The use of metoclopramide to control nausea and vomiting in the first trimester does not increase the risk for congenital malformations, low birth weight, or perinatal death, according to a report in the June 11 issue of the New England Journal of Medicine.

These findings from a large retrospective cohort study “provide reassurance about the safety of metoclopramide,” which has not been convincingly established until now, wrote Ilan Matok of Ben-Gurion University of the Negev, Beer-Sheva, Israel, and associates.

“Despite its extensive use, only a few studies have assessed the safety to the fetus of maternal exposure to metoclopramide during the first trimester, and the relatively small sizes of these studies limited their power to detect adverse effects of the drug,” they noted.

The researchers assessed singleton deliveries between 1998 and 2007 at the largest health maintenance organization in Israel, where metoclopramide is the antiemetic drug of choice during pregnancy. Approximately half of the 81,703 infants in the study were born to Jewish parents and half to Bedouin Muslim parents.

A total of 3,458 (4%) of these infants were exposed to metoclopramide during the first trimester. The mean duration of exposure was 1 week.

The rate of major congenital malformations was 5.3% among exposed infants, compared with 4.9% among unexposed infants, a nonsignificant difference. This difference remained nonsignificant when data from pregnancies that were terminated were included in the analysis.

The rates of minor congenital malformations (3.8% vs. 3.5%) and of multiple malformations (2.5% vs. 2.3%) also were similar between exposed and nonexposed infants. There also were no significant associations between subclasses of congenital malformations and metoclopramide exposure, nor was there any clustering of anomalies among exposed infants.

When the data were analyzed according to subjects’ ethnic backgrounds, the drug did not raise risks to infants of either Jewish or Bedouin Muslim parents (N. Engl. J. Med. 2009;360:2528-35).

Metoclopramide also was not associated with an increased risk of preterm birth, low Apgar scores, perinatal death, or low birth weight.

A subgroup of 758 mothers who took metoclopramide refilled their prescriptions at least once. No dose-response effect of exposure to the drug was found.

The researchers reported having no relevant conflicts of interest.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

6月11日版的《新英格兰医学杂志》中有篇报告指出，妊娠期前3个月内服用甲氧氯普胺(灭吐灵)控制恶心和呕吐不会增加先天畸形、低出生体重或围产期死亡的风险。

以色列贝尔谢巴市内盖夫本-古里安大学Ilan Matok及其同事在文中写道，这些由大型、回顾性队列研究得出的结果“是甲氧氯普胺安全性的定心丸”，此说法至今尚未得到信服地证实。

“尽管甲氧氯普胺应用广泛，但仅有少数研究评价了妊娠期的前3个月中母体内胎儿接触该药的安全性，这些为数不多的几项研究规模亦相对较小，故限制了该药不良反应的检测效力，”他们指出。

这些研究者选择以色列最大的一家、以甲氧氯普胺作为妊娠期止吐药的健康管理组织(HMO)，对1998年至2007年间的单胎分娩进行了评估。81,703例婴儿中近半数双亲为犹太人，半数为贝都因穆斯林人。

这些婴儿中共有3,458例(4%)在妊娠期前3个月接触了甲氧氯普胺，平均接触时间为1w。

接触该药的婴儿中，严重先天畸形的发生率为5.3%，而未接触的婴儿为4.9%，无显著的统计学差异。分析中包括终止妊娠的数据时，此差异仍不显著。

接触该药的婴儿与未接触者之间轻度先天畸形的发生率(3.8%对3.5%)和多发畸形的发生率(2.5%对2.3%)亦相近。先天畸形亚类与接触甲氧氯普胺之间无显著的相关性，接触该药的婴儿中亦未集中发生任何异常现象。

根据受试者种族对数据进行分析时，无论婴儿双亲为犹太人抑或贝都因穆斯林人，该药均不会增加婴儿的发病风险(N. Engl. J. Med. 2009;360:2528-35)。

甲氧氯普胺也不会增加早产、Apgar评分偏低、围产期死亡或低出生体重的风险 。

有758位服用甲氧氯普胺的母亲连续开处方至少一次，研究中未发现该亚组接触此药的剂量效应。

这些研究者均未报告有相关的利益关系。