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Medline ® Abstracts for References 104-108

of 'Treatment and outcome of nausea and vomiting of pregnancy'

104
TI
Update on new developments in the study of human teratogens.
AU
Shepard TH, Brent RL, Friedman JM, Jones KL, Miller RK, Moore CA, Polifka JE
SO
Teratology. 2002;65(4):153.
 
BACKGROUND AND METHODS: The purpose of this annual article is to highlight and briefly review new and significant information on agents that may be teratogenic in pregnant women. Various sources of on-line and printed information are given.
RESULTS: The following topics have been discussed: 1) lithium medication: decreased estimate of risk; 2) cigarette smoking and genotype as contributors to oral-facial clefts and clubfoot; 3) trimethoprim; 4) methimazole syndrome?; 5) glucocorticoids and oral-facial clefts; 6) binge drinking; 7) fetal valproate syndrome; and 8) carbamazepine.
CONCLUSIONS: We have highlighted several maternal exposures during pregnancy that are associated with small but increased rates of birth defects, generally only a few cases per 1,000 infants. These exposures include cigarette smoking, and treatment with lithium, trimethoprim, methimazole, or corticosteroids. This weak teratogenic effect was usually identified by the linkage of an uncommon treatment with an unusual birth defect outcome. The use of modern epidemiologic techniques, especially prospective multicenter studies that provide increased numbers, has helped to strengthen the evidence for these associations. We discuss how teratogenic risks that are small in comparison to the background risk can be presented to at-risk women and their doctors. We have briefly listed some elements that might be used in prioritizing further studies of suspected teratogenic exposures. Various existing methods for expressing the strength of evidence for human teratogenicity are also given.
AD
University of Washington, Department of Pediatrics, Seattle, Washington 98195-6320, USA. shepard@u.washington.edu
PMID
105
TI
Maternal corticosteroid use and risk of selected congenital anomalies.
AU
Carmichael SL, Shaw GM
SO
Am J Med Genet. 1999;86(3):242.
 
Evidence for the teratogenicity of corticosteroids in humans is limited and has resulted in inconsistent recommendations regarding their use during early pregnancy. We examined the association between women's corticosteroid use during the periconceptional period (1 month before to 3 months after conception) and delivering infants with selected congenital anomalies. Data were derived from a population-based case-control study that included cases of orafacial clefts (n = 662), conotruncal heart defects (n = 207), neural tube defects (n = 265), and limb reduction defects (n = 165). Information on medication use was collected via maternal telephone interviews. Corticosteroid use was associated with an increased risk for isolated cleft lip with or without cleft palate (odds ratio 4.3, 95% confidence interval 1.1-17.2) and isolated cleft palate (odds ratio 5.3, 95% confidence interval 1.1-26.5). Increased risks were not observed for the other anomaly groups studied. These data in conjunction with other epidemiologic data suggest a possible causal association between cleft lip and palate and corticosteroid use.
AD
March of Dimes/California Birth Defects Monitoring Program, Emeryville, California 94608, USA. slc@a.crl.com
PMID
106
TI
Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies.
AU
Park-Wyllie L, Mazzotta P, Pastuszak A, Moretti ME, Beique L, Hunnisett L, Friesen MH, Jacobson S, Kasapinovic S, Chang D, Diav-Citrin O, Chitayat D, Nulman I, Einarson TR, Koren G
SO
Teratology. 2000;62(6):385.
 
BACKGROUND: Corticosteroids are first-line drugs for the treatment of a variety of conditions in women of childbearing age. Information regarding human pregnancy outcome with corticosteroids is limited.
METHODS: We collected prospectively and followed up 184 women exposed to prednisone in pregnancy and 188 pregnant women who were counseled by Motherisk for nonteratogenic exposure. The primary outcome was the rate of major birth defects. A meta-analysis of all epidemiological studies was conducted. The Mantel-Haenszel summary odds ratio was calculated for the pooled studies with 95% confidence intervals. A cumulative summary odds ratio was also calculated by combining studies in chronological order. Chi-squared for homogeneity was determined to establish the comparability of the studies.
RESULTS: In our prospective study, there was no statistical difference in the rate of major anomalies between the corticosteroid-exposed and control groups. In the meta-analysis, the Mantel-Haenszel summary odds ratio formajor malformations with all cohort studies was 1.45 [95% CI 0.80, 2.60]and 3.03 [95% CI 1.08, 8. 54]when Heinonen et al. ('77) was removed. This suggests a marginally increased risk of major malformations after first-trimester exposure to corticosteroids. In addition, summary odds ratio for case-control studies examining oral clefts was significant (3.35 [95% CI 1.97, 5.69]).
CONCLUSIONS: Although prednisone does not represent a major teratogenic risk in humans at therapeutic doses, it does increase by an order of 3.4-fold the risk of oral cleft, which is consistent with the existing animal studies.
AD
Faculty of Pharmacy, University of Toronto, Toronto, Canada.
PMID
107
TI
Corticosteroids during pregnancy and oral clefts: a case-control study.
AU
Rodríguez-Pinilla E, Martínez-Frías ML
SO
Teratology. 1998;58(1):2.
 
The question of whether systemic use of corticosteroids during the first trimester of pregnancy increases the risk of congenital malformations in people has still not been resolved. Here, we present the results of a case-control study on the relationship of corticosteroids during pregnancy and oral clefts in the newborn infant. Data are derived from the Spanish Collaborative Study of Congenital Malformations (ECEMC). Case subjects were 1,184 liveborn infants with nonsyndromic oral clefts. The results of the logistic regression analysis, show a relationship between exposure to corticosteroids during the first trimester of pregnancy and an increased risk of cleft lip (with or without cleft palate) in the newborn infants (OR = 6.55; CI = 1.44-29.76; P = 0.015), controlled for potential confounder factors, such as maternal smoking, maternal hyperthermia, first-degree malformed relatives with cleft lip with or without cleft palate, and maternal treatment with antiepileptics, benzodiazepines, metronidazole, or sex hormones during the first trimester of pregnancy. Thus, we believe that the use of corticosteroids during the first trimester of pregnancy, should be restricted to the following situations: for life-threatening situations, for those diseases without any other safe therapeutic alternative, or for those cases with replacement therapy.
AD
ECEMC (Estudio Colaborativo Español de Malformaciones Congénitas), Facultad de Medicina, Universidad Complutense, Madrid, Spain.
PMID
108
TI
First trimester exposure to corticosteroids and oral clefts.
AU
Pradat P, Robert-Gnansia E, Di Tanna GL, Rosano A, Lisi A, Mastroiacovo P, Contributors to the MADRE database
SO
Birth Defects Res A Clin Mol Teratol. 2003;67(12):968.
 
BACKGROUND: The possible association between oral cleft in the newborn and maternal exposure to corticoids during pregnancy is still controversial. The aim of this study was to test this association by a case-control analysis using the large multicentric MADRE database.
METHODS: The MADRE database is a collection of information on malformed infants with a history of maternal first-trimester drug exposure. Nine malformation registries participate in the data collection. Cases were defined as infants presenting with a cleft palate or cleft lip, and exposure was defined by the use of corticosteroids during the first trimester of pregnancy.
RESULTS: After 12 years of data collection, the database includes data on 11,150 malformed infants. A slight association is observed between exposure to corticoids for systemic use and the occurrence of cleft lip with or without cleft palate (OR, 2.59; 95% CI, 1.18-5.67).
CONCLUSIONS: If the observed association is real, an interpretation is suggested, based on a likely interaction between corticosteroids and environmental dioxins. It is indeed possible that human fetuses may become sensitive to the teratogenic effect of corticosteroids when they are exposed in utero to environmental pesticides as well.
AD
Institut Européen des Génomutations, Lyon, France.
PMID