多拉西敏+维生素B6可预防严重孕吐

巴尔的摩——加拿大多伦多病童医院的Caroline Maltepe医生及其同事对59例有妊娠期严重恶心呕吐(NVP)病史的女性进行研究后发现，与首次出现NVP症状时开始治疗相比，在出现症状之前即开始联用多拉西敏与维生素B6，可显著降低严重NVP的发生率。

Maltepe医生在畸形学会年会上介绍，在这项针对有NVP病史者的前瞻性、随机、开放标签研究中，30名女性在得知自己怀孕后尽快开始服用10 mg多拉西敏/10 mg吡哆醇(维生素B6)复合缓释片(提前治疗组)，而另外29名妊娠女性则在开始出现症状时再开始服用该复合片(对照组)。

这些受试者(平均年龄31~32岁)均在前一次妊娠时遭遇了严重NVP或妊娠剧吐(HG)，在计划或已经再次妊娠且尚未出现症状时入组。两组女性均每日服用2~9片多拉西敏/吡哆醇复方片，并接受咨询和电话随访。

该复方片在加拿大的商品名为Diclectin，由Duchesnay公司销售，并且是加拿大唯一获准用于治疗NVP的药物。作为一线治疗，该药的标准剂量是每日4片。Diclectin是Bendectin的仿制药，Bendectin原本在美国销售，但在因导致先天畸形而经历一系列诉讼后，1983年被其生产商Merrell Dow制药公司主动召回。多年来，Duchesnay公司一直在争取FDA批准Diclectin在美国上市，但尚未成功。

研究者采用PUQE(妊娠–呕吐与恶心独特量化)评分对症状进行评估。该评分系统由合著者Gideon Koren博士开发而成。评分为7~12分提示病情为中度，评分≥13分提示病情严重。

结果显示，两组女性平均约在妊娠5~6周时开始出现NVP症状。提前治疗组孕妇在出现症状的前3周内病情为中至重度者比对照组减少了70%：26例孕妇中有4例(15%)在出现NVP症状的前3周内PUQE评分≥11分，而对照组的23例孕妇中有9例(39%)，差异具有显著性。在提前治疗组中19例前一次妊娠发生剧吐的孕妇中，6例(32%)此次妊娠亦出现剧吐，而对照者的11例孕妇中有6例(55%)为这种情况，也有显著性差异。部分受试者因某些原因退出研究，包括流产。

在分娩前NVP消失率方面，提前治疗组明显高于对照组(80% vs. 50%)，而PUQE评分与康乐评分呈负相关，提示提前治疗可这些孕妇的生活质量。

研究者总结称，对于前一次妊娠发生NVP或HG的女性，采用多拉西敏/吡哆醇复合片提前治疗可以减少再次妊娠时的NVP复发，并可改善其妊娠期间的生活质量，还能减少请假时间和对肠内/肠外治疗、住院的需求及其他与严重NVP相关的成本。

这项研究由Duchesnay资助。Maltepe医生及其同事报告称无相关利益冲突。

爱思唯尔  版权所有

By: ELIZABETH MECHCATIE, Clinical Endocrinology News Digital Network

BALTIMORE – Starting treatment with a combination of doxylamine and pyridoxine before the onset of nausea and vomiting significantly reduced the incidence of severe nausea and vomiting of pregnancy, compared with starting treatment at the first sign of symptoms, in a study of 59 women with a history of severe nausea and vomiting of pregnancy, Caroline Maltepe reported.

In the prospective, randomized, open-label study of women with a history of nausea and vomiting of pregnancy (NVP), 30 women began taking the delayed-release combination of 10 mg of doxylamine and 10 mg of pyridoxine (vitamin B6) as soon as they learned they were pregnant, before they started to experience nausea and vomiting (at a mean of 4 weeks’ gestation). Another 29 pregnant women started taking the combination when they started to experience symptoms, Ms. Maltepe said at the annual meeting of the Teratology Society.

Women in both groups started to experience NVP symptoms at a mean of about 5 to almost 6 weeks, said Ms. Maltepe, the lead author of the study, who is with the Motherisk Program at the Hospital for Sick Children in Toronto. The program conducts research and provides information about the safety of maternal exposure to drugs, chemicals, diseases, radiation, and environmental agents to the developing fetus or infant.

The women (mean age, 31-32 years) had experienced severe NVP or hyperemesis gravidarum (HG) in their previous pregnancy, and enrolled when they were planning a pregnancy or in early pregnancy at a point when they had not yet experienced any symptoms. Women in both groups took 2-9 tablets of the doxylamine-pyridoxine combination a day, and received counseling and follow-up calls.

In Canada, the combination is approved and marketed as Diclectin, by Duchesnay, and is the only drug labeled for treating NVP in Canada. There it is considered a first-line treatment and is taken at a standard dose of four tablets a day, said Ms. Maltepe, the coordinator of the NVP helpline at Motherisk.

Diclectin is a generic form of the drug Bendectin, which was marketed in the United States until 1983, when it was voluntarily withdrawn by its manufacturer, Merrell Dow Pharmaceuticals, after a series of lawsuits claiming it caused birth defects. For several years, Duchesnay has been working toward Food and Drug Administration clearance to market Diclectin in the United States, but it would be premature to predict when it would become available in the United States, a spokesman for the company said.

In the study, symptoms were evaluated using the PUQE (Pregnancy–Unique Quantification of Emesis and Nausea) score, a validated scoring system that takes into account the frequency of vomiting; the frequency of retching, gagging, or dry heaves; and the number of hours spent feeling nauseous over a 24-hour period. The score was developed by Dr. Gideon Koren, director of Motherisk and coauthor of this study, and his associates. A score of 7-12 is considered moderate; a score of 13 or higher is considered severe.

In the study, preemptive treatment was associated with 70% fewer cases of moderate to severe NVP during the first 3 weeks women experienced symptoms: 4 of the 26 (15%) evaluable women had a PUQE score of 11 or more during the first 3 weeks of NVP symptoms, compared with 9 of the 23 (39%) evaluable women in the control group, a significant difference. Of the 19 women in the preemptively treated group who had HG during the previous pregnancy, 6 (32%) experienced HG, compared with 6 of the 11 (55%) in the control group, also a significant difference. Some women who enrolled were not evaluable for reasons that included having a miscarriage.

NVP resolved before labor in significantly more of the women in the preemptively treated group than in the control group (almost 80% vs. about 50%), and there was a negative correlation between PUQE scores and a well-being score, indicating that treatment is associated with improved quality of life for these patients, Ms. Maltepe said.

In women who have experienced severe NVP or HG in a previous pregnancy, preemptive treatment with doxylamine-pyridoxine events can reduce the recurrence of NVP in subsequent pregnancies, and improve their quality of life during pregnancy, as well as reduce time off from work and the need for enteral and parenteral therapy, hospitalization, and other costs associated with severe NVP, she concluded.

The NVP helpline at Motherisk is the only dedicated NVP helpline in the world, according to Ms. Maltepe, who provides evidence-based recommendations on pharmaceutical and nonpharmaceutical approaches to treating NVP for pregnant women, their family members, and clinicians via the helpline (800-436-8477 in North America).

The study was funded by Duchesnay. Ms. Maltepe and her coauthors said they had no relevant conflict of interest to disclose.

The Motherisk site is available at www.motherisk.org/women/index.jsp.

---------------------------------------------------------------------------------------------------------------------------------------------
欢迎关注Elseviermed官方微信