Safety and pharmacokinetics of antiretroviral therapy during pregnancy

Combined antiretroviral therapy can reduce the transmission of human immunodeficiency virus (HIV) to an unborn child to less than two percent. An HIV-infected woman of childbearing age and her medical provider are in the unique position of making treatment decisions that not only will impact the woman's health but also that of her child. Treatment recommendations for pregnant women infected with HIV state that therapies of known benefit to women should not be withheld during pregnancy, unless there are known adverse effects for the mother and fetus, and these adverse effects outweigh the benefit for the women. However, the recommendations of antiretroviral drugs for the treatment of HIV-infected pregnant women are subject to unique considerations, including potential changes in dosing requirement resulting from physiologic changes associated with pregnancy, and potential adverse effects on the development of the fetus and/or newborn. Currently there is a general lack of pharmacokinetic data in pregnant HIV-infected women. The limited available information suggests that pregnant women may be exposed to subtherapeutic drug levels of certain antiretroviral agents during the later stages of pregnancy, which can lead to the failure of virologic suppression, development of resistance and increased risk of vertical transmission of HIV infection. The available pharmacokinetic data regarding the use of antiretroviral therapy in pregnancy is reviewed.     

Alteplase Therapy for Acute Ischemic Stroke in Pregnancy: Two Case Reports and a Systematic Review of the Literature

Acute ischemic stroke (AIS) during pregnancy is a rare but serious complication. Intravenous alteplase is the only medication approved for hyperacute treatment of AIS; however, it has not been evaluated prospectively in pregnancy. Pregnancy was an exclusion criterion in prospective AIS studies and was only recently removed as a relative contraindication in the 2018 American Heart Association/American Stroke Association Stroke guidelines. Due to the exclusion of pregnant women from randomized controlled trials, the safety of fibrinolytic therapy in pregnant patients is not well established. In this review, we report the use of intravenous alteplase for AIS in two pregnant patients, with temporally associated clinical improvement and without complications to either the mother or fetus. Additionally, we summarize a systematic review of the literature for both intravenous and intra-arterial alteplase use for AIS in pregnant patients. A total of 31 cases met inclusion criteria for this review of assessment of safety and efficacy of alteplase use in pregnancy. Existing case reports and guidelines support the use of alteplase for AIS in pregnant patients without contraindications.     

妊娠合并心血管病抗凝治疗概况

近年来,抗凝治疗药物的广泛应用使得越来越多的患者从防治血栓栓塞事件中获益。然而,抗凝药物好比一把双刃剑,常常是风险与受益并存。如何平衡防治栓塞和出血的矛盾并优化治疗方案,始终是临床医生必须面对的一个严峻问题。除此之外,妊娠期妇女这类特殊人群的抗凝药物使用更是一个复杂且充满挑战的难题。基于近年来妊娠妇女抗凝药物治疗的临床研究,以及最新相关指南的推荐,本综述从妊娠妇女的高凝状态、主要抗凝药物种类及临床应用几方面介绍妊娠合并心血管病患者的抗凝治疗概况。     

血浆BNP水平在围产期心肌病中应用

目的观察血浆中B型钠尿肽(BNP)水平变化,研究其对围产期心肌病(PPCM)的诊断、治疗评价及预后判断方面的临床价值。方法应用酶联免疫法对26例PPCM患者治疗前后和25名正常围产期妇女对照者的血浆BNP水平进行检测,超声心动图测左室射血分数、心脏指数。结果PPCM患者血浆中BNP治疗前后比较差异有显著性(P<0.05),正常对照组与PPCM组治疗前比较差异有显著性(P<0.001),BNP水平与NYHA心功能分级呈良好正相关,与左心室射血分数、心脏指数呈良好负相关。结论BNP的检测有利于PPCM患者的早期诊断、疗效评价和预后评价有重要的意义,因此具有重要的临床应用价值。     

Pharmacotherapy for the prevention of malaria in pregnant women: currently available drugs and challenges

ABSTRACT

Introduction: Malaria in pregnancy continues to be a significant public health burden globally, with over 100 million women at risk each year. Sulfadoxine-pyrimethamine (SP) is the only antimalarial recommended for intermittent preventive therapy in pregnancy (IPTp) but increasing parasite resistance threatens its viability. There are few other available antimalarial therapies that currently have sufficient evidence of tolerability, safety, and efficacy to replace SP.

Areas covered: Novel antimalarial combinations are under investigation for potential use as chemoprophylaxis and in IPTp regimens. The present review summarizes currently available therapies, emerging candidate combination therapies, and the potential challenges to integrating these into mainstream policy.

Expert opinion: Alternative drugs or combination therapies to SP for IPTp are desperately required. Dihydroartemisinin-piperaquine and azithromycin-based combinations are showing great promise as potential candidates for IPTp but pharmacokinetic data suggest that dose modification may be required to ensure adequate prophylactic efficacy. If a suitable candidate regimen is not identified in the near future, the success of chemopreventive strategies such as IPTp may be in jeopardy.     

89例妊娠并发血小板减少症临床初探

目的探讨妊娠合并血小板减少的原因及临床治疗方法。方法选取我院2004年～2008年5月间就诊的89例妊娠合并血小板减少患者进行回顾性分析。结果妊娠合并血小板减少的原因,最常见为妊娠生理性血小板减少。89例妊娠合并血小板减少的孕妇中52例,占58．4％。特发性血小板减少性紫癜（ITP）引起8例（8．98％）,合并肝脏疾病10例（11．23％）,重度妊高征引起19例（21．4％）。结论引起妊娠血小板减少的原因很多,应注意观察及给予相应治疗．产前适当提高血小板水平,可以减少并发症的出现。     

Antiretroviral use during pregnancy for treatment or prophylaxis

INTRODUCTION: Antiretrovirals are recommended for all pregnant women either for treatment of HIV-1 infection or for prevention of mother-to-child transmission. Distinguishing between HIV-1-infected pregnant women who meet treatment criteria and those who do not (who use antiretrovirals during pregnancy for prophylaxis) is accomplished by assessing the HIV-1 disease stage and has important implications regarding when antiretroviral drugs are initiated during pregnancy, what drugs are used and antiretroviral use after delivery. AREAS COVERED: This review addresses antiretroviral use by HIV-1-infected women during pregnancy. Specifically, the review focuses on antiretroviral therapy for HIV-1-infected pregnant women who meet criteria for treatment and antiretroviral prophylaxis for HIV-1-infected pregnant women (to prevent mother-to-child transmission of HIV-1). The review primarily addresses antiretroviral use in resource-rich settings, but use in resource-poor settings is briefly addressed. EXPERT OPINION: Antiretrovirals represent only one component of the overall management of HIV-1 infected pregnant women and, therefore, cannot be viewed in isolation from other components of optimal care for HIV-1-infected women and from other efficacious interventions to prevent mother-to-child transmission of HIV-1. Antiretrovirals can be used safely and effectively during pregnancy. We concur with current guidelines regarding the threshold that differentiates which women need antiretroviral therapy for HIV-1 infection for their own health versus those who need prophylaxis to prevent transmission of HIV-1 infection to their child. We thus recommend that lifelong antiretroviral therapy be initiated in patients with an AIDS-defining illness, a CD4 count < 350 cells/mm(3) or other co-morbid conditions such as acute opportunistic infections, HIV-1-associated nephropathy or hepatitis B co-infection. Irrespective of whether or not antiretrovirals are used during pregnancy, or whether antiretrovirals during pregnancy are used for treatment or prophylaxis, all infants of HIV-1-infected women should receive antiretroviral post-exposure prophylaxis.     

孕期认知行为治疗对口腔疾病和焦虑症的影响

目的评价认知行为治疗在孕期口腔保健干预,以及孕妇对疼痛焦虑情绪的有效性。方法采用随机对照的的方法,将2011年6月-2012年6月在合肥市妇幼保健院产检并自愿接受孕期口腔保健的80名孕妇作为观察组,此组接受认知行为治疗干预;随机选择同期在该院产检并自愿接受孕期口腔保健的80名孕妇作为对照组,该组不接受认知行为治疗干预。采用综合性医院焦虑／抑郁量表（HAD）以及孕期口腔疾病的发展结果对照表对两组孕期焦虑和121腔保健进行评估。结果孕36-37周时观察组焦虑发病率明显低于对照组,观察组孕期口腔疾病控制率达92％,明显高于对照组的75％。结论认知行为治疗能有效缓解孕妇对口腔疾病及疼痛的焦虑,运用认知行为效法配合临床治疗效果优于单纯治疗。     

妊娠期甲状腺功能减退症的诊治进展

甲状腺功能减退症（甲减）是妊娠期最常见的甲状腺功能异常。妊娠期甲减包括临床甲减和亚临床甲减 （SCH）。SCH （患病率 3%~5%） 比临床甲减 （<1%） 常见。目前, 临床倾向采用妊娠特异性促甲状腺激素 （TSH） 和血清 游离甲状腺素 （FT4） 参考值诊断妊娠期甲减。妊娠前已确诊的临床甲减在妊娠期间需增加血清左甲状腺素 （L-T4） 的剂量; 而妊娠期新诊断的临床甲减, 应立即给予 L-T4 治疗并尽快使 TSH 水平达到目标值。对于 SCH, 虽然对母 胎获益的相关临床研究结果不一致, 国内外指南的治疗建议也不尽相同, 但是, 最近几年的研究提示对 SCH 无论是 否伴有甲状腺自身抗体阳性均可考虑治疗。本文就妊娠期临床甲减及 SCH 诊治相关的研究现状进行综述。     

89例妊娠期并发贫血妇女的流行病学特点及围产期干预

目的:探讨妊娠期并发贫血妇女的流行病学特点及围产期相关干预措施。方法:选取某院妊娠期女性369例(2016年12月~2018年12月),统计所有受检者一般情况(年龄、受教育程度、职业类型、吸烟及饮酒状况、是否经常饮用咖啡、是否喜欢饮浓茶),并抽取血液样本进行检测,针对缺血患者根据具体病情采取硫酸亚铁、甘氨酸亚铁等铁剂进行补充治疗。统计分析本组妊娠期女性贫血发生情况、不同特征及不同生活习惯妊娠期女性贫血发生情况。结果:本组369例妊娠期女性共89例发生贫血,妊娠期合并贫血发病率为24.12%(89/369);不同受教育程度及职业类型妊娠期女性贫血发病率间存在显著差异(P<0.05),不同年龄妊娠期女性贫血发病率间无显著差异(P>0.05);不同吸烟及饮酒状况妊娠期女性贫血发病率间无显著差异(P>0.05),不同是否经常饮用咖啡、是否喜欢饮浓茶妊娠期女性贫血发病率间存在显著差异(P<0.05)。结论:贫血在妊娠期女性中具有较高发病率,且在不同受教育程度及职业类型、生活习惯孕妇中发病率存在一定差异,临床可根据患者特征及早采取对应防控措施,以此预防妊娠期合并贫血,且利于保证母婴健康。     

妊娠中晚期细菌性阴道病与妊娠结局的关系

目的检测妊娠中晚期细菌性阴道病（BV）的发病情况并观察分析妊娠中晚期细菌性阴道病与妊娠结局的关系。方法对2009年6月至2012年3月我院收治的360例28～38周孕妇进行BV检测,检出BV阳性62例,将其中40例BV阳性孕妇列为治疗组采用乳酸菌阴道胶囊治疗,剩下22例BV阳性孕妇不做干预列为观察组,而BY阴性的298例孕妇列为对照组,比较三组孕妇的妊娠结局。结果妊娠中晚期细菌性阴道病的发生率为17．2％,治疗组治疗有效率高达92．5％,且观察组患者的早产、胎膜早破、产褥感染及新生儿感染率较其他两组明显增高（P〈0．05）。结论妊娠中晚期细菌性阴道病会提高患者的早产、产褥感染等不良妊娠结局的发生几率,而乳酸菌阴道胶囊治疗可以有效改善BV阳性孕妇的不良妊娠结局。     

妊娠期肝内胆汁淤积症早期干预措施及对围生儿的影响

目的探讨妊娠期肝内胆汁淤积症(ICP)患者的临床特点、终止妊娠方式的选择及对围生儿预后的影响。方法选择2008年3月—2011年3月分娩的100例妊娠期肝内胆汁淤积症患者作为观察组,同期选取住院分娩的正常孕妇120例作为对照组,比较两组孕妇及新生儿情况以及观察组中分娩方式不同对新生儿的影响。结果两组的早产、胎儿宫内窘迫、死亡及羊水污染明显高于对照组(P<0.05);观察组孕妇血清总胆汁酸值不同对新生儿的影响亦不同。结论妊娠期肝内胆汁淤积症对母婴,特别是新生儿的危害极大,导致早产、胎儿宫内窘迫、胎死宫内、产后出血等并发症,增加了围生儿发病率和死亡率。因此应加强孕妇的健康教育,高度重视产前检查和中期妊娠胆汁酸的监测,做到早发现、早治疗,对减少母婴并发症有重要作用。     

Dosing and Monitoring of Methadone in Pregnancy: Literature Review

Background:

The pharmacokinetics of methadone is altered during pregnancy, but the most appropriate dosing and monitoring regimen has yet to be identified.

Objective:

To review dosing and monitoring of methadone therapy in pregnancy.

Methods:

A literature search was performed in several databases (PubMed, MEDLINE, Embase, International Pharmaceutical Abstracts, and the Cochrane Database of Systematic Reviews) from inception to May 2012. The search terms were “methadone”, “pregnancy”, “pharmacokinetic”, “clearance”, “metabolism”, “therapeutic drug monitoring”, and “methadone dosing”. Additional papers were identified by searching the bibliographies of primary and review articles. All English-language primary articles related to methadone pharmacokinetics in pregnancy were included. Articles not related to maternal outcomes were excluded.

Results:

The literature search yielded 1 case report and 10 studies discussing use of methadone by pregnant women. Methadone pharmacokinetics in pregnancy has been studied in 3 pharmacokinetic trials, and split dosing of methadone in pregnant women has been described in 1 case report and 3 dosing trials. Only 4 trials evaluated monitoring of methadone concentration in pregnancy. The studies included in this review confirm that methadone pharmacokinetics is altered in pregnancy and is potentially correlated with increases in maternal withdrawal symptoms. Insufficient evidence is available to warrant routine monitoring of serum methadone concentrations in pregnant women with opioid dependence.

Conclusions:

Few studies of methadone pharmacokinetics and therapeutic drug monitoring are available for pregnant women with opioid dependence. Although it is known that methadone pharmacokinetics is altered in pregnancy, there is insufficient evidence to guide dosage adjustments and serum concentration monitoring. Until further studies are available, regular follow-up of maternal withdrawal symptoms and empiric dosage adjustments throughout pregnancy are still recommended.     

Pharmacist's guide to pregnancy registry studies

OBJECTIVE: To introduce the concept and design characteristics of pregnancy registries and to discuss opportunities for pharmacist involvement. DATA SOURCES: Previous and ongoing pregnancy registry studies that assess the safety of pharmaceutical agents in pregnant women were identified from the medical literature, Internet, abstracts from professional meetings, and personal communications. DATA EXTRACTION: The development and use of the pregnancy registry study for evaluating drug safety is described. Then, to illustrate the application of scientific principles to this unique study design, examples are given from previous and ongoing pregnancy registry studies. DATA SYNTHESIS: Pregnancy registry studies are increasingly used to assess the safety of drugs and other therapeutic agents during pregnancy. In a pregnancy registry, women who took the study drug while pregnant are identified soon after that exposure and followed until their pregnancy ends and its outcome is determined. Information is compiled from hundreds or thousands of pregnancies and used to make a safety assessment. CONCLUSION: Pharmacists can explain pregnancy registries to pregnant women and encourage enrollment. Also, pharmacists can use information derived from these studies to help patients and health care providers manage inadvertent drug exposures and optimize pharmaceutical therapy during pregnancy.     

Pembrolizumab for melanoma- safety profile and future trends

Background: Pregnant women who continue to smoke expose their developing fetus to a wide range of risks. Assisting these patients to stop smoking can be an important intervention for the health of the baby and the mother. The management of pregnant smokers can be challenging, due to the potential risks of pharmacotherapy. There are a number of options available to the clinician to aid smoking cessation in non pregnant women. These include nicotine replacement therapy (NRT), bupropion, varenicline, and a range of non-drug therapies. Objective: To provide guidance to prescribers on the best way to manage smoking cessation in the pregnant patient, reviewing the risks and efficacy of the different approaches. Methods: An extensive literature search was carried out to find original studies which examined issues surrounding the safety and efficacy of methods of smoking cessation in pregnancy. Results/conclusion: NRT is the agent of choice for smoking cessation in pregnancy as the safety of other therapies in pregnancy have not yet been proved.     

Major malformations after first trimester exposure to aspirin and NSAIDs

The use of aspirin and other NSAIDs during the first trimester of pregnancy is widespread, despite inconclusive evidence regarding the possible risks for the baby. We present an overview of the current evidence relating to the associations between aspirin or NSAID use during the first trimester of pregnancy and the risk of congenital malformations. We systematically searched Medline, Embase, the Cochrane Library and the reference lists of all relevant articles from 1966 to March 2008 that examined the association between aspirin and NSAID use during the first trimester of pregnancy and the risk of congenital malformations in humans. We analyzed 30 studies that met the predefined inclusion criteria: 22 case–control studies, seven cohort studies and one randomized, controlled trial. There are not enough human data available to assess the effect of high-dose aspirin and NSAIDs in pregnant women, such as those used in the treatment of rheumatoid arthritis, osteoarthritis and pain relief. This review suggests that the exposure to aspirin or NSAIDs during the first trimester of pregnancy is associated with an increased risk of gastroschisis (aspirin), cardiac malformations (NSAIDs) and orofacial malformations (naproxen).     

排卵监测指导受孕在减少重复性异位妊娠中的作用

目的探讨排卵监测指导受孕在减少重复性异位妊娠中的作用。方法对14例异位妊娠保守性手术及保守治疗后希望生育的患者,通过常规的输卵管通水或造影、抗感染、理疗、活血化瘀的中药口服或灌肠等综合治疗消除输卵管黏膜及输卵管周围炎,疏通输卵管等综合治疗后,于准备受孕前行子宫输卵管造影,选择健侧或相对健侧输卵管,监测排卵,指导同侧卵巢排卵时受孕。结果 14例患者中11例（78.57%）获得了宫内妊娠;1例（0.71%）再次发生了异位妊娠,2例（14.29%）患者未获得妊娠。结论排卵监测指导健侧或相对健侧输卵管受孕,能有效提高异位妊娠术后患者的宫内再孕概率,减少重复性异位妊娠的发生。