Symptomatic Relief

Anti-inflammatory

1. Parker CR Jr, Hauth JC, Goldenberg RL, Cooper RL, Dubard MB. Umbilical cord serum levels of thromboxane B2 in term infants of women who participated in a placebo-controlled trial of low-dose aspirin. J Matern Fetal Med 2000 Jul-Aug;9(4):209-15

2. Heyborne KD. Preeclampsia prevention: lessons from the low-dose aspirin therapy trials. Am J Obstet Gynecol 2000 Sep;183(3):523-8

3. Baldwin GS. Do NSAIDs contribute to acute fatty liver of pregnancy? Med Hypotheses 2000 May;54(5):846-9

Antinauseants

1. Miklovich L, van den Berg BJ. An evaluation of the teratogenicity of certain antinauseant drugs. Am J Obstet Gynecol 1976 May 15;125(2):244-8

2. Czeizel AE, Szegal BA, Joffe JM, Racz J. The effect of diazepam and promethazine treatment during pregnancy on the somatic development of human offspring. Neurotoxicol Teratol 1999 Mar-Apr;21(2):157-67

3. Kousen M. Treatment of nausea and vomiting in pregnancy. Am Fam Physician 1993 Nov 15;48(7):1279-84

4. Bishai R, Mazzotta P, Atanackovic G, Levichek Z, Pole M, Magee LA, Koren G. Critical appraisal of drug therapy for nausea and vomiting of pregnancy: II. Efficacy and safety of diclectin (doxylamine-B6). Can J Clin Pharmacol 2000 Autumn;7(3):138-43

5. Sorensen HT, Nielsen GL, Christensen K, Tage-Jensen U, Ekbom A, Baron J. Birth outcome following maternal use of metoclopramide. The Euromap study group. Br J Clin Pharmacol 2000 Mar;49(3):264-8. AIMS: Metoclopramide is an antiemetic drug used widely during pregnancy for nausea and vomiting. Because of its frequent use any adverse effects on infant health would have major public health implications. We therefore examined the safety of metoclopramide during pregnancy. METHODS: Using the Pharmaco-Epidemiological Prescription Database of North Jutland County, we identified 309 women with singleton pregnancies who had prescriptions for metoclopramide fom 1 January 1991 to 31 December 1996. Information on malformations, birth weight, preterm deliveries and stillbirth were compared with 13 327 references who did not receive prescriptions of any kind during pregnancy. RESULTS: Mean birth weight among exposed women was 3480 g compared with 3470 g among nonexposed. Based on logistic regression models no major differences in the risk were found concerning malformations (OR= 1.11; 95% confidence interval (CI): 0.6-2.1); low birth weight (OR= 1.79; 95% CI: 0.8-3.9) or preterm delivery (OR= 1.02; 95 CI: 0.6-1.7). CONCLUSIONS: We could not document any association between the use of metoclopramide during pregnancy and adverse pregnancy outcome. Because of the limited power of our study further research is required.

6. Tincello DG, Johnstone MJ. Treatment of hyperemesis gravidarum with the 5-HT3 antagonist ondansetron (Zofran). Postgrad Med J 1996 Nov;72(853):688-9. Ondansetron is a 5-hydroxytryptamine receptor antagonist which is known to be a highly effective anti-emetic drug for chemotherapy-associated nausea and vomiting and for postoperative nausea. We report here a case where ondansetron was used in severe hyperemesis gravidarum to avoid parenteral nutrition. The drug was used intermittently in every trimester with no apparent adverse effects on mother or infant.

7. Magee LA, Mazzotta P, Koren G. Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP). Am J Obstet Gynecol 2002 May;185(5 Suppl Understanding):S256-61. OBJECTIVE: Our goal was to review the safety and effectiveness of available antiemetics for treatment of nausea and vomiting of pregnancy. STUDY DESIGN: We performed a quantitative and qualitative overview of observational controlled studies for drug safety in pregnancy and randomized controlled trials for drug effectiveness for nausea and vomiting in pregnancy. RESULTS: All of the following are safe and effective for treatment of varying degrees of nausea and vomiting in pregnancy: Bendectin/Diclectin (doxylamine, pyridoxine, dicyclomine), antihistamine (H(1)) blockers, and phenothiazines; however, the magnitude of effect, particularly for phenothiazines, is in question and may differ among individual agents. Pyridoxine and vitamin B(12)are safe and may be effective. Metoclopramide, droperidol, and ondansetron may be effective, but safety data are insufficient to recommend them as first-line agents. Corticosteroids may not be as beneficial as first thought, and there may be a small teratogenic risk. The relative effectiveness of various agents is largely unknown. CONCLUSION: Many medications, particularly H(1)-antagonists and phenothiazines, are safe and effective for treatment of varying degrees of NVP.

8. Atanackovic G, Navioz Y, Moretti ME, Koren G. The safety of higher than standard dose of doxylamine-pyridoxine (Diclectin) for nausea and vomiting of pregnancy. J Clin Pharmacol 2001 Aug;41(8):842-5. A delayed-release combination of doxylamine-pyridoxine (D-P) (Diclectin) is the only approved antiemetic medication for use in pregnancy in Canada. The standard recommended dose is up to 4 tablets a day, regardless of body weight or severity of symptoms. The objective of this study was to determine the incidence of adverse maternal and fetal effects and pregnancy outcome in 225 women taking Diclectin at the recommended (n = 123) or higher than recommended (n = 102) doses. In this observational, prospective study, one-third (33.6%) of women reported having adverse effects (sleepiness, tiredness, and/or drowsiness) temporally related to the medication. There was no association between the dose per kg and rates of reported maternal adverse effects with doses ranging from 0.1 mg/kg to 2.0 mg/kg (1-12 tablets). Nausea and vomiting of pregnancy (NVP) was reported as severe by the majority (75.8%) of women. Mean birth weight (BW) was 3,400 g and gestational age (GA) 39 weeks. Multivariate analysis revealed that only prepregnancy weight and GA predicted lower BW, not the dose of D-P or the severity of NVP. There were two pregnancies with major malformation, a finding that is consistent with the rates of birth defects in the general population. It was concluded that the higher than standard dose of Diclectin, when calculated per kg of body weight, does not affect either the incidence of maternal adverse effects or pregnancy outcome. If needed, Diclectin can be given at doses higher than 4 tablets/day to normalize for body weight or optimize efficacy.

Antidiarrheals

1. Lione A. Nonprescription drugs as a source of aluminum, bismuth, and iodine during pregnancy. Reprod Toxicol 1987-88;1(4):243-52

2. Quereux C, Morice J, Level G, Ezes H, Wahl P. [Bismuth encephalopathy in pregnant women. Apropos of a case]. J Gynecol Obstet Biol Reprod (Paris) 1976 Jan-Feb;5(1):97-103. [Article in French] A case of bismuth encephalopathy in a pregnant woman is reported. The neurological picture, characterized especially by myoclonic attacks, is no different from that found in the non-pregnant state. The principal observations are on three points: - the need to think of a toxic origin of convulsions in pregnancy, - the onset of threatened premature labour during repeated convulsive crises, - the passage of bismuth across the placenta : this has been proved by the levels found in the amniotic fluid (55 mcg per 1,000) and in the cord blood (320 mcg per 1,000). The child, who was normal at birth, developed a transient hypotonus which seemed attributable more to the treatment of the mother with Diazepam and pheno-barbitone than to her having taken bismuth during the pregnancy.

3. Einarson A, Mastroiacovo P, Arnon J, Ornoy A, Addis A, Malm H, Koren G. Prospective, controlled, multicentre study of loperamide in pregnancy. Can J Gastroenterol 2000 Mar;14(3):185-7. BACKGROUND: Loperamide is a synthetic piperidine derivative used for the treatment of both acute and chronic diarrhea. Little is known about its safety and risk in pregnancy. Human data are limited to one surveillance study of Michigan Medicaid patients, with 108 women exposed in the first trimester. In this study there were six major birth defects, three of which were cardiovascular anomalies. OBJECTIVES: To determine whether loperamide use in pregnancy is associated with an increased risk of major malformations. The secondary end points were rates of minor malformations, spontaneous and therapeutic abortions, and premature births, and mean birth weights. PATIENTS AND METHODS: Women counselled by five teratogen information centres on the safety and risk of loperamide in pregnancy were followed after delivery and compared with a similar group of women matched for age, smoking, alcohol and other exposures. RESULTS: One hundred and five follow-ups were completed; 89 of the women were exposed to loperamide in the first trimester of pregnancy. There were no statistically significant differences between the study group and the control group in any of the end points that were analyzed. However, of women who took loperamide throughout their pregnancy, 21 of 105 had babies who were 200 g smaller than babies in the control group. CONCLUSIONS: The results of this study suggest that the use of loperamide during pregnancy is not associated with an increased risk of major malformations.

Psychotropics

1. Joffe GM, Kasnic T.. Medical prescription of dextroamphetamine during pregnancy. J Perinatol 1994 Jul-Aug;14(4):301-3

2. Hoover-Stevens S, Kovacevic-Ristanovic R.. Management of narcolepsy in pregnancy. Clin Neuropharmacol 2000 Jul-Aug;23(4):175-81

3. Shangraw RE, Seminer SJ, Zarr ML. Attention deficit disorder, amphetamine, and pregnancy. Biol Psychiatry 1985 Aug;20(8):926-7