnancy did not seem to influence birthweight or increase adverse outcomes.     

Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies.

Congenital adrenal hyperplasia (CAH) refers to a family of monogenic inherited disorders of adrenal steroidogenesis most often caused by enzyme 21-hydroxylase deficiency (21-OHD). In the classic forms of CAH (simple virilizing and salt wasting), androgen excess causes external genital ambiguity in newborn females and progressive postnatal virilization in males and females. Prenatal treatment of CAH with dexamethasone has been successfully used for over a decade. This article serves as an update on 532 pregnancies prenatally diagnosed using amniocentesis or chorionic villus sampling between 1978 and 2001 at New York Presbyterian Hospital-Weill Medical College of Cornell University. Of the 532 pregnancies, 281 were prenatally treated for CAH due to the risk of 21-hydroxylase deficiency. Follow-up telephone interviews with mothers, genetic counselors, endocrinologists, pediatricians, and obstetricians were performed in all cases. Of the pregnancies evaluated, 116 babies were affected with classic 21-OHD. Of these, 61 were female, 49 of whom were treated prenatally with dexamethasone. Dexamethasone administered at or before 9 wk gestation (in proper doses) was effective in reducing virilization. There were no statistical differences in the symptoms during pregnancy between mothers treated with dexamethasone and those not treated with dexamethasone, except for weight gain, edema, and striae, which were greater in the treated group. No significant or enduring side-effects were noted in the fetuses, indicating that dexamethasone treatment is safe. Prenatally treated newborns did not differ in weight from untreated, unaffected newborns. Based on our experience, prenatal diagnosis and proper prenatal treatment of 21-OHD are effective in significantly reducing or eliminating virilization in the newborn female. This spares the affected female the consequences of genital ambiguity, genital surgery, and possible sex misassignment.     

The effect of pre-eclampsia on the levels of coagulation and fibrinolysis factors in umbilical cord blood of newborns.

The effect of pre-eclampsia on coagulation and fibrinolysis in newborns is still under investigation. We have evaluated several coagulation and fibrinolysis parameters in umbilical cord blood of 20 newborns from pre-eclamptic women and of 40 newborns from normotensive women with similar gestational age. Additionally, the presence of factor V Leiden and prothrombin G20210A mutation in cord blood has been assessed. Neonates from pre-eclamptic women exhibited significantly lower birth weight (2.48 +/- 0.92 versus 2.88 +/- 0.68 kg, P < 0.05) and were more frequently admitted to the neonatal intensive care unit (45 versus 20%, P < 0.01) as compared with neonates from normotensive women. Cord blood protein C antigen and activated protein C resistance mean levels were slightly higher in the group of neonates from pre-eclamptic mothers. Fibrinogen levels were lower in this group as compared with control newborns (132.17 +/- 46.97 versus 156.08 +/- 49.58 mg%, P < 0.02), and unrelated to birth weight. No significant differences between cases and controls were found in plasminogen activator inhibitor-1 or tissue plasminogen activator cord blood levels. Heterozygous prothrombin 20210A was found in three newborns from normotensive mothers, whereas no factor V Leiden mutation was found in either group. In conclusion, pre-eclampsia seems to have only mild effects on coagulation and fibrinolytic factors in the cord blood of newborns. Since no excess of common polymorphisms predisposing to thrombosis was found in newborns from pre-eclamptic mothers, it is unlikely that the carriership status of these genetic defects of newborns influences the adverse pregnancy/neonatal outcomes.     

Normalization of pregnancy outcome in pregestational diabetes through functional insulin treatment and modular out-patient education adapted for pregnancy.

AIM: To investigate whether modular out-patient group education for flexible, Functional Insulin Treatment (FIT) adapted for pregnancy can eliminate diabetes-associated neonatal complications in pregestational diabetes. RESEARCH DESIGN AND METHODS: Outcome analysis of the modular out-patient group education and FIT based on separate insulin dosages for fasting, eating or correcting hyperglycaemia in 76 consecutive pregnancies (in 20 cases first after conception) of 59 patients with pregestational diabetes (Type 1 diabetes, n = 54). Controls: (a) diabetic pregnancies: historical controls; (b) non-diabetic pregnancies: retrospective case-controlled study; (c) population-based data of all Austrian newborns registered within the respective time period. RESULTS: HbA1c of 113 +/- 18% of mean value (= 100%) of non-diabetic, non-pregnant population (103 +/- 14% during the last pregnancy trimester), and self-monitored blood glucose of 5.6 +/- 0.7 mmol/l (5.3 +/- 0.7 mmol/l during the last trimester) was achieved throughout all FIT pregnancies. Severe hypoglycaemia occurred in 14 pregnancies. The gestational age at delivery was 39.2 +/- 1.5 weeks (four cases (5.4%) < 37 weeks) with a birth weight of 3305 +/- 496 g. Four newborns (5.3%) were above the 90th, and nine (11.8%) below the 10th percentile for weight of reference population-based data. Hypoglycaemia was recorded in six newborns (8%). Malformations were found in two infants whose mothers booked for diabetes FIT education only after conception. The caesarean delivery rate was 25%. In comparison with historical diabetic pregnancy controls we demonstrated a reduction in major complications, and compared with non-diabetic women, a lowering of diabetes-related neonatal complication rates to general population levels. CONCLUSIONS: Structured, comprehensive, modular out-patient group education promoting self-choice of insulin dose for flexible, normal eating prior to conception normalizes pregnancy outcome in diabetes.     

妊娠期肝病对围产儿的影响

目的：探讨妊娠期肝病对围产儿的影响。方法：测定４７例正常孕妇和６３７例妊娠期肝病孕妇所生６４８名新生儿的Ａｐｇａｒ分值和出生时体重。结果：与病毒性肝炎孕妇相比,对照组和乙肝病毒携带产妇所生新生儿Ａｐｇａｒ分值和出生时体重均有显著差异（均Ｐ〈０．０１）,而ＩＣＰ孕妇所生新生儿Ａｐｇａｒ分值和出生时体重则均无显著差异（均Ｐ〉０．０５）。肝功能异常孕妇血清总胆红素,直接胆红素和总胆汗酸与新生儿Ａｐｇａｒ分值和出生时体重呈非常显著和显著负相关（均Ｐ〈０．０１,均Ｐ〈０．０５）,而血清谷丙转氨酶、谷草转氨酶和碱性磷酸酶与新生儿Ａｐｇａｒ评分和出生时体重却无显著相关关系（均Ｐ〉０．０５）。血清白蛋白和总蛋白水平与１分钟Ａｐｇａｒ评分分别有非常显著和显著正相关（Ｐ〈０．０１,Ｐ〈０．０５）。结论：孕妇病毒性肝炎与ＩＣＰ对围产     

Toxoplasma-IgM and IgG-avidity in single samples from areas with a high infection rate can determine the risk of mother-to-child transmission

Anti-Toxoplasma IgG-avidity was determined in 168 serum samples from IgG- and IgM-positive pregnant women at various times during pregnancy, in order to evaluate the predictive value for risk of mother-to-child transmission in a single sample, taking the limitations of conventional serology into account. The neonatal IgM was considered the serologic marker of transmission. Fluorometric tests for IgG, IgM (immunocapture) and IgG-avidity were performed. Fifty-one of the 128 pregnant women tested gave birth in the hospital and neonatal IgM was obtained. The results showed 32 (62.75%) pregnant women having high avidity, IgM indexes between 0.6 and 2.4, and no infected newborn. Nineteen (37.25%) had low or inconclusive avidity, IgM indexes between 0.6 and 11.9, and five infected newborns and one stillbirth. In two infected newborns and the stillbirth maternal IgM indexes were low and in one infected newborn the only maternal parameter that suggested fetal risk was IgG-avidity. In the present study, IgG-avidity performed in single samples from positive IgM pregnant women helped to determine the risk of transmission at any time during pregnancy, especially when the indexes of the two tests were analysed with respect to gestational age. This model may be less expensive in developing countries where there is a high prevalence of infection than the follow-up of susceptible mothers until childbirth with monthly serology, and it creates a new perspective for the diagnosis of congenital toxoplasmosis.