Senior Medical Officer, Pediatric Day Care Department, Assaf-Harofeh Medical Center, Lecturer, Sackler School of Medicine, Tel-Aviv University, Israel
Nausea and vomiting are very common during pregnancy, particularly during the first trimester, and occur in 60-70% of pregnant women. Hyperemesis gravidarum is less common: approximately three cases per 1,000 pregnancies. The cause of nausea and vomiting during pregnancy is still not fully elucidated. Usually, the problem is mild and does not require any specific therapy; nevertheless, in some cases drug treatment is needed.
Metoclopramide is a drug that blocks the dopamine receptor in the chemoreceptor trigger zone, and depresses the vomiting centre; it stimulates the motility of the upper gastrointestinal tract, increases lower oesophageal sphincter tone, and may also increase motility of the lower gastrointestinal tract. It has been used to treat gastric stasis and gastroesophageal reflux, to increase gastric emptying in postoperative patients, and to inhibit emesis in patients receiving chemotherapy. In Israel, metoclopramide is not authorized for use in pregnancy. The drug readily crosses the placenta at term (in a ratio of 0.57-0.84), however, the extent and significance of placental transfer of metoclopramide during the first and second trimesters of pregnancy is unknown. There are no prospective studies on the safety of metoclopramide during pregnancy. In animal studies there has been no reported increase above normal frequency of malformations in mice, rats or rabbits. Furthermore, in the Michigan Medicaid study of 192 first trimester exposures to metoclopramide between 1985 and 1992, there were 10 (5.2%) major malformations, where eight were expected.1 There was no specific pattern of anomalies. Additionally, in 12 of 26 European countries, metoclopramide is the antiemetic drug of choice in pregnancy.
We conducted a prospective, multicentre (international) study in order to evaluate the safety of metoclopramide during pregnancy, i.e., to investigate the possible teratogenic effects of intrauterine exposure to the drug.2 We studied 126 women who received metoclopramide, and consulted teratogen information centres in Israel, Italy and Brazil. Relevant information was collected by phone whenever a woman or the physician called the centres: drug use, dose of drug, other chemical exposure, alcohol consumption, cigarette smoking. The control group comprised 126 women who also called the centres and were using medication known to be safe in pregnancy. Cases were paired for age, smoking and alcohol consumption. Metoclopramide was administered in a dose of 25 ± 10 (10-40) mg for 10 ± 10 (1-35) days.
There were no differences in maternal history, birth weight, gestational age at delivery, rates of live births, spontaneous or therapeutic abortions, method of delivery, foetal distress and either major or minor malformations between the two study groups. There were five cases of malformations in both groups: 5/111 for metoclopramide and 5/115 for the controls. The difference was not statistically significant. The specific findings were:
Since metoclopramide has a central nervous system effect, it might theoretically affect the psychomotor development of affected children. We therefore compared the gross motor developmental milestones of the children in the two groups. Specific questions were asked about lifting (head), sitting, crawling, standing, and walking. There was no significant difference between the two groups.
Only the study centres in Israel asked about the effectiveness of metoclopramide in treating the mother's symptoms. There was improvement in symptoms reported by 26/40 (65%) of women.
In conclusion, the use of metoclopramide during the first trimester of pregnancy does not appear to be associated with an increased risk of malformations, spontaneous abortions or decreased birth weight, however, larger study numbers are needed.
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