OBJECTIVEThis randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes.RESEARCH DESIGN AND METHODSPatients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8–12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account.RESULTSA total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8–12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, –0.06% [95% CI –0.21 to 0.08]; per protocol, –0.15% [–0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups.CONCLUSIONSTreatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable.

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The transcription factors signal transducer and activator of transcription 5a and 5b (Stat5) are activated by the neuroprotective and neurotrophic cytokines, erythropoietin (EPO) and growth hormone (GH). Here, we show a dissociation of the intracellular pathway mediating the protective effect of EPO against glutamate toxicity from that needed for its neurotrophic activity using hippocampal neuronal cultures from Stat5a/b-knockout (Stat5 À/À ) mouse fetuses. Both pretreatment and post-treatment with EPO counteracted glutamate-induced cell death in Stat5 þ / þ and Stat5 À/À neurons. Acute pharmacological inhibition of Janus kinase 2 (JAK2)/Stat signalling had no effect on EPO neuroprotection, whereas inhibition of phosphatidylinositol-3 0 kinase (PI3K)/Akt pathway abolished the protective effect of EPO in both Stat5 þ / þ and Stat5 À/À neurons. GH effectively protected Stat5 þ / þ cells against glutamate toxicity but had no effect in Stat5 À/À neurons or in Stat5 þ / þ neurons treated with JAK2/Stat or PI3K inhibitor. EPO and GH stimulated neurite outgrowth and branching of Stat5 þ / þ neurons by activating PI3K/Akt signalling but had no trophic effect in Stat5 À/À cells. We conclude that in hippocampal neurons, Stat5 is not required for neuroprotection by EPO but is together with Akt essential for its neurotrophic activity. Both Stat5 and Akt are needed for neuroprotective and neurotrophic signalling of GH in neurons. The transcription factors signal transducer and activator of transcription 5a and 5b (Stat5) control cell fate decisions such as differentiation, proliferation and apoptosis. 1 Stat5 mediates cellular response to cytokines, growth factors and hormones. 1 Upon binding to their membrane receptors, growth factors such as erythropoietin (EPO) and growth hormone (GH) activate Janus kinase 2 (JAK2), causing activation of Stat5 by its phosphorylation, dimerization and translocation to the nucleus, where Stat5 induces expression of various antiapoptotic genes. 1 Indicative of an impaired functioning of EPO and GH receptor-associated signalling, Stat5a/b-knockout mice (Stat5 À/À ) are severely anaemic and growth retarded and the vast majority die perinatally. 2 Stat5 is expressed in the developing nervous system. 3,4 Recent studies suggest a role for Stat5 in neuronal migration and axon guidance in the developing brain 3 and a novel therapeutic potential for constitutively active Stat5 in reducing axonal outgrowth defects in spinal muscular atrophy-like motor neurons. 5 Since activation of Stat5 in neurons accompanies the antiapoptotic and neuroprotective effects of EPO in vitro and in vivo, 6-12 Stat5 has been suggested to mediate the protective effects of EPO in neuronal cells. Nevertheless, the molecular mechanisms of EPO receptor (EPOR) activation in neurons are complex, as multiple neuroprotective signalling pathways are activated downstream of EPOR/JAK2. In addition to Stat5, best characterized from these are the phosphatidylinositol-3 0 kinase (PI3K)/ Akt, nuclear factor-kB and Ras/mitogen-activated p...

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The exercise programme had a beneficial effect on the severity of lumbopelvic pain in pregnancy, reducing the intensity of pain and the level of disability experienced as a result.

ObjectiveThis randomized controlled trial aimed to compare the efficacy and safety of insulin detemir (IDet) with neutral protamine Hagedorn (NPH), both with insulin aspart, in pregnant women with type 1 diabetes. The perinatal and obstetric pregnancy outcomes are presented.MethodsSubjects were randomized to IDet (n = 152) or NPH (n = 158) ≤12 months before pregnancy or at 8–12 gestational weeks.ResultsFor IDet and NPH, there were 128 and 136 live births, 11 and 9 early fetal losses, and two and one perinatal deaths, respectively. Gestational age at delivery was greater for children from the IDet arm than the NPH arm (treatment difference: 0.49 weeks [95% CI 0.11;0.88], p = 0.012, linear regression). Sixteen children had a malformation (IDet: n = 8/142, 5.6%; NPH: n = 8/145, 5.5%). The incidence of adverse events was similar between treatments.ConclusionIDet is as well tolerated as NPH as regards perinatal outcomes in pregnant women with type 1 diabetes and no safety issues were identified.

Women with FPG levels of 5.1-5.5 mmol/L have an increased risk of adverse maternal and perinatal outcome, although they would not be diagnosed with GDM according to NICE criteria.

Objective: The aim of this study was to evaluate perinatal outcome in newborns of mothers who are smokers. Methods: The study included 87 pregnant women with a single pregnancy in the cephalic position, 64 of them nonsmokers (group 1), 13 who smoked 5–20 cigarettes per day (group 2) and 10 who smoked more than 20 cigarettes per day (group 3). Maternal demographic variables and laboratory hemoglobin concentration, hematocrit and erythrocyte count in the last trimester were recorded. Perinatal outcome included type of delivery (vaginal or cesarean section), birth weight, occurrence of meconium in the amniotic fluid, 5-min Apgar score, umbilical arterial blood pH postpartum, sex of the newborn, need for treatment at a neonatal intensive care unit (NICU) and clinically and neurosonographically verified postpartum neurologic complications in the newborn. Results: A statistically significant correlation (p < 0.01) was found with the mean gestational age at delivery in all three groups of women, especially in those smoking >20 cigarettes per day, who had a higher incidence of premature deliveries. Maternal laboratory findings also differed significantly among the three groups of women, i.e. erythrocyte count (p < 0.01), hemoglobin concentration (p < 0.01) and hematocrit (p < 0.001). The rate of delivery by cesarean section was significantly higher in the groups of smokers, irrespective of the number of cigarettes per day (groups 2 and 3). Birth weight was lower by about 250 and 350 g (p < 0.001) in groups 2 and 3, respectively. Five-minute Apgar score and umbilical arterial blood pH were lower in group 3 as compared with groups 1 and 2 (p < 0.01). NICU treatment was required in more than 50% of infants born to group 3 mothers, in whom 70% of perinatal neurologic complications such as subependymal hemorrhage, periventricular hemorrhage, porencephalic cysts, intracranial hemorrhage and swallowing disturbance of the newborn were recorded (p < 0.001). The infants born to group 3 mothers had a longer and more difficult period of adaptation, thus often requiring an NICU stay. Conclusion: Our study confirmed that pregnancy burdened with smoking, especially in the case of >20 cigarettes a day, is associated with a high risk due to the development of maternal anemia and fetal hypoxia and polyglobulia, which in turn result in a significantly poorer perinatal outcome in infants born to smoking mothers and compromised subsequent development of the child, as evidenced by the morphological substrates on the brain resulting from the fetal mechanism of defense against hypoxia. Clinically, there was no other (etiologic) reason for (chronic) fetal hypoxia; thus, the clinical substrate of fetal tobacco syndrome could be presumed to have developed consequentially to chronic smoking during pregnancy, as a preuterine factor of fetal hypoxia. Other gestational or gestation-related diseases (e.g., gestosis, diabetes) that may potentially cause nutritional and respiratory insufficiency of the placenta were ruled out.