Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY.
Department of Biostatistics and Computational Biology, University of Rochester, Rochester, NY.
Am J Obstet Gynecol MFM. 2021 Jan;3(1):100273. doi: 10.1016/j.ajogmf.2020.100273. Epub 2020 Oct 29.
Hyperemesis gravidarum is a disabling disease of nausea, vomiting, and undernutrition in early pregnancy for which there are no effective outpatient therapies. Poor weight gain in hyperemesis gravidarum is associated with several adverse fetal outcomes including preterm delivery, low birthweight, small for gestational age, low 5-minute Apgar scores, and neurodevelopmental delay. Gabapentin is most commonly used clinically for treating neuropathic pain but also substantially reduces chemotherapy-induced and postoperative nausea and vomiting. Pregnancy registry data have shown maternal first-trimester gabapentin monotherapy to be associated with a 1.2% rate of major congenital malformations among 659 infants, which compares favorably with the 1.6% to 2.2% major congenital malformation rate in the general population. Open-label gabapentin treatment in hyperemesis gravidarum was associated with reduced nausea and vomiting and improved oral nutrition.
This study aimed to determine whether gabapentin is more effective than standard-of-care therapy for treating hyperemesis gravidarum.
A double-blind, randomized, multicenter trial was conducted among patients with medically refractory hyperemesis gravidarum requiring intravenous hydration. Patients were randomized (1:1) to either oral gabapentin (1800-2400 mg/d) or an active comparator of either oral ondansetron (24-32 mg/d) or oral metoclopramide (45-60 mg/d) for 7 days. Differences in Motherisk-pregnancy-unique quantification of nausea and emesis total scores between treatment groups averaged over days 5 to 7, using intention-to-treat principle employing a linear mixed-effects model adjusted for baseline Motherisk-pregnancy-unique quantification of nausea and emesis scores, which served as the primary endpoint. Secondary outcomes included Motherisk-pregnancy-unique quantification of nausea and emesis nausea and vomit and retch subscores, oral nutrition, global satisfaction of treatment, relief, desire to continue therapy, Nausea and Vomiting of Pregnancy Quality of Life, and Hyperemesis Gravidarum Pregnancy Termination Consideration. Adjustments for multiple comparisons were made employing the false discovery rate.
A total of 31 patients with hyperemesis gravidarum were enrolled from October 2014 to May 2019. Among the 21 patients providing primary outcome data (12 assigned to gabapentin and 9 to the active comparator arm), 18 were enrolled as outpatients and all 21 were outpatients from days 5 to 7. The study groups' baseline characteristics were well matched. Gabapentin treatment provided a 52% greater reduction in days 5 to 7 baseline adjusted Motherisk-pregnancy-unique quantification of nausea and emesis total scores than treatment with active comparator (95% confidence interval, 16-88; P=.01). Most secondary outcomes also favored gabapentin over active comparator treatment including 46% and 49% decreases in baseline adjusted Motherisk-pregnancy-unique quantification of nausea and emesis nausea (95% confidence interval, 19-72; P=.005) and vomit and retch subscores (95% confidence interval, 21-77; P=.005), respectively; a 96% increase in baseline adjusted oral nutrition scores (95% confidence interval, 27-165; P=.01); and a 254% difference in global satisfaction of treatment (95% confidence interval, 48-459; P=.03). Relief (P=.06) and desire to continue therapy (P=.06) both showed trends favoring gabapentin treatment but Nausea and Vomiting of Pregnancy Quality of Life (P=.68) and Hyperemesis Gravidarum Pregnancy Termination Consideration (P=.58) did not. Adverse events were roughly equivalent between the groups. There were no serious adverse events.
In this small trial, gabapentin was more effective than standard-of-care therapy for reducing nausea and vomiting and increasing oral nutrition and global satisfaction in outpatients with hyperemesis gravidarum. These data build on previous findings in other patient populations supporting gabapentin as a novel antinausea and antiemetic therapy and support further research on gabapentin for this challenging complication of pregnancy.
妊娠剧吐是一种在孕早期出现恶心、呕吐和营养不良的疾病，目前尚无有效的门诊治疗方法。妊娠剧吐患者体重增加不良与早产、低出生体重、小于胎龄儿、5 分钟 Apgar 评分低和神经发育迟缓等多种不良胎儿结局有关。加巴喷丁最常用于治疗神经病理性疼痛，但也能显著减少化疗和术后引起的恶心和呕吐。妊娠登记数据显示，在 659 名婴儿中，母亲在孕早期使用加巴喷丁单药治疗的主要先天畸形发生率为 1.2%，与一般人群中 1.6%至 2.2%的主要先天畸形发生率相比，情况较好。妊娠剧吐患者开放性加巴喷丁治疗可减少恶心和呕吐，改善口服营养。
本研究旨在确定加巴喷丁是否比标准治疗更有效治疗妊娠剧吐。
一项双盲、随机、多中心试验在需要静脉补液的医学难治性妊娠剧吐患者中进行。患者随机（1:1）接受口服加巴喷丁（1800-2400mg/d）或口服昂丹司琼（24-32mg/d）或口服甲氧氯普胺（45-60mg/d）的活性对照药物治疗 7 天。采用意向治疗原则，根据基线母亲妊娠独特的恶心和呕吐总评分进行线性混合效应模型调整，作为主要终点，比较治疗组在第 5 至 7 天的平均母亲妊娠独特的恶心和呕吐总评分差异。次要结局包括母亲妊娠独特的恶心和呕吐的恶心和呕吐以及干呕子评分、口服营养、治疗整体满意度、缓解、继续治疗的意愿、妊娠恶心和呕吐生活质量以及妊娠剧吐终止考虑。采用虚假发现率对多次比较进行调整。
2014 年 10 月至 2019 年 5 月期间共纳入 31 例妊娠剧吐患者。在提供主要结局数据的 21 例患者中（12 例接受加巴喷丁治疗，9 例接受活性对照药物治疗），18 例为门诊患者，所有 21 例患者均为第 5 至 7 天的门诊患者。研究组的基线特征匹配良好。与活性对照药物治疗相比，加巴喷丁治疗可使第 5 至 7 天基线调整后的母亲妊娠独特的恶心和呕吐总评分降低 52%（95%置信区间，16-88；P=.01）。大多数次要结局也倾向于加巴喷丁治疗，包括调整后的母亲妊娠独特的恶心和呕吐的恶心和呕吐子评分降低 46%和 49%（95%置信区间，19-72；P=.005），以及干呕子评分降低 46%和 49%（95%置信区间，19-72；P=.005）；口服营养评分增加 96%（95%置信区间，27-165；P=.01）；以及治疗整体满意度提高 254%（95%置信区间，48-459；P=.03）。缓解（P=.06）和继续治疗的意愿（P=.06）均显示出有利于加巴喷丁治疗的趋势，但妊娠恶心和呕吐生活质量（P=.68）和妊娠剧吐终止考虑（P=.58）则没有。两组不良反应大致相当。没有严重不良事件。
在这项小型试验中，加巴喷丁在减少恶心、呕吐和增加口服营养和妊娠剧吐门诊患者整体满意度方面比标准治疗更有效。这些数据建立在以前在其他患者群体中的发现基础上，支持加巴喷丁作为一种新的止吐和止吐治疗方法，并支持进一步研究加巴喷丁治疗这种妊娠的挑战性并发症。
