Medline ® Abstracts for References 52-54,58
of 'Treatment and outcome of nausea and vomiting of pregnancy'
A risk-benefit assessment of pharmacological and nonpharmacological treatments for nausea and vomiting of pregnancy.
Mazzotta P, Magee LA
Drugs. 2000 Apr;59(4):781-800.
Despite evidence of fetal safety, most antiemetics are contraindicated in pregnancy. We summarise a risk-benefit analysis of the literature on safety and effectiveness of pharmacotherapy and nontraditional therapy for nausea and vomiting of pregnancy (NVP) to provide evidence-based guidelines on the management of NVP. The medical literature was scanned for controlled studies on the human teratogenicity and effect of various antiemetics in pregnant women. Data were pooled based on drug/therapy class and summarised to determine relative risk with 95% confidence interval (for malformations and failure rates for NVP) and homogeneity (chi-square test). Evidence from controlled trials has demonstrated the safety and efficacy of the following drugs for the treatment of varying degrees of NVP: doxylamine/pyridoxine+/-dicycloverine (dicyclomine), antihistamine H1 receptor antagonists, and phenothiazines (as a group). However, pooled data for doxylamine/pyridoxine+/-dicycloverine, H1 antagonists and phenothiazines were not homogeneous. Other therapies, such as pyridoxine alone, metoclopramide, ondansetron and the corticosteroids may be beneficial in managing NVP. However, limited efficacy studies and the paucity of well-controlled safety studies may limit the use of some of these agents among patients not responsive to first-line agents. Well-controlled safety and effectiveness trials in patients with NVP are lacking for nonpharmacological treatments (e.g. acupressure). NVP can be managed safely and effectively. Further trials must be conducted in order to determine the true effectiveness of certain agents in patients with NVP.
Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Use of antihistamine medications during early pregnancy and isolated major malformations.
Gilboa SM, Strickland MJ, Olshan AF, Werler MM, Correa A, National Birth Defects Prevention Study
Birth Defects Res A Clin Mol Teratol. 2009 Feb;85(2):137-50.
BACKGROUND: Antihistamines are commonly used during pregnancy. There is little evidence that they have teratogenic effects, but there are knowledge gaps with respect to newer products, as well as the relationship between specific antihistamines and specific birth defects.
METHODS: Using the National Birth Defects Prevention Study (1997-2003), the authors examined associations between maternal use of 14 antihistamines during early pregnancy and 26 isolated major birth defects. A Bayesian analysis incorporating prior knowledge about the relationships between antihistamines, birth defects, and measured covariates was conducted.
RESULTS: Of the 364 associations investigated, 24 had 95% posterior intervals excluding 1.0. All 24 associations were positive; 23 associations were of weak to moderate magnitude (posterior OR<3.0) and one was strong (OR>6.0) but very imprecise. Of the 24 associations, 20 were with noncardiac defects. Eight associations involved the antihistamine diphenhydramine.
CONCLUSIONS: The results of this study generally were consistent with no association between birth defects and antihistamine use during early pregnancy. Several of the findings might warrant further investigation, although the observed elevated associations should be interpreted in the context of the number of associations investigated and the analysis of retrospective, self-reported data.
National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333, USA.
Assessment of antihistamine use in early pregnancy and birth defects.
Li Q, Mitchell AA, Werler MM, Yau WP, Hernández-Díaz S
J Allergy Clin Immunol Pract. 2013 Nov-Dec;1(6):666-74.e1. Epub 2013 Sep 12.
BACKGROUND: Several studies have reported an association between use of specific antihistamines in early pregnancy and certain specific birth defects.
OBJECTIVE: To test 16 previously hypothesized associations between specific antihistamines and specific birth defects, and to identify possible new associations.
METHODS: We used 1998-2010 data from the Slone Epidemiology Center Birth Defects Study, a multicenter case-control surveillance program of birth defects in North America. Mothers were interviewed within 6 months of delivery about demographic, reproductive, medical, and behavioral factors, and details on the use of prescription and nonprescription medications. We compared first trimester exposure to specific antihistamines between 13,213 infants with specific malformations and 6982 nonmalformed controls by using conditional logistic regression to estimate odds ratios and 95% confidence intervals (CIs), with adjustment for potential confounders, including indication for use.
RESULTS: Overall, 13.7% of controls were exposed to antihistamines during the first trimester. The most commonly used medications were diphenhydramine (4.2%), loratadine (3.1%), doxylamine (1.9%), and chlorpheniramine (1.7%). When estimates were stable, none supported the previously hypothesized associations. Among more than 100 exploratory comparisons of other specific antihistamine-defect pairs, 14 had odds ratios≥1.5, of which 6 had 95% CI bounds excluding 1.0 before but not after adjustment for multiple comparisons.
CONCLUSION: Our findings do not provide meaningful support for previously posited associations between antihistamines and major congenital anomalies; at the same time, we identified associations that had not been previously suggested. We suspect that previous associations may be chance findings in the context of multiple comparisons, a situation that may also apply to our new findings.
Department of Epidemiology, Harvard School of Public Health, Boston, Mass.
A case-control study of congenital abnormality and dimenhydrinate usage during pregnancy.
Czeizel AE, Vargha P
Arch Gynecol Obstet. 2005 Feb;271(2):113-8. Epub 2004 Oct 23.
OBJECTIVE: The objective was to determine the teratogenicity of dimenhydrinate, an anti-emetic drug.
METHODS: We compared patients with congenital abnormalities with matched normal controls. Cases were taken from the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996, while matched controls were from the National Birth Registry of the Central Statistical Office.
RESULTS: Out of 38,151 newborn infants with no congenital abnormalities (control group), 1,726 (4.5%) were treated with dimenhydrinate during pregnancy, while out of 22,843 cases with congenital abnormalities, the number was 914 (4.0%; unadjusted prevalence odds ratio with 95% confidence interval: 0.9, 0.8-1.0). There was thus no indication of teratogenicity with dimenhydrinate. However, a lower rate of obstructive uropathy was found in infants born to mothers treated with dimenhydrinate during the first trimester of pregnancy than in infants whose mothers did not take the drug at that time.
Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary. email@example.com