Neurotrophins: Role in adverse pregnancy outcome

Proper placental development is essential during pregnancy since it forms the interface between the maternal–foetal circulations and is critical for foetal nutrition and oxygenation. Neurotrophins such as nerve growth factor (NGF), brain derived neurotrophin (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) are naturally occurring molecules that regulate development of the placenta and brain. BDNF and NGF also involved in the regulation of angiogenesis. Recent studies suggest that the levels of BDNF and NGF are regulated by docosahexaenoic acid (DHA) which is an important omega-3 fatty acid and is a structural component of the plasma membrane. Oxidative stress during pregnancy may lower the levels of DHA and affecting the fluidity of the membranes leading to the changes in the levels and expression of BDNF and NGF. Therefore altered levels and expression of NGF and BDNF may lead to abnormal foetal growth and brain development that may increase the risk for cardiovascular disease, metabolic syndromes and neurodevelopmental disorders in children born preterm. This review discuss about the neurotrophins and their role in the feto-placental unit during critical period of pregnancy.     

The psychosocial outcome of pregnancy in women with psychotic disorders

OBJECTIVE: To investigate the psychosocial outcome of pregnancies in women with a history of psychotic disorder in an epidemiologically representative sample and to determine the predictors of having a baby looked after by social services in the first year of life. METHOD: Historical matched controlled cohort study and nested case control study using the General Practice Research Database (GPRD), an anonymised primary care database, in women with a history of psychotic disorders who gave birth in 1996-1998 (199 cases and 787 controls). RESULTS: Twenty-seven percent of cases had a psychotic episode and a further 38% had nonpsychotic depression in the first year after birth. Women with nonaffective psychoses were at a significantly higher risk of postnatal depression compared with controls (adjusted rate ratio 2.07, 95% CI 1.45-2.96, p<0.001). Cases were well supported with 72% in a cohabiting relationship and only 38% on benefits. The only significant predictor of parenting difficulties was recent contact with psychiatric services. CONCLUSIONS: Women with a history of psychotic disorder are at high risk of psychiatric illness postpartum, particularly a twofold risk of postnatal depression, even if they have not been in contact with psychiatric services during pregnancy. However, this epidemiologically representative sample has better parenting outcomes than has been previously reported for specialist treated cases. Liaison between all professionals involved in the care of mothers with psychotic disorders during and after pregnancy is essential to optimise care for them and their families.     

Headaches during pregnancy in women with a prior history of menstrual headaches

OBJECTIVE: To evaluate the presence of menstrual headaches prior to pregnancy according to the International Headache Society (IHS) classification criteria, 2004, and also study the outcome (frequency and intensity) of these pre-existing headaches during the gestational trimesters. METHOD: This study involved 1,101 pregnant women (12 to 45 years old). A semi-structured questionnaire was used to interview the women during the first, second and third gestational trimesters as well as after delivery. All the interviews were conducted by one of the researchers by applying the IHS Classification (IHSC-2004). RESULTS: A 1,029 women out of the 1,101 women interviewed presented headaches prior to gestation, which made it possible to study headaches in 993 women during the gestational trimesters. Menstrually related headaches were presented by 360 of the 993 women. Migraine was reported by 332/360 women (92.22%) with menstrual headaches and 516/633 women (81.51%) without menstrual headaches, respectively, prior to gestation. The majority of the women with menstrual migraine presented a headache improvement or disappearance during gestation (62.22% during the first trimester; 74.17% during the second trimester; 77.78% during the third trimester). CONCLUSION: Most of the pregnant women with menstrual or non-menstrual headaches prior to gestation presented migraine, which either improved or disappeared during pregnancy. Women who suffered from non-menstrual headaches improved during pregnancy but not as much as women with menstrual headaches.     

Gestational outcome in thrombophilic women with recurrent pregnancy loss treated by enoxaparin

Inherited and acquired thrombophilia are associated with recurrent pregnancy loss (RPL). We have evaluated the efficacy and safety of the low molecular weight heparin enoxaparin in 50 women, (mean age 26 +/- 3 years) with RPL (> or =3 losses in 1st, > or =2 losses in 2nd and > or =1 loss in 3rd trimester) who were found to harbor thrombophilia. Twenty-seven had a solitary thrombophilic defect, and twenty-three women had combined thrombophilic defects: 17--two defects and 6--three defects. Following diagnosis of thrombophilia, sixty-one subsequent pregnancies were treated with the low molecular weight heparin enoxaparin throughout gestation until 4 weeks after delivery. Dosage was 40 mg/day in women with solitary defect and 80 mg/day in combined defects. Aspirin, 75 mg daily was given in addition to enoxaparin to women with antiphospholipid syndrome. Forty-six out of 61 (75%) gestations treated by enoxaparin resulted in live birth compared to only 38/193 (20%) of the untreated pregnancies in these 50 women prior to diagnosis of thrombophilia (p <0.00001). In 23 women without a single living child following 82 untreated gestations, antithrombotic therapy resulted in 26/31 (84%) successful deliveries (p <0.0001). In 20 women with a prior living child, antithrombotic therapy improved successful delivery from 33/86 (38%) to 20/21 (95%) (p <0.0001). Enoxaparin dose of 40 mg/day resulted in live birth in 24/35 (69%) of gestations, compared to 19/23 (83%) gestations in women treated with 80 mg/day (p = 0.37). Only one thrombotic episode and one mild-bleeding episode were noticed during enoxaparin therapy. Enoxaparin is safe and effective in prevention of pregnancy loss in women with inherited and acquired thrombophilia.     

No increase in adverse pregnancy outcomes for women receiving antiepileptic drugs

The objectives of this study were (1) to investigate the incidence of adverse pregnancy outcomes among the epileptic and general populations, including small for gestational age (SGA), low birth weight (LBW) and preterm delivery, using two large-scale nationwide population-based databases, and (2) to compare the risk of these adverse pregnancy outcomes between epileptic women who did and who did not receive antiepileptic drug (AED) treatment during pregnancy. This study used two national datasets: the National Health Insurance Research Dataset and birth certificate registry. We identified a total of 1,182 women who gave birth from 2001 to 2003 in Taiwan who had been diagnosed with epilepsy within the 2 years preceding the index delivery, together with 5,910 matched women as a comparison cohort. Multivariate logistic regression analyses were performed for estimation of risk. We found that approximately 14% of women with epilepsy received AED treatment during gestation. The adjusted odds of LBW, preterm births and SGA for epileptic women not receiving AED treatment during pregnancy were 1.31 (95% CI, 1.02–1.68), 1.35 (95% CI, 1.07–1.71) and 1.23 (95% CI, 1.03–1.46) times that of women without epilepsy, respectively. In contrast, no significant difference in the risk of LBW infants, preterm births and SGA babies was observed between epileptic mothers receiving AED treatment during pregnancy and women without epilepsy. Our study documents an increased risk of adverse pregnancy outcomes for epileptic women who do not receive AED treatment during pregnancy, but none for epileptic women who do receive treatment.     

Increased insulin resistance and risk of incident cerebrovascular events in patients with pre-existing atherothrombotic disease

Background and purpose:  Diabetes and the metabolic syndrome are known risk factors for ischaemic stroke. Our aim was to examine whether amongst patients with pre-existing atherothrombotic disease, increased insulin resistance is associated with incident cerebrovascular events.
Methods:  Patients with stable coronary heart disease included in a secondary prevention trial were followed up for a mean of 6.2 years. Coronary heart disease was documented by a history of myocardial infarction ≥6 months and <5 years before enrollment and/or stable angina pectoris with evidence of ischaemia confirmed by ancillary diagnostic testing. Main exclusion criteria were insulin treated diabetes, hepatic or renal failure, and disabling stroke. Baseline insulin levels were measured in 2938 patients from stored frozen plasma samples and increased insulin resistance assessed using the homeostatic model assessment of insulin resistance (HOMA-IR), categorized into tertiles or quartiles.
Results:  Crude rates of incident cerebrovascular events rose from 5.0% for HOMA-IR at the bottom tertile to 5.7% at the middle tertile, and 7.0% at the top tertile ( P  = 0.07). HOMA-IR at the top versus bottom tertile was associated with an unadjusted hazard ratio (HR) of 1.37 (95%CI, 0.94–1.98) and a 1-unit increase in the ln HOMA-IR was associated with a HR of 1.14 (95%CI, 0.97–1.35). In further analyses adjusting for potential confounders, or categorizing baseline HOMA-IR into quartiles, or excluding diabetic patients, we did not identify an increased risk for incident cerebrovascular events conferred by the top category.
Conclusions:  Increased insulin resistance did not predict incident cerebrovascular events amongst patients with pre-existing atherothrombotic disease.     

Bone mineral density in premenopausal women with major depressive disorder

This cross-sectional study investigated whether a group of unmedicated patients with major depressive disorder, single episode, had decreased bone mineral density (BMD). The BMD at the lumbar spine and proximal femur in 25 premenopausal women with major depressive disorder and 15 normal women was measured by dual-energy X-ray absorptiometry. Bone turnover markers and serum cortisol levels were also evaluated for each subject. As compared with values in the normal women, the mean BMD in the depressed women was significantly lower at the lumbar spine and at all sites of the proximal femur. There was no statistically significant difference between serum cortisol levels and bone turnover markers except for significantly higher urinary excretion of deoxypyridinoline cross-links in the patients compared with the controls. In conclusion, depressed women may have decreased BMD even at the very early stages of the illness, and this possibility should be taken into consideration in treatment.     

利培酮所致不良反应207例综合分析

目的:综合分析利培酮所致不良反应的临床特征.方法:对1997至2005年国内文献利培酮所致不良反应的病例报道96篇、207例患者进行汇总分析.结果:利培酮不良反应的发生多与用药剂量、加药剂量速度及患者的个体差异有关.结论:利培酮用药剂量不宜过大,加药速度不宜过快,用药剂量应注意遵循个体化原则.     

Antiphospholipid antibodies and hyperhomocysteinaemia in patients with vascular occlusive disease

Hyperhomocysteinemia (HHcy), lupus anticoagulant (LA) and anticardiolipin antibodies (ACA) are independent risk factors for thrombosis. Even though risks are cumulative, the clinical impact of the association is unknown. Preliminary data suggested that HHcy might be associated with transient LA and ACA, disappearing after lowering HHcy. We prospectively evaluated the association of HHcy and LA/ACA, the effect of lowering HHcy with folic acid in LA behavior, and the correlation of the initial dRVVT with LA behavior after folic acid in 210 patients with thrombosis and adverse pregnancy outcomes. Prevalence of HHcy among patients with LA/ACA was 40%. Thirty-one patients exhibited only HHcy (15%; Group 1), 106 (50%; Group 2) had only LA/ACA, while 73 (35%; Group 3) had both. After therapy, 63% and 64% of LA/ACA remained positive in Group 3 and 2, respectively. We observed a trend towards a more positive dRVVT in persistent LA after lowering HHcy. No differences in clinical presentation or in outcomes after two years of followup were observed among the groups. Even though the association of HHcy and LA/ACA is common in patients with thrombosis, it might have no prognostic implications if Hcy levels are lowered. Currently, no laboratory findings correlate with LA behavior, which is independent of homocysteine levels and vitamin treatment.     

Topiramate and psychiatric adverse events in patients with epilepsy

PURPOSE: The aim of this study was to determine the prevalence of psychiatric adverse events (PAEs) in patients with epilepsy treated with topiramate (TPM). Classification, relation to TPM dosing, and outcome were evaluated to identify a patient profile at risk of developing PAEs. METHODS: We evaluated the data of the first consecutive and prospectively collected patients in therapy with TPM. RESULTS: Follow-up information was available for 431 patients. PAEs occurred in 103 (23.9%) patients; M/F ratio, 55:48; mean age (+/-SD), 36.5 +/- 11.2. In 46 (10.7%) patients, an affective disorder developed; in 16 (3.7%), a psychotic disorder; in 24 (5.6%), aggressive behavior with or without irritability; in 17 (3.9%), other behavior abnormalities such as agitated behavior, anger/hostility behavior, or anxiety. High starting dose and rapid titration schedule were relevant for the development of PAEs. Family psychiatric history and family history of epilepsy, personal history of febrile convulsions, psychiatric history, and presence of tonic-atonic seizures were found to be significant risk factors. Low seizure frequency before starting TPM and TPM/lamotrigine coadministration had a protective effect for PAEs. CONCLUSIONS: We found that PAEs associated with TPM were related to the titration schedule of the drug and that a unique patient profile is suggested by the clinical history.     

抗癫痫药物四种对中青年绝经前女性骨代谢的影响

目的研究不同的常用抗癫痫药物对中青年女性骨代谢的影响。方法通过测量各组受试者的血清钙、25-羟基维生素D、碱性磷酸酶、甲状旁腺激素、胰岛素生长因子-1、胰岛素结合蛋白-3、骨密度等,分析长期单药服用不同抗癫痫药物如苯妥英钠(PHT)、卡马西平(CBZ)、丙戊酸钠(VPA)、左乙拉西坦(LEV)等对受试者骨代谢的影响。结果服用CBZ、PHT和VPA的受试者血清钙浓度低于服用LEV的受试者(P=0.002);服用PHT的受试者的ALP浓度显著高于服用CBZ、LEV和VPA的受试者(P=0.000);与LEV组相比,PHT组血清IGF-1水平降低(P=0.03);与LEV组相比,PHT组血清的IGFBP-3浓度显著降低(P=0.000)。结论抗癫痫药物会影响骨代谢,导致患者血清钙下降、骨量减低。LEV较其他抗癫痫药物对骨代谢的影响较小,但仍能造成患者碱性磷酸酶含量下降等。抗癫痫药物对中青年女性的骨代谢会产生一定影响,在临床用药过程中需监测相关指标。     

Preeclampsia and pregnancy loss in women with a history of venous thromboembolism and prophylactic low-molecular-weight heparin (LMWH) during pregnancy

Limited data are available regarding complications of pregnancy and pregnancy outcome under prophylaxis with low-molecular-weight heparin (LMWH) in women with a history of thromboembolism (TE). We retrospectively evaluated pregnancy complications in a cohort of 80 women. All had a history of TE (76 venous, two arterial and two venous and arterial) and received prophylactic LMWH during 86 pregnancies. The rate of preeclampsia and stillbirth in these women was compared to that of a control group of 313 women without a history of TE and LMWH. Prophylaxis was started at a median of 10 weeks of gestation and usually continued until six weeks post partum. In 94% of the cases the outcome of pregnancy was favourable with a live birth. Four pregnancies (4.7%) ended in miscarriage. Two (2.3%) pregnancies were complicated by a thromboembolic event (one deep leg vein thrombosis and PRIND, respectively). One patient developed HELLP-syndrome. Severe preeclampsia occurred in three (3.8%) and stillbirth in one (1.3%) of the patients (n = 80), whereas this was the case in four (1.3%, odds ratio 3.01; 95% confidence interval (CI) 0.66-13.73, p = 0.15) and 10 (3.2%, OR = 0.38; 95% CI 0.05-3.04, p = 0.72) control women. Mean birth weight and standard deviation of infants was 3,160 +/- 930 g in patients and 3,300 +/- 540 g in controls (p = 0.11). We conclude that a favourable pregnancy outcome in women with a history of thromboembolism who use prophylactic LMWH during pregnancy can be expected. There was a trend towards a higher risk of preeclampsia, and these women should be carefully monitored for this complication.     

Non-interventional surveillance study of adverse events in patients with epilepsy

Cruise KE, Bucks RS, Loftus AM, Newton RU, Pegoraro R, Thomas MG. Exercise and Parkinson’s: benefits for cognition and quality of life.
Acta Neurol Scand: 2011: 123: 13–19.
© 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives – The benefits of physical exercise for psychological aspects of quality of life (QoL) are well established in normally ageing adults, yet potential benefits for people with Parkinson’s disease (PD) have received limited attention. This study evaluated the benefits of exercise for cognitive functioning, mood and disease‐specific QoL for people with PD. Methods – Twenty‐eight individuals with PD were allocated to an exercise intervention program (EIP, n = 15) or control group (n = 13). The EIP group undertook a programme of progressive anabolic and aerobic exercise twice weekly for 12 weeks. The control group maintained their usual lifestyle. Results – Exercise was shown to have selective benefits for cognitive functioning by improving frontal lobe based executive function. No significant effects were demonstrated for mood or disease‐specific QoL. Conclusions – These results are consistent with previous research demonstrating selective benefits of exercise for executive function among normal ageing adults and PD.